DHEA Supplementation Research Articles

DHEA down-regulates mitochondrial dynamics and promotes apoptosis of lung adenocarcinoma cells through FASTKD2.

Background: DHEA is a steroid hormone produced by the gonads, adrenal cortex, brain, and gastrointestinal tract. While the anti-obesity, anti-atherosclerosis, anti-cancer, and memory-enhancing effects of DHEA have been substantiated through cell experiments, animal studies, and human trials, the precise mechanisms underlying these effects remain unclear. Altered mitochondrial dynamics can lead to mitochondrial dysfunction, which is closely related to many human diseases, especially cancer and aging. This study was to investigate whether DHEA inhibits lung adenocarcinoma through the mitochondrial pathway and its molecular mechanism. Methods: Through animal experiments and cell experiments, the effect of DHEA on tumor inhibition was determined. The correlation between FASTKD2 expression and DHEA was analyzed by Western blot, Reverse transcription-quantitative PCR, Immunohistochemistry, and TCGA database. Results: In this study, DHEA supplementation in the diet can inhibit the tumor size of mice, and the effect of adding DHEA one week before the experiment is the best. DHEA limits the glycolysis process by inhibiting G6PDH activity, increases the accumulation of reactive oxygen species, and initiates apoptosis in the mitochondrial pathway of cancer cells. Conclusion: DHEA suppresses mitochondrial fission and promotes mitochondrial fusion by downregulating the expression of FASTKD2, thereby inhibiting tumor growth and prolonging the overall survival of lung adenocarcinoma patients, which also provides a new target for the prevention and treatment of lung adenocarcinoma.

Severe hyperandrogenism following DHEA supplementation in menopausal woman: a case report

Severe hyperandrogenism following DHEA supplementation in menopausal woman: a case report

Dehydroepiandrosterone Supplementation Results in Varying Tissue-specific Levels of Dihydrotestosterone in Male Mice.

Dehydroepiandrosterone (DHEA), an adrenal androgen precursor, can be metabolized in target tissues into active sex steroids. It has been proposed that DHEA supplementation might result in restoration of physiological local sex steroid levels, but knowledge on the effect of DHEA treatment on local sex steroid levels in multiple tissues is lacking. To determine the effects of DHEA on tissue-specific levels of sex steroids, we treated orchiectomized (ORX) male mice with DHEA for 3 weeks and compared them with vehicle-treated ORX mice and gonadal intact mice. Intra-tissue levels of sex steroids were analyzed in reproductive organs (seminal vesicles, prostate, m. levator ani), major body compartments (white adipose tissue, skeletal muscle, and brain), adrenals, liver, and serum using a sensitive and validated gas chromatography–mass spectrometry method. DHEA treatment restored levels of both testosterone (T) and dihydrotestosterone (DHT) to approximately physiological levels in male reproductive organs. In contrast, this treatment did not increase DHT levels in skeletal muscle or brain. In the liver, DHEA treatment substantially increased levels of T (at least 4-fold) and DHT (+536%, P < 0.01) compared with vehicle-treated ORX mice. In conclusion, we provide a comprehensive map of the effect of DHEA treatment on intra-tissue sex steroid levels in ORX mice with a restoration of physiological levels of androgens in male reproductive organs while DHT levels were not restored in the skeletal muscle or brain. This, and the unexpected supraphysiological androgen levels in the liver, may be a cause for concern considering the uncontrolled use of DHEA.

Advances in the cellular immunological pathogenesis and related treatment of primary ovarian insufficiency.

To describe the immunological mechanism in the pathogenesis of premature ovarian insufficiency (POI), summarize the alternations in humoral immunity and cellular immunity in patients with POI, and review some associated treatment methods based on these immunological changes. Symptoms of patients with POI are similar to that of menopause, such as amenorrhea, anovulation, early depletion of the ovarian reserve, decreased estrogen, and elevated follicle-stimulating hormone (FSH) levels. Therefore, most previous research has focused on finding ovary-related antibodies. In recent years, advances in the field of immunology have increased our understanding of the pathogenic mechanism of POI, which includes changed levels of cytokines and immunological cells especially Tregs cells and Th17 cells. Based on these advances, many associatedtreatment methods including DHEA supplementation, Traditional Chinese Medicine, adoptive transfer of Treg cells and stem cell transplantation have become research hotspots. This review focuses on the current literature regarding alterations in cellular immunity in patients with POI, as well as the role in the pathogenesis of POI, and summarizes treatment methods based on these immunological alternations, which have a great application potential in the clinical practice.

