Vitamin E modulates androgen receptor gene expression to attenuate ovarian dysfunctions in a rat model of dehydroepiandrosterone-induced polycystic ovary

Objective:To investigate the protective effect of vitamin E in dehydroepiandrosterone(DHEA)-induced polycystic ovary in rats.Methods:Premature female Wistar rats were randomly allocated into four groups,with 7 rats in each group.Group栺received corn oil(vehicle)and served as the control group;group栻received 0.2 mL of 0.06 mg/g DHEA in corn oil;group栿received 200 mg/kg vitamin E;group桇received DHEA plus vitamin E.All treatments lasted for 15 days,with DHEA administered subcutaneously,while vitamin E and corn oil were administered orally.After the experiment,serum samples and ovaries were harvested for biochemical,immunohistochemical,hormonal,and histological analysis.The ovarian mRNA expression of androgen receptor was analyzed by reverse transcriptase quantitative polymerase chain reaction(qPCR).Results:The antioxidant and metabolic enzyme activity significantly decreased in the DHEA-treated rats compared to the control rats(P<0.05).Administration of vitamin E to DHEAtreated rats significantly decreased cytokines and malondialdehyde compared to the DHEA-treated rats.The histological analysis showed reduced atretic and cystic ovaries,increased E-cadherin and Bcl-2 expression,and reduced expression of Bax in the DHEAtreated rats co-treated with vitamin E.The mRNA expression of androgen receptor was upregulated in the DHEA-treated rats compared to the control rats.Conclusions:Vitamin E ameliorates the hyperandrogenic effect of DHEA-induced polycystic ovaries via metabolic,antioxidant,and anti-apoptotic pathways.

Dehydroepiandrosterone sulfate supplementation in health and diseases

Dehydroepiandrosterone sulfate(DHEAS)is a hormone produced by the zona reticularis of the adrenal gland and the ovaries.Initially considered as an inert compound merely serving as an intermediate in the conversion of cholesterol to androgens,interest in DHEA began to grow in the 1960s when it was found that DHEAS is the most abundant steroid hormone in human plasma and that its levels decline with age.In many countries,DHEA is considered a nutritional supplement.It has been used for a multitude of conditions which include sexual dysfunction,infertility,genitourinary syndrome of menopause,musculoskeletal disorders,cardiovascular diseases,ageing,neurological diseases,autoimmune conditions,adrenal insufficiency,and anorexia nervosa.We describe an overview of the historical evolution of DHEA,its physiology,and the disease states where it has been evaluated as a supplement.

<i>In-Vitro</i>Determination of Biological and Anabolic Functions of Weak Androgen Dehydroepiandrosterone (DHEA) Using a Variety of Cell Lines

Dehydroepiandrosterone (DHEA) is a weak androgen and is shown to have anti-cancer, anti-atherogenic, anti-adipogenic and anti-inflammatory effects on mouse, rat and rabbit models. However, human clinical trials data did not support animal findings and were inconclusive. These systemic differences in biological actions between rodents and humans were attributed to the low level of DHEA in rodents. In order to further understand the differences in biological functions between rodents and humans, we resorted to an in-vitroapproach involving mouse, rat and human cell lines to assess DHEA biological and anabolic functions separately and independently without systemic influence. Results indicated that DHEA was effective on mouse and rat cell lines but not on human cell lines, as observed in in-vivo studies. In addition, our in-vitrostudy showed that DHEA was able to induce myogenesis in mouse mesenchymal cells revealing its anabolic function, even though DHEA was considered as a weak androgen. This observation lent credence to the ban on DHEA by IOC medical commission, citing DHEA as an anabolic steroid. These in-vitro experiments suggested that the differences in biological actions of DHEA between rodents and humans existed not only in-vivo at the systemic level, but also in-vitro at the cellular level and thus paving the way to study the mechanism responsible for these differences at the cellular level itself.

