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Histograms representing the mean SD hirsutism score, diameter, and daily growth rate of hair under basal conditions (b) and after 90 (1), 180 (2), 270 (3), and 360 (4) days of therapy with different treatment regimens. In the ketoconazole group, 2 patients of 16 dropped out during the first 90 days of therapy, and 6 patients dropped out during the first 180 days. At 180, 270, and 360 days of treatment, only 8 subjects were studied. a, P 0.05; b, P 0.01; c, P 0.005 (vs. basal within each group). For hirsutism score: by ANOVA among groups in basal conditions, P NS; by ANOVA among groups during treatment, P NS. For hair diameter: by ANOVA among groups in basal conditions, P NS; by ANOVA among groups during treatment, significant differences at 90 (F 3.9; P 0.01), 180 (F 3.9; P 0.01), and 270 (F 6.7; P 0.01) days. For hair growth: by ANOVA among groups in basal conditions, P NS; by ANOVA among groups during treatment, significant differences at 90 (F 3.6; P 0.02) and 180 (F 5.1; P 0.003) days.
Source publication
Sixty-six hirsute women were randomized and treated with 1) flutamide (n = 15), 250 mg/day; 2) finasteride (n = 15), 5 mg/day; 3) ketoconazole (n = 16), 300 mg/day; and 4) ethinyl estradiol (EE)-cyproterone acetate (CPA; n = 20), 0.01 mg EE/day for the first week, 0.02 mg EE/day for the second week, and 0.01 mg EE/day for the third week, followed b...
Contexts in source publication
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... are expressed as the mean sd. Figure 1 shows the results of the different regimens of therapy during the entire treatment period. In each subject who finished the study, not less than 100 hairs were analyzed by IBAS, both under basal conditions and during the entire cycle of treatment. ...
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... group 1 (flutamide), hirsutism improved in all subjects. The mean basal score ( Fig. 1; 14.2 4.5) progressively de- creased and dropped to 6.4 3.5 (P 0.001; 55 13%) after 12 months of treatment. The mean diameter ( Fig. 1) fell from 0.169 0.02 to 0.133 0.02 mm (P 0.001; 21 14%), and the mean daily rate of hair growth ( Fig. 1) fell progressively from 0.153 0.03 to 0.084 0.04 mm/day (P 0.001; 41 ...
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... group 1 (flutamide), hirsutism improved in all subjects. The mean basal score ( Fig. 1; 14.2 4.5) progressively de- creased and dropped to 6.4 3.5 (P 0.001; 55 13%) after 12 months of treatment. The mean diameter ( Fig. 1) fell from 0.169 0.02 to 0.133 0.02 mm (P 0.001; 21 14%), and the mean daily rate of hair growth ( Fig. 1) fell progressively from 0.153 0.03 to 0.084 0.04 mm/day (P 0.001; 41 ...
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... group 1 (flutamide), hirsutism improved in all subjects. The mean basal score ( Fig. 1; 14.2 4.5) progressively de- creased and dropped to 6.4 3.5 (P 0.001; 55 13%) after 12 months of treatment. The mean diameter ( Fig. 1) fell from 0.169 0.02 to 0.133 0.02 mm (P 0.001; 21 14%), and the mean daily rate of hair growth ( Fig. 1) fell progressively from 0.153 0.03 to 0.084 0.04 mm/day (P 0.001; 41 ...
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... group 2 (finasteride), hirsutism improved in all subjects. The mean basal score ( Fig. 1; 12.4 4.8) slowly dropped during therapy to 6.9 3.5 (P 0.02; 44 13%) after 12 months of treatment. The mean diameter (Fig. 1) fell from 0.174 0.02 to 0.147 0.02 mm (P 0.001; 16 12%), and the mean daily rate (Fig. 1) of hair growth fell from 0.127 0.05 to 0.095 0.04 mm/day (P 0.005; 27 ...