P-613 Association between basal androgen concentrations and number of follicles on the day of triggering final oocyte maturation in poor responders undergoing IVF; A prospective study

Abstract Study question Are basal androgen concentrations associated with the number of follicles on the day of triggering final oocyte maturation in poor responders undergoing in vitro fertilization (IVF)? Summary answer A significant negative association is present between (dehydroepiandrosterone sulfate) DHEAS concentrations and the number of follicles on the day of triggering final oocyte maturation. What is known already Studies in animals have shown that androgens promote early follicular development and granulosa cell proliferation, by augmenting follicle-stimulating hormone (FSH) receptor expression in granulosa cells. Several retrospective studies have evaluated the association between basal androgen concentrations and follicular development in normal and poor responders undergoing ovarian stimulation for IVF with conflicting results. Study design, size, duration This prospective study was performed between 02/2020 and 01/2022 in 103 poor responders according to the Bologna criteria. Androgens, including total testosterone, sex hormone-binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEAS), Δ4-androstenedione and 17-OH progesterone (17-OHP), were measured at the initiation of ovarian stimulation, using the automated Elecsys immunoanalyser (Roche Diagnostics, Mannheim, Germany). Ovarian stimulation was performed using a fixed dose of 300 IU of recombinant gonadotrophins and gonadotrophin-releasing hormone (GnRH) analogues. Participants/materials, setting, methods Triggering of final oocyte maturation was performed in the presence of three follicles of ≥ 17mm. The primary outcome measure was the number of follicles ≥11mm on the day of triggering final oocyte maturation. The association between androgen concentrations and the number of follicles ≥11mm on the day of triggering was evaluated using generalized estimating equations, accounting for female age and body mass index (BMI). Values were expressed as coefficient (coef) or mean (95% confidence interval). Main results and the role of chance Female age was 41.9 (41.2-42.6) years, while BMI was 26.1 (24.9-27.3) kg/m2. The duration of ovarian stimulation was 10.3 (9.7-10.8) days and the total dose of gonadotrophins required was 3058 (2903-3213) IU. The number of follicles ≥11 mm on the day of triggering final oocyte maturation was 6.1 (5.3-7.0). The number of COCs retrieved was 3.9 (3.2-4.6), the number of MII oocytes was 3.4 (2.8-3.9) and the number of 2pn oocytes was 2.5 (2.1-2.8). No significant association was found between basal testosterone (coef: -0.008, -0.019 to + 0.003, p = 0.17), 17-OHP (coef: -0.044, -0.391 to + 0.303, p = 0.80), SHBG (coef: -0.002, -0.007 to + 0.002, p = 0.25) Δ4-androstenedione (coef: -0.101, -0.306 to + 0.104, p = 0.33) concentrations and the number of follicles ≥11mm on the day of triggering final oocyte maturation. In contrast, a significant negative association was found between basal DHEAS (coef: -0.011, -0.019 to -0.003, p = 0.007) concentrations and the number of follicles ≥11 mm on the day of triggering final oocyte maturation. Higher DHEAS concentrations were associated with the development of fewer follicles ≥11 mm. Limitations, reasons for caution This prospective study evaluated the association between basal androgen concentrations and the number of follicles on the day of triggering final oocyte maturation in poor responders stimulated with a fixed dose of recombinant FSH. However, the precision of the estimates could be increased by analyzing a larger study population. Wider implications of the findings DHEA supplementation in poor responders undergoing IVF has not been shown to improve ovarian response. Given the significant negative association between DHEAS concentrations and the number of follicles on the day of triggering final oocyte maturation, future studies on DHEA supplementation should consider basal DHEAS concentrations. Trial registration number N/A

