Reposição de testosterona em mulheres cisgênero na menopausa / Testosterone replacement in menopausal cisgender women

Ainda não existe consenso a respeito da prescrição de testosterona terapêutica para mulheres cisgênero na menopausa, seus benefícios e efeitos colaterais. Objetivo: Sumarizar os estudos recentes sobre o uso terapêutico da testosterona em mulheres na menopausa. Método: Revisão sistemática de literatura baseada nos dados da plataforma PubMed. Foram identificados 10.912 estudos potenciais. As palavras-chave usadas foram "testosterone", "women", "therapy", "treatment". Selecionou-se revisões sistemáticas e metanálises dos últimos 5 anos, todas na língua inglesa. Excluiram-se artigos duplicados, os que abordam uso de testosterona como anabolizantes e/ou em atletas e em transexuais e estudos que envolviam homens. O levantamento de dados foi realizado com 9 artigos. Resultados: O uso dessa terapia hormonal no período da pós-menopausa mostrou melhora dos sintomas sexuais. Há diferença entre as vias de aplicação, sendo que a via oral pode acarretar maiores prejuízos, principalmente em relação aos níveis lipídicos séricos. A testosterona intravaginal melhora a função sexual. A prescrição na prática se mostra um problema, pois as apresentações comercializadas não atendem à necessidade fisiológica feminina. Conclusão: A terapia mostra-se eficaz em curto prazo, apesar de ainda haver necessidade de estudos para uso em longo prazo

There is still no consensus regarding the prescription of testosterone therapy for cisgender menopausal woman, its benefits and side effects. Objective: Summarize recent studies on the therapeutic use of testosterone in menopausal woman. Methods: Systematic literature review based on data from the PubMed platform. A total of 10.912 potential studies were identified. The used keywords were "testosterone", "woman", "therapy", "treatment". Systematic reviews and meta-analyses from the last 5 years were selected, all in English. Were excluded: duplicated articles, the ones that address the use of testosterone as anabolic steroid and/or in athletes and transsexuals and studies that involved man. Tthe data collection was made with 9 articles. Results: The use of this hormone therapy in postmenopausal period showed sexual symptoms improvement. There are differences between the routes of administration, for the oral administration could lead to more damage, mainly related to the lipids serum levels. Intravaginal testosterone improves sexual function. The prescription in practice is shown to be a problem, since the commercialized presentations do not meet the feminine physiological necessities. Conclusion: This therapy proves to be effective in short term use, although there is still a need for studies for long-term use

The influence of dehydroepiandrosterone on effector functions of neutrophils

Dehydroepiandrosterone (DHEA) is a steroid hormone secreted by the adrenal glands, gonads and brain. It is a precursor to sex hormones and also is known to have immune modulatory activity. However, little is known about the relationship between DHEA and neutrophils and thus our study evaluates the influence of DHEA in the effector functions of neutrophils. Human neutrophils were treated in vitro with DHEA and further infected with Salmonella enterica serovar Typhimurium. The treatment of neutrophils with 0.01 µM of DHEA increased the phagocytosis of Salmonella independent of TLR4 as the treatment did not modulate the TLR4 expression. Additionally, DHEA caused a decrease in ROS (reactive oxygen species) production and did not influence the formation of the neutrophil extracellular trap (NET). Steroid treated neutrophils, infected or stimulated with LPS (lipopolysaccharide), showed reduced production of IL-8, compared to untreated cells. Also, the protein levels of p-NFκB were decreased in neutrophils treated with DHEA, and this reduction could explain the reduced levels of IL-8. These results led us to conclude that the steroid hormone DHEA has important modulatory functions in neutrophils

Novel mechanisms underlying anti-polycystic ovary like syndrome effects of electroacupuncture in rats: suppressing SREBP1 to mitigate insulin resistance, mitochondrial dysfunction and oxidative stress