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... group 2 (finasteride), hirsutism improved in all subjects. The mean basal score ( Fig. 1; 12.4 4.8) slowly dropped during therapy to 6.9 3.5 (P 0.02; 44 13%) after 12 months of treatment. The mean diameter (Fig. 1) fell from 0.174 0.02 to 0.147 0.02 mm (P 0.001; 16 12%), and the mean daily rate (Fig. 1) of hair growth fell from 0.127 0.05 to 0.095 0.04 mm/day (P 0.005; 27 ...
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... group 2 (finasteride), hirsutism improved in all subjects. The mean basal score ( Fig. 1; 12.4 4.8) slowly dropped during therapy to 6.9 3.5 (P 0.02; 44 13%) after 12 months of treatment. The mean diameter (Fig. 1) fell from 0.174 0.02 to 0.147 0.02 mm (P 0.001; 16 12%), and the mean daily rate (Fig. 1) of hair growth fell from 0.127 0.05 to 0.095 0.04 mm/day (P 0.005; 27 ...
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... group 3 (ketoconazole), 8 of 16 subjects who started the therapy stopped taking the drug within 180 days because of several side-effects and complications; hirsutism had im- proved in the 8 subjects who concluded the 12-month ther- apy period (mean basal score, 13.8 4.4; 12-month therapy score, 6.5 4.8; P 0.005; 53 18%; Fig. 1). The mean diameter (Fig. 1) fell progressively from 0.177 0.01 to 0.148 0.02 mm (P 0.005; 14 12%), and the mean daily rate of hair growth (Fig. 1) fell from 0.129 0.03 to 0.090 0.04 mm/day (P 0.005; 30 21%). Six of 8 hirsute subjects who interrupted the therapy had slower hair growth during the therapy on the basis of their subjective ...
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... group 3 (ketoconazole), 8 of 16 subjects who started the therapy stopped taking the drug within 180 days because of several side-effects and complications; hirsutism had im- proved in the 8 subjects who concluded the 12-month ther- apy period (mean basal score, 13.8 4.4; 12-month therapy score, 6.5 4.8; P 0.005; 53 18%; Fig. 1). The mean diameter (Fig. 1) fell progressively from 0.177 0.01 to 0.148 0.02 mm (P 0.005; 14 12%), and the mean daily rate of hair growth (Fig. 1) fell from 0.129 0.03 to 0.090 0.04 mm/day (P 0.005; 30 21%). Six of 8 hirsute subjects who interrupted the therapy had slower hair growth during the therapy on the basis of their subjective ...
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... side-effects and complications; hirsutism had im- proved in the 8 subjects who concluded the 12-month ther- apy period (mean basal score, 13.8 4.4; 12-month therapy score, 6.5 4.8; P 0.005; 53 18%; Fig. 1). The mean diameter (Fig. 1) fell progressively from 0.177 0.01 to 0.148 0.02 mm (P 0.005; 14 12%), and the mean daily rate of hair growth (Fig. 1) fell from 0.129 0.03 to 0.090 0.04 mm/day (P 0.005; 30 21%). Six of 8 hirsute subjects who interrupted the therapy had slower hair growth during the therapy on the basis of their subjective ...
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... group 4 (EE-CPA), hirsutism improved in all subjects. The mean basal score ( Fig. 1; 13.3 5.1) dropped to 6.1 5.5 (P 0.001; 60 18%) after 12 months of treatment. The mean diameter (Fig. 1) fell from 0.164 0.05 to 0.138 0.02 mm (P 0.001; 20 11%). The mean daily rate (Fig. 1) of hair growth decreased during the first 90 days and fell from 0.127 0.05 to 0.090 0.03 mm/day (P 0.001) (28 21%) after 12 ...
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... group 4 (EE-CPA), hirsutism improved in all subjects. The mean basal score ( Fig. 1; 13.3 5.1) dropped to 6.1 5.5 (P 0.001; 60 18%) after 12 months of treatment. The mean diameter (Fig. 1) fell from 0.164 0.05 to 0.138 0.02 mm (P 0.001; 20 11%). The mean daily rate (Fig. 1) of hair growth decreased during the first 90 days and fell from 0.127 0.05 to 0.090 0.03 mm/day (P 0.001) (28 21%) after 12 ...
