A 27-year-old woman with a diagnosis of polycystic ovary syndrome.

Ms R, a 27-year-old woman with polycystic ovary syndrome (PCOS) diagnosed after irregular menses, hirsutism, and polycystic ovaries, is concerned about weight gain despite regular exercise and watching her diet. Prescribed oral contraceptives to regulate her menses and help reduce her androgen levels, she wants to know the alternatives for treatment of PCOS. The varying definitions of PCOS and its heterogeneity confound the interpretation of studies on PCOS. Specific diagnostic criteria have been established based on expert opinion but have not been validated. Several commonly performed laboratory tests are generally unhelpful and the pathophysiology is poorly understood. Treatment options for Ms R, including those that may affect her weight gain, are reviewed and implications for future fertility are discussed.

[1]  M. Eijkemans,et al.  A meta-analysis of pregnancy outcomes in women with polycystic ovary syndrome. , 2006, Human reproduction update.

[2]  Didier Dewailly,et al.  Ultrasound assessment of the polycystic ovary: international consensus definitions. , 2003, Human reproduction update.

[3]  C. Welt,et al.  Serum inhibin B in polycystic ovary syndrome: regulation by insulin and luteinizing hormone. , 2002, The Journal of clinical endocrinology and metabolism.

[4]  R. Norman,et al.  Positions statement: criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: an Androgen Excess Society guideline. , 2006, The Journal of clinical endocrinology and metabolism.

[5]  S. Fowler,et al.  Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. , 2002 .

[6]  K. Schulz,et al.  Combination Estrogen–Progestin Contraceptives and Body Weight: Systematic Review of Randomized Controlled Trials , 2004, Obstetrics and gynecology.

[7]  R. Norman,et al.  Metformin in polycystic ovary syndrome: systematic review and meta-analysis , 2003, BMJ : British Medical Journal.

[8]  H. Barnhart,et al.  The Pregnancy in Polycystic Ovary Syndrome study: baseline characteristics of the randomized cohort including racial effects. , 2006, Fertility and sterility.

[9]  J. Marshall,et al.  The origins and sequelae of abnormal neuroendocrine function in polycystic ovary syndrome. , 2006, Human reproduction update.

[10]  D. Ehrmann,et al.  Troglitazone decreases adrenal androgen levels in women with polycystic ovary syndrome. , 2003, Fertility and sterility.

[11]  T. McLaughlin,et al.  Differences in insulin resistance do not predict weight loss in response to hypocaloric diets in healthy obese women. , 1999, The Journal of clinical endocrinology and metabolism.

[12]  R Krattenmacher,et al.  Drospirenone: pharmacology and pharmacokinetics of a unique progestogen. , 2000, Contraception.

[13]  S. Yen,et al.  Inappropriate gonadotropin secretion in polycystic ovary syndrome: influence of adiposity. , 1997, The Journal of clinical endocrinology and metabolism.

[14]  M. Muhcu,et al.  Comparison of Letrozole and Clomiphene Citrate in Women with Polycystic Ovaries Undergoing Ovarian Stimulation , 2006, The Journal of international medical research.

[15]  A. Lanzone,et al.  Drospirenone for the treatment of hirsute women with polycystic ovary syndrome: a clinical, endocrinological, metabolic pilot study. , 2004, The Journal of clinical endocrinology and metabolism.

[16]  M. Byrne,et al.  Insulin secretory defects in polycystic ovary syndrome. Relationship to insulin sensitivity and family history of non-insulin-dependent diabetes mellitus. , 1995, The Journal of clinical investigation.

[17]  J. Schlesselman,et al.  Risk of endometrial cancer in relation to use of combined oral contraceptives. A practitioner's guide to meta-analysis. , 1997, Human reproduction.

[18]  Mary E D'Alton,et al.  Obesity, obstetric complications and cesarean delivery rate--a population-based screening study. , 2004, American journal of obstetrics and gynecology.

[19]  W. Crowley,et al.  Insights into hypothalamic-pituitary dysfunction in polycystic ovary syndrome , 1998, Journal of endocrinological investigation.

