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Respiratory Research Jun 2022Dehydroepiandrosterone (DHEA) is a precursor sex hormone with antifibrotic properties. The aims of this study were to investigate antifibrotic mechanisms of DHEA, and to...
BACKGROUND
Dehydroepiandrosterone (DHEA) is a precursor sex hormone with antifibrotic properties. The aims of this study were to investigate antifibrotic mechanisms of DHEA, and to determine the relationship between DHEA-sulfate (DHEAS) plasma levels, disease severity and survival in patients with fibrotic interstitial lung diseases (ILDs).
METHODS
Human precision cut lung slices (PCLS) and normal human lung fibroblasts were treated with DHEA and/or transforming growth factor (TGF)-β1 before analysis of pro-fibrotic genes and signal proteins. Cell proliferation, cytotoxicity, cell cycle and glucose-6-phosphate dehydrogenase (G6PD) activity were assessed. DHEAS plasma levels were correlated with pulmonary function, the composite physiologic index (CPI), and time to death or lung transplantation in a derivation cohort of 31 men with idiopathic pulmonary fibrosis (IPF) and in an independent validation cohort of 238 men and women with fibrotic ILDs.
RESULTS
DHEA decreased the expression of pro-fibrotic markers in-vitro and ex-vivo. There was no cytotoxic effect for the applied concentrations, but DHEA interfered in proliferation by modulating the cell cycle through reduction of G6PD activity. In men with IPF (derivation cohort) DHEAS plasma levels in the lowest quartile were associated with poor lung function and higher CPI (adjusted OR 1.15 [95% CI 1.03-1.38], p = 0.04), which was confirmed in the fibrotic ILD validation cohort (adjusted OR 1.03 [95% CI 1.00-1.06], p = 0.01). In both cohorts the risk of early mortality was higher in patients with low DHEAS levels, after accounting for potential confounding by age in men with IPF (HR 3.84, 95% CI 1.25-11.7, p = 0.02), and for age, sex, IPF diagnosis and prednisone treatment in men and women with fibrotic ILDs (HR 3.17, 95% CI 1.35-7.44, p = 0.008).
CONCLUSIONS
DHEA reduces lung fibrosis and cell proliferation by inducing cell cycle arrest and inhibition of G6PD activity. The association between low DHEAS levels and disease severity suggests a potential prognostic and therapeutic role of DHEAS in fibrotic ILD.
Topics: Dehydroepiandrosterone Sulfate; Female; Fibrosis; Humans; Idiopathic Pulmonary Fibrosis; Lung; Lung Diseases, Interstitial; Male
PubMed: 35676709
DOI: 10.1186/s12931-022-02076-9 -
Psychoneuroendocrinology Aug 2021Hypoandrogenic men showed a higher prevalence of major depressive disorder (MDD), which could be ascribed to overlapping symptoms such as sexual dysfunction, or...
BACKGROUND
Hypoandrogenic men showed a higher prevalence of major depressive disorder (MDD), which could be ascribed to overlapping symptoms such as sexual dysfunction, or additionally to core emotional symptoms such as sadness and anhedonia. We examined whether androgen levels 1) differ between men with and without MDD cross-sectionally, 2) are associated with an elevated risk for onset of MDD prospectively, and 3) associate with all individual MDD symptoms, or only with hypogonadism overlapping symptoms.
METHODS
In 823 men (mean age 43.5 years), baseline plasma levels of total testosterone, 5α-dihydrotestosterone (5α-DHT), and androstenedione were determined with liquid chromatography-tandem mass spectrometry, and dehydroepiandrosterone-sulphate (DHEAS) and sex hormone binding globulin with radioimmunoassay, whereas free testosterone was calculated. MDD status was assessed at baseline and after two years using structured interviews and individual MDD symptoms were self-rated at baseline, and after one and two years.
RESULTS
None of the androgen levels were associated with current or onset (incidence or recurrence) of MDD. Free testosterone was only inversely associated with interest in sex. Also, androstenedione and DHEAS were positively associated with some individual MDD symptoms, and 5α-DHT levels showed non-linear associations (both with low and high levels) with MDD symptom severity and several individual MDD symptoms.
CONCLUSIONS
These results support the idea that circulating androgens synthesised by the testes are of limited clinical relevance to MDD in adult men, but levels of androstenedione, DHEAS and 5α-DHT may be associated with some individual MDD symptoms.
