Lifestyle modifications alone or combined with hormonal contraceptives improve sexual dysfunction in women with polycystic ovary syndrome.

OBJECTIVE: To describe the prevalence of female sexual dysfunction in a well-defined polycystic ovary syndrome (PCOS) population, and to assess the impact of common PCOS treatments on sexual function. DESIGN: Secondary analysis of a randomized controlled trial, oral contraceptive pills and weight loss in PCOS. SETTING: Two academic medical centers. PATIENTS: Women with PCOS (N = 114) defined by the Rotterdam criteria. INTERVENTIONS: Continuous oral contraceptive pill (OCP) or intensive lifestyle modification (Lifestyle) or the combination (Combined) for 16 weeks. MAIN OUTCOME MEASURES: Change in Female Sexual Function Index (FSFI) and Female Sexual Distress Scale-Revised (FSDS-R) scores after 16 weeks. RESULTS: There was no change in total FSFI or FSDS-R score in any treatment group; however, an increase in the FSFI desire domain subscore was observed in the Lifestyle and Combined treatments, indicating improved sexual desire over the 16-week period. Overall, 33 participants (28.9%) met criteria for sexual dysfunction by FSFI criteria (baseline score ≤26.55). Among this group, FSFI score improved after 16 weeks of Lifestyle and Combined treatments. There was no change in prevalence of sexual dysfunction in treatment groups at 16 weeks. Use of OCPs did not alter FSFI scores. CONCLUSION(S): Female sexual dysfunction is highly prevalent among women with PCOS. Our findings suggest that common treatments for PCOS, including intensive lifestyle modification and the combination of intensive lifestyle modification and OCPs, have the potential to improve sexual function in these women; the mechanism for these improvements is likely multifactorial. CLINICAL TRIAL REGISTRATION NUMBER: NCT00704912.

Effects of Oral Contraception and Lifestyle Modification on Incretins and TGF-ß Superfamily Hormones in PCOS.

OBJECTIVE: To examine the effects of common treatments for polycystic ovary syndrome (PCOS) on a panel of hormones (reproductive/metabolic). DESIGN: Secondary analysis of blood from a randomized controlled trial of three 16-week preconception interventions designed to improve PCOS-related abnormalities: continuous oral contraceptive pills (OCPs, N = 34 subjects), intensive lifestyle modification (Lifestyle, N = 31), or a combination of both (Combined, N = 29). MATERIALS AND METHODS: Post-treatment levels of activin A and B, inhibin B, and follistatin (FST), as well as Insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein 2 (IGFBP-2), glucagon, glucagon-like peptide 1 (GLP-1) and 2, and oxyntomodulin were compared to baseline, and the change from baseline in these parameters were correlated with outcomes. RESULTS: Oral contraceptive pill use was associated with a significant suppression in activin A, inhibin A, and anti-mullerian hormone (AMH), but a significant increase in FST. IGF-1, IGFBP-2, glucagon, and GLP-2 levels were significantly decreased. Oxyntomodulin was profoundly suppressed by OCPs (ratio of geometric means: 0.09, 95% confidence interval [CI]: 0.05, 0.18, P < 0.001). None of the analytes were significantly affected by Lifestyle, whereas the effects of Combined were similar to OCPs alone, although attenuated. Oxyntomodulin was significantly positively associated with the change in total ovarian volume (rs = 0.27; 95% CI: 0.03, 0.48; P = 0.03) and insulin sensitivity index (rs = 0.48; 95% CI: 0.27, 0.64; P < 0.001), and it was inversely correlated with change in area under the curve (AUC) glucose [rs = -0.38; 95% CI: -0.57, -0.16; P = 0.001]. None of the hormonal changes were associated with live birth, only Activin A was associated with ovulation (risk ratio per 1 ng/mL increase in change in Activin A: 6.0 [2.2, 16.2]; P < 0.001). CONCLUSIONS: In women with PCOS, OCPs (and not Lifestyle) affect a wide variety of reproductive/metabolic hormones, but their treatment response does not correlate with live birth.

