The therapeutic role of dehydroepiandrosterone (DHEA) supplementation among infertile women with diminished ovarian reserve (DOR) is still unclear. Objective evaluation of different ovarian reserve tests (ORTs) such as serum anti-Mullerian hormone (AMH), serum follicle stimulating hormone (FSH), and antral follicle count (AFC) in women with diminished ovarian reserve is required. This is a cross-sectional study performed in Mosul city, Iraq, with 122 infertile women who had been diagnosed with DOR. The enrolled women\'s age ranged from 18 to 45 years old (mean age of 29.46 ± 2.64 years). The ages of the enrolled women ranged from 18 to 45 years (mean age of 29.46 ± 2.64 years). To assess the influence of DHEA supplements (25 mg, three times/day for 12 weeks) across different age groups, the women were initially divided into three groups (18 to 27 years old, 28 to 37 years old, and ≥ 38 years old). Significant differences were noticed in AMH, FSH, level and AFC before and after DHEA supplementation. (AMH: 0.64 ± 0.82 vs. 1.98 ± 1.32, AFC: 2.86 ± 0.64 vs. 5.82 ± 2.42, and FSH: 12.44 ± 3.85 vs. 8.12 ± 4.64), statistically obvious significant differences regarding the results of AMH (p < 0.001), AFC (p < 0.001), and FSH (p < 0.001). DHEA supplementations improved the ovarian reserve of the enrolled women, which was more evident in younger women (<38 years old) than older women (≥38 years old). The AMH serum levels and AFC value can be considered the best, most reliable and significant OR parameters. However, large randomized multicenter studies are required to confirm the available results and data.

Background: Heat shock protein 60 (HSP60), a potentially homeostatic antigen, is involved in physiological and non-physiological conditions. Experimental data support the role of HSP60 in placental and mitochondrial steroidogenesis. Furthermore, HSP60 is translocated into the endothelial-cell plasma membrane and the extracellular space under stress conditions, promoting the atherosclerotic process. Therefore, we investigated the association between HSP60 and endothelial function in postmenopausal women, considering the possible atherogenic effect of androgenic hormones. Methods: This study included 123 healthy postmenopausal women. Exclusion criteria were treated hypertension or dyslipidaemia, menopause hormone therapy during the last 6 months, and previously diagnosed peripheral vascular disease or cardiovascular disease. Fasting venous blood samples were obtained for biochemical and hormonal assessment and evaluation of HSP60. Sonographic assessment of flow-mediated dilation (FMD) occurred immediately after that in one session. Results: Univariate analysis showed that women with FMD values below median 5.12% had lower logHSP60 values (low vs. high FMD, HSP60 values: 2.01 ± 1.16 ng/ml vs. 3.22 ± 1.17 ng/ml, p-value = 0.031). Multivariable analysis showed that logHSP60 was associated with FMD (b-coefficient = 0.171, p-value = 0.046), adjusting for traditional cardiovascular risk factors (TRFs) and insulin levels. Further adjustment for testosterone and DHEAS rendered the result non-significant. In the multivariable analysis, FMD was associated with insulin (b-coefficient = -0.166, p-value = 0.034), testosterone (b-coefficient = -0.165, p-value = 0.034), DHEAS (b-coefficient = -0.187, p-value = 0.017), adjusting for TRFs. Discussion: The results of this study indicate that the association between androgens and endothelial function is possibly mediated by HSP60 molecules, in women with low insulin resistance and androgenicity. Further prospective studies are needed to explore the significance of our findings.

Research suggests that both tuberculosis (TB) and type 2 diabetes mellitus (T2DM) have an immuno-endocrine imbalance characterized by dysregulated proinflammatory molecules and hormone levels (high cortisol/DHEA ratio), impeding an effective immune response against Mycobacterium tuberculosis (Mtb) driven by cytokines, antimicrobial peptides (AMPs), and androgens like DHEA. Insulin, sulfonylurea derivatives, and metformin are commonly used glucose-lowering drugs in patients suffering from TB and T2DM. For this comorbidity, metformin is an attractive target to restore the immunoendocrine mechanisms dysregulated against Mtb. This study aimed to assess whether metformin influences cortisol and DHEA synthesis in adrenal cells and if these hormones influence the expression of proinflammatory cytokines and AMPs in Mtb-infected macrophages. Our results suggest that metformin may enhance DHEA synthesis while maintaining cortisol homeostasis. In addition, supernatants from metformin-treated adrenal cells decreased mycobacterial loads in macrophages, which related to rising proinflammatory cytokines and AMP expression (HBD-2 and 3). Intriguingly, we find that HBD-3 and LL-37 can modulate steroid synthesis in adrenal cells with diminished levels of cortisol and DHEA, highlighting the importance of crosstalk communication between adrenal hormones and these effectors of innate immunity. We suggest that metformin\'s effects can promote innate immunity against Mtb straight or through modulation of corticosteroid hormones.

