In search of optimal resilience ratios: Differential influences of neurobehavioral factors contributing to stress-resilience spectra.

The ability to adapt to stressful circumstances, known as emotional resilience, is a key factor in the maintenance of mental health. Several individual biomarkers of the stress response (e.g., corticosterone) that influence an animal's position along the continuum that ranges from adaptive allostasis to maladaptive allostatic load have been identified. Extending beyond specific biomarkers of stress responses, however, it is also important to consider stress-related responses relative to other relevant responses for a thorough understanding of the underpinnings of adaptive allostasis. In this review, behavioral, neurobiological, developmental and genomic variables are considered in the context of emotional resilience [e.g., explore/exploit behavioral tendencies; DHEA/CORT ratios and relative proportions of protein-coding/nonprotein-coding (transposable) genomic elements]. As complex and multifaceted relationships between pertinent allostasis biomediators are identified, translational applications for optimal resilience are more likely to emerge as effective therapeutic strategies.

Adrenarcheal hormone-related development of white matter during late childhood.

The aim of the current study was to longitudinally examine how adrenarcheal hormones influence the development of white matter structure from age 8.5 to 10 years. Participants were 120 children (66 female; mean age 8.45 years at Time 1 and 9.97 years at Time 2) who completed two diffusion-weighted imaging scans 1.5 years apart. Morning saliva samples were taken at both assessment time points to measure levels of dehydroepiandrosterone (DHEA), its sulphate (DHEAS), and testosterone. Fixel-based analysis was performed to examine how changes in white matter fibre density (FD) and cross-section (FC) over time were associated with initial levels of hormones, and changes in hormone levels over time. Both FD and FC increased over time in a wide range of white matter tracts. Increases in testosterone over time were related to relatively weaker increases in FC in the inferior fronto-occipital fasciculus. Levels and change in DHEA and DHEAS were not related to FD or FC changes. The results demonstrated development of white matter fibre density and cross-section from age 8.5 to 10 years. Changes in adrenarcheal hormone levels showed limited, localized associations with development of white matter FC. Future research should examine the relevance of adrenarcheal hormone-related white matter development for cognitive functioning; as well as directly compare analysis techniques of white matter structure.

Dehydroepiandrosterone stimulates inflammation and impairs ovarian functions of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is one of the most common causes of infertility in child-bearing-age women. It is characterized by ovulation dysfunction, polycystic ovaries, and hyperandrogenism. Inflammation is likely to be a crucial contributor to the pathogenesis of PCOS. However, the association between the inflammatory cytokines and the development of PCOS has not been reported. To explore the relationship between the inflammatory cytokines and PCOS, alterations of serum proteins in dehydroepiandrosterone (DHEA)-induced PCOS rats were screened by protein array, and the concentration of IFN-γ was further measured by using enzyme-linked immunosorbent assay (ELISA). DHEA-induced PCOS rats had a decreased level of IFN-γ compared with the control rats, which was restored partly in flutamide (an androgen receptor antagonist)-treated rats. Moreover, the level of IFN-γ in serum of patients with PCOS was also lower than that in healthy women. Using the ovarian granulosa cells (KGN), we demonstrated that DHEA downregulated the expression and secretion of IFN-γ in dose- and time-dependent manners, which could be restored to some extent by treating with flutamide. Furthermore, flutamide ameliorated the inhibitory effect on cell proliferation and promotive effect on cell apoptosis by DHEA. The results also revealed that IFN-γ promoted the proliferation but inhibited the apoptosis of KGN cells, which was suppressed by DHEA via activating the downstream PI3K/AKT signaling pathway. Taken together, these results showed that DHEA inhibited the proliferation and promoted the apoptosis of ovarian granulosa cells through downregulating the expression of IFN-γ which could be restored by flutamide, and IFN-γ may serve as a potential inflammatory biomarker for PCOS detection.

Optimizing quality of life through sex steroids by their effects on neurotransmitters.

