Lecturer, Afebabalola University
Oestrogen deficiency-induced cardiometabolic disorder
Globally, cardiometabolic disorder (CMD) is assuming an increasing role as a major cause of morbidity and mortality. It identifies a cluster of metabolic disorders including visceral adiposity, insulin resistance (IR), hyperglycemia, dyslipidemia and hypertension, that occur together and place affected individuals at up to 2 times higher risk of a major cardiovascular event, 3 times higher risk of chronic renal insufficiency, more than 4 times higher danger of type 2 diabetes mellitus, incidence of congestive heart failure and cardiovascular mortality. Gender differences in the development of cardiovascular disease (CVD) are well documented in both human and animal experimental studies. The incidence of CVD among women increases sharply during menopause which is thought to result in part from the deficient endogenous oestrogen and its associated cardioprotective effects. A loss of ovarian function is associated with increased fat, along with metabolic pathologies including insulin resistance (IR) and type 2 diabetes (T2D). The fact that increasing numbers of women, who will spend the second half of their lives in a state of oestrogen deficiency, expect longer life spans requires an understanding of the pathologies of metabolic diseases associated with oestrogen deficiency observed in them. Mineralocorticoid Receptor (MR) activation has been implicated in the pathogenesis of the components of Cardiometabolic Disorder (CMD), an enormously growing public health problem made up of interconnected and heterogenous disorders including IR, dyslipidaemia and endothelial dysfunction. Hence, factors or intervention that could influence the development of CMD in postmenopausal women who are in a state of oestrogen deficiency, will be of great public health importance.
Abstract: Elevated gestational circulating testosterone has been associated with pathological pregnancies that increase the risk of development of cardiometabolic disorder in later life.We hypothesised that gestational testosterone exposure, in late pregnancy, causes glucose deregulation and atherogenic dyslipidaemia that would be accompanied by high plasminogen activator inhibitor-1 (PAI-1). The study also hypothesise that low-dose spironolactone treatment would ameliorate these effects.Pregnant Wistar rats received vehicle, testosterone (0.5 mg/kg; sc), spironolactone (0.5 mg/kg, po) or testosterone and spironolactone daily between gestational days 15 and 19.Gestational testosterone exposure led to increased HOMA-IR, circulating insulin, testosterone, 1-h post-load glucose, atherogenic dyslipidaemia, PLR, PAI-1 and MDA. However, all these effects, except that of circulating testosterone, were ameliorated by spironolactone.These results demonstrate that low-dose spironolactone ameliorates glucose deregulation and atherogenic dyslipidaemia during elevated gestational testosterone exposure, at least in part, by suppressing elevated PAI-1.
Pub.: 10 May '17, Pinned: 21 Jul '17