Oral DHEA Research Articles

Effect of Oral Administration of Dehydroepiandrosterone on PCOS-Like Phenotype of Female C57BL/6 Mice

We aim to evaluate the efficacy and optimal dose of orally administered DHEA in the PCOS mice model by assessing their ovarian morphology and serum FSH, LH, and testosterone levels. Female C57BL/6 mice were divided into a control group (n=5, received daily injections of 0.2 ml sesame oil) and an experimental group, which was further classified into 1) D-45 group (n=5), 2) D-60 (n=5), and 3) D-90 group (n=5) that were treated with 45, 60, and 90 mg/Kg body weight of oral DHEA. After modelling, mice in the control group had a regular estrous cycle, while mice in all experimental groups had a disturbed estrous cycle. Ovarian histology showed several growing follicles and some corpora lutea (CL) in the control, D-60, and D-90 groups. However, some large antral follicles and decreased CL were observed in the D-45 group. Serum FSH was significantly lower in the D-45 group than in the control group (3.73 ± 0.12 vs. 5.28 ± 0.31 mIU/mL, P<0.01), but D-60 and D-90 groups had a similar FSH level to the control group (P>0.05). The serum level of LH and testosterone were significantly elevated in the D-45 group than in the control group (2.52 ± 0.43 vs. 1.30 ± 0.33 mIU/mL, P<0.01 and 1.80 ± 0.32 vs. 1.24 ± 0.23 ng/mL, P<0.01, respectively). Still, the level of LH and testosterone in the D-60 and the D-90 groups was comparable to the control group (P>0.05). Our study suggests that oral administration of DHEA is efficacious in establishing PCOS-like phenotype in mice with the suggested optimal dosage of 45 mg/Kg body weight.

Alert to US physicians: DHEA, widely used as an OTC androgen supplement, may exacerbate COVID-19.

Androgens play a fundamental role in the morbidity and mortality of COVID-19, inducing both the ACE-2 receptor to which SARS-CoV-2 binds to gain entry into the cell, and TMPRS22, the transmembrane protease that primes the viral spike protein for efficient infection. The United States stands alone among developed nations in permitting one androgen, oral DHEA, to be freely available OTC and online as a 'dietary supplement'. DHEA is widely used by males in the US to offset the age-related decline in circulating androgens. This fact may contribute to the disparate statistics of COVID-19 morbidity and mortality in this country. In regulatory antithesis, every other developed nation regulates DHEA as a controlled substance. DHEA is an extremely potent inhibitor of glucose-6-phosphate dehydrogenase (G6PD), with uniquely unstable uncompetitive inhibition kinetics. This has particular relevance to COVID-19 because G6PD-deficient human cells have been demonstrated to be exceptionally sensitive to infection by human coronavirus. Because DHEA is lipophilic and freely passes into cells, oral DHEA bypasses the normal controls regulating androgen biology and uncompetitive G6PD inhibition. DHEA's status as a 'dietary supplement' means that no clinical trials demonstrating safety have been performed, and, in the absence of physician supervision, no data on adverse events have been collected. During the current pandemic, the unrestricted availability of oral DHEA as a 'dietary supplement' cannot be considered safe without proof from placebo-controlled clinical trials that it is not contributing to the severity of COVID-19. US physicians may therefore wish to query their patients' use of DHEA.

Lack of effect of short-term DHEA supplementation on the perimenopausal ovary†.