[20]  G. Kovacs.  Progestogen-only pills and bleeding disturbances. , 1996, Human reproduction.

[21]  A. Dunaif,et al.  Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. , 1997, Endocrine reviews.

[22]  K. Sutton-Tyrrell,et al.  The relationship between C-reactive protein and carotid intima-media wall thickness in middle-aged women with polycystic ovary syndrome. , 2004, The Journal of clinical endocrinology and metabolism.

[23]  Didier Dewailly,et al.  Revisiting the ovarian volume as a diagnostic criterion for polycystic ovaries. , 2005, Human reproduction.

[24]  E. Adashi,et al.  Insulin enhancement of luteinizing hormone and follicle-stimulating hormone release by cultured pituitary cells. , 1981, Endocrinology.

[25]  Richard S Legro,et al.  Polycystic ovary syndrome and cardiovascular disease: a premature association? , 2003, Endocrine reviews.

[26]  Greenblatt Rb,et al.  Update on the safety and efficacy of clomiphene citrate as a therapeutic agent. , 1976 .

[27]  D. Cryer,et al.  Comparative outcomes study of metformin intervention versus conventional approach the COSMIC Approach Study. , 2005, Diabetes care.

[28]  C. Farquhar,et al.  Oral anti-oestrogens and medical adjuncts for subfertility associated with anovulation. , 2005, The Cochrane database of systematic reviews.

[29]  L. Kuller,et al.  Adverse lipid and coronary heart disease risk profiles in young women with polycystic ovary syndrome: results of a case-control study. , 1998, Journal of clinical epidemiology.

[30]  G. Koren,et al.  Pregnancy outcome after first-trimester exposure to metformin: a meta-analysis. , 2006, Fertility and sterility.

[31]  D. Jakubowicz,et al.  Effects of metformin on spontaneous and clomiphene-induced ovulation in the polycystic ovary syndrome. , 1998, The New England journal of medicine.

[32]  G. Kaltsas,et al.  Polycystic ovary syndrome: the spectrum of the disorder in 1741 patients. , 1995, Human reproduction.

[33]  M. Cavaghan,et al.  Prevalence of impaired glucose tolerance and diabetes in women with polycystic ovary syndrome. , 1999, Diabetes care.

[34]  S. Franks,et al.  Improvement in endocrine and ovarian function during dietary treatment of obese women with polycystic ovary syndrome , 1992 .

[35]  J. Zborowski,et al.  Serum testosterone levels decrease in middle age in women with the polycystic ovary syndrome , 2000 .

[36]  R. Kulier,et al.  Progestogens in combined oral contraceptives for contraception. , 2004, The Cochrane database of systematic reviews.

[37]  P. Vandekerckhove,et al.  Clomiphene citrate for ovulation induction in women with oligo-amenorrhoea. , 1996, The Cochrane database of systematic reviews.

[38]  G. Dekker,et al.  Higher risk of preeclampsia in the polycystic ovary syndrome. A case control study. , 1998, European journal of obstetrics, gynecology, and reproductive biology.

[39]  Julie Brown,et al.  Spironolactone versus placebo or in combination with steroids for hirsutism and/or acne. , 2009, The Cochrane database of systematic reviews.

[40]  R. Azziz,et al.  Total testosterone and DHEAS levels as predictors of androgen-secreting neoplasms: a populational study. , 1999, Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology.

[41]  F. D'Amico,et al.  Metformin as Treatment for Overweight and Obese Adults: A Systematic Review , 2005, The Annals of Family Medicine.

[42]  Combined lifestyle modification and metformin in obese patients with polycystic ovary syndrome. A randomized, placebo-controlled, double-blind multicentre study. , 2006 .

[43]  A. Baron,et al.  Polycystic Ovary Syndrome Is Associated With Endothelial Dysfunction , 2001, Circulation.

[44]  Michael J Thun,et al.  Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. , 2003, The New England journal of medicine.

[45]  E. Adashi,et al.  Clomiphene citrate: mechanism(s) and site(s) of action--a hypothesis revisited. , 1984, Fertility and sterility.

[46]  M. Eijkemans,et al.  PCOS according to the Rotterdam consensus criteria: change in prevalence among WHO‐II anovulation and association with metabolic factors , 2006, BJOG : an international journal of obstetrics and gynaecology.

