Article

Reproductive endocrinology: New guidelines for the diagnosis and treatment of PCOS

December 2013
Nature Reviews Endocrinology 10(3)

December 2013
10(3)

DOI:10.1038/nrendo.2013.248

Source
PubMed

Authors:

Francesco Orio

Parthenope University of Naples

Stefano Palomba

Università degli Studi di Modena e Reggio Emilia

An Endocrine Society-appointed task force has developed an evidence-based clinical practice guideline for the diagnosis and treatment of polycystic ovary syndrome. The guidelines provide suggestions for the management of patients with polycystic ovary syndrome and highlight many areas of uncertainty requiring further scientific efforts.

Knowledge of Polycystic Ovarian Syndrome, Its Complications, and Management among Lebanese Women: A Cross-Sectional Survey

Article

Full-text available

Jul 2022

Introduction Polycystic ovarian syndrome (PCOS) is a multi-spectrum disease where a failure to address it correctly can result in various clinical complications. This study aimed to assess the Lebanese women's knowledge and perceptions of PCOS and its management. Materials and Methods This cross-sectional study included women whose ages ranged between 18 and 45 years. Women's demographic characteristics, reproductive health, knowledge, and perception of PCOS were analyzed through an online validated questionnaire. Results Among the 450 included women, 196 (43.6%) had good knowledge about PCOS. The majority of participants were aware that menstrual irregularity is a symptom of PCOS, 327 (72.7%), while only 231 (51.3%) women knew that PCOS may lead to infertility. Almost two-thirds of women were aware of the contribution of metformin, diet, and exercise in refining the progress of the disease. More than 60% of participants believed that PCOS patients need social support and have a low body image. Married women (p < 0.001) and those with undergraduate/ postgraduate degrees (p < 0.001) had better PCOS knowledge. Conclusion A significant percentage of Lebanese women have inadequate knowledge of PCOS and its complications.

Endometrial function in women with polycystic ovary syndrome: A comprehensive review

Article

Dec 2020
HUM REPROD UPDATE

Background: Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility. An endometrial component has been suggested to contribute to subfertility and poor reproductive outcomes in affected women. Objective and rationale: The aim of this review was to determine whether there is sufficient evidence to support that endometrial function is altered in women with PCOS, whether clinical features of PCOS affect the endometrium, and whether there are evidence-based interventions to improve endometrial dysfunction in PCOS women. Search methods: An extensive literature search was performed from 1970 up to July 2020 using PubMed and Web of Science without language restriction. The search included all titles and abstracts assessing a relationship between PCOS and endometrial function, the role played by clinical and biochemical/hormonal factors related to PCOS and endometrial function, and the potential interventions aimed to improve endometrial function in women with PCOS. All published papers were included if considered relevant. Studies having a specific topic/hypothesis regarding endometrial cancer/hyperplasia in women with PCOS were excluded from the analysis. Outcomes: Experimental and clinical data suggest that the endometrium differs in women with PCOS when compared to healthy controls. Clinical characteristics related to the syndrome, alone and/or in combination, may contribute to dysregulation of endometrial expression of sex hormone receptors and co-receptors, increase endometrial insulin-resistance with impaired glucose transport and utilization, and result in chronic low-grade inflammation, immune dysfunction, altered uterine vascularity, abnormal endometrial gene expression and cellular abnormalities in women with PCOS. Among several interventions to improve endometrial function in women with PCOS, to date, only lifestyle modification, metformin and bariatric surgery have the highest scientific evidence for clinical benefit. Wider implications: Endometrial dysfunction and abnormal trophoblast invasion and placentation in PCOS women can predispose to miscarriage and pregnancy complications. Thus, patients and their health care providers should advise about these risks. Although currently no intervention can be universally recommended to reverse endometrial dysfunction in PCOS women, lifestyle modifications and metformin may improve underlying endometrial dysfunction and pregnancy outcomes in obese and/or insulin resistant patients. Bariatric surgery has shown its efficacy in severely obese PCOS patients, but a careful evaluation of the benefit/risk ratio is warranted. Large scale randomized controlled clinical trials should address these possibilities.

A Comparison Between the Effect of Low-Level Laser Therapy and Clomiphene on Rats’ Ovarian Tissue Blood Vessels Under In Vivo Conditions

Article

Aug 2022

Background: Studying the prevalence of infertility as a common disease and its treatment have recently become an important issue. These treatments include drugs and surgery; and lasers have also been used complementarily. However, they affect the ovarian blood vessels number. Accordingly, the present study was conducted to investigate the photo-bio stimulation effect on near-infrared and red laser as of low-level lasers on the blood vessels in ovarian tissue, compared with the clomiphene’s effect. Methods: Twenty-eight female rats were randomly divided into four groups: Control (CT), Clomiphene Drug (D), Red Laser (RL) and Near-Infrared Laser (NIRL). Afterwards, the laser groups received irradiation (5 J/cm2 dose) and the rats in group D received clomiphene (1µg/kg). After the experiment, the animals were anesthetized and their ovaries were removed. Henceforth, the laser’s effect was investigated and compared with that of clomiphene. Results: The number of the blood vessels increased in NIRL (71.96%) and RL (67.070%) groups, compared with CT. It was also increased in NIRL (59.81%) and RL (14%) compared to D group. In addition, it increased in NIRL (53.27%) compared with RL. This increase was significant in the NIRL group indicating that NIRL increases ovarian activity to produce blood vessels that can be certainly used in future studies for finding a cure for ovarian negligence to produce more blood vessels and treat diseases caused by it. Conclusion: The results convinced us to introduce laser as a new method to increase the ovarian activation by increasing the blood vessels in a future study. Although the mechanism of low-level lasers action is not well known, it has been proved to be more effective than clomiphene.

Resistance to the Insulin and Elevated Level of Androgen: A Major Cause of Polycystic Ovary Syndrome

Article

Full-text available

Oct 2021

PCOS has a wide range of negative impacts on women’s health and is one of the most frequent reproductive systemic endocrine disorders. PCOS has complex characteristics and symptom heterogeneity due to the several pathways that are involved in the infection and the absence of a comm14on cause. A recent study has shown that the main etiology and endocrine aspects of PCOS are the increased level of androgen, which is also known as “hyperandrogenemia (HA)” and secondly the “insulin resistance (IR)”. The major underlying cause of the polycystic ovary is these two IR and HA, by initiating the disease and its severity or duration. As a consequence, study on Pathogenesis is crucial to understand the effect of “HA” and “IR” on the pathophysiology of numerous symptoms linked to PCOS. A deep understanding of the pattern of the growth in PCOS for HA and IR can help ameliorate the condition, along with adjustments in nutrition and life, as well as the discovery of new medicinal products. However, further research is required to clarify the mutual role of IR and HA on PCOS development.

PATHOGENETIC ASPECTS OF METABOLIC SYNDROME IN WOMEN OF REPRODUCTIVE AGE (A LITERATURE REVIEW)

Article

Full-text available

May 2019

Aim . The aim of this work was to analyze recently published data on the risk factors and pathogenetic aspects of metabolic syndrome (MS) in women of reproductive age. Materials and methods . This review covers data presented in foreign and Russian literature, which has been published in electronic bibliographic databases Pubmed and the Cochrane Library over the past 10 years. Specifi cally, we carried out an analysis of works containing information on risk factors, pathogenetic aspects and diagnostic criteria of MS in women of reproductive age, as well as on methods currently used for the treatment of this condition. Results . We characterize modern theories that explain mechanisms triggering the development of MS complicated with diabetes 2 type and polycystic ovary syndrome (PCOS). Data on proteomic markers refl ecting the complex pathogenesis of PCOS is generalized, along with their role in the diagnosis and treatment of this disease. The possibility of using these markers for predicting pregnancy outcomes is shown. The importance of regulating metabolic processes for the preparation of women for pregnancy and fertility recovery is emphasized. Conclusion . Hyperandrogenism, insulin resistance, obesity, diabetes 2 type, dyslipidemia, PCOS are shown to be the most signifi cant factors determining pathological changes in fertile age women with metabolic syndrome. The correction of these factors should be included in the course of pregravid preparation for the prevention of adverse pregnancy outcomes.

Inositols in the Treatment of Insulin-Mediated Diseases

Article

Full-text available

Sep 2016

A growing body of research is currently focused on the role of inositol isomers and in particular myo-inositol (MYO-INS) and D-chiroinositol (DCI) in the treatment of insulin resistance states. Both isomers have been shown to exert insulin-mimetic action and to lower postprandial glucose. Further, insulin resistance-related diseases were associated to derangements in inositol metabolism. Thus, the aim of this review is to provide current evidence on the potential benefits of inositol isomers (MYO-INS and DCI) in the treatment of disease associated to insulin resistance such as polycystic ovary syndrome (PCOS), gestational diabetes, and metabolic syndrome. Finally, molecular insights into inositol insulin-sensitizing effects will be covered focusing on the possible role of inositol glycans as insulin second messengers.

Current Insights Into Inositol Isoforms, Mediterranean and Ketogenic Diets for Polycystic Ovary Syndrome: From Bench to Bedside

Article

Full-text available

Jul 2016
CURR PHARM DESIGN

Background: Polycystic ovary syndrome (PCOS) is a complex syndrome characterized by reproductive and metabolic implications. Lifestyle changes, such as diet and exercise, are considered first-line treatment for women affected by PCOS. Pharmacologic treatments target the hormonal and metabolic dysregulations associated to the disease such as insulin resistance, anovulation, hirsutism and menstrual irregularities. Objective: To focus on the role of inositol isoforms, as well as Mediterranean and ketogenic diets, as possible therapeutic strategies in PCOS women. Method: Narrative overview, synthesizing the findings of literature retrieved from searches of computerized databases. Results: Accumulating evidence suggests that two inositol isoforms, myo- and D-chiro-, may play a pivotal role in re-addressing both hormonal and metabolic parameters toward homeostasis, counteracting the symptoms and signs typical of this syndrome. In addition, studies focused on Mediterranean and ketogenic diet provided positive results in patients affected by obesity and type 2 diabetes, so these dietetic regimens could represent a fascinating dietetic treatment for the management of PCOS Conclusion: Both the isoforms of inositol are effective in improving ovarian function and metabolism in patients with PCOS. In spite of accumulating evidence, it is currently not possible to draw firm conclusion(s) about the efficacy of these interventions considering the severe bias due to different samples size, dose, and duration of intervention among the published studies on this topic. Furthermore, future longitudinal cohort studies along with prospective interventional trials may contribute to better clarify the role of Mediterranean and ketogenic diets in the treatment of PCOS.