BACKGROUND: Acupuncture, a therapy of traditional Chinese medicine, is confirmed to exert the therapeutic action on polycystic ovary syndrome (PCOS). However, the detailed therapeutic mechanisms of acupuncture in PCOS remain ambiguous. In this study, we further investigated whether electroacupuncture (EA) alleviated PCOS-like symptoms in rats via regulating a metabolic regulator, sterol regulatory element binding protein-1 (SREBP1). Methods: The PCOS-like rat model was built by hypodermic injection with dehydroepiandrosterone (DHEA). The rats were subjected to EA intervention (ST29 and SP6 acupuncture points) for 5 weeks. Primary granulosa cells were isolated from control and PCOS-like rats for evaluating insulin resistance, mitochondrial dysfunction and oxidative stress in vitro. RESULTS: The expression of SREBP1 was increased in PCOS-like rats, which was suppressed by EA treatment. In addition, lentivirus-mediated overexpression of SREBP1 restrained EA treatment-induced improvement in pathological changes, serum hormone levels and insulin resistance in rats. In addition, overexpression of SREBP1 repressed insulin-stimulated phosphorylation of insulin receptor ß (IR) and AKT in primary granulosa cells. Moreover, upregulation of SREBP1 further exacerbated mitochondrial dysfunction and oxidative stress in granulosa cells isolated from PCOS-like rats. Mechanically, EA treatment suppressed SREBP1 expression through inducing the activation of AMP-activated protein kinase (AMPK) signaling pathway in PCOS-like rats. CONCLUSION: EA intervention alleviated PCOS-like symptoms in rats via improving IR, mitochondrial dysfunction and oxidative stress through regulating SREBP1, a lipid metabolism regulator. Our findings illuminate the novel protective mechanisms of EA in the treatment of PCOS.

Relationship between sexual hormones, quality of life and postmenopausal sexual function / Relação entre hormônios sexuais, qualidade de vida e função sexual na pós-menopausa

Abstract Objective To assess the relationship between sexual hormones, sexual function and quality of life in postmenopausal women. Method A cross-sectional study was conducted with a convenience sample of 36 postmenopausal women between the ages of 45 and 65 in follow-up at a climacteric outpatient clinic. Mood, quality of life, sexual function and hormonal profile were assessed. Results With regard to sexual hormones and sexual function, a relationship was found between orgasm and luteinizing hormone (r=0.37), orgasm and sex hormone-binding globulin (SHBG) (r=0.39), SHBG and less pain (r=0.44), dehydroepiandrosterone (DHEA) and desire (r=-0.45), as well as between prolactin and lubrication (r=0.33). Sexual hormones and quality of life were related as follows: progesterone and limitations due to physical aspects (r=0.35), SHBG and social aspects (r=0.35), cortisol and pain (r=0.46), DHEA and social aspects (r=-0.40). Finally, the following relationships were found between sexual function and quality of life: sexual desire and vitality, social aspects, state of general health and mental health (r=0.46, r=0.51, r=0.35, and r=0.38, respectively). Arousal, orgasm and satisfaction with sexual life showed a relationship with less physical pain (r=0.40, r=0.42, and r=0.43, respectively). Satisfaction with sexual life was correlated with vitality (r=0.33). Conclusion Different correlations than expected were found in this study regarding the effect of some hormones on sexual function and some aspects of the quality of life of postmenopausal women.

Resumo Objetivo Avaliar a relação entre hormônios sexuais, função sexual e qualidade de vida em mulheres na pós-menopausa. Métodos Estudo transversal com amostra de conveniência de 36 mulheres na pós-menopausa, com idades entre 45 e 65 anos, em seguimento ambulatorial de climatério. Humor, qualidade de vida, função sexual e perfil hormonal foram avaliados. Resultados Entre hormônios sexuais e função sexual, foi encontrada relação entre orgasmo e hormônio luteinizante (r=0,37), orgasmo e globulina ligadora de hormônios sexuais (SHBG) (r=0,39), SHBG e menos dor (r=0,44), desidroepiandrosterona (DHEA) e desejo (r=-0,45), bem como entre prolactina e lubrificação (r=0,33). Entre hormônios sexuais e qualidade de vida: progesterona e limitações por aspectos físicos (r=0,35), SHBG e aspectos sociais (r=0,35), cortisol e dor (r=0,46), DHEA e aspectos sociais (r=-0,40). Por fim, entre função sexual e qualidade de vida: desejo sexual e vitalidade, aspectos sociais, estado geral de saúde e saúde mental (r=0,46, r=0,51, r=0,35 e r=0,38, respectivamente). Excitação, orgasmo e satisfação com a vida sexual mostraram uma relação com menos dor física (r=0,40, r=0,42 e r=0,43, respectivamente). A satisfação com a vida sexual foi correlacionada com a vitalidade (r=0,33). Conclusão Correlações diferentes das esperadas foram encontradas neste estudo em relação ao efeito de alguns hormônios sobre a função sexual e alguns aspectos da qualidade de vida de mulheres na pós-menopausa.

