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Does a male polycystic ovarian syndrome equivalent exist?
Abstract
The occurrence of a genetic background in the etiology of polycystic ovarian syndrome (PCOS) represents the rational basis to postulate the existence of a male PCOS equivalent. Hormonal and metabolic abnormalities have been described in male relatives of women with PCOS. These males also have a higher prevalence of early onset (<35 years) androgenetic alopecia (AGA). Hence, this feature has been proposed as a clinical sign of the male PCOS equivalent. Clinical evidence has shown that men with early onset AGA have hormonal and metabolic abnormalities. Large cohort studies have clearly shown a higher prevalence of type II diabetes mellitus (DM II) and cardiovascular diseases (CVDs) in elderly men with early onset AGA. In addition, prostate cancer, benign prostate hyperplasia (BPH) and prostatitis have been described. These findings support the existence of the male PCOS equivalent, which may represent an endocrine syndrome with a metabolic background, and might predispose to the development of DM II, CVDs, prostate cancer, BPH and prostatitis later in life. Its acknowledgment would be helpful for the prevention of these long-term complications.
... The etiopathogenesis of PCOS is most likely multifactorial with genetic susceptibility and environmental exposure playing predominant roles (9). In line with this, recent studies in men suggest the existence of a male PCOS equivalent in the brothers of women with PCOS (23)(24)(25)(26). These men share common endocrine, metabolic and cardiovascular comorbidities with their sisters such as an elevated free androgen index, a low level of FSH leading to an elevated LH/FSH ratio, insulin resistance, type II diabetes and hypertension (23,25,26). ...
... In line with this, recent studies in men suggest the existence of a male PCOS equivalent in the brothers of women with PCOS (23)(24)(25)(26). These men share common endocrine, metabolic and cardiovascular comorbidities with their sisters such as an elevated free androgen index, a low level of FSH leading to an elevated LH/FSH ratio, insulin resistance, type II diabetes and hypertension (23,25,26). Among the current hypotheses of PCOS origins, in utero androgen excess has been highlighted by human and animal-based study as a substantial contributor (9,27). ...
... Epidemiological studies indicate that women with PCOS are more likely to experience sexual dysfunction, including low sex drive and sexual dissatisfaction, that can negatively impact their quality of life (40)(41)(42)(43)(44)(45)(46)(47)(48). Interestingly, men diagnosed with early onset androgenetic alopecia (AGA), now considered as a clinical sign of male PCOS equivalent (23,24,26), also indicate experiencing sexual dysfunction (49,50). In women, the cause of PCOS-related sexual dysfunction is frequently attributed to psychological factors, including reduced selfesteem related to hirsutism and/or obesity, a higher prevalence of anxiety, depression and mood disorders and decreased interest in sexual activities due to infertility issues (40-42, 44-46, 48, 51-56). ...
Introduction
Polycystic ovary syndrome (PCOS) is the most common infertility disorder worldwide, typically characterised by high circulating androgen levels, oligo- or anovulation, and polycystic ovarian morphology. Sexual dysfunction, including decreased sexual desire and increased sexual dissatisfaction, is also reported by women with PCOS. The origins of these sexual difficulties remain largely unidentified. To investigate potential biological origins of sexual dysfunction in PCOS patients, we asked whether the well-characterized, prenatally androgenized (PNA) mouse model of PCOS exhibits modified sex behaviours and whether central brain circuits associated with female sex behaviour are differentially regulated. As a male equivalent of PCOS is reported in the brothers of women with PCOS, we also investigated the impact of maternal androgen excess on the sex behaviour of male siblings.
Methods
Adult male and female offspring of dams exposed to dihydrotestosterone (PNAM/PNAF) or an oil vehicle (VEH) from gestational days 16 to 18 were tested for a suite of sex-specific behaviours.
Results
PNAM showed a reduction in their mounting capabilities, however, most of PNAM where able to reach ejaculation by the end of the test similar to the VEH control males. In contrast, PNAF exhibited a significant impairment in the female-typical sexual behaviour, lordosis. Interestingly, while neuronal activation was largely similar between PNAF and VEH females, impaired lordosis behaviour in PNAF was unexpectedly associated with decreased neuronal activation in the dorsomedial hypothalamic nucleus (DMH).
Conclusion
Taken together, these data link prenatal androgen exposure that drives a PCOS-like phenotype with altered sexual behaviours in both sexes.
... Meta-analytic data provide evidence for increased DHEAS levels and a worse glycolipid profile in male patients with early-onset (<35 years) androgenic alopecia (AGA), defined by a grade of alopecia higher than III according to the Hamilton-Norwood scale [2,3], compared to controls [4]. Early-onset AGA may represent a feature of a male polycystic ovarian syndrome-(PCOS-) equivalent [5], a syndrome which causes gonadal dysfunction in the female gender. ...
... A higher risk with aging to develop type II diabetes mellitus (T2DM) and coronary heart disease has also been observed in men with early-onset AGA [5]. Hence, AGA has been proposed as an independent predictor of mortality for T2DM and cardiovascular diseases (CVDs) [29]. ...
... A trend was assumed for P values ranging from 0.05 to 0.099. Table 1: Clinical, biochemical and anamnestic features of the male equivalent of PCOS [5]. ...
Background:
Increased dehydroepiandrosterone sulfate (DHEAS) levels have been reported in men with early-onset (<35 years) androgenetic alopecia (AGA). It has been suggested that a male polycystic ovarian syndrome- (PCOS-) equivalent, defined as an endocrine syndrome with a metabolic background and a PCOS-like hormonal pattern, predisposing to type II diabetes mellitus (DM II), cardiovascular and prostate diseases later in life, may occur in at least a part of these men. The gonadal function, including sperm parameters and total testosterone (TT) levels, has been investigated in a low number of these men.
Objective:
The aim of the study was to assess gonadal and adrenal function in a subset of men with early-onset AGA and controls.
Methods:
43 men with early-onset AGA and 36 controls were screened for DHEAS, TT, glycaemia, insulin, gonadotropins, 17α-hydroxyprogesterone (17α-hydroxyprogesterone (17n = 21), as those with at least one of the following parameters: body mass index (BMI) >25 kg/m2, insulin resistance (IR), and/or SHBG <25 nmol/l.
Results:
Patients with early-onset AGA had higher mean (±SD) BMI (25.5 ± 3.8 vs. 23.7 ± 3.0 kg/m2; P < 0.05) and 17α-hydroxyprogesterone (17P < 0.05) and 17P < 0.05) and 17P < 0.05) and 17P < 0.05) and 17μg/dl; P < 0.05) and 17P < 0.05) and 17P < 0.05) and 17P < 0.05) and 17.
Conclusion:
Men with early-onset AGA and at least one among BMI >25 kg/m2, IR, and SHBG <25 nmol/l have increased DHEAS levels and a worse gonadal steroidogenesis. They might have a greater risk to develop gonadal dysfunction later in life. These criteria may be used to define male PCOS-equivalent.
... First, an attempt to identify diagnostic criteria of the male PCOS equivalent has already been made. Indeed, male PCOS has been defined as an endocrine syndrome with a metabolic background in the presence of clinical signs of hyperandrogenism [early-onset androgenetic alopecia (AGA), acne or hypertrichosis], PCOS-like hormonal pattern (as confirmed by meta-analytic evidence [2]), metabolic abnormalities, a trend toward higher BMI values [2] and/or a familiar history positive for PCOS in patients younger than 35 years [3] ( Table 1). The possible mechanism underlying the pathogenesis of the male PCOS equivalent is detailed in Fig. 1. ...
... Particularly, the impact that metabolic dysfunction has on gonads is gender-specific: while hyperinsulinemia enhances testosterone (T) production by the ovarian theca cells, thus leading to hyperandrogenism, it is widely accepted a negative role of hyperinsulinemia on Leydig cell steroidogenesis [4]. In turn, low T raises the susceptibility of developing type II diabetes mellitus and cardiovascular diseases [5], which are common features in patients with early-onset AGA [3]. Therefore, hyperinsulinemia could accelerate hair growth cycle and cause AGA itself and, at the same time, increased T levels should not be expected in the male PCOS equivalent. ...
... Clinical, biochemical and anamnestic features of the male polycystic ovary syndrome (PCOS) equivalent[3] Clinical signs of hyperandrogenism (early-onset AGA and/or acne and/or hypertrichosis) (ii) PCOS-like hormonal pattern (increased DHEAS, AMH, 17α-OH-progesterone, FAI, decreased FSH) (iii) Metabolic abnormalities (insulin-resistance, low SHBG levels, hyperglycemia, hyperinsulinemia) and/or a trend towards higher BMI values (iv) A familiar history positive for PCOS Elderly men Diabetes mellitus, Cardiovascular diseases, Benign prostatic hyperplasia, Prostatitis, Prostate cancer ...
We have read the recent article by Di Guardo and colleagues on the male polycystic ovary syndrome (PCOS) equivalent and we would like to further highlight some key-points concerning mainly the male PCOS equivalent definition, the diagnostic criteria, gender-related serum testosterone difference and fertility.
... These post-translational modifications depend on the environment of the maternal organism, which is increasingly influenced by civilizational factors leading to obesity and hormonal and immunological disorders involved in the pathomechanism of PCOS in the developing fetus ( Figure 2) [25]. In addition, there is evidence of a genetically male equivalent of PCOS that rules out the ovary as the starting point for this syndrome [26]. It was shown that men at a high genetic risk of developing the "male counterpart" of PCOS had an increased likelihood of developing obesity, diabetes, cardiovascular disease, and male pattern baldness [27]. ...
... It was shown that men at a high genetic risk of developing the "male counterpart" of PCOS had an increased likelihood of developing obesity, diabetes, cardiovascular disease, and male pattern baldness [27]. It is possible that PCOS-related reproductive dysfunctions may be caused by biological mechanisms that are common to both men and women [26]. There are genetic factors associated with the inheritance of PCOS. ...
Infertility has been recognized as a civilizational disease. One of the most common causes of infertility is polycystic ovary syndrome (PCOS). Closely interrelated immunometabolic mechanisms underlie the development of this complex syndrome and lead to infertility. The direct cause of infertility in PCOS is ovulation and implantation disorders caused by low-grade inflammation of ovarian tissue and endometrium which, in turn, result from immune and metabolic system disorders. The systemic immune response, in particular the inflammatory response, in conjunction with metabolic disorders, insulin resistance (IR), hyperadrenalism, insufficient secretion of progesterone, and oxidative stress lead not only to cardiovascular diseases, cancer, autoimmunity, and lipid metabolism disorders but also to infertility. Depending on the genetic and environmental conditions as well as certain cultural factors, some diseases may occur immediately, while others may become apparent years after an infertility diagnosis. Each of them alone can be a significant factor contributing to the development of PCOS and infertility. Further research will allow clinical management protocols to be established for PCOS patients experiencing infertility so that a targeted therapy approach can be applied to the factor underlying and driving the “vicious circle” alongside symptomatic treatment and ovulation stimulation. Hence, therapy of fertility for PCOS should be conducted by interdisciplinary teams of specialists as an in-depth understanding of the molecular relationships and clinical implications between the immunological and metabolic factors that trigger reproductive system disorders is necessary to restore the physiology and homeostasis of the body and, thus, fertility, among PCOS patients.
... 4,5 Given the genetic basis of PCOS, it has been suggested that early-onset AGA in men could be the phenotypic equivalent of PCOS in females. [6][7][8] The aim of this study was to ascertain the prevalence of hormonal abnormalities in males with early-onset AGA. We also wished to compare the incidence of insulin resistance and metabolic syndrome in patients with early-onset AGA with normal hormonal profiles with those with abnormal profiles. ...
... An altered hormonal profile was defined as two or more of the following: 7,8 (a) SHBG <15 nmol/l (b) free androgen index (total testosterone/ SHBG x 100) >150 (c) FSH <1 mIU/mL or luteinizing hormone:follicle stimulating hormone ratio >1.0 (d) DHEAS levels >3.6 µg/mL. ...
Background
Men with early-onset androgenetic alopecia (AGA) often have an abnormal hormonal milieu.
Objective
To ascertain the clinico-phenotypic characteristics and the prevalence of hormonal and metabolic changes in men with early-onset AGA.
Methods
Consecutive male patients less than 30 years of age with a Norwood-Hamilton grade ≥3 AGA were recruited in this comparative cross-sectional study. After endocrine evaluation they were classified into two groups, that is, Group A consisting of subjects with an altered hormonal profile and Group B with normal hormonal profiles. The groups were assessed for differences in disease phenotype and severity (Norwood-Hamilton grade), insulin resistance and parameters of metabolic syndrome (ATP III guidelines).
Results
Altered hormonal profiles were seen in 34 of the 100 subjects with AGA, while insulin resistance and metabolic syndrome were noted in 44 and 26 respectively. Altered hormonal profiles were significantly associated with insulin resistance and severe alopecia (grade 4 and above Hamilton-Norwood Scale). Insulin resistant Group A patients had a significantly higher prevalence of severe alopecia (>grade 4) ( P = 0.0036). The prevalence of metabolic syndrome was similar in both groups.
Limitation
The cross sectional study design was a drawback of this study. Further, a control arm without AGA was not included and the sample size of 100 was selected arbitrarily.
Conclusion
An altered hormonal profile and insulin resistance was noted in a third of the males with early-onset AGA. Subjects with altered hormonal profiles had a higher prevalence of insulin resistance and were likely to have severe grades of AGA.
... Because an androgenic environment in utero has been linked to neuroendocrine disruption in males (44,45), F 1 male offspring were generated and phenotyped concurrently with their female littermates. No differences in anogenital distance were observed between pAMH and VEH males (Fig. 4A). ...
... Kiss1 may colocalize with Ar in theca cells. However, studies using a theca cell-specific knockout of AR indicate that AR does not influence fertility or androgen levels in female mice (66), and our quantitative PCR experiments did not detect a significant decrease in ovarian Ar expression between Ctrl and assay beginning at age 3 months, Ctrl (VEH n = 15, pAMH n = 15), and KARKO (VEH n = 10, pAMH n = 9) were assessed for number of litters produced in 90 days (treatment × genotype, F 1, 45 pAMH induced reproductive changes in Ctrl but not KARKO mice across the board, suggesting a common underlying androgenic mechanism mediating all changes. The single exception to this pattern was in the male plugging assay, in which pAMH delayed copulatory behavior both in Ctrl and KARKO mice, suggesting that the effect may be driven by a mechanism distinct from that mediating all other phenotypes assayed. ...
Polycystic ovary syndrome (PCOS) is a common reproductive disorder characterized by elevated androgens and anti-Mullerian hormone (AMH). These hormones remain elevated throughout pregnancy, and potential effects of hormone exposure on offspring from women with PCOS remain largely unexplored. Expanding on recent reports of prenatal AMH exposure in mice, we have fully characterized the reproductive consequences of prenatal AMH (pAMH) exposure throughout the lifespan of first- and second-generation offspring of both sexes. We also sought to elucidate mechanisms underlying pAMH-induced reproductive effects. There is a known reciprocal relationship between AMH and androgens, and in PCOS and PCOS-like animal models, androgen feedback is dysregulated at the level the hypothalamus. Kisspeptin neurons express androgen receptors and play a critical role in sexual development and function. We therefore hypothesized that pAMH-induced reproductive phenotypes would be mediated by androgen signaling at the level of kisspeptin cells. We tested the pAMH model in kisspeptin-specific androgen receptor knockout (KARKO) mice and found that virtually all pAMH-induced phenotypes assayed are eliminated in KARKO offspring compared to littermate controls. By demonstrating the necessity of androgen receptor in kisspeptin cells to induce pAMH phenotypes, we have advanced understanding of the interactions between AMH and androgens in the context of prenatal exposure, which could have significant implications for children of women with PCOS.