Insight on the intracrinology of menopause: androgen production within the human vagina

ABSTRACT Introduction The human vagina is extremely sensitive to hormonal changes occurring during the woman's lifetime, in particular the decline in estrogens that characterizes the menopause is known to induce a range of genital and sexual symptoms (dryness, burning, irritation, lack of lubrication, discomfort, pain), known as “genitourinary syndrome of menopause” (GSM). However, this reduction in estrogen levels is also accompanied by a progressive ageing-dependent decline in androgens for which the role of androgens in the development and treatment of GSM has received more attention. It is known that peripheral tissues compensate for circulating hormonal imbalances through the in-situ production of small quantities of sex hormones deriving from inactive precursors metabolized by specific cellular enzymes. This non-classical production and local activity of hormones is defined as “intracrinology”. Objective The aim of the study was to investigate whether the human vagina possesses the specific enzymatic machinery to convert weak androgen precursors, such as DHEA, into active androgens [Δ4-androstenedione (A), testosterone (T) and dihydrotestosterone (DHT)] as already described in other species. Methods In this study, a well established model of human smooth muscle cells (hSMCs), isolated from vagina tissues of women undergoing surgery for benign gynecological diseases, was used. Semi-quantitative RT-PCR was employed in order to evaluate the mRNA expression of the steroidogenic markers in hSMCs and corrispective tissue. The production of androgens was quantified in hSMCs medium by liquid chromatography tandem-mass spectrometry (LC-MS/MS). Results In vaginal tissues, AR mRNA was significantly less expressed than estrogen receptor α (ERα), whereas in hvSMCs, its mRNA expression was higher than progestin and both estrogen receptors. In hvSMCs and in vaginal tissue, when compared to ovaries, the mRNA expression of pro-androgenic steroidogenic enzymes (HSD3β1/β2, HSD17β3/β5), along with 5α-reductase isoforms and sulfo-transferase, resulted as being more abundant. In addition, enzymes involved in androgen inactivation were less expressed than in the ovaries. The LC-MS/MS analysis revealed that, in hvSMCs, short term DHEA supplementation increased Δ4-androstenedione levels in spent medium, while increasing testosterone (T) and dihydrotestosterone (DHT) secretion after longer incubation. Finally, androgenic signaling activation was evaluated through AR-dependent marker mRNA expression, after DHEA and T stimulation. Conclusions This study provides evidence for the presence of steroidogenic machinery in the human vagina, supporting, for the first time, the construct of intracrinology in this organ, emphasizing that the vagina is an androgen-dependent organ. These observations suggest the potential mechanism and resulting action of intravaginally administered DHEA, recently indicated for the treatment of GSM and open new perspectives for the treatment of this common and bothersome condition. Disclosure Work supported by industry: no.