Impact of hormonal contraception and weight loss on high-density lipoprotein cholesterol efflux and lipoprotein particles in women with polycystic ovary syndrome.

OBJECTIVE: To study the effects of oral contraceptive pills (OCP), the first-line treatment for PCOS, on high-density lipoprotein cholesterol (HDL-C) function (reverse cholesterol efflux capacity) and lipoprotein particles measured using nuclear magnetic resonance spectroscopy in obese women. DESIGN: Secondary analysis of a randomized controlled trial (OWL-PCOS) of OCP or Lifestyle (intensive Lifestyle modification) or Combined (OCP + Lifestyle) treatment groups for 16 weeks. PATIENTS: Eighty-seven overweight/obese women with PCOS at two academic centres. MEASUREMENTS: Change in HDL-C efflux capacity and lipoprotein particles. RESULTS: High-density lipoprotein cholesterol efflux capacity increased significantly at 16 weeks in the OCP group [0·11; 95% confidence interval (CI) 0·03, 0·18, P = 0·008] but not in the Lifestyle (P = 0·39) or Combined group (P = 0·18). After adjusting for HDL-C and TG levels, there was significant mean change in efflux in the Combined group (0·09; 95% CI 0·01, 0·15; P = 0·01). Change in HDL-C efflux correlated inversely with change in serum testosterone (rs = -0·21; P = 0·05). In contrast, OCP use induced an atherogenic low-density lipoprotein cholesterol (LDL-C) profile with increase in small (P = 0·006) and large LDL-particles (P = 0·002). Change in small LDL-particles correlated with change in serum testosterone (rs = -0·31, P = 0·009) and insulin sensitivity index (ISI; rs = -0·31, P = 0·02). Both Lifestyle and Combined groups did not show significant changes in the atherogenic LDL particles. CONCLUSIONS: Oral contraceptive pills use is associated with improved HDL-C function and a concomitant atherogenic LDL-C profile. Combination of a Lifestyle program with OCP use improved HDL-C function and mitigated adverse effects of OCP on lipoproteins. Our study provides evidence for use of OCP in overweight/obese women with PCOS when combined with Lifestyle changes.

Normal Pubertal Development in Daughters of Women With PCOS: A Controlled Study.

Context: Daughters of women with polycystic ovary syndrome (PCOS) are thought to be at increased risk for developing stigmata of the syndrome, but the ontogeny during puberty is uncertain. Objective: We phenotyped daughters (n = 76) of mothers with PCOS and daughters (n = 80) from control mothers for reproductive and metabolic parameters characteristic of PCOS. Design, Setting, and Participants: We performed a matched case/control study at Penn State Hershey Medical Center that included non-Hispanic, white girls 4 to 17 years old. Intervention: We obtained birth history, biometric, ovarian ultrasounds, whole-body dual-energy X-ray absorptiometry scan for body composition, 2-hour glucose challenged salivary insulin levels, and two timed urinary collections (12 hours overnight and 3 hours in the morning) for gonadotropins and sex steroids. Main Outcome Measures: We measured integrated urinary levels of adrenal (dehydroepiandrosterone sulfate) and ovarian [testosterone (TT)] steroids. Other endpoints included integrated salivary insulin levels and urinary luteinizing hormone levels. Results: There were no differences in detection rates or mean levels for gonadotropins and sex steroids in timed urinary collections between PCOS daughters and control daughters, nor were there differences in integrated salivary insulin levels. Results showed that 69% of Tanner 4/5 PCOS daughters vs 31% of control daughters had hirsutism defined as a Ferriman-Gallwey score >8 (P = 0.04). There were no differences in body composition as determined by dual-energy X-ray absorptiometry between groups in the three major body contents (i.e., bone, lean body mass, and fat) or in ovarian volume between groups. Conclusions: Matched for pubertal stage, PCOS daughters have similar levels of urinary androgens and gonadotropins as well as glucose-challenged salivary insulin levels.