Neuroactive steroids (i.e., sex steroid hormones and neurosteroids) are important physiological regulators of nervous function and potential neuroprotective agents for neurodegenerative and psychiatric disorders. Sex is an important component of such effects. However, even if fluctuations in sex steroid hormone level during the menstrual cycle are associated with neuropathological events in some women, the neuroactive steroid pattern in the brain across the ovarian cycle has been poorly explored. Therefore, we assessed the levels of pregnenolone, progesterone, and its metabolites (i.e., dihydroprogesterone, allopregnanolone and isoallopregnanolone), dehydroepiandrosterone, testosterone and its metabolites (i.e., dihydrotestosterone, 3α-diol and 17β-estradiol) across the rat ovarian cycle to determine whether their plasma fluctuations are similar to those occurring in the central (i.e., hippocampus and cerebral cortex) and peripheral (i.e., sciatic nerve) nervous system. Data obtained indicate that the plasma pattern of these molecules generally does not fully reflect the events occurring in the nervous system. In addition, for some neuroactive steroid levels, the pattern is not identical between the two brain regions and between the brain and peripheral nerves. Indeed, with the exception of progesterone, all other neuroactive steroids assessed here showed peculiar regional differences in their pattern of fluctuation in the nervous system during the estrous cycle. These observations may have important diagnostic and therapeutic consequences for neuropathological events influenced by the menstrual cycle.

The classical androgens, testosterone and dihydrotestosterone, together with dehydroepiandrosterone, the precusrsor to all androgens, are generally included in diagnostic steroid evaluations of androgen excess and deficiency disorders and monitored in androgen replacement and androgen suppressive therapies. The C11-oxy androgens also contribute to androgen excess disorders and are still often excluded from clinical and research-based steroids analysis. The contribution of the C11-oxy androgens to the androgen pool has not been considered in androgen deficiency. An exploratory investigation into circulating adrenal and gonadal steroid hormones in men was undertaken as neither the classical androgens nor the C11-oxy androgens have been evaluated in the context of concurrent measurement of all adrenal steroid hormones. Serum androgens, mineralocorticoids, glucocorticoids, progesterones and androgens were assessed in 70 healthy young men using ultra high performance supercritical fluid chromatography and tandem mass spectrometry. Testosterone, 24.5 nmol/L was the most prominent androgen detected in all participants while dihydrotestosterone, 1.23 nmol/L, was only detected in 25% of the participants. The 11-oxy androgens were present in most of the participants with 11-hydroxyandrostenedione, 3.37 nmol, in 98.5%, 11-ketoandrostenedione 0.764 in 77%, 11-hydroxytestosterone, 0.567 in 96% and 11-ketotestosterone: 0.440 in 63%. A third of the participants with normal testosterone and comparable 11-ketotestosterone, had significantly lower dehydroepiandrosterone (p < 0.001). In these males 11-hydroxyandrostenedione (p < 0.001), 11-ketoandrostenedione (p < 0.01) and 11-hydroxytestosterone (p < 0.006) were decreased. Glucocorticoids were also lower: cortisol (p < 0.001), corticosterone (p < 0.001), cortisone (p < 0.006) 11-dehydrocorticosterone (p < 0.001) as well as cortisol:cortisone (p < 0.001). The presence of dehydroepiandrosterone was associated with 16-hydroxyprogesterone (p < 0.001), which was also significantly lower. Adrenal and gonadal steroid analysis showed unexpected steroid heterogeneity in normal young men. Testosterone constitutes 78% of the circulating free androgens with the 11-oxy androgens abundantly present in all participants significantly contributing 22%. In addition, a subset of men were identified with low circulating dehydroepiandrosterone who showed altered adrenal steroids with decreased glucocorticoids and decreased C11-oxy androgens. Analysis of the classical and 11-oxy androgens with the additional measurement of dehydroepiandrosterone and 16-hydroxyprogesterone may allow better diagnostic accuracy in androgen excess or deficiency.

