Oral contraceptive use by teenage women does not affect body composition

OBJECTIVE: To assess the effect of oral contraceptive (OC) use during adolescence on body composition parameters and cardiovascular disease risk factors. METHODS: We used 9 years of longitudinal data from 66 non-Hispanic white females who were 12 years old at study entry in 1990, and who were subsequently classified either as OC users or nonusers. The OC users (n = 39) used OCs for a minimum of 6 months, were still using at age 21, and had used OCs, on average, for 28 months. The nonusers (n = 27) never used OCs. Individuals who started and then stopped using OCs before age 21 or used OCs for less than 6 months were excluded from these analyses. Cardiolipoprotein profiles were obtained from fasting blood samples (from age 16 to 21), and body composition measurements were made by dual energy x-ray absorptiometry (from age 12.5 to 21). Longitudinal models were used to examine changes in body composition patterns and in cardiolipoprotein patterns. RESULTS: Between ages 12.5 and 21, gains by OC users and nonusers in height, weight, body mass index (BMI), and percent body fat were not significantly different. However, between ages 16 and 21, the OC users had significantly greater increases in total serum cholesterol, serum low-density cholesterol, and serum triglycerides than did the nonusers. CONCLUSION: The use of OCs in young women is associated with less favorable blood lipid patterns, but is not associated with weight gain or increased body fat. The long-term effects of the alteration in the lipid profiles are unknown.     

Role of androgens in the growth of endometrial carcinoma: an in vivo animal model

OBJECTIVE: We sought to create an animal model for the development of endometrial cancer in women with androgen excess. We examined the effects of estradiol and androgen, both alone and as precursors to estrogen biosynthesis on human endometrial cancers transplanted into a nude mouse model. STUDY DESIGN: We transplanted an estrogen-responsive, well-differentiated, established human endometrial carcinoma, EnCa-101, subcutaneously into athymic male nude mice. We established, first, that aromatase was expressed in this cell line, inducible by estrogen. We measured the growth of the tumor in the various groups weekly with Vernier calipers. We examined the effects of estradiol and androgens, both aromatizable and nonaromatizable, on tumor growth. RESULTS: Estrogen-supplemented tumors showed the greatest rate of growth and were significantly greater than the growth rate in castrate mice. Androgen-supplemented tumors showed a growth rate similar to that of tumors without significant hormonal exposure (castrate mice). Dihydrotestosterone had no effect on tumor growth in comparison with an agonadal state. CONCLUSIONS: Aromatizable and nonaromatizable androgens have little growth-promoting effect on a well-differentiated endometrial carcinoma. Estradiol is the most potent growth stimulus in our model.     

Influenza Vaccination Among Veterans With Spinal Cord Injury: Part 1. A Survey Of Attitudes And Behavior

Abstract

Background/Objective: Persons with spinal cord injury and disorders (SCID) are at increased risk of developing influenza, pneumonia, and ensuing complications. Influenza vaccine has been shown to be effective, yet vaccination rates have been low in this population. To improve these rates, barriers and facilitators to receiving influenza vaccine in this population were identified.

Methods: A cross-sectional telephone survey was conducted with a convenience sample of patients at 1 3 Department of Veterans Affairs (VA) Spinal Cord Injury (SCI) Centers between September and November 2000. Survey questions assessed perceptions regarding the influenza vaccine.

Results: Participants interviewed (N = 377) had a mean age of 5 8.6 years and were predominantly male and white. Most had had received the influenza vaccine at some time in the past; however, 3 5% had not received it in the previous year. The most common reason reported for not being vaccinated was the belief that it was not important. Those who knew the best time to be vaccinated were more likely to have been vaccinated the previous year (OR = 3.57, 9 5%, Cl: 2.1 2-6.01 ). Other predictors of vaccination included being married, being aged 65 and older, and being aware that the vaccine was a good way to prevent some pulmonary problems that can result from influenza.

Conclusions: Barriers to vaccination include poor understanding of the seriousness of influenza and of the vulnerability of someone with SCID to respiratory complications. Availability of the influenza vaccine at VA facilities and knowledge of when to be vaccinated were facilitators. Providers should use every opportunity to vaccinate patients and provide education about the value of influenza vaccination and when to be vaccinated.     

