Evaluation of androgenicity, abdominal adiposity, blood pressure and types of ovulatory patterns in a sample of women with menstrual irregularities

Objective: To determine the prevalence of and the relationships between the degree and source of hyperandrogenemia, ovulatory patterns and cardiovascular disease risk indicators (blood pressure, indices or amount of obesity and fat distribution) in women with menstrual irregularities seen at endocrinologists' clinic. Design: A cross-sectional study design. Participants: A sample of 159 women with menstrual irregularities, aged 15-44, seen at endocrinologists' clinic. Main Outcome Measures: androgen levels, body mass index (BMI), waist-hip ratio (WHR), systolic and diastolic blood pressure (SBP & DBP), source of androgens, ovulatory activity. Results: The prevalence of hyperandrogenemia was 54.7% in this study sample. As expected, women with acne or hirsutism had an odds ratio 12.5 (95%CI = 5.2-25.5) times and 36 (95%CI = 12.9-99.5) times more likely to have hyperandrogenemia than those without acne or hirsutism. The main findings of this study were the following: Hyperandrogenemic women were more likely to have oligomenorrheic cycles (OR = 3.8, 95%CI = 1.5-9.9), anovulatory cycles (OR = 6.6, 95%CI = 2.8-15.4), general obesity (BMI $\ge$ 27) (OR = 6.8, 95%CI = 2.2-27.2) and central obesity (WHR $\ge$ 127) (OR = 14.5, 95%CI = 6.1-38.7) than euandrogenemic women. Hyperandrogenemic women with non-suppressible androgens had a higher mean BMI (29.3 $\pm$ 8.9) than those with suppressible androgens (27.9 $\pm$ 7.9); the converse was true for abdominal adiposity (WHR). Hyperandrogenemic women had a 2.4 odds ratio (95%CI = 1.0-6.2) for an elevated SBP and a 2.7 odds ratio (95%CI = 0.8-8.8) for elevated DBP. When age differences were accounted for, this relationship was strengthened and further strengthened when sources of androgens were controlled. When the differences in BMI were controlled, the odds ratio for elevated SBP in hyperandrogenemic women increased to 8.8 (95%CI = 1.1-69.9). When the age, the source of androgens, the amount of obesity and the type of obesity were controlled, hyperandrogenemic women had 13.5 (95%CI = 1.1-158.9) odds ratio for elevated SBP. Conclusions: In this study population, the presence of menstrual irregularities are highly predictive for the presence of elevated androgens. Women with elevated androgens have a high risk for obesity, more specifically for central obesity. The androgenemic status is an independent predictor of blood pressure elevation. It is probable that in the general population, the presence of menstrual irregularities are predictive of hyperandrogenemia. There is a great need for a population study of the prevalence of hyperandrogenemia and for longitudinal studies in hyperandrogenemic women (adrenarche to menopause) to investigate the evolution of these relationships. ^

Adiposity and the perilipin gene: The role of single locus and multilocus variation, obesity-related quantitative traits, and disease-related phenotypes in the Atherosclerosis Risk in Communities (ARIC) study

Obesity is a complex multifactorial disease and is a public health priority. Perilipin coats the surface of lipid droplets in adipocytes and is believed to stabilize these lipid bodies by protecting triglyceride from early lipolysis. This research project evaluated the association between genetic variation within the human perilipin (PLIN) gene and obesity-related quantitative traits and disease-related phenotypes in Non-Hispanic White (NHW) and African American (AA) participants from the Atherosclerosis Risk in Communities (ARIC) Study. ^ Multivariate linear regression, multivariate logistic regression, and Cox proportional hazards models evaluated the association between single gene variants (rs2304794, rs894160, rs8179071, and rs2304795) and multilocus variation (rs894160 and rs2304795) within the PLIN gene and both obesity-related quantitative traits (body weight, body mass index [BMI], waist girth, waist-to-hip ratio [WHR], estimated percent body fat, and plasma total triglycerides) and disease-related phenotypes (prevalent obesity, metabolic syndrome [MetS], prevalent coronary heart disease [CHD], and incident CHD). Single variant analyses were stratified by race and gender within race while multilocus analyses were stratified by race. ^ Single variant analyses revealed that rs2304794 and rs894160 were significantly related to plasma triglyceride levels in all NHWs and NHW women. Among AA women, variant rs8179071 was associated with triglyceride levels and rs2304794 was associated with risk-raising waist circumference (>0.8 in women). The multilocus effects of variants rs894160 and rs2304795 were significantly associated with body weight, waist girth, WHR, estimated percent body fat, class II obesity (BMI ≥ 35 kg/m2), class III obesity (BMI ≥ 35 kg/m2), and risk-raising WHR (>0.9 in men and >0.8 in women) in AAs. Variant rs2304795 was significantly related to prevalent MetS among AA males and prevalent CHD in NHW women; multilocus effects of the PLIN gene were associated with prevalent CHD among NHWs. Rs2304794 was associated with incident CHD in the absence of the MetS among AAs. These findings support the hypothesis that variation within the PLIN gene influences obesity-related traits and disease-related phenotypes. ^ Understanding these effects of the PLIN genotype on the development of obesity can potentially lead to tailored health promotion interventions that are more effective. ^