Oral contraceptives versus physical exercise on cardiovascular and metabolic risk factors in women with polycystic ovary syndrome: A randomized controlled trial

Article

Full-text available

May 2016
CLIN ENDOCRINOL

Background Although oral contraceptives (OCs) are one the most widespread therapy in young polycystic ovary syndrome (PCOS) women and physical exercise represents a crucial first step in the treatment of overweight and obese PCOS, no studies were performed to compare the effects on cardiovascular risk (CVR) of OCs and physical exercise in PCOS. Objective To compare the effects of OCs administration and physical exercise on the CVR, clinical, hormonal and metabolic parameters in PCOS women. Methods One hundred and fifty PCOS women were enrolled and were randomized to OCs (3 mg drospirenone plus 30 g ethinyloestradiol), structured exercise training programme (SETP) or polyvitamin tablets. The intervention phase study was of 6 months. Primary outcome was intima-media thickness (IMT) and flow-mediated dilation (FMD). Secondary outcomes were clinical, hormonal and metabolic changes. ResultsA significant reduction of IMT and a significant increase of FMD were observed in the SETP group after treatment. Compared to baseline, in the SETP group, a significant improvement in anthropometric measures, insulin sensitivity indexes, lipid profile, cardiopulmonary function, inflammatory markers and frequency of menses was observed. Oral contraceptives use was associated with a significant decrease of hyperandrogenism and a significant improvement of frequency of menses. Further, OCs use had a neutral effect on CVR risk factors. ConclusionOCs effectively treat hyperandrogenism and menstrual disturbances, while SETP is more effective in improving cardiometabolic profile and cardiopulmonary function in PCOS.</IN

The interplay of oxidative stress and immune dysfunction in Hashimoto’s thyroiditis and polycystic ovary syndrome: a comprehensive review

Article

Full-text available

Jul 2023

In recent years, there has been a significant increase in the concomitant incidence of Hashimoto’s thyroiditis (HT) and polycystic ovary syndrome (PCOS), both in terms of incidence, etiology, and clinical consequences. PCOS patients suffering from autoimmune thyroid diseases show insulin resistance, impaired glucose tolerance, weight gain, and metabolic and reproductive complications. Studies have shown that chronic stress and its consequence, i.e. oxidative stress, play an important role in the pathomechanism of both disorders. It has also been shown that long-term exposure to stress triggers biological mechanisms, in particular related to the regulation of the inflammatory cascade, which plays a key role in autoimmune diseases. The paper is a review of the literature on the role of chronic stress, oxidative stress, and immune processes in the pathogenesis of HT and PCOS. In addition, the review is a source of knowledge about the treatment of these diseases, and in particular the use of antioxidants in therapeutic management.

ANGPTL4 inhibits granulosa cell proliferation in polycystic ovary syndrome by EGFR/JAK1/STAT3‐mediated induction of p21

Article

Full-text available

Jan 2023
FASEB J

Polycystic ovary syndrome (PCOS) is one of the most common, heterogenous endocrine disorders and is the leading cause of ovulatory obstacle associated with abnormal folliculogenesis. Dysfunction of ovarian granulosa cells (GCs) is recognized as a major factor that underlies abnormal follicle maturation. Angiopoietin‐like 4 (ANGPTL4) expression in GCs differs between patients with and without PCOS. However, the role and mechanism of ANGPTL4 in impaired follicular development are still poorly understood. Here, the case–control study was designed to investigate the predictive value of ANGPTL4 in PCOS while cell experiments in vitro were set for mechanism research. Results found that ANGPTL4 levels in serum and in follicular fluid, and its expression in GCs, were upregulated in patients with PCOS. In KGN and SVOG cells, upregulation of ANGPTL4 inhibited the proliferation of GCs by blocking G1/S cell cycle progression, as well as the molecular activation of the EGFR/JAK1/STAT3 cascade. Moreover, the STAT3‐dependent CDKN1A(p21) promoter increased CDKN1A transcription, resulting in remarkable suppression effect on GCs. Together, our results demonstrated that overexpression of ANGPTL4 inhibited the proliferation of GCs through EGFR/JAK1/STAT3‐mediated induction of p21, thus providing a novel epigenetic mechanism for the pathogenesis of PCOS.

Effect of Laparoscopic Ovarian Drilling on Outcomes of In-Vitro Fertilization in Clomiphene-Resistant Women with Polycystic Ovary Syndrome

Article

Nov 2022

Fructose-associated elevation of serum uric acid levels may be involved in metabolic disorders in polycystic ovary syndrome: A case-control study

Preprint

Sep 2022

Objective To investigate the relationship between serum fructose and uric acid levels in patients with polycystic ovary syndrome (PCOS). Design A case-control study. Setting University-affiliated in vitro fertilization clinic. Population 292 patients with PCOS and 482 controls. Main Outcome Measures Serum fructose, uric acid and metabolic measurements. Results Compared with controls, serum fructose and uric acid levels were significantly increased in women with PCOS and patients with PCOS accompanied by metabolic disorders exhibited higher serum fructose and uric acid levels (P < 0.001). Restricted cubic splines indicated that serum uric acid levels linearly and positively correlated with serum fructose levels in women with PCOS (Poverall < 0.001, Pnon-linear = 0.30), whereas no correlation was found in controls (Poverall = 0.712, Pnon-linear = 0.43). Additionally, even after adjusting for confounding factors, serum fructose levels were an independent risk factor for hyperuricemia in patients with PCOS (P = 0.001; odds ratio, 1.380; 95% confidence interval, 1.207–1.577). Conclusions There was a significantly positive association of elevated uric acid levels with serum fructose levels in PCOS and was closely correlated with PCOS-related metabolic disorders, highlighting the importance of further research into the biological mechanisms of fructose and uric acid in the development of PCOS. Funding National Natural Science Foundation of China (No. 82071607 and 32100691); LiaoNing Revitalization Talents Program (No. XLYC1907071); Fok Ying Tung Education Foundation (No. 151039); Key Research and Development Program of Liaoning Province (No. 2018225062); Outstanding Scientific Fund of Shengjing Hospital (No. 202003). Keywords Fructose; Uric acid; PCOS; Metabolic disorder

Large randomized controlled trials in reproductive medicine: another battle won by biases and confounders?

Article

Mar 2022

Stefano Palomba

Dear Sir, I read with great interest a randomized controlled trial (RCT) recently published in Human Reproduction (Wen et al., 2021). The study is a well-designed trial with a published protocol (Li et al., 2017) and aimed to evaluate the effect of acupuncture on insulin sensitivity, assessed as HOMA-IR score (homeostasis model assessment of insulin resistance score), in comparison to metformin or sham acupuncture, in a large population of women with polycystic ovary syndrome (PCOS). Insulin resistance was defined as a HOMA-IR index equal or higher than 2.14. No difference was observed between acupuncture and metformin in insulin resistance improvement. However, metformin induced a body weight loss higher than acupuncture did; acupuncture reduced significantly the fasting glucose levels in comparison with metformin albeit this reduction was small enough to be considered significant only from a statistical point of view. It is well known that RCTs are the best way to obtain scientific data with a low risk of bias, and that data analysis using the intention-to-treat analysis is needed to sustain the efficacy of the randomization. However, in the trial by Wen et al. (2021), the drop-out rates were very high, reaching about one-third of the patients in two arms; during study design, no implementation of the sample size was defined to replace subjects that dropped out. Thus, per-protocol analysis might give a more correct direction of the metabolic effect of acupuncture.

Brown adipose tissue activation with ginsenoside compound K ameliorates polycystic ovary syndrome

Article

Full-text available

Jul 2022
BRIT J PHARMACOL

Background and Purpose Polycystic ovary syndrome (PCOS) is a common metabolic and endocrine disease affecting women of reproductive age. Due to its complex aetiology, there is no currently effective cure for PCOS. Brown adipose tissue (BAT) activity is significantly decreased in PCOS patients, and BAT activation has beneficial effects in animal models of PCOS. Here, we investigated the effect of ginsenoside compound K (CK) in an animal model of PCOS and its mechanism of BAT activation. Experimental Approach Primary brown adipocytes, Db/Db mice and dehydroepiandrosterone (DHEA)‐induced PCOS rats were used. The core body temperature, oxygen consumption, energy metabolism related gene and protein expression were assessed to identify the effect of CK on overall energy metabolism. Oestrous cycle, serum sex hormone, ovarian steroidogenic enzyme gene expression and ovarian morphology were also evaluated following CK treatment. Key Results Our results indicated that CK treatment could significantly protect against body weight gain in Db/Db mice via BAT activation. Furthermore, we found that CK treatment could normalize hyperandrogenism, oestrous cyclicity, normalize steroidogenic enzyme expression and decrease the number of cystic follicles in PCOS rats. Interestingly, as a potential endocrine intermediate, C‐X‐C motif chemokine ligand‐14 protein (CXCL14) was significantly up‐regulated following CK administration. In addition, exogenous CXC14 supplementation was found to reverse DHEA‐induced PCOS in a phenotypically similar manner to CK treatment. Conclusion and Implications In summary, CK treatment significantly activates BAT, increases CXCL14 expression and ameliorates PCOS. These findings suggest that CK might be a potential drug candidate for PCOS treatment.

