Dehydroepiandrosterone modulates the PTEN/PI3K/AKT signaling pathway to alleviate 4-vinylcyclohexene diepoxide-induced premature ovarian insufficiency in rats.

Dehydroepiandrosterone (DHEA) is frequently integrated as an adjuvant in over a quarter of controlled ovarian hyperstimulation (COH) protocols, despite the ongoing debate regarding its impact. This study aimed to evaluate the efficacy and mechanism of action of DHEA on ovarian follicular development and ovarian response in rats with varying ovarian reserves. The study involved 75 rats categorized into 15 distinct groups. The ovarian tissues of rats in both the normal ovarian reserve group and the premature ovarian insufficiency (POI) group, induced by 4-vinylcyclohexene diepoxide (VCD) injection, were subjected to histomorphological and biochemical analyses following the administration of DHEA, either alone or in combination with COH. Follicle counting was performed on histological sections obtained from various tissues. Serum concentrations of anti-Müllerian hormone (AMH) and the quantification of specific proteins in ovarian tissue, including phosphatase and tensin homolog of chromosome 10 (PTEN), phosphoinositide 3-kinase (PI3K), phosphorylated protein kinase B (pAKT), cyclooxygenase 2 (COX-2), caspase-3, as well as assessments of total antioxidant status and total oxidant status, were conducted employing the ELISA method. The impact of DHEA exhibited variability based on ovarian reserve. In the POI model, DHEA augmented follicular development and ovarian response to the COH protocol by upregulating the PTEN/PI3K/AKT signaling pathway, mitigating apoptosis, inflammation, and oxidative stress, contrary to its effects in the normal ovarian reserve group. In conclusion, it has been determined that DHEA may exert beneficial effects on ovarian stimulation response by enhancing the initiation of primordial follicles and supporting antral follicle populations.

Dehydroepiandrosterone Shifts Energy Metabolism to Increase Mitochondrial Biogenesis in Female Fertility with Advancing Age.

Female reproductive aging is an irreversible process associated with a decrease in oocyte quality, which is a limiting factor for fertility. Previous studies have shown that dehydroepiandrosterone (DHEA) has been shown to improve in vitro fertilization (IVF) outcomes in older women. Herein, we showed that the decline in oocyte quality with age is accompanied by a significant decrease in the level of bioenergetic metabolism genes. We compared the clinical characteristics between groups of infertile women who either received DHEA or did not. Treatment with DHEA may enhance oocyte quality by improving energy production and metabolic reprogramming in cumulus cells (CCs) of aging women. Our results showed that compared with the group without DHEA, the group with DHEA produced a large number of day-three (D3) embryos, top-quality D3 embryos, and had improved ongoing pregnancy rate and clinical pregnancy rate. This may be because DHEA enhances the transport of oxidative phosphorylation and increases mitochondrial oxygen consumption in CCs, converting anaerobic to aerobic metabolism commonly used by aging cells to delay oocyte aging. In conclusion, our results suggest that the benefit of DHEA supplementation on IVF outcomes in aging cells is significant and that this effect may be mediated in part through the reprogramming of metabolic pathways and conversion of anaerobic to aerobic respiration.

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.

Impact of dehydroepiandrosterone (DHEA) supplementation on testosterone concentrations and BMI in elderly women: A meta-analysis of randomized controlled trials.

BACKGROUND: Despite the fact that numerous clinical studies have evaluated the positive effects of dehydroepiandrosterone (DHEA) supplementation on testosterone concentrations and on the body mass index (BMI), more evidence is needed to certify that DHEA is a BMI-reducing agent in the elderly. This meta-analysis aims to clarify the various incompatible results and investigate the impact of DHEA supplementation on serum testosterone levels and lean body mass in elderly women. METHODS: Four scientific databases (EMBASE, PubMed/MEDLINE, Scopus and Web of Science) were searched from inception until 20 August 2020 for trials comparing DHEA with placebo. Results were presented as weighted mean differences (WMDs) and 95 % confidence intervals (CIs) based on the random effects model (DerSimonian-Laird approach). RESULTS: Nine arms with 793 subjects reported testosterone as an outcome measure. The overall results demonstrated that testosterone levels increased significantly after DHEA administration in elderly women (WMD: 17.52 ng/dL, 95 % CI: 6.61, 28.43, P = 0.002). In addition, DHEA administration significantly decreased the BMI (WMD:-0.39 kg/m2, I2 = 0.0 %). CONCLUSION: The results of the current meta-analysis support the use of DHEA supplementation for increasing testosterone concentrations in elderly women.