Dehydroepiandrosterone (DHEA) hormonal supplementation can improve oocyte quality in women with diminished ovarian function. However, it is unclear whether DHEA supplementation can also enhance ovarian function during the perimenopause (i.e., when the number of follicles in the ovary has undergone a marked reduction). To address this question, we examined the impact of 2.5-months of daily 5-mg oral DHEA supplementation on the number of ovarian follicles and the concentration of anti-Müllerian hormone (AMH) in perimenopausal rhesus macaques. Like women, these long-lived nonhuman primates have ~ 28-day menstrual cycles and eventually undergo menopause. They also show similar age-related neuroendocrine changes, including a marked decrease in circulating concentrations of DHEA and DHEA sulfate (DHEAS). Our experimental design involved the following three groups of animals (N=6 per group): Young adult (mean age=11.6years), Old control (mean age=23.1years), and Old DHEA-treated (mean age=23.5years). Histological examination of the ovaries revealed a significant age-related decrease in the mean number of primordial follicles despite DHEA supplementation. Moreover, AMH concentrations within the ovaries and circulation, assessed by Western analysis and ELISA, respectively, showed significant age-related decreases that were not attenuated by DHEA supplementation. Taken together, these results fail to show a clear effect of short-term physiological DHEA supplementation on the perimenopausal ovary. However, they do not exclude the possibility that alternative DHEA supplementation paradigms (e.g., involving an earlier start date, longer duration and using pharmacological doses) may extend reproductive potential during aging.

Dehydroepiandrosterone supplementation improves ovarian reserve and pregnancy rates in poor responders.

We investigated whether DHEA supplementation had an impact on ovarian reserve parameters and pregnancy rates in patients with poor ovarian response (POR) and primary ovarian insufficiency (POI). A total of 34 people, 6 patients with POI and 28 patients with POR, were included in the study. The patients in the POR group consisted of two different groups: diminished ovarian reserve (DOR) and premature ovarian failure (PMOF). Patients in the POI and POR group were given 50 mg DHEA supplementation daily for 5 months. The primary outcome was to determine spontaneous clinical pregnancy rates. The monthly changes in the serum hormone levels and AFC were recorded for five months. AMH levels were also measured before and after treatment. The total follow-up time was 152 cycles. The number of pregnancies during the follow-up period was 9. The ratio of pregnancies to the number of patients was 26.5% and the rate per cycle was 5.9%. While 8 of 9 pregnancies resulted in a live birth, one resulted in a miscarriage. The rate of abortion was 11.1%. The mean AFC was 0 to 5 before treatment. Following DHEA administration, a significant increase was detected in 30.8% of the patients. There was an increase in AMH levels after DHEA, but this was not significant. The live birth rate and pregnancy rate per cycle were significantly higher in POR patients than those in POF. Patients with POF had no pregnancy. Although the PMOF patients were younger than the DOR patients, the rate of pregnancy (36% vs. 29%), and pregnancy rates per cycle (8.5% vs. 6.35%) were higher in the DOR group. The rates of live birth were the same in the PMOF and DOR groups (29% vs. 29%). Oral DHEA supplementation improves both ovarian reserve and pregnancy rates in women with POR.

Development and Validation of an Enzyme Immunoassay for Fecal Dehydroepiandrosterone Sulfate in Japanese Macaques (Macaca fuscata)

Measuring hormonal profiles is important in monitoring stress, physical fitness, and reproductive status in primates. Noninvasive methods have been used to measure several steroid hormones in primates without causing them stress. However, few studies have used feces or urine to measure dehydroepiandrosterone sulfate (DHEAS), an important precursor of sex steroids that has been studied as a biomarker of aging, pregnancy, and stress in humans and nonhuman primates. We developed an enzyme immunoassay to detect DHEAS in the feces of Japanese macaques (Macaca fuscata). Our subjects included eight singly housed Japanese macaques. To validate the assay, we administrated oral DHEA to one male and one female macaque, collected their feces, and measured DHEAS levels over time. Given that DHEAS is related to gonadal steroids and the stress response, we also measured DHEAS concentrations in response to adrenal (adrenocorticotropic hormone [ACTH]) and gonadal (human chorionic gonadotropin [hCG]) stimulation. Our assay successfully detected DHEAS in Japanese macaque feces, and levels of DHEAS were associated with the amount of DHEA ingested. Parallelism and accuracy tests revealed that fecal extracts were reliable measures of DHEAS. Neither ACTH nor hCG challenge appeared to affect DHEAS levels. The method we describe is less expensive than that using the commercially available kits and is applicable to investigations involving aging, stress, and reproduction in Japanese macaques.