Spinal Nitric Oxide Synthase Type II Increases Neurosteroid-metabolizing Cytochrome P450c17 Expression in a Rodent Model of Neuropathic Pain

We have previously demonstrated that the neurosteroid dehydroepiandrosterone sulfate (DHEAS) induces functional potentiation of N-methyl-D-aspartate (NMDA) receptors via increases in phosphorylation of NMDA receptor GluN1 subunit (pGluN1). However, the modulatory mechanisms responsible for the expression of the DHEA-synthesizing enzyme, cytochrome P450c17 following peripheral nerve injury have yet to be examined. Here we determined whether oxidative stress induced by the spinal activation of nitric oxide synthase type II (NOS-II) modulates the expression of P450c17 and whether this process contributes to the development of neuropathic pain in rats. Chronic constriction injury (CCI) of the sciatic nerve induced a significant increase in the expression of NOS-II in microglial cells and NO levels in the lumbar spinal cord dorsal horn at postoperative day 5. Intrathecal administration of the NOS-II inhibitor, L-NIL during the induction phase of neuropathic pain (postoperative days 0~5) significantly reduced the CCI-induced development of mechanical allodynia and thermal hyperalgesia. Sciatic nerve injury increased the expression of PKC- and PKA-dependent pGluN1 as well as the mRNA and protein levels of P450c17 in the spinal cord at postoperative day 5, and these increases were suppressed by repeated administration of L-NIL. Co-administration of DHEAS together with L-NIL restored the development of neuropathic pain and pGluN1 that were originally inhibited by L-NIL administration alone. Collectively these results provide strong support for the hypothesis that activation of NOS-II increases the mRNA and protein levels of P450c17 in the spinal cord, ultimately leading to the development of central sensitization and neuropathic pain induced by peripheral nerve injury.

The association between serum dehydroepiandrosterone sulfate (DHEAS) levels and job-related stress among female nurses

BACKGROUND: Dehydroepiandrosterone sulfate (DHEAS) is an endogenous steroid hormone produced by the adrenal gland. DHEAS has been suggested to play a protective role against psychosocial stress. The aim of this study was to investigate the association between job-related stress and blood concentrations of DHEAS according to occupational stress factors among female nurses. METHODS: A cross-sectional study was conducted among 118 premenopausal nurses from 4 departments (operating room, emergency room [ER], intensive care unit, and ward) of a university hospital. Participants were all rotating night shift workers who have worked for over a year and mean age of 33.5 ± 4.8 years. Data from structured questionnaires including the Korean Occupational Stress Score, Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), and Pittsburgh Sleep Quality Index (PSQI) were used. RESULTS: In the high job-related stressor group, scores of BDI, BAI, and PSQI were significantly higher than low-stressor group. ER nurses had relatively more work-burden related stressors, but they had significantly lower levels of anxiety and depression than other groups. And, ER nurses showed higher levels of DHEAS than the other department nurses. The differences were significant (p = 0.003). Additionally, there was a statistically significant difference even after adjusting for factors that could affect level of DHEAS, such as age, body mass index, drinking, and physical activity (p = 0.039). CONCLUSIONS: This result suggests the possibility that DHEAS may play a role as a marker of proper stress management. The capacity to secrete DHEAS is not simply due to workload or job stressor but could be determined depending on how individuals and groups deal with and resolve stress. Proper resolution of stress may affect positive hormone secretion.

Live birth outcomes of vitrified embryos generated under growth hormone stimulation are improved for women categorized as poor-prognosis / 대한생식의학회지

OBJECTIVE: To determine the clinical pregnancy (CP) and live birth (LB) rates arising from frozen embryo transfers (FETs) that had been generated under the influence of in vitro fertilization (IVF) adjuvants given to women categorized as poor-prognosis.METHODS: A registered, single-center, retrospective study. A total of 1,119 patients with first FETs cycle include 310 patients with poor prognosis (109 treated with growth hormone [GH], (+)GH group vs. 201 treated with dehydroepiandrosterone, (–)GH group) and 809 patients with good prognosis (as control, (–)Adj (Good) group).RESULTS: The poor-prognosis women were significantly older, with a lower ovarian reserve than the (–)Adj (Good) group, and demonstrated lower chances of CP (p<0.005) and LB (p<0.005). After adjusting for confounders, the chances of both CP and LB in the (+)GH group were not significantly different from those in the (–)Adj (Good) group, indicating that the poor-prognosis patients given GH had similar outcomes to those with a good prognosis. Furthermore, the likelihood of LB was significantly higher for poor-prognosis women given GH than for those who did not receive GH (p<0.028). This was further confirmed in age-matched analyses.CONCLUSION: The embryos cryopreserved from fresh IVF cycles in which adjuvant GH had been administered to women classified as poor-prognosis showed a significant 2.7-fold higher LB rate in subsequent FET cycles than a matched poor-prognosis group. The women with a poor prognosis who were treated with GH had LB outcomes equivalent to those with a good prognosis. We therefore postulate that GH improves some aspect of oocyte quality that confers improved competency for implantation.

