Impact of pharmacological interventions on biochemical hyperandrogenemia in women with polycystic ovary syndrome: a systematic review and meta-analysis of randomised controlled trials
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A. Sahebkar | S. Atkin | T. Sathyapalan | Linda Östlundh | M. Abdalla | Harshal Deshmukh | N. Shah | R. Al-Rifai
[1] G. Úrrutia,et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. , 2021, Revista espanola de cardiologia.
[2] S. Atkin,et al. The Effect of Free Androgen Index on the Quality of Life of Women With Polycystic Ovary Syndrome: A Cross-Sectional Study , 2021, Frontiers in Physiology.
[3] E. Mayo-Wilson,et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews , 2021, BMJ.
[4] Lili Zhou,et al. The role of androgen and its related signals in PCOS , 2020, Journal of cellular and molecular medicine.
[5] L. Thabane,et al. Efficacy of Treatments for Polycystic Ovarian Syndrome Management in Adolescents , 2020, Journal of the Endocrine Society.
[6] C. Yin,et al. Involvement of endogenous testosterone in hepatic steatosis in women with polycystic ovarian syndrome , 2020, The Journal of Steroid Biochemistry and Molecular Biology.
[7] Huaien Bu,et al. The Effect of Metformin on Polycystic Ovary Syndrome in Overweight Women: A Systematic Review and Meta-Analysis of Randomized Controlled Trials , 2020, International journal of endocrinology.
[8] L. Moran,et al. Metformin versus the combined oral contraceptive pill for hirsutism, acne, and menstrual pattern in polycystic ovary syndrome. , 2020, The Cochrane database of systematic reviews.
[9] Z. Saadia. Follicle Stimulating Hormone (LH: FSH) Ratio in Polycystic Ovary Syndrome (PCOS) - Obese vs. Non- Obese Women , 2020, Medical archives.
[10] S. Atkin,et al. miRNAs as a novel clinical biomarker and therapeutic targets in polycystic ovary syndrome (PCOS): A review. , 2020, Life sciences.
[11] R. Smolarczyk,et al. Hormonal Effects on Hair Follicles , 2020, International journal of molecular sciences.
[12] S. Atkin,et al. A review of therapeutic options for managing the metabolic aspects of polycystic ovary syndrome , 2020, Therapeutic advances in endocrinology and metabolism.
[13] D. Khalili,et al. A comparison of the effects of oral contraceptives on the clinical and biochemical manifestations of polycystic ovary syndrome: a crossover randomized controlled trial. , 2020, Human reproduction.
[14] L. Lerman,et al. Effect of Metformin on Microvascular Endothelial Function in Polycystic Ovary Syndrome. , 2019, Mayo Clinic proceedings.
[15] Wei Huang,et al. Comparing the individual effects of metformin and rosiglitazone and their combination in obese women with polycystic ovary syndrome: a randomized controlled trial. , 2019, Fertility and sterility.
[16] B. Mol,et al. Effect of the combined oral contraceptive pill and/or metformin in the management of polycystic ovary syndrome: A systematic review with meta‐analyses , 2019, Clinical endocrinology.
[17] N. Brown,et al. Sitagliptin decreases visceral fat and blood glucoses in women with polycystic ovarian syndrome. , 2019, The Journal of clinical endocrinology and metabolism.
[18] J. Risteli,et al. Metformin decreases bone turnover markers in polycystic ovary syndrome: a post hoc study. , 2019, Fertility and sterility.
[19] A. Nagy,et al. Doppler analysis of ovarian stromal blood flow changes after treatment with metformin versus ethinyl estradiol-cyproterone acetate in women with polycystic ovarian syndrome: A randomized controlled trial. , 2019, Journal of gynecology obstetrics and human reproduction.
[20] A. Dang,et al. Association of Luteinizing hormone and LH receptor gene polymorphism with susceptibility of Polycystic ovary syndrome , 2019, Systems biology in reproductive medicine.
[21] J. Levine,et al. Hyperandrogenic origins of polycystic ovary syndrome – implications for pathophysiology and therapy , 2019, Expert review of endocrinology & metabolism.