DHEA supplementation improves endometrial HOXA-10 mRNA expression in poor responders.

Objective:The study was planned to investigate whether DHEA supplementation had an impact on endometrial receptivity in women who were poor responders (POR).Material and Methods:Twenty-eight POR women who were undergoing hysteroscopy and five fertile control subjects were included. The POR women were equally subdivided into two separate groups as patients who were currently using DHEA and those who were not. Endometrial samples of the subjects were obtained during hysteroscopy at the late follicular phase. Expression levels of endometrial HOXA-10, HOXA-11, and LIF mRNA were measured with the using real-time polymerase chain reaction. Spontaneous clinical pregnancy rates were also noted.Results:Compared with POR women who were not given DHEA, upregulated endometrial HOXA-10 (7.33-fold) and HOXA-11 (2.39-fold) mRNA expression were detected in POR women on DHEA. The increase in HOXA-10 mRNA was significant (p<0.03). The fold increase in HOXA-11 mRNA was found as 2.39, which indicated a positive upregulation. However, this fold increment was insignificant (p<0.45). An insignificant increase in spontaneous clinical pregnancy rates in POR women on DHEA (53.3%) was observed compared with POR women who were not given DHEA (43.8%).Conclusion:Oral DHEA supplementation in POR upregulates endometrial HOXA-10 mRNA expression, which is known to positively modulate endometrial receptivity.

Potential prevention by oral DHEA of superficial tears in elderly atrophic skin

Oral DHEA improves skin hydration and sebum production as well as bone mineral density in older patients while limiting progression of their skin atrophy. Topical DHEA cream stimulates local collagen production. Trials of oral DHEA should be undertaken to examin their potential for preventing tears in fragile aging skin.

Null Effect Of Dhea-s On Muscle Strength And Serving Performance In Young Women

PURPOSE: To determine whether oral DHEA supplementation can increase muscle strength and motor performance. METHODS: A randomized placebo-controlled crossover study was conducted among 10 young women (aged 20.2) with a washout period of one month. DHEA (25 mg per day) or Placebo was orally provided one day before assessments. RESULTS: DHEA supplementation significantly increased plasma DHEA-S level from 0.9 to 1.5 microgram/mL. However, no significant change in average hip isokinetic strength, tennis serving accuracy, and ball serving speed. DHEA supplementation did not affect total mood disturbance and blood pressure among participants. Interestingly, monthly variations in hip muscle strength and ball serving speed decreased during DHEA trial. CONCLUSIONS: Despite an existing relationship between plasma DHEA-S and motor performance, we fail to find significant changes in motor performance and mood state with DHEA supplementation.

Androgen Supplementation During Aging: Development of a Physiologically Appropriate Protocol

Men show an age-related decline in the circulating levels of testosterone (T) and dehydroepiandrosterone sulfate (DHEAS). Consequently, there is interest in developing androgen supplementation paradigms for old men that replicate the hormone profiles of young adults. In the present study, we used old (21-26 years old) male rhesus monkeys as a model to examine the efficacy of an androgen supplementation paradigm that comprised oral T administration (12 mg/kg body weight, dissolved in sesame oil/chocolate) in the evening, and two oral DHEA administrations, 3 hr apart (0.04 mg/kg body weight, dissolved in sesame oil/chocolate) in the morning. After 5 days of repeated hormone supplementation, serial blood samples were remotely collected from each animal hourly across the 24-hr day, and assayed for cortisol, DHEAS, T, 5α-dihydrotestosterone (DHT), estrone (E1), and 17β-estradiol (E2). Following androgen supplementation, T levels were significantly elevated and this was associated with a more sustained nocturnal elevation of T's primary bioactive metabolites, DHT and E1 and E2. Plasma DHEAS levels were also significantly elevated after androgen supplementation; DHEAS levels rose in the early morning and gradually declined during the course of the day, closely mimicking the profiles observed in young adults (7-12 years old); in contrast, cortisol levels were unaltered by the supplementation. Together the data demonstrate a non-invasive androgen supplementation paradigm that restores youthful circulating androgen levels in old male primates. Because this paradigm preserves the natural circulating circadian hormone patterns, we predict that it will produce fewer adverse side effects, such as perturbed sleep or cognitive impairment.

