Mean DHEAS Research Articles

The Correlation Between Interleukin -6 and Dehydroepiandrosterone Sulfate in Patients with Severe COVID-19

Background: Numerous studies have demonstrated that interleukin-6 (IL-6) and serum dehydroepiandrosterone sulfate levels are negatively correlated. Low DHEA-S levels may be associated with severe disease and clinically ailing patients in the context of infectious diseases. Individuals infected with Coronavirus disease who exhibit elevated levels of IL-6 may undergo a cytokine storm, which can result in severe manifestations and a dismal prognosis. Objectives: To examine the relationship between DHEA-S and Il-6 in patients exhibiting severe manifestations of COVID-19. Subjects and Methods: A case-control investigation with 79 patients, ranging in age from 36 to 74 years, who were admitted to the hospital due to severe COVID-19 disease. A control group of 72 ostensibly healthy individuals was also included in the study. Using the ELISA method, the concentrations of IL-6 and DHEA-S in the serum of both groups were determined. The statistical analyses involved the application of the Pearson correlation coefficient and the T-test. None of the authors present any conflicts of interest. Results: With a Pearson correlation coefficient (r) of -0.8349, the study revealed a highly significant negative correlation (P < 0.0001) between the mean IL-6 level (64.369 pg/ml ± 2.6237) and the mean DHEA-S level (1.2728 ng/ml ± 1.7005) in the study group. An exceptionally significant statistical disparity was also identified when IL-6 and DHEA-S levels were compared between the study and control groups. Conclusions: In severely infected COVID-19 patients inverse correlation between the levels of IL-6 and DHEA-S indicates that DHEA-S deficiency may play a role in cytokine storm formation for these patients.

Effect of Surgical-Site, Multimodal Drug Injection on Pain and Stress Biomarkers in Patients Undergoing Plate Fixation for Clavicular Fractures.

BackgroundSurgical-site, multimodal drug injection has recently evolved to be a safe and useful method for multimodal pain management even in patients with musculoskeletal trauma.MethodsFifty consecutive patients who underwent plating for mid-shaft and distal clavicular fractures were included in the study. To evaluate whether surgical-site injections (SIs) have pain management benefits, the patients were divided into two groups (SI and no-SI groups). The injection was administered between the deep and superficial tissues prior to wound closure. The mixture of anesthetics consisted of epinephrine hydrochloride (HCL), morphine sulfate, ropivacaine HCL, and normal saline. The visual analogue scale (VAS) pain scores were measured at 6-hour intervals until postoperative hour (POH) 72; stress biomarkers (dehydroepiandrosterone sulfate [DHEA-S], insulin, and fibrinogen) were measured preoperatively and at POH 24, 48, and 72. In patients who wanted further pain control or had a VAS pain score of 7 points until POH 72, 75 mg of intravenous tramadol was administered, and the intravenous tramadol requirements were also recorded. Other medications were not used for pain management.ResultsThe SI group showed significantly lower VAS pain scores until POH 24, except for POH 18. Tramadol requirement was significantly lower in the SI group until POH 24, except for POH 12 and 18. The mean DHEA-S level significantly decreased in the no-SI group (74.2 ± 47.0 µg/dL) at POH 72 compared to that in the SI group (110.1 ± 87.1 µg/dL; p = 0.046). There was no significant difference in the insulin and fibrinogen levels between the groups. The correlation values between all the biomarkers and VAS pain scores were not significantly different between the two groups (p > 0.05).ConclusionsAfter internal fixation of the clavicular fracture, the surgical-site, multimodal drug injection effectively relieved pain on the day of the surgery without any complications. Therefore, we believe that SI is a safe and effective method for pain management after internal fixation of a clavicular fracture.

Age related endocrine patterns observed in polycystic ovary syndrome patients vs. ovulatory controls: descriptive data from a university based infertility center.

To compare serum anti-Müllerian hormone (AMH) and other endocrine parameters between patients diagnosed with polycystic ovary syndrome (PCOS) and age-matched ovulatory women. AMH, DHEAS, FSH, LH, PRL, TSH and total testosterone (TT) were prospectively measured in oligo-ovulatory PCOS patients (n = 595) and in ovulatory non-PCOS women (n = 157) referred to a tertiary infertility center. Mean BMI was similar across the two study populations and there were no smokers in the sample. Patients in both groups were further classified into three categories by age: < 25 yrs, 25-34 yrs, and ≥ 35 yrs. Selected clinical and demographic characteristics were tabulated for each group. Serum AMH was significantly higher among PCOS patients compared to non-PCOS controls in the non-stratified sample (7.54 ± 5.8 vs. 2.49 ± 2.0 ng/mL, respectively; p < 0.0001), while serum FSH, DHEAS, TSH and prolactin were similar for both groups (p > 0.05). As expected, mean (total) testosterone levels were notably different between PCOS vs. non-PCOS controls (0.84 ± 0.76 vs. 0.43 ± 0.38 ng/mL, respectively; p < 0.001), and mean AMH level was significantly lower in the oldest age category (> 35 yrs) compared to both younger control groups (p < 0.0001). Both DHEAS and total testosterone decreased with age among PCOS patients, although mean serum DHEAS for women age > 35 yrs was significantly lower than DHEAS measured in younger women with PCOS (p < 0.02). For PCOS patients, AMH remained relatively stable irrespective of age. Although AMH can serve as a satisfactory marker of ovarian reserve, for PCOS patients the expected decline in AMH associated with reproductive aging appears attenuated despite ovarian senescence. In contrast, mean DHEAS levels were markedly lower among older PCOS women (> 35 yrs) compared to younger PCOS patients.