[22] J. Qiao,et al. Evidence summaries and recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome: assessment and treatment of infertility , 2019, Human reproduction open.
[23] K. Hari Kumar,et al. A randomized, controlled trial comparing the metformin, oral contraceptive pills and their combination in patients with polycystic ovarian syndrome , 2018, Journal of family medicine and primary care.
[24] Soumitra Das,et al. Cabell's Blacklist: A New Way to Tackle Predatory Journals , 2018, Indian journal of psychological medicine.
[25] W. Liu,et al. Comparison of glycemic control and β-cell function in new onset T2DM patients with PCOS of metformin and saxagliptin monotherapy or combination treatment , 2018, BMC Endocrine Disorders.
[26] W. Xu,et al. Efficacy of exenatide on weight loss, metabolic parameters and pregnancy in overweight/obese polycystic ovary syndrome , 2017, Clinical endocrinology.
[27] A. Janež,et al. DPP4 INHIBITOR SITAGLIPTIN AS A POTENTIAL TREATMENT OPTION IN METFORMIN-INTOLERANT OBESE WOMEN WITH POLYCYSTIC OVARY SYNDROME: A PILOT RANDOMIZED STUDY. , 2017, Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists.
[28] M. Elsersy. Efficacy of Combined Cabergoline and Metformin Compared to Metformin Alone on Cycle Regularity in Patients with Polycystic Ovarian Disease with Hyperprolactinemia: A Randomized Clinical Trial , 2017, The Journal of Obstetrics and Gynecology of India.
[29] J. Holst,et al. Effect of oral contraceptives and/or metformin on GLP-1 secretion and reactive hypoglycaemia in polycystic ovary syndrome , 2017, Endocrine connections.
[30] A. Janež,et al. Short-term effectiveness of low dose liraglutide in combination with metformin versus high dose liraglutide alone in treatment of obese PCOS: randomized trial , 2017, BMC Endocrine Disorders.
[31] M. Karimi-Zarchi,et al. Evaluating the effect of insulin sensitizers metformin and pioglitazone alone and in combination on women with polycystic ovary syndrome: An RCT , 2016, International journal of reproductive biomedicine.
[32] M. Rezaei,et al. Comparison clinical and metabolic effects of metformin and pioglitazone in polycystic ovary syndrome , 2016, Indian journal of endocrinology and metabolism.
[33] D. Ehrmann,et al. The Pathogenesis of Polycystic Ovary Syndrome (PCOS): The Hypothesis of PCOS as Functional Ovarian Hyperandrogenism Revisited. , 2016, Endocrine reviews.
[34] A. Janež,et al. Metformin as an initial adjunct to low-dose liraglutide enhances the weight-decreasing potential of liraglutide in obese polycystic ovary syndrome: Randomized control study , 2016, Experimental and therapeutic medicine.
[35] S. Bhattacharya,et al. Comparison of two contraceptive pills containing drospirenone and 20 μg or 30 μg ethinyl estradiol for polycystic ovary syndrome , 2016, International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics.
[36] D. Glintborg,et al. Increased thrombin generation in women with polycystic ovary syndrome: A pilot study on the effect of metformin and oral contraceptives. , 2015, Metabolism: clinical and experimental.
[37] A. Janež,et al. Short term monotherapy with GLP-1 receptor agonist liraglutide or PDE 4 inhibitor roflumilast is superior to metformin in weight loss in obese PCOS women: a pilot randomized study , 2015, Journal of Ovarian Research.
[38] S. Rattanasiri,et al. Comparison of desogestrel/ethinyl estradiol plus spironolactone versus cyproterone acetate/ethinyl estradiol in the treatment of polycystic ovary syndrome: A randomized controlled trial , 2015, The journal of obstetrics and gynaecology research.
[39] A. Ghaneei,et al. Cabergoline plus metformin therapy effects on menstrual irregularity and androgen system in polycystic ovary syndrome women with hyperprolactinemia , 2015, Iranian journal of reproductive medicine.