Administration of DHEA augments progesterone production in a woman with low ovarian reserve being transplanted with cryopreserved ovarian tissue

In recent years cryopreservation of ovarian tissue prior to potentially gonadotoxic treatment for malignant disease has proved to be an option for preservation of the reproductive function including fertility [1]. Following successful cancer treatment women have chosen to have transplantation of their frozen-thawed tissue if ovarian failure occurred as a consequence of cancer treatment. The autotransplanted tissue has in various centers resulted in the re-establishment of ovarian function leading to the return of fertility and the birth of healthy children [2, 3]. However, the ovarian reserve in the transplanted tissue typically is very low as currently only a limited number of follicles survive the entire procedure including freezing, thawing and transplantation [4]. This diminished reserve is reflected by persistent low levels of AMH [4], limiting the efficacy of controlled ovarian stimulation (COS) with exogenous FSH. In terms of fertility treatment, the women who have had frozen/thawed ovarian tissue transplanted often resemble poor responder patients and patients of advanced reproductive age. Attempts to augment the number of developing follicles by administration of oral DHEA for some months in the latter category of women have been reported [5–7], there being a growing literature describing a higher oocyte yield following COS and oocytes showing a better quality and thereby improving the reproductive outcome [5–7]. The particular mechanism by which DHEA may enhance follicle survival and growth has not yet been fully elucidated, but conversion of DHEA to androgens and an androgen priming effect on early stages of follicular development leading to an increased FSH receptor expression is one possible mechanism [8]. Although the vast majority of DHEA in the body is produced by the adrenals one obstacle in defining a more precise function of DHEA in improving follicle recruitment is the fact that the circulating DHEA is the sum of the local productions in the ovaries and those of adrenal glands [9]. In this study we observed the ovarian and endocrine events following DHEA administration in a woman, who had normal adrenal function but with very low ovarian reserve consequent to transplantation of frozen/thawed ovarian tissue, being postmenopausal at the time of transplantation. Only a fraction of frozen/thawed tissue from one ovary had been grafted with subsequent low ovarian reserve and evidenced by few follicles. This situation allowed a more direct evaluation of the endocrinological effect of DHEA administration on the synthesis of sex steroids.

Effect of acute DHEA administration on free testosterone in middle-aged and young men following high-intensity interval training

With advancing age, plasma testosterone levels decline, with free testosterone levels declining more significantly than total testosterone. This fall is thought to underlie the development of physical and mental weakness that occurs with advancing age. In addition, vigorous exercise can also lower total and free testosterone levels with the decline greatest in physically untrained men. The purpose of the study was to evaluate the effect of oral DHEA supplementation, a testosterone precursor, on free testosterone in sedentary middle-aged men during recovery from a high-intensity interval training (HIIT) bout of exercise. A randomized, double-blind, placebo-controlled crossover study was conducted for 8 middle-aged participants (aged 49.3 ± 2.4 years) and an additional 8 young control participants (aged 21.4 ± 0.3 years). Each participant received DHEA (50 mg) and placebo on separate occasions one night (12 h) before a 5-session, 2-min cycling exercise (100% VO₂max). While no significant age difference in total testosterone was found, middle-aged participants exhibited significantly lower free testosterone and greater luteinizing hormone (LH) levels than the young control group. Oral DHEA supplementation increased circulating DHEA-S and free testosterone levels well above baseline in the middle-aged group, with no significant effect on total testosterone levels. Total testosterone and DHEA-S dropped significantly until 24 h after HIIT for both age groups, while free testosterone of DHEA-supplemented middle-aged men remained unaffected. These results demonstrate acute oral DHEA supplementation can elevate free testosterone levels in middle-aged men and prevent it from declining during HIIT. Therefore, DHEA supplementation may have significant benefits related to HIIT adaptation.

