Marguerite K. Shepard

Polycystic Ovary Syndrome Is Associated With Endothelial Dysfunction

Background —We recently reported endothelial dysfunction as a novel cardiovascular risk factor associated with insulin resistance/obesity. Here, we tested whether hyperandrogenic insulin-resistant women with polycystic ovary syndrome (PCOS) who are at increased risk of macrovascular disease display impaired endothelium-dependent vasodilation and whether endothelial function in PCOS is associated with particular metabolic and/or hormonal characteristics. Methods and Results —We studied leg blood flow (LBF) responses to graded intrafemoral artery infusions of the endothelium-dependent vasodilator methacholine chloride (MCh) and to euglycemic hyperinsulinemia in 12 obese women with PCOS and in 13 healthy age- and weight-matched control subjects (OBW). LBF increments in response to MCh were 50% lower in the PCOS group than in the OBW group (P <0.01). Euglycemic hyperinsulinemia increased LBF above baseline by 30% in the PCOS and 60% in OBW group (P <0.05 between groups). Across all subjects, the maximal LBF response to MCh exhibited a strong inverse correlation with free testosterone levels (r =−0.52, P <0.007). This relationship was stronger than with any other parameter, including insulin sensitivity. Conclusions —PCOS is characterized by (1) endothelial dysfunction and (2) resistance to the vasodilating action of insulin. This endothelial dysfunction appears to be associated with both elevated androgen levels and insulin resistance. Given the central vasoprotective role of endothelium, these findings could explain, at least in part, the increased risk for macrovascular disease in women with PCOS.

Recovery of Chalamydia trachomatis from the endometrium of women at risk for chlamydial infection

Chlamydia trachomatis is the most common sexually transmitted disease in Western Society today and is a major cause of salpingitis and tubal infertility. However, the frequency with which it produces upper genital tract infection in asymptomatic women has not been determined. Endometrial, endocervical, and urethral cultures for C. trachomatis were obtained from 60 women who were at risk for chlamydial infection but who did not have evidence of endometritis or salpingitis on physical examination. Chlamydia was isolated from the lower genitourinary tract in 26 (43%) and from the endometrium in 12 (20%). Thus 12 of 29 (41%) women infected with C. trachomatis had endometrial infections. Upper genital infections appear to be common in women at risk for chlamydial infection, and spread to the upper tract may occur shortly after the infection is acquired.

Recovery of Chlamydia trachomatis from endometrial and fallopian tube biopsies in women with infertility of tubal origin

In order to examine the role of chronic active chlamydial infection in tubal infertility, cultures for Chlamydia trachomatis were performed on endometrial biopsies from 38, and fallopian tube biopsies from all, of 52 women undergoing tubal surgery for infertility. C. trachomatis was recovered from one or both sites in 8 of 52 (15%). Five of 6 women with positive fallopian tube cultures had endometrial cultures performed, and of these, 4 (80%) were positive. Three culture-positive women had been treated with tetracycline or doxycycline. Multiple blind passage in tissue culture was required for recovery of all six fallopian tube and four of the six endometrial isolates. No specific anatomic lesion was associated with documented infection. Chronic active chlamydial infection is frequently associated with tubal infertility, may persist despite therapy, and often can be detected by endometrial biopsy culture.

Müllerian agenesis: an update.

Recently, many advances have been made in the study of sexual differentiation, including the discoveries of the gene for antimüllerian hormone as well as the gene for its receptor. However, the etiology of the clinical syndrome of müllerian agenesis remains elusive. We hypothesize that activating mutations of either the antimüllerian hormone gene or its receptor gene may cause müllerian duct regression in a genetic female during embryogenesis. This clinical commentary discusses the current management of the syndrome including the Abbe-McIndoe procedure, the most commonly used method of surgical correction, and the Frank vaginal dilation method, the most common nonsurgical method of correction.

