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Sex steroid deprivation adversely affects body composition in healthy men

Adverse changes in body composition in healthy men may be caused by short-term sex steroid withdrawal.

“This study demonstrates that significant body composition changes occur in healthy, eugonadal men after only 4 weeks of sex steroid deprivation,” the researchers wrote. “Significant changes in fat mass were observed and attribution to estrogen withdrawal.”

Stephanie T. Page, MD, PhD, of the division of metabolism, endocrinology and nutrition in the department of medicine at the University of Washington in Seattle, and colleagues evaluated 45 healthy men (median age, 36 years; median BMI, 25 kg/m2) to determine the effects of selective sex steroid withdrawal on insulin sensitivity.

Stephanie T. Page

Participants received acyline, a gonadotropin-releasing hormone and were randomly assigned to one of the following: placebo gel (n = 10), 1.25 g testosterone gel (AndroGel, AbbVie Inc.; n = 11; low testosterone group), 5 g testosterone gel (n = 11; normal testosterone group) or 5 g testosterone gel with letrozole (n = 13; normal testosterone plus letrozole group) for 4 weeks. Study visits were conducted at baseline and at 2, 4 and 10 weeks. The Matsuda index was used to quantify insulin sensitivity.

During the treatment period, there were no differences in insulin resistance (P = .16 in overall repeated measure analysis of variance [RM-ANOVA]), time-by-group interaction for insulin sensitivity (P = .14 in overall RM-ANOVA) or pancreatic beta-cell function (P = .66 in overall RM-ANOVA) between the treatment groups.

Over the treatment period, body weight remained stable for all treatment groups whereas significant differences were observered in the change in fat mass over time (P = .003 in overall RM-ANOVA). Between baseline and week 4, fat mass increased significantly in the placebo group (+1.1 kg; P = .004); there were smaller increases in the low testosterone (+0.7 kg) and the normal testosterone plus letrozole groups (+0.5 kg) and no change in the normal testosterone group.

Between baseline and week 4, significant differences in lean mass were observed across the groups (P = .03 in overall RM-ANOVA). Significant decreases in lean mass between baseline and week 4 were found in the placebo group (=1.2 kg; P = .003) and the low testosterone group (-1.4 kg; P = .01) whereas lean mass was unchanged in the other two groups.

Between baseline and week 4, changes in serum estradiol were a significant determinant of changes in fat mass (P = .016), and changes in serum testosterone levels were related to changes in lean mass (P = .003).

“Our findings indicate that even a very brief period of sex steroid deprivation causes metabolic perturbations characterized predominantly by increased adiposity without changes in body weight,” the researchers wrote. “Changes in body composition are apparent with partial as well as complete sex steroid withdrawal, and findings fail to demonstrate body composition-independent effects of sex steroid deprivation on insulin insensitivity.

Disclosure: Page reports receiving drug supplies for an investigator-initiated study from Besins Healthcare.