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Figure1: Is a general biochemical pathway for steroid hormone synthesis in the body. DHEA and Cortisol are both manufactured by the adrenal gland and are the two main secreted products of the hypothalamic-pituitary-adrenal-neuroendocrine axis, which is known to activate the body's response to a physical or emotional stressor.

Figure 1

1. Berr C, Lafont S, Debuire B, Dartigues JF, Bailieu EE. Relationships of dehydroepiandrosterone sulfate in the elderly with functional, psychological, and mental status, and short-term mortality: A French community-based study. PNS Nov 12, 1996; 93(23):13410-13415.

*Quick Summary: This article gives extensive background information on the role that DHEA plays in the body. The experimental portion of this article examines the correlative study of age related decline in DHEA levels in men and women and the effects it may have on functional, psychological and mental status.



"In human beings of both sexes, dehydroepiandrosterone sulfate (DHEAS) circulating in blood is mostly an adrenally secreted steroid whose serum concentration (in the micromolar range and 30¨C50% higher in men than in women) decreases with age, toward ¡Ö20¨C10% of its value in young adults during the 8th and 9th decades. The mechanism of action of DHEA and DHEAS is poorly known and may include partial transformation into sex steroids, increase of bioavailable insulin-like growth factor I, and effects on neurotransmitter receptors. Whether there is a cause-to-effect relationship between the decreasing levels of DHEAS with age and physiological and pathological manifestations of aging is still undecided, but this is of obvious theoretical and practical interest in view of the easy restoration by DHEA administration. Here we report on 622 subjects over 65 years of age, studied for the 4 years since DHEAS baseline values had been obtained, in the frame of the PAQUID program, analyzing the functional, psychological, and mental status of a community-based population in the south-west of France. We confirm the continuing decrease of DHEAS serum concentration with age, more in men than in women, even if men retain higher levels. Significantly lower values of baseline DHEAS were recorded in women in cases of functional limitation (Instrumental Activities of Daily Living), confinement, dyspnea, depressive symptomatology, poor subjective perception of health and life satisfaction, and usage of various medications. In men, there was a trend for the same correlations, even though not statistically significant in most categories. No differences in DHEAS levels were found in cases of incident dementia in the following 4 years. In men (but not in women), lower DHEAS was significantly associated with increased short-term mortality at 2 and 4 years after baseline measurement. These results, statistically established by taking into account corrections for age, sex, and health indicators, suggest the need for further careful trials of the administration of replacement doses of DHEA in aging humans. Indeed, the first noted results of such "treatment" are consistent with correlations observed here between functional and psychological status and endogenous steroid serum concentrations."[1]

2. Weiss EP, Shah K, Fontana L, Lambert CP, Holloszy JO, Villareal DT. Dehydroepiandrosterone replacement therapy in older adults: 1- and 2-y effects on bone. Am J Clin Nutr. 2009 May; 89(5):1459-67.

*Quick Summary: This clinical study examined the role that DHEA concentrations in the blood have on bone mineral density in both men and women. Supplemental administration of DHEA was given in conjunction with Vitamin D and Calcium over a two year period and data was collected on serum steroid levels and bone density verses placebo group.



"Age-related reductions in serum dehydroepiandrosterone (DHEA) concentrations may be involved in bone mineral density (BMD) losses.
The objective was to determine whether DHEA supplementation in older adults improves BMD when co-administered with vitamin D and calcium.
In year 1, a randomized trial was conducted in which men (n = 55) and women (n = 58) aged 65-75 y took 50 mg/d oral DHEA supplements or placebo. In year 2, all participants took open-label DHEA (50 mg/d). During both years, all participants received vitamin D (16 microg/d) and calcium (700 mg/d) supplements. BMD was measured by using dual-energy X-ray absorptiometry. Concentrations of hormones and bone turnover markers were measured in serum.
In men, no difference between groups occurred in any BMD measures or in bone turnover markers during year 1 or year 2. The free testosterone index and estradiol increased in the DHEA group only. In women, spine BMD increased by 1.7 +/- 0.6% (P = 0.0003) during year 1 and by 3.6 +/- 0.7% after 2 y of supplementation in the DHEA group; however, in the placebo group, spine BMD was unchanged during year 1 but increased to 2.6 +/- 0.9% above baseline during year 2 after the crossover to DHEA. Hip BMD did not change. Testosterone, estradiol, and insulin-like growth factor 1 increased in the DHEA group only. In both groups, serum concentrations of bone turnover markers decreased during year 1 and remained low during year 2, but did not differ between groups.
DHEA supplementation in older women, but not in men, improves spine BMD when co-administered with vitamin D and calcium. This trial was registered at clinicaltrials.gov as NCT00182975."[2]

3. Garnero P, Sornay-Rendu E, Claustrat B, Delmas PD. Biochemical markers of bone turnover, endogenous hormones and the risk of fractures in postmenopausal women: the OFELY study. J Bone Miner Res. 2000 Aug; 15(8):1526-36.

