脱氢表雄酮对人脐静脉内皮细胞CD40/CD40L表达的影响

目的:探讨脱氢表雄酮(DHEA)对干扰素-γ(I NF-γ)刺激下的人脐静脉内皮细胞(HUVECs)CD40/CD40L表达的影响。方法:原代培养人脐静脉内皮细胞,给予I NF-γ刺激和不同浓度DHEA干预。采用流式细胞术检测CD40/CD40L在细胞表面的表达,通过反转录-聚合酶链反应(RT-PCR)检测CD40/CD40L mRNA的表达。结果:I NF-γ刺激HUVECs表达CD40/CD40L,DHEA下调I NF-γ诱导的HUVECs表面CD40/CD40L的表达,同时对I NF-γ刺激下的CD40/CD40L mRNA的表达有抑制作用,并且呈剂量依赖性。结论:DHEA能减轻I NF-γ刺激下的人脐静脉内皮细胞CD40/CD40L的表达。     

高健美延缓衰老的临床研究

目的 观察增龄对人血清中甲状腺激素（ＴＨ）、胰岛素样生长因子－１（ＩＧＦ－１）及脱氢表雄酮（ＤＨＥＡ）变化及用高健美治疗老年人后甲状腺功能（甲功）、ＩＧＦ－１、ＤＨＥＡ和肾虚衰老症状的改变。方法 从健康体检的人群中,选择５０例属于肾虚衰老的老年人作为治疗组,选择老年前期及青壮年期各３０例作为对照组,分别检测甲功（ＴＴ３、ＴＴ４、ＦＴ３、ＦＴ４）,ＩＧＦ－１、ＤＨＥＡ、肝功能及心电图;对治疗组用小剂     

Circulatory neurosteroid levels in underweight female adolescent anorexia nervosa inpatients and following weight restoration

Nineteen female adolescent inpatients diagnosed with anorexia nervosa, restricting type (AN-R) and 16 non-eating disordered (ED) controls were assessed for plasma dehydroepiandrosterone (DHEA), dehydroepiandrosterone-sulphate (DHEA-S), and cortisol levels, and for eating-related and non-eating-related psychopathology. AN-R patients were assessed at admission, 1 month and 4 months following hospitalization. The non-ED controls were assessed once. No baseline between-group differences were found in plasma cortisol, DHEA, and DHEA-S levels, whereas the patient group had a significantly lower Cortisol/DHEA-S ratio and elevated scores on most psychopathological parameters. A significant increase was found in the body mass index of the AN-R patients at 4 months post-hospitalization, accompanied by a decrease in plasma cortisol levels and a trend towards decreased Cortisol/DHEA and Cortisol/DHEA-S ratios, whereas no change occurred in psychopathology. The difference in Cortisol/DHEA-S ratio between AN-R patients and non-ED controls, and the different patterns of change in cortisol vs. DHEA(-S) levels following weight restoration, may in part account for the feeding difficulties in AN, particularly during refeeding.     

The Biological Actions of Dehydroepiandrosterone Involves Multiple Receptors

Dehydroepiandrosterone has been thought to have physiological functions other than as an androgen precursor. The previous studies performed have demonstrated a number of biological effects in rodents, such as amelioration of disease in diabetic, chemical carcinogenesis, and obesity models. To date, activation of the peroxisome proliferators activated receptor alpha, pregnane X receptor, and estrogen receptor by DHEA and its metabolites have been demonstrated. Several membrane-associated receptors have also been elucidated leading to additional mechanisms by which DHEA may exert its biological effects. This review will provide an overview of the receptor multiplicity involved in the biological activity of this sterol.     