Unilateral Fimbria/Fornix Transection Prevents the Synaptoplastic Effect of Dehydroepiandrosterone in the Hippocampus of Female, but Not Male, Rats

Dehydroepiandrosterone (DHEA), the most abundant adrenal androgen in primates, is also synthesized from cholesterol in the brain. Like testosterone, DHEA induces spine synapse formation in the hippocampus. In female rats, this response is blocked by co-administration of an inhibitor of aromatase, the enzyme responsible for estrogen biosynthesis. In males, by contrast, the hippocampal synaptic response to DHEA is unaffected by treatment with an aromatase inhibitor. We hypothesized that this sex difference might reflect differential dependence of the hippocampal responses on subcortical afferents from the basal forebrain. To test this hypothesis, we examined the effects of unilateral fimbria/ fornix transection (FFX) on DHEA-induced synapse formation in the cornu ammonis 1 (CA1) hippocampal subfield of gonadectomized female and male rats. In ovariectomized females, CA1 spine synapse density after DHEA treatment was reduced by more than 60% ipsilateral to FFX. In males, however, unilateral FFX transection had no effect on spine synapse density after DHEA treatment. These results suggest that sex differences in the dependence on local estrogen biosynthesis of the CA1 synaptic response to androgen may at least in part be the result of sex differences in the relative contributions of afferents to the hippocampus from the basal forebrain.

Role of Dehydroepiandrosterone Supplementation in Improving Intracytoplasmic Sperm Injection Outcome for Women with Expected Poor Ovarian Response

Background: As regard to adjuvant supplementations, nowadays dehydroepiandrosterone (DHEA) is widely used all over the world and is considered to be a potential agent to ameliorate the assisted reproduction technologies outcomes of infertile women with poor ovarian reserve. Objective: To find out the role of DHEA supplementation in improving intracytoplasmic sperm injection (ICSI) outcome for infertile women with expected poor ovarian response in controlled ovarian stimulation. Setting: Assisted reproduction unit of Obstetrics and Gynecology Department, Faculty of Medicine, South Valley University, Egypt. Duration: From April 2016 to May 2018. Study Design: A randomized double-blinded controlled trial. Methods: One hundred and forty infertile women with expected poor ovarian response prepared for ICSI procedure were included in this study. Patients were divided into two groups;group I (DHEA group) included 70 patients received 25 mg DHEA 12 weeks prior to ICSI cycle and group II (placebo group) included 70 patients received a placebo. Results: There was a highly statistically significant difference in basal AFC at start of ICSI cycle in group I (who received DHEA supplementation for 12 weeks prior to ICSI procedure) than in group II (13.8 ± 5.3 versus 10.7 ± 4.6 respectively) with P < 0.001. There were mildly statistically significant differences between group I and group II as regard to increase in the number and quality of retrieved oocytes, increased in endometrial thickness, fertilization rate and embryo quality with p value < 0.05 but there was no statistically significant difference between the 2 groups as regard to pregnancy (chemical and clinical) rates (p value > 0.05). Conclusions & Recommendations: DHEA supplementations improved basal AFC, increased the number & quality of oocytes and increased quality of embryos in infertile patients with expected poor ovarian response in ICSI procedure. So DHEA supplementations could be an important adjuvant for infertile women with expected poor ovarian response in ICSI procedure.

The Effect of Dehydroepiandrosterone on the Expression of AT_1 receptor and TNF-induced ICAM-1 in Vascular Smooth Muscle Cells