*Quick Summary: This study investigated the correlation between several measurable bone markers as well as serum hormone levels verses bone mineral density in postmenopausal women in order to determine risk of bone fractures.



"The mechanisms leading to increased bone loss and skeletal fragility in women with postmenopausal osteoporosis are still poorly understood. Increased bone resorption, low serum estradiol and high serum sex-hormone-binding globulin (SHBG) recently have been reported as predictors of vertebral and hip fractures in elderly women. In a cohort of healthy untreated younger postmenopausal women aged 50-89 years (mean, 64 years), we compared baseline levels of bone markers and endogenous hormones in 55 women who subsequently had a fracture (20 vertebral and 35 peripheral fractures) with levels in the 380 women who did not fracture during a mean 5 years of follow-up. Women with levels in the highest quartile of four bone resorption markers including urinary-free deoxypyridinoline (D-Pyr), urinary type I collagen N-telopeptides (NTX), and urinary and serum type I collagen C-telopeptides (CTX) had about a 2-fold increased risk of fractures compared with women with levels in the three lowest quartiles with relative risk (RR) and 95% CI of 1.8 (1.0-3.4) for free D-Pyr, 1.7 (0.9-3.2) for urinary NTX, 2.3 (1.3-4.1) for urinary CTX, and 2.1 (1.2-3.8) for serum CTX. Serum levels of bone alkaline phosphatase (BAP) in the highest quartile were associated with an RR of fracture of 2.4 (1.3-4.2). Women with serum levels of estradiol and dehydroepiandrosterone (DHEA) sulfate in the lowest quartile had an RR of fracture of 2.2 (1.2-4.0) and 2.1 (1.2-3.8), respectively. Increased levels of SHBG and intact parathyroid hormone (PTH) were moderately associated with an increased risk of fracture. Similar results were obtained when the analysis was restricted to symptomatic vertebral and nonvertebral fractures. Adjustment of biochemical markers by hormone levels did not significantly alter the results. Women with both high bone resorption markers and low estradiol (or low DHEA sulfate) had a higher risk of fracture with RRs of 3.0-3.3 (p < 0.001). After adjustment for bone mineral density (BMD) of the hip, spine, radius, or total body, bone markers and hormones were still predictive of fracture risk with similar RRs. We conclude that high levels of some biochemical markers of bone turnover, low serum estradiol, low DHEA sulfate, high SHBG, and high PTH are associated with increased risk of osteoporotic fracture in postmenopausal women, independently of each other and of BMD. The mechanism by which some postmenopausal women have an increased rate of bone turnover leading to an increased risk of fracture remains to be elucidated."[3]

4. Feldman HA, Johannes CB, Araujo AB, Mohr BA, Longcope C, McKinlay JB. Low dehydroepiandrosterone and ischemic heart disease in middle-aged men: prospective results from the Massachusetts Male Aging Study. Am J Epidemiol. 2001 Jan 1; 153(1):79-89.

*Quick Summary: This paper has identified the correlation between low DHEA levels in men and the subsequent incidences of ischemic heart disease. The study used the 1,709 male participants from the Massachusetts Male Aging Study to conduct the 9 year follow up study that determined such a correlation.



"The adrenal steroid dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) have been characterized as "protective" against ischemic heart disease (IHD), especially in men, on the basis of sparse epidemiologic evidence. The authors used data from the Massachusetts Male Aging Study, a random sample prospective study of 1,709 men aged 40-70 years at baseline, to test whether serum levels of DHEA or DHEAS could predict incident IHD over a 9-year interval. At baseline (1987-1989) and follow-up (1995-1997), an interviewer-phlebotomist visited each subject in his home to obtain comprehensive health information, body measurements, and blood samples for hormone and lipid analysis. Incident IHD between baseline and follow-up was ascertained from hospital records and death registries, supplemented by self-report and evidence of medication. In the analysis sample of 1,167 men, those with serum DHEAS in the lowest quartile at baseline (<1.6 microg/ml) were significantly more likely to incur IHD by follow-up (adjusted odds ratio = 1.60, 95 percent confidence interval: 1.07, 2.39; p = 0.02), independently of a comprehensive set of known risk factors including age, obesity, diabetes, hypertension, smoking, serum lipids, alcohol intake, and physical activity. Low serum DHEA was similarly predictive. These results confirm prior evidence that low DHEA and DHEAS can predict IHD in men."[4]

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