Dehydroepiandrosterone Sulfate Levels Research Articles

An adrenal incidentaloma that had appeared to produce dehydroepiandrosterone-sulfate in excess before immunohistochemical study of the tumor.

Adrenal incidentaloma is a clinically unapparent adrenal mass more than one cm in diameter detected during imaging performed not for adrenal disease. A 34-year-old man was evaluated for AI with a diameter of 3.5 cm in the left adrenal. He was obese with body mass index of 33,9. Blood pressure was 110-120/90 mmHg. The general laboratory tests were unremarkable. An adrenal hormone screening set revealed that ACTH was 6.9 pg/mL, cortisol 14.9 μg/dL, renin activity 0.9 ng/mL/h, aldosterone 79.4 pg/mL, dehydroepiandrosterone-sulfate (DHEA-S) measured on two occasions 5,217 ng/mL and 6,477 ng/mL (gender- and age-adjusted reference values, 1,060-4,640 ng/mL). The levels of metanephrine and normetanephrine were normal. The tumor was thought to produce solely DHEA-S. The excised left adrenal tissue contained a tumor with a diameter of 26 mm and neighboring adrenal tissue. The tumor consisted mostly of acidophil cells without necrosis, capsular or vascular invasion, and mitosis. Immunohistochemical study revealed followings: the cells of the tumors were stained positive for 3β-hydroxysteroid dehydrogenase, and 17α-hydroxylase, and 11β-hydroxylase, weakly positive for DHEA sulphotransferase, and negative for aldosterone synthetase. The atrophy of neighboring tissue was presumably caused by excess cortisol production. Four months after surgery, the cortisol level was 11.2 μg/dL and DHEA-S level 1,462 ng/mL. The tumor is considered to be a cortisol-producing adenoma with modestly excessive DHEA-S production rather than isolated DHEA-S-producing adenoma. Immunohistochemical study of steroidogenic enzymes is a valuable addition to blood hormone measurement to clarify steroid production profile.

Efficacy of resveratrol in women with polycystic ovary syndrome: a systematic review and meta-analysis of randomized clinical trials.

Polycystic ovarian syndrome (PCOS) is a metabolic and hormonal condition affecting women of a reproductive age. It causes an abnormal menstrual cycle, anovulation, infertility, acne, hirsutism, obesity, hyperlipidemia, and cardiovascular disorders. Because resveratrol decreases testosterone levels, it may be of value in treating PCOS. We aimed to evaluate the efficacy of resveratrol in treating women with PCOS. We searched for randomized clinical trials (RCTs) in PubMed, Cochrane CENTRAL, Scopus and Web of Science. With 95% confidence intervals, the data was retrieved and analyzed as a mean difference (MD) or a standardized mean difference (SMD). Four RCTs with 218 women were included in the analysis. Resveratrol significantly reduced testosterone (SMD = -0.40; 95% CI [-0.71, -0.10], P = 0.009), luteinizing hormone (LH) (SMD = -0.32; 95% CI [-0.62, 0.01], P = 0.04), and dehydroepiandrosterone sulfate (DHEAS) (MD = -0.85; 95% CI [-1.25, -0.45], P < 0.0001) compared with the placebo. Resveratrol is effective in treating women with PCOS due to reducing the levels of testosterone, LH, and DHEAS. In combination with other treatments, especially for hyperlipidemia, resveratrol is beneficial for women diagnosed with PCOS.

Persisting neuropsychiatric symptoms, Alzheimer’s disease, and cerebrospinal fluid cortisol and dehydroepiandrosterone sulfate