Tai Chi for Overweight/Obese Adolescents and Young Women with Polycystic Ovary Syndrome: A Randomized Controlled Pilot Trial

Article

Full-text available

Jun 2022
EVID-BASED COMPL ALT

Background: Exercise is one of the recommended interventions for polycystic ovary syndrome (PCOS), and current evidence has shown that Tai chi may have favorable effects. The objective of this randomized controlled pilot trial was to study the feasibility and potential effects of Tai chi for overweight/obese adolescents and young women with PCOS, so a future definitive randomized controlled trial (RCT) can be well designed and implemented. Materials and methods: This study recruited 50 patients who were randomly assigned to two groups (Tai chi and self-monitored exercise) at a ratio of 3 : 2. The intervention lasted for 3 months, and the feasibility and effectiveness outcomes were measured. Results: A total of 42 patients completed the study, including 24 in the Tai chi group and 18 in the control group. Compared with the self-monitored exercise group, there was a significantly decreased body mass index (BMI) in the Tai chi group adjusted for baseline BMI. The testosterone level and lipid profile were also decreased compared to controls; the same tendency was also observed for the homeostasis model assessment of insulin resistance (HOMA-IR), but the difference did not achieve statistical significance. Twenty-four (out of 30, 80%) patients in the Tai chi group and 18 (out of 20, 90%) patients in the self-monitored exercise group completed the data collection. A total of 36 exercise sessions were held in both groups. Patients in the Tai chi group took a mean of 34.0 ± 2.21 classes (93.06%), and those in the self-monitored exercise group engaged in 32 ± 3.06 exercise sessions (88.27%) out of the 36 required exercise sessions. Conclusions: The present pilot study was feasible to deliver; there was a decrease in BMI, testosterone level, and lipid profile for PCOS patients in the Tai chi group at 3 months. In a future definitive trial, lower recruitment rate and outcome measurements lead to poor patient acceptance such as the 5-time point oral glucose tolerance test need to be considered and one fixed type of aerobic exercise and supervision from the investigator for the control group are also needed. Trial registration: ClinicalTrials.gov, NCT02608554.

COMPARISON OF OVULATION INDUCTION LETROZOLE AND CLOMIPHENE CITRATE IN SUBFERTILE WOMEN WITH POLYCYSTIC OVARIAN SYNDROME

Article

Oct 2021

Objective: To compare the ovulation induction of letrozole and clomiphene citrate in sub-fertile women with polycystic ovarian syndrome. Study Design: Quasi experimental study. Place and Duration of Study: Combined Military Hospital Rawalpindi, from Jun 2018 to Aug 2019. Methodology: A total of 116 married sub-fertile women with polycystic ovarian syndrome, 16-40 years of age were included. Patients with previous surgery related to genital tract, hypothyroidism and chronic renal failure were excluded. Letrozole 5.0mg daily from Day 5-9 of menstruation was prescribed to group A women and clomiphene citrate 100 mg daily from Day 5-9 of menses was given to group B women. Results: In group A and in group B, mean age was 29.78 ± 4.71 years and 29.95 ± 4.22 years respectively. Most of the patients 59 (50.86%) were between 18-30 years of age. Mean duration since marriage was 4.23 ± 1.42 years. Mean body mass index was 29.71 ± 2.65 kg/m2. Frequency of ovulation of clomiphene citrate and letrozole in sub-fertile women with polycystic ovaries was 28 (42.28%) versus 42 (72.41%) respectively (p-value=0.008). Conclusion: This study concluded that ovulation induction of letrozole is better than clomiphene citrate in sub-fertile women with polycystic ovarian syndrome.

Development and validation of a guideline on sexual and reproductive health services for polycystic ovary syndrome in Iran: a mixed-methods study protocol

Article

Full-text available

Dec 2021
Health Res Pol Syst

Background Sexual and reproductive health (SRH) is an important aspect of women's health. Polycystic ovary syndrome is a common disease among women and has long-term negative effects on women’s health. Evidence shows that polycystic ovary syndrome has different impacts on SRH needs among women. The aim of this study is to design and validate an SRH services guideline for healthcare providers in treating women with polycystic ovary syndrome. Methods The guideline will be developed and validated using an exploratory sequential mixed-methods approach in three phases based on the National Institute for Health and Care Excellence (NICE) model: (1) scoping phase (describing the SRH needs of women with polycystic ovary syndrome from the results of both review and qualitative studies); (2) development phase (developing a primary guideline for SRH services); (3) validation phase (validation of the guideline will be performed by a panel of experts and stakeholders using the AGREE [Appraisal of Guidelines for Research and Evaluation] tool). Discussion A specific and practical guideline on the SRH of Iranian women with polycystic ovary syndrome will be developed, which will be compatible with their specific needs and culture, considering the limited resources available. It will help service providers identify and address the specific needs of women with polycystic ovary syndrome.

Improving the sexual activity and reproduction of female zebrafish with high testosterone levels

Article

Full-text available

Feb 2021

High levels of testosterone cause clinical symptoms in female reproduction and possibly, alterations in sexuality. Yet, the underlying mechanisms remain to be examined. Here, we report a study that investigates the effects of testosterone in follicle development and sexual mating using zebrafish models. We developed an acute zebrafish model with high testosterone levels by exposing young female zebrafish to testosterone dissolved in swimming water. After given a high concentration of testosterone treatment (e.g., 100 ng/ml), the fish showed hallmark pathological symptoms similar to those displayed in patients with polycystic ovary syndrome (PCOS), such as follicular growth-arrest, rare ovulation, ovary enlargement, decrease in reproduction, and down regulation of the expression of some PCOS susceptible genes, such as Tox3. These fish are referred to as the PCOS fish. By monitoring mating-like swimming behaviors, we measured the sexual activity of PCOS zebrafish. In general, the PCOS fish showed no desire to interact with males. As a consequence, their mating rate was decreased as compared to control animals. The sexuality levels of PCOS fish, however, could be improved after short periods of rearing in conditions that lack of males. After only 3 days of rearing alone, the PCOS fish showed an increase in sexuality levels and displayed characteristic swimming patterns for mating. After 30 days of separation from males, not only the sexual activity, but also the mating rate was improved in the PCOS fish. Together, the data suggests that zebrafish can serve as a new type of research model to further develop strategies for the treatment of reproductive disorders, such as those related to PCOS.

Exploration of Lifestyle Choices, Reproductive Health Knowledge, and Polycystic Ovary Syndrome (PCOS) Awareness Among Female Emirati University Students

Article

Full-text available

Oct 2020

Sreepoorna Pramodh

Objective Healthy lifestyle and adequate reproductive health knowledge are prerequisites for maintenance of physical and mental well-being of women across the world. With increasing prevalence of metabolic disorders such as polycystic ovary syndrome (PCOS), it is important that sufficient awareness of these issues is generated, especially in conservative communities in Arab regions. The main objective of this study is to assess reproductive health (RH) knowledge and awareness of PCOS among female Emirati students and also to explore their lifestyle choices. Materials and Methods A total of 493 Emirati students were recruited based on convenience sampling and completed a survey containing questions related to demography, lifestyle preferences, RH knowledge, and PCOS awareness. Results Of the students, 13% self-reported being diagnosed with PCOS, with 3.5% also taking medication for the same, 6% reported having high androgen levels, 30.7% reported polymenorrhea, and 3.5% reported oligomenorrhea for frequency of menstrual cycle. Also, 12.4% students experienced abnormal bleeding (heavy/none) during menstruation and 24% reported excessive body hair. It was found that 4.3% of students were taking medication for hyperglycemia and 75% of students reported a family history of diabetes. Students displayed low reproductive health knowledge and poor awareness of PCOS. Lifestyle preferences indicated low physical activity and high indulgence in fast food. Conclusion Lifestyle choices adopted by Emirati University students may predispose them to disorders such as PCOS. Early detection and management of PCOS coupled with a dynamic awareness campaign for RH can help in improving fertility rates of Emirati women. The study identifies major gaps in knowledge and awareness of RH and PCOS in Emirati women that need to be addressed by creating a culturally congruent heathcare policy with emphasis on education and health promotion. Mandatory PA programs and increasing availability of healthy eating options in campus should be considered by all universities, particularly in Arab regions, for improving lifestyle and preventing metabolic disorders in young students.

Melatonin in the Clinical Management of Polycystic Ovarian Syndrome Mini Review JOJ Nurse Health Care

Article

Full-text available

Jan 2018

Polycystic ovarian syndrome (PCOS) is one of the most prevalent endocrine disorders affecting women of reproductive age. PCOS is characterized by oligo ovulation and/or anovulation, and excess androgens. Recently, the pineal hormone melatonin earned serious attention for clinical use in the management of PCOS with infertility. Melatonin treatment led to improvement of ovarian functions, oocyte quality, metabolic and hormonal profiles in PCOS. Accumulating studies provide persuasive evidence in favor of the conjecture that melatonin due to its broad-spectrum antioxidant property may play a critical role in the care and cure of this syndrome.

Roles of follicle stimulating hormone and its receptor in human metabolic diseases and cancer

Article

Jul 2020

Follicle stimulating hormone (FSH) and its receptor (FSHR) play an important role in human metabolic diseases and cancer. Evidence showed that FSHR is not only distributed in ovary and testis but also in other cells or organs such as osteoclast, adipocytes, liver, pituitary cancer and so forth. Moreover, FSH is associated with lipogenesis, inflammation, insulin sensitivity, thermogenesis, skeletal metabolism, osteogenesis and ovarian cancer, all of which have been confirmed closely related to metabolic diseases or metabolic-related cancer. Therefore, FSH and FSHR may be potential therapeutic targets for metabolic diseases and metabolic-related cancer. Epidemiological researches revealed close relationship between FSH/FSHR and metabolic diseases or cancer. Experimental studies elucidated the underlying mechanism both in vivo and in vitro. We reviewed the recent researches and present an integrated framework of FSH/FSHR and metabolic diseases and cancer, which provides potential targets for the treatments of metabolic diseases and cancer.

