Hirsutism In Polycystic Ovary Syndrome Research Articles

Efficacy and safety of anti-androgens in the management of polycystic ovary syndrome: a systematic review and meta-analysis of randomised controlled trials

Anti-androgens and combined oral contraceptive pills (COCPs) may mitigate hyperandrogenism-related symptoms of polycystic ovary syndrome (PCOS). However, their efficacy and safety in PCOS remain unclear as previous reviews have focused on non-PCOS populations. To inform the 2023 International Evidence-based Guideline in PCOS, we conducted the first systematic review and meta-analysis investigating the efficacy and safety of anti-androgens in the management of hormonal and clinical features of PCOS. We systematically searched MEDLINE, Embase, PsycInfo, All EBM reviews, and CINAHL up to 28th June 2023 for randomised controlled trials (RCTs) examining oral anti-androgen use, alone or in combination with metformin, COCPs, lifestyle, or other interventions, in women of any age, with PCOS diagnosed by Rotterdam, National Institutes of Health or Androgen Excess & PCOS Society criteria, and using a form of contraception. Non-English studies and studies of less than 6 months duration or which used the same anti-androgen regimen in both/all groups were excluded in order to establish efficacy for the clinical outcomes of interest. Three authors screened articles against selection criteria and assessed risk of bias and quality using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework. Critical outcomes (prioritised during guideline development for GRADE purposes) included weight, body mass index (BMI), irregular cycles, hirsutism, liver function, and quality of life. Random effects meta-analyses were conducted where appropriate. This study is registered with PROSPERO, CRD42022345640. From 1660 studies identified in the search, 27 articles comprising 20 unique studies were included. Of these, 13 studies (n=961) were pooled in meta-analysis. Seven studies had a high risk of bias, nine moderate and four low. Anti-androgens included finasteride, flutamide, spironolactone, or bicalutamide. In meta-analysis, anti-androgens+lifestyle were superior to metformin+lifestyle for hirsutism (weighted mean difference [WMD] [95% CI]:-1.59 [-3.06,-0.12], p=0.03; I2=74%), SHBG (7.70nmol/l [0.75, 14.66], p=0.03; I2=0%), fasting insulin and fasting insulin: glucose ratio (-2.11 μU/ml [-3.97,-0.26], p=0.03; I2=0% and-1.12 [-1.44,-0.79], p<0.0001, I2=0%, respectively), but were not superior to placebo+lifestyle for hirsutism (-0.93, [-3.37, 1.51], p=0.45; I2=76%) or SHBG (9.72nmol/l [-0.71, 20.14], p=0.07; I2=31%). Daily use was more effective for hirsutism than use every three days (-3.48 [-4.58,-2.39], p<0.0001, I2=1%), and resulted in lower androstenedione levels (-0.30ng/ml [-0.50,-0.10], p=0.004; I2=0%). Combination treatment with anti-androgens+metformin+lifestyle resulted in lower testosterone compared with metformin+lifestyle (-0.29nmol/l [-0.52,-0.06], p=0.01; I2=61%), but there were no differences in hirsutism when anti-androgens+metformin+lifestyle were compared with either anti-androgens+lifestyle or metformin+lifestyle. In limited meta-analyses (n=2 trials), combining anti-androgens with COCP resulted in poorer lipid profiles compared with COCP±placebo, with no differences in other outcomes. Current evidence does not support the use of anti-androgens preferentially to COCPs to treat hyperandrogenism in PCOS. Anti-androgens could be considered to treat hirsutism in PCOS, where COCPs are contraindicated, poorly tolerated, or present a sub-optimal response after a minimum 6-month period, with consideration of clinical context and individual risk factors and characteristics. National Health and Medical Research Council (NHMRC) of Australia Monash University.

Not what it seems: an exuberant case of hirsutism in polycystic ovary syndrome

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

The Association Between Increment of Interleukin-1 and Interleukin-6 in Women with Polycystic Ovary Syndrome and Body Mass Index.

