Dehydroepiandrosterone (DHEA), DHEA sulfate, and aging: Contribution of the DHEAge Study to a sociobiomedical issue

Abstract

The secretion and the blood levels of the adrenal steroid dehydroepiandrosterone (DHEA) and its sulfate ester (DHEAS) decrease profoundly with age, and the question is posed whether administration of the steroid to compensate for the decline counteracts defects associated with aging. The commercial availability of DHEA outside the regular pharmaceutical-medical network in the United States creates a real public health problem that may be resolved only by appropriate long-term clinical trials in elderly men and women. Two hundred and eighty healthy individuals (women and men 60 -79 years old) were given DHEA, 50 mg, or placebo, orally, daily for a year in a double-blind, placebo-controlled study. No potentially harmful accumulation of DHEAS and active steroids was recorded. Besides the reestablishment of a ''young'' concentration of DHEAS, a small increase of testosterone and estradiol was noted, particularly in women, and may be involved in the significantly demonstrated physiological-clinical manifestations here reported. Bone turnover improved selectively in women >70 years old, as assessed by the dual-energy x-ray absorptiometry (DEXA) technique and the decrease of osteoclastic activity. A significant increase in most libido parameters was also found in these older women. Improvement of the skin status was observed, particularly in women, in terms of hydration, epidermal thickness, sebum production, and pigmentation. A number of biological indices confirmed the lack of harmful consequences of this 50 mg͞day DHEA administration over one year, also indicating that this kind of replacement therapy normalized some effects of aging, but does not create ''supermen͞women'' (doping). C urrently, many strategies for delaying͞diminishing physiological deficits associated with aging are offered to a public, whose mean life expectancy is increasing, without appropriate scientific justifications and͞or medical precautions. Because of the profound age-related decrease of blood levels of the steroid dehydroepiandrosterone (DHEA; prasterone) and its sulfate ester (DHEAS), both essentially secreted by adrenals in human beings (1-5), it has been suggested that there is an ''adrenopause'' characterized by low value of blood DHEA(S) with maintenance of cortisol level. If this condition is involved in some impairment of health, the compensatory administration of DHEA may be of benefit, as is estrogen in women after menopause. The commercial availability of DHEA outside the regular pharmaceutical-medical network in the United States (because of passage of the Dietary Supplement Health and Education Act of 1994) creates a real public health problem. Not only may the quality of, and sometimes the very presence of, DHEA in some samples on sale in supplement stores or supermarkets be questioned, but the usage of a product in the absence of medical indication and supervision could be improper for a number of consumers. Extravagant publicity based on fantasy (''fountain of youth,'' ''miracle pill'') or pseudoscientific assertion (''moth...

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

“…In this study, the daily co-administration of 50 mg DHEA did not give rise to safety concerns, as supported by data from the literature [54][55][56][57][58][59][60][61]. As demonstrated also in this study…”

Low Serum DHEAS Predicts Increased Fracture Risk in Older Men: The MrOS Sweden Study

“…This is consistent with the marginal association between serum DHEAS and BMD observed in the present study and no or limited site-specific increases in BMD in DHEA intervention studies. (9)(10)(11)(12)(13)(14) Also, our observed associations were only slightly attenuated by physical activity or muscle strength, which makes it unlikely that muscle mass mediates the impact of DHEAS on fracture risk. This is in agreement with the lack of effect of DHEA on muscle mass in treatment studies.…”

“…This study is, to the best of our knowledge, the first one to describe the associations between serum DHEAS levels and incident fracture risk in older men. Previous studies examining the associations between serum DHEAS and BMD (4,(6)(7)(8) or the effect of DHEA treatment on BMD (9)(10)(11)(12)(13)(14) reported conflicting findings, with the positive results, if any, being small, sitespecific, and not reproducible. In our cohort, we found a marginal association between serum DHEAS levels and BMD Cox proportional hazards regression models for a base model (adjusted for age, body mass index, prevalent fractures, morning sample yes/no, and MrOS Sweden site) and base models with additional adjustments for confounding risk factors for fracture (smoking, alcohol use, calcium intake, falls during the past 12 months, prevalent diseases [diabetes, stroke, chronic obstructive pulmonary disease, rheumatoid arthritis, and cancer], and glucocorticoid use), femoral neck BMD and/or physical performance variables (grip strength, daily physical activity) or exclusion of men with a follow-up time of 1 year or less.…”

“…Most studies reported no significant associations, (6)(7)(8) whereas Khosla and colleagues showed positive univariate correlations between serum DHEAS and several BMD sites in a populationbased, age-stratified sample of 346 Rochester men. (4) Intervention studies, mostly in men with low baseline DHEAS levels (below $1.50 mg/mL), showed no beneficial effect of DHEA treatment on BMD in men, (9)(10)(11)(12)(13) except for one study reporting a modest increase in femoral neck BMD after 2 years of treatment. (14) These data are in agreement with a recent metaanalysis concluding that DHEA supplementation in elderly men has no effect on BMD.…”

“…(14) These data are in agreement with a recent metaanalysis concluding that DHEA supplementation in elderly men has no effect on BMD. (15) Modest positive effects of supplemental DHEA on BMD were reported in postmenopausal women, (10)(11)(12)(13)(14)16) but a meta-analysis of seven studies indicated no significant effect of DHEA treatment on BMD in women. (17) DHEA supplementation in adolescent and young women with anorexia nervosa, who characteristically have subnormal serum DHEA and estrogen levels, maintained BMD, but there was no significant increase after accounting for the accompanying weight gain.…”