Young obese women with polycystic ovary syndrome have evidence of early coronary atherosclerosis.

CONTEXT: Polycystic ovary syndrome (PCOS) is associated with comorbidities that may contribute to increased risk of cardiovascular disease. PCOS is associated with increased risk of metabolic syndrome, dyslipidemia, and diabetes, but it remains unclear whether traditional cardiovascular (CV) risk factors can help predict coronary artery disease in this population. OBJECTIVE: The objectives of the study were to detect early-onset subclinical coronary atherosclerosis (using coronary artery calcium as a marker) in young women with PCOS, compared with age- and body mass index-matched controls, and to compare traditional CV risk factors and inflammatory markers in the two groups. DESIGN: This was a prospective case-control study. SETTING: The study was conducted at a university hospital. SUBJECTS: Twenty-four obese (body mass index >or= 30 kg/m2) PCOS subjects and 24 obese controls participated. OUTCOME MEASURES: Coronary artery calcium, inflammatory markers (high-sensitivity C-reactive protein, IL-6, TNFalpha, adiponectin, leptin), fasting blood tests (glucose, lipids, insulin), and dual-energy x-ray absorptiometry scan for body fat distribution were measured. RESULTS: Coronary artery calcium was detected in eight of 24 PCOS subjects (33%) and two of 24 controls (8%) (odds ratio 5.5, 95% confidence interval 1.03, 29.45, P < 0.03). Traditional CV risk factors did not differ significantly between the two groups, nor did markers of inflammation or adiposity, body fat distribution, or metabolic parameters with the exception of significantly lower quantitative insulin sensitivity check index (marker for insulin resistance) in the PCOS group (P < 0.05). CONCLUSIONS: Young, obese women with PCOS have a high prevalence of early asymptomatic coronary atherosclerosis, compared with obese controls. This increased risk is independent of traditional CV risk factors and novel markers of inflammation. These findings underscore the need to screen and aggressively counsel and treat these women to prevent symptomatic CV disease.

Increased risk of depressive disorders in women with polycystic ovary syndrome.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is associated with several metabolic complications. A few small studies have also suggested an increased risk of depression in women with PCOS. The goals of this study were to estimate the prevalence of depressive disorders in women with PCOS compared with controls and to evaluate the correlation between depression, hyperandrogenism, and other metabolic markers. DESIGN: Cohort study. SETTING: University Hospital. PATIENT(S): Women with PCOS (Rotterdam criteria; n = 103). Women without PCOS seen during the same time period for an annual exam were used as control subjects (n = 103). INTERVENTION(S): Primary Care Evaluation of Mental Disorders Patient Health Questionnaire (PRIME-MD PHQ) and the Beck Depression Inventory. MAIN OUTCOME MEASURE(S): Depressive disorders. RESULT(S): Women with PCOS were at an increased risk for depressive disorders (new cases) compared with controls (21% vs. 3%; odds ratio 5.11 [95% confidence interval (CI) 1.26-20.69]; P<.03). The overall risk of depressive disorders in women with PCOS was 4.23 (95% CI 1.49-11.98; P<.01) independent of obesity and infertility. Compared with the nondepressed PCOS subjects, the depressed PCOS subjects had a higher body mass index (BMI) and evidence of insulin resistance (P<.02). CONCLUSION(S): We report a significantly increased risk of depressive disorders (as defined by the Diagnostic and Statistical Manual IV) in women with PCOS and recommend routine screening in this population.