The influence of dehydroepiandrosterone (DHEA) on fasting plasma glucose, insulin levels and insulin resistance (HOMA-IR) index: A systematic review and dose response meta-analysis of randomized controlled trials.

AIMS: The effect of DHEA supplementation on fasting plasma glucose (FPG), insulin levels (IN) and the homeostasis model assessment-estimated insulin resistance (HOMA-IR) index in humans has not been assessed so far. Thus, we aimed to conduct a systematic review and meta-analysis of the randomized controlled trials (RCT) which assessed the effects of DHEA supplementation on FPG, IN and the HOMA-IR index in humans. METHODS: An extensive search was performed in Scopus, PubMed/MEDLINE, and Web of Science from inception to June 2020. Data was combined using the random effects model. RESULTS: 14 publications were included in this study. Overall results demonstrated that FPG was significantly altered after DHEA consumption (WMD: -2.185 mg/dl, P = 0.029). DHEA administration did not result in any significant changes in IN (WMD: 0.057 µU/mL, P = 0.067), and the HOMA - IR index (WMD: 0.174, P = 0.060). In the subgroup analyses, FPG significantly decreased in the subgroup who received DHEA supplementation in dosages of ≤50 mg/day (WMD: -2.29 mg/dl), when the treatment duration was <12 weeks (WMD: -5.25 mg/dl), and in subjects aged ≥60 years (WMD: -2.94 mg/dl). CONCLUSION: This systematic review evaluated the association between FPG and DHEA, revealing that the administration of DHEA reduces FPG levels. However, we found no association between DHEA administration and IN levels or insulin resistance.

Supplementation of dehydroepiandrosterone (DHEA) in pre- and postmenopausal women - position statement of expert panel of Polish Menopause and Andropause Society.

Dehydroepiandrosterone (DHEA) concentration decreases with age, therefore, DHEA has been considered a hormone that reduces the symptoms associated with aging, so the usefulness of DHEA in premenopausal and postmenopausal women, and the options of hormone therapy have received a large amount of attention. The effectiveness of DHEA in the premenopausal women remains unclear, while in postmenopausal women with coexisting estrogens deficiency is controversial. Despite many years of study, the use of DHEA is still controversial, especially regarding its effectiveness. The aim of present article was to evaluate DHEA specific effects on metabolic parameters, bone mineral density, insulin resistance as well as the therapeutic potential of DHEA in pre- and postmenopausal women using measures of sexual activity, cognition and well-being. The summary of this article is the position statement of expert group of the Polish Menopause and Andropause Society regarding the efficacy and safety of DHEA supplementation in women. We concluded, that currently available clinical trials and meta-analyses indicate that DHEA supplementation is effective in women with adrenal insufficiency and chronically treated with exogenous glucocorticoids, postmenopausal women with low bone mineral density and/or osteoporosis, premenopausal women with sexual disorders and low libido, and in women with vulvovaginal atrophy due to menopause or genitourinary syndrome of menopause. Currently available clinical trials also suggest that DHEA supplementation is probably effective in postmenopausal women with hypoactive sexual disorders, infertile women with diminished ovarian reserve, women suffering from depression and anxiety, and women with obesity and insulin resistance. No serious adverse effects have been reported.

Effects of dehydroepiandrosterone on quality of life in premenopausal women with rheumatoid arthritis: A preliminary randomized clinical trial.