Vitamin C (Ascorbic acid, AA), as vital micro-nutrient, plays an essential role for male animal reproduction. Previously, we showed that vitamin C reprogrammed the transcriptome and proteome to change phenotypes of porcine immature Sertoli cells (iSCs). Here, we used LC-MS-based non-targeted metabolomics to further investigate the metabolic effects of vitamin C on porcine iSCs. The results identified 43 significantly differential metabolites (DMs) (16 up and 27 down) as induced by vitamin C (L-ascorbic acid 2-phosphate sesquimagnesium salt hydrate, AA2P) treatment of porcine iSCs, which were mainly enriched in steroid related and protein related metabolic pathways. ELISA (Enzyme-Linked ImmunoSorbent Assay) showed that significantly differential metabolites of Dehydroepiandrosterone (DHEA) (involved in steroid hormone biosynthesis) and Desmosterol (involved in steroid degradation) were significantly increased, which were partially consistent with metabolomic results. Further integrative analysis of metabolomics, transcriptomics and proteomics data identified the strong correlation between the key differential metabolite of Dehydroepiandrosterone and 6 differentially expressed genes (DEGs)/proteins (DEPs) (HMGCS1, P4HA1, STON2, LOXL2, EMILIN2 and CCN3). Further experiments validated that HMGCS1 could positively regulate Dehydroepiandrosterone level. These data indicate that vitamin C could modulate the metabolism profile, and HMGCS1-DHEA could be the pathway to mediate effects exerted by vitamin C on porcine iSCs.

Osteoporosis easily causes delayed fracture union, even non-union. It has been demonstrated that dehydroepiandrosterone (DHEA) supplementation can increase estrogen levels and improve bone mineral density (BMD) in the elderly, while the role of DHEA on fracture healing remains unknown. This study aimed to elucidate the impact of DHEA supplementation on osteoporotic fracture healing. Seventy-two female Sprague-Dawley rats were used. Forty-eight rats received ovariectomy (OVX), and the remaining rats received a sham OVX operation (sham group). A right transverse femoral osteotomy was performed in all rats at 12 weeks post-OVX. OVX rats were randomly allocated into 2 groups (n = 24 in each group): (i) ovariectomized rats (control group) and (ii) ovariectomized rats treated with DHEA (DHEA group, 5 mg/kg/day). The DHEA supplementation was initiated on the first day post-fracture for 3, 6, and 12 weeks. Fracture healing was evaluated by radiography, histology, biomechanical analysis, and dual-energy X-ray absorptiometry (DEXA). Serum biomarkers were analyzed using enzyme-linked immunosorbent assay (ELISA). At 3 and 6 weeks, radiographs revealed reduced calluses formation and lower radiographic scores in the control group than in other groups. The sham and DHEA groups showed higher BMD and bone mineral content (BMC) at the fracture site than the control group after fracture. Histological analysis revealed the fracture callus was remodeled better in the sham and DHEA groups than in the control group. At the early phase of healing, DHEA supplementation increased osteoblast number, callus area, and cartilage area than the control group. An increased bone area was observed in the DHEA group than in the control group at the late phase of healing. Additionally, improved biomechanical characteristics were observed in both the sham and DHEA groups than those in the control group post-fracture. ELISA showed higher levels of insulin-like growth factor-1 (IGF-1) and 17β-estradiol (E2) in the DHEA group than in the control group post-fracture. Furthermore, the DHEA group exhibited significantly elevated alkaline phosphatase (ALP) and osteocalcin (OC) levels compared to the control group at 6 and 12 weeks. The DHEA group and the control group did not exhibit a notable difference in TRAP-5b levels. The present study demonstrated that the DHEA treatment has a favorable impact on osteoporotic fracture healing by enhancing callus formation, consolidation, and strength in the OVX rats.

