Effects of replacement dose of dehydroepiandrosterone in men and women of advancing age.

Abstract

Aging in humans is accompanied by a progressive decline in the secretion of the adrenal androgens dehydroepiandrosterone (DHEA) and DHEA sulfate (DS), paralleling that of the GH-insulin-like growth factor-I (GH-IGF-I) axis. Although the functional relationship of the decline of the GH-IGF-I system and catabolism is recognized, the biological role of DHEA in human aging remains undefined. To test the hypothesis that the decline in DHEA may contribute to the shift from anabolism to catabolism associated with aging, we studied the effect of a replacement dose of DHEA in 13 men and 17 women, 40-70 yr of age. A randomized placebo-controlled cross-over trial of nightly oral DHEA administration (50 mg) of 6-month duration was conducted. During each treatment period, concentrations of androgens, lipids, apolipoproteins, IGF-I, IGF-binding protein-1 (IGFBP-1), IGFBP-3, insulin sensitivity, percent body fat, libido, and sense of well-being were measured. A subgroup of men (n = 8) and women (n = 5) underwent 24-h sampling at 20-min intervals for GH determinations. DHEA and DS serum levels were restored to those found in young adults within 2 weeks of DHEA replacement and were sustained throughout the 3 months of the study. A 2-fold increase in serum levels of androgens (androstenedione, testosterone, and dihydrotestosterone) was observed in women, with only a small rise in androstenedione in men. There was no change in circulating levels of sex hormone-binding globulin, estrone, or estradiol in either gender. High density lipoprotein levels declined slightly in women, with no other lipid changes noted for either gender. Insulin sensitivity and percent body fat were unaltered. Although mean 24-h GH and IGFBP-3 levels were unchanged, serum IGF-I levels increased significantly, and IGFBP-1 decreased significantly for both genders, suggesting an increased bioavailability of IGF-I to target tissues. This was associated with a remarkable increase in perceived physical and psychological well-being for both men (67%) and women (84%) and no change in libido. In conclusion, restoring DHEA and DS to young adult levels in men and women of advancing age induced an increase in the bioavailability of IGF-I, as reflected by an increase in IGF-I and a decrease in IGFBP-1 levels. These observations together with improvement of physical and psychological well-being in both genders and the absence of side-effects constitute the first demonstration of novel effects of DHEA replacement in age-advanced men and women.

Effects of Low- and High-Nicotine Cigarette Smoking on Mood States and the HPA Axis in Men

“…In a 6-week, placebo-controlled cross-over trial in men and women with major or minor depression, DHEA administration (90 mg/ day for 3 weeks; 450 mg/day for 3 weeks) significantly improved mood and depression ratings in comparison to pretreatment baseline and placebo conditions (Schmidt et al, 2005). In the present study, peak levels of DHEA after smoking a high-nicotine cigarette (21.1372.55 ng/ml or 73.3278.84 nmol/l or 2113.0 ng/dl) were over four times higher than average DHEA levels achieved after 3 months of DHEA replacement in men (14.7271.4 nmol/l) (Morales et al, 1994) and over twice as high as average DHEA levels after 6 weeks of high-dose DHEA treatment (1047.27709.1 ng/dl) (Schmidt et al, 2005). Taken together, these data suggest that increases in DHEA levels may contribute to the mood-elevating effects reported after cigarette smoking.…”

“…In a 6-month, placebo-controlled cross-over trial, DHEA administration at physiological levels (50 mg, p.o.) consistently increased energy and improved mood and feelings of well-being in both men and women (Morales et al, 1994). In a 6-week, placebo-controlled cross-over trial in men and women with major or minor depression, DHEA administration (90 mg/ day for 3 weeks; 450 mg/day for 3 weeks) significantly improved mood and depression ratings in comparison to pretreatment baseline and placebo conditions (Schmidt et al, 2005).…”

“…DHEA formulations are sold over the counter as dietary supplements, and DHEA is believed to improve a sense of well-being and sexuality in the elderly, and in persons with adrenal insufficiency. Although the evidence is conflicting (see for review Spark, 2002), two placebo-controlled clinical trials support the notion that DHEA treatment improves mood and alleviates depression (Morales et al, 1994;Schmidt et al, 2005). In a 6-month, placebo-controlled cross-over trial, DHEA administration at physiological levels (50 mg, p.o.)…”

Endocrine and metabolic changes in human aging

“…In rodents, major effects of DHEA have been reported on memory (41) and the immune system (42). In the absence of adrenal insufficiency (43), studies in humans have been controversial, with high dose DHEA (100 mg per day) increasing muscle mass in males (44) but having varied effects on immune function (44) and behavior (45,46). Pregnenolone, the precursor adrenal hormone, also declines with age (47).…”

Restoring testosterone levels by adding dehydroepiandrosterone to a drospirenone containing combined oral contraceptive: II. Clinical effects

“…Therefore, by normalizing androgen levels, especially T, the negative effects of COCs on sexual function and mood could be ameliorated. Maintaining physiological androgen levels in women using a COC may be achieved by the addition of the natural human adrenal hormone dehydroepiandrosterone (DHEA); DHEA is partially metabolized into T [29][30][31] and could be incorporated into a COC pill because it is orally bioavailable [32].…”