IntroductionNeuropsychiatric symptoms are important treatment targets in the management of dementia and can be present at very early clinical stages of neurodegenerative diseases. Increased cortisol has been reported in Alzheimer’s disease (AD) and has been associated with faster cognitive decline. Elevated cortisol output has been observed in relation to perceived stress, depression, and anxiety. Dehydroepiandrosterone sulfate (DHEAS) has known anti-glucocorticoid effects and may counter the effects of cortisol.ObjectivesWe aimed to examine whether CSF cortisol and DHEAS levels were associated with (1) neuropsychiatric symptoms at baseline, (2) changes in neuropsychiatric symptoms over 3 years, and (3) whether these associations were related to or independent of AD pathology.MethodsOne hundred and eighteen participants on a prospective study in a memory clinic setting, including patients with cognitive impairment (n = 78), i.e., mild cognitive impairment or mild dementia, and volunteers with normal cognition (n = 40), were included. Neuropsychiatric symptoms were assessed using the Neuropsychiatric Inventory Questionnaire (NPI-Q). CSF cortisol and DHEAS, as well as CSF AD biomarkers, were obtained at baseline. Neuropsychiatric symptoms were re-assessed at follow-up visits 18 and 36 months from baseline. We constructed linear regression models to examine the links between baseline neuropsychiatric symptoms, the presence of AD pathology as indicated by CSF biomarkers, and CSF cortisol and DHEAS. We used repeated-measures mixed ANCOVA models to examine the associations between the neuropsychiatric symptoms’ changes over time, baseline CSF cortisol and DHEAS, and AD pathology.ResultsHigher CSF cortisol was associated with higher NPI-Q severity scores at baseline after controlling for covariates including AD pathology status (B = 0.085 [0.027; 0.144], p = 0.027; r = 0.277). In particular, higher CSF cortisol was associated with higher baseline scores of depression/dysphoria, anxiety, and apathy/indifference. Elevated CSF cortisol was also associated with more marked increase in NPI-Q scores over time regardless of AD status (p = 0.036, η2 = 0.207), but this association was no longer significant after controlling for BMI and the use of psychotropic medications. CSF DHEAS was associated neither with NPI-Q scores at baseline nor with their change over time. Cortisol did not mediate the association between baseline NPI-Q and changes in clinical dementia rating sum of boxes over 36 months.ConclusionHigher CSF cortisol may reflect or contribute to more severe neuropsychiatric symptoms at baseline, as well as more pronounced worsening over 3 years, independently of the presence of AD pathology. Our findings also suggest that interventions targeting the HPA axis may be helpful to treat neuropsychiatric symptoms in patients with dementia.

Dehydroepiandrosterone Sulfate and Mortality in Middle-Aged and Older Men and Women-A J-shaped Relationship.

The relationship between dehydroepiandrosterone sulfate (DHEAS) and mortality is of scientific and public health interest, yet it remains poorly understood. We examined the association between DHEAS and mortality from cancer, cardiovascular disease, and all causes in middle-aged and older men and women. DHEAS was measured in stored serum samples collected from 1994 to 1998 from a case-cohort nested within EPIC-Heidelberg, that included 7370 men (mean age = 55.0) and women (mean age = 52.4 years). Median follow-up for incident mortality events was 17.7 years. All deaths due to cancer (n = 1040), cardiovascular diseases (n = 598), and all causes (n = 2407) that occurred in EPIC-Heidelberg until end of 2014 were included. The association between DHEAS and mortality was nonlinear such that both participants in the lowest (Q1) and highest (Q5) sex- and 5-year age-group specific quintiles of DHEAS were at increased hazard ratios (HR) of mortality from cardiovascular [Q1: HR = 1.83 (95% CI: 1.33-2.51), Q5: 1.39 (1.00-1.94)], cancer [Q1: 1.27 (1.01-1.60), Q5: 1.27 (1.02-1.60)] and all causes [Q1: 1.51 (1.25-1.82), Q5: 1.31 (1.08-1.58)], compared with participants in Q3. In men and women with below-median DHEAS levels, doubling of DHEAS was associated with lower hazards of cardiovascular [0.87, (0.78-0.96)], cancer [0.90, (0.83-0.97)], and total mortality [0.89, (0.83-0.95)]. In contrast, a doubling in DHEAS among participants with above-median levels was associated with 1.20, (1.01-1.42), 1.28, (1.01-1.62), and 1.19 (1.03-1.37) higher hazards of mortality from cancer, cardiovascular, and all causes, respectively. In this large population-based study, DHEAS showed a J-shaped association with mortality. Both participants with lowest and highest levels experienced higher hazards of mortality from cancer, cardiovascular disease, and all causes.

Premature adrenarche in Prader-Willi syndrome is associated with accelerated pre-pubertal growth and advanced bone age.

Prader-Willi syndrome (PWS) is characterized by obesity, growth hormone deficiency, hypogonadism, and a high prevalence of premature adrenarche despite reported hypothalamic-pituitary-adrenal axis dysfunction. While idiopathic premature adrenarche is associated with accelerated pre-pubertal growth and advanced bone age, the consequences of elevated adrenal androgens on growth and bone maturation in PWS remain unknown. This study therefore sought to describe age-related changes in dehydroepiandrosterone sulfate (DHEAS) and their effects on growth and bone maturation in PWS. This retrospective observational study included 62 children with PWS. Simple and multiple regression models were constructed to relate age and BMI-SDS with DHEAS levels. Height velocity was compared to age andsex-based norms with t-tests and two-way ANOVA. Patterns in bone age Z-score were examined with two-way ANOVA, and the contributions of age, BMI-SDS, and DHEAS to bone age Z-score were analyzed with multiple regression. DHEAS levels rose earlier and were less strongly correlated with age in males and females with PWS (R2=0.12 and 0.30) compared to healthy controls (R2=0.89 and 0.88) in a pattern unrelated to BMI-SDS (adjusted R2=0.076, p=0.10 for age, and 0.29 for BMI-SDS). Mid-childhood height velocity was increased in males and preserved in females with PWS before declining at the age of expected puberty (p<0.0001). Peri-adrenarchal bone age was advanced in a manner associated with DHEAS but not BMI-SDS (p<0.0001; adjusted R2=0.48, p=0.0014 for DHEAS, and 0.78 for BMI-SDS). An obesity-independent increase in adrenal androgens is associated with accelerated mid-childhood growth and bone maturation in PWS.

