Short-Term Sex Steroid Withdrawal in Men Adversely Affects Body Composition

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Even short-term testosterone and estrogen withdrawal may increase fat mass in men.
Even short-term testosterone and estrogen withdrawal may increase fat mass in men.

Healthy men who underwent sex steroid withdrawal began to show symptoms of body composition change as early as 4 weeks into treatment, according to a study published in the Journal of Clinical Endocrinology & Metabolism.

“Our results are consistent with previous data demonstrating a substantial role of estradiol in the regulation of adiposity in men and show for the first time that changes in fat mass are evident as soon as 4 weeks after estrogen withdrawal,” Jing Chao, MD, from the Center for Research in Reproduction and Contraception at the University of Washington School of Medicine, and colleagues wrote in their study. “Further, our findings suggest that even transient sex steroid deficiency may yield metabolic aberrations that persist beyond normalization of circulating sex steroid levels.”

In the study (ClinicalTrials.gov identifier: NCT01686828), Dr Chao and colleagues evaluated 56 men aged 15  to 55 years who underwent varying levels of estrogen withdrawal after receiving a gonadotropin-releasing hormone (GnRH) antagonist acyline. Patients in the Castrate group received a placebo gel, while patients in the low T/E group and normal T/E groups received daily 1.25 g and 5 g of testosterone gel for 4 weeks, respectively. Patients in the normal T/low E group received 5 g of testosterone gel with letrozole daily. The researchers analyzed body composition at baseline and at final follow-up.

At 2 weeks, the researchers found the Castrate group's serum total testosterone levels decreased (0.98 ± 1.5 ng/mL) from baseline (4.9 ± 1.5 ng/mL), while 17β-estradiol serum levels decreased to 5 pg/mL from 25 pg/mL at baseline. Patients in the low T/E group had decreased serum total testosterone levels of 3.0 ± 1.1 ng/mL at 2 weeks from 5.4 ± 1.6 ng/mL at baseline, and 17β-estradiol serum levels decreased to 12 pg/mL from 27 pg/mL. Patients in the normal T/E and normal T/low E groups showed similar testosterone levels from baseline at week 2; however, the normal T/low E group showed a significant suppression of serum estradiol at week 2 from the letrozole.

While there was no weight change in any treatment groups during the 4-week period, patients in the Castrate group experienced a significant increase in fat mass (+1.1 ± 0.8 kg; P=.004) from baseline, with smaller fat mass increases seen in the low T/E (+0.7 ± 0.8 kg) and normal T/low E groups (+0.5 ± 0.8 kg). There was no change in fat mass in the normal T/E group.

The researchers also saw a decrease in lean mass during the 4-week study period, with patients in the Castrate (–1.2 ± 1.0 kg; P=.003) and low T/E groups (–1.4 ± 1.5 kg; P=.01) showing a significant decrease.

Results also demonstrated time-by-group interactions for fat mass (P=.001) and lean mass (P=.03). The former was primarily influenced by estrogen exposure in linear regression analysis (P=.016) while the latter was influenced by androgen exposure (P=.003).

Disclosures: Transdermal and testosterone gel were provided by AbbVie.

Reference

  1. Chao J, Rubinow KB, Kratz M, Amory JK, Matsumoto AM, Page St. Short-term estrogen withdrawal increases adiposity in healthy men. J Clin Endocrinol Metab. 2016. doi:10.1210/jc.2016-1482.
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