Estrogen, Hormone Replacement Therapy and Mitochondrial Action

Estrogen is a critical participant in in metabolic regulation. Clinical trials and animal studies have shown that reductions in  circulating estrogen causes swift changes in metabolism, fat distribution, and insulin function. The metabolic effects of estrogen are caused primarily by estrogen receptor-a on within the cells. Research suggests that estrogen receptor-α elicits the metabolic effects of estrogen through mitochondrial mechanisms that regulate insulin signaling, and energetics.

 Loss of the main circulating estrogen, β-estradiol (E2), due to either natural or surgical menopause has effects that go far beyond reproductive health. Estradiol deficiency and its downstream effects on mitochondrial cellular functioning lead to an abrupt reduction in metabolic rate, shift to increased central adiposity, increased cholesterol and progression of metabolic syndrome (MetS) and, hence,  ‘inflammaging’. 

Together these changes increase the risk of nonalcoholic fatty liver with elevated liver enzymes, type 2 diabetes, and cardiovascular disease. With increasing life expectancies, women now spend three to five decades of their life in Estrogen deficient status and experience health challenges from which Estrogen had previously provided protection. 

Unfortunately, due to the Women’s Health Initiative (WHI) in the early 2000s, perimenopausal women have been reluctant to try replacement of Estradiol due to fears of adverse reactions which were demonstrated in that study. However, the Hormones that were used in that study, and the modes of delivery are not the same as the Estrogens of today. And, the vast majority of women who take hormone replacement therapy (HRT) report improved metabolic benefits of Estrogen; they report increased energy, better glucose metabolism, decreased hot flashes, better weight control, and improved bone density.