Role of hypothalamic-pituitary-adrenal axis and catecholamine factors in independent and primary multiple types of tumor growth

Purpose of the study. To study the levels of adrenal axis factors in the hypothalamus, adrenal glands, blood serum of mice and catecholamines in the adrenal glands during the independent growth of B16 melanoma and Lewis lung carcinoma (LLC) and their combined growth in female mice, and in males – with independent growth of B16 and combined growth of B16 and LLC.Materials and methods. Male and female BALB/c Nude mice were divided into groups, n = 7 each: group 1 involved intact animals, group 2 involved mice with B16/F10 melanoma, group 3 – mice with LLC, group 4 – synchronous growth of melanoma and LLC. Levels of corticotropin releasing, noradrenaline and dopamine were determined in homogenates of the hypothalamus and adrenal glands and in the blood serum of all animals by ELISA, and levels of 17‑hydroxyprogesterone (17-OHP), dehydroepiandrosterone sulfate (DHEA-S) and cortisol were determined by RIA. Statistical processing of results was performed using the Statistica 10.0 program.Results. All tumor-bearing females showed elevated corticotropin releasing in the hypothalamus together with an increase of all stress-characterizing parameters: cortisol, the cortisol/DHEA-S ratio, and noradrenaline. However, an increase in serum levels of cortisol was blocked by high levels of DHEA-S, and as a result, the cortisol/DHEA-S ratio was either within the normal range (B16 melanoma and B16+LLC combination) or reduced (LLC). Levels of corticotropin releasing in the hypothalamus of tumor-bearing males decreased, together with opposite changes in stress-characterizing parameters in the adrenal glands: cortisol increased, the cortisol/DHEA-S ratio did not differ significantly from the control values, and noradrenaline decreased. An increase in serum levels of cortisol was not blocked by high levels of DHEA-S, and as a result, the cortisol/DHEA-S ratio was sharply elevated in B16 melanoma and B16+LLC combination.Conclusion. At independent and primary multiple types of tumor growth, the sex-specific features of the functioning of the adrenal axis at the central and peripheral levels are observed, which determines a more pronounced stressful state of the body with B16+LLC combination growth, realized by various mechanisms.

Exploring the natural history of polycystic ovary syndrome: still a long road to traverse.

I read with keen interest the systematic review by Kiconco et al. (2022) that makes a sincere effort to throw light on the understanding of the natural history of polycystic ovary syndrome (PCOS). The authors found that there was consistent evidence, though from limited studies, that the level of total testosterone and dehydroepiandrosterone sulfate declined to a greater degree and the risk of gestational diabetes was higher in women with PCOS as compared to those without it. However, the evidence was found to be conflicting or insufficient for the other outcomes which are more likely to have practical long-term implications in the lives of women with PCOS. In the process of the selection of articles for the review, the participants were females of any age group and weight with a diagnosis of PCOS. The fact of extreme heterogeneity among the studies notwithstanding, it is conceptually imprecise to include women with PCOS of all age and weight categories in one common group. The international evidence-based guidelines on the assessment and management of PCOS recommends to assess the BMI in all patients and also the prevention of excess weight gain (Teede et al., 2018). Visceral adiposity is known to result in an increase in insulin resistance as well as aggravation of reproductive and metabolic features in PCOS. Obesity is significantly associated with menstrual irregularity, hyperandrogenemia and hirsutism (Rosenfield and Ehrmann, 2016). PCOS in the adolescent age group presents diagnostic challenges due to a considerable overlap of physiological features of the pubertal transition phase with the diagnostic criteria of adult PCOS (Peña et al., 2020). A meta-analysis of differentially expressed genes across various tissue types in PCOS indicated that the etiology, genetic contributors, and expression profile of genes from similar cell types are different in the obese and the lean phenotypes (Idicula-Thomas et al., 2020). Consequently, it is of paramount importance to understand the natural history of this chronic disease according to its different phenotypes.

