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Reproductive Biology and Endocrinology... Apr 2024Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder associated with infertility and pregnancy complications. The pathogenesis of PCOS and its impact on...
BACKGROUND
Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder associated with infertility and pregnancy complications. The pathogenesis of PCOS and its impact on reproductive function may be influenced by the source of androgens, including testosterone, free androgen, dehydroepiandrosterone sulfate (DHEAS). However, the differential effects of these androgen on pregnancy and neonatal outcomes and the cut-off value of East Asian population with PCOS remain unclear.
METHODS
A retrospective cohort study was conducted at the Reproductive Medicine Center of the First Affiliated Hospital of Sun Yat-sen University from January 2015 to November 2022, involving 636 cycles of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). Subgroup analyses were performed using cut-off values of 6.4 for free androgen index (FAI), 9.5 µmol/L for DHEAS. Pregnancy and neonatal outcomes were compared between groups. Restricted cubic spline (RCS) was used to identify significant cut-off values affecting pregnancy.
RESULTS
Higher FAI levels (> 6.4) were associated with decrease in clinical pregnancy rate (PR) (50.61% vs. 41.66%, p = 0.024), live birth rate (LBR) (42.42% vs. 32.35%, p = 0.011). When DHEAS levels exceeded 9.5 µmol/L, there was a significant decrease in clinical PR (51.27% vs. 42.73%, P = 0.039), LBR (42.73% vs. 32.73%, P = 0.012). Negative correlations were also observed between DHEAS levels and cumulative pregnancy rate (70.57% vs 56.62% p = 0.002) and cumulative live birth rate (CLBR) (59.35% vs 43.37%, p = 0.0007). Both FAI and DHEAS elevated is associated with the lowest clinical pregnancy rate (37.84%). Conversely, when solely FAI is elevated, the pregnancy rate increases to 52.38%, while an elevation in DHEAS alone is associated with a pregnancy rate of, both of which are lower than when neither FAI nor DHEAS are elevated (60.68%). The live birth rates exhibit a similar trend (30.00% vs 40.00% vs 41.83% vs 44.48%). RCS revealed a significant decrease in CPR and CLBR when DHEA levels exceeded 7.69 umol/L, while the cut-off value of FAI was 6.36 for CPR and CLBR.
CONCLUSION
In conclusion, PCOS patients with biochemical hyperandrogenism show unsatisfactory clinical PR and CLBR when undergoing assisted reproductive technology (ART). This may be attributed to the influence of both adrenal-derived DHEAS and ovarian-derived FAI on the unfavorable pregnancy outcomes.
Topics: Male; Pregnancy; Female; Infant, Newborn; Humans; Polycystic Ovary Syndrome; Androgens; Dehydroepiandrosterone Sulfate; Retrospective Studies; Semen; Dehydroepiandrosterone
PubMed: 38627777
DOI: 10.1186/s12958-024-01212-y -
The Journal of Clinical Endocrinology... Nov 2023Epidemiological and preclinical data support cardiovascular, mainly protective, effects of sex steroids in men, but the mechanisms underlying the cardiovascular actions...
CONTEXT
Epidemiological and preclinical data support cardiovascular, mainly protective, effects of sex steroids in men, but the mechanisms underlying the cardiovascular actions of sex steroids are poorly understood. Vascular calcification parallels the development of atherosclerosis, but is increasingly recognized as a diversified, highly regulated process, which itself may have pathophysiological importance for clinical cardiovascular events.
OBJECTIVE
To investigate the association between serum sex steroids and coronary artery calcification (CAC) in elderly men.
METHODS
We used gas chromatography tandem mass spectrometry to analyze a comprehensive sex steroid profile, including levels of dehydroepiandrosterone (DHEA), androstenedione, estrone, testosterone, estradiol, and dihydrotestosterone, in men from the population-based AGES-Reykjavik study (n = 1287, mean 76 years). Further, sex hormone-binding globulin (SHBG) was assayed and bioavailable hormone levels calculated. CAC score was determined by computed tomography. The main outcome measures were cross-sectional associations between dehydroepiandrosterone, androstenedione, estrone, testosterone, dihydrotestosterone, and estradiol and quintiles of CAC.