[40] Ali Bijani,et al. Effect of Metformin and Flutamide on Anthropometric Indices and Laboratory Tests in Obese/Overweight PCOS Women under Hypocaloric Diet , 2014, Journal of reproduction & infertility.
[41] Jessica Babineau,et al. Product Review: Covidence (Systematic Review Software) , 2014 .
[42] B. Richelsen,et al. Adiponectin, interleukin-6, monocyte chemoattractant protein-1, and regional fat mass during 12-month randomized treatment with metformin and/or oral contraceptives in polycystic ovary syndrome , 2014, Journal of Endocrinological Investigation.
[43] A. Hermann,et al. Body composition is improved during 12 months' treatment with metformin alone or combined with oral contraceptives compared with treatment with oral contraceptives in polycystic ovary syndrome. , 2014, The Journal of clinical endocrinology and metabolism.
[44] C. Ateş,et al. Comparison of two oral contraceptive forms containing cyproterone acetate and drospirenone in the treatment of patients with polycystic ovary syndrome: a randomized clinical trial , 2014, Archives of Gynecology and Obstetrics.
[45] A. Janež,et al. Short-term combined treatment with liraglutide and metformin leads to significant weight loss in obese women with polycystic ovary syndrome and previous poor response to metformin , 2013, European journal of endocrinology.
[46] A. Ruokonen,et al. Statin therapy worsens insulin sensitivity in women with polycystic ovary syndrome (PCOS): a prospective, randomized, double-blind, placebo-controlled study. , 2013, The Journal of clinical endocrinology and metabolism.
[47] A. Lanzone,et al. Clinical efficacy and metabolic impact of two different dosages of ethinyl-estradiol in association with drospirenone in normal-weight women with polycystic ovary syndrome: A randomized study , 2013, Journal of Endocrinological Investigation.
[48] U. Puistola,et al. Metformin decreases serum 8-hydroxy-2'-deoxyguanosine levels in polycystic ovary syndrome. , 2013, Fertility and sterility.
[49] E. Jude,et al. Effects of low-dose metformin and rosiglitazone on biochemical, clinical, metabolic and biophysical outcomes in polycystic ovary syndrome , 2013, Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology.
[50] E. Diamanti-Kandarakis,et al. Insulin resistance and the polycystic ovary syndrome revisited: an update on mechanisms and implications. , 2012, Endocrine reviews.
[51] E. Baracat,et al. Assessing the benefits of rosiglitazone in women with polycystic ovary syndrome through its effects on insulin-like growth factor 1, insulin-like growth factor-binding protein-3 and insulin resistance: a pilot study , 2012, Clinics.
[52] J. Sterne,et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials , 2011, BMJ : British Medical Journal.
[53] I. Anaforoglu,et al. Higher metabolic risk with National Institutes of Health versus Rotterdam diagnostic criteria for polycystic ovarian syndrome in Turkish women. , 2011, Metabolic syndrome and related disorders.
[54] J. Chan,et al. The reproductive and metabolic effect of rosiglitazone on Chinese women with polycystic ovarian syndrome--a double-blind randomized placebo-controlled study. , 2011, Fertility and sterility.
[55] N. Georgopoulos,et al. The impact of oral contraceptives and metformin on anti-Müllerian hormone serum levels in women with polycystic ovary syndrome and biochemical hyperandrogenemia , 2011, Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology.
[56] B. Yan,et al. Metformin vs thiazolidinediones for treatment of clinical, hormonal and metabolic characteristics of polycystic ovary syndrome: a meta‐analysis , 2011, Clinical endocrinology.
[57] A. Badawy,et al. Treatment options for polycystic ovary syndrome , 2011, International journal of women's health.
[58] J. Frystyk,et al. Adiponectin levels in women with polycystic ovary syndrome: impact of metformin treatment in a randomized controlled study. , 2010, Fertility and sterility.
[59] F. Ghaffarpasand,et al. Effects of metformin plus simvastatin on polycystic ovary syndrome: a prospective, randomized, double-blind, placebo-controlled study. , 2010, Fertility and sterility.
[60] C. Tempfer,et al. Metformin versus acarbose therapy in patients with polycystic ovary syndrome (PCOS): a prospective randomised double-blind study , 2010, Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology.