The 40:1 myo-inositol/D-chiro-inositol plasma ratio is able to restore ovulation in PCOS patients: comparison with other ratios

Article

Jun 2019

Objective: The aim of this clinical trial was to evaluate the efficacy of seven different ratios between two inositols stereoisomers, myo-inositol (MI) and D-chiro-inositol (DCI), in the therapy of polycystic ovary syndrome (PCOS). Patients and methods: fifty-six PCOS patients (8 for each group) were treated by oral route using the following formulations: DCI alone, and 1:3.5; 2.5:1; 5:1; 20:1; 40:1, 80:1 MI/DCI ratio. They received 2 g of inositols twice a day for 3 months. The primary outcome was ovulation, the secondary outcome included the improvement of FSH, LH, Sex Hormone Binding Globulin (SHBG), 17-beta-Estradiol (E2), free testosterone, basal and postprandial insulin levels, as well as HOMA index, BMI and menses. Results: We found that the 40:1 MI/DCI ratio is the best for PCOS therapy aimed at restoring ovulation and normalizing important parameters in these patients. The other formulations were less effective. In particular, a decreased activity was observed when the 40:1 ratio was modified in favour of DCI. Conclusions: Our data demonstrated that DCI activity is beneficial mainly at a specific ratio with MI, whereas the increase of DCI causes the loss of the beneficial effects at reproductive level. These results in humans validate a previous preclinical study with different MI/DCI ratios carried out in an experimental model of PCOS mice.

Effects of a ketogenic diet in overweight women with polycystic ovary syndrome

Article

Full-text available

Feb 2020
J TRANSL MED

Background: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women during reproductive age. It is characterised clinically by oligo-ovulation or anovulation, hyper-androgenism, and the presence of polycystic ovaries. It is associated with an increased prevalence of metabolic syndrome, cardiovascular disease and type 2 diabetes. The onset of PCOS has been associated to several hereditary and environmental factors, but insulin resistance plays a key pathogenetic role. We sought to investigate the effects of a ketogenic diet (KD) on women of childbearing age with a diagnosis of PCOS. Methods: Fourteen overweight women with diagnosis of PCOS underwent to a ketogenic Mediterranean diet with phyoextracts (KEMEPHY) for 12 week. Changes in body weight, body mass index (BMI), fat body mass (FBM), lean body mass (LBM), visceral adipose tissue (VAT), insulin, glucose, HOMA-IR, total cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL), triglycerides (TGs), total and free testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH); dehydroepiandrosterone sulfate (DHEAs), estradiol, progesterone, sex hormone binding globulin (SHBG) and Ferriman Gallwey score were evaluated. Results: After 12 weeks, anthropometric and body composition measurements revealed a significant reduction of body weight (- 9.43 kg), BMI (- 3.35), FBM (8.29 kg) and VAT. There was a significant, slightly decrease of LBM. A significant decrease in glucose and insulin blood levels were observed, together with a significant improvement of HOMA-IR. A significant decrease of triglycerides, total cholesterol and LDL were observed along with a rise in HDL levels. The LH/FSH ratio, LH total and free testosterone, and DHEAS blood levels were also significantly reduced. Estradiol, progesterone and SHBG increased. The Ferriman Gallwey Score was slightly, although not significantly, reduced. Conclusions: Our results suggest that a KD may be considered as a valuable non pharmacological treatment for PCOS. Longer treatment periods should be tested to verify the effect of a KD on the dermatological aspects of PCOS. Trial registration Clinicaltrial.gov, NCT04163120, registrered 10 November 2019, retrospectively registered, https://clinicaltrials.gov.

A Rat Model of Maternal Polycystic Ovary Syndrome Shows that Exposure to Androgens In Utero Results in Dysbiosis of the Intestinal Microbiota and Metabolic Disorders of the Newborn Rat

Article

Full-text available

Dec 2019
MED SCI MONITOR

Background Intestinal dysbiosis, or dysbacteriosis, is an abnormal interaction between the intestinal microbiota and the host cells due to altered microbial diversity. This study aimed to investigate the metabolic effects and changes in the intestinal microbiota in newborn rats following exposure to increased levels of maternal androgens in a rat model of maternal polycystic ovary syndrome (PCOS). Material/Methods The administration of androgen developed the rat maternal PCOS model during pregnancy. Maternal rat ovarian follicles were counting and assessed by histology. The metabolic phenotype of newborn rats was evaluated and included an insulin tolerance test, a glucose tolerance test, and measurement of serum levels of triglyceride, insulin, cholesterol, adiponectin, and leptin. Expression of pro-inflammatory cytokines was detected using quantitative reverse transcription-polymerase chain reaction (qRT-PCR), serum levels were measured by enzyme-linked immunosorbent assay (ELISA), and proteins associated with adipose tissue remodeling and adipocyte differentiation were measured by Western blot. Results Markers of systemic inflammation were significantly increased in the female offspring but not in the male offspring born to rat in the PCOS model. Following birth, newborn rats that received antibiotics showed an improved metabolic phenotype, with reduced serum lipid levels, insulin resistance, body weight, inflammation of adipose tissue, and serum levels of inflammatory cytokines compared with controls. Probiotics had no significant effects on these parameters in newborn rats. Conclusions In a rat model of maternal PCOS, exposure to androgens in utero resulted in dysbiosis of the intestinal microbiota and metabolic disorders of the newborn female rats.

Mistaken Oophorectomy in an Adolescent with McCune–Albright Syndrome: A Case Report and Literature Review

Article

Full-text available

Dec 2018

Jason Zhu

McCune–Albright syndrome (MAS) is a rare disease characterized by café au lait spots, bone fibrous dysplasia, and precocious puberty. Most MAS cases are diagnosed before adolescence. Here, we reported an adolescent girl underwent mistaken oophorectomy for suspected ovarian tumor, and later, she was diagnosed with MAS. An 11‑year‑old girl was found to have an irregular pelvic mass measuring 9.74 cm × 9.01 cm × 7.30 cm with a cyst–solid component and a clear boundary by magnetic resonance imaging. She underwent right oophorectomy for the suspected ovarian tumor. However, histopathological examination showed ovarian tissue with many antral follicles. One week after the surgery, ultrasonography revealed a left pelvic irregular echo‑free mass measuring 60 mm × 53 mm × 48 mm. The patient was then examined by endocrine specialists, and café au lait spots were found predominantly located on the right side of her waist, hip, and thigh. She had her first period before the surgery, and her serum concentrations of sex hormones were normal. Thus, MAS was diagnosed. The patient has been taking dydrogesterone 20 mg/d for 10 days from the 14th day of her period for 2 years. Ultrasonography performed every 3–6 months revealed no enlargement of her left ovary. Awareness of MAS and careful physical and imaging examination should be emphasized, even in the absence of full classic triad of syndromes. Hence, unnecessary oophorectomy and irreversible loss of fertility potential can be avoided in these patients.

Association between the persistent organic pollutants and polycystic ovary syndrome: A protocol for a systematic review and meta-analysis

Article

Full-text available

Aug 2019

Background: Current evidence concerning the association between persistent organic pollutants (POPs) and polycystic ovary syndrome (PCOS) is inconsistent. The aim of the present systematic review and meta-analysis is to evaluate the role of POPs in PCOS. Methods: Databases including PubMed, Embase, Web of Science, and CNKI will be searched to identify qualified studies. All qualified studies regarding the association between POPs and PCOS will be included. The primary outcome of the present study is POPs levels in serum of subjects. Pooled analysis with corresponding 95% confidence intervals will be performed. Results: The comprehensive analysis and quantitative assessment will provide a better understanding of POPs concentrations in patients with PCOS. Conclusion: This meta-analysis and systematic review will generate evidence of the association between POPs and PCOS. Prospero registration number: PROSPERO CRD42019126373.

RS1799817 in INSR associates with susceptibility to polycystic ovary syndrome

Article

Full-text available

Jul 2019

Maha Daghestani

Background Insulin and its receptor ( INSR ) have been implicated in the etiology of the polycystic ovarian syndrome (PCOS). Here, we investigate the association between INSR rs1799817 polymorphism and PCOS in Saudi Arabian women. Methods study group included 126 PCOS women and 118 normo-ovulatory matched controls. The demographic data was recorded, and the plasma levels of glucose, lipids, leptin, E2, LH, FSH, T, SHBG, and insulin were determined. The genotypic and allele frequencies of rs1799817 were evaluated in both PCOS and control group. Polymerase chain reaction (PCR) was used to amplify Exon 17 of the INSR gene, and the amplified products were analyzed by direct sequencing. A single-nucleotide polymorphism (C to T) was found at locus 10923 (His1058) of rs1799817. Results In the PCOS group, the mutant allele T occurs at a significantly higher frequency (0.306) compared to the control group (0.174) (p<0.001). It shows a dominant effect and elevates the relative risk of PCOS even in the heterozygotes (RR=2.82). After stratification of the participants by body mass index, the frequency of T allele was significantly higher in the lean patients with PCOS compared to the lean control. The obese PCOS also had a higher frequency than the obese control, but the difference was not statistically significant. Several parameter values were affected by the INSR genotype, particularly W/H ratio, lipid, insulin and glucose levels and insulin resistance in PCOS patients. Conclusion The INSR gene polymorphism rs1799817 is a susceptibility locus associated with PCOS in Saudis and associated metabolic and hormonal changes, particularly, in the lean PCOS females.

Mistaken Oophorectomy in an Adolescent with McCune-Albright Syndrome: A Case Report and Literature Review

Article

Full-text available

Oct 2018

McCune–Albright syndrome (MAS) is a rare disease characterized by café au lait spots, bone fibrous dysplasia, and precocious puberty. Most MAS cases are diagnosed before adolescence. Here, we reported an adolescent girl underwent mistaken oophorectomy for suspected ovarian tumor, and later, she was diagnosed with MAS. An 11-year-old girl was found to have an irregular pelvic mass measuring 9.74 cm × 9.01 cm × 7.30 cm with a cyst–solid component and a clear boundary by magnetic resonance imaging. She underwent right oophorectomy for the suspected ovarian tumor. However, histopathological examination showed ovarian tissue with many antral follicles. One week after the surgery, ultrasonography revealed a left pelvic irregular echo-free mass measuring 60 mm × 53 mm × 48 mm. The patient was then examined by endocrine specialists, and café au lait spots were found predominantly located on the right side of her waist, hip, and thigh. She had her first period before the surgery, and her serum concentrations of sex hormones were normal. Thus, MAS was diagnosed. The patient has been taking dydrogesterone 20 mg/d for 10 days from the 14th day of her period for 2 years. Ultrasonography performed every 3–6 months revealed no enlargement of her left ovary. Awareness of MAS and careful physical and imaging examination should be emphasized, even in the absence of full classic triad of syndromes. Hence, unnecessary oophorectomy and irreversible loss of fertility potential can be avoided in these patients.