Topics: Adult; Androgens; Androstenedione; Dehydroepiandrosterone Sulfate; Depression; Depressive Disorder, Major; Dihydrotestosterone; Humans; Male; Sex Hormone-Binding Globulin; Testosterone
PubMed: 34049017
DOI: 10.1016/j.psyneuen.2021.105278 -
Journal of Ovarian Research May 2020Previous studies have shown that chronic inflammation and oxidative stress may play an important role in the pathophysiology of polycystic ovary syndrome (PCOS), and... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Previous studies have shown that chronic inflammation and oxidative stress may play an important role in the pathophysiology of polycystic ovary syndrome (PCOS), and glutamine (Gln) have showed the anti-inflammatory and antioxidant properties. So the aim of this study is to investigate the effect of glutamine supplementation on PCOS rats.
METHODS
Female Sprague-Dawley rats were randomly assigned into four groups (n = 10 /group), control group, PCOS group, PCOS+ 0.5 g/kg Gln group and PCOS+ 1.0 g/kg Gln group. All the PCOS rats were administrated with 6 mg/100 g dehydroepiandrosterone (DHEA) for 20 consecutive days, all the PCOS+Gln groups were intraperitoneal injected glutamine twice in the next morning after the last DHEA injection. All the samples were collected 12 h after the last administration. Ovarian histological examinations were analyzed and the concentration of serum hormone, inflammatory and oxidative stress factors were measured.
RESULTS
There was no obvious ovarian histological change among the PCOS group and PCOS+Gln groups. All the detected inflammation factors [C-reactive protein, interleukin (IL)-6, IL-18, tumor necrosis factor] showed significantly higher in all the PCOS groups compared to the control group (P < 0.01), and were significantly decreased with the supplementation of 0.5 g/kg glutamine (P < 0.01). Concentrations of superoxide dismutase were significantly lower in all the PCOS groups (P < 0.01) compared to the control group, and increased significantly with the supplementation of 0.5 g/kg glutamine (P < 0.01). Serum concentrations of malondialdehyde, nitric oxide synthase and nitric oxide were significantly higher in PCOS group (P < 0.01) compared with the control group, and significantly decreased to the comparative levels of control group with supplementation of 0.5 g/kg glutamine (P < 0.01).
CONCLUSION
There is low-grade inflammation and oxidative stress in DHEA-induced PCOS rats. The supplementation of 0.5 g/kg glutamine could effectively ameliorate the inflammation and oxidative stress conditions of PCOS.
Topics: Animals; Dehydroepiandrosterone; Female; Glutamine; Humans; Inflammation; Oxidative Stress; Polycystic Ovary Syndrome; Rats; Rats, Sprague-Dawley
PubMed: 32386521
DOI: 10.1186/s13048-020-00650-7 -
Frontiers in Endocrinology 2023Dehydroepiandrosterone (DHEA) may improve the outcomes of patients with poor ovarian response (POR) or diminished ovarian reserve (DOR) undergoing IVF/ICSI. However, the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dehydroepiandrosterone (DHEA) may improve the outcomes of patients with poor ovarian response (POR) or diminished ovarian reserve (DOR) undergoing IVF/ICSI. However, the evidence remains inconsistent. This study aimed to investigate the efficacy of DHEA supplementation in patients with POR/DOR undergoing IVF/ICSI.
METHODS
PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI) were searched up to October 2022.
RESULTS
A total of 32 studies were retrieved, including 14 RCTs, 11 self-controlled studies and 7 case-controlled studies. In the subgroup analysis of only RCTs, DHEA treatment significantly increased the number of antral follicle count (AFC) (weighted mean difference : WMD 1.18, 95% confidence interval(CI): 0.17 to 2.19, 0.022), while reduced the level of bFSH (WMD -1.99, 95% CI: -2.52 to -1.46, <0.001), the need of gonadotropin (Gn) doses (WMD -382.29, 95% CI: -644.82 to -119.76, 0.004), the days of stimulation (WMD -0.90, 95% CI: -1.34 to -0.47, <0.001) and miscarriage rate (relative risk : RR 0.46, 95% CI: 0.29 to 0.73, 0.001). The higher clinical pregnancy and live birth rates were found in the analysis of non-RCTs. However, there were no significant differences in the number of retrieved oocytes, the number of transferred embryos, and the clinical pregnancy and live birth rates in the subgroup analysis of only RCTs. Moreover, meta-regression analyses showed that women with lower basal FSH had more increase in serum FSH levels (b=-0.94, 95% CI: -1.62 to -0.25, 0.014), and women with higher baseline AMH levels had more increase in serum AMH levels (b=-0.60, 95% CI: -1.15 to -0.06, 0.035) after DHEA supplementation. In addition, the number of retrieved oocytes was higher in the studies on relatively younger women (b=-0.21, 95% CI: -0.39 to -0.03, 0.023) and small sample sizes (b=-0.003, 95% CI: -0.006 to -0.0003, 0.032).