... Androgenetic alopecia diagnosed before the age of 30-35 years often occurs in firstgeneration relatives of women with polycystic ovary syndrome and is commonly regarded as the phenotypic equivalent of polycystic ovary syndrome in men, which carries the risk of developing obesity, metabolic syndrome, type 2 diabetes, and cardiovascular disease [11]. It seems that early-onset androgenetic alopecia is a state of mild androgen excess. ...
... This finding indicates that men with early-onset androgenetic alopecia are phenotypically distinct from brothers of women with polycystic ovary syndrome. The obtained results also indicate that subjects with early-onset male-pattern baldness are characterized by impaired insulin sensitivity, which may partially explain their increased susceptibility to the development of obesity, metabolic syndrome, and type 2 diabetes [11]. ...
Introduction:
Administration of testosterone or dehydroepiandrosterone to subjects with low levels of these hormones was found to reduce thyroid antibody titers. Male-pattern baldness is accompanied by mildly increased androgen levels. The present study was aimed at investigating whether early-onset androgenetic alopecia determines the impact of exogenous levothyroxine on thyroid autoimmunity and hypothalamic-pituitary-thyroid axis activity in young men with autoimmune hypothyroidism.
Material and methods:
The study included two thyroid-antibody-matched groups of men with autoimmune hypothyroidism: subjects with early-onset androgenetic alopecia (group 1; n=24) and subjects with no evidence of hair loss (group 2; n=24). All patients were treated with exogenous levothyroxine. Circulating titers of thyroid peroxidase and thyroglobulin antibodies, as well as levels of thyrotropin, free thyroxine, free triiodothyronine, prolactin, total testosterone, calculated bioavailable testosterone, dehydroepiandrosterone-sulfate and estradiol were measured before levothyroxine treatment and 6 months later.
Results:
In both study groups, levothyroxine decreased thyroid antibody titers, reduced thyrotropin levels and increased free thyroid hormone levels. However, these effects were less pronounced in men with early-onset male-pattern baldness than in control men. The degree of reduction in antibody titers and thyrotropin levels correlated with baseline levels of total and calculated bioavailable testosterone, as well with baseline insulin sensitivity and treatment-induced improvement in insulin sensitivity. Concentrations of the remaining variables remained unchanged throughout the study period.
Conclusions:
The results of the current study suggest that the benefits of levothyroxine therapy in men with autoimmune hypothyroidism are less pronounced in individuals with early-onset androgenetic alopecia.
... Some studies of our group were published even earlier (Stárka et al., 2000(Stárka et al., , 2005Dušková et al., 2004). Currently, however, the male equivalent of PCOS has been demonstrated by multiple studies and has generally been accepted (Cannarella et al., 2017(Cannarella et al., , 2018(Cannarella et al., , 2020Di Guardo et al., 2019. ...
... Lowered SHBG likely plays a role, so that even in men with lower total testosterone the free fraction is still normal. Lowered SHBG levels were already documented in the first hormonal studies on the male equivalent of PCOS (Stárka et al., 2000) and confirmed in many later studies (Arias-Santiago et al., 2011;Sanke et al., 2016;Cannarella et al., 2017Cannarella et al., , 2018Cannarella et al., , 2020. Levels of free testosterone, however, do not by themselves explain the clinically observed hyperandrogenization, so other androgens must be considered, including the already-mentioned adrenal androgens, but also other less-studied markers such as adrenal 11-oxygenated C19-steroids. ...
The hypothesis that the most common female endocrine disease, the polycystic ovarian syndrome (PCOS), has a male equivalent, has recently become more widely accepted. The male form of PCOS is marked by alterations in the secretion of gonadotropins, increased insulin resistance, and changes of the levels of several steroid hormones, with clinical manifestations including premature androgenic alopecia (AGA). Because these symptoms are not always found in men with genetic predispositions, knowledge of the male equivalent of PCOS needs to be supplemented by measurements of adrenal 11-oxygenated C19 steroids, particularly 11-keto-, and 11β-hydroxy-derivatives of testosterone and dihydrotestosterone, by focusing on the newly-realized role of skin as an endocrine organ, and by confirming any age-related factors in glucose metabolism disorders in such predisposed men.
... There are a lot of studies showing the association of EAGA with insulin resistance and metabolic syndrome (3). Although it is really difficult to compare the results of the sex hormone parameters in male and female patients, there are studies in the literature that reports similar hormonal changes in men affected by the EAGA as seen in PCOS (5). It was found that this characteristic EAGA type is mostly present in male family members of PCOS women. ...
... The high DHEAS value is an important finding as DHEAS has some special features such as it has a long halflife and it doesn't have any pulsatility. It is widely accepted as a useful marker of hyperandrogenism in men (5,13). In this study, we didn't define any correlation between the DHEAS -ACTH levels but there correlation between F. testosterone and DHEAS was significant and positive. ...
Objective: Polycystic ovarian syndrome (PCOS) was thought to be a gynecologic disorder and then accepted as a general endocrine and metabolic syndrome. The genetic component of PCOS seems to be very important in its etiology. Because of this reason there should be a male PCOS equivalent. Early androgenetic alopecia (EAGA) is a specific pattern of hair loss and it should start before age 30 years and it is claimed to be a male equivalent of PCOS in women. Materials and Methods: In this study we aimed to investigate the hormonal and metabolic parameters of men with EAGA and compare them with healthy age-matched controls. Thirty men with EAGA and 30 controls were screened for free testosterone, DHEAS, gonadotropins, 17OH progesterone, ACTH, fasting glucose, fasting insulin, homocysteine and metabolic profile. Homeostasis model assessment (HOMA) results were used for the marker of insulin sensitivity. Alopecia classification was made by using the scale of Hamilton with Norwood modification. Results: Patients with EAGA had higher free testosterone (25,12±3,05 vs 21,3±1,77), DHEAS (634,90±27,09 vs 578±17,82), LH (9,16±0,28 vs 5,13±0,40). The EAGA group had insulin resistance but the control group did not (HOMA results were 3,34±0,47 vs 1,43±0,3). The homocysteine levels of EAGA group were higher than controls (12,37±1,31 vs 9,33±2,12) which is another cardiovascular risk factor. The correlations that we found in our study among HOMA, serum androgen levels, homocysteine and alopecia scores were positive in EAGA patients. We didn’t find any correlations among those parameters in control group. Because of these findings men with EAGA can be considered as male synonym to PCOS syndrome. These young men should be followed for the same long time risk profile like PCOS women. Insulin resistance and its results like metabolic syndrome, diabetes and cardiovascular diseases are real risks but there may be even a risk for infertility. Conclusion: We aimed to investigate whether EAGA can be accepted as the male phenotype of PCOS and if they have elevated risk factors for chronic complications than their age and sex matched controls.
... The high prevalence of PCOS worldwide suggests that there could be an evolutionary basis for the syndrome (43)(44)(45). The occurrence of a genetic basis for PCOS, and the evolutionary adaptive advantage of having this genotype, have also provided a rational basis for postulating the existence of a male equivalent of PCOS (46,47). A number of studies have found similar metabolic and endocrine changes in the male relatives of women with PCOS (47,48). ...
... A number of studies have found similar metabolic and endocrine changes in the male relatives of women with PCOS (47,48). The most studied clinical phenotype in males is premature androgenic alopecia (46,49). Genome-wide association studies have also identified genetic evidence of a male phenotype for PCOS (33). ...
Polycystic Ovary Syndrome (PCOS) is a clinical condition that effects millions of women world-wide. The pathophysiology of PCOS involves a series of reciprocal feedback mechanisms between biological, metabolic, immune and neuroendocrine systems. It is widely accepted that the pathogenesis of PCOS involves a complex interplay between inherited genetic polymorphisms, developmental epigenetic programming and a wide range of environmental factors that act together to cause the observed pathophysiological changes. International treatment guidelines emphasise the importance of lifestyle interventions as the first priority in the management of patients with PCOS.
In order to develop a model that encompasses all of these complex findings, it is necessary to examine the evolutionary and genetic origins of the observed metabolic and endocrine findings, the influence of in-utero epigenetic programming and the postnatal impact of lifestyle-related factors such as diet, physical activity, environmental chemicals, circadian disruption and stress. This manuscript provides an expanded discussion of the evolutionary and genetic components of the “transgenerational evolutionary theory” of the pathogenesis of PCOS. PCOS is increasingly being considered to be an ecological disorder. Having an evolutionary/ecological perspective has important implications for lifestyle-based treatment and prevention of PCOS.
... The genetic background of PCOS (105) suggests the existence of a male PCOS equivalent (106). Indeed, even male relatives inherit the same genetic factors predisposing to female PCOS. ...
... Also, still in the youth, PCOS women have a higher risk of developing GDM compared to their counterparts, and therefore, proper counseling has to be made in those women who wish to become pregnant (97). Interestingly, the evidence pointed out to the possible existence of a male PCOS equivalent (106), which, similarly to the classic female phenotype (119), deserves to be early detected to avoid its long-term cardiometabolic (125) and, possibly, reproductive complications. Several therapeutic choices are currently available for the management of PCOS women. ...
Polycystic ovary syndrome (PCOS) is a very common endocrine and metabolic disorder with the involvement of both genetic and environmental factors. Although much has been clarified on its pathogenesis, diagnosis, clinical manifestations, and therapy, there are still areas of uncertainty. To address fundamental concepts, novel aspects and hypotheses, and future perspectives, including the possible additional benefits of treatment with nutraceuticals, an expert consensus panel formed by endocrinologists and gynecologists was established. After an independent review of the literature, the panel convened electronically on February 3, 2020, and six resolutions were created, debated, and agreed upon discussion, and finally approved in their final form in a consensus livestream meeting held on April 15. The summary of the resolutions are: (1) PCOS is a well-established medical condition that negatively affects reproduction, general health, sexual health, and quality of life; (2) the symptoms and signs of PCOS appear early in life especially in female newborns from PCOS carriers; (3) women with PCOS have significantly increased risk of pregnancy-related complications including gestational diabetes mellitus; (4) a male PCOS equivalent exists, and it may impact on metabolic health and probably on reproduction; (5) the evidence supports that medical therapy for PCOS is effective, rational, and evidence-based; (6) the evidence supports a major research initiative to explore possible benefits of nutraceutical therapy for PCOS. The proposed resolutions may be regarded as points of agreement based on the current scientific evidence available.
... Lifestyle changes, such as diet modification, more physical activity (5), and some nutrient supplements, can reduce the risk of BPH (6). Because of the close relationship between BPH and metabolic conditions, some researchers have named BPH a new type of metabolic disease (7,8). ...
Introduction
Benign prostatic hyperplasia (BPH) is a frequent illness in aged men that impacts their quality of life; early childhood exposure to famines may have long-term effects on the chance of developing BPH. The aim of this study is to investigate the relationship between early-life famine exposure and benign prostatic hyperplasia (BPH) risk in Chinese men born during 1959–1961.
Methods
We used medical records from a large, comprehensive hospital to screen people born in China during the years of famine (1959–1961). Birthplaces were identified as indicators of famine exposure status. In the time window between 2017 and 2022, people born during the famine years who had prostatic ultrasonic examinations were selected, and their medical records were retrieved from the database. Univariate and multivariate logistic regression analyses investigated the relationship between famine exposure and BPH risk.
Results
A total of 3,009 subjects were included in this study. Patients with heavy famine exposure had older age, shorter height, lighter weight, lower cholesterol, lower uric acid (UA), lower aspartate aminotransferase (ALT), and a higher incidence of BPH than those with light famine exposure (all p < 0.05). Univariate logistic regression showed that BPH was positively related to famine exposure, age, height, weight, and body mass index (BMI) but negatively related to UA (all p < 0.05). Multivariate logistic regression showed that age and famine exposure were still independent risk factors ( p < 0.05), while UA was an independent protective factor for BPH ( p < 0.05). Heavy famine exposure increased the risk of BPH (adjusted OR = 1.214, 95% CI = 1.05–1.467, p = 0.045).
Conclusions and recommendation
Famine and malnutrition exposure during early life may be independent risk factors for BPH in Chinese adults. This relationship provides additional evidence to support the fetal origins of adult diseases and offers clues for the pathological mechanisms of BPH.
... Polycystic ovary syndrome (PCOS) is an important problem with a prevalence of 5-10% in women of reproductive age (1). It is an endocrine-metabolic disorder characterized by menstrual irregularities, anovulation, clinical and/or biochemical signs of hyperandrogenism (hirsutism and/or acne), micropolycystic ovaries and metabolic abnormalities (2). Some clinical and laboratory phenotypic features that are not included in the definition criteria for PCOS, but complement the clinical picture and influence the severity and morbidity of the disease, have also been defined (3,4). ...
Objective: The aim of this study was to investigate the clinical and demographic characteristics of patients diagnosed with polycystic ovary syndrome (PCOS) who were followed up in our hospital. Material and Methods: We conducted a retrospective, case-controlled observational study of patients treated at the PCOS Clinic of University of Health Sciences Etlik Zubeyde Hanim Women’s Health Training and Research Hospital between November 2023 and January 2024. The gynecologic history, demographic characteristics, and biochemical parameters of each patient were obtained from the hospital records. Results: The number of patients who presented to our PCOS outpatient clinic and were enrolled in the study was 48, and the mean age of the patients was 23±5.6 years. The mean body mass index was 26.1± 4.9 kg/m2. The most common reason for presentation to the PCOS outpatient clinic was irregular menstruation (83.3%). The most frequently observed phenotypic group was group A (47.9%). The preferred treatment was lifestyle modification (75.0%), the second most common treatment was oral contraceptives (45.8%). Conclusion: PCOS is one of the most common endocrine disorders worldwide and can affect women of all ages. In our study, the most common phenotype in our clinic was found to be group A. In addition to oral contraceptives, which are the treatment of first choice, lifestyle changes are also among the treatments used in patients.
... Występowanie AGA jest czynnikiem zwiększonego ryzyka chorób sercowo-naczyniowych, zaburzeń metabolizmu glukozy, cukrzycy typu 2 i powiększenia prostaty. [3,4,5,6,7] AGA jest dolegliwością uwarunkowaną czynnikami genetycznymi i hormonalnymi, związaną z nadmiernym pobudzeniem receptora androgenowego (AR) w komórkach mieszka włosowego. [8] Endogenne androgeny obejmują testosteron i dihydrotestosteron. ...
Androgenetic alopecia is the most common type of hair loss and affects at least 80% of men and half of women before the age of 70, with the incidence increasing with age. Androgenetic alopecia is an ailment conditioned by genetic and hormonal factors, associated with excessive stimulation of the androgen receptor in the cells of the hair follicle. With the development of medicine, more and more therapeutic methods for androgenetic alopecia appear on the market, including minoxidil, 5-α-reductase inhibitors, microneedling, platelet-rich plasma, low-energy laser therapy, rosemary oil, or siRNA. Thanks to the constantly growing amount of scientific research, progressively more is known about the mechanisms of androgenetic alopecia development and potential strategies to stop it. The article analyzes the literature using electronic databases and textbooks to compile methods that can be an effective alternative for people who do not want to undergo surgery. Some of the methods presented in the article have the potential to not only slow down, but also reverse the progression of the disease. However, each of them still has its limitations.