Regulation of Inositol Biosynthesis: Balancing Health and Pathophysiology

Chapter

Dec 2018
Handbook Exp Pharmacol

Inositol is the precursor for all inositol compounds and is essential for viability of eukaryotic cells. Numerous cellular processes and signaling functions are dependent on inositol compounds, and perturbation of their synthesis leads to a wide range of human diseases. Although considerable research has been directed at understanding the function of inositol compounds, especially phosphoinositides and inositol phosphates, a focus on regulatory and homeostatic mechanisms controlling inositol biosynthesis has been largely neglected. Consequently, little is known about how synthesis of inositol is regulated in human cells. Identifying physiological regulators of inositol synthesis and elucidating the molecular mechanisms that regulate inositol synthesis will contribute fundamental insight into cellular processes that are mediated by inositol compounds and will provide a foundation to understand numerous disease processes that result from perturbation of inositol homeostasis. In addition, elucidating the mechanisms of action of inositol-depleting drugs may suggest new strategies for the design of second-generation pharmaceuticals to treat psychiatric disorders and other illnesses.

Tai chi for overweight/obese adolescent and young women with polycystic ovary syndrome: Study protocol for a randomized controlled trial

Article

Full-text available

Sep 2018
TRIALS

Background: Tai Chi is a moderately intense exercise that dates back to ancient China. It has been reported that Tai Chi not only has beneficial effects on metabolic disorders, such as diabetes, cardiovascular diseases and obesity, but also has favorable effects on psychological well-being. Since these conditions are quite closely associated with polycystic ovary syndrome (PCOS), we hypothesis that Tai Chi could be a potential treatment option for PCOS patients. We aim to determine the feasibility and effectiveness of Tai Chi on overweight/obese adolescent and young women with PCOS. Methods: A total of 50 patients will be randomized into two arms: (1) Tai Chi or (2) self-monitored exercise. Both groups will exercise for 3 months. The primary hypothesis is that Tai Chi results in a significantly lower Body Mass Index (BMI) than self-monitored exercise. The study was approved by the Ethics Committee of the First Affiliated Hospital of Heilongjiang University of Chinese Medicine. Discussion: This is the first study to determine the feasibility and effectiveness of Tai Chi in treating overweight/obese adolescent and young women with PCOS. The trial will provide evidence to assess the feasibility of a future multicenter, randomized controlled trial. Trial registration: ClinicalTrials.gov, ID: NCT02608554 . Registered on 17 November 2015.

Polycystic Ovary Syndrome: Insights into the Therapeutic Approach with Inositols

Article

Full-text available

Jun 2017

Polycystic ovary syndrome (PCOS) is characterized by hormonal abnormalities that cause menstrual irregularity and reduce ovulation rate and fertility, associated to insulin resistance. Myo-inositol (cis-1,2,3,5-trans-4,6-cyclohexanehexol, MI) and D-chiro-inositol (cis-1,2,4-trans-3,5,6-cyclohexanehexol, DCI) represent promising treatments for PCOS, having shown some therapeutic benefits without substantial side effects. Because the use of inositols for treating PCOS is widespread, a deep understanding of this treatment option is needed, both in terms of potential mechanisms and efficacy. This review summarizes the current knowledge on the biological effects of MI and DCI and the results obtained from relevant intervention studies with inositols in PCOS. Based on the published results, both MI and DCI represent potential valid therapeutic approaches for the treatment of insulin resistance and its associated metabolic and reproductive disorders, such as those occurring in women affected by PCOS. Furthermore, the combination MI/DCI seems also effective and might be even superior to either inositol species alone. However, based on available data, a particular MI:DCI ratio to be administered to PCOS patients cannot be established. Further studies are then necessary to understand the real contents of MI or DCI uptaken by the ovary following oral administration in order to identify optimal doses and/or combination ratios.

Worldwide Dissatisfaction With the Diagnostic Process and Initial Treatment of PCOS

Article

Feb 2017

Melanie Cree-Green

Combining treatment with myo-inositol and D -chiro-inositol (40:1) is effective in restoring ovary function and metabolic balance in PCOS patients

Article

Nov 2016

Polycystic ovary syndrome (PCOS), a relevant cause of infertility, is a heterogeneous, endocrine disorder affecting up to 10–15% of women in reproductive age. Besides hyperandrogenism, insulin resistance (IR) plays a key role in such syndrome. Insulin-sensitizing drugs, such as Metformin, are effective in treating hyper-insulinemic PCOS patients. Recently, inositols – myo-inositol (MI) and D-chiro-inositol (DCI) – have shown to be an efficient and safe alternative in PCOS management, as both inositol isoforms are able to counteract downstream consequences of insulin resistance. Yet, whereas DCI contributes in mediating insulin activity mainly on non-ovarian tissues, MI displays specific effects on ovary, chiefly by modulating glucose metabolism and FSH-signaling. Moreover, MI may also improve ovarian functions by modulating steroid metabolism through non-insulin-dependent pathways. As DCI and MI activity likely involves different biological mechanisms, both inositol isoforms can be synergistically integrated according to a multitargeted design, by combining MI and DCI in a ratio corresponding to their physiological plasma relative amount (40:1). New experimental and clinical evidence with MI plus DCI evidenced the suitability of such integrated approach, and provided promising results. Further studies need to investigate thoroughly the molecular mechanism and confirm such preliminary data.

Pregnancy complications in women with polycystic ovary syndrome: Importance of diagnostic criteria or of phenotypic features?

Article

Nov 2015
HUM REPROD

Complications and challenges associated with polycystic ovary syndrome: current perspectives

Article

Full-text available

Jul 2015

Polycystic ovary syndrome (PCOS) represents the most common endocrine dysfunction in fertile women and it is considered a heterogeneous and multifaceted disorder, with multiple reproductive and metabolic phenotypes which differently affect the early- and long-term syndrome’s risks. Women with PCOS present an adverse reproductive profile, including a high risk of pregnancy-induced hypertension, preeclampsia, and gestational diabetes mellitus. Patients with PCOS present not only a higher prevalence of classic cardiovascular risk factors, such as hypertension, dyslipidemia, and type-2 diabetes mellitus, but also of nonclassic cardiovascular risk factors, including mood disorders, such as depression and anxiety. Moreover, at the moment, clinical data on cardiovascular morbidity and mortality in women with PCOS are controversial. Finally, women with PCOS show an increased risk of endometrial cancer compared to non-PCOS healthy women, particularly during premenopausal period. Currently, we are unable to clarify if the increased PCOS early- and long-term risks are totally due to PCOS per se or mostly due to obesity, in particular visceral obesity, that characterized the majority of PCOS patients. In any case, the main endocrine and gynecological scientific societies agree to consider women with PCOS at increased risk of obstetric, cardiometabolic, oncology, and psychological complications throughout life, and it is recommended that these women be accurately assessed with periodic follow-up.

Relative importance of AMH and androgens changes with aging among non-obese women with polycystic ovary syndrome

Article

Jul 2015

To assess the changes in phenotypes and endocrine profiles of women with polycystic ovary syndrome (PCOS) with advancing age. In a cross-sectional study conducted at a private tertiary fertility clinical and research center we identified anonymized electronic records of 37 women who had presented with a prior diagnosis of PCOS. They were stratified as younger (<35 years) and older (≥40 years). As controls, we identified 43 women with age-specific low functional ovarian reserve and 14 young women with normal functional ovarian reserve. Endocrine profiles for each group were evaluated based on total (TT) and free testosterone (FT), anti-Müllerian hormone (AMH) and sex hormone binding globulin (SHBG). Patients including those with PCOS were mostly non-obese, evidenced by normal BMIs (21.6 ± 6.0) with no differences between study groups. Young PCOS patients presented with a typical pattern of significant hyperandrogenemia and elevated AMH in comparison to young women with normal functional ovarian reserve [TT 44.0 (32.9-58.7) vs. 23.9 (20.3-28.1) ng/dL, (P<0.05); and AMH 7.7 (6.2-9.1) vs. 2.5 (2.0-3.0) ng/mL, (P<0.05)]. With advancing age, hyperandrogenemia in PCOS diminished in comparison to young women with normal functional ovarian reserve, resulting in similar TT levels [28.6 (19.7-37.5) vs. 23.9 (20.3-28.1) ng/dL]. Though also declining, AMH remained significantly elevated in older PCOS women in comparison to young women with normal functional ovarian reserve [4.0 (2.7-5.2) vs. 2.5 (2.0-3.0) ng/mL, (P<0.05)]. Patients with low functional ovarian reserve demonstrated significantly lower AMH at both young and older ages compared to women with normal functional ovarian reserve (P<0.05 for both). However, among patients with low functional ovarian reserve no differences were observed at young compared to older ages in TT [17.6 (12.9-24.1) vs. 18.1 (13.6-24.1) ng/dL)] and AMH [0.4 (0.3-0.6) vs. 0.3 (0.2-0.5) ng/mL]. SHBG did not differ significantly between groups but trended opposite to testosterone. The PCOS population predominantly consisted of non-obese phenotype at both young and advanced ages. This suggests that patients with "classical" obese PCOS phenotype rarely reach tertiary infertility care, while non-obese PCOS patients may be more resistant to lower levels of infertility treatments. PCOS patients also demonstrate more precipitous declines in testosterone then AMH with advancing age. These data support incorporation of AMH as diagnostic criterion for PCOS regardless of age, and imply that testosterone should not be relied upon in the diagnosis of PCOS in older women.

Pregnancy complications in women with polycystic ovary syndrome

Article

Jun 2015
HUM REPROD UPDATE

BACKGROUND The great majority of studies performed so far concerning women diagnosed with polycystic ovary syndrome (PCOS) have focused on diagnosis, menstrual cycle abnormalities, hirsutism and infertility. Although progress has been made in developing methods for achieving a pregnancy and reducing multiple gestations in women with PCOS, little attention has been paid to pregnancy complications and subsequent child outcomes. This review aims to summarize current knowledge regarding the clinical and pathophysiological features of pregnancy and children in women with PCOS.