Menopause-related symptoms such as hot flushes, night sweats, weight gain, and decreased sexual functioning all have negative impacts on quality of life and affect daily activities such as sleep, work, and leisure activities. During the menopause transition, neurotransmitters, neuropeptides, and neurosteroids undergo important changes as a consequence of the failure of gonadal hormone production, at a time when many central nervous system activities deteriorate. Sex hormones have been implicated in neurite outgrowth, synaptogenesis, dendritic branching, myelination, and other important mechanisms of neural plasticity. Knowledge of interactions between sex steroid hormones and the dominant neurotransmitters, such as serotonin, dopamine, GABA, and glutamate, will give women and health providers an important tool for improving their health and well-being. From the concept of neurosteroids derives another treatment strategy: the use of pharmaceutical agents that increase the synthesis of endogenous neurosteroids within the nervous system. This approach has so far been hampered by lack of knowledge concerning the regulation of the biosynthetic pathways of neurosteroids and their relationship with sex steroids produced by the peripheral gland or with exogenous steroids. The present review summarizes some of the available clinical and experimental findings supporting the critical role of neurosteroids in postmenopausal women and their impact on quality of life.

The Effect of Statins on Levels of Dehydroepiandrosterone (DHEA) in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis.

BACKGROUND Currently, statins are used to treat polycystic ovary syndrome (PCOS). This systematic review and meta-analysis aimed to investigate the effect of statins on serum or plasma levels of dehydroepiandrosterone (DHEA) in women with PCOS. MATERIAL AND METHODS Databases that were searched included PubMed, Embase, and the Cochrane Library from their inception to August of 2018. Published randomized controlled trials (RCTs) were identified that evaluated the impact of statins on plasma DHEA levels in women with PCOS. The Cochrane risk of bias tool was used to assess the quality of the included RCTs. A random-effects model was used to analyze the pooled results. RESULTS Meta-analysis was performed on data from ten published studies that included 735 patients and showed that statin treatment could significantly reduce plasma DHEA levels when compared with controls (SMD, -0.43; 95% CI, -0.81-0.06; p=0.02; I²=82%). Statins were significantly more effective than placebo in reducing the levels of DHEAs. Subgroup analysis based on statin type showed that atorvastatin significantly reduced DHEA levels (SMD, -0.63; 95% CI, -1.20 - -0.05; p=0.03; I²=38%) but simvastatin did not significantly reduce DHEA levels (SMD: -0.14; 95% CI, -0.49-0.28; p=0.43; I²=77%). Subgroup analysis based on duration of treatment showed no significant difference between 12 weeks of statin treatment (SMD, -0.61; 95% CI, -1.23-0.02; p=0.06; I²=85%) and 24 weeks (SMD, -0.34; 95% CI -0.95-0.28; p=0.29; I²=83%). CONCLUSIONS Meta-analysis showed that statins significantly reduced the levels of DHEA when compared with placebo in patients with PCOS.

The influence of androgens on hibernation phenology of free-living male arctic ground squirrels.

Free-living ground squirrel species are sexually dimorphic in hibernation phenology. The underlying causes of these differences are not yet known. Androgens, testosterone (T) in particular, inhibit hibernation. To determine the influence of endogenous androgens on annual timing of hibernation we first measured circulating levels of T and dehydroepiandrosterone (DHEA), an adrenal androgen implicated in non-mating season aggression in other species, in free-living male arctic ground squirrels (Urocitellus parryii, AGS). We also manipulated endogenous androgen levels by surgical castration, and consequently compared body temperature records from intact (n=24) and castrated (n=9) males to elucidate the influence of endogenous androgens on annual body temperature cycles. The highest T levels (0.53±0.10ng/mL) were in reproductively mature male AGS in spring; whereas, both immature males in spring and all males in late summer had T levels an order of magnitude lower (0.07±0.01 and 0.06±0.00ng/mL, respectively). DHEA levels were higher in males during the late summer compared to reproductively mature males in spring (120.6±18.9 and 35.9±2.3pg/mL, respectively). Eliminating gonadal androgens via castration resulted in males delaying euthermy by extending heterothermy significantly in spring (Apr 22 ±2.9) than reproductive males (Mar 28 ±3.9) but did not change the timing of hibernation onset (castrate: Oct 12 ±1.0 vs. intact: Oct 3 ±3.1). We conclude that while androgens play a significant role in spring hibernation phenology of males, their role in fall hibernation onset is unclear.