[47]  D. Ehrmann,et al.  Troglitazone improves ovulation and hirsutism in the polycystic ovary syndrome: a multicenter, double blind, placebo-controlled trial. , 2001, The Journal of clinical endocrinology and metabolism.

[48]  K. van Grootheest,et al.  Thromboembolism associated with the new contraceptive Yasmin , 2003, British medical journal.

[49]  Ricardo Azziz,et al.  0021-972X/04/$15.00/0 The Journal of Clinical Endocrinology & Metabolism 89(6):2745–2749 Printed in U.S.A. Copyright © 2004 by The Endocrine Society doi: 10.1210/jc.2003-032046 The Prevalence and Features of the Polycystic Ovary Syndrome in an Unselected , 2022 .

[50]  P. Claman.  Men at risk: occupation and male infertility. , 2004, Fertility and sterility.

[51]  D. Guzick,et al.  A randomized, 48-week, placebo-controlled trial of intensive lifestyle modification and/or metformin therapy in overweight women with polycystic ovary syndrome: a pilot study. , 2004, Fertility and sterility.

[52]  R. Kaaks,et al.  Obesity , Endogenous Hormones , and Endometrial Cancer Risk : A Synthetic Review 1 , 2002 .

[53]  D. Driscoll,et al.  Insulin resistance in the sisters of women with polycystic ovary syndrome: association with hyperandrogenemia rather than menstrual irregularity. , 2002, The Journal of clinical endocrinology and metabolism.

[54]  A. Kunselman,et al.  A randomized trial of the effects of two types of short-term hypocaloric diets on weight loss in women with polycystic ovary syndrome. , 2004, Fertility and sterility.

[55]  B. Fauser,et al.  Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). , 2004, Human reproduction.

[56]  D. Jakubowicz,et al.  Effects of metformin and rosiglitazone, alone and in combination, in nonobese women with polycystic ovary syndrome and normal indices of insulin sensitivity. , 2004, Fertility and sterility.

[57]  Paul Hardiman,et al.  Polycystic ovary syndrome and endometrial carcinoma , 2003, The Lancet.

[58]  D. Jakubowicz,et al.  A modern medical quandary: polycystic ovary syndrome, insulin resistance, and oral contraceptive pills. , 2003, The Journal of clinical endocrinology and metabolism.

[59]  A fasting glucose to insulin ratio is a useful measure of insulin sensitivity in women with polycystic ovary syndrome. , 1998, The Journal of clinical endocrinology and metabolism.

[60]  M. Noakes,et al.  Short-term meal replacements followed by dietary macronutrient restriction enhance weight loss in polycystic ovary syndrome. , 2006, The American journal of clinical nutrition.

[61]  R. Fanchin,et al.  Mono-ovulatory cycles: A key goal in profertility programmes , 2003 .

[62]  A. Venkatesan,et al.  Insulin resistance in polycystic ovary syndrome: progress and paradoxes. , 2001, Recent progress in hormone research.

[63]  U. Goktolga,et al.  Predictive value of glucose-insulin ratio in PCOS and profile of women who will benefit from metformin therapy: obese, lean, hyper or normoinsulinemic? , 2005, European journal of obstetrics, gynecology, and reproductive biology.

[64]  G. Guyatt,et al.  Development of a health-related quality-of-life questionnaire (PCOSQ) for women with polycystic ovary syndrome (PCOS). , 1998, The Journal of clinical endocrinology and metabolism.

[65]  S Fiorini,et al.  Effect of long-term treatment with metformin added to hypocaloric diet on body composition, fat distribution, and androgen and insulin levels in abdominally obese women with and without the polycystic ovary syndrome. , 2000, The Journal of clinical endocrinology and metabolism.

[66]  P. Bossuyt,et al.  Effect of clomifene citrate plus metformin and clomifene citrate plus placebo on induction of ovulation in women with newly diagnosed polycystic ovary syndrome: randomised double blind clinical trial , 2006, BMJ : British Medical Journal.

