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Increases in hip BMD mediated by increase in serum estradiol

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In adults aged 60 to 88 years undergoing dehydroepiandrosterone replacement, increases in hip bone mineral density were mediated primarily by increases in serum estradiol rather than direct effects of dehydroepiandrosterone sulfate.

The researchers randomly assigned men (n=61) and women (n=58) with low serum DHEA sulfate levels to 50 mg oral DHEA per day or placebo for 12 months.

The average changes in hip and spine BMD in the DHEA group were 1.1% to 1.6%, according to the researchers. DHEA replacement increased serum DHEA sulfate, testosterone, free testosterone index, estrone, estradiol, free testosterone and estrogen indices, and insulin-like growth factor I in women (P<.001). DHEA replacement decreased sex hormone–binding globulin in women (P=.02).

In men, DHEA replacement increased DHEA sulfate, estrone, free estrogen and estrogen indices (P<.001) and estradiol (P=.02). DHEA replacement also decreased sex hormone–binding globulin in men (P=.037), according to the researchers.

“The changes in total and regional hip BMD were associated with 12-month estradiol (all P<.001) and free testosterone and estrogen indices (all P<.013),” they wrote. “The effects of DHEA treatment were eliminated by adjustment for 12-month estradiol.”

J Clin Endocrinol Metab. 2008;93:4767-4773.

The researchers concluded that the DHEA treatment effect can be attributed primarily to increases in circulating estrogens. This conclusion, in my opinion, is not warranted by the reported data, as there is no basis for asserting a causal link between the changes in estradiol and the change in BMD. This study is unlikely to result in changes in clinical practice, unless more robust confirmatory data are generated in the future.