... Supporting evidence for this view can be found in a recent definition of "male PCOS" published by several authors [18]. The term PCOS in this case obviously refers to metabolic disorders with phenotypic signs that include alopecia, elevated BMI, erectile dysfunction, fertility problems, and prostate hyperplasia [19]. As previously discussed, all the phenotypic features characterizing PCOS in men reflect the existence of an endocrine and metabolic syndrome, which, as a consequence, produces aberrations in the reproductive apparatus. ...
Citation: Unfer, V.; Dinicola, S.; Russo, M. A PCOS Paradox: Does Inositol Therapy Find a Rationale in All the Different Phenotypes?. Int. J. Mol. Sci. 2023, 24, 6213. https:// Abstract: A recent evaluation of the published data regarding the PCOS topic has highlighted a paradox in the definition of this condition. Even though the name of the syndrome refers to ovarian dysfunction, it seems that patients diagnosed with PCOS are more likely affected by an endocrine and metabolic issue. The term PCOS might not be appropriate to indicate the phenotypes described by the Rotterdam criteria, since the only phenotype with a gynecological issue alone is PCOS phenotype D. This novel perspective regarding how PCOS is currently defined leads the way to a reinterpretation of the entire pathological context and the treatment prescribed, such as inositols. A new point of view on the etiopathogenesis of the disease completely changes the current meaning of PCOS and consequently the therapeutic rationale evaluated to date.
... La obesidad, el síndrome metabólico, síndrome de ovarios poliquísticos, así como la deficiencia de algunos esfingolípidos por parte de los adipocitos, son entre otras patologías los principales factores de riesgo para desarrollar resistencia a la insulina (RI). 1,2 La obesidad es un problema de salud pública en países en vías de desarrollo y su asociación con alteraciones en los lípidos, 3 con diabetes mellitus tipo 2 (DM2) y con enfermedades cardiovasculares también sigue en ascenso. El riesgo de síndrome de muerte súbita es 3 veces mayor en personas obesas; la posibilidad de que estos pacientes desarrollen DM2 es 93 veces mayor cuando el índice de masa corporal (IMC) supera los 35 kg/m2. ...
Introduction: Genetics, obesity and the metabolic syndrome are the main risk factors in the development of insulin resistance (IR). IR is associated with diabetes mellitus 2, obesity and cardiovascular diseases, among others. Our aim was to reduce insulin resistance by treatment with low doses of polyunsaturated fatty acids (PUFAs, 300 mg/day) in people diagnosed with IR. Material and Methods: 20 subjects between 18 and 60 years were studied. 14 subjects had grade 1 obesity and 6 people had grade 2 obesity. Acanthosis nigrans was found in 10 subjects. Glucose, cholesterol, triglycerides, and insulin levels were measured. The HOMA, QUICKI indexes and the atherogenic index of plasma were calculated. Two samples were taken, before administration of PUFAs and 8 days after the administration of PUFAs. Results: Reduced triglycerides (p=0,0001), glucose (p=0,0040), and insulin (p=0,0295) levels were found, also the HOMA (p=0,0085) and the QUICKI index (p=0,0081), and the atherogenic index of plasma (p=0,002) were significantly different. Conclusions: Insulin resistance indies ameliorated with low doses of PFA by oral administration, also triglyceri-des and the atherogenic index of plasma were diminished significantly.
... As for women with PCOS, psychiatric disorders have also been reported [11]. An increased prevalence of early-onset (<35 years) androgenic alopecia (AGA) is observed in male relatives of women with PCOS, which has been proposed as a phenotypic sign of the male PCOS equivalent [12]. It is more likely that AGA is related to their high dehydroepiandrosterone, 17α-hydroxyprogesterone and low sex hormone-binding globulin levels, than to their testosterone concentrations for which the data are contradictory. ...
This article reviews the main findings on anti-Müllerian hormone (AMH) and its involvement in the pathogenesis of polycystic ovary syndrome (PCOS) and its male equivalent. In women, AMH is produced by granulosa cells from the mid-fetal life to menopause and is a reliable indirect marker of ovarian reserve. AMH protects follicles from atresia, inhibits their differentiation in the ovary, and stimulates gonadotrophin-releasing hormone neurons pulsatility. AMH overexpression in women with PCOS likely contributes to the increase of the follicle cohort and of androgen levels, leading to follicular arrest and anovulation. In the male, AMH is synthesized at high levels by Sertoli cells from fetal life to puberty when serum AMH falls to levels similar to those observed in women. AMH is involved in the differentiation of the genital tract during fetal life and plays a role in Sertoli and Leydig cells differentiation and function. Serum AMH is used to assess Sertoli cell function in children with disorders of sex development and various conditions affecting the hypothalamic–pituitary–testicular axis. Although the reproductive function of male relative of women with PCOS has been poorly investigated, adolescents have elevated levels of AMH which could play a detrimental role on their fertility.
... An aberrant intrauterine environment would also be expected to have detrimental effects also on male fetuses, but this is less studied. There is no wellestablished male PCOS phenotype in mouse or man, although early androgenetic alopecia in men is proposed as a sign of hormonal and metabolic abnormalities (ie, a male PCOS equivalent) (74). Indeed, both sons (75)(76)(77) and brothers (78)(79)(80)(81)(82)(83)(84) of women with PCOS display cardiometabolic and reproductive dysfunctions. ...
Polycystic ovary syndrome (PCOS) is a complex disease affecting up to 15% of women in reproductive age. Women with PCOS suffers from reproductive dysfunctions with excessive androgen secretion and irregular ovulations leading to reduced fertility and pregnancy complications. The syndrome is associated with a wide range of comorbidities including type 2 diabetes, obesity, and psychiatric disorders. Despite the high prevalence of PCOS, the etiology remains unclear. To understand the pathophysiology of PCOS, how it is inherited, and how to predict, prevent and treat women with the syndrome, animal models provide an important approach to answer these fundamental questions. This minireview summarizes recent investigative efforts on PCOS-like rodent models aiming to define underlying mechanisms of the disease and provide guidance in model selection. The focus is on new genetic rodent models, on a naturally occurring rodent model, and provides an update on prenatal and peripubertal exposure models.
... Malepattern hair loss diagnosed before the age of 30-35 years and reaching at least stage 3 of Hamilton-Norwood classification is termed as early-onset androgenic alopecia [3]. This disorder is a frequent finding in first-generation male relatives of women with polycystic ovary syndrome [4], and both disorders share similar genetic backgrounds (CAG and GGC triplet repetition polymorphisms, WNT10A gene mutations and APCDD1 gene mutations) [5,6]. Moreover, hormonal and metabolic abnormalities characterizing early-onset androgenic alopecia (elevated levels of testosterone, dehydroepiandrosterone-sulfate [DHEA-S], luteinizing hormone [LH] and prolactin, decreased levels of follicle-stimulating hormone [FSH] and sex hormone-binding globulin, higher values of the free androgen index and the LH/FSH ratio, and insulin resistance) resemble those observed in women with polycystic ovary syndrome and their brothers [7][8][9]. ...
Background
Early-onset androgenic alopecia is considered the phenotypic equivalent of polycystic ovary syndrome in men. The purpose of the current study was to investigate whether the presence of early-onset male-pattern baldness modulates metabolic effects of metformin.
Methods
This prospective case–control study included 2 groups of men at high risk for type 2 diabetes: 72 individuals with androgenic alopecia (group A) and 75 subjects with normal hair growth (group B). Both groups were matched for age, blood pressure, body mass index, insulin sensitivity and plasma lipids. Glycated hemoglobin, glucose, plasma lipids, indices of insulin sensitivity/resistance, sex hormones, high-sensitivity C-reactive protein (hsCRP) and 25-hydroxyvitamin D were determined before and after metformin treatment (1.7 g daily).
Results
Twelve-month metformin treatment reduced fat content, waist circumference, glycated hemoglobin, glucose and triglycerides, as well as improved insulin sensitivity. Although observed in both study populations, these effects were more pronounced in group B. Moreover, metformin decreased hsCRP and bioavailable testosterone levels in group B, as well as reduced 25-hydroxyvitamin D concentration in group A. Treatment-induced changes in glucose homeostasis markers correlated with the impact of metformin on hsCRP and 25-hydroxyvitamin D levels.
Conclusions
Metabolic effects of metformin in males are attenuated if they have coexisting early-onset androgenic alopecia. This finding may be partially explained by differences in severity of low-grade systemic inflammation and vitamin D status. The obtained results, requiring confirmation in large prospective studies, suggest that men with early-onset male-pattern baldness benefit to a lesser degree from metformin treatment than other men at high risk for type 2 diabetes.
... There are a lot of studies showing the association of EAGA with insulin resistance and metabolic syndrome [2]. Although it is really difficult to compare the results of the sex hormone parameters in male and female patients, there are studies in the literature that reports similar hormonal changes in men affected by the EAGA as seen in PCOS [4]. It was found that this characteristic EAGA type is mostly present in male family members of PCOS women. ...
The genetic component of Polycystic ovarian syndrome (PCOS) proved to play an important role in its etiology. Early androgenetic alopecia (EAGA) is widely accepted as its male equivalent of PCOS if it starts before age of 30. In this study, we aimed to investigate metabolic and oxidative stress parameters of men with EAGA and compare them with healthy age-matched controls. Fasting glucose, fasting insulin, homocysteine, serum malondialdehyde (MDA), total antioxidant capacity (TAC), folic acid, and vitamin B12 were measured from the blood samples of thirty men with EAGA and 30 controls. Homeostasis model assessment (HOMA) results were used for the marker of insulin sensitivity. Alopecia classification was made by using the scale of Hamilton with Norwood modification. We demonstrated a significantly lower TAC activity (p [Med-Science 2021; 10(2.000): 609-13]
... Obesity, MetS, insulin resistance, T2DM and hypogonadism are closely linked in men. 10,11 Strong evidence has been reported on the relationship between the maintenance of normal metabolic parameters and the testicular function. Both MetS and T2DM associate with TD and levels of total and free T are inversely correlated with the body mass index (BMI). ...
Male hypogonadism, defined as an inadequate production of testosterone (T), is associated with a greater morbidity and mortality. Epidemiological studies identified T deficiency as a risk factor for cardiovascular disease. Also, low serum T levels impact on glucose homeostasis through a worse glucose uptake, utilization, and disposal, and the general negative impact on metabolism. The aim of this review is to provide a comprehensive and updated overview of the effects of T replacement therapy on metabolic and cardiovascular systems and prostate tissue in patients with hypogonadism, including molecular mechanisms through which T exerts its actions. Furthermore, recent findings on novel coronavirus disease (COVID-19) epidemiology have shown a greater mortality in male compared with female patients and a role of T in promoting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection of the host cells has been demonstrated. Hence, the secondary aim of this review is to provide preliminary indications on the management in patients with COVID-19.
... In addition, the second Nord-Trondelag Health Study, involving 21,694 patients, showed a higher risk for LUTS in patients with diabetes mellitus than in non-diabetic men [125], being the risk of BPH even fourfold higher in diabetic patients with high LDL cholesterol serum levels [126]. Taken together, these data strongly highlight the close association between LUTS-BPH with metabolic abnormalities and cardiovascular risk factors which has been ascribed by some authors to the male equivalent of polycystic ovarian syndrome (PCOS) occurring in these men [127][128][129]. In this view, the role of PDE-5i on metabolism and endothelial dysfunction deserves to be promoted and further addressed by focused studies. ...
Introduction:
Benign prostate hyperplasia (BPH) is one of the most prevalent diseases in aging men. It may adversely affect quality-of-life due to the presence of low urinary tract symptoms (LUTS) and its effects on sexuality.
Areas covered:
The impact of α1-blockers, 5α-reductase inhibitors (5-ARI), and phosphodiesterase 5 inhibitors (PDE-5i) on erectile and ejaculatory functions in men with BPH are covered. Endocrinological aspects have also been addressed, including the management of hypogonadism, which affects many patients with BPH, and the impact of the use of 5-ARI use on bone health.
Expert opinion:
The adverse-event profile of α1-blockers depends on their affinity for the α1-adrenoceptors rather than selectivity. The probability of ejaculatory dysfunction is highest with silodosin than other nonselective drugs (tamsulosin, alfuzosin, doxazosin, and terazosin). Concerning the impact of finasteride and dutasteride on sexual desire, erectile function, and ejaculation, the vast majority of the studies have shown a low prevalence of treatment-related adverse events. Due to the benefits of erection, PDE5i represents the perfect class of drugs for the treatment of LUTS-BPH in patients with erectile dysfunction. Testosterone replacement therapy could be considered in some hypogonadal patients with BPH. Finally, current evidence support the safety of 5-ARI on bone tissue.
... The precise gene influenced has not still been fixed. The clinical acuity of PCOS features seems to become mostly fixed via causes such as obesity [69][70][71][72][73][74] . Hyperandrogenism Hyperandrogenism (HA) is often looked to be the crucial chief characteristic stamp of PCOS and was relevant to early events of this disturbance in 1935 by Stein and Leventhal. ...
Polycystic Ovary Syndrome (PCOS) is the most prevalent hormone disorder of fruitful-aged women in the entire world. This rapid review aims to highlight the essential clinical points face up to physicians and their patients in identify PCOS in different age stage and its complications in female's life Introduction Throughout the last 20th years, the issue of Polycystic ovary syndrome (PCOS) has risen as a genuine problem for women in the world. What is PCOS? PCOS is the most spreadendocrinopathy-metabolic irregularities in adult females of childbearing age, recognized by menstrual irregularities, androgenemia, and polycystic ovaries 1-4. Its morphology is seen on ultrasound in nearly 22% of women 5, with prevalence among females of reproductive age in the wide-ranging population has been estimated at 5.6%-16% reported by recent studies 6.PCOS infertility cover more than one-fourth of the reason for infertility 7. Additionally, it is valued that 90% of totally anovulation conditions are affected by PCOS 8 Polycystic ovaries (PCO) are engage symptoms in patients with PCOS, hence the term of the syndrome. PCO is defined as an ovarian size of larger than 10 milliliters and/or existence of 12 or more follicles measuring 2-9 mm in diameter in both ovary 9. It is assessed that PCO is currently more than 75% of patients with PCOS 10 even so, 20% of females in the overall population also have PCO 11.
... PCOS disease is developed only in the reproductive-aged women; whereas, T2D will occur in both genders. However, Cannarella et al [84] studies confirmed the PCOS symptoms was observed in male subjects. From this review work, the author concludes as PCOS is connected by IR and other metabolic diseases, but genetically there was no link established. ...
Polycystic ovarian syndrome (PCOS) in reproductive-aged women is identified to be one of the endocrine disorders. This heterogeneous disorder is categorized through oligo-anovulation and hyperandrogenemia. National institutes of health and Rotterdam criterions were used to diagnose PCOS women. Type 2 Diabetes (T2D) is one of the complications in PCOS which is connected through insulin resistance (IR), which is a condition in which liver, muscles and fat infrequently respond to the hormones, and this leads to extreme IR and consequently leads to T2D disease. PCOS is inherited by the autosomal dominant mode of inheritance and may also with the different intricate patterns. Till now, many studies have been performed in PCOS with the genes identified by T2D and till now no studies have shown the similar genetic association and pathophysiology between both the diseases. So, the current review aims to investigate the genetic relation between PCOS and T2D and why both the diseases cannot be reverted. In this review, published data were screened with the T2D related genes and single nucleotide polymorphisms in PCOS women. The case-control, hospital-based and meta-analysis molecular studies disclosed both positive and negative connotations. Genetically, no relationship has been established between PCOS and T2D. Maximum studies have shown as PCOS women had developed T2D later in life because as a risk-factor, but none of the studies documented T2D women having developed PCOS as a risk factor. Apart from this, the disease PCOS is developed in women with reproductive age and T2D develops in both the men and women during adulthood. This review concludes as there is a genetic relation only in between PCOS and T2D, but not with T2D to PCOS and further it cannot be explicitly reverted from T2D to PCOS.