Effect of dehydroepiandrosterone administration on recovery from mix-type exercise training-induced muscle damage

This study aimed to determine the role of DHEA-S in coping against the exercise training mixing aerobic and resistance components. During 5-day successive exercise training, 16 young male participants (19.2 ± 1.2 years) received either a placebo (flour capsule) or DHEA (100 mg/day) in a double-blinded and placebo-controlled design. Oral DHEA supplementation significantly increased circulating DHEA-S by 2.5-fold, but a protracted drop (~35 %) was observed from Day 3 during training. In the Placebo group, only a minimal DHEA-S reduction (~17 %) was observed. Changes in testosterone followed a similar pattern as DHEA-S. Muscle soreness was elevated significantly on Day 2 for both groups to a similar extent. Lower muscle soreness was observed in the DHEA-supplemented group on Day 3 and Day 6. In the Placebo group, training increased circulating creatine kinase (CK) levels by approximately ninefold, while only a threefold increase was observed in the DHEA-supplemented group. This mix-type exercise training improved glucose tolerance in both groups, while lowering the insulin response to the glucose challenge, but no difference between treatments was observed. Our results suggest that DHEA-S may play a role in protecting skeletal muscle from exercise training-induced muscle damage.

Effect of 1-year, low-dose DHEA therapy on climacteric symptoms and female sexuality

ABSTRACTBackground Sexual desire is affected by endocrine and psychosocial factors. Menopausal hormonal changes are relevant to the causes of sexual dysfunction during reproductive aging.Aim To evaluate the effects of different types of hormonal replacement therapy (HRT) on sexual function, frequency of sexual intercourse, and quality of relationship in early postmenopausal women. We recruited 48 healthy postmenopausal women aged 50–60 years (mean age 54.5 ± 3.3 years). Women with climacteric symptoms were uniformly randomized into three groups receiving either dehydroepiandrosterone (DHEA 10 mg) daily, or daily oral estradiol (1 mg) plus dihydrogesterone (5 mg), or daily oral tibolone (2.5 mg) for 12 months. Women who refused hormonal therapy were treated with oral vitamin D (400 IU). Efficacy was evaluated using the McCoy Female Sexuality Questionnaire before treatment and after 12 months. We evaluated the hormonal profile before treatment and after 3, 6 and 12 months.Results The groups receiving DHEA or HRT reported a significant improvement in sexual function compared to baseline (p < 0.001 and p < 0.01, respectively) using the McCoy total score. The quality of relationship was similar at baseline and after 3, 6 and 12 months of treatment. There were significant increases in the numbers of episodes of sexual intercourse in the previous 4 weeks in women treated with DHEA, HRT and tibolone in comparison with the baseline value (p < 0.01, p < 0.05, p < 0.01, respectively). No changes in the McCoy score occurred in women receiving vitamin D.Conclusions Daily oral DHEA therapy at the dose of 10 mg, HRT and tibolone all provided a significant improvement in comparison with vitamin D in sexual function and in frequency of sexual intercourse in early postmenopausal women.

Effects of dehydroepiandrosterone on fatigue and well-being in women with quiescent systemic lupus erythematosus: a randomised controlled trial

ObjectiveDehydroepiandrosterone (DHEA) has been reported to improve fatigue and reduced well-being. Both are major problems in patients with systemic lupus erythematosus (SLE), even with quiescent disease. Low serum DHEA levels...