RESULTS
Serum levels of DHEA, androstenedione, testosterone, dihydrotestosterone, and bioavailable testosterone showed significant inverse associations with CAC, while estrone, estradiol, bioavailable estradiol, and SHBG did not. DHEA, testosterone, and bioavailable testosterone remained associated with CAC after adjustment for traditional cardiovascular risk factors. In addition, our results support partially independent associations between adrenal-derived DHEA and testes-derived testosterone and CAC.
CONCLUSION
Serum levels of DHEA and testosterone are inversely associated with CAC in elderly men, partially independently from each other. These results raise the question whether androgens from both the adrenals and the testes may contribute to male cardiovascular health.
Topics: Aged; Humans; Male; Androstenedione; Coronary Artery Disease; Dehydroepiandrosterone; Dihydrotestosterone; Estradiol; Estrone; Sex Hormone-Binding Globulin; Testosterone; Vascular Calcification
PubMed: 37391895
DOI: 10.1210/clinem/dgad351 -
The Journal of Clinical Endocrinology... Mar 2022Male sex is a major risk factor for abdominal aortic aneurysms (AAA) but few studies have addressed associations between sex hormone levels and AAA.
CONTEXT
Male sex is a major risk factor for abdominal aortic aneurysms (AAA) but few studies have addressed associations between sex hormone levels and AAA.
OBJECTIVE
We aimed to describe the associations between serum sex steroids and early, screening-detected AAA in men.
METHODS
We validated a high-sensitivity liquid chromatography-tandem mass spectrometry assay for comprehensive serum sex hormone profiling. This assay was then employed in a case-control study including 147 men with AAA (infrarenal aorta ≥ 30 mm) and 251 AAA-free controls recruited at the general population-based ultrasound screening for AAA in 65-year-old Swedish men.
OUTCOMES INCLUDED
associations between dehydroepiandrosterone, progesterone, 17α-hydroxyprogesterone, androstenedione, estrone, testosterone, dihydrotestosterone, and estradiol and AAA presence.
RESULTS
Dehydroepiandrosterone, progesterone, 17α-hydroxyprogesterone, testosterone, and estradiol, but not the other hormones, were lower in men with AAA. In models with adjustments for known AAA risk factors and comorbidity, only progesterone (odds ratio per SD decrease 1.62 [95% CI, 1.18-2.22]) and estradiol (1.40 [95% CI, 1.04-1.87]) remained inversely associated with the presence of AAA. Progesterone and estradiol contributed with independent additive information for prediction of AAA presence; compared with men with high (above median) levels, men with low (below median) levels of both hormones had a 4-fold increased odds ratio for AAA (4.06 [95% CI, 2.25-7.31]).
CONCLUSION
Measured by a high-performance sex steroid assay, progesterone and estradiol are inversely associated with AAA in men, independent of known risk factors. Future studies should explore whether progesterone and estradiol, which are important reproductive hormones in women, are protective in human AAA.
Topics: Aged; Aortic Aneurysm, Abdominal; Case-Control Studies; Dehydroepiandrosterone; Dihydrotestosterone; Estradiol; Female; Humans; Male; Progesterone; Testosterone
PubMed: 34865072
DOI: 10.1210/clinem/dgab867 -
Frontiers in Endocrinology 2023Sex steroid hormones are associated with the advancement of metabolic diseases such as dyslipidemia. This cross-sectional study aimed to investigate the relationship...
OBJECTIVE
Sex steroid hormones are associated with the advancement of metabolic diseases such as dyslipidemia. This cross-sectional study aimed to investigate the relationship between dehydroepiandrosterone, dehydroepiandrosterone sulfate, androstenedione, and testosterone levels and the risk of dyslipidemia in people with type 2 diabetes mellitus.
MATERIALS AND METHODS
The analysis included 1,927 patients with type 2 diabetes mellitus. Serum dehydroepiandrosterone, dehydroepiandrosterone sulfate, androstenedione, and testosterone levels were determined using lipid chromatography-tandem mass spectrometry. Multivariable analyses were performed to investigate the association between the variables and dyslipidemia.