Inflammation in Response to Glucose Ingestion Is Independent of Excess Abdominal Adiposity in Normal-Weight Women with Polycystic Ovary Syndrome

CONTEXT Inflammation and excess abdominal adiposity (AA) are often present in normal-weight women with polycystic ovary syndrome (PCOS). OBJECTIVE We determined the effects of hyperglycemia on nuclear factor-κB (NFκB) activation in mononuclear cells (MNC) of normal-weight women with PCOS with and without excess AA. DESIGN This was a prospective controlled study. SETTING The study was conducted at an academic medical center. PATIENTS Fifteen normal-weight, reproductive-age women with PCOS (seven normal AA, eight excess AA) and 16 body composition-matched controls (eight normal AA, eight excess AA) participated in the study. MAIN OUTCOME MEASURES Body composition was measured by dual-energy absorptiometry. Insulin sensitivity was derived from an oral glucose tolerance test (IS(OGTT)). Activated NFκB and the protein content of p65 and inhibitory-κB were quantified from MNC, and TNFα and C-reactive protein (CRP) were measured in plasma obtained from blood drawn while fasting and 2 h after glucose ingestion. RESULTS Compared with controls, both PCOS groups exhibited lower IS(OGTT), increases in activated NFκB and p65 protein, and decreases in inhibitory-κB protein. Compared with women with PCOS with excess AA, those with normal AA exhibited higher testosterone levels and lower TNFα and CRP levels. For the combined groups, the percent change in NFκB activation was negatively correlated with IS(OGTT) and positively correlated with androgens. TNFα and CRP were positively correlated with abdominal fat. CONCLUSION In normal-weight women with PCOS, the inflammatory response to glucose ingestion is independent of excess AA. Circulating MNC and excess AA are separate and unique sources of inflammation in this population.

Hyperglycemia-induced oxidative stress is independent of excess abdominal adiposity in normal-weight women with polycystic ovary syndrome

STUDY QUESTION What is the effect of glucose ingestion on leukocytic reactive oxygen species (ROS) generation in normal-weight women with polycystic ovary syndrome (PCOS) with and without excess abdominal adiposity (AA)? SUMMARY ANSWER Normal-weight women with PCOS exhibit an increase in leukocytic ROS generation in response to glucose ingestion, and this increase is independent of excess AA. WHAT IS KNOWN ALREADY Excess adipose tissue is a source of oxidative stress. Normal-weight women with PCOS exhibit oxidative stress and can have excess AA. STUDY DESIGN AND SIZE This is a cross-sectional study involving 30 reproductive-age women. PARTICIPANTS/MATERIALS, SETTING AND METHODS Fourteen normal-weight women with PCOS (6 normal AA, 8 excess AA) and 16 body composition-matched controls (8 normal AA, 8 excess AA) underwent body composition assessment by dual-energy absorptiometry and an oral glucose tolerance test (OGTT) at a university medical center. Insulin sensitivity was derived from the OGTT (IS(OGTT)). Blood was drawn while fasting and 2 h after glucose ingestion to measure leukocytic ROS generation and p47(phox) protein content and plasma thiobarbituric acid-reactive substances (TBARS) and C-reactive protein (CRP). MAIN RESULTS AND THE ROLE OF CHANCE Compared with controls, both PCOS groups exhibited lower IS(OGTT) (43-54%) and greater percentage change (% change) in ROS generation (96-140%), p47(phox) protein (18-28%) and TBARS (17-48%). Compared with women with PCOS with excess AA, those with normal AA exhibited higher testosterone levels (29%) and lower CRP levels (70%). For the combined groups, IS(OGTT) was negatively correlated with the % change in ROS generation and p47(phox) protein. CRP was positively correlated with abdominal fat. The % change in p47(phox) protein was positively correlated with CRP and androgens. LIMITATIONS, REASONS FOR CAUTION Although this study is adequately powered to assess differences in ROS generation between the women with PCOS and control participants, the modest sample size merits caution when interpreting the corroborative results of the additional measures of oxidative stress and inflammation. WIDER IMPLICATIONS OF THE FINDINGS This study highlights the unique pro-oxidant contribution of circulating leukocytes in the development of insulin resistance and hyperandrogenism in PCOS. STUDY FUNDING/COMPETING INTEREST(S) Supported by NIH grant HD-048535 to F.G. The authors have nothing to disclose.