There is an association between inflammatory factors and polycystic ovary syndrome (PCOS) and most of women with PCOS experience the symptoms of hirsutism. The purpose of this study was to evaluate the role of obesity in PCOS occurrence, which is linked with inflammation and hirsutism. This study was designed as a case-control research. It was performed on 102 women with PCOS and 102 healthy women as controls who were age-matched. Serum concentrations of testosterone, estradiol (E2), IL-1, IL-6, high-sensitivity c-reactive protein (hs-CRP), and aromatase activity were measured in blood samples. Statistical tests including unpaired t-tests, Mann-Whitney U test, Kruskal-Wallis, Spearman's correlation, and Chi-square tests were used for data analysis. Statistical significance was set at p<0.05. A significant difference was found between hs-CRP, IL-1, and IL-6 in PCOS patients and healthy individuals (p<0.001). Aromatase activity was markedly lower in PCOS cases. The serum level of IL-1 (p=0.392) and IL-6 (p=0.764) was not different between overweight and normal weight women. In both studied groups (case and control), hirsutism frequency was markedly higher in individuals with BMI ≥25 kg/m 2 (p<0.05). Inflammatory factors significantly affected the PCOS group (p<0.05). However, logistic regression showed that hs-CRP increment is more effective on increasing the risk of PCOS (OR: 6.324, p<0.001). In this study, hs-CRP, IL-1, and IL-6 levels increased in all PCOS women. Although the incidence of hirsutism in PCOS is associated with obesity, in PCOS pathogenesis, only IL-1 and IL-6 were independent of BMI.

Hirsutism, Normal Androgens and Diagnosis of PCOS.

Hirsutism is defined as the presence of terminal hair with male pattern distribution in women. While in the general population, hirsutism affects around 4–11% of women, it is the main manifestation of hyperandrogenism in women with polycystic ovary syndrome (PCOS), with a prevalence estimated at 65–75%. Hirsutism in PCOS is associated with both androgen excess and individual response of the pilosebaceous unit to androgens. The modified Ferriman–Gallwey (mFG) scoring system has been widely used in clinical practice to visually score excessive terminal hair, thus standardizing hirsutism evaluation and facilitating data comparison. Although a universal mFG score cutoff would be useful for comparisons, ethnic variations, as well as skin type and other factors, should be considered when evaluating hirsutism in distinct populations. In turn, androgen levels, measured by conventional techniques, have been shown to correlate poorly with the severity of hirsutism. Indeed, while most women with PCOS and hirsutism also have higher than reference values for serum androgen levels, some of them may not present with biochemical hyperandrogenism, representing a challenge to the diagnosis of PCOS. In this article, we critically review this not uncommon condition in women with PCOS presenting with hirsutism but normal androgen levels.

Prenatal Androgenization of Ewes as a Model of Hirsutism in Polycystic Ovary Syndrome.

The main clinical feature associated with hyperandrogenism in polycystic ovary syndrome (PCOS) in humans is hirsutism, where hair increases its length, pigmentation, and particularly its diameter. Currently, it is not known whether PCOS animal models also exhibit changes in the hair. Therefore, the aim of this study was to explore the wool characteristics in sheep prenatally androgenized (PA) with testosterone propionate. After 4 and 13 months of life, wool was collected from the top of the shoulder of both females and males (both androgenized and controls). The offspring sheep were followed for up to 19 months of life to evaluate testosterone and androstenedione serum levels by ultra-high-performance liquid chromatography-tandem mass spectrometry, determine insulin and glucose response to intravenous glucose tolerance test, and address estrus cyclicity during the second breeding season. PA male animals showed a reduction in wool fiber diameter at 4 months of age compared with controls (P = 0.02) but not at 13 months, whereas PA females showed increased hair diameter at 13 months (P = 0.002), with no difference at 4 months. No substantial changes in other hair parameters (length, color, and medullation) were identified. In addition, increased levels of serum testosterone were observed in PA female sheep compared with controls at 12 months (P = 0.03). Our results indicate for the first time, to our knowledge, that changes in wool fiber diameter observed in PA ewes replicate, at the translational level, the increase in hair diameter in hirsute women with PCOS.

Evaluation of Clinical Efficacy of Metformin Therapy in Polycystic Ovary Syndrome

: Objective: To evaluate the metformin efficacy in Polycystic Ovary Syndrome (PCOS), intent to regulate the menstrual cycle and achieving pregnancy rate (live birth, stillbirth) in infertile women with PCOS proportions experiencing spontaneous abortion and time of pregnancy and investigation of the neonatal out comes. Methods: The cross sectional observational study was conducted between January 2012 and December 2014. Totally 310 patients with PCOS in the age group of 18 to 35 enrolled in the study and 220 patients with PCOS were included in the study. Evaluation included the collection of laboratory data, efficacy assessment of hirsutism, acne in PCOS and pre and post therapy of metformin in abortion rate, malformation and live birth rates. Result: Totally 101 subjects had a symptoms of acne and 117 subjects were had symptoms of hirsutism. Metformin therapy significantly reduced incidence of acne and hirsutism. Metformin therapy also significantly increased the number of conceptions from 112 to 138 and reduced abortion and malformation rates. Conclusion: This study has shown a consistent efficacy of metformin in PCOS of patients and improves the live birth rates. Thus, it demonstrates that the therapy of metformin was efficient and well tolerated, especially in teritoginicity and resumes the menstrual cyclicity and reduces the acne and hirsutism in PCOS patients.Key words: Acne, Hirsutism, Metformin, Pregnancy, Polycystic Ovary Syndrome.