[61] Michele Tarsilla. Cochrane Handbook for Systematic Reviews of Interventions , 2010, Journal of MultiDisciplinary Evaluation.
[62] A. Lanzone,et al. Metformin effects on ovarian ultrasound appearance and steroidogenic function in normal-weight normoinsulinemic women with polycystic ovary syndrome: a randomized double-blind placebo-controlled clinical trial. , 2010, Fertility and sterility.
[63] C. Roehrborn,et al. Effects of finasteride on serum testosterone and body mass index in men with benign prostatic hyperplasia. , 2010, Urology.
[64] C. Taner,et al. Oral contraceptives alone and with spironolactone increase sCD40 ligand in PCOS patients , 2010, Archives of Gynecology and Obstetrics.
[65] S. Carlsen,et al. Anti-Müllerian hormone concentrations in androgen-suppressed women with polycystic ovary syndrome. , 2009, Human reproduction.
[66] Ş. Çetinkalp,et al. The Effects of Rosiglitazone, Metformin, and Estradiol-cyproterone Acetate on Lean Patients With Polycystic Ovary Syndrome , 2009 .
[67] B. Keevil,et al. Effect of metformin, orlistat and pioglitazone treatment on mean insulin resistance and its biological variability in polycystic ovary syndrome , 2009, Clinical endocrinology.
[68] R. Norman,et al. The Androgen Excess and PCOS Society criteria for the polycystic ovary syndrome: the complete task force report. , 2009, Fertility and sterility.
[69] S. Mudaliar,et al. Metabolic and hormonal changes induced by pioglitazone in polycystic ovary syndrome: a randomized, placebo-controlled clinical trial. , 2009, The Journal of clinical endocrinology and metabolism.
[70] R. Norman,et al. Comparison of clomiphene citrate, metformin, or the combination of both for first-line ovulation induction, achievement of pregnancy, and live birth in Asian women with polycystic ovary syndrome: a randomized controlled trial. , 2009, Fertility and sterility.
[71] A. Janež,et al. Improvement of endothelial function with metformin and rosiglitazone treatment in women with polycystic ovary syndrome. , 2008, European journal of endocrinology.
[72] K. Elkind-Hirsch,et al. Comparison of single and combined treatment with exenatide and metformin on menstrual cyclicity in overweight women with polycystic ovary syndrome. , 2008, The Journal of clinical endocrinology and metabolism.
[73] A. Janež,et al. Impact of metformin and rosiglitazone treatment on glucose transporter 4 mRNA expression in women with polycystic ovary syndrome. , 2008, European journal of endocrinology.
[74] G. Guyatt,et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations , 2008, BMJ : British Medical Journal.
[75] Abdur Rahman Khan,et al. Comparison of metabolic effects of metformin and rosiglitazone in the management of polycystic ovary syndrome (PCOS): A prospective, parallel, randomized, open-label study , 2008 .
[76] Jie Wu,et al. Effects of metformin and ethinyl estradiol-cyproterone acetate on clinical, endocrine and metabolic factors in women with polycystic ovary syndrome , 2008, Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology.
[77] F. Manguso,et al. Insulin sensitivity after metformin suspension in normal-weight women with polycystic ovary syndrome. , 2007, The Journal of clinical endocrinology and metabolism.
[78] W. Dodson,et al. The effects of metformin and rosiglitazone, alone and in combination, on the ovary and endometrium in polycystic ovary syndrome. , 2007, American journal of obstetrics and gynecology.
[79] J. Dziura,et al. Effects of simvastatin and oral contraceptive agent on polycystic ovary syndrome: prospective, randomized, crossover trial. , 2007, The Journal of clinical endocrinology and metabolism.
[80] Antonio Maria Morselli-Labate,et al. Treatment with flutamide, metformin, and their combination added to a hypocaloric diet in overweight-obese women with polycystic ovary syndrome: a randomized, 12-month, placebo-controlled study. , 2006, The Journal of clinical endocrinology and metabolism.
