Cardiometabolic Effects of Chronic Hyperandrogenemia in a New Model of Postmenopausal Polycystic Ovary Syndrome

Abstract

Postmenopausal women who have had polycystic ovary syndrome (PCOS) and chronic hyperandrogenemia may be at a greater risk for cardiovascular disease than normoandrogenemic postmenopausal women. The cardiometabolic effect of chronic hyperandrogenemia in women with PCOS after menopause is unclear. The present study was performed to test the hypothesis that chronic hyperandrogenemia in aging female rats would have more deleterious effects on metabolic function, blood pressure, and renal function than in normoandrogenemic age-matched females. Female Sprague Dawley were implanted continuously, beginning at 4-5 weeks, with dihydrotestosterone (postmenopausal hyperandrogenemic female [PMHAF]) or placebo pellets (controls), and were studied at 13 months of age. Plasma DHT was 3-fold higher, and estradiol was 90% lower in PMHAF than controls. Body weights were higher; EchoMRI showed greater fat and lean mass; and computed tomography showed more sc and visceral adiposity in PMHAF, but with similar femur length compared with controls. Insulin resistance was present in PMHAF with higher plasma insulin, normal fasting blood glucose, abnormal oral glucose tolerance test, and higher nonfasting blood glucose. Blood pressure (radiotelemetry) was significantly higher and heart rate was lower, and renal function (glomerular filtration rate) was reduced by 40% in PMHAF. Thus the aging chronically hyperandrogenemic female rat is a new model of postmenopausal PCOS, which exhibits insulin resistance and visceral obesity, hypertension, and impairment in renal function. This new model provides a unique tool to study the deleterious effects of chronic androgen excess in postmenopausal females rats.

Long-Lasting Androgen-Induced Cardiometabolic Effects in Polycystic Ovary Syndrome

“…Monthly body weight and food intake were measured for 6 months after DHT withdrawal. At 13 months of age, body composition of ex-DHT and control rats (n = 10/group), including total body fat mass, total body lean mass, and total body water, were measured (4 in1 900 model Body Composition Analyzer; Echo-MRI, Houston, TX) according to the manufacturer’s instructions, as we previously reported [ 30 ].…”

Association Between Idiopathic Intracranial Hypertension and Risk of Cardiovascular Diseases in Women in the United Kingdom

“… 11 Androgen excess is a key driver of increased cardiovascular risk. 12 , 13 , 14 , 15 , 16 , 17 We hypothesized that patients with IIH may have an increased risk of cardiometabolic disease compared with a cohort matched for obesity (BMI), age, and sex. The aim of this study was to define cardiometabolic risk in IIH, independent of BMI, and to identify trends in prevalence and incidence.…”

MECHANISMS IN ENDOCRINOLOGY: Aging and anti-aging: a Combo-Endocrinology overview

“…An important issue is that, after menopause, PCOS women still have elevated androgen levels (144, 145), which in turn may have some negative impact in favoring metabolic alterations and, possibly, an increased cardiovascular (CV) risk. Preliminary data from a new rat model of postmenopausal PCOS have in fact shown that they are characterized by higher insulin and non-fasted glucose levels than aged controls (146).…”