Obesity and insulin resistance but not hyperandrogenism mediates vascular dysfunction in women with polycystic ovary syndrome.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is associated with biochemical evidence of early atherosclerosis; however, data regarding vascular function are controversial. We hypothesized that resistance vessel function (mediated by the endothelium or smooth muscle) would be impaired in women with PCOS and aimed to determine the contribution of hyperandrogenism, obesity, or insulin resistance to vascular dysfunction. DESIGN: Prospective study. SETTING: University practice. PATIENT(S): Women with PCOS (n = 24) and age/weight-matched controls (n = 22). INTERVENTION(S): Vascular function was assessed by measuring forearm vasodilatation in response to both endothelium-dependent (acetylcholine/bradykinin) and endothelium-independent dilators (nitroprusside/verapamil). MAIN OUTCOME MEASURE(S): Resistance vessel function. RESULT(S): Forearm vasodilatation to all four drugs was reduced (>50%) in obese PCOS compared to lean PCOS subjects. There was no significant difference in vascular function between obese or lean women with PCOS compared to corresponding controls. Androgen levels did not correlate with vascular function. Stepwise regression analysis showed that body mass index (BMI) contributed maximally to vascular dysfunction (R(2) = 0.47). CONCLUSION(S): This comprehensive study demonstrates for the first time that obese women with PCOS have markedly reduced vascular smooth muscle function compared to lean subjects with PCOS. In our study obesity and insulin resistance, but not hyperandrogenism, appeared to be significant modulators of vascular function.

A prospective randomized trial comparing anastrozole and clomiphene citrate in an ovulation induction protocol using gonadotropins.

OBJECTIVE: To compare the ovarian and endometrial effects of anastrozole and clomiphene when used with gonadotropins in a combination protocol. DESIGN: Prospective randomized trial. SETTING: Academic infertility center. PATIENT(S): Fifty infertile women. INTERVENTIONS(S): Women were randomized to receive either 1 mg anastrozole or 100 mg clomiphene citrate for 5 days (cycle days 3-7) followed by FSH injections (days 7-11) for ovulation induction. A subset participated in a crossover arm of the study. MAIN OUTCOME MEASURE(S): Ovarian follicle number and size, E(2) levels, endometrial thickness, pregnancy, and cancellation rates. RESULT(S): On cycle day 12, anastrozole cycles were associated with fewer total follicles (1.4 vs. 3.6, P=0.01), fewer mature follicles (0.6 vs. 1.6, P<.01), lower serum E(2) (131 pg/mL vs. 613 pg/mL, P<.01,) and the same endometrial stripe thickness compared with clomiphene citrate cycles. Cycle cancellation rates were similar between the two groups. On the day of hCG administration in noncancelled cycles, anastrozole cycles were associated with fewer total follicles (1.6 vs. 3.8, P<.01), fewer mature follicles (1.3 vs. 2.1, P<.01), and an equal endometrial stripe thickness compared with clomiphene citrate cycles. Pregnancy rates were similar between clomiphene (20%) and anastrozole (12%) cycles. CONCLUSION(S): Anastrozole when used in conjunction with gonadotropins results in lower E(2) levels and fewer follicles than clomiphene citrate. A combination protocol of anastrozole and gonadotropins may be a safer protocol for patients at higher risk of hyperstimulation and multiple births after infertility treatments.

Decision making regarding multifetal reduction.

OBJECTIVE: To identify salient variables that influence decision making regarding multifetal reduction (MFR) and describe their effect on individuals over time. DESIGN: Prospective, exploratory, descriptive design, using qualitative and quantitative methods. SETTING: Midwestern tertiary care center. PARTICIPANTS: A convenience sample of 11 consecutive consenting couples with triplet or higher-order pregnancies who elected to undergo MFR. METHODS: Semistructured audiotaped telephone interviews at three points: (a) 2 weeks postreduction, (b) 6 weeks postpartum, and (c) 6 months postpartum; a demographic and marital adjustment questionnaire. MAIN OUTCOME MEASURES: Themes identified by content analysis and compared via matrix analysis between males and females and at three points in time; trends in marital adjustment. RESULTS: Dominant variables influencing MFR decision making were risks associated with higher-order pregnancies and preservation of infants' and mothers' health. Most participants identified emotional issues, including moral and ethical dilemmas, as the most difficult aspect of reduction. Over time, participants reported feeling more positive about their decision; nonetheless, negative feelings emerged progressively. CONCLUSIONS: Risk aversion favored MFR decision making. Yet, both making and living with the decision were emotionally difficult for this sample. Interventions are needed to assist couples with this decision and its consequences.