RESULTS
The multivariable-adjusted odds ratio (OR) and 95% confidence interval (CI) of dyslipidemia across DHEA tertiles were 0.39 and 0.24-0.64, respectively (p trend = 0.001). This relationship was still maintained when analyzed as a continuous variable (odds ratio, 0.96; 95% confidence interval, 0.92-0.99; P < 0.01). However, in males with type 2 diabetes mellitus, no significant correlations were found between rising levels of dehydroepiandrosterone sulfate, androstenedione, and total testosterone and the risk of dyslipidemia (all P > 0.05). Furthermore, there was no significant association between androgen precursors and total testosterone with regard to the risk of developing dyslipidemia (all P > 0.05).
CONCLUSIONS
Serum dehydroepiandrosterone levels were substantially and adversely correlated with dyslipidemia in adult men with T2DM. These results indicated that dehydroepiandrosterone may have an essential role in the development of dyslipidemia. More prospective research is required to validate this link.
Topics: Adult; Humans; Male; Androstenedione; Cross-Sectional Studies; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Diabetes Mellitus, Type 2; Prospective Studies; Testosterone; Dyslipidemias; Risk Factors
PubMed: 38075062
DOI: 10.3389/fendo.2023.1272797 -
JBRA Assisted Reproduction Oct 2019One in six couples worldwide will experience at least one infertility problem during their reproductive years. Between 5.6% and 35.1% of women will exhibit poor ovarian... (Review)
Review
One in six couples worldwide will experience at least one infertility problem during their reproductive years. Between 5.6% and 35.1% of women will exhibit poor ovarian response. A variety of methods have been applied to improve ovarian response, including dehydroepiandrosterone. In the ovaries, dehydroepiandrosterone promotes follicular development and granulosa cell proliferation by increasing intraovarian androgen concentrations while simultaneously enhancing the level of follicular insulin-like growth factor-1, which promotes folliculogenesis. Dehydroepiandrosterone supplementation may improve in vitro fertilization outcomes and ovarian response in patients with poor ovarian response. However, a few questions still loom over the effectiveness of dehydroepiandrosterone.
Topics: Adult; Dehydroepiandrosterone; Female; Fertilization in Vitro; Humans; Infertility, Female; Ovulation Induction; Pregnancy; Pregnancy Rate; Treatment Outcome
PubMed: 31251010
DOI: 10.5935/1518-0557.20190045 -
Frontiers in Immunology 2022Effective control of () infection is mediated by multifaceted factors that involve both the endocrine and immune system. Profiling hormones and antibodies in different...
Effective control of () infection is mediated by multifaceted factors that involve both the endocrine and immune system. Profiling hormones and antibodies in different stages of TB provides insight in the pathogenesis of the disease. In this study, we profiled endocrine hormones (dehydroepiandrosterone (DHEA), cortisol, testosterone, estradiol, growth hormone and leptins) and strain H37RV lipoarabinomannan (LAM)-specific antibody levels in plasma samples, collected from pulmonary TB (PTB) patients, TB lymphadenitis (TBLN) patients and latently infected (QFT-positive) or uninfected (QFT-negative) apparently healthy individuals using ELISA. Plasma levels of leptin and DHEA were significantly low in PTB and TBLN patients compared to healthy controls (P<0.0001 and P=0.02, respectively), whereas these levels significantly increased following anti-TB treatment (P=0.002 and P=0.0001, respectively) among TB patients. The levels of estradiol and testosterone significantly improved following anti-TB treatment (P=0.03 and P=0.0003, respectively), whereas cortisol and growth hormones declined significantly (P <0.05). Similarly, LAM-specific IgG, IgM and IgA were significantly higher in PTB patients compared to other groups, whereas levels of IgG1 subtype were significantly higher among LTBI groups compared to both TB patients and QFT-negative individuals (P<0.0001). Overall, we observed significantly variable levels of endocrine hormones as well as immunoglobulins across the spectrum of TB illness and such profiling has a significant contribution in selection of effective biomarkers that have roles in TB treatment monitoring or diagnostics. Although this study did not show a functional association between hormones and antibodies, alterations in the levels of these biomarkers suggest the key roles these markers play in TB pathogenesis.
Topics: Antibody Formation; Biomarkers; Dehydroepiandrosterone; Estradiol; Humans; Hydrocortisone; Testosterone; Tuberculosis; Tuberculosis, Pulmonary
PubMed: 35281036
DOI: 10.3389/fimmu.2022.849321 -
Scientific Reports Jan 2023To determine association paths between prenatal androgens and cord blood androgens. The concentrations of T, FT, DHT, DHEA and SHBG in prenatal venous blood and cord...