Diagnosis of an indistinct Leydig cell tumor by positron emission tomography-computed tomography

A 51-year-old perimenopausal female patient presented with hirsutism and voice thickening which was started approximately one and a half years ago. Her initial hormone assay revealed elevated plasma testosterone, 5a-dihydrotestosterone, and dehydroepiandrosterone (DHEA) levels and therefore androgen-secreting tumor was first suspected. However, the lesion was inconspicuous on transvaginal sonography, abdominal-pelvic computed tomography (CT) scan, and pelvic magnetic resonance (MRI) imaging. Consequently, 18F-fluorodeoxyglucose (FDG) positron emission tomography-CT was performed, which localized the lesion as a focal FDG uptake within the right adnexa. Total laparoscopic hysterectomy with bilateral salpingo-oophorectomy was performed, and although visible gross mass lesions were not observed intraoperatively, pure Leydig cell tumor was pathologically confirmed within the right ovary. Plasma testosterone, 5a-dihydrotestosterone, and DHEA levels were normalized postoperatively. Clinical signs of virilization were also significantly resolved after 3-months of follow-up.

Study on the Marker Steroids of New Zealand Deer (Cervus elaphus var. scoticus) Velvet Antler by UPLC-MS/MS and HPLC-PDA Methods

Eleven steroid hormones (SHs: androstene-3,17-dione, estrone, β-estradiol, α-estradiol, testosterone, dehydroepiandrosterone, 17á-hydroxyprogesterone, medroxyprogesterone, megestrol acetate, progesterone, and androsterone) were detected from New Zealand deer (Cervus elaphus var. scoticus) velvet antler (NZA, 鹿茸). A method for the quantification of eleven SHs was established by using ultraperformance liquid chromatography (UPLC)-MS/MS. The linearities (R² > 0.991), limits of quantification (LOQ values, 0.3 ng/mL to 23.1 ng/mL), intraday and interday precisions (relative standard deviation: RSD 0.999), LOQ values (30 ng/mL to 350 ng/mL), intraday and interday precisions (RSD < 1.93%), and recovery rates (97.2% to 103.5%) for the three 7-O-CSs were determined. These quantitative methods are accurate, precise, and reproducible. As a result, it is suggested that the five steroid compounds of androstene-3,17-dione, androsterone, 7-ketocholesterol, 7α-hydroxycholesterol, and 7β-hydroxycholesterol could be marker steroids of NZA. These methods can be applied to quantify or standardize the marker steroids present in NZA.

Functional Identification of Compound Heterozygous Mutations in the CYP17A1 Gene Resulting in Combined 17α-Hydroxylase/17,20-Lyase Deficiency

BACKGROUND: We previously reported a patient with congenital adrenal hyperplasia (CAH) with compound heterozygous mutations in the cytochrome P450 17A1 (CYP17A1) gene. One allele had a p.His373Leu and the other a new p.Glu383fsX36 mutation. The aim of this study was to investigate the functional properties of a new allele present in a compound heterozygote of CYP17A1. METHODS: To understand how p.His373Leu and p.Glu383fsX36 affect P450c17 enzymatic activity, wild type and mutant CYP17A1 cDNAs were cloned into flag-tagged pcDNA3 vector and introduced into human embryonic kidney cells 293T (HEK293T) cells. Protein expression levels of CYP17A1 were then analyzed. And the activities of 17α-hydroxylase and 17,20-lyase of CYP17A1 were evaluated by measuring the conversion of progesterone to 17α-hydroxyprogesterone and of 17α-hydroxypregnenolone to dehydroepiandrosterone, respectively. In addition a computer model was used to create the three-dimensional structure of the mutant CYP17A1 enzymes. RESULTS: Production of the p.His373Leu mutant protein was significantly lower than that of the wild type protein, and the p.Glu383fsX36 protein was hardly produced. Similarly the enzymatic activity derived from the p.His373Leu mutant vector was significantly lower than that obtained from the wild type vector, and little activity was obtained from the p.Glu383fsX36 vector. Three-dimensional modeling of the enzyme showed that p.His373 was located in region important for heme-binding and proper folding. Neither the p.His373Leu nor the p.Glu383fsX36 mutant protein formed a heme-binding structure. CONCLUSION: Enzyme activity measured in both mutants disappeared completely in both 17α-hydroxylase and 17,20-lyase. This result accounts for the clinical manifestations of the patient with the compound heterozygous CYP17A1 mutations.