[81] H. Beck-Nielsen,et al. Effect of pioglitazone on glucose metabolism and luteinizing hormone secretion in women with polycystic ovary syndrome. , 2006, Fertility and sterility.
[82] T. Wilkin,et al. The effect of metformin on fat distribution and the metabolic syndrome in women with polycystic ovary syndrome—a randomised, double‐blind, placebo‐controlled trial , 2006, BJOG : an international journal of obstetrics and gynaecology.
[83] A. Ruokonen,et al. Endocrine and metabolic effects of rosiglitazone in overweight women with PCOS: a randomized placebo-controlled study. , 2006, Human reproduction.
[84] A. Duleba,et al. Simvastatin improves biochemical parameters in women with polycystic ovary syndrome: results of a prospective, randomized trial. , 2006, Fertility and sterility.
[85] T. Strowitzki,et al. Early effects of metformin in women with polycystic ovary syndrome: a prospective randomized, double-blind, placebo-controlled trial. , 2006, The Journal of clinical endocrinology and metabolism.
[86] A. Hermann,et al. Pioglitazone treatment increases spontaneous growth hormone (GH) secretion and stimulated GH levels in polycystic ovary syndrome. , 2005, The Journal of clinical endocrinology and metabolism.
[87] R. M. Reis,et al. Acarbose in obese patients with polycystic ovarian syndrome: a double-blind, randomized, placebo-controlled study. , 2005, Human reproduction.
[88] A. Sanabria,et al. Randomized controlled trial. , 2005, World journal of surgery.
[89] L. Hernández,et al. Responses of serum androgen and insulin resistance to metformin and pioglitazone in obese, insulin-resistant women with polycystic ovary syndrome. , 2005, The Journal of clinical endocrinology and metabolism.
[90] N. Çakır,et al. The effects of rosiglitazone and metformin on menstrual cyclicityand hirsutism in polycystic ovary syndrome , 2005, Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology.
[91] K. Salvesen,et al. Metformin reduces pregnancy complications without affecting androgen levels in pregnant polycystic ovary syndrome women: results of a randomized study. , 2004, Human reproduction.
[92] C. De Geyter,et al. Effect of the insulin sensitizer pioglitazone on insulin resistance, hyperandrogenism, and ovulatory dysfunction in women with polycystic ovary syndrome. , 2004, The Journal of clinical endocrinology and metabolism.
[93] K. Salvesen,et al. Six-month treatment with low-dose dexamethasone further reduces androgen levels in PCOS women treated with diet and lifestyle advice, and metformin. , 2004, Human reproduction.
[94] U. Pagotto,et al. Effect of flutamide and metformin administered alone or in combination in dieting obese women with polycystic ovary syndrome , 2004, Clinical endocrinology.
[95] A. Dunaif,et al. Polycystic ovary syndrome: Syndrome XX? , 2003, Trends in Endocrinology & Metabolism.
[96] N. Sattar,et al. Metformin or antiandrogen in the treatment of hirsutism in polycystic ovary syndrome. , 2003, The Journal of clinical endocrinology and metabolism.
[97] I. Vauhkonen,et al. Metformin versus ethinyl estradiol-cyproterone acetate in the treatment of nonobese women with polycystic ovary syndrome: a randomized study. , 2003, The Journal of clinical endocrinology and metabolism.
[98] P. Spritzer,et al. Clinical, metabolic and endocrine parameters in response to metformin in obese women with polycystic ovary syndrome: a randomized, double-blind and placebo-controlled trial. , 2003, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.
[99] F. Durmuşoǧlu,et al. Clinical, endocrine and metabolic effects of metformin added to ethinyl estradiol-cyproterone acetate in non-obese women with polycystic ovarian syndrome: a randomized controlled study. , 2002, Human reproduction.
[100] H. Malkawi,et al. The effect of metformin plus clomiphene citrate on ovulation and pregnancy rates in clomiphene-resistant women with polycystic ovary syndrome. , 2002, Saudi medical journal.
[101] A. Paoletti,et al. The antiandrogenic effect of flutamide improves uterine perfusion in women with polycystic ovary syndrome. , 2002, Fertility and sterility.