... For example, the exposure of female foetuses to elevated maternal androgen levels is suspected to contribute to the development of some forms of polycystic ovary syndrome (PCOS) 8,9 , a prevalent female neuroendocrine disorder 8,10 . Notably, there is also some evidence linking an elevated maternal androgen environment to similar disruptions in the reproductive axis of males 11,12 . However, given the critical role that foetal testosterone plays in normal sexual differentiation of males, it is not clear how maternal androgen excess impacts the function of the adult male reproductive axis. ...
Prenatal androgen excess is suspected to contribute to the development of polycystic ovary syndrome (PCOS) in women. Evidence from preclinical female animal models links maternal androgen excess with the development of PCOS-like features and associated alterations in the neuronal network regulating the reproductive axis. There is some evidence suggesting that maternal androgen excess leads to similar reproductive axis disruptions in men, despite the critical role that androgens play in normal sexual differentiation. Here, the specific impact of maternal androgen excess on the male hypothalamic-pituitary-gonadal axis was investigated using a prenatal androgenization protocol in mice shown to model PCOS-like features in females. Reproductive phenotyping of prenatally androgenised male (PNAM) mice revealed no discernible impact of maternal androgen excess at any level of the reproductive axis. Luteinising hormone pulse characteristics, daily sperm production, plasma testosterone and anti-Müllerian hormone levels were not different in the male offspring of dams administered dihydrotestosterone (DHT) during late gestation compared to controls. Androgen receptor expression was quantified through the hypothalamus and identified as unchanged. Confocal imaging of gonadotropin-releasing hormone (GnRH) neurons revealed that in contrast with prenatally androgenised female mice, PNAM mice exhibited no differences in the density of putative GABAergic innervation compared to controls. These data indicate that a maternal androgen environment capable of inducing reproductive dysfunction in female offspring has no evident impact on the reproductive axis of male littermates in adulthood.
... PCOS is a hyperandrogenetic syndrome 21 and patients present with a combination of infertility, hirsutism, acne, menstrual changes and metabolic syndrome 19,21 . Although PCOS is a well-defined clinical syndrome that only affects females, it has recently been suggested that there may be a male equivalent characterised by early-onset MPB and metabolic syndrome 22 n_Height = 697). Volcano plots and a histogram (using absolute z-score) were generated of z-scores ( Supplementary Fig.6). ...
Homo sapiens, despite being the most hairless among apes, places profound importance on the limited hair they possess due to its role in sexual identification and identity [1]. This has led to a surge in the market for hair-care products and management techniques in the last two decades, accompanied by a renewed interest in the physiology, pathology, and management of hair. This chapter critically examines various aspects, including the pathophysiology and psychology of hair loss, and provides an overview of the current state of management.
Both hyperprolactinemia and early-onset androgenic alopecia are associated with increased cardiometabolic risk. The aim of this study was to assess whether early-onset male-pattern baldness modifies cardiometabolic effects of bromocriptine in men with prolactin excess. The study included two groups of men with prolactin excess: individuals with early-onset androgenic alopecia (group 1) and individuals with normal hair growth (group 2). Both groups were matched for age, smoking habits, the body mass index, blood pressure and prolactin levels. Over the entire study period (4 months), all participants were treated with bromocriptine (7.5 mg daily). Plasma levels of hormones (prolactin, total testosterone and bioavailable testosterone), glucose homeostasis markers, lipids, uric acid, high-sensitivity C-reactive protein (hsCRP), fibrinogen and homocysteine, and the urinary albumin-to-creatinine ratio (UACR) were measured at the beginning and at the end of the study period. Both groups differed in total testosterone, bioavailable testosterone, insulin sensitivity, HDL-cholesterol, triglycerides, uric acid, hsCRP, fibrinogen, homocysteine and UACR. In both groups, bromocriptine reduced prolactin, increased total and bioavailable testosterone, improved insulin sensitivity, and decreased uric acid, hsCRP and homocysteine. The impact on prolactin, insulin sensitivity, uric acid, hsCRP and homocysteine was stronger in group 2 than group 1. Only in group 2, the drug increased HDL-cholesterol and decreased triglycerides, fibrinogen and UACR. The impact on cardiometabolic risk factors correlated with a reduction in prolactin levels, the improvement in insulin sensitivity, and in group 1 inversely with testosterone levels. The obtained results suggest that men with early-onset androgenic alopecia are partially resistant to cardiometabolic effects of bromocriptine. This article is protected by copyright. All rights reserved.
Males with early‐onset androgenic alopecia are characterized by elevated androgen levels. The aim of the present study was to investigate whether the presence of this condition modulates the impact of metformin on pituitary hormone production. This study compared two groups of young men with prediabetes, matched for age, blood pressure and insulin sensitivity: 23 subjects with early‐onset male‐pattern baldness (group 1) and 25 individuals with normal hair growth (group 2). Throughout the study, both groups were treated with metformin for six months. Circulating levels of glucose, insulin, glycated hemoglobin, gonadotropins, thyrotropin, prolactin, ACTH, insulin‐like growth factor‐1 and androgens were determined at the beginning of the study and six months later. At entry, LH, the LH/FSH ratio, total testosterone, bioavailable testosterone, ACTH and DHEA‐S were higher in group 1 than in group 2. The effect of metformin on fasting glucose, insulin sensitivity and glycated hemoglobin was more pronounced in group 2 than in group 1. Only in group 1, metformin reduced LH levels and the LH/FSH ratio. Metformin did not affect plasma levels of the remaining hormones. In untreated men with androgenic alopecia (group 3, n = 22), glucose homeostasis markers and hormone levels remained at a similar level throughout the study period. The obtained results suggest that the impact of metformin on gonadotroph secretory function is stronger in men with early‐onset androgenic alopecia than in men with normal hair growth. Metformin treatment may protect men with early‐onset androgenic alopecia against the development of gonadotroph hyperplasia and/or of focal testicular changes. This article is protected by copyright. All rights reserved
Women with polycystic ovary syndrome are at high cardiometabolic risk. Early-onset male-pattern baldness is considered the phenotypic equivalent of polycystic ovary syndrome in men. The aim of the present study was to assess whether early-onset androgenetic alopecia modifies cardiometabolic effects of lisinopril in men with arterial hypertension. The study population consisted of 62 young men with grade 1 hypertension, 31 of whom were diagnosed with early-onset male-pattern baldness (group A). Thirty-one blood pressure-matched men with normal hair growth (group B) served as a control group. All participants were treated with lisinopril (10-40 mg daily). Blood pressure, glucose homeostasis markers, urinary albumin-to-creatinine ratio (UACR), as well as plasma levels of uric acid, high-sensitivity C-reactive protein (hsCRP), fibrinogen, homocysteine, total and calculated free testosterone, dehydroepiandrosterone-sulfate and estradiol were assessed before lisinopril treatment and six months later. At baseline, levels of all cardiometabolic risk factors were higher in group A than group B. Although lisinopril reduced systolic and diastolic blood pressure, UACR, hsCRP and fibrinogen in both study groups, these effects were stronger in group B than in group A. Only in group B, the drug decreased levels of uric acid and homocysteine, as well as improved insulin sensitivity. The impact of lisinopril on uric acid, hsCRP, fibrinogen, homocysteine and UACR correlated weakly with its hypotensive properties, androgen levels and insulin sensitivity. The obtained results suggest that cardiometabolic effects of lisinopril in men are less pronounced in case of coexisting early-onset androgenetic alopecia.
Benign prostate hyperplasia (BPH), one of the most common diseases in older men, adversely affects quality-of-life due to the presence of low urinary tract symptoms (LUTS). Numerous data support the presence of an association between BPH-related LUTS (BPH-LUTS) and metabolic syndrome (MetS). Whether hormonal changes occurring in MetS play a role in the pathogenesis of BPH-LUTS is a debated issue. Therefore, this article aimed to systematically review the impact of hormonal changes that occur during aging on the prostate, including the role of sex hormones, insulin-like growth factor 1, thyroid hormones, and insulin. The possible explanatory mechanisms of the association between BPH-LUTS and MetS are also discussed. In particular, the presence of a male polycystic ovarian syndrome (PCOS)-equivalent may represent a possible hypothesis to support this link. Male PCOS-equivalent has been defined as an endocrine syndrome with a metabolic background, which predisposes to the development of type II diabetes mellitus, cardiovascular diseases, prostate cancer, BPH and prostatitis in old age. Its early identification would help prevent the onset of these long-term complications.
Infertility is one of the most common non communicable diseases affecting both men and women equally. Ovarian reserve, the number of primordial follicles in the ovaries is believed to be the most important determinants for women fertility. Anti-Müllerian hormone (AMH) secreted from granulosa cells of growing follicles is recognized as the most important biomarker for ovarian reserve. Ovarian reserve models have been developed using AMH and other hormonal indicators, thus childbearing plans and reproductive choices could be arranged by women. In assisted reproductive technology (ART) cycles, measurement of AMH helps to predict ovarian response and guide recombinant follicle-stimulating hormone dosing in women. Serum AMH level is increasingly being recognized as a potential surrogate marker for poly cystic ovarian morphology (PCOM) one of the criteria for diagnosis of poly cystic ovarian syndrome (PCOS). AMH is also secreted by Sertoli cells of testes in men, and AMH measurements in the prediction of surgical sperm recovery rate in men has also been investigated. AMH levels are significantly higher in boys than in girls before puberty. Therefore, serum levels of AMH in combination with testosterone is used for the differential diagnosis of disorders of sex development, anorchia, nonobstructive azoospermia, and persistent Müllerian duct syndrome. Recently, serum AMH measurement is also used in fertility preservation program in oncofertility, screening for granulosa cell tumors and prediction of menopause applications. In this review, we will focus on clinical application of AMH in fertility assessment for healthy men and women, as well as for cancer patients.
Recent studies identified the presence of a male polycystic ovarian syndrome (PCOS), which mainly affects men whose female relatives are afflicted with PCOS, caused by genes responsible for the susceptibility of this syndrome in women. Similar hormonal, metabolic, and clinical alterations occurring in PCOS women have also been reported in their male relatives, suggesting a association between the male and female forms of the syndrome. Although the remarkable clinical manifestation of the male equivalent PCOS is diagnosed by the early-onset androgenetic alopecia, character-ized by hair recession, pronounced hypertrichosis, insulin resistance, biochemical and hormonal abnormalities, the hormonal/metabolic profile is still controversial. Men affected by early-onset androgenetic alopecia (AGA) are at risk of developing hyperinsulinemia, insulin-resistance, dyslipidaemia, and cardiovascular diseases. However, there is no consensus on the association of male equivalent PCOS with hypertension and obesity. Moreover, reduced levels of sex hormone-binding globulin have been detected in these male patients, accompanied by increased free androgens. Conversely, literature reported lower concentrations of testosterone in male equivalent PCOS when compared with the normal range, indicating a crucial role for the conversion of cortical androgens. Finally, further studies are warranted to investigate a possible link among AGA, metabolic/hormonal alterations, and acne. Our study assessed the hormo-nal, metabolic and clinical aspects of male equivalent PCOS syndrome reported in the literature to evaluate similar and divergent elements involved in the female version of the syndrome.
PCOS is a common and heterogeneous endocrine disorder in women of reproductive age, frequently associated with metabolic abnormalities. It was estimated that about 75% of these subjects have an impairment of insulin action, as measured by gold standard methods. While the relationship between insulin resistance and PCOS is consistently shown by a number of studies, the mechanisms underlying its primary origin still remains an unsolved issue. Insulin resistance and the associated hyperinsulinemia can induce both the endocrine and reproductive traits of PCOS. However, androgen excess, in turn, can impair insulin action, directly and/or through several changes occurring in different tissues. Body fat excess, which is another common feature in these women, can contribute to worsening the whole picture. Nevertheless, insulin resistance may also be found in many normal-weight individuals. Endocrine and metabolic abnormalities can develop in different moments, and probably there is fetal programming of these alterations. However, a number of vicious circles, with bidirectional relationships between androgen excess and insulin resistance, and with the contribution of several other factors, make it extremely difficult to understand where this process really originates. This review summarizes available evidence on this topic, in order to better understand the complex relationships linking hyperandrogenism and impaired insulin action in women with PCOS.
Polycystic ovarian syndrome (PCOS) is a frequent disorder commonly found in reproductive-aged
women. The disease PCOS in women is considered to be complex heterogeneity, which indicates the
combined combination of genetics and environmental interaction factors. Insulin resistance, type 2
diabetes mellitus, and obesity are known to be the risk factors for the development of PCOS. The
prevalence of obesity in Saudi Arabia is ripening equally in both men and women. Herbal Medicines
are often used for the treatment of human diseases by traditional medicine. Herbal remedies are
often used to treat PCOS women due to the similar effectiveness exists as Western anti-obesity drugs.
This study aimed to acknowledge the usage of herbal medicines for the prevention of obesity in PCOS
women. This is a cross-sectional study carried out in reproductive-aged women in the Saudi population.
PCOS women were provided with the questionnaire form if they are using the herbal products for
the treatment of obesity. In this study, 85 PCOS women with obesity have been selected. The clinical
and usage of herbal details have been recorded. In this study, 70.5% of women were using green tea,
19.8% and 11.7% were using the ginger and flax seeds. Turmeric, Capsicum and fenugreeks were used
by 25.8%, 4.7% and 18.8% respectively. In conclusion, the PCOS women has high usage of green tea
rather than other herbal medicines.
Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder affecting women of reproductive age. The origin of PCOS is still not clear and appears to be a function of gene × environment interactions. This review addresses the current knowledge of the genetic and developmental contributions to the etiology of PCOS, the ovarian and extraovarian mediators of PCOS and the gaps and key challenges that need to be addressed in the diagnosis, treatment and prevention of PCOS. © 2018 Society for Endocrinology Published by Bioscientifica Ltd.
Objective:
To investigate for differences in reproductive hormone levels in male relatives of women with polycystic ovary syndrome (PCOS).
Design:
Cross-sectional study.
Setting:
Academic medical center.
Patient(s):
Sixty-three fathers and 66 brothers of women with PCOS as well as two groups of control men of comparable age to fathers (older control, n = 30) and brothers (younger control, n = 58).
Intervention(s):
A single early morning fasting blood sample was obtained for the measurement of reproductive hormone levels.
Main outcome measure(s):
Testosterone, LH, FSH, antimüllerian hormone (AMH), inhibin B, E2, and estrone (E1) levels were measured.
Result(s):
The AMH, LH, and FSH levels were significantly increased in male relatives compared with their respective control groups. The levels of E2, E1, T, and inhibin B did not differ between the groups.
Conclusion(s):
The AMH, LH, and FSH levels were increased in adult male relatives of women with PCOS, suggesting that they may have altered testicular function and changes in neuroendocrine regulation of gonadotropin secretion. These changes may reflect effects of PCOS susceptibility genes such as the recently mapped chromosome 11p14.1 locus in the region of the FSH B polypeptide gene.