Dehydroepiandrosterone and Erectile Function: A Review

To review the contemporary knowledge regarding the dehydroepiandrosterone and erectile function. Medline was reviewed for English-language journal articles spanning the time between January 1990 and December 2017, using the terms ‘erectile function’, ‘dehydroepiandrosterone’. We used original articles and review articles that found to be relevant to the purpose of this review. Criteria included all pertinent review articles, randomized controlled trials with tight methodological design, cohort studies and retrospective analyses. We also manually revised references from selected articles. Several interesting studies have addressed the age-related decline in dehydroepiandrosterone levels with many age-related phenomena or deterioration in various physiological functions. Particularly, aging; neurological functions including decreased well-being, cognition, and memory; increased depression, decreased bone mineral density, obesity, diabetes, increased cardiovascular morbidity, erectile dysfunction (ED), and decreased libido. Supporting this result, some trials of dehydroepiandrosterone supplementation in healthy, middle-aged, and elderly subjects have reported improvements in different aspects of well-being. Several studies had demonstrated that dehydroepiandrosterone level is declined as a part of aging. Large-scale well-designed prospective studies are warranted to better define indications and therapeutic implications of dehydroepiandrosterone in men with ED.

Efeito do método canguru na redução do estresse crônico em gestantes, mães e bebês pré-termo através da análise do cortisol e desidroepiandrosterona em unhas / Effect of the kangaroo mother care on the reduction of chronic stress in pregnant women, mothers and preterm infants through the analysis of cortisol and dehydroepiandrosterone in fingernails

INTRODUÇÃO: O estresse tem sido foco de interesse em diferentes áreas de estudo devido às consequências no processo saúde-doença. Destaca-se a inexistência de estudos sobre o estresse crônico no período pré e pós-natal em unhas de mulheres que tiveram parto prematuro e sua relação o método canguru (MC). OBJETIVOS: Avaliar o efeito do Método Canguru na redução do estresse psicológico materno através de escalas psicométricas e o estresse biológico crônico através dos níveis de cortisol e desidroepiandrosterona (DHEA) em unhas de mães e bebês pré-termo (PT). MÉTODO: Trata-se de estudo comparativo prospectivo. A amostra contou com 59 mães e 63 bebês, coletada num hospital com o MC implantado e em dois hospitais controle, sem o MC. Foram incluídos PT (?37 semanas), sem malformações, internados em UN; mães alfabetizadas, que tiveram contato prévio com o filho, não usuárias de drogas ou hormônios. O estresse crônico materno e do PT foi avaliado pelo Cortisol e DHEA das unhas. A primeira amostra de unhas maternas foi coletada na terceira semana de vida do PT. A segunda amostra das mães e a amostra das unhas dos PT foram coletadas três meses após parto. Para análise do cortisol e DHEA das unhas das mães foi utilizada a técnica de enzima imunoensaio e dos bebês a cromatografia líquida de alto desempenho com espectrometria de massa. As unhas foram analisadas em laboratórios especializados no Canadá. O estresse psicológico da mães foi analisado com uso das PSS-10 e PSS:NICU que foram respondidas pelas mães na semana da admissão e alta do PT. RESULTADOS: Os níveis de Cortisol e DHEA nas unhas das mães referente a gestação e puerpério não diferiu significativamente entre os grupos canguru e controle, porém, diferiu entre os tempos, sendo que, os níveis dos esteroides na gestação foi maior do que no puerpério em ambos os grupos. O estresse percebido (PSS-10) pelas mães referente a gestação (p=0,846) e puerpério (p=0,465) também não diferiu significativamente entre os dois grupos. O estresse indicado pela PSS:NICU na admissão foi moderado nos dois grupos. O maior escore foi observado na subescala alteração no papel de pais. Na alta o escore foi significativamente menor (p=0,00) no canguru do que no controle. Não houve qualquer relação entre o estresse crônico (cortisol, DHEA e razão Cort:DHEA) e o psicológico (PSS-10 na gestação e PSS:NICU no puerpério) e nem entre as duas medidas de estresse psicológico (PSS-10 e PSS:NICU na alta). O nível de cortisol foi menor nos PT submetidos ao canguru, porém, sem diferença significante (p=0,08). Diferiram significativamente a DHEA - menor no controle e a razão Cort:DHEA - menor nos PT do grupo canguru. Da análise da relação entre estresse crônico constataram-se: associação positiva entre Cort:DHEA da mãe e PT (?= 0,51canguru; ?= 0,43 controle). CONCLUSÃO: O estudo mostrou que é possível medir cortisol e DHEA em unhas de mães e de bebês PT de forma restrospectiva. Os dados sugerem que o MC pode contribuir com a regulação e redução do estresse crônico do PT e do estresse psicológico materno