脱氢表雄酮可以改善卵巢低反应患者的体外受精结局

目的探讨卵巢低反应患者补充脱氢表雄酮（DHEA）后卵巢储备指标及体外受精结局的变化。方法纳入50名前次IVF—ET治疗失败,证明是卵巢低反应,并再次要求IVF—ET治疗的患者。采用前瞻性单因素自身对照研究。入选患者接受DHEA75mg／日,至少治疗3个月后,每个患者采用与前一周期相同的卵巢刺激方案和FSH起始剂量促排卵。比较DHEA治疗前后,月经周期第三天AFC数量、FSH、抑制素B、抗苗勒氏管激素水平等卵巢储备指标;比较前后周期血清雌二醇（E2）峰值、HCG日〉15mm卵泡数量、回收卵母细胞和MII卵母细胞的数量、胚胎的数量和质量等治疗反应指标;比较治疗前后,临床妊娠率、流产率、活产率等体外受精周期结局差异。结果50例患者DHEA治疗前后AFC数量显著增加（P〈0．05）,月经第3天FSH、抑制素B和抗苗勒氏管激素水平无明显改变（P〉0．05）;补充DHEA后,卵巢刺激反应得到了显著改善,E2峰值水平、〉15mm的卵泡数量、获卵数、MII的卵子数量均有显著增加（P〉0．05）,治疗前后受精率相似（分别为67±42％和72±30％,P〉0．05）,可移植胚胎数量显著增加,由平均数量0．85个增至2．0个（P〈0．05）,可移植胚胎的优胚率由26％增至47％,但没有统计学意义（P〉0．05）。由于反应不良取消周期的比例显著降低（P〈0．05）,使用DHEA后周期妊娠率为30％,活产率为20％。50例患者对DHEA耐受良好,无严重不良反应。结论补充DHEA后可以增加胚胎数量,改善胚胎质量,提高临床妊娠率,改善卵巢低反应体外受精结局。其改善结局的机制可能是通过减少2—10mm的窦卵泡闭锁,增加AFC途径实现的。     

Low plasma DHEA-S increases mortality risk among male hemodialysis patients

Objective

The incidence of chronic kidney disease (CKD) is on the rise. CKD patients are at high risk of cardiovascular (CVD) and all-cause mortality. CKD patients have several endocrine disorders, including low levels of dehydroepiandrosterone sulfate (DHEA-S). In the general population, low levels of DHEA-S are associated with high CVD and all-cause mortality. The aim of this study was to analyze the prognostic value of plasma DHEA-S on the survival of CKD patients on hemodialysis.

Method

This was a single-center prospective cohort study on two hundred CKD patients on hemodialysis, which assessed the prognostic value of plasma DHEA-S on their survival.

Result

We found that plasma DHEA-S levels were negatively associated with age, and positively associated with dialysis duration and plasma creatinine, albumin, and phosphate levels in hemodialysis men. Elderly patients with co-morbidities (i.e. diabetes mellitus, congestive heart failure, and chronic obstructive pulmonary disease), poorer fluid control which was evaluated by higher cardiothoracic ratio, and low plasma creatinine and albumin levels seemed to have poor prognosis in hemodialysis men. Furthermore, low plasma DHEA-S levels were significantly associated with CVD-related [hazard ratio (HR) = 3.877; P = 0.021], non-CVD-related (HR = 3.522; P = 0.016), and all-cause mortality (HR = 3.667; P = 0.001) in hemodialysis men. But low plasma DHEA-S levels were not significantly associated with CVD-related, non-CVD-related, and all-cause mortality in hemodialysis women. Multivariate Cox regression analysis suggested that low plasma DHEA-S levels are significantly and independently associated with all-cause mortality in hemodialysis men (HR = 2.933; P = 0.033).

Conclusion

The study suggested that low plasma DHEA-S was independently and significantly associated with all-cause mortality in CKD hemodialysis men.     

Lower serum DHEAS levels are associated with a higher degree of physical disability and depressive symptoms in middle-aged to older African American women