Polycystic ovary syndrome (PCOS) is a common, highly heritable complex disorder of unknown aetiology characterized by hyperandrogenism, chronic anovulation and defects in glucose homeostasis. Increased luteinizing hormone relative to follicle-stimulating hormone secretion, insulin resistance and developmental exposure to androgens are hypothesized to play a causal role in PCOS. Here we map common genetic susceptibility loci in European ancestry women for the National Institutes of Health PCOS phenotype, which confers the highest risk for metabolic morbidities, as well as reproductive hormone levels. Three loci reach genome-wide significance in the case-control meta-analysis, two novel loci mapping to chr 8p32.1 and chr 11p14.1, and a chr 9q22.32 locus previously found in Chinese PCOS. The same chr 11p14.1 SNP, rs11031006, in the region of the follicle-stimulating hormone B polypeptide (FSHB) gene strongly associates with PCOS diagnosis and luteinizing hormone levels. These findings implicate neuroendocrine changes in disease pathogenesis.
Androgenic alopecia as a physiologic process and benign prostatic hyperplasia (BPH) as a pathologic process in the older population are androgen-dependent processes influenced by 5-alpha reductase enzyme which converts testosterone to dihydrotestosterone. This cross sectional study was done to evaluate the relationship between androgenic alopecia and BPH. 150 men older than 50 years old, who presented to the free prostate screening clinic, were included. They were asked about urinary symptoms. PSA level, prostate volume with sonography and alopecia grading using Hamilton-Norwood classification (grade I to VII) were evaluated. Analysis was done by SPSS statistical method. 59.6% of men had mild alopecia (grade I, II, III), 34.1% had moderate alopecia (grade IV, V) and 6.3% had severe alopecia (grade VI, VII).The mean PSA level was 1.37 ± 1.48 ng/ml. The minimum PSA level was 0.1 ng/ml, and the maximum level was 6.8 ng/ml. The mean prostate volume was 37.85 ± 21.85cc. The minimum prostate size was 10 ml, and the maximum volume was 173 ml. The mean international prostate symptom score (IPSS) was 7.6 ± 6.11 with the minimum score 0 and the maximum score 27. However, no relationship between these parameters and androgenic alopecia was detected. This study showed that there is no relationship between androgenic alopecia, PSA level, IPSS, and prostate volume. Occurrence of alopecia in younger age and a positive family history correlated with a higher grade of alopecia.
STUDY QUESTION Are there abnormalities in gonadotrophin secretion, adrenal steroidogenesis and/or testicular steroidogenesis in brothers
of women with polycystic ovary syndrome (PCOS)?
Alopecia in male is considered as a genetically determined disorder characterized by increased level of local androgen metabolite and increase androgen receptor binding in balding areas. Frequent deviations of hormones from normal values have been reported in men diagnosed with premature androgenetic alopecia (AGA) especially for androgens, gonadotropins and sex hormone binding globulin (SHBG). Different studies in the past have inferred that premature baldness before the age of thirty in males could be considered equivalent to the polycystic ovary syndrome (PCOS) in female.
Hormonal profile of 50 men with severe premature balding before 30 years of age were compared with same numbers of age matched controls. The serum concentrations of total testosterone, dehydroepiandrosterone sulfate, luteinizing hormone, follicle stimulating hormone, SHBG, insulin and fasting blood sugar were estimated. Statistical analysis was performed with paired Student's t-test for cases and controls.
Decreased levels of SHBG with high free androgen index were found in cases when compared with the controls.
Though altered hormonal profile may coexist in some of men with premature AGA it can't be considered as male equivalent to PCOS in female or the metabolic syndrome.
Testosterone level is low in insulin-resistant type 2 diabetes. Whether this is due to negative effects of high level of insulin on the testes caused by insulin resistance has not been studied in detail. In this study, we found that insulin directly binds to insulin receptors in Leydig cell membranes and activates phospho-insulin receptor-β (phospho-IR-β), phospho-IRS1, and phospho-AKT, leading to up-regulation of DAX-1 (dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1) gene expression in the MA-10 mouse Leydig cell line. Insulin also inhibits cAMP-induced and liver receptor homolog-1 (LRH-1)-induced steroidogenic enzyme gene expression and steroidogenesis. In contrast, knockdown of DAX-1 reversed insulin-mediated inhibition of steroidogenesis. Whether insulin directly represses steroidogenesis through regulation of steroidogenic enzyme gene expression was assessed in insulin-injected mouse models and high fat diet-induced obesity. In insulin-injected mouse models, insulin receptor signal pathway was activated and subsequently inhibited steroidogenesis via induction of DAX-1 without significant change of luteinizing hormone or FSH levels. Likewise, the levels of steroidogenic enzyme gene expression and steroidogenesis were low, but interestingly, the level of DAX-1 was high in the testes of high fat diet-fed mice. These results represent a novel regulatory mechanism of steroidogenesis in Leydig cells. Insulin-mediated induction of DAX-1 in Leydig cells of testis may be a key regulatory step of serum sex hormone level in insulin-resistant states.
Background: High insulin in T2D is associated with low testosterone, but the role of insulin has not been fully studied in testis.
Results: Insulin directly inhibits testicular steroidogenesis via induction of DAX-1 in Leydig cells.
Conclusion: Insulin induces DAX-1 in Leydig cells, and DAX-1 inhibits LRH-1-mediated testicular steroidogenesis.
Significance: Elevated insulin level in insulin-resistant states such as T2D suppresses the synthesis of testicular steroidogenesis.
Context:
A polymorphism in the FSHB promoter (-211G>T, rs10835638) was shown to influence male serum FSH levels, whereas a polymorphism in the FSH receptor gene (FSHR; 2039A>G, rs6166) was previously shown to be associated with FSH levels in women only.
Objective:
The objective of the study was to analyze the effects of both FSHB -211G>T and FSHR 2039A>G on male reproductive parameters.
Design and setting:
A total of 1213 German men attending an infertility clinic were genotyped by TaqMan assay.
Patients:
Patients included male partners in infertile couples without known causes for male infertility.
Main outcome measures:
An association analysis of single and combined single-nucleotide polymorphism genotypes with clinical parameters was performed.
Results:
The FSHB -211G>T T-allele showed significant dosage effects for FSH (-0.51 U/liter per T-allele), LH (0.28 U/liter), and bitesticular volume (-3.2 ml). Statistical significance was enhanced severalfold after a meta-analysis comprising 3017 men. TT carriers were significantly more prevalent among men with lower sperm counts. The FSHR 2039A>G G-allele exhibited nonsignificant trends for associations with higher FSH and reduced testicular volumes. However, in the combined model, FSHR 2039A>G significantly modulated the more dominant effect of FSHB -211G>T on serum FSH and testicular volume among the T-allele carriers.
Conclusions:
By analyzing both single-nucleotide polymorphisms for the first time, we convincingly show that indeed FSHR 2039A>G has an effect also in males. In the proposed model of the combined effects, FSHB -211G>T acts strongly on male reproductive parameters, whereas the FSHR 2039A>G effects were approximately 2-3 times smaller. Clinically this is of importance because oligozoospermic patients carrying unfavorable variants affecting FSH action may benefit from FSH treatment.
Androgenetic alopecia is recognized as a risk factor for cardiovascular diseases, glucose metabolism disorders, and benign prostate hyperplasia and/or carcinoma. Finasteride, used for treatment of androgenetic alopecia at a dose of 1mg/day, is an effective inhibitor of type II 5alpha-reductase, the enzyme responsible for the reduction of testosterone to dihydrotestosterone. Recent studies reported that dihydrotestosterone, among other activities, might play some role in visceral fat metabolism. It thus seemed reasonable to examine whether finasteride treatment of androgenetic alopecia ameliorates some features of metabolic syndrome frequently seen associated with this condition.
We examined 12 men with premature balding (defined as frontoparietal and vertex hair loss before age 30 with alopecia defined as grade 3 vertex or more on the Norwood-modified Hamilton alopecia classification). Hormonal levels and metabolic parameters were determined and insulin tolerance tests performed for all individuals. Finasteride (1 mg/day) was administrated for 12 months. The hormonal profile and lipid spectrum were monitored after 4, 8 and 12 months of treatment and insulin tolerance tests were repeated after 12 months of the treatment.
After treatment with finasteride the expected changes in the steroid spectrum were seen, namely a decrease in dihydrotestosterone and increase in testosterone, androstenedione and free testosterone index. We observed an initial increase in total cholesterol and HDL- and LDL-cholesterol, which stabilized with prolonged treatment. We founded a significant decrease in glycated hemoglobin HbA1c and insulin resistance measured using rate constant for plasma glucose disappearance (kITT) showed only a borderline decrease.
Finasteride is an efficient 5alpha-reductase inhibitor even at low doses of 1 mg/day. In men treated with this dose for 12 months, we observed mild differences in metabolic profile with slight amelioration of glucose metabolism regulation.
Background:
Polycystic Ovary Syndrome (PCOS) is a complex heterogeneous disorder and the most common endocrinopathy amongst women of reproductive age. It is characterized by androgen excess, chronic anovulation and an altered cardiometabolic profile. PCOS is linked to impaired adipose tissue (AT) physiology and women with this disorder present with greater risk for insulin resistance (IR), hyperinsulinemia, central adiposity, nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) than matched for age and body mass index (BMI) women without PCOS. Hyperandrogenaemia appears to be driving adipocyte hypertrophy observed in PCOS under the influence of a hyperinsulinaemic state. Changes in the function of adipocytes have an impact on the secretion of adipokines, adipose tissue-derived proinflammatory factors promoting susceptibility to low grade inflammation.
Methods:
In this article, we review the existing knowledge on the interplay between hyperandrogenaemia, insulin resistance, impaired adipocyte biology, adipokines and chronic low-grade inflammation in PCOS.
Results:
In PCOS, more than one mechanisms have been suggested in the development of a chronic low-grade inflammation state with the most prevalent being that of a direct effect of the immune system on adipose tissue functions as previously reported in obese women without PCOS. Despite the lack of conclusive evidence regarding a direct mechanism linking hyperandrogenaemia to pro-inflammation in PCOS, there have been recent findings indicating that hyperandrogenaemia might be involved in chronic inflammation by exerting an effect on adipocytes morphology and attributes.
Conclusion:
Increasing evidence suggests that there is an important connection and interaction between pro-inflammatory pathways, hyperinsulinemia, androgen excess and adipose tissue hypertrophy and, dysfunction in PCOS. While lifestyle changes and individualized prescription of insulin-sensitizing drugs are common in managing PCOS, further studies are warranted to eventually identify an adipokine that could serve as an indirect marker of adipocyte dysfunction in PCOS, used as a reliable and path gnomic sign of metabolic alteration in this syndrome.
Importance
Early androgenetic alopecia (AGA) is patterned hair loss occurring before age 30 years. Early AGA in men is frequently reported as the phenotypic equivalent of polycystic ovarian syndrome (PCOS) in women, which carries the risk of developing obesity, metabolic syndrome, and cardiovascular diseases. Very few studies have been conducted to evaluate this.
Objective
To study the hormonal profile of men with early AGA and to evaluate if early AGA in men can be considered as the phenotypic equivalent of PCOS, the associated risks of which are well known.
Design, Setting, and Participants
This case-control study was conducted from January 1, 2014, to March 31, 2015, in a tertiary care government hospital. Fifty-seven men aged 19 to 30 years presenting with patterned hair loss were recruited as study participants. Thirty-two age-matched men with no evidence of hair loss were recruited as controls. Men who had any established endocrine disorder, diabetes mellitus, or cardiovascular disease and those who took any oral medication or hormonal treatment for hair loss were excluded from the study. The serum concentrations of total testosterone, sex hormone–binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEAS), luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin, fasting plasma glucose, and insulin levels were measured. Insulin resistance (IR) and free androgen index (FAI) were calculated and compared with age- and sex-matched controls.
Main Outcomes and Measures
The primary outcome was to measure the clinico-endocrinological profiles (LH, FSH, SHBG, DHEAS, and testosterone levels) of men with early AGA and to compare it with the PCOS profile; the secondary outcome was to establish a relationship between this endocrinological profile and IR.
Results
Compared with the 32 controls, the 57 participants with AGA showed significantly increased mean (SD) levels of testosterone (24.61 [7.97] vs 20.57 [4.9] nmol/L; P = .04), DHEAS (3.63 [2.19] vs 2.64 [1.49] µg/mL; P = .02), LH (7.78 [3.19] vs 4.56 [2.01] mIU/mL; P < .001), and prolactin (14.14 [9.48] vs 9.97 [3.12] ng/mL; P = .01) and decreased mean levels of FSH (4.02 [2.69] vs 5.66 [1.93] mIU/mL; P < .001) and SHBG (35.07 [11.11] vs 46.41 [14.03] nmol/L; P < .001). The mean FAI and LH/FSH ratio were was also increased in the AGA group. These hormonal parameters resemble the well-known profile of women with PCOS. The mean (SD) insulin levels did not show any significant difference between the cases and controls (6.34 [3.92] vs 5.09 [3.38] μIU/mL; P = .07). There was no statistically significant association between hormone levels and AGA or IR grade severity.
Conclusions and Relevance
Men with early AGA could be considered as male phenotypic equivalents of women with PCOS. They can be at risk of developing the same complications associated with PCOS, including obesity, metabolic syndrome, IR, cardiovascular diseases, and infertility.
This study examined whether a defect of steroid synthesis in ovarian theca cells may lead to the development of PCOS, through contributions to excess androgen secretion.Polycystic ovarian syndrome (PCOS) is one of the leading causes of infertility worldwide affecting around 1 in 10 of women of a reproductive age. One of the fundamental abnormalities in this syndrome is the presence of hormonal irregularities, including hyperandrogenemia, hyperinsulinemia and hypersecretion of luteinizing hormone (LH). Studies suggest that insulin treatment increases progesterone and androstenedione secretion in PCOS theca cells when compared to insulin treated normal theca cells. Furthermore the augmented effects of LH and insulin have been seen to increase ovarian androgen synthesis in non-PCOS theca cultures whilst also increasing the expression of steroidogenic enzymes specific to the PI3-K pathway.Our examination of primary thecal cultures showed an increase in both the expression of the steroidogenic enzyme CYP17 and androgen secretion in PCOS theca cells under basal conditions, when compared to non-PCOS cells. This was increased significantly under treatments of LH and insulin combined.Our results support the previous reported hypothesis that a dysfunction may exist within the PI3-K pathway. Specifically, that sensitivity exists to physiological symptoms including hyperinsulinemia and hyper secretion of LH found in PCOS through co-stimulation. The impact of these findings may allow the development of a therapeutic target in PCOS. © 2016 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn.
Executive Summary
Polycystic ovary syndrome (PCOS) is recognized as the most common endocrine disorder of reproductive-aged women around the world. This document, produced by the collaboration of the American Association of Clinical Endocrinologists and the Androgen Excess Society aims to highlight the most important clinical issues confronting physicians and their patients with PCOS. It is a summary of current best practices in 2014.
Insulin resistance is believed to play an intrinsic role in the pathogenesis of PCOS. The mechanism by which insulin resistance or insulin give rise to oligomenorrhea and hyperandrogenemia, however, is unclear.
Hyperinsulinemic-euglycemic clamp studies have shown that both obese and lean women with PCOS have some degree of insulin resistance. Insulin resistance is implicated in the ovulatory dysfunction of PCOS by disrupting the hypothalamic- pituitary-ovarian axis.
Given the association with insulin resistance, all women with PCOS require evaluation for the risk of metabolic syndrome (MetS) and its components, including type 2 diabetes, hypertension, hyperlipidemia, and the possible risk of clinical events, including acute myocardial infarction and stroke.