Objectives To further invest- igate the molecular mechanism of vasoprotective role of dehydroepiandrosterone (DHEA), we examined DHEA on AT1 receptor and ICAM-1 gene expression in vascular smooth muscle cells (VSMCs). Methods RT-PCR and Western Blot was used to determine the change of the expressions of mRNA and protein of AT1 and ICAM- 1 when given various concentration dehydroepian- drosterone. Results 1.AT1 was abundant under the basal condition. The expression of AT1 mRNA and protein decreased after stimulated by DHEA (at 10- 10mol/L , 10-8 mol/L, 10-6 mol/L) , and the effects of DHEA on AT1 protein was dose-dependent. ER inhibitor Tamoxifen and AR inhibitor Flutamide enhanced AT1 protein expression, but did not influence the mRNA expression. 2. The exp-ression of ICAM-1 gene was low under the basal condition.It increased when induced by TNF-α,but decreased when induced by DHEA (at 10-10 mol/L, 10-8 mol/L, 10-6 mol/L) , and the effects of DHEA on ICAM-1 gene expression were dose-dependent. Conclusions These findings suggest that DHEA modulates AT1 and inflammatory factor induced ICAM-1 gene expression in VSMC, but further studies are necessary in the mecha-nism of DHEA action.

Human-like adrenal features in Chinese tree shrews revealed by multi-omics analysis of adrenal cell populations and steroid synthesis

The Chinese tree shrew(Tupaia belangeri chinensis)has emerged as a promising model for investigating adrenal steroid synthesis,but it is unclear whether the same cells produce steroid hormones and whether their production is regulated in the same way as in humans.Here,we comprehensively mapped the cell types and pathways of steroid metabolism in the adrenal gland of Chinese tree shrews using single-cell RNA sequencing,spatial transcriptome analysis,mass spectrometry,and immunohistochemistry.We compared the transcriptomes of various adrenal cell types across tree shrews,humans,macaques,and mice.Results showed that tree shrew adrenal glands expressed many of the same key enzymes for steroid synthesis as humans,including CYP11B2,CYP11B1,CYB5A,and CHGA.Biochemical analysis confirmed the production of aldosterone,cortisol,and dehydroepiandrosterone but not dehydroepiandrosterone sulfate in the tree shrew adrenal glands.Furthermore,genes in adrenal cell types in tree shrews were correlated with genetic risk factors for polycystic ovary syndrome,primary aldosteronism,hypertension,and related disorders in humans based on genome-wide association studies.Overall,this study suggests that the adrenal glands of Chinese tree shrews may consist of closely related cell populations with functional similarity to those of the human adrenal gland.Our comprehensive results(publicly available at http://gxmujyzmolab.cn:16245/scAGMap/)should facilitate the advancement of this animal model for the investigation of adrenal gland disorders.

Dehydroepiandrosterone:a potential therapeutic agent in the treatment and rehabilitation of the traumatically injured patient

Severe injuries are the major cause of death in those aged under 40,mainly due to road traffic collisions.Endocrine,metabolic and immune pathways respond to limit the tissue damage sustained and initiate wound healing,repair and regeneration mechanisms.However,depending on age and sex,the response to injury and patient prognosis differ significantly.Glucocorticoids are catabolic and immunosuppressive and are produced as part of the stress response to injury leading to an intra-adrenal shift in steroid biosynthesis at the expense of the anabolic and immune enhancing steroid hormone dehydroepiandrosterone(DHEA)and its sulphated metabolite dehydroepiandrosterone sulphate(DHEAS).The balance of these steroids after injury appears to influence outcomes in injured humans,with high cortisol:DHEAS ratio associated with increased morbidity and mortality.Animal models of trauma,sepsis,wound healing,neuroprotection and burns have all shown a reduction in proinflammatory cytokines,improved survival and increased resistance to pathological challenges with DHEA supplementation.Human supplementation studies,which have focused on post-menopausal females,older adults,or adrenal insufficiency have shown that restoring the cortisol:DHEAS ratio improves wound healing,mood,bone remodelling and psychological well-being.Currently,there are no DHEA or DHEAS supplementation studies in trauma patients,but we review here the evidence for this potential therapeutic agent in the treatment and rehabilitation of the severely injured patient.

