Sex-Specific Effects of Dehydroepiandrosterone (DHEA) on Bone Mineral Density and Body Composition

A Pooled Analysis of Four Clinical Trials

Catherine M. Jankowski; Pamela Wolfe; Sarah J. Schmiege; K. Sreekumaran Nair; Sundeep Khosla; Michael Jensen; Denise von Muhlen; Gail A. Laughlin; Donna Kritz-Silverstein; Jaclyn Bergstrom; Richele Bettencourt; Edward P. Weiss; Dennis T. Villareal and Wendy M. Kohrt

Disclosures

Clin Endocrinol. 2019;90(2):293-300. 

In This Article

Results

Baseline Characteristics

The pooled ITT cases from the four RCTs demonstrated a balanced representation of sex and allocation to treatment arms (P = 0.77; Table 1). A total of 295 women (144 DHEA, 151 placebo) and 290 men (145 DHEA, 145 placebo) were included. Of the 468 cases with evaluable T-scores for BMD, 138 women and 98 men had low bone mass and 29 women and 11 men had osteoporosis according to the criteria of the International Society of Clinical Densitometry.[11] There were significant differences across RCTs in baseline body weight and BMI (women only), FFM, BMD, DHEAS (men only), T, E2, SHBG, IGF-1 and IGFBP-3 (Table 2).

Changes in Hormones

The absolute and relative changes in sex hormones and IGF-1 pooled across RCTs are in Table 3 and Supporting Information Table S1, respectively.

When expressed as absolute change from baseline to 12 months, serum DHEAS increased by 231 μg/dL (6.24 μmol/L) and 269 μg/dL (7.26 μmol/L) in DHEA-treated women and men, respectively (both P < 0.001 vs placebo; Table 3). In DHEA-treated women, there were increases in serum T, E2 and IGF-1 and a decrease in SHBG (all P < 0.001). In DHEA-treated men, there were increases in serum E2 (P < 0.001) and IGF-1 (P = 0.04) and a decrease in SHBG (P = 0.001). When expressed as the per cent of change from baseline (Table S1), the statistical results were similar to those for absolute changes.

Differences among the RCTs in the hormone responses to DHEA were not statistically compared because there was considerable variability among the RCTs in the responses. For example, serum E2was increased in response to DHEA in men in the Mayo, CU-AMC and WUSM RCTs, but not the UCSD RCT.

Changes in BMD and Body Composition

In women, DHEA therapy increased or attenuated the decrease in lumbar spine, total hip and subtrochanter BMD when compared with the placebo group (all P < 0.01; Figure 1). In contrast, the changes in BMD were not different between DHEA- and placebo-treated men.

Figure 1.

Between-group differences (DHEA minus placebo) in the 12-month changes in lumbar spine, total hip, femoral neck and trochanter BMD. Estimates were adjusted for baseline and site for pooled results. Values are mean ± SE. **P < 0.01; ***P < 0.001

In women, there was a nonsignificant increase in FFM (P = 0.02) in response to DHEA when compared with placebo and no change in FM. In men only, there was no change in FFM and a decrease in FM (P = 0.006) in response to DHEA when compared with placebo (Figure 2).

Figure 2.

Between-group differences (DHEA minus placebo) in the 12-month changes in fat-free mass and fat mass. Estimates were adjusted for baseline and site for pooled results. Values are mean ± SE. *P < 0.05; **P < 0.01

Adverse Events

Different categorization of events across the four trials precluded pooling of these data. In the summaries of adverse events provided in the original trial publications, more cardiovascular events occurred in participants in the DHEA-treated groups in two trials.[8,9]

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