BACKGROUND: Changes in androgen levels and associations with chronic disease, physical and neuropsychological function and disability in women over the middle to later years of life are not well understood and have not been extensively studied in African American women. AIMS: The present cross-sectional analysis reports such levels and associations in community dwelling, African American women aged 49-65 years from St. Louis, Missouri. METHODS: A home-based physical examination and a health status questionnaire were administered to randomly sampled women. Body composition (DEXA), lower limb and hand-grip muscle strength, physical and neuropsychological function and disability levels were assessed. Blood was drawn and assayed for total testosterone (T), sex hormone-binding globulin (SHBG), dehydroepiandrosterone-sulfate (DHEAS), oestradiol (E2), adiponectin, leptin, triglycerides, glucose, C-reactive protein (CRP) and cytokine receptors (sIL2r, sIL6r, sTNFr1 and sTNFr2). Multiple linear regression modelling was used to identify the best predictors of testosterone, DHEAS and free androgen index (T/SHBG). RESULTS: Seventy-four percent of women were menopausal and a quarter of these were taking oestrogen therapy. DHEAS and E2 declined between the ages of 49 and 65 years, whereas total T, SHBG and FAI remained stable. Total T and DHEAS levels were strongly correlated. In this population sample there were no independent associations of either total T or FAI with indicators of functional limitations, disability or clinically relevant depressive symptoms. Unlike total T and FAI, lower DHEAS levels were independently associated with both higher IADL scores (indicating a higher degree of physical disability) and higher CESD scores (indicating a higher degree of clinically relevant depressive symptoms). CONCLUSION: There is an age-related decline in serum DHEAS in African American women. Lower DHEAS levels appear to be associated with a higher degree of physical disability and depressive symptoms in this population.     

生长激素和脱氢表雄酮在卵巢低反应患者的临床应用及其研究进展

卵巢低反应（POR）是指在控制性超促排卵（COH）过程中,卵巢对促性腺激素（Gn）刺激反应不佳的病理状态。随着社会发展,女性生育年龄普遍推迟,以及“二孩政策”的放开,目前高龄欲生育的女性逐年增加。而年龄大于40岁的女性,POR发生率较高,如何解决这部分患者的生育问题,不仅是我国今后辅助生殖领域的热点话题,也是国际性的研究趋势。目前临床上常使用一些药物预处理来改善患者治疗结局。本文就近促排卵周期前,临床上最常用的预治疗药物生长激素和脱氢表雄酮的研究进展进行综述。     

Genome-wide association studies on serum sex steroid levels

Even though the levels of circulating sex steroid hormones are to a large extent heritable, their genetic determinants are largely unknown. With the advent of genome-wide association studies (GWAS), much progress has been made and several genetic loci have been identified to be associated with serum levels of dehydroepiandrosterone sulfate, testosterone and sex hormone-binding globulin. The variants identified so far only explain a small amount of the overall heritability, but may help to elucidate the role of sex steroid hormones in common disorders such as hypogonadism, type 2 diabetes and hormone-sensitive cancers. This review provides an overview of the current state of knowledge of the genetic determinants of sex steroid hormones, with a focus on recent GWAS and brief directions for elucidating the remaining heritability.     

Effects of dehydroepiandrosterone (DHEA) supplementation on the lipid profile: A systematic review and dose-response meta-analysis of randomized controlled trials

Background and aimsDehydroepiandrosterone (DHEA) supplementation has gained attention in individuals with adrenal insufficiency, and as a tool for increasing androgens and estrogens whereby is proposed to improve the accretion of muscle and bone mass. However, DHEA supplementation has demonstrated negative effects on the lipid profile and, thus, we aimed to analyze the body of evidence in this regard.Methods and resultsA systematic review and dose-response meta-analysis of randomized controlled trials (RCTs) was performed employing in Scopus, PubMed/Medline, Web of Science, Embase and Google Scholar, then including relevant articles that addressed the effects of DHEA supplementation on the lipid profile, up to February 2020. Combined findings were generated from 23 eligible articles. Hence, total cholesterol (TC) (weighted mean difference (WMD): −3.5 mg/dl, 95% confidence interval (CI): −8.5 to 1.6)), low-density lipoprotein-cholesterol (LDL-C) (WMD: 0.34 mg/dl, 95% CI: −3 to 3.7) and triglycerides (TG) levels (WMD: −2.85 mg/dl, 95% CI: −9.3 to 3.6) did not alter in DHEA group compared to the control, but HDL-C levels significantly reduced in DHEA group (WMD: −3.1 mg/dl, 95% CI: −4.9 to −1.3). In addition, a significant reduction in HDL-C values was observed in studies comprising women (WMD: −5.1 mg/dl, 95% CI: −7.2 to −3) but not in males (WMD: 0.13 mg/dl, 95% CI: −1.4 to 1.7).ConclusionsOverall, supplementation with DHEA did not change circulating values of TC, LDL-C and TG, whereas it may decrease HDL-C levels. Further long-term RCTs are required to investigate the effects of DHEA particularly on major adverse cardiac events.