Obese women with PCOS are at increased risk for MetS with impaired glucose tolerance (IGT; 31 to 35%) and type 2 diabetes mellitus (T2DM; 7.5 to 10%). Rates of progression from normal glucose tolerance to IGT, and in turn to T2DM, may be as high as 5 to 15% within 3 years.
Data suggest the need for baseline oral glucose tolerance test every 1 to 2 years based on family history of T2DM as well as body mass index (BMI) and yearly in women with IGT.
Compared with BMI- and age-matched controls, young, lean PCOS women have lower high-density lipoprotein (HDL) size, higher verylow- density lipoprotein particle number, higher low-density lipoprotein (LDL) particle number, and borderline lower LDL size.
Statins have been shown to lower testosterone levels either alone or in combination with oral contraceptives (OCPs) but have not shown improvement in menses, spontaneous ovulation, hirsutism, or acne. Statins reduce total and LDL cholesterol but have no effect on HDL, C-reactive protein, fasting insulin, or homeostasis model assessment of insulin resistance in PCOS women, in contrast to the general population.
There have been no long-term studies of statins on clinical cardiac outcomes in women with PCOS.
Coronary calcification is more prevalent and more severe in PCOS than in controls.
In women under 60 years of age undergoing coronary angiography, the presence of polycystic ovaries on sonography has been associated with more arterial segments with >50% stenosis, but the relationship between PCOS and actual cardiovascular events remains unclear.
Therapies for PCOS are varied in their effects and targets and include both nonpharmacologic as well as pharmacologic approaches.
Weight loss is the primary therapy in PCOS—reduction in weight of as little as 5% can restore regular menses and improve response to ovulation- inducing and fertility medications.
Metformin in premenopausal PCOS women has been associated with a reduction in features of MetS.
Clamp studies using ethinyl estradiol/drosperinone combination failed to reveal evidence of an increase in either peripheral or hepatic insulin resistance.
Subjects with PCOS have a 1.5-times higher baseline risk of venous thromboembolic disease and a 3.7-fold greater effect with OCP use compared with non-PCOS subjects.
There is currently no genetic test to screen for or diagnose PCOS, and there is no test to assist in the choice of treatment strategies.
Persistent bleeding should always be investigated for pregnancy and/or uterine pathology—including transvaginal ultrasound exam and endometrial biopsy—in women with PCOS.
PCOS women can have difficulty conceiving. Those who become pregnant are at risk for gestational diabetes (which should be evaluated and managed appropriately) and the microvascular complications of diabetes.
Assessment of a woman with PCOS for infertility involves evaluating for preconceptional issues that may affect response to therapy or lead to adverse pregnancy outcomes and evaluating the couple for other common infertility issues that may affect the choice of therapy, such as a semen analysis.
Women with PCOS have multiple factors that may lead to an elevated risk of pregnancy, including a high prevalence of IGT—a clear risk factor for gestational diabetes—and MetS with hypertension, which increases the risk for pre-eclampsia and placental abruption.
Women should be screened and treated for hypertension and diabetes prior to attempting conception.
Women should be counseled about weight loss prior to attempting conception, although there are limited clinical trial data demonstrating a benefit to this recommendation.
Treatment for women with PCOS and anovulatory infertility should begin with an oral agent such as clomiphene citrate or letrozole, an aromatase inhibitor.
Abbreviations:
AMH = anti-Müllerian hormone
BMI = body mass index
BP = blood pressure
CIMT = carotid intima media thickness
CV = cardiovascular
GnRH = gonadotropin-releasing hormone
GWAS = genomewide association study
HDL = high-density lipoprotein
HOMA-IR = homeostasis model assessment of insulin resistance
IGT = impaired glucose tolerance
LDL = low-density lipoprotein
LH = luteinizing hormone
MetS = metabolic syndrome
MI = myocardial infarction
NIH = National Institutes of Health
OCP = oral contraceptive
OGTT = oral glucose tolerance test
PCOM = polycystic ovary morphology
PCOS = polycystic ovary syndrome
RR = relative risk
SSPG = steady-state plasma glucose
T = testosterone
T2DM = type 2 diabetes mellitus
TG = triglyceride
VTE = venous thromboembolic
WHR = waist to hip ratio
Objective:
Transgender patients may seek hormone therapy to induce physical changes to simulate their expressed or experienced gender. However, many providers are uncomfortable prescribing transgender hormones due to fears over safety. The goal of this study was to determine if transgender hormone therapy with estrogen and spironolactone for male-to-female (MtF) patients or with testosterone for female-to-male (FtM) patients had adverse anthropomorphic or metabolic effects.
Methods:
This retrospective chart review study analyzed changes over time for 33 MtF and 19 FtM endocrine clinic patients at an academic endocrine practice with follow up for up to 18 months after hormone initiation.
Results:
Compared to baseline labs obtained prior to initiation of hormone therapy statistically significant changes for the MtF cohort included an increase in HDL and decrease in creatinine; however, triglycerides did not show a statistically significant change. In the FtM cohort, there was a statistically significant increase in body mass index, creatinine, hemoglobin, and hematocrit. These changes were minimal for both cohorts.
Conclusion:
In our practice, hormone therapy was found to be safe in this retrospective study.
We carried out a systematic review in order to determine the connection between lower urinary tract symptoms secondary to bladder outlet obstruction and metabolic syndrome with its components. We searched the Cochrane Central Register of Controlled Trials, PubMed, EMBASE, the Cochrane Database of Systematic Review and Web of Science from their inception until January 2015 to identify all eligible studies on the effect of metabolic syndrome (or component factors) on the presence or severity of lower urinary tract symptoms/bladder outlet obstruction in men. This analysis was carried out according to the STrengthening the Reporting of OBservational studies in Epidemiology guidelines. In total, 19 studies were identified as eligible for this systematic review. The quality assessment score was ≥50% in more than half of the studies (11/19). The evidence synthesis showed a positive association between metabolic syndrome, number of components and lower urinary tract symptoms/bladder outlet obstruction. In particular, the major endocrine aberrations of this connection are central obesity and hypertriglyceridemia. The links between insulin resistance and lower urinary tract symptoms/bladder outlet obstruction should be better investigated. Ethnic disparities in all examined studies showed a different impact of metabolic syndrome on lower urinary tract symptoms/bladder outlet obstruction severity and such influence still remain unclear. The relationship between metabolic syndrome and lower urinary tract symptoms/bladder outlet obstruction open the way for introducing physical activity and diet as recognized first-line interventions for treating lower urinary tract symptoms. However, this connection should be investigated in two different ethnic cohorts (i.e. Asian vs Caucasian) in order to better understand the impact of ethnic disparities on metabolic syndrome and lower urinary tract symptoms/bladder outlet obstruction severity.
© 2015 The Japanese Urological Association.
Polycystic ovary syndrome (PCOS) is an oligogenic condition, with a heritability of ∼70%. PCOS is also associated with obesity, which itself is heavily influenced by genetic variants. PCOS is inherently difficult to study genetically, and most of the current literature (>70 studies based on the candidate gene approach) is inconclusive, with many studies being underpowered resulting in inconsistencies, controversies and lack of clear consensus. A further problem is that the candidate gene approach relies upon some prior understanding of pathogenesis to determine the candidacy of the gene chosen (with >20,000 genes to choose from within the human genome). PCOS has a complex and incompletely understood pathogenesis, thereby limiting the candidate gene approach for this condition. Thankfully, this limitation is overcome through use of the genome-wide association study (GWAS), the first of which in PCOS has already been published. The GWAS does not rely upon any a priori understanding of pathogenesis, and as such holds the potential to reveal hitherto unexpected or even unknown pathogenic pathways that may be implicated in the development of PCOS. Data from future GWAS in PCOS should transform our understanding of PCOS pathogenesis, and also provide a basis on which to develop future novel therapeutic strategies.
Background:
Alopecia has been associated with an increased risk of coronary heart disease as well as the following risk factors for cardiovascular disease: hyperinsulinaemia, insulin resistance, metabolic syndrome, dyslipidaemia, and hypertension. We performed a meta-analysis to quantitatively determine the level of risk of coronary heart disease and risk factors in individuals with alopecia.
Methods:
A systematic literature search was conducted using several databases. We calculated pooled odds ratios and 95% confidence intervals using a random effects model.
Results:
In total, 31 studies comprising 29,254 participants with alopecia were eligible for the meta-analysis and showed that alopecia is associated with an increased risk of coronary heart disease (OR 1.22, 95% CI: 1.07-1.39), hyperinsulinaemia (OR 1.97, 95% CI: 1.20-3.21), insulin resistance (OR 4.88, 95% CI: 2.05-11.64), and metabolic syndrome (OR 4.49, 95% CI: 2.36-8.53). Individuals with alopecia were also shown to be more likely compared to those without alopecia to have higher serum cholesterol levels (OR 1.60, 95% CI: 1.17-2.21), higher serum triglyceride levels (OR 2.07, 95% CI: 1.32-3.25), higher systolic blood pressures (OR 1.73, 95% CI: 1.29-2.33), and higher diastolic blood pressures (OR 1.59, 95% CI: 1.16-2.18).
Conclusions:
Alopecia is associated with an increased risk of coronary heart disease, and there appears to be a dose-response relationship with degree of baldness whereby the greater the severity of alopecia, the greater the risk of coronary heart disease. Alopecia is also associated with an increased risk of hypertension, hyperinsulinaemia, insulin resistance, metabolic syndrome, and having elevated serum total cholesterol and triglyceride levels.
Both androgenetic alopecia (AGA) and carcinoma of the prostate (CaP) or benign prostatic hyperplasia (BPH) are androgen-dependent disorders.
To investigate the relationships between male androgenetic alopecia, androgen receptor (AR) gene polymorphism (SNP rs6152) and clinical characteristics of BPH and prostate cancer.
Overall, 309 male subjects with prostate disease (BPH or CaP) were examined. We evaluated the standard grades of AGA (I-VII) by Hamilton-Norwood classification and 195 patients were also assessed by phototrichogram. Prostate-specific antigen (PSA) and testosterone levels were also measured. Polymorphism rs6152 of the AR was evaluated from blood samples by PCR-RFLP. Data were statistically evaluated.
The expected positive correlation between age and AGA grade and the expected negative correlation between hair density and age and between anagen/telogen and AGA were found. A statistically significant difference between patients with A and G alleles in terms of AGA grade was found. The predominant G allele was more frequent in patients with higher grade of alopecia and in patients with significantly higher PSA. There was no correlation between diagnosis (BPH or CaP) and polymorphism. Patients with prostate inflammation had a statistically significant higher grade of AGA, together with higher PSA.
We confirmed that the AR gene polymorphism (SNP rs6152 G>A) is associated with the development of AGA and higher PSA levels in patients with BPH but not cancer. A novel finding of our study is that BPH patients with prostate inflammation had a significantly higher grade of AGA together with significantly higher PSA levels.
There are many studies of the association between early-onset androgenetic alopecia (AGA) and metabolic syndrome (MS), which is known to increase the risk of cardiovascular diseases. However the results are inconsistent. There is no study in a Thai population.
To evaluate the association of early-onset AGA and metabolic syndrome in Thai male patients.
Patients were recruited from the check-up clinic. There were 80 male subjects: 40 with a diagnosis of early-onset AGA (before 35 years of age) and 40 control subjects without alopecia. Data from medical records, self-administered forms, and interview were collected and analyzed.
Patients with early-onset AGA had the 3.48-fold higher risk of metabolic syndrome than in a control group (p = 0.015, odd ratio = 3.48, 95% confidence interval = 1.25-9.75). There was no relationship between AGA severity and metabolic syndrome (p = 0.629). There were no significant differences between the groups in terms of metabolic syndrome parameter
The present study found the association between early onset A GA and metabolic syndrome in Thai men. Early detection of metabolic syndrome in this population may be useful to prevent cardiovascular diseases.
Background and objectivesThe relationship between androgenetic alopecia and cardiovascular disease has been studied by some authors in the past, although the results of epidemiological studies have been variable. The objective of this study was to determine the prevalence of metabolic syndrome and carotid arteriosclerosis in patients with early-onset androgenetic alopecia.
Importance:
Identifying predictors of mortality from diabetes mellitus (DM) and heart disease can help shape treatment strategies. Presence of androgenetic alopecia (AGA) might be such a predictor.
Objective:
To determine whether the presence of AGA is associated with an elevated rate of mortality from DM and heart disease in both sexes after adjustment for potential confounders.
Design:
A population-based prospective cohort study.
Setting:
Community-based integrated screening in Taiwan.
Participants:
A total of 7252 subjects aged 30 to 95 years participated in the baseline AGA survey using the Norwood and Ludwig classifications between April and June 2005. Baseline information on metabolic syndrome (MetS) and other possible risk factors was also collected. We then followed this cohort over time to ascertain death and cause of death until December 2010. INTERVENTIONS OR EXPOSURES: Application of Norwood and Ludwig ALA classifications to study population.
Main outcomes and measures:
Deaths from DM and heart disease.
Results:
Among the 7126 subjects (2429 men and 4697 women) who provided complete data, there were 70 deaths from DM and heart disease during the 57-month follow-up period. Subjects with moderate to severe AGA vs normal or mild AGA had a significantly higher risk of mortality from DM (adjusted hazard ratio [HR], 2.97; 95% CI, 1.26-7.01) (P = .01) and heart disease (adjusted HR, 2.28; 95% CI, 1.00-5.23) (P = .05) after adjusting for age, family history of DM or heart disease, and MetS.
Conclusions and relevance:
AGA is an independent predictor of mortality from DM and heart disease in both sexes. This finding may have significant implications for the identification of risk factors for DM and heart disease in patients with moderate or severe AGA, regardless of whether MetS is present.
BACKGROUND: Androgenetic alopecia (AGA) is a genetically determined skin condition strongly age dependent and androgens are assumed to play an important role in its development. A link between AGA and prostate cancer has been hypothesized because of their similar risk factors. OBJECTIVE: We sought to systematically review the evidence available on the association between AGA and risk of prostate cancer. METHODS: We searched the electronic databases MEDLINE and Cochrane for studies examining the association between AGA and risk of prostate cancer. We estimated pooled odds ratios (OR) and 95% confidence intervals. We also analyzed the OR for individual hair loss patterns, as defined by the Hamilton scale. RESULTS: A total of 7 case-control studies including 8994 patients-4078 cases and 4916 controls-were reviewed. One cohort study was identified but did not meet our inclusion criteria. There was statistically significant association between vertex baldness and prostate cancer (OR 1.25; 95% confidence interval 1.09-1.44; Z = 3.13; P = .002). No statistically significant association between AGA (any pattern) and prostate cancer was identified (OR 1.03; 95% confidence interval 0.93-1.13; Z = 0.55; P = .58). LIMITATIONS: Only case-control studies, which may be subject to bias, met the inclusion criteria for this meta-analysis. CONCLUSIONS: Vertex pattern AGA was associated with a significant increased risk of prostate cancer. Any pattern AGA did not show a significant increase in the risk of prostate cancer.