Heyan Kuntai capsule versus dehydroepiandrosterone in treating Chinese patients with infertility caused by diminished ovarian reserve： a multicenter, randomized controlled trial

OBJECTIVE: To evaluate the clinical efficacy and safety of Heyan Kuntai capsule(HYKT) in treating women with infertility caused by diminished ovarian reserve(DOR).METHODS: One hundred eight eligible patientsfrom three Chinese hospitals were randomly divided into an HYKT treatment group(n = 55) or a dehydroepiandrosterone(DHEA) treatment group(n =53). Patients in the HYKT group were treated orally with four 0.5 g HYKT three times a day; patients in the DHEA group were treated with one 25.0 mg DHEA capsule three times a day. All patients were treated for 3 months and followed up over a3-month period.RESULTS: Of 108 patients, 12 dropped out: six from the HYKT group, and six from the DHEA group. Eleven patients got pregnant during the treatment. Serum anti-Müllerian hormone levels and antral follicle counts increased significantly in both groups after treatment(P < 0.05) especially in the HYKT group(P < 0.05). Serum follicle stimulating hormone(FSH) levels and FSH/luteinizing hormone ratios decreased(P < 0.05) with no significant difference between the two groups. Estradiol levels in the HYKT group and DHEA-sulfate levels in the DHEA group both increased(P < 0.05). The spontaneous pregnancy rates were 12% and 11% in the HYKT and DHEA groups, respectively(not significant). During the follow-up period, 16 patients in the HYKT group underwent in vitro fertilization-embryo transfer(IVF-ET) and the number of retrieved oocytes was(5.1 ± 1.8). In DHEA group, 20 patients underwent IVF-ET and the number of retrieved oocyte was(4.2 ± 1.9)(not significant); clinical pregnancy rates were 38% in the HYKT group and 20%in DHEA group(not significant). No significant adverse reactions were observed.CONCLUSION: HYKT can improve the ovarian re-serve and hormone levels in patients with infertility caused by DOR. Pregnancy rates after HYKT treatment were similar to those of DHEA treatment.HYKT might be an alternative to the treatment of infertility caused by DOR.

Dehydroepiandrosterone Inhibited the Bone Resorption through the Upregulation of OPG/RANKL

The plasma level of dehydroepiandrosterone （DHEA） is decreases gradually along with aging. The beneficial effects of DHEA as an anti-aging steroid, such as the stimulatory effect on immune system, anti-diabetes mellitus, antl-atherosclerosis, anti.dementia, anti-obesity and anti-osteoporosis have been demonstrated in experiment both in vitro and in vivo. It is important to investigate the effective mechanism of DHEA in therapeutics for postmenopausal osteoporosis. Having isolated and cultured osteoblasts （OBs） and osteoclasts （OCs）, we analysed the effect of DHEA on osteoblastic viability, regulation of DHEA on the expression of osteoprotegerin （OPG）/receptor activator of NF-κB Ugand （RANKL） mRNA in OBs, and then observed the action of DHEA on bone resorption of OCs in the presence or absence of OBs. The results showed that DHEA improved viability of OBs within the concentration range of 10^-8-10^-6 M, especially at the concentration of 10^-7 M. DHEA could apparently increase the ratio of OPG/RANKL mRNA in OBs. In the presence of OBs, DHEA could decrease the number and area of absorption lacuna of specula. We concluded, therefore, only in the presence of OBs, DHEA could inhibit the bone resorption of OCs, which may be mediated by OPG/RANKL of OBs.

Effects of Ziyin Jianghuo Ningxin decoction plus dehydroepiandrosterone and femoston in treatment of patients with menopausal symptoms