AIM: Chronic inflammation and subsequent use of glucocorticoids can lead to relative adrenocortical insufficiency in patients with rheumatoid arthritis (RA). Previously, adrenocortical hormone, dehydroepiandrosterone (DHEA) was shown as a potential therapy for autoimmune disorders. However, data regarding effects of DHEA in RA are limited. The aim of this study was to investigate the effects of DHEA on quality of life (QOL) in premenopausal rheumatoid arthritis patients. METHOD: In this randomized double blinded, controlled trial 46 premenopausal rheumatoid arthritis patients were assigned to receive 50 mg/d DHEA (23 patients) or placebo (23 patients) for 12 weeks. Disease Activity Score of 28 joints - erythrocyte sedimentation rate (DAS28-ESR) questionnaire, visual analog score and swollen and tender joint counts (both 0-28) were used for assessment of disease activity. Persian-validated World Health Organization Quality of Life Brief version (WHOQOL BREF) questionnaire was used to assess quality of life. RESULTS: In comparison to the control group more improvement in QOL (P = .025) and environment health (P = .001) was observed in the DHEA group. After adjustment for age and disease duration DHEA was associated with more improvement in QOL (P = .01), psychological (P = .02) and physical health (P = .03). A trend toward a decrease in ESR was observed in DHEA group (P = .06). DAS was improved in both groups; however, there was no significant change in DAS28 between groups (P = .88). Frequency of adverse events albeit minor was similar in both groups. CONCLUSION: Our study supports a slightly superior effect of DHEA over placebo to improve QOL in premenopausal female patients with rheumatoid arthritis. We did not find improvement in DAS in the DHEA group over placebo.

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

OBJECTIVE: 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). PATIENTS AND METHODS: 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. RESULTS: 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%). CONCLUSIONS: Oral DHEA supplementation improves both ovarian reserve and pregnancy rates in women with POR.

Does Dehydroepiandrosterone (DHEA) improve in vitro fertilisation (IVF) outcomes in poor responders?

BACKGROUND: In reproductive medicine poor ovarian response (POR) among women undergoing in vitro fertilisation (IVF) is of great concern. Meta-analysis showed that Dehydroepiandrosterone (DHEA) administration resulted in a significant increase in the number of oocytes retrieved in women with POR. The aim of this study was to assess the effectiveness of DHEA supplementation on IVF outcomes among poor responders undergoing IVF. METHODS: Sixteen patients who were diagnosed with POR scheduled to undergo their second cycle of Intracytoplasmic sperm injection (ICSI)/embryo transfer cycle were enrolled. All enrolled patients had earlier undergone their first ICSI/embryo transfer cycle at least four months prior to this study. All subjects were given DHEA supplementation of 25mg three times daily for at least three months prior to their second ICSI/embryo transfer cycle. Statistical analysis of various ovarian response and ICSI outcomes parameter were compared pre and post DHEA. RESULTS: Sixteen women with the mean age of 35 years were enrolled in the study. The comparative analysis of results showed a significant increase in the number of good quality of embryos obtained (p<0.05). After the treatment with DHEA, there was an improvement in the number of oocytes retrieved, Metaphase II (MII) oocyte (mature) oocytes obtained, fertilised and transferrable embryos and the pregnancy rate. There was no significant effect of DHEA treatment on the number of days of stimulation and cumulative dose of gonadotrophins used. CONCLUSION: Our results is able to show that DHEA supplementation may help to enhance IVF-ICSI outcomes in women with POR especially in those age 35 years and below.

Premature ovarian insufficiency - novel hormonal approaches in optimizing fertility.

Premature ovarian insufficiency (POI) is a delicate medical problem in young women. This condition is not unchangeable and permanent but is associated with intermittent and unpredictable ovarian activity, resulting in low conception rate. Over the period of 8 years, the evaluation of secondary amenorrhea was conducted in 90 patients below the age of 40 who wished to restore fertility. Having confirmed the diagnosis and investigated the etiology of POI, hormone replacement therapy was applied (sequential administration of estradiol and norethisterone acetate) in the first 30 patients (group A). Estrogen-progestogen therapy with daily supplementation of 25 mg of micronized oral dehydroepiandrosterone (DHEA) was conducted in 44 patients (group B), whereas a combined regime (estrogen-progestogen therapy, DHEA supplementation in daily dose of 25 mg, and melatonin supplementation in daily dose of 3 mg) was conducted in 16 patients (group C). In the course of our study, 16 pregnancies were realized (18% of all cases: 17% in group A; 18% in group B; 19% in group C) 6 to 20 months after the initiation of hormone therapy, and there have been 13 completed term pregnancies so far with normal fetal growth and development. We concluded that estrogen-progestogen therapy combined with DHEA and melatonin could optimize fertility and lead to successful pregnancy in POI patients.

HSD3B1 Genotypes Conferring Adrenal-Restrictive and Adrenal-Permissive Phenotypes in Prostate Cancer and Beyond.