Polycystic ovary syndrome (PCOS) is associated with obesity and manifests with reproductive, hyperandrogenic and metabolic features. Although the etiology of PCOS is complex and incompletely understood, genetics plays an important role (heritability: ∼70%). Potential problems with studying the genetics of PCOS include the heterogeneity of the condition and associated sub-fertility. A candidate gene approach has been used in over 70 published studies on PCOS, most of which have been inadequately powered to detect a statistically meaningful association. Furthermore, these studies often fail to replicate prior published studies on the same candidate gene in different populations. The first genome-sequence variant (identified from a genome-wide association study in subjects with Type 2 diabetes mellitus) to be studied in PCOS (FTO gene) has been shown by our group to associate with susceptibility for the development of PCOS. This is the first genetic corroboration of a link between PCOS and obesity. Future directions include a genome-wide association study in PCOS.
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in females, with a high prevalence. The etiology of this heterogeneous condition remains obscure, and its phenotype expression varies. Two widely cited previous ESHRE/ASRM sponsored PCOS consensus workshops focused on diagnosis (published in 2004) and infertility management (published in 2008), respectively. The present third PCOS consensus report summarizes current knowledge and identifies knowledge gaps regarding various women's health aspects of PCOS. Relevant topics addressed-all dealt with in a systematic fashion-include adolescence, hirsutism and acne, contraception, menstrual cycle abnormalities, quality of life, ethnicity, pregnancy complications, long-term metabolic and cardiovascular health, and finally cancer risk. Additional, comprehensive background information is provided separately in an extended online publication.
Androgenetic alopecia (AGA) and benign prostatic hyperplasia are both androgen-dependent entities that respond to the blocking of 5-alpha-reductase.
The objective of this study was to determine whether prostatic volumes and urinary flow changes were higher in patients with early-onset AGA than in healthy control subjects.
This was an observational case-control study of 87 men: 45 with early-onset AGA diagnosed in the dermatology department and 42 control subjects. End-point variables were prostatic volume, measured by transrectal ultrasound, and urinary flow, measured by urinary flowmetry. A hormone study was performed on all participants, and the International Prostate Symptom Score and International Index of Erectile Function score were determined.
The groups did not significantly differ in mean age (cases, 52.7 years vs control subjects, 49.8 years; P = .12). Patients with AGA had significantly higher mean prostate volume (29.65 vs 20.24 mL, P < .0001), International Prostate Symptom Score (4.93 vs 1.23, P < .0001), and prostate-specific antigen value (1.53 vs 0.94 ng/mL, P < .0001) and significantly lower maximum urinary flow (14.5 vs 22.45 mL/s, P < .0001) versus control subjects. Binary logistic regression analysis showed a strong association between the presence of AGA and benign prostatic hyperplasia after adjusting for age, urinary volume, urination time, International Prostate Symptom Score, abdominal obesity, glucose levels, systolic blood pressure, insulin levels, fibrinogen, and C-reactive protein (odds ratio = 5.14, 95% confidence interval 1.23-47.36, P = .041).
The study of larger sample sizes would facilitate stratified analyses according to the Ebling type of androgenetic alopecia.
There is a relationship between the presence of AGA and prostate growth-associated urinary symptoms, likely attributable to their pathophysiological similarity. This study suggests that early-onset AGA may be an early marker of urinary/prostatic symptomatology. Future studies may clarify whether treatment of patients with AGA may benefit the concomitant benign prostatic hypertrophy, which would be present at an earlier stage in its natural evolution.
A body of evidence points to a familial aggregation of hormonal abnormalities in first-degree relatives of women with polycystic ovary syndrome (PCOS). The aim of this study was to determine whether siblings of women with PCOS had evidence of hormonal abnormalities typical of PCOS.
Eighty-six siblings of women with PCOS (44 sisters, 42 brothers) were recruited. Two control groups consisted of 70 healthy women and 30 healthy men. Anthropometric, hormonal (testosterone, androstenedione, DHEA-S, LH, FSH) parameters and SHBG were assessed in all subjects.
Mean testosterone and DHEA-S levels were higher in sisters of women with PCOS than in the control women. In eight of the 44 (18.2%) sisters, a diagnosis of PCOS was made. Mean testosterone and androstenedione levels, and free androgen index (FAI) were significantly higher in sisters with PCOS compared to the sisters without PCOS. Brothers of women with PCOS had higher DHEA-S level than the control men. Eleven of the 42 (26.2%) brothers had alopecia occurring before the age of 30. Prematurely balding brothers did not differ from the non-balding brothers in hormonal parameters.
Siblings of women with PCOS are predisposed to hormonal abnormalities typical of PCOS. The symptom of premature balding under the age of 30 in brothers of women with PCOS should not be considered as a male PCOS equivalent.
Low circulating levels of sex hormone-binding globulin (SHBG) are a strong predictor of the risk of type 2 diabetes. Androgenetic alopecia (AGA) has been related to an increase in cardiovascular risk, but the mechanism of this association has not been elucidated. AGA can be associated with low levels of SHBG and insulin resistance, which could be related to hyperglycemia and type 2 diabetes.
The objective of this study was to evaluate SHBG and blood glucose levels in men and women with early-onset AGA and control subjects to determine whether low levels of SHBG are associated with hyperglycemia.
This case-control study included 240 patients consecutively admitted to the outpatient clinic (Dermatology Department of San Cecilio University Hospital, Granada, Spain), 120 with early-onset AGA (60 men and 60 women) and 120 control subjects (60 men and 60 women) with skin diseases other than alopecia.
Of patients with AGA, 39.1% presented with hyperglycemia (>110 mg/dL) versus 12.5% of controls (P < 0.0001). AGA patients with hyperglycemia or diabetes presented lower significant levels of SHBG than alopecic patients without hyperglycemia or type 2 diabetes, respectively. Patients with AGA and hyperglycemia presented significantly lower levels of SHBG than controls with hyperglycemia (22.3 vs 39.4 nmol/L for AGA patients and controls, respectively, P = .004). No significant differences in SHBG levels were noticed between patients and controls without hyperglycemia. Binary logistic regression showed a strong association between lower SHBG levels and glucose levels greater than 110 mg/dL in patients with AGA even after additional adjustment for sex, abdominal obesity, and free testosterone (odds ratio = 3.35; 95% confidence interval = 1.9-5.7; P < .001).
The study of a wider sample of AGA patients would confirm these findings and would permit analysis of the pathogenic mechanisms underlying the increase in cardiovascular risk in patients with AGA.
An association between early-onset AGA, hyperglycemia/diabetes, and low levels of SHBG was observed in the current study. Low levels of SHBG could be a marker of insulin resistance and hyperglycemia/diabetes in patients with AGA.
Because of the paucity of studies and inconsistencies regarding the impact of diabetes mellitus (DM) on semen quality, this disease is seldom looked for in the infertile patient. Recently, this view has been challenged by findings showing that DM induces subtle molecular changes that are important for sperm quality and function. This brief review shows the main sperm parameters in patients with DM and presents the mechanisms hypothesized to explain the changes observed in these patients. The data available suggest that DM alters conventional sperm parameters. In addition, DM causes histologic damage of the epididymis, with a negative impact on sperm transit. Various mechanisms may explain the sperm damage observed in patients with DM. These include endocrine disorders, neuropathy, and increased oxidative stress. Many authors suggest that DM decreases serum testosterone levels. This is associated with a steroidogenetic defect in Leydig cells. In addition, diabetic neuropathy seems to cause atonia of seminal vesicles, bladder, and urethra. Furthermore, DM is associated with an increased oxidative stress, which damages sperm nuclear and mitochondrial DNA. Finally, spermatogenesis derangement and germ cell apoptosis in type 1 DM may relate to a local autoimmune damage, whereas insulin resistance, obesity, and other related comorbidities may impair sperm parameters and decrease testosterone serum levels in patients with type 2 DM.
Epidemiological studies have shown that diseases associated with insulin resistance and coronary artery disease are more frequently observed in men with androgenetic alopecia (AGA). We aimed to identify the presence of insulin resistance and metabolic syndrome in male patients with early-onset AGA. Fifty male patients (18-30 years) with AGA stage ≥ 3 (Hamilton-Norwood scale), body mass index < 27 and 40 weight- and age-matched male subjects were the study population. The weight, height, and waist circumference of all patients was measured. Levels of fasting glucose, insulin, and lipids were evaluated and oral glucose tolerance tests undertaken. Insulin resistance was analyzed through various indices and the presence of metabolic syndrome was assessed. Values of diastolic blood pressure and total cholesterol were significantly higher in the AGA group. Among insulin indices, only HOMA insulin resistance (HOMA-IR) and fasting insulin resistance index (FIRI) were higher in the AGA group. Given the criteria for metabolic syndrome, no significant differences were observed between the two groups. Although not supported by the other indices, high scores of HOMA-IR and FIRI suggest that male patients with early onset-AGA have insulin resistance. These data may raise awareness in susceptible individuals that lifestyle changes in the early period of life can reduce the risk of insulin resistance.
Several previous studies have investigated the association between factors related to metabolic syndrome, which is known to increase the risk of type 2 diabetes mellitus and cardiovascular disease, and androgenetic alopecia (AGA). However, the results of these studies have been inconsistent.
To determine if there is an association between metabolic syndrome and AGA after adjustment for potential confounders.
A population-based cross-sectional survey was conducted in Tainan, Taiwan. A total of 740 subjects aged 40-91 years participated in the survey between April and June 2005. The Norwood classification was used to assess the degree of hair loss. Information on components of metabolic syndrome together with other possible risk factors was collected.
A statistically significant association was found between AGA and the presence of metabolic syndrome [odds ratio (OR) 1.67, 95% confidence interval (CI) 1.01-2.74] as well as between AGA and the number of fulfilled metabolic syndrome components (OR 1.21, 95% CI 1.03-1.42) after controlling for age, family history of AGA and smoking status. Among metabolic syndrome components, high-density lipoprotein cholesterol (HDL-C) (OR 2.36, 95% CI 1.41-3.95; P = 0.001) was revealed as the most important factor associated with AGA.
Our population-based study found a significant association between AGA and metabolic syndrome; among the components of metabolic syndrome, HDL-C was found to be of particular importance. This finding may have significant implications for the identification of metabolic syndrome in patients with moderate or severe AGA. Early intervention for metabolic syndrome is critical to reduce the risk and complications of cardiovascular disease and type 2 diabetes mellitus later in life.
The relationship between androgenetic alopecia and cardiovascular disease has been studied by some authors in the past, although the results of epidemiological studies have been variable. The objective of this study was to determine the prevalence of metabolic syndrome and carotid arteriosclerosis in patients with early-onset androgenetic alopecia.
Seventy men were studied, 35 with diagnosis of early-onset (before 35 years of age) androgenetic alopecia and 35 control subjects who consulted for other skin conditions. In both groups, the criteria for metabolic syndrome according to the Adult Treatment Panel-III were studied (obesity, triglycerides, high-density lipoprotein cholesterol, systolic and diastolic blood pressure, and blood glucose), presence of atheromatous plaques, and carotid intima-media thickness using Doppler ultrasonography. Other cardiovascular risk factors, hormones, and acute-phase reactants were also analyzed.
Criteria for metabolic syndrome were met by 57.1% of the patients with androgenetic alopecia compared to 14.3% of the controls (P<0001). Thirty-four percent of the patients with androgenetic alopecia had atheromatous plaques compared to 8.6% of the controls (P=.018). In an independent correlation analysis, abdominal obesity, systolic blood pressure, triglycerides, and blood glucose levels were significantly greater among patients with androgenetic alopecia. Testosterone and sex hormone binding globulin levels were similar in the 2 groups whereas insulin and aldosterone levels were higher in patients with androgenetic alopecia (P<05).
The high frequency of metabolic syndrome and carotid atheromatous plaques in patients with androgenetic alopecia suggests cardiovascular screening should be done to enable early detection of individuals at risk and initiation of preventive treatment before cardiovascular disease becomes established.
Epidemiological studies have associated androgenetic alopecia (AGA) with severe young-age coronary artery disease and hypertension, and linked it to insulin resistance. We carried out a case-control study in age- and weight-matched young males to study the link between AGA and insulin resistance using the homeostasis model assessment of insulin resistance (HOMA-IR) index or metabolic syndrome clinical manifestations.
Eighty young males, 18-35 years old, with AGA > or = stage III in the Hamilton-Norwood classification, and 80 weight- and age-matched controls were included. Alopecia, glucose, serum insulin, HOMA-IR index, lipid profile and androgen levels, as well as metabolic syndrome criteria, were evaluated.
The HOMA-IR index was significantly higher in cases than controls. Nonobese cases had a higher mean diastolic blood pressure and a more frequent family history of AGA than nonobese controls. A borderline difference in the HOMA-IR index was found in obese AGA cases vs. obese controls [P = 0.055, 95% confidence interval (CI) 2.36-4.20 vs. 1.75-2.73]. Free testosterone values were significantly higher in controls than cases, regardless of body mass index (BMI). A statistically significant additive effect for obesity plus alopecia was found, with significant trends for insulin, the HOMA-IR index, lipids and free testosterone when BMI and alopecia status were used to classify the participants.
Our results support the recommendation for assessing insulin resistance and cardiovascular-related features and disorders in all young males with stage III or higher AGA, according to the Hamilton-Norwood classification.
The need for a widely accepted, accurate, and reproducible standard of classification for male pattern baldness has increased with the advent and increasing popularity of hair transplant surgery. This report establishes such a classification, and reports its use in determining the incidence of male pattern baldness at various ages in 1,000 white adult male subjects. The action of testosterone as an incitant in male pattern baldness is well known, but this study points out the continued effect of time, even in later years. Since most hair transplant surgery is peformed on subjects with male pattern baldness, and because the success of hair transplant surgery is largely dependent on proper patient selection, a complete understanding of male pattern baldness is essential for consistently good results with hair transplantation.
To assess the degree of familial clustering and the mode of inheritance of the polycystic ovarian syndrome (PCO), the prevalence of PCO-related symptoms among first- and second-degree relatives of 132 PCO patients and 71 controls was studied using questionnaire data. 19.7% of male first-degree relatives of PCO patients were reported to have early baldness or excessive hairiness, as opposed to 6.5% of relatives of controls. For female first-degree relatives, the percentages for PCO-related symptoms were 31.4 and 3.2, respectively, in the two groups. In a subgroup of 52 families of PCO patients where one of the parents was reported to have symptoms, 35% of brothers and 58% of sisters had symptoms. Although autosomal dominant inheritance could be excluded as an explanation for PCO in the whole data set, the findings were consistent with this mode of inheritance for a sizeable fraction of families. X-linked dominant inheritance of PCO could be discarded.
Eighteen men aged 18 to 32 with rapidly progressive male pattern baldness had serum dehydroepiandrosterone sulfate and testosterone measured. Dehydroepiandrosterone sulfate levels were elevated in all patients, ranging from 340 to 730 micrograms/dl. The patients were otherwise healthy and serum testosterone levels were within normal limits. A control group of men of similar age without hair loss had lower dehydroepiandrosterone sulfate levels ranging from 124 to 300 micrograms/dl (p less than 0.005). The biochemistry of androgens, particularly dehydroepiandrosterone sulfate, suggests that adrenal hyperactivity may initiate alopecia in young men who are genetically susceptible.