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... group 4 (EE-CPA), hirsutism improved in all subjects. The mean basal score ( Fig. 1; 13.3 5.1) dropped to 6.1 5.5 (P 0.001; 60 18%) after 12 months of treatment. The mean diameter (Fig. 1) fell from 0.164 0.05 to 0.138 0.02 mm (P 0.001; 20 11%). The mean daily rate (Fig. 1) of hair growth decreased during the first 90 days and fell from 0.127 0.05 to 0.090 0.03 mm/day (P 0.001) (28 21%) after 12 ...
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... were no significant differences among groups with respect to their clinical basic data, endocrine parameters (Tables 1 and 2), hirsutism score, or basal hair characteristics (Fig. ...
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... the hirsutism score ( Fig. 1), no differences (by ANOVA, P NS) were observed among the groups during the control period, confirming the efficacy of all four treat- ments. However significantly higher differences were ob- served in the percentage of decrease (Fig. 2) at the end of treatment in the cases of flutamide vs. finasteride (55 ...
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... hair diameter ( Fig. 1), significant differences were ob- served at 90 days (F 3.94; P 0.01), 180 days (F 3.6; P 0.01), and 270 days (F 6.7; P 0.001) among the groups. Flutamide induced the quickest decrease in hair diameter during treatment (at 90 days of treatment) even though the differences in the percent decrease disappeared at the end of treatment ...
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... the hair growth rate (Figs. 1 and 2), significant differ- ences among groups were observed at 90 days (F 3.6; P 0.02) and 180 days (F 5.1; P 0.003). Finasteride was the slowest in decreasing hair growth, whereas EE-CPA was the quickest. ...
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... hirsutism score decreased progressively (55%), and the improvement of hirsutism was associated with a rapid decrease in hair diameter (11% after 3 months) and a progressive decrease in the daily hair growth rate (41% after 12 months). A net decrease in T, Tf, DHT, A, 17-P, DHA, and DHAS plasma levels during treatment was observed, in agreement with some reports (26,27) and in disagreement with others (1, 2, 5, 28), suggesting that the efficacy of flutamide must be ascribed to a reduction of androgen synthesis and to its action on target tissues. At a dose of 250 mg/day flutamide, neither liver failure nor the side-effects generally seen with high doses (2,4,27,29,30) were observed. ...
Citations
... [23] It was tough to point out a single reason for elevated androgens. Activation of various pathogenic pathways due to hyperinsulinemia, use of drugs, environmental factors, and endocrinological events were associated with HA. [24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43] Down-regulation of aromatase might lead to the inhibition of estrogen synthesis. [44] Deficiency of this enzyme was also observed in the number of patients with HA. [45,46] ...
... CPA competitively inhibits the binding of testosterone and its more potent conversion product 5a-dihydrotestosterone to the androgen receptor. Used in high doses (50-100 mg) and in a reverse sequential regimen (for the first 10 days of cycle), in combination with ethinyl estradiol 20-50 µg (to ensure regular menses), it was shown to be more effective than finasteride, a 5-α-reductase inhibitor [58]. Flutamide is a nonsteroidal, selective antiandrogen without progestogenic effect. ...
Polycystic Ovary syndrome (PCOS) is an underdiagnosed metabolic and endocrine disorder found in women of reproductive age in which ovaries develop follicles and does not release egg regularly. Its symptoms include menstrual irregularity, polycystic ovaries, hirsutism, infertility, insulin-resistance, impaired glucose tolerance. Currently the exact cause for the PCOS is unknown but research suggest that it may be related to lifestyle changes, environmental traits and genetical factors. Prevalence of PCOS in India ranges from 3.7 %to 22.5%. The syndrome is associated with increased gonadotropin-releasing diagnose PCOS till the date. , Rotterdam diagnostic criteria is highly accepted by the healthcare providers. Weight loss has been a major contributor in the non-pharmacological management of PCOS. Moderate exercise, behavioral therapy and psychological counselling is suggested for affected women. In pharmacological treatment, combined oral contraceptive pills (COCP), metformin, anti-androgen agents, clomiphene citrate, letrozole as fertility inducing agents are used and surgical options are also considered when necessary. In India, PCOS is still underdiagnosed disorder with long term morbidities involved and its time that it should be discussed more openly and treated holistically.
