SEARCHMETA-ANALYSISendocrinology, obstetrics and gynecology

meta-analysis·endocrinology, obstetrics and gynecology, systematic review, meta-analysis, clinical trial·PMC10424142

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

eClinicalMedicine · 9 authors, 6 centres

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TL;DR

This systematic review and meta-analysis of 20 RCTs (13 pooled, n=961) evaluated anti-androgens in women with PCOS. Anti-androgens combined with lifestyle were superior to metformin combined with lifestyle for reducing hirsutism, but current evidence does not support their preferential use over combined oral contraceptive pills for treating hyperandrogenism in PCOS.

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This systematic review and meta-analysis pooled 13 of 20 included RCTs (n=961) to evaluate anti-androgens (finasteride, flutamide, spironolactone, bicalutamide) in women with PCOS. Combining anti-androgens with COCP resulted in poorer lipid profiles compared with COCP alone in two trials. Risk of bias was high in seven studies, moderate in nine, and low in four; GRADE certainty was low or very low for most outcomes. The authors conclude that anti-androgens could be considered for hirsutism where COCPs are contraindicated, poorly tolerated, or show sub-optimal response after a minimum six-month period.

STUDY TYPE

meta-analysis

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endocrinology

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ORIGINAL PAPER

PMC10424142

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

eClinicalMedicine

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ABSTRACT

Summary Background 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. Methods 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. Findings 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; I 2 = 74%), SHBG (7.70 nmol/l [0.75, 14.66], p = 0.03; I 2 = 0%), fasting insulin and fasting insulin: glucose ratio (−2.11 μU/ml [−3.97, −0.26], p = 0.03; I 2 = 0% and −1.12 [−1.44, −0.79], p < 0.0001, I 2 = 0%, respectively), but were not superior to placebo + lifestyle for hirsutism (−0.93, [−3.37, 1.51], p = 0.45; I 2 = 76%) or SHBG (9.72 nmol/l [−0.71, 20.14], p = 0.07; I 2 = 31%). Daily use was more effective for hirsutism than use every three days (−3.48 [−4.58, −2.39], p < 0.0001, I 2 = 1%), and resulted in lower androstenedione levels (−0.30 ng/ml [−0.50, −0.10], p = 0.004; I 2 = 0%). Combination treatment with anti-androgens + metformin + lifestyle resulted in lower testosterone compared with metformin + lifestyle (−0.29 nmol/l [−0.52, −0.06], p = 0.01; I 2 = 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. Interpretation 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. Funding National Health and Medical Research Council (NHMRC) of Australia Monash University. Keywords: Anti-androgens, Combined oral contraceptives, Guideline, Meta-Analyses, Systematic review, Polycystic ovary syndrome (PCOS), Spironolactone

CITATION EXPORT

Simon Alesi, Maria Forslund, Johanna Melin et al.. Efficacy and safety of anti-androgens in the management of polycystic ovary syndrome: a systematic review and meta-analysis of randomised controlled trials. eClinicalMedicine. (2023). https://doi.org/10.1016/j.eclinm.2023.102162

AUTHORS

9 · 6 CENTRES

Simon Alesi, Maria Forslund, Johanna Melin, Daniela Romualdi, Alexia Peña, Chau Thien Tay, Selma Feldman Witchel, Helena Teede, Aya Mousa

aMonash Centre for Health Research and Implementation (MCHRI), Monash University, Clayton, VIC, Australia
bDepartment of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
cDepartment of Obstetrics and Gynecology, University of Helsinki, Helsinki University Hospital, Helsinki, Finland
dDivision of Paediatric Endocrinology, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA, USA
eFondazione Policlinico Universitario Agostino Gemelli, Rome, Italy
fDiscipline of Paediatrics, The University of Adelaide and Robinson Research Institute, Adelaide, Australia