Polycystic ovary syndrome (PCOS) is the most common gynaecological, endocrine disorder that occurs during reproductive age and is a significant cause of anovulatory infertility. Letrozole is an aromatase inhibitor which negates the action of the aromatase enzyme, which results in the buildup of male hormones (testosterone) in the females, causing hyperandrogenism, which is a hallmark of Polycystic Ovarian Syndrome. Mifepristone (RU486) is a progestin antagonist that acts to arrest the actions of the progesterone hormone, resulting in follicular atresia and anovulation. DHEA is an androgen which was also administered in a bid to cause hyperandrogenism in the rats.This study aimed to evaluate the effects of these hormones on the cytoarchitecture of the ovaries and uterus to assess their various PCOS-like histological features.Animals were grouped mainly into three: Letrozole, Mifepristone and DHEA groups, which were further divided into two subgroups each, administered low and high doses of letrozole orally, Mifepristone and Dehydroepiandosterone (DHEA) subcutaneously. Each of the subgroups also had a comparison control group. Following the completion of administration, the Wistar rats were euthanized, and their ovaries and uterus were collected for histological analysis.Increased proliferation of ovarian follicles was noted in the treated groups compared to control, as well as thickening of the endometrial layer.

BACKGROUND: The neuroprotective effects of Dehydroepiandrosterone (DHEA) and Hericium erinaceus (H. erinaceus) mushroom extract against scopolamine-induced Alzheimer\'s disease-like symptoms in male Wistar rats were investigated.
METHODS: Sixty-four male Wistar rats were divided into eight groups (n = 8). Scopolamine (SCO) was intraperitoneally injected at a dose of 1 mg/kg/day for 10 days. The treatment groups orally received DHEA (250 mg/kg/day) and/or H. erinaceus (300 mg/kg/day) for 14 days. Afterward, the Morris water maze (MWM) and novel object recognition tests were implemented. Then, animals were anesthetized and the brain tissue samples were separated. Levels of lipid peroxidation (LPO), total antioxidant capacity (TAC), catalase activity (CAT), and brain-derived neurotrophic factor (BDNF) were determined. Also, histopathological studies were evaluated in the brain tissue samples.
RESULTS: Administration of SCO significantly decreased spatial and cognitive memory (p < 0.001). Not only did SCO injection significantly increase the levels of the LPO but also the SCO markedly reduced the levels of the TAC, CAT activity, and the BDNF in the brain tissue. On the other hand, a combination of the DHEA and H. erinaceus showed higher efficacy than the DHEA or H. erinaceus in attenuating behavioral anomalies and improving the antioxidant defense system and BDNF levels. Histological examination was well correlated with biochemical findings regarding SCO neurodegeneration and DHEA and/or H. erinaceus neuroprotection.
CONCLUSIONS: Interestingly, ADHE and/or H. erinaceus may due to their potential neurotrophic properties be used as a new and beneficial concurrent therapy in the treatment of Alzheimer\'s disease-like symptoms caused by SCO.

Dehydroepiandrosterone (DHEA) and cortisol release appear to have contrasting effects on stress perception during stressful tasks. This study aimed to investigate anticipatory examination stress in college students by considering DHEA, cortisol, psycho-emotional aspects and examination performance. Seventy-six students (66 females, 10 males; age range 18-25 years) provided saliva samples and completed questionnaires in two sessions 48 hours apart. During the second session, the students performed the examination. The questionnaires used were the State-Trait Anxiety Inventory, the Positive and Negative Affect Scale, and the Brief-Coping Orientation to Problems Experienced Inventory. DHEA, cortisol, anxiety and negative affect showed an anticipatory rise before the examination (all ps < 0.001). This rise of DHEA and cortisol was associated with lower positive affect (p = 0.001 and p = 0.043, respectively). However, only the DHEA anticipatory levels were linked to poorer examination marks (p = 0.020). Higher levels of the DHEA/cortisol ratio in anticipation of the examination were related to lower scores on the support-seeking strategy (p = 0.022). There was no association between DHEA and cortisol levels and anxiety, negative affect, active and avoidant coping strategies, or academic record. These results suggest that how DHEA and cortisol respond in anticipation of examination stress significantly impacts students\' emotional well-being during examination periods and how they cope with stress. They also suggest that levels of DHEA in anticipation of an academic stressor have detrimental effects on stress management.