Body composition and bone mineral density after ovarian hormone suppression with or without estradiol treatment

Abstract

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 (E2) is unknown. This study aims to evaluate the effects of GnRH(AG) with placebo (PL) or E2 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 E2 (GnRH(AG) + E2, 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) + E2 + 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). 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) + E2 (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) + E2. GnRH(AG) + PL induced a decrease in BMD at the lumbar spine and proximal femur that was prevented by E2. Preliminary data suggest that exercise may have favorable effects on FM, FFM, and hip BMD.

Conclusions: Suppression of ovarian E2 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.

Figure 1

Percent change from baseline in fat-free mass and fat mass measured by DXA in response to 5 months of GnRH_AG therapy with placebo or estradiol treatment (Panel A) and resistance exercise training or no exercise (Panel B). * p<0.05, within-group change; ‡ p <0.05, between-group difference.

Figure 2

Percent change in area of abdominal subcutaneous and visceral fat and thigh muscle and fat measured by CT in response to 5 months of GnRH_AG therapy with placebo or estradiol treatment. * p<0.05, within-group change; ‡ p <0.01, between-group difference.

Figure 3

Percent change from baseline in bone mineral density in response to 5 months of GnRH_AG therapy with placebo or estradiol treatment (Panel A) and resistance exercise training or no exercise (Panel B). * p <0.05, within-group change; ‡ p <0.05, between-group difference.