Weight Loss and Lowering Androgens Predict Improvements in Health-Related Quality of Life in Women With PCOS.

CONTEXT: Polycystic ovary syndrome (PCOS) is associated with reduced health-related quality of life (HRQOL) and increased prevalence of depressive and anxiety disorders. The impact of PCOS-specific treatments on these co-morbidities is unclear. OBJECTIVE: To assess the impact of weight loss and decreasing hyperandrogenism on HRQOL and mood and anxiety disorders in women with PCOS. DESIGN/SETTING/PARTICIPANTS: A secondary analysis of a randomized controlled trial (OWL-PCOS) of preconception treatment conducted at two academic centers in women (age, 18-40 years; body mass index, 27-42 kg/m(2)) with PCOS defined by Rotterdam criteria. INTERVENTION: Continuous oral contraceptive pill (OCP) or intensive lifestyle intervention or the combination (Combined) for 16 weeks. MAIN OUTCOME MEASURE(S): Changes in HRQOL assessed by PCOSQ and SF-36 and prevalence of depression and anxiety disorder assessed by PRIME-MD PHQ. RESULTS: The lowest scores were noted on the general health domain of the SF-36 and the weight and infertility domains on the PCOSQ. All three interventions resulted in significant improvement in the general health score on the SF-36. Both the OCP and Combined groups showed improvements in all domains of the PCOSQ (P < .01) compared to baseline scores. The Combined group had significant improvements in the weight, body hair, and infertility domains compared to a single treatment group (P < .05). In a linear regression model, change in weight correlated with improvements in the weight domain (P < .001) and physical well-being (P < .02), change in T correlated with improvements in the hair domain (P < .001), and change in both weight and T correlated with the infertility (P < .001) and menstrual domains (P < .05). CONCLUSIONS: Both weight loss and OCP use result in significant improvements in several physical and mental domains related to quality of life, depressive symptoms, and anxiety disorders, and combined therapies offer further benefits in overweight/obese women with PCOS.

Benefit of Delayed Fertility Therapy With Preconception Weight Loss Over Immediate Therapy in Obese Women With PCOS.

CONTEXT: In overweight/obese women with polycystic ovary syndrome (PCOS), the relative benefit of delaying infertility treatment to lose weight vs seeking immediate treatment is unknown. OBJECTIVE: We compared the results of two, multicenter, concurrent clinical trials treating infertility in women with PCOS. DESIGN, SETTING, AND PARTICIPANTS: This was a secondary analysis of two randomized trials conducted at academic health centers studying women 18-40 years of age who were overweight/obese and infertile with PCOS. INTERVENTION: We compared immediate treatment with clomiphene from the Pregnancy in Polycystic Ovary Syndrome II (PPCOS II) trial (N = 187) to delayed treatment with clomiphene after preconception treatment with continuous oral contraceptives, lifestyle modification (Lifestyle: including caloric restriction, antiobesity medication, behavioral modification, and exercise) or the combination of both (combined) from the Treatment of Hyperandrogenism Versus Insulin Resistance in Infertile Polycystic Ovary Syndrome (OWL PCOS) trial (N = 142). MAIN OUTCOME MEASURES: Live birth, pregnancy loss, and ovulation were measured. RESULTS: In PPCOS II, after four cycles of clomiphene, the cumulative per-cycle ovulation rate was 44.7% (277/619) and the cumulative live birth rate was 10.2% (19/187), nearly identical to that after oral contraceptive pretreatment in the OWL PCOS trial (ovulation 45% [67/149] and live birth: 8.5% [4/47]). In comparison, deferred clomiphene treatment preceded by lifestyle and combined treatment in OWL PCOS offered a significantly better cumulative ovulation rate compared to immediate treatment with clomiphene. (Lifestyle: 62.0% [80/129]; risk ratio compared to PPCOS II = 1.4; 95% confidence interval [CI], 1.1-1.7; P = .003; combined: 64.3% [83/129]; risk ratio compared to PPCOS II = 1.4; 95% CI, 1.2-1.8; P < .001 and a significantly better live birth rate lifestyle: 25.0% [12/48]; risk ratio compared to PPCOS II = 2.5; 95% CI, 1.3-4.7; P = .01 and combined: 25.5% [12/47]; risk ratio compared to PPCOS II = 2.5; 95% CI, 1.3-4.8; P = .01). CONCLUSIONS: These data show the benefit of improved ovulation and live birth with delayed infertility treatment with clomiphene citrate when preceded by lifestyle modification with weight loss compared with immediate treatment. Pretreatment with oral contraceptives likely has little effect on the ovulation and live birth rate compared with immediate treatment.

