Dhea Replacement Therapy in Hypoadrenal Women

Adrenally produced dehydroepiandrosterone (DHEA) and its sulfated ester (DHEA-S) are the most abundant steroid hormones found in the circulation. These hormones peak during the late teenage years and steadily decrease by 10% per decade thereafter. As a result, healthy elderly men and women have lower DHEA and DHEA-S levels than younger healthy individuals. Levels are low or almost undetectable in women with primary hypoadrenalism due to Addison disease or in those who have undergone bilateral adrenalectomies. Although DHEA is not required for survival, it is known to be a precursor of sex hormones and is converted into androgens and estrogens in peripheral tissues. Its other physiologic functions in healthy adults remain unclear. A recent review of the epidemiological associations and effects of replacement of DHEA on body composition, bone density, and muscle function has shown conflicting reports. Studies have examined the effect of DHEA replacement on skeletal muscle strength and lean body mass in patients with low DHEA levels, including those who are hypoadrenal and healthy elderly people. The study of elderly people with low DHEA-S levels showed no improvement of physical performance, body composition, insulin sensitivity, or bone density. However, the studies of elderly patients cannot be translated to hypoadrenal patients, who have markedly lower DHEA-S levels. Levels of DHEA-S decrease with age, reducing skeletal muscle oxidative capacity, muscle protein synthesis, and exercise performance. Whether DHEA replacement improves these muscle functions in hypoadrenal women with low DHEA-S levels remains to be determined. The low or absent levels of DHEA or DHEA-S found in women who have Addison disease or who have undergone adrenalectomy may contribute to the decline in their muscle mass and function. Although short-term resistance exercise programs significantly improve skeletal muscle mass, small changes in muscle mass after short-term therapy with DHEA may not have been detected and so not reported in previous studies. Measurement of muscle protein synthesis responds more intensely to short-term intervention and may be a better method of detecting these changes. Recent studies of DHEA replacement in an addisonian population showed an increase in truncal lean body mass, and other OBJECTIVE: To determine whether dehydroepiandrosterone (DHEA) replacement therapy in hypoadrenal women improves performance, muscle protein accretion, and mitochondrial functions.