The authors assessed the relation between the extent and progression of baldness and coronary heart disease. Baldness was assessed twice, in 1956 and in 1962, in a cohort of 2,017 men from Framingham, Massachusetts. Extent of baldness was classified in terms of number of bald areas: no areas bald (n = 153), one area bald (n = 420), two areas bald (n = 587), and all areas bald (n = 857). Men who were assessed both times and who had two or fewer bald areas during the first evaluation were classified into one of three groups: "mild or no progression," "moderate progression," or "rapid progression." The cohort was followed for up to 30 years for new occurrences of coronary heart disease, coronary heart disease death, cardiovascular disease, and death due to any cause. The relations between the extent and progression of baldness and the aforementioned outcomes were assessed using a Cox proportional hazards model, adjusting for age and other known cardiovascular disease risk factors. Extent of baldness was not associated with any of the outcomes. However, the amount of progression of baldness was associated with coronary heart disease occurrence (relative risk (RR) = 2.4, 95% confidence interval (CI) 1.3-4.4), coronary heart disease mortality (RR = 3.8, 95% CI 1.9-7.7), and all-cause mortality (RR = 2.4, 95% CI 1.5-3.8). Rapid hair loss may be a marker for coronary heart disease.
Polycystic ovary syndrome is one of the most common endocrine disorders but its aetiology remains unknown. It is highly prevalent within families, suggesting a genetic basic for the syndrome, but the mode of inheritance is unclear. The purpose of this study was to determine the mode of inheritance of polycystic ovary syndrome, within the families of affected individuals, by classic segregation analysis.
All first degree relatives of affected individuals were screened for the presence or absence of polycystic ovaries in post-menarchal-premenopausal women and early onset male pattern baldness (MPB) in the males. In extended pedigrees, assignment of affected status in post-menopausal women was made by consideration of the clinical history alone.
Fourteen women (probands), presenting with a variety of clinical symptoms, were identified sequentially as having polycystic ovaries (PCO) by ultrasound scan. They were examined in detail to determine their family structure, clinical and endocrine status. Ten families were found to have sufficient members for further study.
All family members had their body mass index calculated, their degree of hirsutism assessed using the Ferriman and Gallwey score and serum levels of gonadotrophins (FSH and LH), testosterone, prolactin and 17 alpha-hydroxyprogesterone measured by radioimmunoassay. A careful reproductive history was taken for each woman and any menstrual disturbance was noted. Obese probands had their glucose and insulin response to a standard 75-g oral glucose tolerance test determined. Each male family member was also assessed for the degree and time of onset of balding.
First degree female relatives of affected individuals had a 51% chance of being affected. Early onset male pattern baldness (MPB) was found to be an accurate phenotype for obligate male carriers. Each family showed autosomal dominant inheritance for PCO with greater than 90% penetrance.
We postulate that PCO and male pattern baldness are caused by alleles of the same gene which affect androgen production or action. The different frequencies of PCO and male pattern baldness arise from differing thresholds for phenotypic expression in females and males respectively. The modifying effects of other genes is the most likely explanation of the somewhat variable phenotype.
To examine the relationship between male pattern baldness and the risk of myocardial infarction in men under the age of 55 years.
A hospital-based, case-control study was conducted in eastern Massachusetts and Rhode Island. Cases were men admitted to a hospital for a first nonfatal myocardial infarction (n = 665); controls were men admitted to the same hospitals with noncardiac diagnoses (n = 772). Extent of baldness was assessed using the 12-point modified Hamilton Baldness Scale; other information was obtained by personal interview. Among the controls, the prevalence of any baldness was 34%, while the prevalence of baldness involving the vertex scalp was 23%.
After allowing for age, the relative risk estimate for frontal baldness compared with no hair loss was 0.9 (95% confidence interval, 0.6 to 1.3), for baldness involving the vertex scalp it was 1.4 (95% confidence interval, 1.2 to 1.9). Risk of myocardial infarction increased as the degree of vertex baldness increased (P < .01); for severe vertex baldness the relative risk was 3.4 (95% confidence interval, 1.7 to 7.0). The relationship between vertex baldness and myocardial infarction was consistent within strata defined by age and other risk factors for coronary artery disease.
These data support the hypothesis that male pattern baldness involving the vertex scalp is associated with coronary artery disease in men under the age of 55 years.
A weak positive association between male pattern baldness and ischemic heart disease has been suggested previously. The authors
examined this issue by using data from the Epidemiologic Follow-up Study of the First National Health and Nutrition Examination
Survey. As part of the baseline medical examination between 1971 and 1975, the presence and degree of male alopecia (none,
minimal, moderate, and severe) were recorded for a subset of participants. Among 3, 932 men aged 25–76 years who had complete
data, 378 deaths and 939 incident events from ischemic heart disease occurred during an average follow-up period of 14 years.
Among 2,019 men who were younger than age 55 years at baseline (61 deaths and 239 incident events of ischemic heart disease),
severe baldness was positively associated with ischemic heart disease mortality (rate ratio = 2.51, 95% confidence interval
1.01–6.24) and somewhat less associated with ischemic heart disease incidence (rate ratio = 1.72, 95% confidence interval
0.96–3.08). No dose-response relation with degree of baldness was seen. Arthough these findings are tempered by the absence
of information concerning the type of baldness (frontal or vertex), they provide support for earlier studies that indicate
male pattern baldness that occurs before age 55 years may be by some mechanism related to ischemic heart disease.
To determine whether disorders of insulin secretion are common in male and female family members of subjects with polycystic ovary syndrome (PCOS).
Family study of siblings and parents of PCOS subjects (five families). All proband cases met the criteria of polycystic ovaries (PCO) by ultrasound (US) and hyperandrogenism.
University Reproductive Medicine Unit.
Family members of PCOS subjects.
Oral glucose tolerance testing (OGTT), insulin, and lipids were measured. Clinical examination including assessment of premature baldness in men and US of ovaries in female members.
Insulin, lipids, and clinical parameters.
Hyperinsulinemia (69%) and hypertriglyceridemia (56%) was common in family members as were PCO in 79% of 24 females and premature baldness in men in 88% of eight subjects.
Hyperinsulinemia is a potential metabolic and genetic marker for subjects who may be carriers of a familial tendency for PCO.
Both benign prostatic hyperplasia (BPH) and male pattern baldness (androgenic alopecia) share the pathogenesis of an androgen-dependent disorder and afflict a large population of elderly men with chronobiologic progress. However, it is unclear whether these diseases are related epidemiologically. We evaluated the association of frequency and severity of male pattern baldness between patients with BPH and a control group.
A total of 225 patients with BPH (mean age 69.3 +/- 6.5 years) and 1 60 controls (mean age 68.5 +/- 6.4 years), all over 60 years of age, were included in this study. The estimation of baldness severity was based on Norwood's classification (grade I to VII). The International Prostate Symptom Score (IPSS) and genetic tendency for baldness were also evaluated. The difference between IPSS and grade of baldness between the two groups was analyzed by the Mann-Whitney test and the frequency of inherited baldness was compared by the chi-square test. Correlation between severity of baldness and IPSS in each group was estimated by Spearman's rank correlation method.
The patients with BPH had an apparently higher grade of male pattern baldness in comparison with that of controls (median value of grade IV versus III, P <0.001). The proportion of men with male pattern baldness of grade IV or higher in the BPH group was significantly larger than that of controls (53.8% versus 36.9%, P <0.01). There was a greater frequency of inherited baldness in the BPH group than in the controls (31.6% versus 12.5%, P <0.001). No significant correlation was noted between baldness severity and IPSS in either group.
This study demonstrates a strong association of BPH with male pattern baldness.
The aim of this study was to obtain evidence for the genetic basis of polycystic ovaries (PCO) and premature male pattern baldness (PMPB) by screening first-degree relatives of women affected by polycystic ovary syndrome (PCOS). Because of the high prevalence of PCO in the general population, we also studied first-degree relatives of ten asymptomatic control volunteers of reproductive age. The probands were recruited prospectively from infertility and endocrine clinics, where they presented with various clinical symptoms of PCOS. Each had PCO, on transvaginal ultrasound scan. The families of 29 probands and 10 volunteers agreed to take part in the study. Clinical, ultrasound, and biochemical parameters were used to define PCO/PCOS. All female relatives had an ovarian ultrasound scan and hormone profile performed. History was used to assign status in postmenopausal women. All male relatives were assessed for early onset (<30 yr old) male pattern baldness, by photographs. All relatives were assigned affected (PCO/PMPB) or nonaffected status, and segregation analysis was performed.
Of the relatives of 29 PCOS probands, 15 of 29 mothers (52%), 6 of 28 fathers (21%), 35 of 53 sisters (66%), and 4 of 18 brothers (22%) were assigned affected status. First-degree female relatives of affected individuals had a 61% chance of being affected. Of the first-degree male relatives, 22% were affected.
Of a total of 71 siblings of PCOS probands, 39 were affected, giving a segregation ratio of 39/32 (55%), which is consistent with autosomal dominant inheritance for PCO/PMPB. In the control families, 1 of 10 probands (10%), 1 of 10 mothers (10%), no fathers, 2 of 13 sisters (15%), and 1 of 11 brothers (9%) were affected. Of a total of 24 siblings, 3 were affected (13%), giving a segregation ratio (observed/expected) of 3/12, which was significantly different from autosomal dominant inheritance.
The inheritance of PCO and PMPB is consistent with an autosomal dominant inheritance pattern in PCOS families, perhaps caused by the same gene. There was no such genetic influence in families of women without PCOS. Sisters of PCOS probands with polycystic ovarian morphology were more likely to have menstrual irregularity and had larger ovaries and higher serum androstenedione and dehydroepiandrosterone-sulfate levels than sisters without PCO. This suggests a spectrum of clinical phenotype in PCOS families. Men with PMPB had higher serum testosterone than those without. Collectively, these data are consistent with a role for genetic differences in androgen synthesis, metabolism, or action in the pathogenesis of PCOS.
To examine the association between male pattern baldness and the risk of coronary heart disease (CHD) events.
Retrospective cohort study among 22,071 US male physicians aged 40 to 84 years enrolled in the Physicians' Health Study. Of these, 19,112 were free of CHD at baseline and completed a questionnaire at the 11-year follow-up concerning their pattern of hair loss at age 45 years. Response options included no hair loss, frontal baldness only, or frontal baldness with mild, moderate, or severe vertex baldness.
Coronary heart disease events defined as nonfatal myocardial infarction (MI), angina pectoris, and/or coronary revascularization.
During 11 years of follow-up, we documented 1446 CHD events in this cohort. Compared with men with no hair loss, those with frontal baldness had an age-adjusted relative risk (RR) of CHD of 1.09 (95% confidence interval [CI], 0.94-1.25), while those with mild, moderate, or severe vertex baldness had RRs of 1.23 (95% CI, 1.05-1.43), 1.32 (95% CI, 1.10-1.59), and 1.36 (95% CI, 1.11-1.67), respectively (P for trend, <.001). Multivariate adjustment for age, parental history of MI, height, body mass index (weight in kilograms divided by the square of the height in meters as a continuous variable), smoking, history of hypertension, diabetes, high cholesterol level, physical activity, and alcohol intake did not materially alter these associations. Results were similar when nonfatal MI, angina, and coronary revascularization were examined separately, and when events were analyzed among men older and younger than 55 years at baseline. Vertex baldness was more strongly associated with CHD risk among men with hypertension (multivariate RR, 1.79; 95% CI, 1.31-2.44) or high cholesterol levels (multivariate RR, 2.78; 95% CI, 1.09-7.12).
Vertex pattern baldness appears to be a marker for increased risk of CHD events, especially among men with hypertension or high cholesterol levels.
Androgenetic alopecia especially that with premature onset can be a cause of serious psychic trauma. As far as the treatment with antiandrogens, inhibitors of 5 alpha-reductase or hair transplantation represents a heavy economic burden for the patient, we tried to exclude other hormonal causes or to find a criterion for the apt candidates for the treatment in 15 young men with premature androgenetic alopecia. Hormonal analysis discovered a significantly lower plasma level of sexual binding globulin (SHBG) and FSH and nearly significantly higher concentration of 17 alpha-hydroxyprogesterone. These data resemble those in the hormonal pattern of women suffering from the syndrome of polycystic ovaries (PCOS). The finding of premature balding as the possible male phenotype hormonal equivalent of polycystic ovaries is in concordance with several pedigree studies in kindreds with PCOS, which have suggested a genetic basis of this syndrome in some families in which balding and pilosity was frequent in male members.
The previously proven association between androgenetic, alopecia and serious cardiovascular events raises a question of the common pathogenetic mechanism of these disorders. Our practice-based case-control study in men aged 19-50 years showed a strikingly increased risk of hyperinsulinaemia and insulin-resistance-associated disorders such as obesity, hypertension, and dyslipidemia in men with early onset of alopecia (<35), compared with age-matched controls. This finding supports the hypothesis that early androgenetic alopecia could be a clinical marker of insulin resistance.
The male phenotype in PCOS is still uncertain. Multiple possible phenotypes have been proposed including such abnormalities in male hair distribution as premature balding and metabolic abnormalities such as insulin resistance. Problems with phenotyping to date are reviewed and potential new paths for familial phenotyping are discussed. Identifying a male phenotype would increase the sample size for genetic analyses of the causative gene. It may also improve the phenotyping of female family members by identifying familial traits that are gender independent.
Androgenetic alopecia (AGA), also known in women as female pattern hair loss, is caused by androgens in genetically susceptible women and men. The thinning begins between ages 12 and 40 years, the inheritance pattern is polygenic, and the incidence is the same as in men. In susceptible hair follicles, dihydrotestosterone binds to the androgen receptor, and the hormone-receptor complex activates the genes responsible for the gradual transformation of large terminal follicles to miniaturized follicles. Both young women and young men with AGA have higher levels of 5α reductase and androgen receptor in frontal hair follicles compared to occipital follicles. At the same time, young women have much higher levels of cytochrome p-450 aromatase in frontal follicles than men who have minimal aromatase, and women have even higher aromatase levels in occipital follicles. The diagnosis of AGA in women is supported by early age of onset, the pattern of increased thinning over the frontal/parietal scalp with greater density over the occipital scalp, retention of the frontal hairline, and the presence of miniaturized hairs. Most women with AGA have normal menses and pregnancies. Extensive hormonal testing is usually not needed unless symptoms and signs of androgen excess are present such as hirsutism, severe unresponsive cystic acne, virilization, or galactorrhea. Topical minoxidil solution is the only drug available for promoting hair growth in women with AGA. Efficacy has been shown in double-blind studies using hair counts and hair weight.
About 60% of patients with polycystic ovary syndrome (PCOS) have insulin resistance, predisposing them to the premature coronary disease and type 2-diabetes mellitus. However, the history of metabolic disorders in family members of patients with PCOS has been seldom documented in the literature.
To evaluate the family profile of metabolic disorders of PCOS patients and to determine their relative risk of developing one of them in comparison to a control group.
Sixty PCOS patients were evaluated. The control group were 60 normal women. The data were obtained from the clinical history and personal interview with the patients, the controls and their relatives (brothers, parents and grandparents). The metabolic disorders considered were: dyslipidemia, obesity, hypertension and diabetes.
The ages were similar between groups (PCOS: 24.0 +/- 6.3; control group: 24.8 +/- 6.2 years). The prevalence of metabolic disorders was 62% in the relatives of the PCOS patients and 27.8% in the relatives of the control group (p < 0.005). The probability to develop a metabolic disorder within the family was 2.7 (2.2-3.3) fold higher in the PCOS group compared to the control group. The risk of developing hypertension, dyslipidemia, obesity and diabetes was 2.1 (1.5-2.9); 1.8 (1.5-2.7); 3.6 (2.6-4.9) and 2.7 (1.8-3.9), respectively, in the PCOS group compared to the control group.
The probability of finding a metabolic disorder in the families of PCOS patients, is 2.7 fold higher than in the control group families. The metabolic disorders are more frequent in parents and grandparents of the PCOS patients than in those of normal women.