OBJECTIVE: To determine the therapeutic effect of Ziyin Jianghuo Ningxin Decoction(ZYJHNXD) plus dehydroepiandrosterone(DHEA) and menopausalhormone therapy(MHT) in patients suffering from menopausal symptoms identified as, in terms of Traditional Chinese Medicine, symptom pattern of Yin deficiency with hyperactive fire.METHODS: Totally 180 postmenopausal women aged 40 to 60 years were assigned into four groups and accepted femoston, femoston with ZYJHNXD,femoston with DHEA, femoston with ZYJHNXD and DHEA therapies, respectively, for three months.Common questionnaire-based measure instruments included modified Kupperman index(MKI),Hamilton Rating Scale for Anxiety(HAMA), and Hamilton Rating Scale for Depression(HAMD). Follicle-stimulating hormone(FSH), luteinizing hormone(LH), estradiol(E2), 5-hydroxyindole-3-acetic acid(5-HIAA), norepinephrine(NE), dopamine(DA),bone mineral density(BMD), and sleep quality were evaluated before and three months after the treatments.RESULTS: In all four groups, the scores of MKI, HAMA, HAMD and the levels of FSH, LH decreased significantly(P < 0.05) after the treatment, while the levels of E2, 5-HIAA, NE, and DA showed obvious elevation(P < 0.05). The group receiving ZYJHNXD and DHEA combined with femoston had superiority in the preservation of bone mineral density and improvement of total sleep time and nighttime sleep time over the other three groups.CONCLUSION: ZYJHNXD and DHEA combined with MHT therapy have a favorable outcome in managing menopausal symptoms, restoring hormone levels, preventing skeletal rarefaction or osteoporosis,and improving sleep quality for postmenopausal women.

Dehydroepiandrosterone indirectly inhibits human osteoclastic resorption via activating osteoblastic viability by the MAPK pathway

Background Dehydroepiandrosterone （DHEA） is widely known for its beneficial effect on postmenopausal osteoporosis, although the underlying mechanisms remain mainly unclear. In this study, we tried to determine the activation of mitogen-activated protein kinase signal pathways during DHEA treatment and the indirect role of osteoblasts （OBs） on osteoclasts under the DHEA treatment of postmenopausal osteoporosis. Methods Primary human OBs and osteoclast-like cells were cultured and, we pretreated OBs with or without U0126 （a highly selective inhibitor of both MEK1 and MEK2）. The OBs were treated with DHEA. We then tested the effects of DHEA on human osteoblastic viability, osteoprotegerin production and the expression of phosphor-ERK1/2 （extracellular signal-regulated kinase）. In the presence or absence of OBs, the function of osteoclastic resorption upon DHEA treatment was calculated. Results DHEA promoted the human osteoblastic proliferation and inhibited the osteoblastic apoptosis within the concentration range of 108-106 mol/L （P 〈0.05, P 〈0.01, respectively）. Within the effective concentration range, the expression of phosphor-ERK1/2 and osteoprotegerin was increased by DHEA and blocked by U0126. In the presence of OBs, DHEA could significantly decrease the number and the area of bone resorption lacuna （P 〈0.05 and P 〈0.01, respectively）. Without OBs, however, the effects of DHEA on the bone resorption lacuna were almost completely abolished. Conclusions DHEA could indirectly inhibit the human osteoclastic resorption through promoting the osteoblastic viability and osteoprotegerin production, which is mediated by mitogen-activated protein kinases signal pathway involving the phosphor-ERK1/2.

Screening of novel synthetic derivatives of dehydroepiandrosterone for antivirals against flaviviruses infections

Flaviviruses are important arthropod-borne pathogens that represent an immense global health problem.Their unprecedented epidemic rate and unpredictable clinical features underscore an urgent need for antiviral interventions.Dehydroepiandrosterone(DHEA)is a natural occurring adrenal-derived steroid in the human body that has been associated in protection against various infections.In the present study,the plaque assay based primary screening was conducted on 32 synthetic derivatives of DHEA against Japanese encephalitis virus(JEV)to identify potent anti-flaviviral compounds.Based on primary screening,HAAS-AV3026 and HAAS-AV3027 were selected as hits from DHEA derivatives that exhibited strong antiviral activity against JEV(IC_(50)=2.13 and 1.98μmol/L,respectively)and Zika virus(ZIKV)(IC_(50)=3.73 and 3.42μmol/L,respectively).Mechanism study indicates that HAAS-AV3026 and HAAS-AV3027 do not exhibit inhibitory effect on flavivirus binding and entry process,while significantly inhibit flavivirus infection at the replication stage.Moreover,indirect immunofluorescence assay,Western blot analyses,and quantitative reverse transcription-PCR(qRT-PCR)revealed a potent antiviral activity of DHEA derivatives hits against JEV and ZIKV in terms of inhibition of viral infection,protein production,and viral RNA synthesis in Vero cells.Taken together,our results may provide a basis for the development of new antivirals against flaviviruses.