Metabolic Syndrome Rather Than Other Phenotypes in PCOS as a Predictive Indicator for Clinical Outcomes in IVF: Comprehensive Phenotypic Assessment across All PCOS Classifications

Article

Full-text available

Aug 2023

Polycystic ovary syndrome (PCOS) is a well-recognized, multi-system metabolic disorder affecting fertility. Although various classification methods have been proposed to assess the phenotypic heterogeneity of PCOS, there is currently no reliable phenotype for predicting clinical IVF outcomes. This retrospective study, as a comprehensive phenotypic assessment across all PCOS classifications, aimed to identify dependable phenotypes that can serve as predictors for IVF and pregnancy outcomes. The study included 1313 PCOS patients who received their initial IVF treatment between January 2019 and December 2021. The phenotypes reflect the diverse metabolic and hormonal characteristics in this study. Phenotype A, within the Rotterdam criteria classification, exhibited the highest anti-Müllerian hormone levels (AMH), while phenotype D displayed the lowest Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) values. Both the hyperandrogenism (HA) phenotype within HA-based classification and the overweight phenotype within the body-mass-index-based classification showed increased HOMA-IR and metabolic syndrome (MetS). The MetS phenotype had higher free androgen index and a lower AMH. Notably, the MetS-based classification system demonstrated an independent association of MetS with cumulative live birth, preterm birth, and gestational diabetes mellitus as a contributing risk factor for PCOS patients undergoing IVF (p < 0.05). These findings carry noteworthy implications for advancing clinical management strategies for PCOS.

Alpha Lipoic Acid Efficacy in PCOS Treatment: What Is the Truth?

Article

Full-text available

Jul 2023

Polycystic ovary syndrome (PCOS) is among the most common female endocrinopathies, affecting about 4–25% of women of reproductive age. Women affected by PCOS have an increased risk of developing metabolic syndrome, type 2 diabetes mellitus, cardiovascular diseases, and endometrial cancer. Given the pivotal role of insulin resistance (IR) in the pathogenesis of PCOS, in the last years, many insulin-sensitizing factors have been proposed for PCOS treatment. The first insulin sensitizer recommended by evidence-based guidelines for the assessment and treatment of PCOS was metformin, but the burden of side effects is responsible for treatment discontinuation in many patients. Inositols have insulin-mimetic properties and contribute to decreasing postprandial blood glucose, acting by different pathways. ALA is a natural amphipathic compound with a very strong anti-inflammatory and antioxidant effect and a very noteworthy role in the improvement of insulin metabolic pathway. Given the multiple effects of ALA, a therapeutic strategy based on the synergy between inositols and ALA has been recently proposed by many groups with the aim of improving insulin resistance, reducing androgen levels, and ameliorating reproductive outcomes in PCOS patients. The purpose of this study is to review the existing literature and to evaluate the existing data showing the efficacy and the limitation of a treatment strategy based on this promising molecule. ALA is a valid therapeutic strategy applicable in the treatment of PCOS patients: Its multiple actions, including antinflammatory, antioxidant, and insulin-sensitizing, may be of utmost importance in the treatment of a very complex syndrome. Specifically, the combination of MYO plus ALA creates a synergistic effect that improves insulin resistance in PCOS patients, especially in obese/overweight patients with T2DM familiarity. Moreover, ALA treatment also exerts beneficial effects on endocrine patterns, especially if combined with MYO, improving menstrual regularity and ovulation rhythm. The purpose of our study is to review the existing literature and to evaluate the data showing the efficacy and the limitations of a treatment strategy based on this promising molecule.

Investigation of the mechanisms and experimental verification of Cuscuta-Salvia in the treatment of polycystic ovary syndrome (PCOS) via network pharmacology

Article

Full-text available

Apr 2022

Polycystic ovary syndrome (PCOS) is an endocrine disease associated with reproduction. The Cuscuta-Salvia formula has been widely used to treat for PCOS in clinic. However, its chemical and pharmacological properties remain unclear. We identified the active components and related targets of Cuscuta-Salvia using UHPLC-ESI-Q-TOF-MS and TCMSP database. Disease targets were obtained from the DisGeNET and GeneCards databases. Subsequently, common targets between Cuscuta-Salvia and PCOS were identified using a Venn diagram. PPI network was established. Core genes were selected using a Cytoscape software plugin. GO and KEGG enrichment analyses were performed for common targets using the “pathview” package in R . Several core targets were verified using molecular and Immunological methods. By combining UHPLC-ESI-Q-TOF-MS with a network pharmacology study, 14 active components and a total of 80 common targets were obtained. Ten core genes were regulated by Cuscuta-Salvia in PCOS, including IL6, AKT1, VEGFA, TP53, TNF, MAPK1, JUN, EGF, CASP3, and EGFR. GO results showed that cellular response to drugs, response to oxygen levels, response lipopolysaccharides, and response to molecule of bacterial origin in BP category; membrane, transcription regulator complex, nuclear chromatin, postsynaptic membrane, and vesicle lumen in CC category; DNA-binding transcription factor binding, RNA polymerase II-specific DNA-binding transcription factor binding, DNA-binding transcription activator activity, RNA polymerase II-specific, DNA-binding transcription activator activity, and cytokine receptor binding in MF terms. The KEGG enrichment pathway was mainly involved in the PI3K − Akt, MAPK, TNF, IL-17 signalling pathways, and in cellular senescence. Furthermore, the results of the experimental study showed that Cuscuta-Salvia ameliorated the pathological changes in the ovaries, liver and adipose tissue. And it improved the expressions of the genes or proteins. Our results demonstrate that Cuscuta-Salvia may provide a novel pharmacological basis in an experimental model of PCOS by regulating gene expression. This study provides a basis for future research and clinical applications.

Prevalance and role of Melatonin on PCOS in its treatment using Herbal Drugs

Article

Sep 2021

The polycystic ovarian syndrome is a convoluted endocrine disorder of the reproductive system which influences several girls with puberty and 6-8% of germinating women in endemic populations and displays a wide spectrum of clinical phenomenon. This disorder was first reported in 1935 as a synthetic clinical error for its associations with high androgen levels, hyperinsulinemia, and PCOS. The pineal hormone melatonin is known to regulate a mixture of central and peripheral actions related to circadian rhythms. It is a pleiotropic fragment, which plays a vital role in female reproduction as a capable free radical hunter and involves many gynecological and obstetrical pathology. PCOS is a compound condition for which the symptoms are irregular, and the cause is anonymous. Herbal products like Yastimadhu (Glycyrrhiza glabra), Kumari (Aloe vera), Tvaka (Cinnamomum Zeylanicum), Mostly the Ayurvedic drugs used for the PCOS, all are Vata-kapha shamaka. Neurological associated in pcos is still in the platform of research, no drugs melatonin an important modulator in pcos can be concentrated to cure pcos. Melatonin might be effective against neurological associate pcos. In ayurvedic way of treatment it can be cured with several natural drugs.

Molecular Sciences Therapeutic Potentials of Low-Dose Tacrolimus for Aberrant Endometrial Features in Polycystic Ovary Syndrome

Preprint

Full-text available

Mar 2021
INT J MOL SCI

Polycystic ovary syndrome (PCOS) is a major anovulatory infertility affecting a great proportion of women of childbearing age and is associated with obesity, insulin resistance and chronic inflammation. Poor endometrial receptivity and recurrent implantation failure are major hurdles to the establishment of pregnancy in women with PCOS. The accumulating body of evidence obtained from experimental and clinical studies suggests a link between inherent adaptive and innate immune irregularities and aberrant endometrial features in PCOS. The use of conventional therapeutic interventions such as lifestyle modification, metformin and ovarian stimulation has achieved limited clinical success in restoring ovulation and endometrial receptivity in women with PCOS. Unlike other immunosuppressive drugs prescribed in the clinical management of autoimmune and inflammatory disorders that may have deleterious effects on fertility and fetal development, preclinical studies in mice and in women without PCOS but with repeated implantation failure revealed potential therapeutic benefits for the use of low-dose tacrolimus in treating female infertility. Improved systemic and ovarian immune functions, endometrial progesterone receptor and coreceptor expressions and uterine vascular adaptation to pregnancy were among features of enhanced progesterone-receptor sensitivity in the low-dose tacrolimus-treated mouse model of the disease. In this review, we have compiled available experimental and clinical data in literature on endometrial progesterone resistance and current therapeutic options, as well as mechanisms of actions and reported outcomes relevant to the potential therapeutic benefits for the use of low-dose tacrolimus in treating PCOS-associated female infertility.

Effect of d -chiro-inositol and alpha-lipoic acid combination on COH outcomes in overweight/obese PCOS women

Article

Mar 2020

Insulin resistance (IR) plays a central role in the onset of polycystic ovary syndrome (PCOS). Insulin so insulin-sensitizing like inositols have been proposed as first line therapy. Among them d-chiro-inositol (DCI) seems to improve glucose metabolism and to increase ovulation frequency. Other studies have demonstrated that alpha-lipoic acid (ALA), with its antioxidant role, can also improve endocrine and metabolic profile of PCOS patients especially with familial diabetes. This a retrospective observational study with the aim to evaluate possible advantages of an integrative preparation combining DCI 500 mg and ALA 300 mg in overweight/obese PCOS patients with or without diabetic relatives who underwent IVF. Twenty PCOS patients who were taking the integrative preparation underwent controlled ovarian hyperstimulation in our center. The group with diabetic relatives tended to have a lower dose of gonadotropin, shorter stimulation days, higher number of MII oocytes, and higher number of fertilized oocytes. A combined regimen of DCI and ALA could be an interesting strategy in overweight PCOS patients with familial diabetes underwent ART.