Castration-resistant prostate cancer (PCa) almost invariably occurs after androgen deprivation therapy for metastatic disease and is driven in part by androgen synthesis within the tumor. 3ß-hydroxysteroid dehydrogenase isoenzyme-1 catalyzes the conversion of adrenal precursor steroids into potent androgens essential for PCa progression. A common 1245 A→C missense-encoding single nucleotide polymorphism in HSD3B1 (rs1047303), the gene that encodes this enzyme, leads to a more stable protein that is resistant to degradation and thus increased production of potent androgens from adrenal precursors, facilitating castration-resistant PCa development. Consistent with this mechanism, this adrenal-permissive HSD3B1(1245C) genotype is associated with inferior outcomes after androgen deprivation therapy for advanced PCa, and increased sensitivity to pharmacologic blockade of adrenal precursors in metastatic disease. Herein, we review current knowledge of the mechanisms conferred by HSD3B1 genotype to alter androgen physiology and accelerate development of castration-resistant disease and its associations with clinical PCa outcomes. In light of its effect on steroid physiology, we also discuss its potential associations with non-PCa phenotypes.

Impact of Adrenal Hormone Supplementation on Bone Geometry in Growing Teens With Anorexia Nervosa.

PURPOSE: Adolescents with anorexia nervosa (AN) have decreased dehydroepiandrosterone (DHEA) and estrogen concentrations that may contribute to skeletal deficits. We sought to determine whether DHEA + estrogen replacement (ERT) prevented bone loss in young adolescents with AN. METHODS: We recruited females with AN (n = 70, ages 11-18 years) into a 12-month, randomized, double-blind placebo-controlled trial. Participants were randomized to oral micronized DHEA 50 mg + 20 mcg ethinyl estradiol/.1 mg levonorgestrel daily (n = 35) or placebo (n = 35). Outcomes included serial measures of bone mineral density (BMD) by dual-energy X-ray absorptiometry (total body, hip, spine) and peripheral quantitative computed tomography (pQCT; tibia). Magnetic resonance imaging of T1-weighted images of the left knee determined physeal status (open/closed). RESULTS: Sixty-two subjects completed the trial. Physeal closure status was the strongest predictor of aBMD changes. Among girls with open physes, those who received DHEA + ERT showed a decline in BMD Z-scores compared with those receiving placebo, whereas there was no effect in those with at least one closed physis. Treatment did not affect any pQCT measures, regardless of physeal closure status. CONCLUSIONS: Combined DHEA + ERT did not significantly improve dual-energy X-ray absorptiometry or pQCT BMD measurements in young adolescent girls with AN, in contrast to an earlier trial showing benefit in older adolescents and young women. In girls with open physes, the mean change in the placebo arm was greater than that of the DHEA + ERT group. We conclude that DHEA + ERT is ineffective for preserving bone health in growing young adolescents with AN at the dose and route of administration described in this report.

The impact of dehydroepiandrosterone in poor ovarian responders on assisted reproduction technology treatment.

One in six couples worldwide will experience at least one infertility problem during their reproductive years. Between 5.6% and 35.1% of women will exhibit poor ovarian response. A variety of methods have been applied to improve ovarian response, including dehydroepiandrosterone. In the ovaries, dehydroepiandrosterone promotes follicular development and granulosa cell proliferation by increasing intraovarian androgen concentrations while simultaneously enhancing the level of follicular insulin-like growth factor-1, which promotes folliculogenesis. Dehydroepiandrosterone supplementation may improve in vitro fertilization outcomes and ovarian response in patients with poor ovarian response. However, a few questions still loom over the effectiveness of dehydroepiandrosterone.

Molecular Alterations and Effects of Acute Dehydroepiandrosterone Treatment Following Brief Bilateral Common Carotid Artery Occlusion: Relevance to Transient Ischemic Attack.