CONCLUSIONS
DHEA treatment didn't significantly improve the live birth rate of women with DOR or POR undergoing IVF/ICSI in the subgroup analysis of only RCTs. The higher clinical pregnancy and live birth rates in those non-RCTs should be interpreted with caution because of potential bias. Further studies using more explicit criteria to subjects are needed.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD 42022384393.
Topics: Pregnancy; Humans; Female; Sperm Injections, Intracytoplasmic; Fertilization in Vitro; Pregnancy Rate; Ovulation Induction; Follicle Stimulating Hormone; Dehydroepiandrosterone
PubMed: 37361534
DOI: 10.3389/fendo.2023.1156280 -
Journal of Obstetrics and Gynaecology :... Dec 2023Total testosterone (TT), sex hormone-binding globulin (SHBG), dehydroepiandrosterone (DHEA) levels, and cervical length (CL) were investigated in pregnant Egyptian women...
Testosterone, sex hormone-binding globulin and dehydroepiandrosterone levels and cervical length of Egyptian women with a history of recurrent miscarriages, polycystic ovary syndrome and without the conditions at three stages of pregnancy.
Total testosterone (TT), sex hormone-binding globulin (SHBG), dehydroepiandrosterone (DHEA) levels, and cervical length (CL) were investigated in pregnant Egyptian women with polycystic ovary syndrome (PCOS, = 38), history of miscarriages (RM, = 40) and without the conditions (HC, = 40). At week 8, the RM had lower levels of TT ( 0.000) and free androgen index (FAI) ( = 0.000) and higher SHBG ( = 0.000) and DHEA ( < 0.05) than the PCOS. Compared with the HC, they had elevated SHBG ( < 0.05) and DHEA ( = 0.001) and reduced CL ( = 0.000). TT ( = 0.001) and FAI ( = 0.000) were higher and SHBG ( = 0.000) and CL ( = 0.001) lower in the PCOS than in the HC group. At week 16, TT ( = 0.000) and FAI ( = 0.000) were higher, and SHBG ( = 0.000) and CL ( < 0.05) lower in PCOS than in RM and HC. The PCOS had elevated FAI than the RM ( = 0.000) and HC ( = 0.001) at week 20. The DHEA, SHBG and CL abnormalities in PCOS and RM may compromise pregnancy outcomes.IMPACT STATEMENT Hyperandrogenaemia, low sex hormone-binding globulin (SHBG), shortened cervical length (CL) and polycystic ovary syndrome (PCOS) are the most cited risk factors for recurrent miscarriages (RM). However, the published data are inconsistent, perhaps because of the confounding effects of ethnicity and nutritional milieu. The study's findings comprising ethnically and socially homogenous women demonstrate that PCOS and RM are characterised by elevated dehydroepiandrosterone (DHEA) and shortened CL, and PCOS by reduced SHBG. These abnormalities would be expected to have an adverse impact on pregnancy outcomes. Twenty-weeks DHEA and CL values have the potential to predict outcome risk in women with a history of RM and PCOS. Further research on other population groups is required to validate the current study's findings.
Topics: Pregnancy; Female; Humans; Testosterone; Polycystic Ovary Syndrome; Sex Hormone-Binding Globulin; Egypt; Dehydroepiandrosterone; Abortion, Habitual
PubMed: 36689253
DOI: 10.1080/01443615.2022.2163625 -
Problemy Endokrinologii May 2023Hodgkin's lymphoma (HL) is one of the most common malignant lymphoproliferative diseases. Chemotherapy and radiotherapy used in the treatment of LH induce a number of...
BACKGROUND
Hodgkin's lymphoma (HL) is one of the most common malignant lymphoproliferative diseases. Chemotherapy and radiotherapy used in the treatment of LH induce a number of toxic effects leading to dysfunction of endocrine system. Hormonal disorders in HL and their relationships with the therapy used remain to be clarified.
AIM
To assess disorders of the endocrine function of thyroid, parathyroid glands and gonads in HL survivors.
