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

The Clinical Research Center and the Department of Medicine, Medical College of Wisconsin Milwaukee, Wisconsin 53226

Address requests for reprints to: Dr. A. Kissebah, Medical College of Wisconsin, 9200 West Wisconsin Avenue, Milwaukee, Wisconsin 53226.

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.

^* This work was supported by General Clinical Research Center Grant RR-00058, Research Grants AM-24087 and AM-10305 from the NIH (Bethesda, MD), and grants from the TOPS Club, Inc., Obesity and Metabolic Research Program, Milwaukee, WI. Presented in part at the 64th Annual Meeting of The Endocrine Society, San Francisco, CA, June 16–18, 1982.

Received November 5, 1982.

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