Transient ischemic attack (TIA) represents brief neurological dysfunction of vascular origin without detectable infarction. Despite major clinical relevance characterization of post-TIA molecular changes using appropriate experimental model is lacking and no therapeutic agent has been established yet. Neurosteroid dehydroepiandrosterone (DHEA) arose as one of the candidates for cerebral ischemia treatment but its effects on TIA-like condition remain unknown. Seeking an animal model applicable for investigation of molecular alterations in mild ischemic conditions such as TIA, 15-min bilateral common carotid artery occlusion with 24-h reperfusion was performed to induce ischemia/ reperfusion (I/R) injury in adult male Wistar rats. Additionally, effects of 4-h post-operative DHEA treatment (20 mg/kg) were investigated in physiological and I/R conditions in hippocampus (HIP) and prefrontal cortex (PFC). The study revealed absence of sensorimotor deficits, cerebral infarcts and neurodegeneration along with preserved HIP and PFC overall neuronal morphology and unaltered malondialdehyde and reduced glutathione level following I/R and/or DHEA treatment. I/R induced nitric oxide burst in HIP and PFC was accompanied with increased neuronal nitric oxide synthase protein level exclusively in HIP. DHEA had no effects in physiological conditions, while increase of Bax/Bcl2 ratio and dissipation of mitochondrial membrane potential in treated I/R group suggested DHEA-mediated exacerbation of post-ischemic changes that might lead to pro-apoptotic events in HIP. Interestingly, DHEA restored I/R-induced NO to the control level in PFC. Obtained results indicated that I/R may serve as an appropriate model for investigation of molecular changes and treatment outcome following mild ischemic conditions such as TIA.

Efficacy of intravaginal dehydroepiandrosterone (DHEA) on moderate to severe dyspareunia and vaginal dryness, symptoms of vulvovaginal atrophy, and of the genitourinary syndrome of menopause.

OBJECTIVE: The aim of this study is to confirm the local beneficial effects of intravaginal dehydroepiandrosterone (DHEA, Prasterone) on moderate to severe dyspareunia or pain at sexual activity, the most frequent symptom of vulvovaginal atrophy due to menopause or genitourinary syndrome of menopause (GSM). METHODS: In a prospective, randomized, double-blind, and placebo-controlled phase III clinical trial, the effect of daily intravaginal 0.50% DHEA (6.5 mg) (Prasterone, EndoCeutics) was examined on four coprimary objectives, namely percentage of parabasal cells, percentage or superficial cells, vaginal pH, and moderate to severe pain at sexual activity (dyspareunia) identified by the women as their most bothersome vulvovaginal atrophy symptom. The intent-to-treat population included 157 and 325 women in the placebo and DHEA-treated groups, respectively. RESULTS: After daily intravaginal administration of 0.50% DHEA for 12 weeks, when compared to baseline by the analysis of covariance test, the percentage of parabasal cells decreased by 27.7% over placebo (P < 0.0001), whereas the percentage of superficial cells increased by 8.44% over placebo (P < 0.0001), vaginal pH decreased by 0.66 pH unit over placebo (P < 0.0001), and pain at sexual activity decreased by 1.42 severity score unit from baseline or 0.36 unit over placebo (P = 0.0002). On the other hand, moderate to severe vaginal dryness present in 84.0% of women improved at 12 weeks by 1.44 severity score unit compared to baseline, or 0.27 unit over placebo (P = 0.004). At gynecological evaluation, vaginal secretions, epithelial integrity, epithelial surface thickness, and color all improved by 86% to 121% over the placebo effect (P < 0.0001 for all comparisons with placebo). Serum steroid levels remained well within the normal postmenopausal values according to the involved mechanisms of intracrinology. The only side effect reasonably related to treatment is vaginal discharge due to melting of the vehicle at body temperature and this was reported in about 6% of the participants. CONCLUSIONS: The daily intravaginal administration of 0.50% (6.5 mg) DHEA (Prasterone) has shown clinically and highly statistically significant effects on the four coprimary parameters suggested by the US Food and Drug Administration. The strictly local action of Prasterone is in line with the absence of significant drug-related adverse events, thus showing the high benefit-to-risk ratio of this treatment based upon the novel understanding of the physiology of sex steroids in women.

Effect of Dehydroepiandrosterone (DHEA) on Diabetes Mellitus and Obesity.

Type 2 diabetes is a metabolic disorder that is characterized by an impaired capacity to secrete insulin, insulin resistance, or both. Dehydroepiandrosterone (DHEA), a steroid hormone produced by the adrenal cortex, has been reported to have beneficial effects on diabetes mellitus and obesity in animal models. DHEA and DHEA-sulfate (DHEA-S) have been reported to increase not only insulin secretion of the pancreas but also insulin sensitivity of the liver, adipose tissue, and muscle. We investigated the effects of DHEA on glucose metabolism in animal models and reported decrease of liver gluconeogenesis. Recently, we reported the effect of DHEA on the liver and muscle by using insulin-stimulated insulin receptor substrate 1 and 2 (IRS1 and IRS2)-deficient mice. DHEA increased Akt phosphorylation in the liver of C57BL6 IRS1- and IRS2-deficient mice fed with a high-fat diet (HFD), which suggests that the increase in DHEA-induced Akt signaling is sufficient in the presence of IRS1 or IRS2. In addition, other studies have also reported the effect of DHEA on diabetes mellitus in the liver, muscle, adipose tissue, and pancreatic ß-cell and its effect on obesity in animal models. A meta-analysis in elderly men and women has found that DHEA supplementation has no effects on blood glucose levels. However, DHEA supplementation to patients with type 2 diabetes has not been fully elucidated. Therefore, further studies are needed to provide greater insight into the effect of DHEA on diabetes and obesity in animal and human models.