[102] H. Zeyneloglu,et al. Co-administration of metformin during rFSH treatment in patients with clomiphene citrate-resistant polycystic ovarian syndrome: a prospective randomized trial. , 2002, Human reproduction.
[103] V. de Leo,et al. Clinical, endocrine and metabolic effects of acarbose, an alpha-glucosidase inhibitor, in PCOS patients with increased insulin response and normal glucose tolerance. , 2001, Human reproduction.
[104] P. Ho,et al. Effects of metformin on ovulation rate, hormonal and metabolic profiles in women with clomiphene-resistant polycystic ovaries: a randomized, double-blinded placebo-controlled trial. , 2001, Human reproduction.
[105] W. Evans,et al. Metformin increases the ovulatory rate and pregnancy rate from clomiphene citrate in patients with polycystic ovary syndrome who are resistant to clomiphene citrate alone. , 2001, Fertility and sterility.
[106] I. Vauhkonen,et al. Endocrine and metabolic effects of metformin versus ethinyl estradiol-cyproterone acetate in obese women with polycystic ovary syndrome: a randomized study. , 2000, The Journal of clinical endocrinology and metabolism.
[107] L. Falsetti,et al. Comparison of finasteride versus flutamide in the treatment of hirsutism. , 1999, European journal of endocrinology.
[108] L. Falsetti,et al. Treatment of hirsutism by finasteride and flutamide in women with polycystic ovary syndrome. , 1997, Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology.
[109] A. Murdoch,et al. Treatment of hirsutism in polycystic ovary syndrome with bromocriptine , 1987, British journal of obstetrics and gynaecology.
[110] P. Fossati,et al. A Double Blind Controlled Study of the Hormonal and Clinical Effects of Bromocriptine in the Polycystic Ovary Syndrome , 1986 .
[111] K. Elkind-Hirsch,et al. Short-term therapy with combination dipeptidyl peptidase-4 inhibitor saxagliptin/metformin extended release (XR) is superior to saxagliptin or metformin XR monotherapy in prediabetic women with polycystic ovary syndrome: a single-blind, randomized, pilot study. , 2017, Fertility and sterility.
[112] A. Janež,et al. A 12-week treatment with the long-acting glucagon-like peptide 1 receptor agonist liraglutide leads to significant weight loss in a subset of obese women with newly diagnosed polycystic ovary syndrome , 2015, Hormones.
[113] G. Chrousos,et al. Effect of the insulin sensitizers metformin and pioglitazone on endothelial function in young women with polycystic ovary syndrome: a prospective randomized study. , 2011, Fertility and sterility.
[114] S. Zoungas,et al. Endothelial function and insulin resistance in polycystic ovary syndrome: the effects of medical therapy. , 2010, Fertility and sterility.
[115] C. Taner,et al. Comparison of four different treatment regimens on coagulation parameters, hormonal and metabolic changes in women with polycystic ovary syndrome , 2009, Archives of Gynecology and Obstetrics.
[116] G. Bozkaya,et al. The effect of ethinylestradiol (EE)/cyproterone acetate (CA) and EE/CA plus metformin treatment on adhesion molecules in cases with polycystic ovary syndrome (PCOS). , 2009, Internal medicine.
[117] E. Kilpatrick,et al. The effect of atorvastatin in patients with polycystic ovary syndrome: a randomized double-blind placebo-controlled study. , 2009, The Journal of clinical endocrinology and metabolism.
[118] D. Cibula,et al. The effect of combination therapy with metformin and combined oral contraceptives (COC) versus COC alone on insulin sensitivity, hyperandrogenaemia, SHBG and lipids in PCOS patients. , 2005, Human reproduction.
[119] N. Sut,et al. Comparison of the effects of acarbose and metformin use on ovulation rates in clomiphene citrate-resistant polycystic ovary syndrome. , 2005, Human reproduction.
[120] B. Fauser,et al. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). , 2004, Human reproduction.
[121] E. Çalışkan,et al. Metformin therapy improves ovulatory rates, cervical scores, and pregnancy rates in clomiphene citrate-resistant women with polycystic ovary syndrome. , 2002, Fertility and sterility.