A Randomized Trial of Oral DHEA Treatment for Sexual Function, Well-Being, and Menopausal Symptoms in Postmenopausal Women with Low Libido

IntroductionDehydroepiandrosterone (DHEA) and its sulfate DHEAS, which are the most abundant steroids in women, decline with age. We have shown association between low sexual function and low circulating DHEAS levels in women. AimThe aim of this study was to evaluate whether restoration of circulating DHEA levels in postmenopausal women to the levels seen in young individuals improves sexual function. MethodsNinety-three postmenopausal women not using concurrent estrogen therapy were enrolled in a 52-week randomized, double-blind, placebo controlled trial and received either DHEA 50 mg or placebo (PL) daily. Main Outcome MeasuresEfficacy was assessed through 26 weeks. The main outcome measures were the change in total satisfying sexual events (SSE) and the change in the Sabbatsberg Sexual Self-Rating Scale (SSS) total score. Secondary measures were the Psychological General Well-Being Questionnaire (PGWB), and the Menopause—Specific Quality of Life Questionnaire (MENQOL). Hormonal levels, adverse events (AEs), serious adverse events (SAEs) and clinical labs were evaluated over 52 weeks. ResultsEighty-five participants (91%) were included in the 26-week efficacy analysis. There were no significant differences between the DHEA and PL groups in the change in total SSE per month or the SSS, PGWB, and MENQOL change scores. Overall AE reports and number of withdrawals as a result of AEs were similar in both groups; however more women in the DHEA group experienced androgenic effects of acne and increased hair growth. ConclusionsIn this study treatment of postmenopausal women with low sexual desire with 50 mg/day DHEA resulted in no significant improvements in sexual function over PL therapy over 26 weeks. Panjari M, Bell RJ, Jane F, Wolfe R, Adams J, Morrow C, and Davis SR. A randomized trial of oral DHEA treatment for sexual function, well-being and menopausal symptoms in postmenopausal women with low libido. J Sex Med 2009;6:2579–2590.

The safety of 52 weeks of oral DHEA therapy for postmenopausal women

Objective The aim of this study was to evaluate the safety of 52 weeks of DHEA 50 mg daily oral dose given to postmenopausal women with low libido to improve sexual function. Method 93 postmenopausal women were enrolled in a 52-week randomised, double-blind, placebo-controlled trial and received either DHEA 50 mg or placebo (PL) daily. The effects of DHEA versus placebo on lipid profile, insulin–glucose homeostasis and the endomentrium were assessed over 52 weeks. Results Oral DHEA, 50 mg/day, was not associated with any effects on blood lipids or insulin resistance. The pattern of breakthrough bleeding did not substantially differ between the DHEA and PL groups and no significant adverse endometrial effects were apparent. Conclusions The use of 50 mg oral DHEA did not significantly alter lipid profile, insulin sensitivity or adversely affect the endometrium in postmenopausal women.

Lack of Hepatic Conversion of Dehydroepiandrosterone Sulfate (DHEAS) to DHEA

DHEA and its sulfate ester DHEAS are the most abundant steroids in the human circulation. Only desulfated DHEA is biologically active and can be converted downstream toward sex steroids. The current concept is that DHEAS serves as the hydrophilic storage pool for DHEA regeneration and that DHEA and DHEAS are interconverted freely via hydroxysteroid sulfotransferases and steroid sulfatase. Here we sought to analyze DHEA/DHEAS interconversion in 16 healthy young and elderly men (n = 8 in each group; ages 23 –29 and 52 –66 yrs, BMI 20– 26 kg/m 2 and 23– 28 kg/m 2 , respectively). They were studied with frequent serum sampling (0830 h –1500 h) on three occasions: at baseline, after oral administration of 100 mg DHEA at 0900 h, and after i.v. administration of 25 mg DHEAS at 0900 h. Oral DHEA and i.v. DHEAS resulted in similar long-standing increases in serum DHEAS (oral DHEA versus i.v. DHEAS: AUC0-6 h 98 ± 9 versus 95 ± 7 mmol/lxh, n.s.). Oral DHEA also led to a significant increase in serum DHEA (AUC0-6 h 400 ± 32 versus 263 ± 20 nmol/lxh at baseline, p < 0.05). However, surprisingly, DHEAS i.v. did not result in any significant DHEA increase (AUC0-6 h 295 ± 20 versus 263 ± 20 nmol/lxh at baseline, n.s.). Analysis of downstream conversion revealed a similar pattern with a significant increase in androstenedione after oral DHEA (p < 0.05) but not after DHEAS i.v. (n.s.). Similarly, androstanediol glucoronide, a marker of peripheral androgen synthesis,

Dehydroepiandrosterone modulates endothelial nitric oxide synthesis via direct genomic and nongenomic mechanisms.