Cortisol and DHEA in development and psychopathology.

Dehydroepiandrosterone (DHEA) and cortisol are the most abundant hormones of the human fetal and adult adrenals released as end products of a tightly coordinated endocrine response to stress. Together, they mediate short- and long-term stress responses and enable physiological and behavioral adjustments necessary for maintaining homeostasis. Detrimental effects of chronic or repeated elevations in cortisol on behavioral and emotional health are well documented. Evidence for actions of DHEA that offset or oppose those of cortisol has stimulated interest in examining their levels as a ratio, as an alternate index of adrenocortical activity and the net effects of cortisol. Such research necessitates a thorough understanding of the co-actions of these hormones on physiological functioning and in association with developmental outcomes. This review addresses the state of the science in understanding the role of DHEA, cortisol, and their ratio in typical development and developmental psychopathology. A rationale for studying DHEA and cortisol in concert is supported by physiological data on the coordinated synthesis and release of these hormones in the adrenal and by their opposing physiological actions. We then present evidence that researching cortisol and DHEA necessitates a developmental perspective. Age-related changes in DHEA and cortisol are described from the perinatal period through adolescence, along with observed associations of these hormones with developmental psychopathology. Along the way, we identify several major knowledge gaps in the role of DHEA in modulating cortisol in typical development and developmental psychopathology with implications for future research.

Interactive effects of dehydroepiandrosterone and testosterone on cortical thickness during early brain development.

Humans and the great apes are the only species demonstrated to exhibit adrenarche, a key endocrine event associated with prepubertal increases in the adrenal production of androgens, most significantly dehydroepiandrosterone (DHEA) and to a certain degree testosterone. Adrenarche also coincides with the emergence of the prosocial and neurobehavioral skills of middle childhood and may therefore represent a human-specific stage of development. Both DHEA and testosterone have been reported in animal and in vitro studies to enhance neuronal survival and programmed cell death depending on the timing, dose, and hormonal context involved, and to potentially compete for the same signaling pathways. Yet no extant brain-hormone studies have examined the interaction between DHEA- and testosterone-related cortical maturation in humans. Here, we used linear mixed models to examine changes in cortical thickness associated with salivary DHEA and testosterone levels in a longitudinal sample of developmentally healthy children and adolescents 4-22 years old. DHEA levels were associated with increases in cortical thickness of the left dorsolateral prefrontal cortex, right temporoparietal junction, right premotor and right entorhinal cortex between the ages of 4-13 years, a period marked by the androgenic changes of adrenarche. There was also an interaction between DHEA and testosterone on cortical thickness of the right cingulate cortex and occipital pole that was most significant in prepubertal subjects. DHEA and testosterone appear to interact and modulate the complex process of cortical maturation during middle childhood, consistent with evidence at the molecular level of fast/nongenomic and slow/genomic or conversion-based mechanisms underlying androgen-related brain development.

Dehydroepiandrosterone modulates T-cell response after major abdominal surgery.

BACKGROUND: The immune balance controlled by T-helper (Th)1 and Th2 cells is critical in protecting the host from pathogenic invasion, and its imbalance may increase susceptibility to infection in patients undergoing major surgery. The differentiation of naive T cells to Th1 and Th2 cells is largely driven by cytokines. In addition, steroid hormones have been shown to affect Th1/Th2 balance, particularly in autoimmune diseases. The regulation of Th1/Th2 balance in patients undergoing surgery and its potential clinical relevance remain unclear. MATERIALS AND METHODS: Blood samples were obtained from patients both before and 2 h after major abdominal surgery. Peripheral blood mononuclear cells were isolated and cultured in wells coated with either anti-CD3 (direct T-cell stimulation) or phytohemagglutinin (PHA) (indirect T-cell stimulation), with or without 10(-5) M dehydroepiandrosterone (DHEA). The release of interleukin (IL)-2, interferon gamma, and IL-10 was measured by an enzyme-linked immunosorbent assay, and the expression of CD4, CD8, and CD69 was determined by flow cytometry. RESULTS: DHEA decreased the release of IL-2 and IL-10 in directly (anti-CD3) and indirectly (PHA)-stimulated T cells from postoperative samples, whereas the release of interferon gamma in PHA-stimulated T cells was not affected. The distribution of CD4/CD8 was not significantly different after surgery or DHEA. DHEA was associated with a decrease in the expression of the activation marker CD69 on CD4(+) T cells, whereas the activation of CD8(+) T cells remained unchanged. CONCLUSIONS: These results demonstrate that DHEA plays a critical role in controlling Th1/Th2 balance in the immediate postoperative period. Attenuation of both the Th1 and Th2 responses has been suggested to have immunoprotective effects. The role of DHEA in the regulation of Th1/Th2 balance in patients undergoing major abdominal surgery may, therefore, also be of significant clinical relevance and warrants further investigation.