Randomized Controlled Trial of Preconception Interventions in Infertile Women With Polycystic Ovary Syndrome.

CONTEXT: Lifestyle modification is recommended in women with polycystic ovary syndrome (PCOS) prior to conception but there are few randomized trials to support its implementation or benefit. OBJECTIVE: This study aimed to determine the relative efficacy of preconception intervention on reproductive and metabolic abnormalities in overweight/obese women with PCOS. DESIGN, SETTING, AND PARTICIPANTS: This was a randomized controlled trial of preconception and infertility treatment at Academic Health Centers in women with infertility due to PCOS, age 18-40 y and body mass index 27-42 kg/m(2). INTERVENTION: Women were randomly assigned to receive either 16 weeks of 1) continuous oral contraceptive pills (OCPs) (ethinyl estradiol 20 mcg/1 mg norethindrone acetate) ("OCP"); 2) lifestyle modification consisting of caloric restriction with meal replacements, weight loss medication (either sibutramine, or orlistat), and increased physical activity to promote a 7% weight loss ("Lifestyle"); or 3) combined treatment with both OCP and lifestyle modification ("Combined"). After preconception intervention, women underwent standardized ovulation induction with clomiphene citrate and timed intercourse for four cycles. Pregnancies were followed with trimester visits until delivery. MAIN OUTCOME MEASURES: Weight, ovulation, and live birth were measured. RESULTS: We consented 216 and randomly assigned 149 women (Lifestyle: n = 50; OCP: n = 49; Combined: n = 50). We achieved significant weight loss with both Lifestyle (mean weight loss, -6.2%; 95% confidence interval (CI), -7.4--5.0; and Combined (mean weight loss, -6.4%; 95% CI, -7.6--5.2) compared with baseline and OCP (both P < .001). There was a significant increase in the prevalence of metabolic syndrome at the end of preconception treatment compared with baseline within OCP (odds ratio [OR, 2.47; 95% CI, 1.42-4.27) whereas no change in metabolic syndrome was detected in the Lifestyle (OR, 1.18; 95% CI, 0.63-2.19) or Combined (OR, 0.72; 95% CI, 0.44-1.17) groups. Cumulative ovulation rates were superior after weight loss: OCP, 46%; Lifestyle, 60%; and Combined, 67% (P < .05). Live birth rates were OCP, 12%; Lifestyle, 26%; and Combined, 24% (P = .13). CONCLUSIONS: A preconception weight loss intervention eliminates the adverse metabolic oral contraceptive effects and, compared with oral contraceptive pretreatment, leads to higher ovulation rates.

Effects of gastric bypass surgery on female reproductive function.