Sleep and Anabolic/Catabolic Hormonal Profile in Sedentary Middle-Aged Adults: The FIT-AGEING Study

Sleep quality plays an important role in the modulation of several aging markers. This influence could be explained by aging-induced hormonal changes. Indeed, poor sleep quality has been associated with the development of several endocrine-related health complications. This study examined the relationship of both subjective and objective sleep quantity and quality, with basal levels of selected plasma anabolic and catabolic hormones in sedentary middle-aged adults. A total of 74 volunteers (52.7% women; aged 53.7 ± 5.1) were recruited for this study. Subjective sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI; higher scores indicate worse sleep quality), and objective sleep quality parameters (total sleep time [TST], wake after sleep onset [WASO], and sleep efficiency [SE]) were measured using a wrist-worn accelerometer. Basal levels of plasma dehydroepiandrosterone sulphate (DHEAS), total testosterone, sex hormone binding globulin (SHBG), somatotropin, and cortisol levels, were determined. Free testosterone was calculated from the total testosterone and SHBG levels. No associations of global PSQI score, TST, WASO, and SE with DHEAS, free testosterone, and somatotropin plasma levels were found, neither in men nor in women (all p ≥ 0.05). Global PSQI score was inversely related to cortisol plasma levels in women (p = 0.043). WASO was positively associated with cortisol plasma levels, while SE was negatively associated with cortisol plasma levels in women (all p ≤ 0.027). Sleep quality is not related to levels of plasma anabolic hormones, but to levels of catabolic hormones, in sedentary middle-aged adults. Therefore, these results suggest that potential changes in aging biomarkers associated with sleep disturbances, could be mediated by age-related changes in the catabolic endocrine system.

Assessing the androgenic and metabolic heterogeneity in polycystic ovary syndrome using cluster analysis.

Some but not all women with polycystic ovary syndrome (PCOS) develop the metabolic syndrome (MS). The objective of this study was to determine if a subset of women with PCOS had higher androgen levels predisposing them to MSand whether routinely measured hormonal parameters impacted the metabolic syndrome score (siMS). We included data from a discovery (PCOS clinic data) and a replication cohort (Hull PCOS Biobank) and utilized eight routinely measured hormonal parameters in our clinics (free androgen index [FAI], sex hormone-binding globulin, dehydroepiandrosterone sulphate (DHEAS), androstenedione, luteinizing hormone [LH], follicular stimulating hormone, anti-Müllerian hormone and 17 hydroxyprogesterone [17-OHP]) to perform a K-means clustering (an unsupervised machine learning algorithm). We used NbClust Package in R to determine the best number of clusters. We estimated the siMS in each cluster and used regression analysis to evaluate the effect of hormonal parameters on SiMS. The study consisted of 310 women with PCOS (discovery cohort: n = 199, replication cohort: n = 111). The cluster analysis identified two clusters in both the discovery and replication cohorts. The discovery cohort identified a larger cluster (n = 137) and a smaller cluster (n = 62), with 31% of the study participants. Similarly, the replication cohort identified a larger cluster (n = 74) and a smaller cluster (n = 37) with 33% of the study participants. The smaller cluster in the discovery cohort had significantly higher levels of LH (7.26 vs. 16.1 IU/L, p < .001), FAI (5.21 vs. 9.22, p < .001), androstenedione (3.93 vs. 7.56 nmol/L, p < .001) and 17-OHP (1.59 vs.3.12 nmol/L, p < .001). These findings were replicated in the replication cohort. The mean (±SD) siMS score was higher in the smaller cluster, 3.1 (±1.1) versus 2.8 (±0.8); however, this was not statistically significant (p = .20). In the regression analysis, higher FAI (β = .05, p = .003) and androstenedione (β = .03, p = .02) were independently associated with a higher risk of SiMS score, while higher DHEAS levels were associated with a lower siMS score (β = -.07, p = .03) CONCLUSION: We identified a subset of women in our PCOS cohort with significantly higher LH, FAI, and androstenedione levels. We show that higher levels of androstenedione and FAI are associated with a higher siMS, while higher DHEAS levels were associated with lower siMS.

Establishing and Verifying a Robust Liquid Chromatography-Tandem Mass Spectrometry Method to Simultaneously Measure Seven Androgens Present in Plasma Samples