... However, hyperandrogenism represents the main attribute of PCOS (5,6). Evidence from human (7)(8)(9)(10)(11) and animal (12,13) studies establish that androgens in excess play a key role in PCOS etiology that significantly contributes to the development of the large number of comorbidities such as reproductive, endocrine, metabolic, and psychological dysfunctions (14,15) associated with PCOS (16,17). ...
In women, excess androgen causes polycystic ovary syndrome (PCOS), a common fertility disorder with comorbid metabolic dysfunctions including diabetes, obesity, and nonalcoholic fatty-liver disease (NAFLD). Using a PCOS mouse model, this study shows that chronic high androgen levels cause hepatic steatosis while hepatocyte-specific androgen receptor (AR)-knockout rescues this phenotype. Moreover, through RNA-seq and metabolomic studies, we have identified key metabolic genes and pathways affected by hyperandrogenism. Our studies reveal that a large number of metabolic genes are directly regulated by androgens through AR binding to androgen response element sequences on the promoter region of these genes. Interestingly, a number of circadian genes are also differentially regulated by androgens. In vivo and in vitro studies using a circadian reporter (Per2::LUC) mouse model demonstrate that androgens can directly disrupt the hepatic timing system, which is a key regulator of liver metabolism. Consequently, studies show that androgens decrease H3K27me3, a gene silencing mark on the promoter of core clock genes, by inhibiting the expression of histone methyltransferase, Ezh2, while inducing the expression of the histone demethylase, JMJD3, that is responsible for adding and removing the H3K27me3 mark, respectively. Finally, we report that under hyperandrogenic conditions, some of the same circadian/metabolic genes that are upregulated in the mouse liver are also elevated in non-human primate livers. In summary, these studies not only provide an overall understanding of how hyperandrogenism associated with PCOS affects liver gene expression and metabolism, but also offer an insight of the underlying mechanisms leading to hepatic steatosis in PCOS.
... In a group of PCOS women, Lackryc et al. [70] found no changes in blood pressure and heart rate after 6 months of FND treatment (5 mg/day). Similarly, no changes in metabolic parameters such as carbohydrates and/or lipids after FND treatment in hyperandrogenic women have been reported [56, 69,73]. By contrast, recent data have shown that FND (5 mg/day) improves IR (HOMA-IR) as well as glycemic and insulinemic responses after OGTT (AUC-glucose and AUC-insulin until 180 min) independently of weight reduction, thus suggesting FND as an alternative therapy for PCOS-related metabolic disease [74]. ...
Polycystic ovary syndrome (PCOS) is characterized by elevated androgen production and subclinical changes in cardiovascular and metabolic risk markers. Total cholesterol, high-density lipoprotein (HDL) cholesterol, fasting glucose, and fasting insulin appear to increase specifically in PCOS compared with fertile women. PCOS also confers an increased risk of cardiometabolic disease in later life. Novel biomarkers such as serum’s cholesterol efflux capacity and blood-derived macrophage activation profile may assist in more accurately defining the cardiometabolic risk profile in these women. Aldosterone antagonists, androgen receptor antagonists, 5α-reductase inhibitors, and synthetic progestogens are used to reduce hyperandrogenism. Because increased insulin secretion enhances ovarian androgen production, short-term treatment with metformin and other hypoglycemic agents results in significant weight loss, favorable metabolic changes, and testosterone reduction. The naturally occurring inositols display insulin-sensitizing effects and may be also used in this context because of their safety profile. Combined oral contraceptives represent the drug of choice for correction of androgen-related symptoms. Overall, PCOS management remains focused on specific targets including assessment and treatment of cardiometabolic risk, according to disease phenotypes. While new options are adding to established therapeutic approaches, a sometimes difficult balance between efficacy and safety of available medications has to be found in individual women.