CONTEXT: Reproductive function may improve after bariatric surgery, although the mechanisms and time-related changes are unclear. OBJECTIVE: The objective of the study was to determine whether ovulation frequency/quality as well as associated reproductive parameters improve after Roux en Y gastric bypass surgery. DESIGN: This was a prospective cohort study that enrolled female subjects from 2005 to 2008 with study visits at baseline and then 1, 3, 6, 12, and up to 24 months after surgery. SETTING: The study was conducted at an academic health center. PATIENTS: Twenty-nine obese, reproductive-aged women not using confounding medications participated in the study. MAIN OUTCOME MEASURES: The primary outcome was integrated levels of urinary progestin (pregnanediol 3-glururonide) from daily urinary collections at 12 months postoperatively. Secondary outcomes were changes in vaginal bleeding, other biometric, hormonal, ultrasound, dual-energy x-ray absorptiometry measures, and Female Sexual Function Index. RESULTS: Ninety percent of patients with morbid obesity had ovulatory cycles at baseline, and the ovulatory frequency and luteal phase quality (based on integrated pregnanediol 3-glururonide levels) were not modified by bariatric surgery. The follicular phase was shorter postoperatively [6.5 d shorter at 3 months and 7.9-8.9 d shorter at 6-24 months (P < 0.01)]. Biochemical hyperandrogenism improved, largely due to an immediate postoperative increase in serum SHBG levels (P < 0.01), with no change in clinical hyperandrogenism (sebum production, acne, hirsutism). Bone density was preserved, contrasting with a significant loss of lean muscle mass and fat (P < 0.001), reflecting preferential abdominal fat loss (P < 0.001). Female sexual function improved 28% (P = 0.02) by 12 months. CONCLUSIONS: Ovulation persists despite morbid obesity and the changes from bypass surgery. Reproductive function after surgery is characterized by a shortened follicular phase and improved female sexual function.

Brachial artery conductance during reactive hyperemia is increased in women with polycystic ovary syndrome.

OBJECTIVE: To examine changes in brachial artery conductance (BAC) during reactive hyperemia in women with polycystic ovary syndrome (PCOS) compared to controls. STUDY DESIGN: This is a pilot case-control study performed at a single academic medical center. Changes in BAC during reactive hyperemia were evaluated in 31 women with PCOS and 11 healthy control women. Fasting glucose, insulin, lipids and androgen levels were also determined. A mixed-effects model was used to compare the PCOS curve to the control curve for change in BAC from baseline during reactive hyperemia. RESULTS: Body mass index (BMI) and testosterone levels were significantly increased in the PCOS group compared to controls (P<0.05). In addition, the PCOS group had higher total and LDL cholesterol levels (P=0.05 and 0.09, respectively). Change in BAC from baseline during reactive hyperemia was significantly increased in the PCOS group compared to controls even after adjusting for age, BMI and LDL cholesterol levels (P<0.0001). There were no significant differences between the two groups in age, blood pressure, or fasting glucose or insulin levels. CONCLUSIONS: Brachial artery conductance during reactive hyperemia is significantly increased in women with PCOS compared to controls and may be a novel early indicator of increased cardiovascular risk in women with PCOS.

Comparison of hormonal and metabolic markers after a high-fat, Western meal versus a low-fat, high-fiber meal in women with polycystic ovary syndrome.

OBJECTIVE: To determine the effect of meal composition on postprandial T levels in women with polycystic ovary syndrome (PCOS). DESIGN: Randomized, crossover design. SETTING: Academic research center. PATIENT(S): Fifteen women with PCOS. INTERVENTION(S): We evaluated changes in T, sex hormone binding globulin (SHBG), DHEAS, cortisol, glucose, and insulin for 6 hours after a high-fat, Western meal (HIFAT) (62% fat, 24% carbohydrate, 1 g fiber) and an isocaloric low-fat, high-fiber meal (HIFIB) (6% fat, 81% carbohydrate, 27 g fiber). MAIN OUTCOME MEASURE(S): Change in T levels. RESULT(S): Testosterone decreased 27% within 2 hours after both meals. However, T remained below premeal values for 4 hours after the HIFIB meal and 6 hours after the HIFAT meal. Insulin was twofold higher for 2 hours after the HIFIB meal compared with the HIFAT meal. Glucose was higher for 1 hour after the HIFIB meal compared with the HIFAT meal. DHEAS decreased 8%-10% within 2-3 hours after both meals, then increased during the remainder of the study period. Cortisol decreased during the 6-hour period after both meals. CONCLUSIONS: Diet plays a role in the regulation of T levels in women with PCOS. Further studies are needed to determine the role of diet composition in the treatment of PCOS.