Objectives: To develop a robust liquid chromatography-tandem mass spectrometry (LC–MS/MS) method to simultaneously measure seven human plasma androgens, namely testosterone (T), dihydrotestosterone (DHT), androstenedione (A4), dehydroepiandrosterone sulfate (DHEAS), dehydroepiandrosterone (DHEA), 11-ketotestosterone (11-KetoT), and 11β-hydroxytestosterone (11β-OHT). Design and Methods: Plasma was extracted via a solid phase extraction method, and the analytical performance of the assay was validated according to the Clinical &amp; Laboratory Standards Institute guidelines. Overall, 73 apparently healthy volunteers were recruited to evaluate the distribution of these seven androgens; their levels in 25 females with acne and 33 obese females were also evaluated. Results: The developed method exhibited a good precision, with the total coefficient variations (CV) and the intra-assay CVs being within 10%. Furthermore, the recoveries of T, DHT, A4, DHEA, DHEAS, 11-KetoT, and 11β-OHT were 90.3–105.8, 88.7–98.1, 92.4–102.5, 90.5–106.7, 87.6–99.9, 93.3–105.3, and 90.2–104.4%, respectively, and no significant matrix effect was observed after internal standard correction (&lt;20%). Moreover, the limits of quantification were 0.01, 0.01, 0.01, 0.10, 5.00, 0.02, and 0.02 ng/mL for T, DHT, A4, DHEA, DHEAS, 11-KetoT, and 11β-OHT, respectively, which are adequate for their accurate measurement in human plasma samples. It was also determined that patients diagnosed with acne had significantly higher levels of DHT, A4, and DHEAS, while those suffering from obesity had significantly higher levels of T and A4 but lower levels of DHT. Conclusions: A robust LC-MS/MS method for the simultaneous determination of seven androgens in plasma samples was successfully established and validated, which plays important roles in clinical application.

Age, adrenal steroids, and cognitive functioning in captive chimpanzees (Pan troglodytes).

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. 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: spatial relationship tasks, tool use and social communication tasks, and auditory-visual sensory perception tasks. DHEAS levels, but not the DHEAS/cortisol ratio, declined with age in chimpanzees. Our analyses for spatial relationships tasks revealed a significant, positive correlation with the DHEAS/cortisol ratio. Tool use and social communication 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.

Early Changes in Androgen Levels in Individuals with Spinal Cord Injury: A Longitudinal SwiSCI Study

We aimed to explore longitudinal changes in androgen levels in individuals with spinal cord injury (SCI) within initial inpatient rehabilitation stay and identify clinical/injury characteristics associated with hormone levels. Linear regression analysis was applied to explore the association between personal/injury characteristics and androgen hormones (total testosterone, free testosterone, sex hormone-binding globulin (SHBG), dehydroepiandrosterone (DHEA), and dehydroepiandrosterone sulfate (DHEA-S)) at admission to rehabilitation. Longitudinal changes in androgen levels were studied using linear mixed models. Analyses were stratified by sex and by injury type. We included 70 men and 16 women with SCI. We observed a non-linear association between age, time since injury, and androgens at baseline. At admission to initial rehabilitation, mature serum SHBG (full-length, protein form which lacks the N-terminal signaling peptide) was higher, while DHEA and DHEA-S were lower among opioid users vs. non-users. Serum levels of total testosterone and DHEA-S increased over rehabilitation period [β 3.96 (95%CI 1.37, 6.56), p = 0.003] and [β 1.77 (95%CI 0.73, 2.81), p = 0.01], respectively. We observed no significant changes in other androgens. Restricting our analysis to men with traumatic injury did not materially change our findings. During first inpatient rehabilitation over a median follow up of 5.6 months, we observed an increase in total testosterone and DHEA-S in men with SCI. Future studies need to explore whether these hormonal changes influence neurological and functional recovery as well as metabolic parameters during initial rehabilitation stay.

Severe intrahepatic cholestasis of pregnancy due to a Sertoli-Leydig cell tumour in a woman with polycystic ovary syndrome: a case report

BackgroundIntrahepatic cholestasis of pregnancy (ICP) is a common gestational complication characterized by pruritus and elevated bile acids, usually occurring in the third trimester when the serum estrogen and progesterone levels are highest. Hyperandrogenism during pregnancy is a pathological state that is mostly induced by polycystic ovary syndrome (PCOS) but rarely by concomitant androgen-secreting ovarian tumours. To date, no correlation has been drawn between ICP and hyperandrogenism.Case presentationHere, we present a rare case of early-onset severe ICP in a PCOS patient conceived via in vitro fertilization-embryo transfer, with worsening hirsutism and acne due to high levels of testosterone and dehydroepiandrosterone sulphate, both of which were produced by a fast-growing ovarian Sertoli–Leydig cell tumour. Her serum estradiol was also very high, which was speculated to be converted from the circulating androgens by the placenta. She had preterm premature rupture of membranes and delivered at 30 weeks, followed by a rapid remission of ICP as her serum estradiol dropped. However, the excessive androgens did not retreat until the large ovarian tumour was surgically removed.ConclusionThis unusual case highlights the concurrence of original hyperandrogenism and subsequent hyperestrogenism during pregnancy and the resultant confounding manifestations. Obstetricians should be aware of the potential association between androgen excess and ICP via placental aromatization.

Total cholesterol/high-density lipoprotein and inflammatory parameters in patients with polycystic ovary syndrome.