... The AR antagonist restores the decreased sensitivity of the GnRH pulse generator by estrogen and progesterone [36,37]. It improves hirsutism and acne in PCOS patients [38][39][40]. The human AR gene contains a CAG repeats region in it's N terminal transcription activation region. ...
... Flutamide, a competitive antagonist of the AR, is most widely used and has been reported to have a favourable effect in women with PCOS as it decreases hirsutism and acne [25][26][27]. PCOS patients under flutamide treatment also experienced improved menstrual cycle regularity and ovulation [28,29]. Additionally, treatment of both obese and lean PCOS women with flutamide revealed that independent of weight changes, flutamide improved the lipid profile of women with PCOS, with a significant decrease in total cholesterol, low-density lipoproteins (LDL) and triglycerides [30]. ...
Polycystic ovary syndrome (PCOS) is the most common endocrine condition in reproductive-age women. By comprising reproductive, endocrine, metabolic and psychological features—the cause of PCOS is still unknown. Consequently, there is no cure, and management is persistently suboptimal as it depends on the ad hoc management of symptoms only. Recently it has been revealed that androgens have an important role in regulating female fertility. Androgen actions are facilitated via the androgen receptor (AR) and transgenic Ar knockout mouse models have established that AR-mediated androgen actions have a part in regulating female fertility and ovarian function. Considerable evidence from human and animal studies currently reinforces the hypothesis that androgens in excess, working via the AR, play a key role in the origins of polycystic ovary syndrome (PCOS). Identifying and confirming the locations of AR-mediated actions and the molecular mechanisms involved in the development of PCOS is critical to provide the knowledge required for the future development of innovative, mechanism-based interventions for the treatment of PCOS. This review summarises fundamental scientific discoveries that have improved our knowledge of androgen actions in PCOS etiology and how this may form the future development of effective methods to reduce symptoms in patients with PCOS.
... The effect of finasteride is reported to be sustained for 1 year after treatment. The treatment is reported to be better tolerated in comparison to other antiandrogens [53], while the probability of pregnancy is considered a contraindication because of the increased risk of hypospadias in the male fetus [54]. Because of its teratogenicity, contraception is advocated in female patients [52]. ...
Background
Hidradenitis suppurativa/acne inversa is a disease with deep-seated chronic painful nodules, abscesses, and draining sinus tracts, which manifests on the apocrine gland-rich skin areas of the body. Observational findings demonstrate that the disease usually appears after puberty, exhibits pre-menstrual flares in women, improves in pregnancy, and worsens post-partum, which indicates a role of hormones and particularly of androgens in its pathophysiology. Because increased androgen levels in serum have not been widely reported, an end-organ androgen hypersensitivity has been postulated.
Objective
The aim of this systematic review was to identify and present evidence for antiandrogen therapeutic options for the treatment of hidradenitis suppurativa/acne inversa.
Methods
A literature search was conducted in different medical electronic databases using the keywords “hidradenitis”, “suppurativa”, “acne inversa”, and “antiandrogen” on 1 December, 2018. The main therapeutic options were subsequently used as separate keywords with the disease terms in a separate search.
Results
The main therapeutic options yielded were cyproterone acetate, spironolactone, finasteride, and metformin. One randomized controlled crossover trial and seven case series were identified following use of a standard extraction form for eligibility.
Conclusion
The existing studies do not allow a robust evidence-based recommendation for the use of antiandrogens in the treatment of hidradenitis suppurativa/acne inversa. Further randomized controlled trials are needed to define the role of hormonal treatment as an alternative or concomitant therapy together with antibiotics or biologics.
... It is the most effective antiandrogen which has shown demonstrable effect on hirsutism even over and above OCPs. [48,49] It has been found to be effective for acne and alopecia. Spironolactone is an aldosterone antagonist havingaction on androgen receptor and 5-alpha reductase inhibitor activity. ...
