Kathleen M. Hoeger

Diagnosis and Treatment of Polycystic Ovary Syndrome: An Endocrine Society Clinical Practice Guideline

Objective: The aim was to formulate practice guidelines for the diagnosis and treatment of polycystic ovary syndrome (PCOS). Participants: An Endocrine Society-appointed Task Force of experts, a methodologist, and a medical writer developed the guideline. Evidence: This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. Consensus Process: One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of The Endocrine Society and the European Society of Endocrinology reviewed and commented on preliminary drafts of these guidelines. Two systematic reviews were conducted to summarize supporting evidence. Conclusions: We suggest using the Rotterdam criteria for diagnosing PCOS (presence of two of the following criteria: androgen excess, ovulatory dysfunction, or polycystic ovaries). Establishing a diagnosis of PCOS is problematic in adolescents and menopausal women. Hyperandrogenism is central to the presentation in adolescents, whereas there is no consistent phenotype in postmenopausal women. Evaluation of women with PCOS should exclude alternate androgen-excess disorders and risk factors for endometrial cancer, mood disorders, obstructive sleep apnea, diabetes, and cardiovascular disease. Hormonal contraceptives are the first-line management for menstrual abnormalities and hirsutism/acne in PCOS. Clomiphene is currently the first-line therapy for infertility; metformin is beneficial for metabolic/glycemic abnormalities and for improving menstrual irregularities, but it has limited or no benefit in treating hirsutism, acne, or infertility. Hormonal contraceptives and metformin are the treatment options in adolescents with PCOS. The role of weight loss in improving PCOS status per se is uncertain, but lifestyle intervention is beneficial in overweight/obese patients for other health benefits. Thiazolidinediones have an unfavorable risk-benefit ratio overall, and statins require further study.

Consensus on infertility treatment related to polycystic ovary syndrome

The treatment of infertile women with polycystic ovary syndrome (PCOS) is surrounded by many controversies. This paper describes, on the basis of the currently available evidence, the consensus reached by a group of experts regarding the therapeutic challenges raised in these women. Before any intervention is initiated, preconceptional counselling should be provided emphasizing the importance of life style, especially weight reduction and exercise in overweight women, smoking and alcohol consumption. The recommended first-line treatment for ovulation induction remains the anti-estrogen clomiphene citrate (CC). Recommended second-line intervention, should CC fail to result in pregnancy, is either exogenous gonadotrophins or laparoscopic ovarian surgery (LOS). The use of exogenous gonadotrophins is associated with increased chances for multiple pregnancy and, therefore, intense monitoring of ovarian response is required. LOS alone is usually effective in <50% of women and additional ovulation induction medication is required under those circumstances. Overall, ovulation induction (representing the CC, gonadotrophin paradigm) is reported to be highly effective with a cumulative singleton live birth rate of 72%. Recommended third-line treatment is in vitro fertilization. More patient-tailored approaches should be developed for ovulation induction based on initial screening characteristics of women with PCOS. Such approaches may result in deviation from the above mentioned first-, second- or third-line ovulation strategies in well-defined subsets of patients. Metformin use in PCOS should be restricted to women with glucose intolerance. Based on recent data available in the literature, the routine use of this drug in ovulation induction is not recommended. Insufficient evidence is currently available to recommend the clinical use of aromatase inhibitors for routine ovulation induction. Even singleton pregnancies in PCOS are associated with increased health risk for both the mother and the fetus.

Treatment of obesity in polycystic ovary syndrome: a position statement of the Androgen Excess and Polycystic Ovary Syndrome Society

OBJECTIVEnTo summarize current evidence on lifestyle management (dietary, exercise, or behavioral interventions) of obesity in women with polycystic ovary syndrome (PCOS), to indicate gaps in knowledge, and to review the medical and surgical alternatives for weight management.nnnDESIGNnExpert panel appointed by the Androgen Excess and PCOS Society (AEPCOS Society) to review the literature and draft the initial report after a consensus process via electronic communication. The initial report was reviewed and critiqued by all expert panel members and the AEPCOS Society Board of Directors and modified based on their comments.nnnCONCLUSION(S)nLifestyle management should be used as the primary therapy in overweight and obese women with PCOS for the treatment of metabolic complications. For reproductive abnormalities, lifestyle modification may improve ovulatory function and pregnancy. Data are preliminary for improvement in pregnancy and live-birth rates, and further research is needed. There is currently no evidence that modifying dietary macronutrient composition offers additional benefits over conventional dietary approaches for weight loss, and further research is needed. Emerging evidence suggests that exercise offers additional benefits to dietary energy restriction for reproductive features of PCOS.