Hyperandrogenemia and insulin resistance: The chief culprit of polycystic ovary syndrome

Article

Oct 2019
LIFE SCI

Polycystic ovary syndrome (PCOS) is one of the most common systemic reproductive endocrine diseases, which has a variety of effects on a woman's health. Because of the involvement of multiple pathways and the lack of common clues, PCOS demonstrates multifactorial properties and heterogeneity of symptoms. Recent studies have demonstrated that the core etiology and primary endocrine characteristics of PCOS are hyperandrogenemia (HA) and insulin resistance (IR). HA and IR are the main causes of PCOS and they can interplay each other in the occurrence and development of PCOS. Just because of this, the study about the effects of HA and IR on pathophysiology of various related symptoms of PCOS is very important to understand the pathogenesis of PCOS. This paper reviews the main symptoms of PCOS, including neuroendocrine disorders, reproductive processes, dyslipidemia, obesity, hypertension, nonalcoholic fatty liver disease (NAFLD), and sleep disordered breathing, which seriously affect the physical and mental health of PCOS women. The increasing knowledge of the development pattern of HA and IR in PCOS suggests that changes in diet and lifestyle, and the discovery of potential therapeutic agents may improve PCOS. However, further studies are needed to clarify the mutual influence and relation of HA and IR in development of PCOS. This review provides an overview of the current knowledge about the effects of HA and IR on PCOS.

Probabilistic Guided Polycystic Ovary Syndrome Recognition using Learned Quality Kernel

Article

Jul 2019

Image recognition aims to automatically search special objects in an image, such as human faces, vehicles, or buildings. In medical research, image recognition technique can also be applied for disease diagnosis and disease classification. Aiming at disadvantages of traditional methods in polycystic ovary syndrome (PCOS) recognition, we propose a probabilistic model for disease recognition using a deeply-learned image quality kernel. Specifically, we first segment training images into several equal-size grids for better cues discovery. Then, each grid within an image is quantitatively represented by a quality score according to grayscale and texture features. In this way, each image can be represented by a score matrix. Then, we leverage statistic based method to generate a long feature vector according to the score matrix. Afterward, we propose a probabilistic model to learn the distribution of obtained feature vector, which will be further fed into a SVM kernel for PCOS recognition. Experimental results show the effectiveness of our proposed method.

Granulosa cells as sources of reactive oxygen species

Article

Feb 2019

Pregnancy complications in infertile patients with polycystic ovary syndrome: updated evidence

Article

Apr 2018
Minerva Ginecol

Polycystic ovary syndrome (PCOS) is a common female disorder with a pathogenesis still today not completely known. To the present, PCOS is considered more than just a reproductive disorder since several metabolic consequences that could affect women's health during different stages of reproductive and post-reproductive life were reported. The aim of the current review was to evaluate present evidence-based data regarding the pregnancy complications in infertile patients with PCOS. An extensive literature search until February 2018 was performed in PubMed, Medline, the Cochrane Library and Web of Science. Outcomes were classified in: early pregnancy complications, late pregnancy complications, perinatal complications, offspring health and long-term offspring and maternal health. Even if the exact mechanisms involved are still unclear, women with PCOS have an increased risk of pregnancy-related complications, such as gestational diabetes mellitus (GDM), pregnancy- induced hypertension (PIH), preeclampsia (PE), premature delivery and caesarean section. Moreover, the offspring of women with PCOS are also at increased risk of congenital anomalies and hospitalization in childhood. Further study are needed to study the mechanism underlying pregnancy complications in PCOS and to identify any interventions to reduce the risk of obstetric and neonatal risks in women affected by PCOS and in their offspring.

Diagnostic Criteria for PCOS

Chapter

Jan 2018

Leukaemia inhibitory factor in serum and follicular fluid of women with polycystic ovary syndrome and its correlation with IVF outcome

Article

Jan 2018
REPROD BIOMED ONLINE

Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, ovarian dysfunction and polycystic ovarian morphology. Leukaemia inhibitory factor (LIF) affects many reproductive activities, including follicular development, embryo implantation and growth. The aim of this study was to evaluate LIF concentrations in serum and follicular fluid of women with PCOS and controls who underwent IVF with embryo transfer (IVF-ET). Serum and follicular fluid LIF concentrations were lower in women with PCOS compared with controls. Oestradiol concentrations in follicular fluid were higher in PCOS subjects compared with controls. LIF concentrations in serum (r = 0.6263, P < 0.05) and follicular fluid (r = 0.7093, P < 0.05) were negatively correlated with oestradiol concentration in the PCOS group. LIF concentrations in follicular fluid showed no difference between women who conceived and women who did not in both PCOS and control groups. However, LIF concentrations in embryo culture medium were higher in women who conceived following IVF compared with women who did not, in combined PCOS and control groups. The findings indicate that low LIF concentrations in serum and follicular fluid may contribute to disordered folliculogenesis in PCOS. LIF concentrations in embryo culture medium may predict the outcome of IVF treatment.

Ovarian Function and Obesity: PCOS, Menopause

Article

Oct 2015

Ovarian function and energy metabolism are tightly connected and reciprocally regulated to enable reproduction in food-scarce environment. Reproductive disorders can lead to metabolic disorders and obesity both of which may in turn induce alterations of the menstrual cycle and fertility. A growing body of research documents the effects of endocrine-disrupting chemicals on the differentiation of adipocytes and the central nervous system circuits that control food intake and energy expenditure, as well as influence on reproduction and insulin secretion. Insulin resistance is related to abdominal obesity, and in women, it is often inextricably linked with ovarian dysfunctions, leading to clinical manifestations across the entire female reproductive life. Specifically, obesity in women manifests, as early menarche, subfertility, polycystic ovary syndrome, symptomatic menopause, and increased risk of breast cancer. Overall, obese women with superimposed reproductive complications including PCOS may be considered to be at high risk for further progression to metabolic syndrome, type 2 diabetes mellitus, and potentially cardiovascular diseases. These patients can then be targeted for early screening, lifestyle optimization, and the prevention of the subsequent metabolic derangement. Considering the reciprocal interactions between pathways that control fertility and energy metabolism and the key roles of molecules such as estrogens and IGF-1 in these pathways, it is possible to consider changing the current therapeutic strategiesâ€”amelioration of metabolic disorders, for example, might become an important goal of hormone replacement therapy (HRT) in menopausal obese women.

Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS)

Article

Full-text available

Jan 2004

Since the 1990 NIH‐sponsored conference on polycystic ovary syndrome (PCOS), it has become appreciated that the syndrome encompasses a broader spectrum of signs and symptoms of ovarian dysfunction than those defined by the original diagnostic criteria. The 2003 Rotterdam consensus workshop concluded that PCOS is a syndrome of ovarian dysfunction along with the cardinal features hyperandrogenism and polycystic ovary (PCO) morphology. PCOS remains a syndrome and, as such, no single diagnostic criterion (such as hyperandrogenism or PCO) is sufficient for clinical diagnosis. Its clinical manifestations may include: menstrual irregularities, signs of androgen excess, and obesity. Insulin resistance and elevated serum LH levels are also common features in PCOS. PCOS is associated with an increased risk of type 2 diabetes and cardiovascular events.

Diagnosis and Treatment of Polycystic Ovary Syndrome: An Endocrine Society Clinical Practice Guideline

Article

Full-text available

Oct 2013
J CLIN ENDOCR METAB

Objective: The aim was to formulate practice guidelines for the diagnosis and treatment of polycystic ovary syndrome (PCOS). Participants: An Endocrine Society-appointed Task Force of experts, a methodologist, and a medical writer developed the guideline. Evidence: This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. Consensus process: One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of The Endocrine Society and the European Society of Endocrinology reviewed and commented on preliminary drafts of these guidelines. Two systematic reviews were conducted to summarize supporting evidence. Conclusions: We suggest using the Rotterdam criteria for diagnosing PCOS (presence of two of the following criteria: androgen excess, ovulatory dysfunction, or polycystic ovaries). Establishing a diagnosis of PCOS is problematic in adolescents and menopausal women. Hyperandrogenism is central to the presentation in adolescents, whereas there is no consistent phenotype in postmenopausal women. Evaluation of women with PCOS should exclude alternate androgen-excess disorders and risk factors for endometrial cancer, mood disorders, obstructive sleep apnea, diabetes, and cardiovascular disease. Hormonal contraceptives are the first-line management for menstrual abnormalities and hirsutism/acne in PCOS. Clomiphene is currently the first-line therapy for infertility; metformin is beneficial for metabolic/glycemic abnormalities and for improving menstrual irregularities, but it has limited or no benefit in treating hirsutism, acne, or infertility. Hormonal contraceptives and metformin are the treatment options in adolescents with PCOS. The role of weight loss in improving PCOS status per se is uncertain, but lifestyle intervention is beneficial in overweight/obese patients for other health benefits. Thiazolidinediones have an unfavorable risk-benefit ratio overall, and statins require further study.

Divergences in Insulin Resistance Between the Different Phenotypes of the Polycystic Ovary Syndrome

Article

Full-text available

Mar 2013
J CLIN ENDOCR METAB

Context/objective: Current diagnostic criteria for polycystic ovary syndrome (PCOS) have generated distinct PCOS phenotypes, based on the different combinations of diagnostic features found in each patient. Our aim was to assess whether either each single diagnostic feature or their combinations into the PCOS phenotypes may predict insulin resistance in these women. Patients/design: A total of 137 consecutive Caucasian women with PCOS, diagnosed by the Rotterdam criteria, underwent accurate assessment of diagnostic and metabolic features. Insulin sensitivity was measured by the glucose clamp technique. Results: Among women with PCOS, 84.7% had hyperandrogenism, 84.7% had chronic oligoanovulation, and 89% had polycystic ovaries. According to the individual combinations of these features, 69.4% of women had the classic phenotype, 15.3% had the ovulatory phenotype, and 15.3% had the normoandrogenic phenotype. Most subjects (71.4%) were insulin resistant. However, insulin resistance frequency differed among phenotypes, being 80.4%, 65.0%, and 38.1%, respectively, in the 3 subgroups (P < .001). Although none of the PCOS diagnostic features per se was associated with the impairment in insulin action, after adjustment for covariates, the classic phenotype and, to a lesser extent, the ovulatory phenotype were independently associated with insulin resistance, whereas the normoandrogenic phenotype was not. Metabolic syndrome frequency was also different among phenotypes (P = .030). Conclusions: There is a scale of metabolic risk among women with PCOS. Although no single diagnostic features of PCOS are independently associated with insulin resistance, their combinations, which define PCOS phenotypes, may allow physicians to establish which women should undergo metabolic screening. In metabolic terms, women belonging to the normoandrogenic phenotype behave as a separate group.