O-176 Secondary ovarian insufficiency (SOI) - a new infertility diagnosis

Abstract Study question Can, in contrast to primary ovarian insufficiency (POI), ovarian insufficiency also be caused as a secondary event (SOI)? Summary answer Adrenal hypo-androgenism, caused by insufficiency in androgen production by the zona reticularis, may mimic POI in clinical presentation. What is known already A variety of small and large animal models have, especially at small growing follicle stages, conclusively demonstrated the dependence of normal follicle maturation on adequate testosterone levels, a process mediated via the androgen receptor on granulosa cells. Increasing clinical evidence, moreover, has demonstrated clinical improvements in oocyte numbers and oocyte quality following androgen supplementation at these stages in hypo-androgenic women with premature ovarian aging (POA). Whether adrenal hypo-androgenism in extreme cases can, however, also lead to complete ovarian insufficiency mimicking POI, is unknown. Study design, size, duration Based on FSH levels &amp;gt;40.0 mIU/mL and amenorrhea, we searched our center’s electronic research data bank for patients who between 2016-2018 presented with a diagnosis of presumed POI. Participants/materials, setting, methods Among 78 POIs, 13 demonstrated low DHEAS (&amp;lt; 100 ug/dL), i.e., adrenal hypo-androgenism, 6 rejected egg donation and received DHEA (Fertinatal®, 25mg TID, Fertility Nutraceuticals, LLC, New York, N.Y., USA) and Coq10 (Ovoenergen®, 333mg TID,same ­manufacturer) before stimulation with 450IU FSH and 150 IU hMG (different ­manufacturers). All women were &amp;lt; age 41, demonstrated menopausal FSH (&amp;gt;40.0 mIU/mL), undetectable AMH, amenorrhea, &amp;gt; prior cycle cancellation, elevated SHBG, low total testosterone and low DHEAS (high DHEA/DHEAS). Main results and the role of chance Out of the 6 patients so stimulated, 5 demonstrated follicular responses following DHEA supplementation and 2/6 conceived spontaneously and delivered healthy offspring. One of these two is currently in treatment for another child. Limitations, reasons for caution To better understand adrenal control of ovaries via androgen production, further elucidation of endocrine signaling between adrenals and ovaries is required, including detection of unknown, though increasingly likely, feedback loops, considering that adrenals and ovaries share a primordium. Wider implications of the findings We confirmed existence of SOI due to adrenal hypoandrogenism, defined its phenotype, demonstrating that some patients with alleged POI actually exhibit SOI. Better pregnancy chances with adrenal SOI than POI, reemphasize the importance of correct differential diagnoses to avoid premature referrals of women into third-party egg donations Trial registration number N/A

A form of secondary ovarian insufficiency (SOI) due to adrenal hypoandrogenism as new infertility diagnosis.

Mediated via the androgen receptor on granulosa cells, models of small growing follicle stages demonstrate dependence on testosterone. Androgen deficiency reduces ovarian response to follicle stimulation hormone (FSH), granulosa cell mass and estradiol (E2) production falls and FSH, therefore, rises. Though potentially of adrenal and/or ovarian origin, androgen deficiency in association with female infertility is almost universally primarily of adrenal origin, raising the possibility that women with presumptive diagnosis of primary ovarian insufficiency (POI), also called primary ovarian failure (POF) may actually suffer from secondary ovarian insufficiency (SOI) due to adrenal hypoandrogenism that leads to follicular arrest at small-growing follicle stages. This retrospective cohort study was performed in a private, academically affiliated infertility center in New York City. We searched the center's anonymized electronic research data bank for consecutive patients who presented with a diagnosis of POI, defined by age <41 year, FSH > 40.0 mIU/mL, amenorrhea for at least 6 month, and low testosterone (T), defined as total T (TT) in the lowest age-specific quartile of normal range. This study did not include patients with oophoritis. Since dehydroepiandrosterone sulfate (DHEAS) is the only androgen almost exclusively produce by adrenals, adrenal hypoandrogenism was defined by DHEAS < 100ug/dL. Thirteen of 78 presumed POI women (16.67%) qualified and represented the original study population. POI patients are usually treated with third-party egg donation; 6/13, however, rejected egg donation for personal or religious reasons and insisted on undergoing at least one last IVF cycle attempt (final study population). In preparation, they were supplemented with DHEA 25 mg TID and CoQ10 333 mg TID for at least 6 weeks prior to ovarian stimulation for IVF with FSH and human menopausal gonadotropins (hMG). Since POI patients are expected to be resistant to ovarian stimulation, primary outcome for the study was ovarian response, while secondary outcome was pregnancy/delivery. Though POI/POF patients usually are completely unresponsive to ovarian stimulation, to our surprise, 5/6 (83.3%) patients demonstrated an objective follicle response. In addition, 2/6 (33.3%) conceived spontaneously between IVF cycles, while on DHEA and CoQ10 supplementation and delivered healthy offspring. One of those is currently in treatment for a second child. This preliminary report suggests that a surprising portion of young women below age 41, tagged with a diagnosis of POI/POF, due to adrenal hypoandrogenism actually suffer from a form of SOI, at least in some cases amenable to treatment by androgen supplementation. Since true POI/POF usually requires third-party egg donation, correct differentiation between POI and SOI in such women appears of great importance and may warrant a trial stimulation after androgen pre-supplementation for at least 6 weeks.

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.

Ovarian stimulation after dehydroepiandrosterone supplementation in poor ovarian reserve: a randomized clinical trial.

