Evelyn O. Talbott

Assessment of Cardiovascular Risk and Prevention of Cardiovascular Disease in Women with the Polycystic Ovary Syndrome: A Consensus Statement by the Androgen Excess and Polycystic Ovary Syndrome (AE-PCOS) Society

OBJECTIVE Women with polycystic ovary syndrome (PCOS) often have cardiovascular disease (CVD) risk factors. The Androgen Excess and Polycystic Ovary Syndrome (AE-PCOS) Society created a panel to provide evidence-based reviews of studies assessing PCOS-CVD risk relationships and to develop guidelines for preventing CVD. PARTICIPANTS An expert panel in PCOS and CVD reviewed literature and presented recommendations. EVIDENCE Only studies comparing PCOS with control patients were included. All electronic databases were searched; reviews included individual studies/databases, systematic reviews, abstracts, and expert data. Articles were excluded if other hyperandrogenic disorders were not excluded, PCOS diagnosis was unclear, controls were not described, or methodology precluded evaluation. Inclusion/exclusion criteria were confirmed by at least two reviewers and arbitrated by a third. CONSENSUS PROCESS Systematic reviews of CVD risk factors were compiled and submitted for approval to the AE-PCOS Society Board. CONCLUSIONS Women with PCOS with obesity, cigarette smoking, dyslipidemia, hypertension, impaired glucose tolerance, and subclinical vascular disease are at risk, whereas those with metabolic syndrome and/or type 2 diabetes mellitus are at high risk for CVD. Body mass index, waist circumference, serum lipid/glucose, and blood pressure determinations are recommended for all women with PCOS, as is oral glucose tolerance testing in those with obesity, advanced age, personal history of gestational diabetes, or family history of type 2 diabetes mellitus. Mood disorder assessment is suggested in all PCOS patients. Lifestyle management is recommended for primary CVD prevention, targeting low-density and non-high-density lipoprotein cholesterol and adding insulin-sensitizing and other drugs if dyslipidemia or other risk factors persist.

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.

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

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.

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

Abstract Objective: To determine whether testosterone levels change as women with the polycystic ovary syndrome (PCOS) grow older. Design: A follow-up cross-sectional study of a cohort of women with PCOS identified up to 20–25 years ago. Setting: Women with PCOS were recruited primarily from practice records between 1970 and 1990. Voter registration tapes and household directories were used to identify age-, race-, and neighborhood-matched controls. Participant(s): Eighty-four women with PCOS, 20–57 years of age, and 37 age-matched controls participating in a study of the risk for cardiovascular disease in women with PCOS. Intervention(s): Clinical data were collected by questionnaire and fasting blood samples were obtained randomly throughout the menstrual cycle. Main Outcome Measure(s): Total and non–SHBG-bound testosterone levels. Result(s): Total and non–SHBG-bound testosterone levels were similar in women with PCOS who were 20–42 years of age but were reduced by approximately 50% among women 42–47 years of age and remained stable in women older than 47 years of age. Testosterone levels were increased in younger and older women with PCOS compared with controls but were similar to controls in women 42–47 years of age. Conclusion(s): Hyperandrogenism partly resolves before menopause in women with PCOS. This change may explain the tendency of women with PCOS to cycle regularly as they grow older. Testosterone levels remain elevated in older women with PCOS, however, and may contribute to their increased risk for cardiovascular disease, endometrial cancer, and other diseases.

CARDIOVASCULAR RISK IN WOMEN WITH POLYCYSTIC OVARY SYNDROME

Compared with normal cycling women of similar age, women with polycystic ovary syndrome (PCOS) have an adverse lipid profile and an increased prevalence of Type II diabetes and hypertension. These woman also appear to have greater subclinical atherosclerotic disease, as demonstrated by greater carotid intimamedia wall thickness and higher levels of coronary calcification. Given the high prevalence of PCOS in the female population, this condition may potentially account for a significant proportion of the atherosclerotic heart disease observed in younger women. This article reviews the issues and uncertainties surrounding the PCOS-CHD association.

Occupational stress, suppressed anger, and hypertension.

&NA; The present study examined the modifying effect of suppressed anger on the relationship between job stress and hypertension. The study population consisted of a random sample of male hourly workers, aged 40–63 years, employed at one of two plants in the metropolitan Pittsburgh, Pennsylvania area. Those men currently taking antihypertensive medication were excluded from the analyses. With both plants combined, stratified analyses indicated that, compared to men who do not habitually suppress their anger, hypertension was more strongly associated with self‐reports of an uncertain job future and dissatisfaction with coworkers and promotions among men who suppress their anger. Using logistic regression procedures, these interactions between suppressed anger and job stress significantly predicted hypertension status, controlling for age, body mass index, smoking, alcohol consumption, and family history of hypertension. These findings suggest that a coping‐related characteristic such as anger expression may be an important modifier of the relationship between job stress and hypertension.