Hirsutism in Polycystic Ovary Syndrome: Pathophysiology and Management.

Hirsutism is defined as the presence of terminal hair with male distribution in women, and polycystic ovary syndrome (PCOS) is the most common etiology of hirsutism. The aim of this study is to review aspects of hair growth that are relevant for the understanding of hirsutism in PCOS, along with current treatment alternatives. The prevalence of hirsutism in PCOS ranges from 70 to 80%, vs. 4% to 11% in women in the general population. Hirsutism in PCOS is associated with both ovarianderived androgen excess and individual sensitivity of the pilosebaceous unit to androgens. Interventions to decrease hirsutism in PCOS include the suppression of androgen excess by combined oral contraceptives (OCPs). If OCPs are contraindicated, mainly in the presence of insulin-resistance related comorbidities, a second-line option for reducing androgen secretion may be metformin associated with lifestyle changes. Other interventions should be guided by hirsutism severity, determined by the modified Ferriman-Gallwey score, and by the amount of distress hirsutism causes to the patient, and should be maintained for at least 6-12 months. Mild hirsutism is usually treated with a combination of non-pharmacological methods and OCPs, whereas moderate and severe hirsutism may require a combination of antiandrogens and OCPs, or, if OCPs cannot be used, antiandrogens plus a safe contraceptive method. In all cases, strong clinical support is crucial to ensure treatment adherence and success. The understanding of the pathophysiology of hirsutism in PCOS, as well as classifying its severity and the distress it causes to each patient is essential to choose the proper treatment. The presence of metabolic comorbidities and menstrual disturbances will also guide the individualized management of hirsutism in women with PCOS.

Relationship of body mass index and insulin resistance to degree of hirsutism in polycystic ovary syndrome (PCOS)

Hyperandrogenism in the form of hirsutism is frequently encountered in women with PCOS. Little is known about what factors in the hormonal milieu of PCOS women determine expression of hirsutism. Androgen levels have not correlated well with degree of hirsutism; we set out to find if elevated BMI or insulin resistance altered the degree of hirsutism in the PCOS woman.

Insulin, Independent of Serum Androgens of Androgen Receptor CAG Repeat Polymorphism, is Associated with Hirsutism in Polycystic Ovary Syndrome

Insulin, Independent of Serum Androgens of Androgen Receptor CAG Repeat Polymorphism, is Associated with Hirsutism in Polycystic Ovary Syndrome

Barriers to conducting clinical research in reproductive medicine: Australia and the United Kingdom

There are several major barriers to research in reproductive medicine in the United Kingdom and Australia. In Australia these mainly reflect income disparity between research and private practice whereas in United Kingdom they reflect the consequences of the economic downturn.

Health-related quality of life and psychological distress in polycystic ovary syndrome: a hidden facet in South Asian women

polycystic ovary syndrome (PCOS) is associated with symptoms that affect psychological wellbeing and health-related quality of life (HRQoL). We wished to assess psychological distress and HRQoL among Sri Lankan women with PCOS. case-control study. Gampaha District, Sri Lanka. a total of 146 newly diagnosed women with PCOS, according to the Rotterdam criteria, and 170 age-matched controls recruited from community screening of 3030 eligible women between 15 and 39 years of age. World Health Organization Quality of Life questionnaire (WHOQOL-BREF), validated for Sri Lankans with PCOS and a 30-item General Health Questionnaire (GHQ30) were used to assess HRQoL and psychological distress, respectively. assessment of psychological distress, HRQoL and their correlates. the mean GHQ score was significantly higher (P < 0.001) among women with PCOS (5.25 ± 6.25 SD) than among controls (1.58 ± 1.46 SD), indicating greater psychological distress. Hirsutism in PCOS (defined as a Ferriman-Gallwey, FG, score ≥ 8) was significantly associated with psychological distress (P = 0.002). Multivariate analysis revealed the FG score as a significant predictor of psychological distress (P < 0.05). Mean scores for the physical, psychological and social relationships domains of the WHOQOL-BREF were significantly lower (P = 0.01) in women with PCOS than in controls, indicating poorer HRQoL. No significant predictors of HRQoL emerged from the multivariate analysis. Women with PCOS did not perceive excess body weight as a factor affecting their psychological wellbeing and HRQoL. PCOS occurring in South Asians adversely affects their psychological wellbeing and HRQoL. Their psychological distress is related to hirsutism rather than to obesity, which affects white Europeans with PCOS.