Catechol-O-methyltransferase (COMT) single nucleotide polymorphisms and haplotypes are not major risk factors for polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is an endocrine disorder that affects 5-8% of reproductive age women. The primary features of PCOS are hyperandrogenemia, chronic anovulation and infertility. It has been suggested that defects in ovarian steroid metabolism contribute to the follicular growth arrest and abnormal production of ovarian steroid hormones that are characteristic of PCOS. 2-Methoxyestradiol (2-ME) is formed by the action of catechol-O-methyltransferase (COMT) on 2-hydroxyestradiol. COMT expression is increased in the follicles and ovarian stroma of women with PCOS. Moreover, 2-ME decreases granulosa cell proliferation and steroidogenesis, raising the possibility that ovarian dysfunction associated with PCOS is due, in part, to increased synthesis of 2-ME resulting from increased COMT activity. Four single-nucleotide polymorphisms (SNPs) (rs6269, rs4633, rs4818, rs4680) in the COMT gene characterize haplotypes, which are associated with large variations in COMT enzymatic activity. The aim of this study was to determine whether individual COMT SNPs and the COMT haplotypes are associated with PCOS using a family-based test of association and linkage. Additionally, we examined the relationships between COMT SNPs and haplotypes with quantitative variables usually assessed in the evaluation of women with PCOS. There were no significant correlations between genotype and total testosterone, non-SHBG bound testosterone and BMI. However, we found that the prolactin level in women with PCOS varied significantly with COMT haplotype, and suggest that this association reflects a genetic factor influencing the stress response. Our findings suggest that common variants and haplotypes of the COMT gene are not major contributors to risk for PCOS, but that COMT genotype may influence prolactin levels.     

Prevalence and predictors of dyslipidemia in women with polycystic ovary syndrome.

PURPOSE: Women with polycystic ovary syndrome are hyperandrogenemic and insulin resistant, which are associated with alterations in circulating lipid and lipoprotein levels. We sought to determine the prevalence of, and risk factors for, lipid abnormalities in these women. SUBJECTS AND METHODS: Non-Hispanic white women with polycystic ovary syndrome (n = 195) and ethnically matched control women (n = 62) had fasting blood obtained for hormone and lipid levels. Subjects were categorized by body mass index (nonobese <27 kg/m(2), obese > or =27 kg/m(2)), and analyses were adjusted for age. RESULTS: Total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels increased significantly in obese women with polycystic ovary syndrome (n = 153) compared with obese control women (n = 35; mean difference in total cholesterol level = 29 mg/dL; 95% confidence interval [CI]: 14 to 45 mg/dL; P <0.001; mean difference in LDL-C level = 16 mg/dL; 95% CI: 4 to 30 mg/dL; P = 0.006). Similarly, total cholesterol and LDL-C levels increased significantly in nonobese women with polycystic ovary syndrome (n = 42) compared with nonobese control women (n = 27; mean difference in total cholesterol = 32 mg/dL; 95% CI: 13 to 52 mg/dL; P <0.001; mean difference in LDL-C level = 32 mg/dL; 95% CI: 15 to 52 mg/dL; P <0.001). In obese women, high-density lipoprotein cholesterol (HDL-C) and triglyceride levels increased significantly in women with polycystic ovary syndrome compared with control women (mean difference in HDL-C level = 6 mg/dL; 95% CI: 2 to 12 mg/dL; P = 0.002; mean difference in triglyceride level = 34 mg/dL; 95% CI: 1 to 77 mg/dL; P = 0.04). Differences in LDL-C and HDL-C levels, but not triglyceride levels, remained significant after adjusting for alcohol intake, smoking, and exercise. Although age, body mass index, and polycystic ovary syndrome status were significant predictors of lipid levels, these factors accounted for no more than 25% of the variance. CONCLUSIONS: In this large study of non-Hispanic white women, elevations in LDL-C levels were the predominant lipid abnormality in women with polycystic ovary syndrome, independent of obesity. The characteristic dyslipidemia of insulin resistance was absent. Indeed, obese women with polycystic ovary syndrome had relatively elevated HDL-C levels, which may confer some protection against cardiovascular disease.     