[Cortisol as a marker of stress].

The role of cortisol (Crt), dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEA-S) in stress responses were shown. The fluctuations in concentration of Crt, DHEA and DHEA-S depending on age, sex and time of the day in norm and under acute and chronic stress were quoted. The main techniques of assessment of serum, urine and saliva Crt concentrations were discussed. A special attention had been paid to the use of Crt concentration in anthropological and psychological research. Bibliography comprises 181 works.

Mothers' prenatal distress accelerates adrenal pubertal development in daughters.

Human life history schedules vary, partly, because of adaptive, plastic responses to early-life conditions. Little is known about how prenatal conditions relate to puberty timing. We hypothesized that fetal exposure to adversity may induce an adaptive response in offspring maturational tempo. In a longitudinal study of 253 mother-child dyads followed for 15 years, we investigated if fetal exposure to maternal psychological distress related to children's adrenarche and gonadarche schedules, assessed by maternal and child report and by dehydroepiandrosterone sulfate (DHEA-S), testosterone, and estradiol levels. We found fetal exposure to elevated maternal prenatal psychological distress predicted earlier adrenarche and higher DHEA-S levels in girls, especially first-born girls, and that associations remained after covarying indices of postnatal adversity. No associations were observed for boys or for gonadarche in girls. Adrenarche orchestrates the social-behavioral transition from juvenility to adulthood; therefore, significant findings for adrenarche, but not gonadarche, suggest that prenatal maternal distress instigates an adaptive strategy in which daughters have earlier social-behavioral maturation. The stronger effect in first-borns suggests that, in adverse conditions, it is in the mother's adaptive interest for her daughter to hasten social maturation, but not necessarily sexual maturation, because it would prolong the duration of the daughter allomothering younger siblings. We postulate a novel evolutionary framework that human mothers may calibrate the timing of first-born daughters' maturation in a way that optimizes their own reproductive success.

Cortisol and depression: three questions for psychiatry.

BACKGROUND: Cortisol plays a multifaceted role in major depression disorder (MDD). Diurnal rhythms are disturbed, there is increased resistance to the feedback action of glucocorticoids, excess cortisol may induce MDD, basal levels may be higher and the post-awakening cortisol surge accentuated in those at risk for MDD. Does this suggest new avenues for studying MDD or its clinical management? METHOD: The relevant literature was reviewed. RESULTS: Cortisol contributes to genetic variants for the risk for MDD and the way that environmental events amplify risk. The corticoids' influence begins prenatally, but continues into adulthood. The impact of cortisol at each phase depends not only on its interaction with other factors, such as psychological traits and genetic variants, but also on events that have, or have not, occurred previously. CONCLUSIONS: This review suggests that the time is now right for serious consideration of the role of cortisol in a clinical context. Estimates of cortisol levels and the shape of the diurnal rhythm might well guide the understanding of subtypes of MDD and yield additional indicators for optimal treatment. Patients with disturbed cortisol rhythms might benefit from restitution of those rhythms; they may be distinct from those with more generally elevated levels, who might benefit from cortisol blockade. Higher levels of cortisol are a risk for subsequent depression. Should manipulation of cortisol or its receptors be considered as a preventive measure for some of those at very high risk of future MDD, or to reduce other cortisol-related consequences such as long-term cognitive decline?

Hormonal causes of male sexual dysfunctions and their management (hyperprolactinemia, thyroid disorders, GH disorders, and DHEA).