Degree of hyperinsulinemia, independent of androgen levels, is an important determinant of the severity of hirsutism in PCOS

To determine whether the severity in hyperandrogenemia determines, to a significant degree, the severity of hirsutism in patients with polycystic ovary syndrome (PCOS). Cross-sectional study. Tertiary care academic referral center. A total of 749 patients with PCOS. History and physical examination, blood sampling. Hirsutism defined by a value of >or=6 using the modified Ferriman-Gallwey (mFG) score, age, body mass index (BMI), calculated homeostatic assessment for insulin resistance (HOMA-IR) value, and levels of total (TT) and free (FT) testosterone, dehydroepiandrosterone sulfate (DHEAS) 17-hydroxyprogesterone (17OH-P), and fasting insulin (INS) and glucose (GLC). Univariate correlations revealed associations between the mFG score and INS, 17OH-P, HOMA-IR, and BMI. Multivariate classification and regression tree analysis indicated that INS had the most significant association with mFG score and that at higher INS levels T played an additional role whereas at lower INS levels 17OH-P had an effect; however, this model accounted for only 8.2% of total variation in mFG score. Insulin appears to have a direct effect on the severity of hirsutism in PCOS and appears to have a synergistic interaction with TT. Notably, over 90% of the variation in the mFG score was not related to the factors studied and likely reflects intrinsic factors related to pilosebaceous unit function or sensitivity and to other factors not yet assessed.

Correction: Spironolactone for Hirsutism in Polycystic Ovary Syndrome

Correction: Spironolactone for Hirsutism in Polycystic Ovary Syndrome

Spironolactone for Hirsutism in Polycystic Ovary Syndrome

To evaluate the level of evidence for treatment of hirsutism associated with polycystic ovary syndrome (PCOS) with spironolactone. Studies and reports were located in MEDLINE (1966-January 2005), EMBASE, and International Pharmaceutical Abstracts through the second week of January 2005. Hirsutism is a common clinical problem and is often associated with PCOS. Research has been performed to assess the efficacy of spironolactone therapy in patients with hirsute characteristics. Five studies that evaluated the effectiveness of spironolactone for hirsutism in PCOS were identified and reviewed. The effects of multiple treatment options on the subjective and objective measures of hirsutism have displayed varying results. The outcomes reported to date have shown a positive trend toward using spironolactone in women with PCOS and hirsutism.

The effects of rosiglitazone and metformin on menstrual cyclicityand hirsutism in polycystic ovary syndrome

Objective. The aim of the present study was to assess the effects of metformin and rosiglitazone on menstrual cyclicity and hirsutism in patients with polycystic ovary syndrome (PCOS).Materials and methods. Ninety-six patients were included in the study. Serum sex steroids, serum fasting glucose and insulin levels, and insulin response to a 75-g oral glucose tolerance test were assessed in all patients. Menstrual cyclicity, with recording of menses in the 6-month periods before the study and during treatment, was evaluated in each patient. Patients were divided into two groups: one was treated with metformin (MET group, n = 48), while the other received rosiglitazone (ROSI group, n = 48). At baseline and after 24 weeks of treatment all patients underwent hormonal and clinical assessments, including body mass index (BMI), waist and hip measurements and Ferriman – Gallwey (FG) scores.Results. Of the 96 patients included in the study, 88 (91.7%) were able to complete it and yielded data for analyses. After the 24-week treatment period, fasting insulin levels and area under the curve for serum insulin decreased significantly, while the glucose/insulin ratio increased in both groups. The degree of reduction in serum free testosterone and androstenedione levels was similar in the two groups. The decreases in luteinizing hormone/follicle-stimulating hormone ratio and serum dehydroepiandrosterone sulfate levels were significantly greater in the ROSI group compared with the MET group. BMI increased in the ROSI group, while it decreased in the MET group. In patients with menstrual disturbance treated with rosiglitazone, menstrual cycles became regular in 87.8%, while improvement occurred in 79.3% of the patients treated with metformin. FG score decreased in both ROSI and MET groups, but the degree of decrease was significantly greater in the ROSI group than in the MET group.Conclusion. Our data show that both metformin and rosiglitazone improve ovarian function and hirsutism in patients with PCOS. Rosiglitazone appears better than metformin in the treatment of hirsutism and has better patient tolerance.