This study aimed at improving fertility rates among infertile women with poor ovarian reserve. This was a randomized clinical trial conducted in the outpatient clinic of a tertiary hospital. We recruited infertile women with poor ovarian reserve. The study population was divided into 2 groups, each of 25 participants. Both had induction of ovulation for three consecutive cycles. Study group took DHEA supplementation 25mg/8h for two consecutive cycles before induction of ovulation. Both groups were compared for outcomes of induction. Baseline ovarian reserve tests and antral follicle count (AFC) were done for both groups before induction of ovulation. The study group repeated these baseline tests after DHEA treatment to compare ovarian reserve before and after DHEA supplementation. Outcome measures were the number of mature follicles at the time of ovulation, the number of gonadotrophin ampoules needed for induction of ovulation, the duration of ovarian stimulation, E2 level at the day of HCG injection. The study group baseline investigations after DHEA treatment showed a statistically significant improvement compared to the control group. The outcomes of induction of ovulation in the study group showed a statistically better response than the control group. DHEA may help many poor responders so better considered for poor responder patients. PACTR201911829230395.

Effect of dehydroepiandrosterone on the liver of perimenopausal rat: multiple doses study

ABSTRACTDehydroepiandrosterone (DHEA) is a widespread nutritional “anti-aging” supplement. Exogenous supplementation of DHEA is now being commonly used to augment ovarian stimulation in perimenopausal women with diminished ovarian reserve. Whether DHEA causes side effects in such age is, however, unknown. Thus, this study investigates the effects of pharmacological doses of DHEA supplementation on the liver of perimenopausal rats. DHEA supplementation to perimenopausal rats resulted in slight hepatomegaly and steatosis, hepatocytic hypertrophy, mitochondrial swelling, elevation in serum alanine aminotransaminase levels, in addition to the accumulation of lipid droplets and lipolysosomes in a dose-dependent manner. In conclusion, long-term administration of high doses of DHEA causes ultrastructural alterations and changes in the levels of cholesterol and triglyceride in hepatocytes of perimenopausal rats. DHEA at a dose of 50 mg/kg improves health and decreases the body weight, with the least side effects on the liver of perimenopausal rats.

Dehydroepiandrosterone supplementation is not beneficial in the late postmenopausal period in diet-induced obese rats

AimsDehydroepiandrosterone (DHEA) is an adrenal steroid hormone that is a precursor of sexual hormones. It is reduced during aging and is strongly associated with insulin resistance and obesity. There is evidence for beneficial effects of this steroid, in both human and animal models, during perimenopause. However, the impact of DHEA treatment during late postmenopause on glucose metabolism is not clearly documented. We tested the hypothesis that DHEA supplementation could improve insulin sensitivity in an ovariectomized obese rat model (OVX) that was fed a high-fat diet for 11 weeks. Main methodsFemale Wistar rats at 8 weeks of age were OVX or SHAM-operated. Eight weeks after the surgery, the animals were randomly treated with vehicle or DHEA for 3 weeks. Food intake, metabolic parameters and insulin sensitivity were evaluated. Key findingsFollowing the ovariectomy, increased body weight gain, adiposity index, and feeding efficiency were observed, despite there being no change in food and energy intake. The OVX rats also displayed glucose intolerance, insulin resistance, decreased insulin-induced IRS1/2 tyrosine phosphorylation in the skeletal muscle, and reduced serum VLDL-c and TAG levels. OVX rats treated with 10 mg/kg DHEA (OVX + DHEA) exhibited estradiol (E2) serum levels similar to SHAM animals, with no change in uterus mass. DHEA treatment also resulted in an increase in energy intake. SignificanceDespite the positive effects of DHEA supplementation observed in menopausal women and ovariectomized rats, a potential negative effect on glucose metabolism and insulin action in the late postmenopausal condition in diet-induced obese OVX rats are reported.

The effect of 12-month dehydroepiandrosterone supplementation on the menstrual pattern, ovarian reserve markers, and safety profile in women with premature ovarian insufficiency.