INTRODUCTION: Besides hypogonadism, other endocrine disorders have been associated with male sexual dysfunction (MSD). AIM: To review the role of the pituitary hormone prolactin (PRL), growth hormone (GH), thyroid hormones, and adrenal androgens in MSD. METHODS: A systematic search of published evidence was performed using Medline (1969 to September 2011). Oxford Centre for Evidence-Based Medicine-Levels of Evidence (March 2009) was applied when possible. MAIN OUTCOME MEASURES: The most important evidence regarding the role played by PRL, GH, thyroid, and adrenal hormone was reviewed and discussed. RESULTS: Only severe hyperprolactinemia (>35 ng/mL or 735 mU/L), often related to a pituitary tumor, has a negative impact on sexual function, impairing sexual desire, testosterone production, and, through the latter, erectile function due to a dual effect: mass effect and PRL-induced suppression on gonadotropin secretion. The latter is PRL-level dependent. Emerging evidence indicates that hyperthyroidism is associated with an increased risk of premature ejaculation and might also be associated with erectile dysfunction (ED), whereas hypothyroidism mainly affects sexual desire and impairs the ejaculatory reflex. However, the real incidence of thyroid dysfunction in subjects with sexual problems needs to be evaluated. Prevalence of ED and decreased libido increase in acromegalic patients; however, it is still a matter of debate whether GH excess (acromegaly) may create effects due to a direct overproduction of GH/insulin-like growth factor 1 or because of the pituitary mass effects on gonadotropic cells, resulting in hypogonadism. Finally, although dehydroepiandrosterone (DHEA) and its sulfate have been implicated in a broad range of biological derangements, controlled trials have shown that DHEA administration is not useful for improving male sexual function. CONCLUSIONS: While the association between hyperprolactinemia and hypoactive sexual desire is well defined, more studies are needed to completely understand the role of other hormones in regulating male sexual functioning.

Advances in neurosteroids: role in clinical practice.

The steroidogenic endocrine glands and local synthesis both contribute to the pool of steroids present in the central nervous system and peripheral nervous system. Although the synthesis of neurosteroids in the nervous system is now well established, the spectrum of respective functions in regulating neuronal and glial functions remains to be fully elucidated. From the concept of neurosteroids derives another treatment strategy: the use of pharmaceutical agents that increase the synthesis of endogenous neurosteroids within the nervous system. This approach has so far been hampered by lack of knowledge concerning the regulation of the biosynthetic pathways of neurosteroids and their relationship with sex steroids produced by the peripheral gland or with exogenous steroids. The present review summarizes some of the available clinical and experimental findings supporting the critical role of neurosteroids during fertile life and reproductive aging and their relationship with endogenous and exogenous sex steroids. The brain metabolism of synthetic progestins and the implications of DHEA treatment in postmenopausal women will also be discussed.

Inhibition by female sex hormones of collagen degradation by corneal fibroblasts.

PURPOSE: Corneal fibroblasts contribute to collagen remodeling in the corneal stroma in part by mediating collagen degradation. Given that corneal structure is influenced by sex hormone status, we examined the effects of sex hormones on collagen degradation by corneal fibroblasts. METHODS: Rabbit corneal fibroblasts were cultured in three-dimensional collagen gels with or without sex hormones including 17ß-estradiol, progesterone, testosterone, and dehydroepiandrosterone (DHEA). Collagen degradation was determined by measurement of hydroxyproline after acid hydrolysis. The expression and activity of matrix metalloproteinases (MMPs) were evaluated by immunoblot analysis and gelatin zymography. The phosphorylation of mitogen-activated protein kinases (MAPKs) and the nuclear factor-kappa B (NF-κB) inhibitor NF kappa B Inhibitor-alpha (IκB-α) in corneal fibroblasts was examined by immunoblot analysis. Cell proliferation and viability were evaluated by measurement of bromodeoxyuridine incorporation and the release of lactate dehydrogenase, respectively. RESULTS: 17ß-Estradiol and progesterone each inhibited interleukin (IL)-1ß-induced collagen degradation by corneal fibroblasts in a concentration-dependent manner, whereas testosterone and DHEA had no such effect. MMP expression and activation in corneal fibroblasts exposed to IL-1ß were also inhibited by 17ß-estradiol and progesterone. These female sex hormones did not affect cell proliferation or viability. Both 17ß-estradiol and progesterone inhibited the IL-1ß-induced phosphorylation of p38 MAPK without affecting that of the MAPKs extracellular Signal-regulated Kinase (ERK) or c-jun N-terminal kinase (JNK). 17ß-Estradiol also inhibited the IL-1ß-induced phosphorylation of IκB-α. CONCLUSIONS: 17ß-Estradiol and progesterone inhibited MMP expression and activity in IL-1ß-stimulated corneal fibroblasts and thereby suppressed collagen degradation by these cells.