INTRODUCTION: Stress has been a focus of interest in different areas of study due to the consequences in the health-disease process. We highlight the lack of studies on chronic stress in pre and postnatal period using fingernails of women who had preterm birth and its relation to the kangaroo mother care (KMC) to reduce chronic and psychological stress. OBJECTIVES: To evaluate maternal psychological stress using psicometrics tools and avaluate chronic stress of mothers and Preterm infant (PT) using the analysis of cortisol and DHEA in fingernails and analyse the implication of the kangaroo care (KMC) in reduce chronic stress. METHOD: This is a prospective comparative study. The sample were 59 mothers and 63 babies collected in a KMC's hospital and two controls (without the KMC). Were included PT babies (? 37 weeks), who were admitted to the NICU, those with no malformations. With regard to mothers were included that one who had saw the PT at least once and excluded those using drugs or taking hormones. Maternal and PT chronic' stress were evaluated by fingernails' cortisol and DHEA. The first maternal sample was collected in the third week post-delivery and the second sample in the third month after baby's birth. The baby's fingernail sample was collected in the third month of life. The enzyme immunoassay was used for analysis of mothers' fingernails (cortisol and DHEA) and for babies' were used high performance liquid chromatography with mass spectrometry. Fingernail's analysis was done in Canada. The PSS-10 and PSS: mothers filled up NICU tools on first week in NICU and at discharge of the baby from this unit. RESULTS: The cortisol and DHEA's level in mothers' fingernails showed no significant difference between groups. Steroids levels in pregnancy time were higher than in puerperium in both groups (KMC and control) however, showed significant difference between times, steroids levels were higher during gestation time than the puerperium in both groups. The same occurred with the PSS-10 score (KMC's score referring to pregnancy (p=0,846) and puerperium (p=0,465), also had no difference was between groups. The PSS: NICU's stress level at admission in both groups was moderate. The highest score was showed in the subscale Parental Role. At discharge the score was significantly lower (p=0,00) in the kangaroo than in the control. There was no relationship between chronic stress (cortisol, DHEA and Cort:DHEA) and psychological stress (PSS-10 in pregnancy and PSS: NICU in the puerperium) or between the two psychological measures of stress (PSS-10 and PSS: NICU on discharge). The cortisol level was lower in PT submitted to kangaroo, however, without significant difference (p = 0.08). They differed significantly in DHEA - lower in the control and the ratio Cort:DHEA - lower in the kangaroo group. From the analysis of the relationship between chronic stress, there was a positive association between Cort: DHEA of the mother and PT (? = 0.51 kangaroo; ? = 0.43 control). CONCLUSION: The study showed that it is possible to measure cortisol and DHEA in preterm infant and mothers' fingernails retrospectively. The data suggests that KMC can contribute to regulate and to reduce chronic stress in preterm infant and to reduce psychological mother's stress

Dehydroepiandrosterone Sulfate Level Varies Nonlinearly with Symptom Severity in Major Depressive Disorder

OBJECTIVE: The pathophysiology of major depressive disorder (MDD) is still not well understood. Conflicting results for surrogate biomarkers in MDD have been reported, which might be a consequence of the heterogeneity of MDD patients. Therefore, we aim to investigate how the severity of depression and various symptom domains are related to the levels of dehydroepiandrosterone sulfate (DHEA-s) in MDD patients. METHODS: We recruited 117 subjects from a general practice. Depressive symptoms were assessed using the Beck Depression Inventory (BDI). Depressive symptoms were divided into three subdomains according to BDI items; somatic symptoms, guilt and failure, and mood and inhibition. RESULTS: In subjects with very-mild-to-moderate depression, the DHEA-s level increased as BDI score did. However, the DHEA-s levels in the subjects with severe depression were significantly lower than in subjects with moderate depression (p=0.003). DHEA-s level was correlated with the BDI subscore for guilt and failure in very-mild-to-moderate depression (r=0.365, p=0.006). CONCLUSION: The DHEA-s level appears to be indicative of MDD severity with respect to depressive symptoms, especially regarding guilt and failure. Our findings suggest that the upregulation of DHEA-s may be a part of a compensatory process in very-mild-to-moderate depression, and the failure of this compensation mechanism may underlie the development of severe depression.