In this study, the hormone profile, lipid profile, and inflammatory parameters of patients with polycystic ovary syndrome were compared with those of non-polycystic ovary syndrome patients to determine predictive markers in young polycystic ovary syndrome patients who have not yet had children. Patients' age, height, weight, body mass index, waist circumference, degree of hirsutism, and ultrasound findings were recorded. Hormone profile, lipid levels, ratio of complete blood count parameters, monocyte/high-density lipoprotein ratio, and total cholesterol/high-density lipoprotein ratio were compared between groups. No statistically significant differences were found between groups in terms of age, weight, waist circumference, body mass index, and dysmenorrhea (p>0.05). A significant relationship was found between the height and the degree of hirsutism in the groups (p<0.05). It was found that prolactin, total testosterone, and dehydroepiandrosterone sulfate levels were statistically significantly higher in the polycystic ovary syndrome group compared to the control group. The polycystic ovary syndrome group had hemoglobin, leukocytes, lymphocytes, neutrophils, platelets, and statistically higher ratios of total cholesterol/high-density lipoprotein, Low-density lipoprotein/high-density lipoprotein, and triglycerides/high-density lipoprotein. No statistically significant relationships were found between homeostatic model assessment insulin resistance, neutrophil-to-lymphocyte ratio, and monocyte-to-high-density lipoprotein ratio between the groups (p<0.05). There was no significant difference in systemic immune inflammation index values between the groups. Polycystic ovary syndrome patients are at risk for short- and long-term complications, and the use of the total cholesterol/high-density lipoprotein, Low-density lipoprotein/high-density lipoprotein, and triglycerides/high-density lipoprotein ratios in clinical practice during the follow-up of these patients may allow easy follow-up for patients. The health status of polycystic ovary syndrome patients can be objectively determined by tracking these outcomes at regular intervals.

PSUN19 One-step serum screening for discriminating subtypes of congenital adrenal hyperplasia in metabolic signatures of adrenal steroids

Abstract Various metabolic signatures may be associated with individual subtypes of congenital adrenal hyperplasia (CAH). However, the ability of commonly used antibody-based immunoassays is limited to discriminate the different subtypes. To address this, liquid chromatography-mass spectrometry (LC-MS) based quantitative profiling of 34 serum adrenal steroids was developed. The validated LC-MS assay has been then applied to serum samples obtained from 67 CAH patients and 38 healthy subjects to characterize their different subtypes. The significantly increased serum levels of 17α-hydroxyprogesterone (17α-OH-Prog; AUC = 0.997, P &amp;lt; 1×10-16) and 21-deoxycortisol (21-deoxyF; AUC = 0.993, P &amp;lt; 1×10-15) and the increased their metabolic ratios to cortisol (AUC = 1.0, P &amp;lt; 1×10-16 for both) were observed in 21-hydroxylase deficiency (21-OHD; N=63), while the 11-deoxyF/17α-OH-Prog could also be practical marker (AUC = 1.0, P &amp;lt; 1×10-16). Higher levels of mineralocorticoids, including corticosterone (B), 18-hydroxyB, and pregnenolone sulfate (Preg-S) and lower levels of dehydroepiandrosterone sulfate (DHEA-S) indicated 17α-hydroxylase deficiency (17α-OHD; N=3), which was associated with significantly decreased metabolic ratios of 17α-OH-Prog/Prog and DHEA-S/Preg-S. The patient with 11β-hydroxylase deficiency (11β-OHD; N=1) showed remarkably increased levels of 11-deoxyF and tetrahydro-11-deoxyF, while the metabolic ratios of 11β-hydroxytestosterone/testosterone and 11β-hydroxyandrostenedione/androstenedione were characterized. Although both 17α-OHD and 11β-OHD groups included a small number of patients, the present LC-MS screening panel with proposed individual steroids and their metabolic ratios could be valuable for assessing different CAH subtypes in clinical practice through a single run. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

PMON163 Effect of Osilodrostat on Androgens and Adrenal Hormones in Patients With Cushing's Disease: Long-Term Findings From the Phase III, Prospective LINC 3 Study