Effects of Ning Shen Ling Granule (宁神灵冲剂) and Dehydroepiandrosterone on Cognitive Function in Mice Undergoing Chronic Mild Stress

Objective： To investigate the changes of spontaneous and cognitive behavior, and cholinergic M receptors in the brain of mice subjected to chronic mild stress （CMS）, and to determine the effect of Ning Shen Ling Granule （宁神灵冲剂, NSL） and dehydroepiandrosterone （DHEA） on them. Methods：CMS model mice were established by applying stress every day for 3 consecutive weeks with 7 kinds of unforeseeable stress sources, and they were medicated for 1 week beginning at the 3rd week of modeling. The changes in behavior were determined by Morris Water Maze and spontaneous movement test, and M-receptor binding activity in cerebral cortex, hippocampus and hypothalamus were measured by radioactive ligand assay with 3H-QNB. Results： （1） The spontaneous movement in CMS model mice was significantly reduced, with the latency for searching platform in Morris Water Maze obviously prolonged （P〈0.01）, and these abnormal changes in behavior were improved in those treated with NSL and DHEA. （2） The binding ability of M-receptor in cerebral cortex and hippocampus of CMS mice was significantly decreased as compared with those in the control group （P〈0.05）, but could be restored to the normal level after intervention with NSL or DHEA. Conclusion： The decline of spontaneous movement and spatial learning and memory ability could be induced in animals by chronic mild stress, and that may be related to the low activity of central cholinergic M-receptors. Both NSL and DHEA could effectively alleviate the above-mentioned changes.

Effects of Dehydroepiandrosterone on Embryo Quality and Follicular Fluid Markers in Patients with Diminished Ovarian Reserves

Background:To examine the effects of dehydroepiandrosterone(DHEA)on in vitro fertilization(IVF)intracytoplasmic sperm injection(ICSI)and the levels of follicular fluid(FF)markers,namely,anti-Müllerian hormone(AMH),insulin-like growth factor(IGF)-1,bone morphogenetic protein(BMP)-15,and growth differentiation factor(GDF)-9,in patients with diminished ovarian reserves(DORs).Methods:116 patients with DOR were randomized into two groups,DHEA group and control group.Each group contained 58 patients.The DHEA group received 75 mg/d of DHEA for 12 weeks prior to the start of IVF treatment,while the control group entered IVF treatment directly.All patients were treated with the same ovarian stimulation protocol.The primary outcome was high-quality embryo yield.Other IVF parameters,such as the clinical pregnancy rate,embryo survival rate,and intact blastomere rate,were compared between the two groups.FF samples from patients of both groups were collected to measure the levels of AMH,IGF-1,DHEA-sulfate,BMP-15,and GDF-9.Blood was also collected on day 3 of the menstrual cycle to define the baseline hormonal profile and to examine ovarian reserve markers.Results:The high-quality embryo yield was higher in DHEA group than that in control group(P=0.033).AMH and IGF-1 concentrations in FF were significantly higher in DHEA group than that in the control group(2.83±1.14 ng/L vs.1.37±0.55 ng/L,P=0.000;94.02±38.28 ng/L vs.74.03±25.46 ng/L,P=0.004,respectively).The BMP-15 level was also higher in DHEA group(relative expression were 1.80±0.41)than that in control group(relative expression were 0.79±0.16,P<0.0001);however,there was no difference in GDF-9 expression between the two groups(relative expression were 1.29±0.54 and 1.16±0.50 respectively,P>0.05)and in the clinical pregnancy rate between the two groups(13.79%vs.7.27%,respectively,P>0.05).Conclusions:In women with DOR undergoing IVF treatment,pretreatment with DHEA may increase the number of high-quality embryos,which may be due to increased levels of AMH,IGF-1,and BMP-15 in the FF.

