David S. Guzick

Evidence for Association Between Polycystic Ovary Syndrome and Premature Carotid Atherosclerosis in Middle-Aged Women

Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder characterized by obesity, hyperandrogenism, and insulin resistance. An adverse lipid profile has also been observed in PCOS-affected women, suggesting that these individuals may be at increased risk for coronary heart disease at a young age. The objective of the present study was to evaluate subclinical atherosclerosis among women with PCOS and age-matched control subjects. A total of 125 white PCOS cases and 142 controls, aged ≥30 years were recruited. Collection of baseline sociodemographic data, reproductive hormone levels, and cardiovascular risk factors was conducted from 1992 to 1994. During follow-up (1996 to 1999), these women underwent B-mode ultrasonography of the carotid arteries for the evaluation of carotid intima-media wall thickness (IMT) and the prevalence of plaque. A significant difference was observed in the distribution of carotid plaque among PCOS cases compared with controls: 7.2% (9 of 125) of PCOS cases had a plaque index of ≥3 compared with 0.7% (1 of 142) of similarly aged controls (P =0.05). Overall and in the group aged 30 to 44 years, no difference was noted in mean carotid IMT between PCOS cases and controls. Among women aged ≥45 years, PCOS cases had significantly greater mean IMT than did control women (0.78±0.03 versus 0.70±0.01 mm, P =0.005). This difference remained significant after adjustment for age and BMI (P <0.05). These results suggest that (1) lifelong exposure to an adverse cardiovascular risk profile in women with PCOS may lead to premature atherosclerosis, and (2) the PCOS-IMT association is explained in part by weight and fat distribution and associated risk factors. There may be an independent effect of PCOS unexplained by the above variables that is related to the hormonal dysregulation of this condition.

Adverse Lipid and Coronary Heart Disease Risk Profiles in Young Women with Polycystic Ovary Syndrome: Results of a Case-Control Study

Polycystic ovary syndrome (PCOS), a disorder of hyperandrogenism and chronic anovulation affects 5%-10% of all women. Women with PCOS often have elevated cardiovascular risk factors. A total of 244 PCOS cases were identified through the Division of Reproductive Endocrinology at Magee-Womens Hospital and were age-matched to 244 neighborhood controls. The average age of cases and controls was 35.3 +/- 7.4 and 36.7 +/- 7.7. Women with PCOS compared to controls had substantially higher LDL-C and total cholesterol levels at each age group under 45 years after adjustment for body mass index, hormone use, and insulin levels. In the over 40-year age group, little difference was noted between cases and controls. Among cases and controls (<40), PCOS predicted LDL-C, total cholesterol and triglycerides, but did not have a significant effect on lipid levels in older cases and controls after controlling for the other variables. The primarily pre- to perimenopausal PCOS cases > or =40 years of age have similar LDL-C and total cholesterol levels as their age-matched controls, probably reflecting the LDL-C increase with age among controls.

Efficacy of treatment for unexplained infertility

OBJECTIVE To analyze the efficacy and cost-effectiveness of alternative treatments for unexplained infertility. DESIGN Retrospective analysis of 45 published reports. SETTING Clinical practices. PATIENT(S) Couples who met criteria for unexplained infertility. Women with Stage I or Stage II endometriosis were included. INTERVENTION(S) Observation; clomiphene citrate (CC); gonadotropins (hMG); IUI; and GIFT and IVF. MAIN OUTCOME MEASURE(S) Clinical pregnancy rate. RESULT(S) Combined pregnancy rates per initiated cycle, adjusted for study quality, were as follows: no treatment = 1.3%-4.1%; IUI = 3.8%; CC = 5.6%; CC + IUI = 8.3%; hMG = 7.7%; hMG + IUI = 17.1%; IVF = 20.7%; GIFT = 27.0%. The estimated cost per pregnancy was

Carotid atherosclerosis in women with polycystic ovary syndrome: Initial results from a case-control study☆☆☆★★★

10,000 for CC + IUI,

A prospective comparison of selective and universal electronic fetal monitoring in 34,995 pregnancies

17,000 for hMG + IUI, and

Low-dose mifepristone for uterine leiomyomata.