To evaluate the effect of 12-month DHEA supplementation on menstrual pattern and ovarian reserve markers in women with premature ovarian insufficiency (POI) METHODS: This is a prospective observational study. Women with POI were given DHEA supplements (25mg three times daily) for 12months. Sonographic assessment for ovarian volume and antral follicle count (AFC) and serum measurement for anti-Mullerian hormone (AMH), follicle stimulating hormone (FSH), estradiol, testosterone, liver function, and hemoglobin level were performed at baseline and monthly for 13months after the supplementation. Menstrual pattern, ovarian reserve markers, and side-effects were recorded. Between August 2011 and July 2014, 38 women with POI were recruited and 31 completed the study. The median age of women was 36years, and the median baseline FSH and AMH concentrations were 82.2IU/L and 0.01ng/ml, respectively. No women had resumption of regular menstruation after DHEA supplementation. AMH, FSH, and AFC did not change significantly. No serious side effects were reported. Our results do not support any significant improvement in ovarian function by 12-month DHEA supplementation in women with POI.

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.

MP87-12 ADRENAL ANDROGENS FACILITATE PROSTATE CANCER CELL RESISTANCE TO ANDROGEN DEPRIVATION THERAPY

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology III1 Apr 2017MP87-12 ADRENAL ANDROGENS FACILITATE PROSTATE CANCER CELL RESISTANCE TO ANDROGEN DEPRIVATION THERAPY Michael Fiandalo, John Stocking, Elena Pop, Krystin Mantione, John Wilton, and James Mohler Michael FiandaloMichael Fiandalo More articles by this author , John StockingJohn Stocking More articles by this author , Elena PopElena Pop More articles by this author , Krystin MantioneKrystin Mantione More articles by this author , John WiltonJohn Wilton More articles by this author , and James MohlerJames Mohler More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.2716AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Prostate Cancer (CaP) growth and survival is dependent on the interaction of androgen receptor (AR) and testicular androgens, testosterone and dihydrotestosterone (DHT). Men that fail potential curative treatment are treated with androgen deprivation therapy (ADT). ADT is palliative and CaP recurs as the lethal phenotype. One mechanism that contributes to CaP recurrence is intratumoral intracrine androgen metabolism, which is the conversion of weak adrenal androgens (androstenedione [ASD] or dehydroepiandrosterone [DHEA]) to T or DHT. Mice lack adrenal androgens and therefore adrenal androgen contribute to CaP xenograft recurrence is overlooked. The hypothesis for these studies is adrenal androgen supplementation will facilitate androgen dependent human CaP CWR22 xenograft resistance to ADT. METHODS Mice were castrated, implanted with CWR22 and silastic tubes that contained T and empty silastic tubes that contained ASD or DHEA. T silastic tubes were removed after CWR22 tumor volumes reached 0.5 cc to simulate ADT. Digital calipers were used to measure changes in CWR22 tumor volume. Mouse serum, prostate and CWR22 were harvested at designated time points and liquid chromatography tandem-mass spectrometry (LC-MS/MS) was performed to measure androgen levels. RESULTS CWR22 xenografts treated with no adrenal androgen regressed and began to grow 120 days after T silastic tube removal. ASD treated CWR22 tumors did not regress; CWR22 tumor growth increased and mice were euthanized because tumors grew beyond veterinary limits. DHEA treated CWR22 did not regress and did not grow like ASD treated CWR22. However, CWR22 xenografts recurred faster than control CWR22 xenografts. Serum PSA levels correlated with tumor volume. CWR22 androgen levels decreased in all treatment groups, but T levels remained sufficient to activate AR in ASD treated CWR22, but not control or DHEA treated CWR22 xenografts. CONCLUSIONS DHEA and ASD supplementation facilitated CWR22 resistance to ADT. However, CWR22 xenografts responded differently to DHEA and ASD, which suggests that adrenal androgens may play different roles when CaP cells undergo ADT. These studies show that adrenal androgen contributes should be taken into account when in vivo studies are performed to test CaP responses to ADT or therapeutic agents. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e1170 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Michael Fiandalo More articles by this author John Stocking More articles by this author Elena Pop More articles by this author Krystin Mantione More articles by this author John Wilton More articles by this author James Mohler More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Hemoglobin during ribavirin-based HCV therapy is closely related to circulating levels of DHEA.

