Relationship of Androgenic Activity to Body Fat Topography, Fat Cell Morphology, and Metabolic Aberrations in Premenopausal Women*

TLDR

The study examined whether increased androgenic/estrogenic activity contributes to upper‑body fat distribution and related cellular and metabolic traits in premenopausal women. The authors studied 80 healthy, nonhirsute, premenopausal Caucasian women spanning a broad range of waist‑to‑hip ratios and obesity levels. Higher androgenicity, reflected by lower SHBG and higher free testosterone, was linked to greater waist‑to‑hip ratio, larger abdominal fat cells, elevated glucose and insulin levels, and reduced insulin sensitivity, suggesting that excess unbound androgens contribute to upper‑body fat accumulation and metabolic dysregulation in premenopausal women.

Abstract

A possible role for increased androgenic/estro-genic activity in the pathogenesis of upper body fat localization and its accompanying cellular and metabolic characteristics was examined. Eightly healthy, nonhirsute, premenopausal, Caucasian women with a wide range of body fat topography [waist to hips girth ratio (WHR), 0.64 to 1.02] and obesity level (percentage of ideal body weight, 92–251%) were studied. Increasing androgenicity, as reflected by a decrease in plasma sex hormone-binding globulin capacity and an increase in the percentage of free testosterone, was accompanied by 1) increasing WHR, this relationship being independent of and additive to that of obesity level; 2) increasing size of abdominal, but not femoral, adipo-cytes; 3) increasing plasma glucose and insulin levels, both basally and in response to oral glucose loading; and 4) diminished in vivo insulin sensitivity, as revealed by increasing steady state plasma glucose levels at comparable plasma insulin levels, attained by the infusion of somatostatin, insulin, and glucose. No association was found between total plasma testosterone, andro-stenedione, dehydroepiandrosterone sulfate, or estradiol concentrations and WHR, fat cell size, or metabolic profiles. We, therefore, propose that in premenopausal women, a relative increase in tissue exposure to unbound androgens may be responsible in part for localization of fat in the upper body, enlargement of abdominal adipocytes, and the accompanying imbalance in glucose-insulin homeostasis.