Associations of serum concentrations of organochlorine pesticides with breast cancer and prostate cancer in U.S. adults.

Background Organochlorine (OC) pesticides are a group of environmental endocrine disruptors that may be associated with an increased risk for hormone-related cancers including cancers of the breast and prostate. However, epidemiologic evidence is limited and inconsistent. Objectives and methods We used 1999–2004 National Health and Nutrition Examination Survey data to examine associations between serum concentrations of OC pesticides and prostate and breast cancers. Results After adjustment for other covariates, serum concentrations of β-hexachlorocyclohexane (HCH) (p for trend = 0.02), trans-nonachlor (p for trend = 0.002), and dieldrin (p for trend = 0.04) were significantly associated with the risk of prevalent prostate cancer. Adjusted odds ratios for the second and third tertiles of detectable values were 1.46 [95% confidence interval (CI), 0.52–4.13] and 3.36 (95% CI, 1.24–9.10) for β -HCH; 5.84 (95% CI, 1.06–32.2) and 14.1 (95% CI, 2.55–77.9) for trans-nonachlor; and 1.06 (95% CI, 0.30–3.73) and 2.74 (95% CI, 1.01–7.49) for dieldrin compared with concentrations in the lowest tertile or below the limit of detection. However, there was no positive association between serum concentrations of OC pesticides and breast cancer prevalence. Conclusion Although further study is necessary to confirm these findings, these results suggest that OC pesticide exposures may have a significant effect on cancer risk. Efforts to reduce worldwide OC use are warranted.

Biologic and psychosocial risk factors of sudden death from coronary disease in white women

The relation of the risk of sudden death from arteriosclerotic heart disease to psychosocial and biologic factors was studied retrospectively in 64 white women who died suddenly of arteriosclerotic heart disease and in 64 age-related neighborhood control women. All sudden deaths occurred outside the hospital within 24 hours of the onset of symptoms in women who were not incapacitated before death. Women who died suddenly were less often married, exhibited more educational incongruity with their spouses and had fewer children than the control population. Twelve of the 64 women who died suddenly of heart disease and none of the control women had a definite history of psychiatric treatment. The women who died suddenly also smoked more cigarette and consumed greater quantities of alcoholic beverages than age-matched neighborhood control women. Multiple regression analysis revealed that history of psychiatric illness, cigarette smoking, alcohol consumption, educational incongruity and number of children contributed significantly to differences between women who died suddenly of heart disease and control subjects.

Carotid artery intima-media thickness in polycystic ovary syndrome: a systematic review and meta-analysis

BACKGROUND Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder associated with cardiovascular disease (CVD) risk factors and metabolic disturbances. This systematic review and meta-analysis was conducted to determine whether carotid intima-media thickness (CIMT), a marker of subclinical atherosclerosis, is higher in women with PCOS compared with women without PCOS. METHODS Primary articles reporting the mean CIMT in women with PCOS and controls were identified using Ovid MEDLINE, EMBASE and PUBMED. We performed a random-effects meta-analysis and created forest plots of the mean difference in CIMT and conducted tests for heterogeneity and publication bias. Studies were grouped by quality, defined by reporting reproducibility of CIMT and averaging both common carotid arteries versus one side for CIMT. RESULTS From the 36 eligible full-text studies, 8 studies were included in the systematic review and 19 studies were included in the meta-analysis (total n= 1123 women with PCOS, n= 923 controls). The summary mean difference in CIMT among women with PCOS compared with controls was 0.072 mm [95% confidence interval (CI) 0.040, 0.105, P < 0.0001] for highest quality studies, 0.084 mm (95% CI 0.042, 0.126, P = 0.0001) for good quality studies, 0.041 (95% CI -0.038, 0.120, P = 0.310) for fair-quality studies and 0.045 (95% CI -0.020, 0.111, P = 0.173) for lower quality studies. CONCLUSIONS Larger studies with a well-defined PCOS population using rigorous methodology may be required to draw a more robust conclusion. However, these results suggest women with PCOS are at a greater risk of premature atherosclerosis, which emphasizes the importance of screening and monitoring CVD risk factors in women with PCOS.

Environmental events preceding sudden death in women.

&NA; The present case‐control study examined if sudden cardiac death in women is preceded by death of a significant other, change in residence, or change in work. The sample included 81 Caucasian women ages 25‐64 years in Allegheny County, Pennsylvania, who died suddenly from arteriosclerotic heart disease (ASHD) within a 11/2 year interval. Each case was matched to a neighborhood control on the basis of race, age, and sex. Results revealed that relative to matched controls, cases were six times as likely to have experienced the death of a significant other within the last months; they were no more likely to have experienced changes in living conditions or in work. These findings raise the issue of whether death of a significant other is an antecedent event of death due to ASHD only or death due to all causes. Possible explanations for the temporal association between sudden death and death of a significant other are discussed.