Berberine cooperates with adrenal androgen dehydroepiandrosterone sulfate to attenuate PDGF-induced proliferation of vascular smooth muscle cell A7r5 through Skp2 signaling pathway.

Platelet-derived growth factor (PDGF) is released from vascular smooth muscle cell (VSMC), after percutaneous coronary intervention and is related with neointimal proliferation and restenosis. Adrenal steroid dehydroepiandrosterone sulfate (DHEAS), the sulfated prohormone of dehydroepiandrosterone has shown remarkable biological activity against proliferation of VSMC in some animal and clinical studies. Combinations of DHEAS with other agents have also shown promising results, with acquiring more efficient effect. Berberine is a naturally occurring isoquinoline alkaloid. To investigate their effects in combination, a VSMC cell line A7r5 was stimulated by PDGF-BB (dimer of the B chain of PDGF), and then treated with berberine and/or DHEAS in the current study. Cell proliferation assay, cell cycle assay, Western blot, and co-immunoprecipitation were analyzed in A7r5 cells. Antiproliferative effects of berberine and/or DHEAS targeting the Skp2/p27 pathways were evaluated. Berberine and DHEAS can both inhibit the growth of A7r5 cells. Berberine induces cell cycle arrest and potentiates the inhibitory effect of DHEAS through disrupting the binding of p27, p21 with Skp2. Berberine and DHEAS decreased the expression of CDK2, CDK4, PCNA, cyclin D1, and cyclin E, which was induced by PDGF-BB. Being treated with berberine and DHEAS also promoted p27 and p21 bind to CDK2, so the proliferation of A7r5 cells induced by PDGF-BB was inhibited. The data provide evidence that berberine acts through the inhibition of p27-Skp2 and p21-Skp2 with subsequent activation of the cell cycle arrest, which leads to the increase in sensitivity to DHEAS. In summary, the findings suggest that combined berberine and DHEAS will be active in the prevention of restenosis after angioplasty treatment, and the treatment of atherosclerosis.

Dehydroepiandrosterone (DHEA)--a precursor steroid or an active hormone in human physiology.

INTRODUCTION: The circulation of large amounts of dehydroepiandrosterone (DHEA) and its sulfated derivative (DHEA-S) suggests a physiological role in human physiology. In the central nervous system, DHEA is considered a neurosteroid with a wide range of functions. AIM: The goal of this review is to discuss metabolism, biochemical, and physiological mechanism of DHEA action and the potential role of DHEA in aging and in ameliorating a host of pathological conditions, associated with aging. METHODS: We examined preclinical and clinical data reported in various studies from the available literature concerning the effects of DHEA in normal and pathological conditions. MAIN OUTCOME MEASURES: Data reported in the literature were analyzed, reviewed, and discussed. RESULTS: DHEA mediates its action via multiple signaling pathways involving specific membrane receptors and via transformation into androgen and estrogen derivatives (e.g., androgens, estrogens, 7α and 7ß DHEA, and 7α and 7ß epiandrosterone derivatives) acting through their specific receptors. These pathways include: nitric oxide synthase activation, modulation of γ-amino butyric acid receptors, N-methyl D-aspartate, receptors sigma receptors (Sigma-1), differential expression of inflammatory factors, adhesion molecules and reactive oxygen species, among others. Clinical and epidemiological studies suggested that low DHEA levels might be associated with ischemic heart disease, endothelial dysfunction, atherosclerosis, bone loss, inflammatory diseases, and sexual dysfunction. Most importantly, no significant adverse or negative side effects of DHEA were reported in clinical studies of men and women. CONCLUSIONS: DHEA modulates endothelial function, reduces inflammation, improves insulin sensitivity, blood flow, cellular immunity, body composition, bone metabolism, sexual function, and physical strength in frailty and provides neuroprotection, improves cognitive function, and memory enhancement. DHEA possesses pleiotropic effects and reduced levels of DHEA and DHEA-S may be associated with a host of pathologies; however, the clinical efficacy of DHEA supplementation in ameliorating patho-physiological symptoms remains to be evaluated.