Dehydroepiandrosterone (DHEA) and its sulfate ester (DHEAS) are the major circulating steroid hormones in humans, and their levels progressively decline with age. Epidemiological studies suggest that DHEA/DHEAS concentrations may be inversely related to cardiovascular risk, but disagreement exists on this issue. Preliminary studies show that DHEA regulates vascular function, but few data have been published on the mechanisms. We show that DHEA administration to human endothelial cells triggers nitric oxide synthesis, due to enhanced expression and stabilization of endothelial nitric oxide synthase (eNOS). Additionally, DHEA rapidly activates eNOS, through a nontranscriptional mechanism that depends on ERK1/2 MAPK, but not on phosphatidylinositol 3-kinase/Akt. DHEA is not converted to estrogens or androgens by endothelial cells, and its genomic and nongenomic effects are not blocked by antagonists of the estrogen, progesterone, glucocorticoid, or androgen receptors, suggesting that DHEA acts through a specific receptor. Oral DHEA administration to ovariectomized Wistar rats dose-dependently restores aortic eNOS levels and eNOS activity, confirming the effects of DHEA in vivo. Our present data suggest that DHEA may have direct genomic and nongenomic effects on the vascular wall that are not mediated by other steroid hormone receptors, leading to eNOS activation and induction.

Decreased Testosterone in Regularly Menstruating Women with Decreased Libido: A Clinical Observation

Much more information is available concerning decreased libido in postmenopausal than in premenopausal women. Even less is known about androgen deficiency in younger women. We measured total and free testosterone levels in 12 consecutive premenopausal women complaining of decreased libido. Of the 12 women, 8 had low or immeasurable levels of testosterone despite having regular menstrual periods. Androgen precursor hormones, DHEA-S and Androstenedione, were low-normal to high-normal. Treatment with oral DHEA, 50 to 100 mg per day, restored sexual desire in 6 of the 8 women, gave partial improvement in one, and failed in another. Possible significance and etiological mechanism are discussed.

Lifelong treatment with oral DHEA sulfate does not preserve immune function, prevent disease, or improve survival in genetically heterogeneous mice.

To determine whether lifelong exposure to dehydroepiandrosterone sulfate extends the lifespan or retards immune senescence in mice. Double-blind, placebo-controlled intervention trial. A specific pathogen-free rodent vivarium. 120 mice bred as a cross between CB6F1 females and C3D2F1 males. DHEAS at 100 microg/mL in drinking water from weaning until death. Age at death, cause of death, antibody production after erythrocyte immunization, and T cell subset profiles in peripheral blood at ages 8 and 18 months. DHEAS ingestion did not lead to a significant increase in mean or maximal longevity: the 95% confidence interval for DHEAS effect on mean lifespan ranged from +35 days to -80 days. There were no significant effects of DHEAS on incidence of lethal illnesses, except for a trend toward higher levels of mammary adenocarcinoma in DHEAS-treated females and mouse urinary syndrome in DHEAS-treated males. DHEAS treatment did not improve the ability of middle-aged mice to produce antibody to a foreign particulate antigen, and it did not alter the proportions of age-sensitive T cell subsets in middle-aged animals. Although differences among species in pharmacokinetics complicate interpretation of studies in which DHEA or DHEAS is administered to rodents, our data provide no support for the idea that chronic exposure to this steroid retards immune senescence or prevents late life illness.