50,000 for IVF. CONCLUSION(S) Clomiphene citrate + IUI is a cost-effective treatment for unexplained infertility. If this treatment fails, hMG + IUI and assisted reproduction are efficacious therapeutic options.

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

OBJECTIVE Our purpose was to determine whether women with polycystic ovary syndrome have greater subclinical atherosclerosis as measured by carotid artery ultrasonography. STUDY DESIGN Sixteen premenopausal women > or = 40 years old with a history of clinical polycystic ovary syndrome and a current total testosterone concentration > or = 2.0 nmol/L and 16 age-matched (+/- 5 years) cycling women underwent carotid scanning. Intima-media thickness and plaque were compared between cases and controls, as were risk factors for atherosclerosis including body mass index and fasting insulin and lipid levels. Statistical analysis included t tests, Fishers exact test, and multiple linear regression. RESULTS Mean +/- SE intima-media thickness was found to be significantly greater for cases with polycystic ovary syndrome (0.680 +/- 0.019 mm) than for controls (0.630 +/- 0.012 mm) (t = 2.31, p = 0.035). Five cases (31.3%) and two controls (12.5%) had ultrasonographic evidence of plaque (not significant). Univariate regressions of intima-media thickness yielded significant coefficients for insulin, total cholesterol, low-density lipoprotein cholesterol and body mass index. When either total cholesterol or low-density lipoprotein were included in the model simultaneously with polycystic ovary syndrome, each retained significance. This was not true for insulin and body mass index, however, suggesting that these factors covaried with polycystic ovary syndrome in a dimension affecting intima-media thickness. CONCLUSIONS In spite of a major limitation of small sample size, these data suggest that women with polycystic ovary syndrome have an increased risk of subclinical atherosclerosis in their 40s.

Effect of mifepristone for symptomatic leiomyomata on quality of life and uterine size: a randomized controlled trial.

Abstract We investigated the effects of using intrapartum electronic fetal monitoring in all pregnancies, as compared with using it only in cases in which the fetus is judged to be at high risk. Pr...

Gabapentin, estrogen, and placebo for treating hot flushes : A randomized controlled trial

OBJECTIVE To compare the effect of 5 and 10 mg of mifepristone on uterine leiomyoma size and symptoms, and to measure side effects. METHODS Forty premenopausal women with large, symptomatic leiomyomata were randomized to receive either 5 or 10 mg of mifepristone daily for 6 months in an open-label study. Uterine volume was measured at bimonthly intervals by sonography. Serum concentrations of hemoglobin levels, follicle-stimulating hormone, and liver enzymes were obtained, and endometrial samples, symptoms, and menstrual bleeding were also assessed. RESULTS Nineteen of 20 subjects taking 5 mg and all 20 subjects taking 10 mg completed all 6 months of the study. Mean uterine volume shrank by 48% (P < .001) in the 5-mg group and 49% (P < .001) in the 10-mg group, a nonsignificant difference. Leiomyoma-related symptoms were comparably reduced in both groups. Amenorrhea occurred in 60–65% of both groups. Hemoglobin levels increased by 2.5 g/dL in anemic subjects. The incidence of hot flashes increased significantly over baseline in the 10-mg group but not in the 5-mg group. Simple endometrial hyperplasia occurred in 28% of all subjects, with no difference between groups. No atypical hyperplasia was noted. CONCLUSION Mifepristone in doses of 5 mg or 10 mg results in comparable leiomyoma regression, improvement in symptoms, and few side effects. Further study is needed to assess the long-term safety and efficacy of low-dose mifepristone.

Serum testosterone levels decrease in middle age in women with the polycystic ovary syndrome

CONTEXT Polycystic 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. OBJECTIVE We investigated the effects of metformin, oral contraceptives (OCs), and/or lifestyle modification in obese adolescent women with PCOS. DESIGN Two small, randomized, placebo-controlled clinical trials were performed. PATIENTS AND PARTICIPANTS A total of 79 obese adolescent women with PCOS participated. INTERVENTIONS In 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. MAIN OUTCOME MEASURES Serum concentrations of androgens and lipids were measured. RESULTS Lifestyle 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%). CONCLUSIONS In 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.