DHEA and polycystic ovarian syndrome: Meta-analysis of case-control studies.

BACKGROUND: Polycystic ovarian syndrome is a heterogenous endocrine disorder characterized by irregular menstrual cycles, hirsuitism and polycystic ovaries. It is further complicated by metabolic syndrome, infertility and psychological stress. Although the etiopathogenesis is unclear, many studies have pointed out the role of stress in this syndrome. DHEA, being a stress marker is being used by scientists to compare the stress levels between polycystic ovarian cases and healthy controls. However, the results obtained from previous studies are equivocal. OBJECTIVE: To perform meta-analysis and find the association between stress and the syndrome. DATA SOURCES: Relevant data till January 2021 were retrieved from PubMed, Scopus, Embase and Web of Science using MeSH terms. STUDY SELECTION: Case-control studies having PCOS subjects as cases and healthy women as controls were selected provided; their basal DHEA levels were mentioned in the published articles. DATA EXTRACTION: Two authors independently extracted the articles and qualified the final studies. DATA SYNTHESI: Pooled meta-analysis was done using random effect model and showed level of DHEA statistically significant in PCOS compared to healthy controls (SMD = 1.15, 95% CI = 0.59-1.71).Heterogeneity was statistically significant as well (I2 = 95%). CONCLUSION: Thismeta-analysis on DHEA and PCOS has helped in generating evidence regarding the involvement of stress in the pathogenesis of PCOS.

Neurobiological and neuropsychiatric effects of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS).

DHEA and DHEAS are steroids synthesized in human adrenals, but their function is unclear. In addition to adrenal synthesis, evidence also indicates that DHEA and DHEAS are synthesized in the brain, further suggesting a role of these hormones in brain function and development. Despite intensifying research into the biology of DHEA and DHEAS, many questions concerning their mechanisms of action and their potential involvement in neuropsychiatric illnesses remain unanswered. We review and distill the preclinical and clinical data on DHEA and DHEAS, focusing on (i) biological actions and putative mechanisms of action, (ii) differences in endogenous circulating concentrations in normal subjects and patients with neuropsychiatric diseases, and (iii) the therapeutic potential of DHEA in treating these conditions. Biological actions of DHEA and DHEAS include neuroprotection, neurite growth, and antagonistic effects on oxidants and glucocorticoids. Accumulating data suggest abnormal DHEA and/or DHEAS concentrations in several neuropsychiatric conditions. The evidence that DHEA and DHEAS may be fruitful targets for pharmacotherapy in some conditions is reviewed.

DHEA therapy in postmenopausal women: the need to move forward beyond the lack of evidence.

The marked age-related decline in serum dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) has suggested that a deficiency of these steroids may be causally related to the development of a series of diseases that are generally associated with aging. Postulated consequences of low DHEA levels include insulin resistance, obesity, cardiovascular disease, cancer, reduction of the immune defence system as well as psychosocial problems such as depression and a general deterioration in the sensation of well-being and cognitive function. Clinically, the spectrum of women that would benefit from DHEA therapy is not clearly defined and nor is the dosage of hormone treatment. Whether DHEA therapy could be prescribed as a general anti-aging therapy or could be an alternative treatment for women suffering from androgen deficiency syndrome remains uncertain across studies. The lack of definitive evidence for biological mechanisms and the presence of only a few studies that address these emerging issues of DHEA therapy in postmenopausal women might encourage a new critical analysis of the available literature, evidencing current limits and incongruities.