Objective:

Suppression of ovarian hormones in premenopausal women on gonadotropin-releasing hormone agonist (GnRH AG) therapy can cause fat mass (FM) gain and fat-free mass (FFM) loss. Whether this is specifically caused by a decline in serum estradiol (E 2) is unknown. This study aims to evaluate the effects of GnRH AG with placebo (PL) or E 2 add-back therapy on FM, FFM, and bone mineral density (BMD). Our exploratory aim was to evaluate the effects of resistance exercise training on body composition during the drug intervention.

Methods:

Seventy healthy premenopausal women underwent 5 months of GnRH AG therapy and were randomized to receive transdermal E 2 (GnRH AG+ E 2, n= 35) or PL (GnRH AG+ PL, n= 35) add-back therapy. As part of our exploratory aim to evaluate whether exercise can minimize the effects of hormone suppression, some women within each drug arm were randomized to undergo a resistance exercise program (GnRH AG+ E 2+ Ex, n= 12; GnRH AG+ PL+ Ex, n= 12).

Results:

The groups did not differ in mean (SD) age (36 [8] and 35 [9] y) or mean (SD) body mass index (both 28 [6] kg/m 2). FFM declined in response to GnRH AG+ PL (mean,− 0.6 kg; 95% CI,− 1.0 to− 0.3) but not in response to GnRH AG+ E 2 (mean, 0.3 kg; 95% CI,− 0.2 to 0.8) or GnRH AG+ PL+ Ex (mean, 0.1 kg; 95% CI,− 0.6 to 0.7). Although FM did not change in either group, visceral fat area increased in response to GnRH AG+ PL but not in response to GnRH AG+ E 2. GnRH AG+ PL induced a decrease in BMD at the lumbar spine and proximal femur that was prevented by E 2. Preliminary data suggest that exercise may have favorable effects on FM, FFM, and hip BMD.

Conclusions:

Suppression of ovarian E 2 results in loss of bone and FFM and expansion of abdominal adipose depots. Failure of hormone suppression to increase total FM conflicts with previous studies of the effects of GnRH AG. Further research is necessary to understand the role of estrogen in energy balance regulation and fat distribution.