Hyperandrogenism and hyperinsulinism in children of women with polycystic ovary syndrome: a controlled study.

OBJECTIVE: Hyperandrogenia and insulin resistance are heritable family traits, likely to cluster in children of polycystic ovary syndrome (PCOS) mothers. DESIGN: We performed a case control study of PCOS children (n = 32) compared with children from control women (n = 38) for reproductive and metabolic abnormalities, stratifying results by three Tanner stage groupings. The children underwent history and physical examinations, a 3-h timed urine collection, a 2-h oral glucose tolerance test, and abdominal ultrasound examination (females only). Serum was obtained in older children (age > 8 yr) who consented. RESULTS: Urine LH levels were significantly lower in the Tanner IV-V PCOS girls compared with controls (P = 0.04). Urine testosterone levels were significantly elevated in Tanner II-III PCOS boys compared with controls (P = 0.007). There were no significant differences in dehydroepiandrosterone levels. We validated the correlation between salivary and serum levels of insulin (insulin areas under the curve) in an adult population [n =30, Pearson correlation coefficient (r) = 0.67; P < 0.0001], which also replicated in the children (2-h insulin r = 0.57; P = 0.0004). Mean area under the curve salivary insulin levels were significantly higher in the Tanner IV-V PCOS girls in the later stages of puberty when compared with controls (3625 +/- 1372 vs. 1766 +/- 621 min x muU/ml, 95% confidence interval 475-3242; P < 0.02). CONCLUSIONS: Hyperinsulinism may be a familial characteristic of PCOS children (or at least girls) but does not appear until the later stages of puberty. Other reproductive abnormalities that characterize PCOS may develop later.

Effects of continuous versus cyclical oral contraception: a randomized controlled trial.

CONTEXT: Continuous oral contraception may better suppress the ovary and endometrium, lending itself to the treatment of other medical conditions. OBJECTIVE: Our objective was to determine the effects of continuous vs. cyclical oral contraception. DESIGN: This was a randomized double-blind trial. SETTING: This trial was performed at an academic medical center in Pennsylvania. PATIENTS: A total of 62 healthy women with regular menses were included in the study. INTERVENTION: Cyclical oral contraception (21-d active/7-d placebo given for six consecutive 28-d cycles) vs. continuous (168-d active pill) therapy using a monophasic pill (20 microg ethinyl estradiol and 1 mg norethindrone acetate) was examined. MAIN OUTCOME MEASURES: The primary outcome was vaginal bleeding, and secondary outcomes included hormonal, pelvic ultrasound, quality of life, and safety measures. RESULTS: There was no statistically significant difference in the number of total bleeding days between groups, but moderate/heavy bleeding was significantly greater with the cyclical regimen [mean 11.0 d (sd 8.5) vs. continuous 5.2 d (sd 6.8); P = 0.005], with both groups decreasing over time. Endogenous serum and urinary estrogens measured over six cycles were significantly lower (P = 0.02 and 0.04, respectively) in the continuous group than the cyclical group. Women in the continuous group also had a smaller ovarian volume and lead follicle size over the course of the trial by serial ultrasound examinations. The Moos Menstrual Distress Questionnaire showed that women on continuous therapy had less associated menstrual pain (P = 0.01) and favorable improvements in behavior (P = 0.04) during the premenstrual period. CONCLUSIONS: Continuous oral contraception does not result in a reduction of bleeding days over a 168-d period of observation but provides greater suppression of the ovary and endometrium. These effects are associated with improved patient symptomatology.

The effects of metformin and rosiglitazone, alone and in combination, on the ovary and endometrium in polycystic ovary syndrome.