Dehydroepiandrosterone supplementation combined with Weight-Loading Whole-Body Vibration Training (WWBV) affects exercise performance and muscle glycogen storage in middle-aged C57BL/6 mice.

Background: Adequate nutritional intake and an optimal training program are important elements of any strategy to preserve or increase muscle mass and strength during aging. Purpose: In the current study, we investigate the effects of Dehydroepiandrosterone (DHEA), one of the most abundant circulating steroids in humans and a precursor hormone, supplementation combined with a weight-loading whole-body vibration (WWBV) on exercise performance, physical fatigue-related biochemical responses and testosterone content in middle-aged 9 months old C57BL/6 mice. Methods: Male middle-aged C57BL/6 mice were divided into 3 groups (n = 8 per group) and treated for 4 weeks with the following: 1) Sedentary control (SC) with vehicle 2) DHEA supplementation (DHEA, 10.2 mg/kg) and 3) DHEA supplementation with WWBV training (DHEA: 10.2 mg/kg; WBV: 5.6 Hz, 2 mm, 0.13 g). Exercise performance was evaluated by forelimb grip strength and time to exhaustion, as well as changes in body composition and anti-fatigue levels after a 15-min swimming exercise. Fatigue-related biochemical responses of serum lactate, ammonia, glucose, creatine kinase (CK), and blood urea nitrogen (BUN) were measured following the swimming exercise. In addition, the biochemical parameters and the testosterone levels were measured at the end of the experiment. Results: DHEA supplementation combined with WWBV training for 4 weeks significantly decreased the amount of white adipose tissue and increased the food and water intake. Additionally, WWBV+DHEA supplementation improved exercise performance, testosterone levels and glycogen contents of both liver and muscle. WWBV+DHEA supplementation also decreased serum lactate, ammonia and BUN levels, while increasing glucose levels following the 15-min swim test. Conclusion: Taken together, our results suggest that combining the WWBV training program with DHEA supplementation could provide an anti-fatigue pharmacological effect for elderly populations.

Efficacy of dehydroepiandrosterone (DHEA) supplementation for in vitro fertilization and embryo transfer cycles: a systematic review and meta-analysis.

Dehydroepiandrosterone (DHEA) supplementation might hold some promise in vitro fertilization and embryo transfer cycles. However, the results remain controversial. We conducted a systematic review and meta-analysis to evaluate the efficacy of DHEA in patients for in vitro fertilization. PubMed, EMbase, Web of science, EBSCO and Cochrane library databases were systematically searched. Randomized controlled trials (RCTs) assessing the effect of DHEA versus placebo on in vitro fertilization were included. Two investigators independently searched articles, extracted data and assessed the quality of included studies. The primary outcomes were clinical pregnancy and live birth rate. Meta-analysis was performed using random-effect model. Six RCTs involving 745 patients were included in the meta-analysis. Overall, compared with placebo, DHEA supplementation was associated with the significant increase in clinical pregnancy (OR = 1.45; 95% CI = 1.04-2.03; p = .03), live birth rate (OR = 2.70; 95% CI = 1.24-5.85; p = .01) and endometrial thickness (Std. mean difference = 0.67; 95% CI = 0.02-1.32; p = .04) but showed no influence on E2 on hCG day (Std. mean difference = 0.69; 95% CI = -0.46 to 1.85; p = .24), embryos transferred (Std. mean difference = 0.42; 95% CI = -0.04 to 0.88; p = .07) and miscarriage rate (OR = 0.43; 95% CI = 0.03-6.66; p = .55). DHEA supplementation could significantly improve clinical pregnancy, live birth rate, endometrial thickness and retrieved oocytes but failed to alter E2 on hCG day, embryos transferred and miscarriage rate.