New Insights on the Environment of Sex Steroids in Adipose Tissue of Postmenopausal Women at Hormone Therapy

In postmenopausal women, most circulating estrogens are the product of conversion of androgen precursors in peripheral tissues, especially adipose tissue. This tissue contains higher concentrations of androgens and estrogens compared to their circulating levels, underscoring its role as an important reservoir and site of metabolism for sex steroids. Indeed, adipose tissue has long been known to be an active endocrine organ that plays regulatory roles in the function of multiple tissues, with activity varying by location (visceral or subcutaneous). Adipose tissue distribution differs by sex; men are more likely to exhibit android (visceral) adiposity, which confers an adverse cardiometabolic profile. Conversely, reproductive-aged women have higher overall adiposity than men, but their adipose tissue predominantly accumulates in a gynoid (subcutaneous) distribution, which is associated with lower metabolic risk. In turn, menopause has been associated with an increased likelihood of central adiposity—a surrogate for visceral adipose tissue accumulation and metabolic comorbidities (1, 2). Low estrogen levels and an imbalance in the estrogen-to-androgen ratio are likely key factors in explaining these body fat changes at menopause, though other hormonal influences may also contribute. The increase in abdominal visceral adipose tissue during the menopausal years has been associated with cardiovascular risk (3). These changes in body fat distribution in the postmenopausal years may be mitigated by menopausal hormone therapy (MHT) (4).