Polycystic ovarian syndrome (PCOS) is the commonest endocrine disorder in women having wide range of clinical manifestation. These women may present with reproductive, dermatological, metabolic, psychological, or neoplastic implications from adolescence to menopause. The common dermatological manifestations include hirsutism, acne, alopecia, or acanthosis nigricans. Women presenting with these dermatological manifestations must be evaluated for PCOS. A multidisciplinary team approach involving a reproductive endocrinologist, dermatologist, psychologist/psychiatrist, dietician, and sometimes a bariatric surgeon should be undertaken for long-term management of these patients. Unless metabolic and underlying endocrinal disturbances arecorrected and simultaneous life-style modification is adopted, cosmetic treatment would give only temporary relief.
... Despite these findings, a review of 47 randomized trials found that there is low-quality evidence to support finasteride's efficacy over placebo in treating female AGA [18]. Finasteride has reportedly been successful in treating idiopathic hirsutism in several studies [29][30][31][32]. Despite moderate quality evidence favoring finasteride's efficacy over placebo, to treat hirsutism, still only a weak recommendation exists [34]. ...
... Eleven of 21 (52%) studies reported no change in LH/FSH [32, 55-58, 61, 65-69], and 12 of 21 (57%) reported no change in SHBG [32, 55-60, 62-64, 66, 69]. However, 8 of 21 (38%) studies reported an increase in total testosterone [29,31,32,55,56,60,62,69]. As expected, DHT was generally decreased with finasteride use in women with hirsutism, with as high as 90.2% serum DHT reduction from baseline, after 24 months of treatment [70][71][72]. ...
Purpose
To provide dermatologists and oncologists with a foundation for practical understanding and uses of 5α-reductase inhibitors and spironolactone for breast cancer patients and survivors receiving endocrine therapies (ETs), including the effect of these treatments on sex hormone levels, any reported drug interactions, and any risk of malignancy.
Methods
All published studies from January 1978 through April 2018 were considered, using databases such as PubMed, Google Scholar, and Science Direct. Forty-seven studies were included in this review.
Results
There is no evidence of interactions between 5α-reductase inhibitors and spironolactone with ETs used in breast cancer. Sex hormone alteration with 5α-reductase inhibitor or spironolactone use is variable. Three randomized controlled trials, 1 case–control study, and 6 retrospective cohort studies, including 284 female patients, studied the effects of 5α-reductase inhibitors on serum estrogen levels. Levels were increased in 97 of 284 (34%) patients, decreased in 15 of 284 (5.3%) patients, and unchanged in 162 of 284 (57%) patients. Four retrospective cohort studies, 1 case study, and 1 double-blinded crossover study, including 95 female patients, assessed the effect of spironolactone on estrogen levels. Levels were increased in 25 of 95 (26%) patients, decreased in 6 of 95 (6.3%) patients, and unchanged in 64 of 95 (67%) patients. Ultimately, most patients did not have a significant alteration in the level of estrogen when using 5α-reductase inhibitors or spironolactone. No consistent evidence of increased risk of female breast cancer while on spironolactone was reported in 3 studies including 49,298 patients; the risk of breast cancer with the use of 5α-reductase inhibitors has not been studied.
Conclusions
Most patients did not show increased estrogen levels with spironolactone and there were no data suggesting increased risk of breast cancer. Based on hormonal and pharmacological activity, spironolactone may be considered for further research on alopecia and hirsutism in breast cancer patients.
... 16 In a study conducted by Marescalchi et al, at University of Bologna, Italy, it was concluded that despite different effects on androgen levels, flutamide, finasteride and EE-CPA constitute very satisfactory alternative therapeutic regimens in the treatment of hirsutism. 17 Seaman and De Vries et al ., concluded that the risk of venous thromboembolism associated with EE-CPA does not differ significantly from that associated with the use of conventional COCs 18 . Cochrane data base analysis showed that OCP containing EE-CPA resulted in subjective improvement in hirsutism. ...
... In their study, those who were treated with spironolactone only, the hirsutism scores returned to baseline scores after 1 year. A study by Marescalchi et al., Italy showed that OCP containing EE-CPA was most efficacious in treating hirsutism 17 . In their study, the hirsutism scoring was done after 6, 9 and 12 months. ...