To determine association paths between prenatal androgens and cord blood androgens. The concentrations of T, FT, DHT, DHEA and SHBG in prenatal venous blood and cord blood were measured in 342 pregnant women and their neonates. The association paths between these hormones in prenatal and cord blood were revealed using Pearson correlation, multiple linear regression and path analysis. CB-T, CB-FT and CB-DHT in male neonates were higher than those in female neonates. In male and female neonates, P-FT was lower than CB-FT; however, P-DHT and P-SHBG were higher than CB-DHT and CB-SHBG, respectively. P-DHEA was lower than CB-DHEA in female newborns. In male neonates, there were association paths of P-T → CB-T → CB-FT → CB-DHT, P-T → CB-FT → CB-DHT, P-T → P-FT → CB-FT → CB-DHT, P-T → P-DHT, CB-DHEA → CB-DHT, CB-DHEA → P-DHT, and CB-DHEA → P-DHEA. In female neonates, there were association paths of P-T → CB-T → CB-FT → CB-DHT, P-T → P-FT → CB-FT → CB-DHT, P-T → P-FT → P-DHT, P-T → P-DHT, P-DHEA → P-DHT, CB-DHEA → P-DHEA, and CB-DHEA → CB-FT. There were differences in the T, FT and DHT concentrations in cord blood between male and female neonates and in the FT, DHT, DHEA, and SHBG concentrations between prenatal and cord blood. P-T and P-FT concentrations were positively associated with CB-T and CB-FT concentrations, while CB-DHEA concentration was positively associated with P-DHEA concentration.
Topics: Female; Male; Infant, Newborn; Humans; Pregnancy; Androgens; Testosterone; Dehydroepiandrosterone; Fetal Blood
PubMed: 36611054
DOI: 10.1038/s41598-022-25531-5 -
Frontiers in Endocrinology 2023This study aimed to investigate the neuroendocrine responses based on cortisol, dehydroepiandrosterone (DHEA), cortisol/DHEA ratio, and chromogranin A levels, which...
INTRODUCTION
This study aimed to investigate the neuroendocrine responses based on cortisol, dehydroepiandrosterone (DHEA), cortisol/DHEA ratio, and chromogranin A levels, which reflect the activity of the hypothalamic-pituitary-adrenal axis, according to the presence or absence of psychological stress in patients with gingivitis and periodontitis compared to that in healthy controls.
METHODS
In total, 117 patients (60 women, mean age: 36.29 ± 19.03 years) participated in this case-control study, comprising 32 healthy controls, 49 patients with gingivitis, and 36 patients with periodontitis. We investigated the presence of psychological stress and salivary characteristics, and analyzed the stress-related biomarkers of cortisol, DHEA, cortisol/DHEA ratio, and chromogranin A in the stimulated saliva.
RESULTS
Salivary cortisol and chromogranin A levels increased with the severity of periodontal disease; their levels were the highest in the periodontitis group and were significantly higher in the following descending order: periodontitis, gingivitis, and healthy control groups (all values of p < 0.001). Additionally, the DHEA levels and cortisol/DHEA ratio were higher in the periodontitis group than those in the healthy control group (all values of p < 0.001). A multivariate logistic regression analysis revealed that the factors predicting above-average cortisol levels were periodontitis (odds ratio [OR] = 256.829; p < 0.001), women (OR = 6.365; p = 0.004), and psychological stress (OR = 6.036; p = 0.007); those predicting above-average cortisol/DHEA ratios were periodontitis (OR = 11.436; p < 0.001), psychological stress (OR = 3.977; p = 0.003), and women (OR = 2.890; p = 0.026). Thus, periodontitis and psychological stress were significant and strong predictors of above-average cortisol levels and cortisol/DHEA ratios. In the gingivitis group, salivary cortisol levels (r = 0.381, p = 0.007) and cortisol/DHEA ratios (r = 0.479, p < 0.001) were correlated with the presence of psychological stress. In the periodontitis group, increased cortisol/DHEA ratios (r = 0.412, p = 0.013) and lowered salivary buffer capacities (r = -0.334, p = 0.047) were correlated with the presence of psychological stress.