MIF May Participate in Pathogenesis of Polycystic Ovary Syndrome in Rats through MAPK Signalling pathway

The polycystic ovary syndrome (PCOS) model was established in fats and correlation between the expression of macrophage migration inhibitory factor (MIF) and cytokinesis with the MAPK signalling pathway in the rat ovary was measured. The PCOS model in rats was established by dehydroepiandrosterone (DHEA).Thirty sexually immature female Sprague-Dawley rats were randomly and equally assigned to three groups:control group,PCOS group,and PCOS with high-fat diet (HFD) group.Serum hormones were assayed by radioimmunoassay (RIA).The ovaries'were immunohistochemically stained with MIF,and the expression of MIF,p-JNK and p-p38 was detected by Western blotting in ovaries.The serum testosterone level,LH concentration,LH/FSH ratio,fasting insulin level and HOMA IR index in the PCOS group (6.077±0.478,13.809±1.701,1.820±0.404,10.83±1.123 and 1.8692±0.1096)and PCOS with HFD group (6.075±0.439,14.075±1.927,1.779±0.277,10.20±1.377 and 1.7736±0.6851)were significantly higher than those in the control group (4.949±0.337, 2.458±0.509,1.239±0.038,9.53±0.548 and 1.5329±0.7363),but there was no significant difference between the PCOS group and PCOS with HFD group.The expression levels of MIF,p-JNK,and p-p38 in the PCOS group (0.4048±0.013,0.6233±0.093 and 0.7987±0.061)and PCOS withHFD group (0.1929±0.012,0.3346±0.103 and 0.3468±0.031)were obviously higher than those in control group (0.2492±0.013, 0.3271±0.093 and 0.3393±0.061),but no Significant difference was observed between PCOS group and PCOS with HFD group.It was suggested that MIF may participate in the pathogenesis of PCOS through the MAPK signalling pathway in PCOS rats induced by DHEA.

Dydrogesterone treatment for menstrual-cycle regularization in abnormal uterine bleeding-ovulation dysfunction patients

BACKGROUND Dydrogesterone has shown significant efficacy in treatment of irregular menstrual cycle due to abnormal uterine bleeding-ovulation dysfunction(AUB-O),but there were few relevant studies.This observational study was designed to evaluate the effectiveness of dydrogesterone for the treatment of Chinese patients with AUB-O.AIM To evaluate the effects of dydrogesterone on menstrual-cycle(MC)regularization and metabolism in the patients with AUB-O.METHODS A prospective,non-interventional,single-arm,post-marketing observational study was conducted.Chinese women aged 16 years or above with AUB-O who had been prescribed dydrogesterone were enrolled.The patients were treated with dydrogesterone 10 mg from day 16 to day 25 of each cycle,consecutively for at least 3 cycles.The main outcome was defined as the percentage of patients whose MCs returned to normal(defined as 21 d<menstrual cycle≤35 d)after three cycles of dydrogesterone treatment.RESULTS One hundred and fourteen women with AUB-O were enrolled in the present study.Of 89 patients who completed treatment,72(80.9%)achieved a regular MC at the end of the 3rd circle.The level of androgen,including testosterone and dehydroepiandrosterone sulfate,declined significantly(P=0.01 and 0.031,respectively),whereas other hormone levels remained steady.During the treatment,44/80(55.0%)subjects in the per-protocol set had reported biphasic basal body temperature.CONCLUSION Dydrogesterone therapy was effective in achieving MC regularization for Chinese patients with AUB-O.