Abstract Introduction Osilodrostat decreases cortisol production by inhibiting 11β-hydroxylase, which increases adrenal hormones proximal to the blockade. Here, we describe these effects of osilodrostat and associated adverse events (AEs). The efficacy and safety of osilodrostat in patients with Cushing's disease (CD) were confirmed in the published Phase III, prospective LINC 3 study (NCT02180217). Methods 137 patients with CD and mUFC &amp;gt;1.5×upper limit of normal were enrolled into a 48-week (W) core phase that included an 8W double-blind, randomized-withdrawal period for eligible patients. Of 113 patients who completed W48, 106 opted to enter the extension, ending when all ongoing patients completed ≥72W of treatment or discontinued. Testosterone, 11-deoxycortisol, 11-deoxycorticosterone and aldosterone were assessed centrally at baseline and regular intervals by liquid chromatography-tandem mass spectrometry and dehydroepiandrosterone sulfate (DHEAS) by chemiluminescence immunoassay. Hirsutism (females; rated on a semi-quantitative scale: 0=absent; 1=mild; 2=moderate; 3=severe), blood pressure, edema and serum potassium were assessed at regular intervals. Results Median osilodrostat exposure was 130W (range, 1–245); median osilodrostat dose was 7.4 mg/day (range, 0.8–46.6). Following an initial increase during the core phase, mean (SD) testosterone levels stabilized in males and decreased towards baseline levels in females during long-term treatment. Of female patients with assessments at baseline and W48 (n=76) and W72 (n=64), hirsutism score improved from baseline in 26 and 22 patients at W48 and W72, respectively and remained unchanged in 37 and 33 patients, respectively. Mean (SD) DHEAS levels decreased during the core phase to within the normal range, then stabilized during the extension in females (1.6 [1.6] and 1.0 [0.9] µmol/L at W48 and W72, respectively) and males (3.4 [3.3] and 3.0 [3.1] µmol/L at W48 and W72, respectively). Aldosterone levels also decreased and then stabilized during long-term treatment. Adrenal hormone precursor accumulation-related AEs were reported in 58.4% (n=80/137) of patients, regardless of study drug relationship and managed with additional therapy in 36.5% (n=50/137) of patients. They mostly occurred during the first 26W of treatment (35.5% and 49.1% in females and males, respectively) and at different osilodrostat doses (1–60 mg), with no discernable dose-related effect. Although mean potassium levels remained stable, AEs of hypertension, peripheral edema and hypokalemia were the most common adrenal hormone precursor accumulation-related AEs and were reported in 24 (17.5%), 22 (16.1%) and 18 (13.1%) patients, respectively; managed with concomitant medication in 17, 6 and 14 patients, respectively. Overall, few patients discontinued because of adrenal hormone precursor accumulation-related AEs (1.5%; n=2/137). Conclusions Adrenal hormone levels frequently change upon initiation of osilodrostat but stabilize during long-term treatment. AEs associated with these changes can occur and are manageable without osilodrostat discontinuation. These AEs should be closely monitored and treatment initiated as needed to achieve optimal patient outcomes. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Serum levels of dehydroepiandrosterone sulfate are associated with a lower risk of mobility-subtype frailty in older Japanese community-dwellers

PurposePrevious studies suggest that lower serum levels of dehydroepiandrosterone sulfate (DHEA-S) are associated with physical frailty. Associations with subtypes of physical frailty have not been studied. This study aimed to investigate associations between serum DHEA-S levels and physical frailty and its subtypes in older Japanese community-dwellers using panel data. MethodsThis study was conducted within the National Institute for Longevity Sciences-Longitudinal Study of Aging (NILS-LSA). Repeated measurement data were collected from 1,886 older community-dwellers (60–91 years). Frailty was identified according to modified Cardiovascular Health Study criteria (weight loss, weakness, slowness, exhaustion, low physical activity) and was classified into following subtypes: mobility (weakness/slowness), non-mobility (weight loss/exhaustion), and low physical activity. Associations with serum DHEA-S (sex-specific tertiles [T1−T3]) were estimated by random-effects logistic regression models adjusting for age, sex, education, disease history (stroke, hypertension, heart disease, diabetes), smoking status, depressive symptoms, and survey wave. ResultsWe found an average prevalence of 6.0% for frailty (mobility subtype, 7.0%; non-mobility subtype, 34.8%; low physical activity subtype, 9.4%) across survey waves. Mean (SD) sex-specific DHEA-S levels (μg/dL) at T1, T2, and T3 were 46.8 (20.8), 88.7 (28.4), and 158.0 (58.9), respectively. Compared with T1, the adjusted ORs (95% CIs) for frailty were 0.69 (0.44, 1.08) for T2 and 0.50 (0.30, 0.83) for T3 (P trend = 0.007). The corresponding values for mobility subtype were 0.80 (0.51, 1.24) for T2 and 0.55 (0.33, 0.90) for T3. ConclusionHigher serum DHEA-S levels were associated with lower risk of frailty, especially mobility-subtype frailty, in older community-dwellers.