[67]  J. Lindström,et al.  Sustained reduction in the incidence of type 2 diabetes by lifestyle intervention: follow-up of the Finnish Diabetes Prevention Study , 2006, The Lancet.

[68]  B. Sherman,et al.  Hyperprolactinemia in polycystic ovary syndrome. , 1984, Fertility and sterility.

[69]  E. Feskens,et al.  Glucose tolerance and mortality: comparison of WHO and American Diabetic Association diagnostic criteria , 1999, The Lancet.

[70]  C. Berne,et al.  High prevalence of polycystic ovaries and associated clinical, endocrine, and metabolic features in women with previous gestational diabetes mellitus. , 1998, The Journal of clinical endocrinology and metabolism.

[71]  R. Legro,et al.  Difference in body weight between American and Italian women with polycystic ovary syndrome: influence of the diet. , 2003, Human reproduction.

[72]  F. Manguso,et al.  Prospective parallel randomized, double-blind, double-dummy controlled clinical trial comparing clomiphene citrate and metformin as the first-line treatment for ovulation induction in nonobese anovulatory women with polycystic ovary syndrome. , 2005, The Journal of clinical endocrinology and metabolism.

[73]  J. Habbema,et al.  Quantitative transvaginal two‐ and three‐dimensional sonography of the ovaries: reproducibility of antral follicle counts , 2002, Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology.

[74]  S. Daskalopoulou,et al.  Prevention and Treatment of the Metabolic Syndrome , 2004, Angiology.

[75]  D. Driscoll,et al.  Evidence for a genetic basis for hyperandrogenemia in polycystic ovary syndrome. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[76]  V. Fonseca,et al.  Efficacy, tolerability, and safety of a novel once-daily extended-release metformin in patients with type 2 diabetes. , 2006, Diabetes care.

[77]  C. Duman,et al.  Endothelial dysfunction in young women with polycystic ovary syndrome: relationship with insulin resistance and low-grade chronic inflammation. , 2004, The Journal of clinical endocrinology and metabolism.

[78]  T. Bridger,et al.  Randomized placebo-controlled trial of metformin for adolescents with polycystic ovary syndrome. , 2006, Archives of pediatrics & adolescent medicine.

[79]  W. Atiomo,et al.  The plasminogen activator system in women with polycystic ovary syndrome. , 1998, Fertility and sterility.

[80]  A. Oberg,et al.  Prevalence and predictors of coronary artery calcification in women with polycystic ovary syndrome. , 2003, The Journal of clinical endocrinology and metabolism.

[81]  J. Habbema,et al.  Predictors of chances to conceive in ovulatory patients during clomiphene citrate induction of ovulation in normogonadotropic oligoamenorrheic infertility. , 1999, The Journal of clinical endocrinology and metabolism.

[82]  Maternal Morbid Obesity and the Risk of Adverse Pregnancy Outcome , 2004 .

[83]  T. Lloyd,et al.  Oral Contraceptive Use by Teenage Women Does Not Affect Body Composition , 2002, Obstetrics and gynecology.

[84]  L. Heinemann,et al.  Safety of a New Oral Contraceptive Containing Drospirenone , 2004, Drug safety.

[85]  D. Ehrmann,et al.  Effects of race and family history of type 2 diabetes on metabolic status of women with polycystic ovary syndrome. , 2005, The Journal of clinical endocrinology and metabolism.

[86]  S. Fowler,et al.  Prevention of type 2 diabetes with troglitazone in the Diabetes Prevention Program. , 2005, Diabetes.

[87]  D. Guzick.  Cardiovascular risk in PCOS. , 2004, The Journal of clinical endocrinology and metabolism.

[88]  R. Azziz.  Diagnosis of Polycystic Ovarian Syndrome: The Rotterdam Criteria Are Premature , 2006 .

[89]  E. Gracely,et al.  A low-carbohydrate as compared with a low-fat diet in severe obesity. , 2003, The New England journal of medicine.

[90]  K. Fujioka,et al.  Efficacy, dose–response relationship and safety of once‐daily extended‐release metformin (Glucophage® XR) in type 2 diabetic patients with inadequate glycaemic control despite prior treatment with diet and exercise: results from two double‐blind, placebo‐controlled studies , 2005, Diabetes, obesity & metabolism.