MATERIALS AND METHODS
Screening of endocrine dysfunction of the thyroid, parathyroid glands and gonads was performed in 160 adult patients with HL, 55 men and 105 women, at remission stage induced by chemotherapy or chemoradiotherapy. Forty healthy subjects, matched by age, were acted as control. The levels of TSH, T3, free T4, PTH, FSH, LH, free testosterone, dehydroepiandrosterone sulfate (DHEA-S), and sex-hormone binding globulin (SHBG) were measured in blood serum by ELISA. Bone mineral density (BMD) was assessed by DEXA.
RESULTS
Hypothyroidism (25%), hyperparathyroidism (15.6%) and hypogonadism (29% of men and 25.3% of women) were the most prevalent endocrine disorders in LH survivors. Hypothyroidism was significantly more common in patients after chemoradiotherapy than in those who received only chemotherapy (χ2=9.4, р=0.002). In patients with hyperparathyroidism, there were negative correlations between PTH levels and BMD in the lumbar spine (r=-0.74, p=0.00002) and in the femoral neck (r=-0.66, p=0.0003). Men with HL demonstrated lower free testosterone concentrations when compared to control (p=0.04); LH and FSH levels were elevated (p=0.0004 and p=0.04, respectively). In men with HL the levels of DHEA-S were reduced (p=0.0009). The increased SHBG concentrations were revealed in 13 (23.6%) men. Women of reproductive age with HL had higher levels of LH in the luteal phase (p=0.05) and FSH in the follicular phase (p=0.02) than controls.
CONCLUSION
The data indicate a high prevalence of the dysfunctions of thyroid, parathyroid glands, and gonads in HL survivors. Screening for endocrine disorders in these patients is highly recommended.
Topics: Male; Adult; Humans; Female; Hodgkin Disease; Testosterone; Follicle Stimulating Hormone; Dehydroepiandrosterone; Chemoradiotherapy; Hypothyroidism; Survivors
PubMed: 37448267
DOI: 10.14341/probl13124 -
Biological Psychology Sep 2020Chronic stress during childhood negatively impacts cognition and physical and mental health. Exposure to stressors over time can cause hypothalamic-pituitary-adrenal...
Chronic stress during childhood negatively impacts cognition and physical and mental health. Exposure to stressors over time can cause hypothalamic-pituitary-adrenal (HPA) axis dysregulation, leading to abnormal stress hormone levels, which can be reflected in hair cortisol concentration (HCC) and hair dehydroepiandrosterone (DHEA) concentration. Although the use of HCC and DHEA to measure chronic stress in children is increasing, their effects on cognition (as indexed by executive function) remain unexplored. Accordingly, we aimed to investigate the associations of HCC, DHEA, and their ratio with measures of executive function (cognitive flexibility and working memory) in a sample of kindergarten children (N=100). We found that the expected negative association between HCC and working memory approached significance, and DHEA was significantly and positively related to cognitive flexibility. We discuss possible interpretations of our findings. Our results suggest promising areas for future investigation and encourage further exploration into HCC and DHEA as measures of chronic stress.
Topics: Child; Child, Preschool; Dehydroepiandrosterone; Executive Function; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System
PubMed: 32805299
DOI: 10.1016/j.biopsycho.2020.107946 -
Frontiers in Endocrinology 2023The time of onset of puberty has been increasingly earlier, but its mechanism is still unclear. This study aimed to reveal the mechanism of leptin and NPY in the onset...
OBJECTIVES
The time of onset of puberty has been increasingly earlier, but its mechanism is still unclear. This study aimed to reveal the mechanism of leptin and NPY in the onset of puberty in male offspring rats after androgen intervention during pregnancy.
METHODS
Eight-week-old specific pathogen-free (SPF) healthy male Sprague-Dawley (SD) rats and 16 female SD rats were selected and caged at 1:2. The pregnant rats were randomly divided into the olive oil control group (OOG) and testosterone intervention group (TG), with 8 rats in each group. Olive oil and testosterone were injected from the 15th day of pregnancy, for a total of 4 injections (15th, 17th, 19th, 21st day). After the onset of puberty, the male offspring rats were anesthetized with 2% pentobarbital sodium to collect blood by ventral aorta puncture and decapitated to peel off the hypothalamus and abdominal fat. Serum testosterone (T), free testosterone (FT), dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA), sex hormone binding globulin (SHBG), and leptin were detected by ELISA, and then the free androgen index (FAI) was calculated. The mRNA levels of androgen receptor (AR), estrogen receptor α (ERα), NPY, leptinR, and NPY2R in the hypothalamus and abdominal fat were detected by RT-PCR. Protein expression levels of AR, ERα, NPY, leptinR, and NPY2R in the arcuate nucleus (ARC) of the hypothalamus were detected by immunohistochemistry.