Analysis of the pathogenic &lt;i&gt;CYP21A2&lt;/i&gt; gene variants in patients with clinical, biochemical and combined manifestations of hyperandrogenism

BACKGROUND: The association of heterozygous carriage of pathogenic variants in the CYP21A2 gene with various manifestations of hyperandrogenism remains poorly understood to date.&#x0D; AIM: The aim of this study was to analyze the relationship between the carriage of pathogenic variants in the CYP21A2 gene in women and various manifestations of hyperandrogenism.&#x0D; MATERIALS AND METHODS: Clinical description, hormonal testing and molecular genetic analysis of the CYP21A2 gene were performed in 97 women with clinical, biochemical and combined manifestations of hyperandrogenism and in 46 people in the control group. The mean age of the patients was 27.3 0.6 years. Levels of 17-hydroxyprogesterone, dehydroepiandrosterone sulfate and androstenedione were measured in the blood serum of the study participants. To identify pathogenic variants in the CYP21A2 gene, we used next generation sequencing, restriction fragment length polymorphism analysis, real-time polymerase chain reaction, and multiplex ligation-dependent probe amplification analysis. A statistical analysis of the frequency of pathogenic CYP21A2 gene variants in the study groups and hormone levels in different study subgroups was carried out.&#x0D; RESULTS: In patients with hirsutism, acne, menstrual irregularity, miscarriage and infertility, pathogenic variants in the CYP21A2 gene were identified in 31% (30/97) of cases in the heterozygous state and in 6% (5/97) of cases in the homozygous state. The frequency of these variants (in the heterozygous state only) was significantly higher 6.5% (3/46) of cases, when compared to the control group (p 0.0001). The identified pathogenic variants included both single nucleotide substitutions such as P31L (n = 1), I2splice (n = 1), V282L (n = 15), I173N (n = 3), Q319X (n = 8), R357W (n = 1), P454S (n = 1), and P483S (n = 1) and deletions of various lengths (n = 10). We found no significant difference in the levels of dehydroepiandrosterone sulfate and androstenedione between heterozygous carriers and the control group and between heterozygous carriers and patients with the wild type CYP21A2 gene (p 0.05), while 17-hydroxyprogesterone level in the group of patients with heterozygous changes was higher, when compared to the control group (p 0.001).&#x0D; CONCLUSIONS: Heterozygous carriage of pathogenic variants in the CYP21A2 gene is associated with manifestations of hyperandrogenism. However, further study of the mechanisms underlying this association is required.

The Effects of Ficus carica on Male and Female Reproductive Capabilities in Rats.

The basic purpose of pharmacology is to look into the benefits of natural remedies and make them available to the general populace. Herbal medicines are now considered to be the future of humanity. The current study explored the effects of Ficus carica (FC) extract in rats of two-generation F0 (parents) and F1 (offspring) in either sex. The F. carica extract was initially tested for acute and sub-chronic toxicity. Extracts were also tested for fertility assessment and effects on reproductive hormones like follicle-stimulating hormone (FSH), luteinizing hormone (LH), gonadotropin-releasing hormone (GnRH), estradiol, testosterone, dihydrotestosterone (DHT), dehydroepiandrosterone-sulfate (DHEAS), insulin, progesterone, and prolactin. The antioxidant activity of the extract was also evaluated by testing mRNA expressions of SOD2, GPX1, CAT, and GR in male testes and female ovaries. The animals treated with 100 mg/kg FC extract produced a more pronounced fertility effect in both genders. Expression of CAT, SOD2, GPX1, and GR was found to be increased in the reproductive organs of both sexes. Histology of the testes reveals increased spermatogenesis and increased folliculogenesis in ovaries. The hormone profile showed an increase in FSH, DHT, estradiol, and DHEAS levels in males and FSH, LH, estrogen, and DHEAS in females. The results of the study establish the effectiveness of natural products in improving fertility issues in either sex.

Relationship between handgrip strength and endogenous hormones in postmenopausal women.

This study aimed to evaluate the endogenous hormonal factors related to dominant handgrip strength (HGS) in postmenopausal women. A cross-sectional study was performed on 402 postmenopausal women aged 47 to 83 years. The following variables were recorded: age, age at menopause, smoking status, adiposity, HGS, and physical activity. Hormonal parameters (follicle-stimulating hormone, estradiol, testosterone, cortisol, dehydroepiandrosterone sulfate, ∆4 androstenedione, insulin-like growth factor-1 [IGF-1], vitamin D, and parathormone levels) were measured and results reported as odds ratios (ORs), β coefficients and 95% confidence interval (95% CI). A directed acyclic graph was used to identify potential confounding variables and was adjusted in the regression model to assess associations between endogenous hormones and HGS. The mean dominant HGS was 22.8 ± 3.7 kg, and 25.6% of women had dynapenia. There were significant differences in plasma levels of follicle-stimulating hormone (OR, 0.99; 95% CI, 0.98-1.00), cortisol (OR, 1.07; 95% CI, 1.02-1.12), and dehydroepiandrosterone sulfate (OR, 0.99; 95% CI, 0.98-1.00) between women with normal HGS and those who presented with dynapenia. After adjusting for confounding variables, no significant association was found between endogenous hormones and HGS. Our results showed that studied ovarian steroids, adrenal hormones, IGF-1, parathormone, and vitamin D were not associated with HGS.