OBJECTIVE: To examine the effects of metformin and rosiglitazone, alone and in combination, on endometrial histology and ovarian steroid production. STUDY DESIGN: Randomized open-label study of metformin and rosiglitazone in 16 women with polycystic ovary syndrome (PCOS) performed at a single academic health center. The study consisted of a 6-week baseline observation period, a 3-month treatment period of single-agent therapy (rosiglitazone or metformin), and then a 3-month period of combined therapy. RESULTS: Abnormal endometrial histology was found in 3 subjects at baseline, including 1 case of adenocarcinoma of the endometrium in an asymptomatic subject, who was excluded from further study. The 2 other abnormal cases (simple hyperplasia) resolved with treatment. Three months of single-agent therapy showed a benefit of rosiglitazone (n = 9) over metformin (n = 6) in terms of reducing circulating unbound testosterone levels (-11.8; 95% CI: -21.7 to -2.0 ng/dL) and 2-hour glucose (-42.0; 95% CI: -76.2 to -7.8 mg/dL), 2-hour insulin (-150.4; 95% CI: -272.7 to -28.1 microU/mL) as well as a significant decrease in integrated levels of glucose and insulin by area under the curve analysis, all obtained from oral glucose tolerance testing. Daily urinary progestin-to-estrogen ratios improved on rosiglitazone compared to metformin therapy (0.08; 95% CI: 0.02 to 0.14). Ovulatory rates tended to improve on both single-agent and combined treatments (30/90 cycles, 33%), compared to baseline ovulatory rate (2/15, 13%). Despite 6 months of therapy alone or in combination, 5 women displayed no evidence of biochemical ovulation by urinary or serum progestin measurements. CONCLUSION: This study provides preliminary evidence that insulin-sensitizing drugs may have beneficial effects on the endometrium, although the exact mechanism beyond improving ovulatory function is still unknown. In addition, we suggest that rosiglitazone may be more beneficial than metformin therapy on raised insulin and androgen levels in an obese PCOS population. Combined therapy did not demonstrate significant benefit above and beyond single-agent therapy.

Changes in glucose tolerance over time in women with polycystic ovary syndrome: a controlled study.

We performed this study to access the changes in glucose tolerance over time in a group of women with polycystic ovary syndrome (PCOS) (n = 71) and control women (n = 23) with regular menstrual cycles and baseline normal glucose tolerance. Mean follow-up was between 2 and 3 yr for both groups (PCOS 2.5 +/- 1.7 yr; controls 2.9 +/- 2.1 yr). Based on World Health Organization glucose tolerance categories, there was no significant difference in the prevalence of glucose intolerance at follow-up in the PCOS group. In the PCOS group, 25 (37%) had impaired glucose tolerance (IGT) and seven (10%) had type 2 diabetes mellitus at baseline, compared with 30 (45%) and 10 (15%), respectively, at follow-up. There were also no differences within groups (PCOS or control) or between groups (PCOS vs. control) in the oral glucose tolerance test-derived measure of insulin sensitivity, but in the women with PCOS who converted to either IGT or type 2 diabetes mellitus, there was a significant decrease (P < 0.0001). At the follow-up visit, the mean glycohemoglobin level was 6.1 +/- 0.9% in women with PCOS vs. 5.3 +/- 0.7% in the control women (P < 0.001). Women with PCOS and baseline IGT had a low conversion risk of 6% to type 2 diabetes over approximately 3 yr, or 2% per year. The effect of PCOS, given normal glucose tolerance (NGT) at baseline, is more pronounced with 16% conversion to IGT per year. Our study supports that women with PCOS (especially with NGT) should be periodically rescreened for diabetes due to worsening glucose intolerance over time, but this interval may be over several years and not annually.

The controversy over estrogen replacement therapy: an update on clinical trials.

This is a review and presentation of recent clinical trials designed to ascertain the effects of estrogen or estrogen plus progesterone on the risks of heart disease. The framework of the epidemiologic evidence that estrogen is cardioprotective is reviewed and the impact of these data on apparent findings from clinical trials discussed. The Heart and Estrogen/Progestin Replacement Study is examined in detail, and the most frequent criticisms of its findings are presented. Findings from other clinical trials are presented and the clinical implications from the data discussed in relation to the larger body of literature pertaining to hormone replacement therapy and heart disease.