CONCLUSION
Periodontitis is a multifactorial disease resulting in inflammatory tissue destruction, which differs from gingivitis and a healthy state. Differences in stress-related neuroendocrine markers were revealed based on the severity of periodontal disease. The biomarkers that could be classified according to disease severity were salivary cortisol and chromogranin A levels. Above-average cortisol levels and cortisol/DHEA ratios are significant predictors of psychological stress in patients with gingivitis and periodontitis.
Topics: Adolescent; Adult; Female; Humans; Middle Aged; Young Adult; Biomarkers; Case-Control Studies; Chromogranin A; Dehydroepiandrosterone; Gingivitis; Hydrocortisone; Hypothalamo-Hypophyseal System; Periodontitis; Pituitary-Adrenal System; Stress, Psychological; Male
PubMed: 37113482
DOI: 10.3389/fendo.2023.1147739 -
Physiological Research Dec 2022Pulmonary hypertension is a group of disorders characterized by elevated mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance. To test our hypothesis...
Pulmonary hypertension is a group of disorders characterized by elevated mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance. To test our hypothesis that combining two drugs useful in experimental pulmonary hypertension, statins and dehydroepiandrosterone sulfate (DHEA S), is more effective than either agent alone, we induced pulmonary hypertension in adult male rats by exposing them to hypoxia (10%O2) for 3 weeks. We treated them with simvastatin (60 mg/l) and DHEA S (100 mg/l) in drinking water, either alone or in combination. Both simvastatin and DHEA S reduced mPAP (froma mean±s.d. of 34.4±4.4 to 27.6±5.9 and 26.7±4.8 mmHg, respectively), yet their combination was not more effective (26.7±7.9 mmHg). Differences in the degree of oxidative stress (indicated by malondialdehydeplasma concentration),the rate of superoxide production (electron paramagnetic resonance), or blood nitric oxide levels (chemiluminescence) did not explain the lack of additivity of the effect of DHEA S and simvastatin on pulmonary hypertension. We propose that the main mechanism of both drugs on pulmonary hypertension could be their inhibitory effect on 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, which could explain their lack of additivity.
Topics: Rats; Male; Animals; Hypertension, Pulmonary; Simvastatin; Dehydroepiandrosterone Sulfate; Pulmonary Artery; Hypoxia; Dehydroepiandrosterone
PubMed: 36426885
DOI: 10.33549/physiolres.934913 -
Human Brain Mapping Dec 2023The anterior pituitary gland (PG) is a potential locus of hypothalamic-pituitary-adrenal (HPA) axis responsivity to early life stress, with documented associations...
INTRODUCTION
The anterior pituitary gland (PG) is a potential locus of hypothalamic-pituitary-adrenal (HPA) axis responsivity to early life stress, with documented associations between dehydroepiandrosterone (DHEA) levels and anterior PG volumes. In adults, elevated anxiety/depressive symptoms are related to diminished DHEA levels, and studies have shown a positive relationship between DHEA and anterior pituitary volumes. However, specific links between responses to stress, DHEA levels, and anterior pituitary volume have not been established in developmental samples.
METHODS
High-resolution T1-weighted MRI scans were collected from 137 healthy youth (9-17 years; M = 12.99 (SD = 1.87); 49% female; 85% White, 4% Indigenous, 1% Asian, 4% Black, 4% multiracial, 2% not reported). The anterior and posterior PGs were manually traced by trained raters. We examined the mediating effects of salivary DHEA on trauma-related symptoms (i.e., anxiety, depression, and posttraumatic) and PG volumes as well as an alternative model examining mediating effects of PG volume on DHEA and trauma-related symptoms.
RESULTS
DHEA mediated the association between anxiety symptoms and anterior PG volume. Specifically, higher anxiety symptoms related to lower DHEA levels, which in turn were related to smaller anterior PG.
CONCLUSIONS
These results shed light on the neurobiological sequelae of elevated anxiety in youth and are consistent with adult findings showing suppressed levels of DHEA in those with greater comorbid anxiety and depression. Specifically, adolescents with greater subclinical anxiety may exhibit diminished levels of DHEA during the pubertal window, which may be associated with disruptions in anterior PG growth.
Topics: Adult; Humans; Adolescent; Child; Female; Male; Dehydroepiandrosterone; Hydrocortisone; Hypothalamo-Hypophyseal System; Anxiety; Pituitary-Adrenal System
PubMed: 37853842
DOI: 10.1002/hbm.26516