The altered mononuclear cell-derived cytokine response to glucose ingestion is not regulated by excess adiposity in polycystic ovary syndrome.

CONTEXT Excess adipose tissue is a source of inflammation. Polycystic ovary syndrome (PCOS) is a proinflammatory state and is often associated with excess abdominal adiposity (AA) alone and/or frank obesity. OBJECTIVE To determine the effect of glucose ingestion on cytokine release from mononuclear cells (MNC) in women with PCOS with and without excess AA and/or obesity. DESIGN A cross-sectional study. SETTING Academic medical center. PATIENTS Twenty-three women with PCOS (seven normal weight with normal AA, eight normal weight with excess AA, eight obese) and 24 ovulatory controls (eight normal weight with normal AA, eight normal weight with excess AA, eight obese). INTERVENTION Three-hour 75-g oral glucose tolerance test (OGTT). MAIN OUTCOME MEASURES Body composition was measured by dual energy x-ray absorptiometry. Insulin sensitivity was derived from the OGTT (ISOGTT). TNFα, IL-6, and IL-1β release was measured in supernatants of cultured MNC isolated from blood samples drawn while fasting and 2 hours after glucose ingestion. RESULTS Insulin sensitivity was lower in obese subjects regardless of PCOS status and in normal-weight women with PCOS compared with normal-weight controls regardless of body composition status. In response to glucose ingestion, MNC-derived TNFα, IL-6, and IL-1β release decreased in both normal-weight control groups but failed to suppress in either normal-weight PCOS group and in obese women regardless of PCOS status. For the combined groups, the cytokine responses were negatively correlated with insulin sensitivity and positively correlated with abdominal fat and androgens. CONCLUSIONS Women with PCOS fail to suppress MNC-derived cytokine release in response to glucose ingestion, and this response is independent of excess adiposity. Nevertheless, a similar response is also a feature of obesity per se. Circulating MNC and excess adipose tissue are separate and distinct sources of inflammation in this population.

The effects of baseline ovarian cysts on cycle fecundity in controlled ovarian hyperstimulation

Patients undergoing COH were prospectively studied in 174 cycles for the presence of baseline ovarian cysts. In 37.4% of all cycles, a baseline cyst > 10 mm mean diameter was found, but a cyst was more common in subsequent cycles than on the first (41.5% versus 15.8%). Cycle fecundity as determined by life table analysis was significantly higher if no baseline cyst were present (0.25 versus 0.06, P > 0.01). These findings suggest that baseline ovarian cysts may adversely affect the chances for pregnancy in COH not associated with IVF or GIFT.

The effects of spontaneous luteinizing hormone surges on superovulatory cycles

OBJECTIVE To determine the effect of a spontaneous luteinizing hormone (LH) surge on the cycle fecundity during superovulation induction. DESIGN Superovulatory cycles of patients with various diagnoses are retrospectively compared. SETTING Reproductive Endocrinology Outpatient Clinic. PATIENTS A total of 1,185 superovulatory cycles from July 1, 1982 until November 1, 1991 are compared. MAIN OUTCOME MEASURE The probability of achieving a pregnancy per treatment cycle. RESULTS Patients with unexplained infertility and hyperprolactinemia were more likely to have a spontaneous LH surge during superovulation than patients with either endometriosis or polycystic ovarian disease. However, the cycle fecundity rate did not differ whether or not an LH surge occurred, regardless of the diagnosis. CONCLUSIONS Spontaneous onset of an LH surge during superovulation induction does not influence the chances for pregnancy.