Acne and hirsutism in polycystic ovary syndrome: clinical, endocrine-metabolic and ultrasonographic differences

Acne and hirsutism in polycystic ovary syndrome: clinical, endocrine-metabolic and ultrasonographic differences

Acne and hirsutism in polycystic ovary syndrome: clinical, endocrine–metabolic and ultrasonographic differences

The aim of this study was to investigate whether the absence or presence of acne or hirsutism in 248 women with polycystic ovary syndrome was associated with different clinical, endocrine, metabolic andultrasonographic factors. Patients were divided into three groups: 96 (38.7%) without any androgenic symptoms; 94 (37.9%) with only hirsutism; and 58 (23.4%) with only acne. The cycle alterations (oligomenorrheaor amenorrhea) and the echographic ovarian morphology (polycystic or multifollicular ovaries) showed no significant differences between the three groups. Hirsutism was associated with a greater incidenceof obesity and insulin resistance, with an increase of 17-hydroxyprogesterone, ovarian and adrenal androgens, 3α-androstanediol glucuronide, insulin, insulin-like growth factor-I and low luteinizinghormone, sex hormone binding globulins and insulin-like growth factor binding protein-1 levels. Acne was associated only with the lowest 3α-androstanediol glucuronide levels. Therefore, twodifferent pathogenetic mechanisms may play a role in the onset of acne and hirsutism.

Prolonged treatment of hirsutism with flutamide alone in patients affected by polycystic ovary syndrome.

Hirsutism is a common symptom of women affected by polycystic ovary syndrome (PCOS). The effectiveness of the antiandrogen flutamide alone was studied in 25 patients affected by PCOS with severe hirsutism for a period of 24 months. Seventeen of these patients had not been treated before and eight had had previous but unsatisfactory therapy. Nineteen patients showed a normal body weight (BMI < 25 kg/m2) whereas six were obese (BMI > 35 kg/m2). A chemical and endocrinological evaluation and an assessment of the degree of hirsutism, assigned by Ferriman-Gallwey score (mean 22 +/- 3.038), was performed under baseline conditions. Patients started treatment with flutamide (Eulexin, Schering-Plough, Kenilworth, USA) at the dose of 500 mg daily. A chronobiological assessment of gonadotropin episodic secretion and of gonadotropin response to GnRH challenge (10 micrograms in bolus) was done before and on day 7 of flutamide administration. During treatment, our patients showed a marked and significant reduction of hirsutism starting from a score of 6 and reaching the maximum (9.6 + 2.1) at 24 months of therapy. No relevant hormonal changes or side-effects were observed during therapy. Our data demonstrate that hirsutism in PCOS can rapidly and markedly respond to treatment with flutamide alone without important side-effects even if administered for a long period.

Hirsutism in Polycystic Ovary Syndrome

Hirsutism in Polycystic Ovary Syndrome

Evidence for the importance of peripheral tissue events in the development of hirsutism in polycystic ovary syndrome.

Hirsutism can occur in the presence of normal or near normal levels of serum testosterone, unbound testosterone (uT), dehydroepiandrostene sulfate, androstenedione, and dihydrotestosterone. However, we have found that serum androstanediol glucuronide (3 alpha-diol G) is markedly increased in idiopathic hirsutism and it serves as an excellent marker of peripheral androgen metabolism and action. In the present work, we studied 12 hirsute (H) and 12 nonhirsute (NH) patients with polycystic ovary syndrome (PCO) and 13 age and weight matched controls in order to determine if differences in sex steroid levels or peripheral tissue androgen events were associated with hirsutism. Serum unbound estradiol levels and LH-FSH ratios were similar in both groups of women with PCO, and both were significantly higher than levels in controls (P less than 0.05). Whereas serum testosterone, uT, and androstenedione were elevated in both H-PCO and NH-PCO patients compared to controls, the levels in these two groups were similar. Serum dehydroepiandrostene sulfate was higher in PCO patients compared to controls, but H-PCO patients had slightly higher levels than NH-PCO patients. Serum delta 5-androstenediol was also slightly higher in H-PCO compared to NH-PCO patients. Dihydrotestosterone was normal and unconjugated; 3 alpha-diol was higher than normal in both groups of patients with PCO, although H-PCO patients had higher levels than NH-PCO patients. Compared to these relatively minor changes between the PCO patient groups, serum 3 alpha-diol G was markedly elevated in H-PCO patients (approximately 10-fold), yet normal in NH-PCO patients (P less than 0.01). The ratios of serum 3 alpha-diol G-uT were similar in NH-PCO patients and controls, but were elevated in H-PCO patients (P less than 0.01). These data indicate that: 1) women with PCO have increased circulating androgen levels regardless of the presence or absence of hirsutism; and 2) the presence of hirsutism is not only a function of circulating androgen levels, but may also be determined by events in peripheral tissues.