[91]  S. Vesely,et al.  Ferriman Gallwey self-scoring I: performance assessment in women with polycystic ovary syndrome. , 2005, The Journal of clinical endocrinology and metabolism.

[92]  L. Kuller,et al.  Evidence for Association Between Polycystic Ovary Syndrome and Premature Carotid Atherosclerosis in Middle-Aged Women , 2000, Arteriosclerosis, thrombosis, and vascular biology.

[93]  D. Jakubowicz,et al.  Decreases in ovarian cytochrome P450c17 alpha activity and serum free testosterone after reduction of insulin secretion in polycystic ovary syndrome. , 1996, The New England journal of medicine.

[94]  W. Wiser,et al.  Dynamics of suppression and recovery of plasma FSH, LH, androstenedione and testosterone in polycystic ovarian disease using an oral contraceptive. , 1974, The Journal of clinical endocrinology and metabolism.

[95]  D. Rader,et al.  A randomized trial of a low-carbohydrate diet for obesity. , 2003, The New England journal of medicine.

[96]  W. Dodson,et al.  Prevalence and predictors of risk for type 2 diabetes mellitus and impaired glucose tolerance in polycystic ovary syndrome: a prospective, controlled study in 254 affected women. , 1999, The Journal of clinical endocrinology and metabolism.

[97]  R. J. Chang,et al.  Hirsutism and acne in polycystic ovary syndrome. , 2004, Best practice & research. Clinical obstetrics & gynaecology.

[98]  J. Adams,et al.  Influence of serum luteinising hormone concentrations on ovulation, conception, and early pregnancy loss in polycystic ovary syndrome. , 1988, BMJ.

[99]  J. Clore,et al.  A direct effect of hyperinsulinemia on serum sex hormone-binding globulin levels in obese women with the polycystic ovary syndrome. , 1991, The Journal of clinical endocrinology and metabolism.

[100]  S. Elsenbruch,et al.  Quality of life, psychosocial well-being, and sexual satisfaction in women with polycystic ovary syndrome. , 2003, The Journal of clinical endocrinology and metabolism.

[101]  G. Reaven.  Role of Insulin Resistance in Human Disease , 1988, Diabetes.

[102]  S. Deitcher,et al.  Risk of venous thromboembolic disease associated with hormonal contraceptives and hormone replacement therapy: a clinical review. , 2004, Archives of internal medicine.

[103]  J. Nestler.  Obesity, insulin, sex steroids and ovulation , 2000, International Journal of Obesity.

[104]  I. Stein,et al.  Amenorrhea associated with bilateral polycystic ovaries , 1935 .

[105]  F. Naftolin,et al.  Characterization of the inappropriate gonadotropin secretion in polycystic ovary syndrome. , 1976 .

[106]  M. McCarthy,et al.  Metabolic Cardiovascular Disease Risk Factors in Women with Self-Reported Symptoms of Oligomenorrhea and/or Hirsutism: Northern Finland Birth Cohort 1966 Study , 2004 .

[107]  E. Myers,et al.  Surrogate end-points or primary outcomes in clinical trials in women with polycystic ovary syndrome? , 2004, Human reproduction.

[108]  R. Casper,et al.  Aromatase Inhibitors for Ovulation Induction , 2006 .

[109]  I. Fraser.  Vaginal bleeding patterns in women using once-a-month injectable contraceptives. , 1994, Contraception.

[110]  M. Noakes,et al.  Dietary composition in restoring reproductive and metabolic physiology in overweight women with polycystic ovary syndrome. , 2003, The Journal of clinical endocrinology and metabolism.

[111]  B. Kahn,et al.  Insulin resistance in the skeletal muscle of women with PCOS involves intrinsic and acquired defects in insulin signaling. , 2005, American journal of physiology. Endocrinology and metabolism.

[112]  Christina Wang,et al.  Measurement of total serum testosterone in adult men: comparison of current laboratory methods versus liquid chromatography-tandem mass spectrometry. , 2004, The Journal of clinical endocrinology and metabolism.