Metformin versus clomiphene citrate for infertility in non-obese women with polycystic ovary syndrome: A systematic review and meta-analysis

Article

Full-text available

Sep 2012
HUM REPROD UPDATE

BACKGROUND Recent studies suggest that metformin may be more effective in women with polycystic ovary syndrome (PCOS) who are non-obese. The objective here is to determine and compare the effectiveness of metformin and clomiphene citrate for improving fertility outcomes in women with PCOS and a BMI < 32 kg/m(2) (BMI 32 kg/m(2) was used to allow for international differences in BMI values which determine access to infertility therapy through the public health system).METHODS Databases were searched for English language articles until July 2011. Inclusion criteria: women of any age, ethnicity and weight with PCOS diagnosed by all current criteria, who are infertile; at least 1000 mg of any type of metformin at any frequency, including slow release and standard release, compared with any type, dose and frequency of clomiphene citrate. Outcomes: rates of ovulation, live birth, pregnancy, multiple pregnancies, miscarriage, adverse events, quality of life and cost effectiveness. Data were extracted and risk of bias assessed. A random effects model was used for meta-analyses of data, using risk ratios (relative risk).RESULTSThe search returned 4981 articles, 580 articles addressed metformin or clomiphene citrate and four randomized controlled trials (RCTs) comparing metformin with clomiphene citrate were included. Upon meta-analysis of the four RCTs, we were unable to detect a statistically significant difference between the two interventions for any outcome in women with PCOS and a BMI < 32 kg/m(2), owing to significant heterogeneity across the RCTs.CONCLUSIONS Owing to conflicting findings and heterogeneity across the included RCTs, there is insufficient evidence to establish a difference between metformin and clomiphene citrate in terms of ovulation, pregnancy, live birth, miscarriage and multiple pregnancy rates in women with PCOS and a BMI < 32 kg/m(2). However, a lack of superiority of one treatment is not evidence for equivalence, and further methodologically rigorous trials are required to determine whether there is a difference in effectiveness between metformin and placebo (or no treatment) or between metformin and clomiphene citrate for ovulation induction in women with PCOS who are non-obese. Until then, caution should be exercised when prescribing metformin as first line pharmacological therapy in this group of women.

The Androgen Excess and PCOS Society Criteria for the Polycystic Ovary Syndrome: the complete task force report

Article

Full-text available

Nov 2008

To review all available data and recommend a definition for polycystic ovary syndrome (PCOS) based on published peer-reviewed data, whether already in use or not, to guide clinical diagnosis and future research. Literature review and expert consensus. Professional society. None. None. A systematic review of the published peer-reviewed medical literature, by querying MEDLINE databases, to identify studies evaluating the epidemiology or phenotypic aspects of PCOS. The Task Force drafted the initial report, following a consensus process via electronic communication, which was then reviewed and critiqued by the Androgen Excess and PCOS (AE-PCOS) Society AE-PCOS Board of Directors. No section was finalized until all members were satisfied with the contents, and minority opinions noted. Statements were not included that were not supported by peer-reviewed evidence. Based on the available data, it is the view of the AE-PCOS Society Task Force that PCOS should be defined by the presence of hyperandrogenism (clinical and/or biochemical), ovarian dysfunction (oligo-anovulation and/or polycystic ovaries), and the exclusion of related disorders. However, a minority considered the possibility that there may be forms of PCOS without overt evidence of hyperandrogenism, but recognized that more data are required before validating this supposition. Finally, the Task Force recognized and fully expects that the definition of this syndrome will evolve over time to incorporate new research findings.

Statin Therapy Worsens Insulin Sensitivity in Women With Polycystic Ovary Syndrome (PCOS): A Prospective, Randomized, Double-Blind, Placebo-Controlled Study

Article

Oct 2013
J CLIN ENDOCR METAB

Context: Statins have been shown to improve hyperandrogenism in women with polycystic ovary syndrome (PCOS). However, their use has also been associated with impairment of glucose metabolism and an increased risk of type 2 diabetes mellitus. Because women with PCOS are prone to disturbances in glucose metabolism, statin therapy could also have negative effects. Objective: Our objective was to explore the effects of atorvastatin therapy on hormonal and metabolic parameters in women with PCOS. Design and setting: We conducted a randomized, double-blind, placebo-controlled 6-month follow-up study conducted at Oulu University Hospital, Finland. Patients: Women with PCOS (Rotterdam criteria) were treated with atorvastatin (20 mg/d, n = 15) or placebo (n = 13) for 6 months. Interventions: Fasting serum samples were collected at baseline and at 3 and 6 months. Oral and iv glucose tolerance tests were performed at 0 and 6 months. Main outcome measures: Androgen secretion and glucose metabolism were measured. Results: Fasting levels and area under the curve of insulin increased significantly and insulin sensitivity (insulinogenic and Matsuda indexes) decreased during 6 months of atorvastatin therapy. Serum levels of dehydroepiandrosterone sulfate decreased in the atorvastatin group, whereas no change was observed in serum testosterone levels. Levels of C-reactive protein, total and low-density lipoprotein-cholesterol, and triglycerides decreased significantly during statin therapy. Conclusions: Atorvastatin therapy improves chronic inflammation and lipid profile, but it impairs insulin sensitivity in women with PCOS. Because women with PCOS have an increased risk of developing type 2 diabetes mellitus, the results suggest that statin therapy should be initiated on the basis of generally accepted criteria and individual risk assessment of cardiovascular disease, and not only because of PCOS.

Is the fertile window extended in women with polycystic ovary syndrome? Utilizing the Society for Assisted Reproductive Technology registry to assess the impact of reproductive aging on live-birth rate

Article

Apr 2013

Objective: To assess whether women with polycystic ovary syndrome (PCOS) follow the same age-related decline in IVF outcomes as women with tubal factor infertility over the reproductive life span. PCOS is characterized by increased ovarian reserve as assessed by antral follicle counts and anti-Müllerian hormone levels. It is unclear whether these surrogate markers of ovarian reserve reflect a true lengthening of the reproductive window. Design: Retrospective cohort. Setting: Not applicable. Patient(s): Women with PCOS and tubal factor infertility (42,286 cycles). Intervention(s): IVF. Main outcome measure(s): Pregnancy and live-birth rates. Result(s): The mean number of oocytes retrieved was higher in women with PCOS compared with in women with tubal factor (16.4 vs. 12.8; odds ratio [OR], 1.27; 95% confidence interval [CI], 1.25-1.29). The clinical pregnancy (42.5% vs. 35.8%; OR, 1.32; 95% CI, 1.27-1.38) and live-birth rates were also increased in women with PCOS (34.8% vs. 29.1%; OR, 1.30; 95% CI, 1.24-1.35). A similar rate of decline in clinical pregnancy and live-birth rates was noted in both groups (20-44 years). The implantation, clinical pregnancy, miscarriage, and live-birth rates were not significantly different for each year after age 40 in the two groups. Conclusion(s): Despite a higher oocyte yield in all age groups, women with PCOS over age 40 had similar clinical pregnancy and live-birth rates compared with women with tubal factor infertility. These findings suggest that the reproductive window may not be extended in PCOS and that patients with infertility should be treated in a timely manner despite indicators of high ovarian reserve.

Pregnancy in women with polycystic ovary syndrome: The effect of different phenotypes and features on obstetric and neonatal outcomes

Article

Dec 2009

To test the hypothesis that the risk of adverse obstetric or neonatal outcomes varies according to different phenotypes of polycystic ovary syndrome (PCOS), and to evaluate the clinical impact of the main features of PCOS. Prospective controlled clinical study. Academic Departments of Obstetrics and Gynecology, and of Endocrinology, Italy. Ninety-seven pregnant women with PCOS and 73 healthy pregnant subjects were recruited as cases and controls, respectively. Clinical, biochemical, and ultrasonographic evaluations. Obstetric and neonatal outcomes. The relative risk (RR) for adverse obstetric or neonatal outcomes was increased (1.7, 95% confidence interval [CI] 1.12-2.96) in patients with PCOS and varied according to the PCOS phenotype (1.93, 95% CI 1.12-2.96; 2.23, 95% CI 1.21-3.15; 0.54, 95% CI 0.09-1.63, and 0.48, 95% CI 0.31-0.78 for full-blown, nonpolycystic ovaries [PCO], nonhyperandrogenic, and ovulatory phenotypes, respectively). The RRs were 1.57 (95% CI 0.85-2.52) and 0.48 (95% CI 0.31-0.78) for oligoanovulatory and ovulatory patients with PCOS, respectively. The risk for adverse obstetric or neonatal outcomes was affected significantly by ovarian dysfunction and biochemical hyperandrogenism, whereas no significant effect was detected for clinical hyperandrogenism and PCO. The increased risk for adverse obstetric and neonatal outcomes that was observed in patients with PCOS varies widely according to the different phenotypes and features of PCOS.

Evidence-Based and Potential Benefits of Metformin in the Polycystic Ovary Syndrome: A Comprehensive Review

Article

Feb 2009
ENDOCR REV

Metformin is an insulin sensitizer widely used for the treatment of patients affected by type 2 diabetes mellitus. Because many women with polycystic ovary syndrome (PCOS) are insulin resistant, metformin was introduced in clinical practice to treat these patients also. Moreover, metformin's effect has other targets beside its insulin-sensitizing action. The present review was aimed at describing all evidence-based and potential uses of metformin in PCOS patients. In particular, we will analyze the uses of metformin not only for the treatment of all PCOS-related disturbances such as menstrual disorders, anovulatory infertility, increased abortion, or complicated pregnancy risk, hyperandrogenism, endometrial, metabolic and cardiovascular abnormalities, but also for the prevention of the syndrome.

Cardiovascular risk in women with polycystic ovary syndrome

Article

Aug 2006

Polycystic ovary syndrome (PCOS) is not only a reproductive problem but a complex, endocrine, multifaceted disease with several health complications. Cardiovascular abnormalities represent important long-term sequelae of PCOS.

Metformin versus clomiphene citrate for infertility in non-obese women with polycystic ovary syndrome: a systematic review and meta-analysis

Jan 2013
2

M L Misso
ML Misso

Reproductive endocrinology: New guidelines for the diagnosis and treatment of PCOS

Abstract

No full-text available

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