RESULTS
The time of onset of puberty was significantly earlier in the TG than in the OOG ( 0.05) and was positively correlated with body weight, body length, abdominal fat, and leptinR mRNA levels in adipose tissue in the OOG ( 0.05), while it was positively correlated with serum DHT and DHEA concentrations and FAI and AR mRNA levels in the hypothalamus in the TG ( 0.05). The NPY2R mRNA level and protein expression levels of ERα, NPY2R, and leptinR in the TG were significantly higher than those in the OOG, while the protein expression levels of AR and NPY in the TG were significantly lower than those in the OOG ( 0.05).
CONCLUSIONS
Testosterone intervention during pregnancy led to an earlier onset of puberty in male offspring rats, which may render the male offspring rats more sensitive to androgens, leptin, and NPY at the onset of puberty.
Topics: Pregnancy; Rats; Male; Female; Animals; Androgens; Leptin; Estrogen Receptor alpha; Olive Oil; Rats, Sprague-Dawley; Sexual Maturation; Testosterone; Dihydrotestosterone; Dehydroepiandrosterone; RNA, Messenger
PubMed: 37056673
DOI: 10.3389/fendo.2023.1090552 -
PeerJ 2022Dehydroepiandrosterone-sulfate is the most abundant circulating androgen in humans and other catarrhines. It is involved in several biological functions, such as...
BACKGROUND
Dehydroepiandrosterone-sulfate is the most abundant circulating androgen in humans and other catarrhines. It is involved in several biological functions, such as testosterone production, glucocorticoid antagonist actions, neurogenesis and neuroplasticty. Although the role of dehydroepiandrosterone-sulfate (DHEAS) in cognition remains elusive, the DHEAS/cortisol ratio has been positively associated with a slower cognitive age-decline and improved mood in humans. Whether this relationship is found in nonhuman primates remains unknown.
METHODS
We measured DHEAS and cortisol levels in serum of 107 adult chimpanzees to investigate the relationship between DHEAS levels and age. A subset of 21 chimpanzees was used to test the potential associations between DHEAS, cortisol, and DHEAS/cortisol ratio in cognitive function, taking into account age, sex, and their interactions. We tested for cognitive function using the primate cognitive test battery (PCTB) and principal component analyses to categorize cognition into three components: tasks, tasks, and tasks.
RESULTS
DHEAS levels, but not the DHEAS/cortisol ratio, declined with age in chimpanzees. Our analyses for tasks revealed a significant, positive correlation with the DHEAS/cortisol ratio. had a negative relationship with age. Our data show that the DHEAS/cortisol ratio, but not DHEAS individually, is a promising predictor of spatial cognition in chimpanzees.
Topics: Adult; Animals; Humans; Dehydroepiandrosterone Sulfate; Pan troglodytes; Hydrocortisone; Steroids; Cognition; Sulfates
PubMed: 36389417
DOI: 10.7717/peerj.14323 -
Physiology & Behavior Dec 2022This longitudinal study examines the growth of psychological characteristics and adaptation of physiological markers of stress during a six-month assessment and...
This longitudinal study examines the growth of psychological characteristics and adaptation of physiological markers of stress during a six-month assessment and selection course for U.S. Navy SEALs. Resilience, hardiness, and grit instruments were used to evaluate the psychological characteristics. Blood samples were taken to determine physiological markers related to stress adaptation; specifically, evaluating DHEA, DHEA-to-cortisol ratio, BDNF, NPY, and cortisol. Data was collected at four timepoints throughout the assessment and selection course from 353 students over three classes. Results indicated that resilience and hardiness grow after an initial decline, DHEA and DHEA-to-cortisol increased suggesting physiological adaptation. However, psychological and physiological markers do not exhibit the same growth patterns for participants in the course. This study enhances the understanding of psychological growth and physiological adaptation in a high-stress environment over an extended duration.
Topics: Animals; Humans; Hydrocortisone; Dehydroepiandrosterone; Longitudinal Studies; Resilience, Psychological; Seals, Earless; Biomarkers; Stress, Psychological
PubMed: 36179811
DOI: 10.1016/j.physbeh.2022.113970