Effects of race and family history of type 2 diabetes on metabolic status of women with polycystic ovary syndrome

Racial origin and family history of type 2 diabetes impact upon the risk of developing impaired glucose tolerance (IGT) and type 2 diabetes, both of which are common in women with polycystic ovary syndrome (PCOS). We examined the effects of race and family history of type 2 diabetes on the risk of IGT and type 2 diabetes in a large cohort of women with PCOS. Data obtained at baseline were analyzed from 408 premenopausal women with PCOS. Multivariate linear regression models were used to assess the impact of race (white, black, and other) and family history of type 2 diabetes on body mass index, waist circumference, and waist to hip ratio; glycemic measures (glucose and insulin levels obtained during a standard 75-g oral glucose tolerance test, fasting glucose to insulin ratio, and homeostasis model assessment model of insulin resistance derived from fasting levels of glucose and insulin), hemoglobin A(1c), and SHBG, and dehydroepiandrosterone sulfate levels. Sixteen (4%) of the 408 patients had type 2 diabetes, 94 (23%) had IGT, and the remaining 298 (73%) had normal glucose tolerance. A history of type 2 diabetes in either parent (FHxPOS) was present in seven (44%) of the 16 diabetic women with PCOS, 37 (39%) of the 94 women with IGT, and 62 (21%) of those with normal glucose tolerance (P < 0.01, by chi(2) test). The prevalences of IGT and type 2 diabetes were significantly higher in FHxPOS PCOS women compared with FHxNEG PCOS women, IGT evident in 37 (35%) FHxPOS compared with 57 (19%) FHxNEG women, and type 2 diabetes evident in seven (7%) FHxPOS compared with nine (3%) FHxNEG women. Among the 392 nondiabetic subjects, after adjustment for the effects of race, FHxPOS differed significantly from FHxNEG patients in having a higher mean waist to hip ratio, hemoglobin A(1c) level, 2-h glucose level, fasting glucose and insulin levels, glucose to insulin ratio, homeostasis model assessment model of insulin resistance, and areas under the glucose and insulin curves during the oral glucose tolerance test. A family history of type 2 diabetes was present with a significantly greater frequency among women with PCOS who had IGT or type 2 diabetes compared with those with normal glucose tolerance. Conversely, a family history of type 2 diabetes in a first-degree relative was associated with a significantly higher risk for IGT or type 2 diabetes in women with PCOS. Even among nondiabetic women with PCOS, a positive family history of type 2 diabetes was strongly associated with metabolic characteristics associated with an increased risk for type 2 diabetes. Finally, the fasting glucose concentration was poorly associated with 2-h glucose concentrations among PCOS women with IGT, suggesting that the fasting glucose concentration is inadequate to predict the presence of IGT in PCOS.     

Plasma interleukin 6 levels are elevated in polycystic ovary syndrome independently of obesity or sleep apnea

Premenopausal women with polycystic ovary syndrome (PCOS) are at a much higher risk for excessive daytime sleepiness, fatigue, and insulin resistance than control women. Elevated levels of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) are presumably part of the pathogenesis of these clinical manifestations. Forty-two obese women with PCOS, 17 body mass index-comparable obese controls, and 15 normal-weight controls free from apnea participated in the study that included one 8-hour nighttime polysomnography, single morning cytokine plasma concentrations, and insulin resistance indices. Women with PCOS exhibited higher plasma concentrations of IL-6 than obese controls, who had intermediate values, or normal-weight controls, who had the lowest values (4.75 +/- 0.5 vs 3.65 +/- 0.4 vs 1.84 +/- 0.3 pg/mL, P < .01). Tumor necrosis factor alpha values were higher in PCOS and obese controls compared with normal-weight controls, but the difference was not statistically significant (4.05 +/- 0.3 vs 3.79 +/- 0.2 vs 3.14 +/- 0.2 pg/mL, P = .103). Based on backward regression analysis, IL-6 levels had a stronger association with the PCOS group than with the obese group, and the sleep or hypoxia variables did not make a significant contribution to either IL-6 or TNF-alpha. Both IL-6 and TNF-alpha correlated positively with body mass index (P < .01) in obese controls but not in women with PCOS. Furthermore, within the PCOS group, IL-6 and TNF-alpha correlated more strongly with indices of insulin resistance than obesity. We conclude that IL-6 levels are elevated in obese women with PCOS independently of obesity or sleep apnea and may represent a pathophysiologic link to insulin resistance.     

A twenty-first century research agenda for polycystic ovary syndrome

Notwithstanding the significant progress made in our understanding of polycystic ovary syndrome (PCOS), the field remains ripe for further discovery and more intensive translational research. Immediate priorities include developing evidence-based criteria for diagnosing PCOS and for assessing the response to the various treatments available. The basis for the identification of PCOS remains mainly expert opinion, and the lack of universally accepted evidence-based criteria limits the generalizability of research studies on PCOS. Additional important areas requiring intensive investigation include the natural history and etiology and the long-term sequelae and prevention of the disorder. Overall, this disorder is a prototype for the benefits of translational science and a transdisciplinary approach to understanding the pathophysiology and therapy for anovulatory infertility.