Interactions among age, adiposity, bodyweight, lifestyle factors and sex steroid hormones in healthy Singaporean Chinese men

Aim： To examine the inter-relationships among age, lifestyle factors, anthropometric parameters, percent body fat and steroid hormone parameters in 531 healthy Singaporean Chinese men aged between 29 and 72 years old. Methods： Various lifestyle parameters were quantified through a survey, and testosterone （T）, estradiol （E2）, dehydroepiandrosterone sulphate （DHEAS） and sex hormone binding globulin （SHBG） were measured using established methods. Anthropometric parameters were collected and computed, and percent body fat （Siri） was measured using the DEXA scanner. Results： SHBG, DHEAS, bioavailable-T （Bio-T）, E2, Siri, Ht, W/H, W/Ht and work stress were independently correlated with age. Using multivariate analyses and adjusting for age and other related factors, exercise, smoking and alcohol consumption have positive impacts on androgen levels and body composition. However, black and green tea consumption was associated with negative effects on body composition and with higher levels of E2 and Free Estradiol Index （FEI）. Men with shorter sleep duration had significantly lower T levels as compared to those with 6 h or more of nightly sleep. Higher T levels were associated with lower levels of adiposity and other indices of adiposity, whereas higher E2 levels were related to higher levels of adiposity. Men with higher DHEAS were significantly taller and heavier than those with low DHEAS levels. Conclusion： The study showed the close interactions among the gonadal/adrenal and metabolic compartments, with age being a key determinant in their interactions. Lifestyle factors such as exercise, smoking, sleeping and alcohol and tea consumption might play significantly roles in determining the status of health in men.

Low DHEAS levels are associated with depressive symptoms in elderly Chinese men： results from a large study

This study investigated the association between depressive symptoms in elderly Chinese men and the total testosterone, dehydroepiandrosterone （DHEA）, DHEA sulphate （DHEAS）, oestradiol and sex hormone-binding globulin （SHBG） levels, and the free androgen index. Cross-sectional data from 1147 community-dwelling elderly men, aged 65 and older, were used. Depressive symptoms were measured using the Chinese Geriatric Depression Scale （GDS）. Total testosterone, free testosterone, DHEA, DHEAS, total oestradiol, the free androgen index and SHBG levels were assessed. DHEA was significantly associated with GDS score, and there was a trend towards DHEAS association, but this was not significant （p=-0. 110, P=0.015; p=-0.074, P=0.055）. However, no association was seen between depressive symptoms and total testosterone levels, free testosterone levels, oestradiol levels or SHBG levels. In terms of the presence of clinically relevant depressive symptoms, there were no statistically significant differences between patients in the lowest quartile of sex steroid hormone levels and those in other quartiles of sex steroid hormone levels. Similarly to Western studies, our study shows that DHEA and DHEAS levels are associated with depressive symptoms.

Cognitive, behavioural and psychiatric phenotypes associated with steroid sulfatase deficiency

The enzyme steroid sulfatase(STS)desulfates a variety of steroid compounds thereby altering their activity.STS is expressed in the skin,and its deficiency in this tissue has been linked to the dermatological condition X-linked ichthyosis.STS is also highly expressed in the developing and adult human brain,and in a variety of steroidogenic organs(including the placenta and gonads);therefore it has the potential to influence brain development and function directly and/or indirectly(through influencing the hormonal milieu).In this review,we first discuss evidence from human and animal model studies suggesting that STS deficiency might predispose to neurobehavioural abnormalities and certain psychiatric disorders.We subsequently discuss potential mechanisms that may underlie these vulnerabilities.The data described herein have potential implications for understanding the complete spectrum ofclinical phenotypes associated with X-linked ichthyosis,and may indicate novel pathogenic mechanisms underlying psychological dysfunction in developmental disorders such as attention deficit hyperactivity disorder and Turner syndrome.