The Impact of Metformin, Oral Contraceptives, and Lifestyle Modification on Polycystic Ovary Syndrome in Obese Adolescent Women in Two Randomized, Placebo-Controlled Clinical Trials

CONTEXTnPolycystic ovary syndrome (PCOS) presents in adolescence, and obesity is a common finding. The benefits and risks of alternate approaches to the management of PCOS in obese adolescent women are not clear.nnnOBJECTIVEnWe investigated the effects of metformin, oral contraceptives (OCs), and/or lifestyle modification in obese adolescent women with PCOS.nnnDESIGNnTwo small, randomized, placebo-controlled clinical trials were performed.nnnPATIENTS AND PARTICIPANTSnA total of 79 obese adolescent women with PCOS participated.nnnINTERVENTIONSnIn the single treatment trial, subjects were randomized to metformin, placebo, a lifestyle modification program, or OC. In the combined treatment trial, all subjects received lifestyle modification and OC and were randomized to metformin or placebo.nnnMAIN OUTCOME MEASURESnSerum concentrations of androgens and lipids were measured.nnnRESULTSnLifestyle modification alone resulted in a 59% reduction in free androgen index with a 122% increase in SHBG. OC resulted in a significant decrease in total testosterone (44%) and free androgen index (86%) but also resulted in an increase in C-reactive protein (39.7%) and cholesterol (14%). The combination of lifestyle modification, OC, and metformin resulted in a 55% decrease in total testosterone, as compared to 33% with combined treatment and placebo, a 4% reduction in waist circumference, and a significant increase in HDL (46%).nnnCONCLUSIONSnIn these preliminary trials, both lifestyle modification and OCs significantly reduce androgens and increase SHBG in obese adolescents with PCOS. Metformin, in combination with lifestyle modification and OC, reduces central adiposity, reduces total testosterone, and increases HDL, but does not enhance overall weight reduction.

Prevalence of Metabolic Syndrome and Related Characteristics in Obese Adolescents with and without Polycystic Ovary Syndrome

CONTEXTnAdults with polycystic ovary syndrome (PCOS) may be at increased risk for metabolic syndrome (MBS) and related cardiovascular disease. It is not clear whether PCOS diagnosed in adolescence increases the risk of MBS in this age group.nnnOBJECTIVEnThe aim was to compare the prevalence and related characteristics of MBS in obese adolescents with and without PCOS.nnnDESIGNnWe conducted a cross-sectional study of overweight and obese PCOS adolescents and BMI matched controls.nnnPATIENTS AND PARTICIPANTSnA total of 74 subjects, 43 with PCOS and 31 controls, participated in the study.nnnINTERVENTIONSnEach subject underwent a physical examination and laboratory evaluation for a diagnosis of MBS. Regional fat distribution was determined by computerized tomography scan in the PCOS adolescents.nnnMAIN OUTCOME MEASURESnWe measured the prevalence of MBS and its components in adolescent subjects and controls.nnnRESULTSnThe PCOS group had larger ovarian volume and higher measures of total testosterone and free androgen index than controls, but there were no differences in waist circumference, fasting glucose, blood pressure, or lipids. PCOS adolescents demonstrated more glucose abnormalities and higher plasminogen activator inhibitor-1. By pediatric criteria, 53% of the PCOS and 55% of the control adolescents had MBS. By adult criteria, 26% of PCOS and 29% of controls met diagnostic criteria for MBS.nnnCONCLUSIONSnObese adolescent women have a high prevalence of MBS, and PCOS does not add additional risk for MBS. There appears to be an association between MBS and visceral adiposity. PCOS is associated with increased incidence of glucose intolerance and increased plasminogen activator inhibitor-1. Our results reinforce the importance of obesity counseling in adolescents to recognize the possible risk of future cardiovascular disease in these young women.

PCOS Forum: research in polycystic ovary syndrome today and tomorrow.

Objectiveu2002 To summarize promising areas of investigation into polycystic ovary syndrome (PCOS) and to stimulate further research in this area.

Obesity and Weight Loss in Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) and obesity are common and complicated disorders that are influenced by genetic and environmental factors. Obesity is a prominent feature of PCOS; at least 50% of patients with PCOS are obese. Obesity appears to exert an additive, synergistic effect on the manifestations of PCOS, independently impacting insulin sensitivity, risk for diabetes, and adverse cardiovascular profile. There is evidence for the benefit of weight reduction in the management of PCOS in the obese patient. Weight loss remains a primary intervention in treatment of this disorder.