The Association between Dehydroepiandrosterone Sulfate (DHEA-S) and Bone Mineral Density in Korean Men and Women

BACKGROUND: The relationship between dehydroepiandrosterone sulfate (DHEA-S) and bone mineral density (BMD) is controversial. And findings of most studies that have investigated this relationship are restricted to postmenopausal women. In this study, we investigated the relationship between serum DHEA-S and BMD in both men and women. METHODS: This cross-sectional study evaluated a total of 294 healthy Korean participants through a medical examination program. And a subgroup of 154 participants was subjected to a longitudinal analysis. We measured BMD by dual energy X-ray absorptiometry and assayed DHEA-S by a chemiluminescent immunoassay. RESULTS: We evaluated the association between serum DHEA-S concentration and BMD at the femur trochanter after adjusting for cofounders such as age, body mass index, lifestyle factors, serum cortisol level, serum insulin-like growth factor 1 (IGF-1) level, and sex. Through our longitudinal study, we found that the changes in BMD at the total spine, at the femur neck, and at the femur trochanter were all smaller in the ΔDHEA-S 0 group. CONCLUSIONS: We found that there was a positive correlation between serum DHEA-S and femur BMD, which suggests that controlling serum DHEA-S levels may retard age-related BMD reduction in Koreans.

Dehydroepiandrosterone and cortisol concentrations in the cerebrospinal fluid of dogs

Concentrations of cortisol, dehydroepiandrosterone and dehydroepiandrosterone-sulfate were measured by performing radioimmunoassay of the cerebrospinal fluid of 68 dogs diagnosed with idiopathic epilepsy or inflammatory, degenerative, or non-neurological disease. No steroid concentration differences were found among diagnoses. Dehydroepiandrosterone and dehydroepiandrosterone-sulfate concentrations were higher in males than in females and dehydroepiandrosterone-sulfate decreased with increasing age. No sex or age effects were observed on cortisol or hormone ratios. Although limited to a relatively small sample, our results show sex- and age-dependent variations in these neurosteroid concentrations in cerebrospinal fluid. The role of such variations in the pathophysiology of the dog brain warrants further investigation.

Induction of Integrin Signaling by Steroid Sulfatase in Human Cervical Cancer Cells

Steroid sulfatase (STS) is an enzyme responsible for the hydrolysis of aryl and alkyl sulfates. STS plays a pivotal role in the regulation of estrogens and androgens that promote the growth of hormone-dependent tumors, such as those of breast or prostate cancer. However, the molecular function of STS in tumor growth is still not clear. To elucidate the role of STS in cancer cell proliferation, we investigated whether STS is able to regulate the integrin signaling pathway. We found that overexpression of STS in HeLa cells increases the protein and mRNA levels of integrin β1 and fibronectin, a ligand of integrin α5β1. Dehydroepiandrosterone (DHEA), one of the main metabolites of STS, also increases mRNA and protein expression of integrin β1 and fibronectin. Further, STS expression and DHEA treatment enhanced phosphorylation of focal adhesion kinase (FAK) at the Tyr 925 residue. Moreover, increased phosphorylation of ERK at Thr 202 and Tyr 204 residues by STS indicates that STS activates the MAPK/ERK pathway. In conclusion, these results suggest that STS expression and DHEA treatment may enhance MAPK/ERK signaling through up-regulation of integrin β1 and activation of FAK.

Effects of Adrenal Androgen Levels on Bone Age Advancement in Prepubertal Children: Using the Ewha Birth and Growth Cohort Study

Bone age (BA) advancement in prepubertal children may be associated with earlier onset of puberty and obesity. This study aimed to define the effects of adrenal androgen levels on the advancement of BA in prepubertal children, independent of obesity. During July and August 2011, we examined BA in 200 prepubertal children aged 7–9 years who were part of the Ewha Birth & Growth Cohort Study. BA was assessed by the Greulich-Pyle method. An index of BA advancement was calculated as the ratio of BA to chronological age (CA) (BA/CA), and this ratio was classified into 3 tertiles. We analyzed the relationship between BA advancement and anthropometric characteristics and adrenal hormone levels. The number of overweight children increased from the first group to the third group (P(Trend) = 0.03). The levels of adrenal androgens showed a significant positive correlation with the tertile groups after adjusting for age and sex (testosterone: r = 0.26, P < 0.001; dehydroepiandrosterone: r = 0.21, P < 0.001; androstenedione: r = 0.20, P < 0.001). Further, after controlling for body mass index (BMI), sex, and age, the BA/CA was found to be positively correlated with androstenedione (β = 0.04, R² = 3.7%) and testosterone levels (β = 0.05, R² = 4.7%). Based on our results, it is suggested that adrenal androgen levels are associated with BA advancement independent of BMI.