Ribavirin-induced anemia is the major side effect observed during HCV therapy. In an in vitro study, we recently discovered that DHEA can strongly inhibit this adverse event. We also evaluated a possible link between pre-treatment serum DHEA and hemoglobin during HCV therapy. Among the 108 patients of our cohort serum baseline DHEA levels were associated with hemoglobin levels at week 12 of treatment (r = 0.35; P = 0.0021). Patients with low baseline serum DHEA developed severe anemia. A serum level of DHEA less than 1,500 ng/ml had a sensitivity of 94.3% and a positive predictive value of 93.1% for the detection of hemoglobin less than 11 g/dl during the first 12 week of treatment. With pre-treatment DHEA levels below the cutoff, anemia was observed in 24.4% and 60.5% of patients treated with dual therapy and triple therapy, respectively, versus 0% and 15% of patients with higher DHEA levels. At week 12, the mean difference between patients with serum DHEA below and above the cutoff, in terms of absolute hemoglobin for dual and triple therapy groups were 1.2 and 1.7 g/dl, respectively (P = 0.005 and <0.001). Pretreatment DHEA levels are associated with hemoglobin levels during treatment. Based on these data, pretreatment assay of DHEA could be considered systematically in order to propose DHEA supplementation to potentiate the efficacy of the current and future use of ribavirin for HCV and HEV therapy. J. Med. Virol. 89:1033-1039, 2017. © 2016 Wiley Periodicals, Inc.

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.

Effect of dehydroepiandrosterone administration in Chinese women over 37 years undergoing assisted reproductive techniques

ObjectiveTo evaluate the effect of DHEA supplementation on in vitro fertilization (IVF) parameters and pregnancy outcomes in patients older than 37 years with normal ovarian reserve. Study designA retrospective cohort study was conducted to evaluate the impact of DHEA supplementation on IVF outcome of infertile women over 37 years with normal ovarian reserve between January 2012 and July 2014. 243 patients (study group) received 75mg of DHEA daily (25mg three times daily) before the IVF cycle. Another 243 patients (control group) received infertility treatment, but did not receive DHEA. The IVF outcome parameters in each group were compared. ResultsBoth groups did not show statistically significant differences in terms of patient demographics characteristics, mean numbers of oocytes retrieved and mature oocytes rate. While patients in the DHEA group have the significantly higher implantation rate and live birth rate compared with controls (30.13% versus 22.70%, 43.33% versus 28.26%). We also found that the cycle cancellation rate and miscarriage rate were lower in the DHEA group (1.23% versus 5.34%, 13.33% versus 28.89%). ConclusionDHEA supplementation may significantly improve IVF outcomes in infertile women over the age of 37.

Expression of Prostate Specific Antigen(PSA) by Etoposide and Androgen in Human Prostate Cancer Cells

Prostate cancer(PrCa) is a leading cause of cancer-related death in man. Prostate specific antigen(PSA) is widely utilized as a marker for the diagnosis and monitoring of prostate cancer. This study examined effects of androgen 5α-dihydrotestosterone(DHT) vs DHEA and/or anticancer agent etoposide on proliferation and PSA expression of the prostate cancer LNCaP cells. A progressive increase in PSA secretion was observed at higher DHT concentration in case of 48 h treatment. compared to DHEA. Androgen played a significant role in the regulation of cellular proliferation and production of PSA in human prostate cancer LNCaP cells. In contrast with DHT, DHEA administration stimulated LNCaP cell proliferation in a time and dose-response manner, etoposide had a strong cytotoxic and apoptotic effect on LNCaP cells. Moreover, etoposide reduced cell growth and PSA expression induced by DHT and DHEA. These results demonstrate that etoposide could be a potential agent for the treatment of hormone refractory prostate cancer. Further studies of the mechanisms of DHEA will be required to discern the implication of DHEA supplementation on prostatic health because supplemental DHEA use may pose a cancer risk in patients with nascent or occult prostate cancer