Lifestyle modification programs in polycystic ovary syndrome: systematic review and meta-analysis.

CONTEXTnPolycystic ovary syndrome (PCOS) is a prevalent disorder that affects women of childbearing age and may be related to obesity and insulin resistance.nnnOBJECTIVEnThe purpose of this systematic review was to appraise the evidence of the impact of lifestyle modification (LSM) interventions on outcomes of women with PCOS.nnnDATA SOURCESnSources included Ovid Medline, OVID Embase, OVID Cochrane Library, Web of Science, Scopus, PsycINFO, and CINAHL (up to January 2011).nnnSTUDY SELECTIONnWe included randomized controlled trials that enrolled woman of any age with PCOS who received LSM and compared them against women who received no intervention, minimal intervention, or metformin.nnnDATA EXTRACTIONnTwo authors performed the data extraction independently.nnnDATA SYNTHESISnWe included 9 trials enrolling 583 women with a high loss to follow-up rate, lack of blinding, and short follow-up. Compared with minimal intervention, LSM significantly reduced fasting blood glucose (weighted mean difference, -2.3 mg/dL; 95% confidence interval, -4.5 to -0.1, I² = 72%, P = .04) and fasting blood insulin (weighted mean difference, -2.1 μU/mL, 95% confidence interval, -3.3 to -1.0, I² = 0%, P < .001). Changes in body mass index were associated with changes in fasting blood glucose (P < .001). Metformin was not significantly better than LSM in improving blood glucose or insulin levels. We found no significant effect of LSM on pregnancy rate, and the effect on hirsutism was unclear.nnnCONCLUSIONSnThe available evidence suggests that LSM reduces fasting blood glucose and insulin levels in women with PCOS. Metformin has similar effects. Translation of these short-term effects to patient-important outcomes, beyond diabetes prevention, remains uncertain.

Serum anti-mullerian hormone concentrations are elevated in oligomenorrheic girls without evidence of hyperandrogenism.

CONTEXTnSerum anti-Müllerian hormone (AMH) levels are significantly elevated in adolescents with polycystic ovary syndrome (PCOS) compared to normal controls. Whether adolescents with oligomenorrhea have elevated AMH levels is unknown.nnnOBJECTIVEnThis study was performed to assess serum AMH levels in oligomenorrheic (OLIGO) girls without evidence of hyperandrogenism.nnnDESIGNnThis was a prospective study comparing AMH levels in OLIGO, PCOS, and normal control adolescents.nnnSETTINGnThe study was conducted through four tertiary academic medical centers.nnnPARTICIPANTSnThe study groups were comprised of OLIGO (n = 24), PCOS (n = 153), and normal adolescent girls (n = 39), as well as PCOS (n = 73) and normal adult women (n = 36).nnnINTERVENTIONSnIn each subject, serum AMH levels were assessed in the early to midfollicular phases for regularly menstruating subjects and on an arbitrary day for OLIGO or PCOS subjects.nnnMAIN OUTCOME MEASURE(S)nBasal serum AMH levels were assessed among OLIGO, PCOS, and normal girls, in addition to PCOS and normal women.nnnRESULTSnOLIGO girls had serum AMH levels (5.33 +/- 0.47 ng/ml) that were significantly greater than the normal adolescents (3.05 +/- 0.31 ng/ml) and adults (2.33 +/- 0.22 ng/ml), but similar to values seen in the PCOS adolescents (5.28 +/- 0.26 ng/ml) and adults (6.36 +/- 0.47 ng/ml). Obese adolescents and PCOS women had significantly lower AMH levels compared to lean controls (P < 0.02).nnnCONCLUSIONnIn OLIGO adolescents, elevated serum AMH levels suggest increased antral follicle number similar to that observed in girls with PCOS.

Improvement in quality-of-life questionnaire measures in obese adolescent females with polycystic ovary syndrome treated with lifestyle changes and oral contraceptives, with or without metformin.

We studied the effect of metformin or placebo in a lifestyle modification program combined with oral contraceptives (OC) on quality-of-life parameters measured by the polycystic ovary syndrome (PCOS) questionnaire in obese adolescent women with validated PCOS. The quality-of-life indicators were measured at baseline and conclusion for five domains on the PCOS questionnaire, with equal improvement in scores in both placebo and metformin groups, suggesting that the addition of metformin does not add improvement to quality-of-life measures above those observed with lifestyle modification and OC treatment.