DHEA and frontal fibrosing alopecia: molecular and physiopathological mechanisms

Abstract The transforming growth factor-beta 1 (TGFβ1) promotes fibrosis, differentiating epithelial cells and quiescent fibroblasts into myofibroblasts and increasing expression of extracellular matrix. Recent investigations have shown that PPAR (peroxisome proliferator-activated receptor*) is a negative regulator of fibrotic events induced by TGFβ1. Dehydroepiandrosterone (DHEA) is an immunomodulatory hormone essential for PPAR functions, and is reduced in some processes characterized by fibrosis. Although scarring alopecia characteristically develops in the female biological period in which occurs decreased production of DHEA, there are no data in the literature relating its reduction to fibrogenic process of this condition. This article aims to review the fibrogenic activity of TGFβ1, its control by PPAR and its relation with DHEA in the frontal fibrosing alopecia.

Cortisol, DHEA, and depression in the elderly: the influence of physical capacity / Cortisol, DHEA e a depressão no idoso: a influência da capacidade física

ABSTRACT Objective Major depression have been associated with cortisol and dehydroepiandrosterone (DHEA) changes in old depressed patients. We examined the association between depression, cortisol, and DHEA, correcting for confounding variables, including physical capacity. In addition, the association between hormone levels and physical capacity in these two experimental groups was also analyzed. Method Depressed patients (n = 32) and healthy control (n = 31) old adults, both matched for age, were analyzed. Subjects were submitted to a physical capacity evaluation, including physical activity levels, functional fitness test, and balance scale. Results Depressed patients showed significant lower levels of cortisol than controls, which became non-significant after controlling for physical capacity. A positive correlation was observed between cortisol levels and physical capacity. Conclusions The data suggest that physical capacity modulates the relationship between depression and cortisol levels and needs to be taken into consideration in the future investigations.

RESUMO Objetivo A depressão maior tem sido associada a alterações nos níveis de cortisol e dehidroepiandrosterona (DHEA) em pacientes idosos depressivos. O presente estudo objetivou investigar a associação entre depressão, cortisol e DHEA, corrigindo por variáveis intervenientes, incluindo a capacidade física. Além disso, a associação entre os níveis hormonais e a capacidade física nos dois grupos experimentais também foi analisada. Método Pacientes idosos depressivos (n = 32) e idosos controles saudáveis (n = 31), pareados pela idade foram analisados. Os sujeitos foram submetidos a uma avaliação da capacidade física, incluindo níveis de atividade física, testes de capacidade funcional e escalas de equilíbrio. Resultados Os pacientes depressivos mostraram níveis significativamente menores de cortisol, os quais tornaram-se não significantes após controlados pela capacidade física. Uma correlação positiva foi observada entre os níveis de cortisol e a capacidade física. Resultados não significativos foram observados para DHEA, possivelmente devido a inclusão de pacientes depressivos e uma única coleta de amostra. Conclusão Os dados sugerem que a capacidade física modula a relação entre depressão e os níveis de cortisol e deve ser considerada em futuras investigações.

Effect of Guishen Pill on expression levels of Oct-4, MVH, and Egr-1 in mice with diminished ovarian reserve / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the effect of Guishen Pill (GSP) on expression levels of Oct-4, MVH, and Egr-1 in mice with diminished ovarian reserve (DOR).</p><p><b>METHODS</b>Totally 40 female C57BL/6J mice were randomly divided into 4 groups, the normal control group, the model group, the GSP group, and the dehydroepiandrosterone (DHEA) group, 10 in each group. Pregnant mare serum gonadotropin (PMSG), human chorionic gonadotropin (HCG), and prostaglandin F2α (PGF2α) were sequentially administrated to produce superovulation. The DOR model was established by exposing to ozone inhalation. Mice in the GSP group were intragastrically administered with GSP at 0.3 mL. Those in the DHEA group were intragastrically administered with DHEA at 0.3 mL. Equal volume of normal saline was intragastrically administered to mice in the normal control group and the model group. All mice wer treated for 21 days. Serum levels of estrogen (E2), progestogen (P), and anti-Müllerian hormone (AMH) were measured by ELISA. Changes of Oct-4, anti-AMH, and early growth response gene-1 (Egr-1) mRNA in ovaries were dtected by Real-time PCR.</p><p><b>RESULTS</b>Compared with the model group, serum levels of E2, P, and AMH, as well as contents of estrogen receptor (ER), progestogen receptor (PR), MVH, and Oct-4 mRNA significantly increased in the GSP group and the DHEA group (P < 0.05).</p><p><b>CONCLUSION</b>GSP could improve expression levels of Oct-4, MVH, and Egr-1 mRNA in DOR mice and their ovarian function.</p>