Development of a Model of Functional Endocrine Age in Japanese People

Objective: As the concentrations of some hormones are known to decrease with age, the aim of the present study was to develop a method to predict the functional age of the endocrine system.Methods: We retrospectively examined data for blood serum or plasma hormone concentration from 3,313 healthy Japanese (2,006 men and 1,307 women, aged 40-79 years) who gave blood samples between 2005 and 2009. Data for DHEA-s, insulin-like growth factor (IGF-I), cortisol, thyroid-stimulating hormone (TSH), free triiodothyronine (FT3) and free thyroxine (FT4) were analyzed, and the correlation between concentration of each hormone and age was calculated. In a second stage, data were grouped in 10-year age intervals, subjected to one-way analysis of variance (ANOVA) and evaluated using Tukey’s post-hoc test.Results: In both men and women, TSH was positively correlated with age. IGF-I, DHEA-s and cortisol were negatively correlated with age; in men, age was negatively correlated with FT3. Although correlation coefficients (r) and significance levels differed between sexes and hormones, DHEA-s concentration was highly correlated with age and declined with age in both men and women. An age-structured model was developed from the regression of mean DHEA-s concentration and median age of each group. The confidence limits for the regression were small and imply that the predictions from the model are accurate.Conclusion: We developed an age-structured model of age related to serum DHEA-s concentration. It may be useful as an index for evaluating the functional age of the endocrine system in Japanese men and women.

Lower circulating levels of dehydroepiandrosterone, independent of insulin resistance, is an important determinant of severity of non‐alcoholic steatohepatitis in Japanese patients

The biological basis of variability in histological progression of non-alcoholic fatty liver disease (NAFLD) remains unknown. Dehydroepiandrosterone (DHEA), the most abundant steroid hormone, has been shown to influence sensitivity to reactive oxygen species, insulin sensitivity and expression of peroxisome proliferator-activated receptor-α. Our aim was to determine whether more histologically advanced NAFLD is associated with low circulating levels of DHEA in Japanese patients. Serum samples were obtained in 133 Japanese patients with biopsy-proven NAFLD and in 399 sex- and age-matched healthy people undergoing health checkups. Serum levels of sulfated DHEA (DHEA-S) were measured by chemiluminescent enzyme immunoassay. Serum DHEA-S levels in NAFLD patients were similar to those in the control group. Of 133 patients, 90 patients were diagnosed as non-alcoholic steatohepatitis (NASH): 73 patients had stage 0-2, and 17 had stage 3 or 4. Patients with advanced NAFLD (NASH with fibrosis stage 3 or 4) had lower plasma levels of DHEA-S than patients with mild NAFLD (simple steatosis or NASH with fibrosis stage 0-2). The area under the receiver operating characteristic curve for DHEA in separating patients with and without advanced fibrosis was 0.788. A "dose effect" of lower DHEA-S and incremental fibrosis stage was observed with a mean DHEA-S of 170.4 ± 129.2, 137.6 ± 110.5, 96.2 ± 79.3, 61.2 ± 46.3 and 30.0 ± 32.0 µg/dL for fibrosis stages 0, 1, 2, 3, and 4, respectively. The association between DHEA-S and severity of NAFLD persisted after adjusting for age, sex and insulin resistance. Low circulating DHEA-S might have a role in the development of advanced NASH.

No evidence to support the concept that low serum dehydroepiandrosterone (DHEA) sulfate (S) levels are associated with less oocyte production or lower pregnancy rates

OBJECTIVE: Some studies suggest that low levels of DHEA are associated with diminished development of mature follicles and thus yield of oocytes and lower pregnancy rates (PRs). The objective of the present study was to determine if we could corroborate or refute this aforementioned concept. DESIGN: Prospective observational study. MATERIALS AND METHODS: Women aged <40 who had diminished oocyte reserve as evidenced by a day 3 serum follicle stimulating hormone (FSH) level >12 mIU/mL and who were undergoing in vitro fertilization-embryo transfer (IVF-ET) had DHEA sulfate levels drawn before any follicle stimulating drugs were started. Mean DHEA-s levels (ng/dL) were determined according to whether the woman was a relatively poor responder (<4 oocytes retrieved) or a relatively good responder (>5 oocytes). Also, DHEA-s levels were compared in those achieving a pregnancy vs. those who did not. Only the first IVF cycle was evaluated to determine oocyte response. Also DHEA levels were compared in those conceiving vs. not within three ETs. RESULTS: There were 39 first IVF-ET cycles with <4 eggs and 14 with >5. The mean serum DHEA-s level for the <4 group was 148.0+82.8 for the non-pregnant group vs. 143.9+47.7 for the pregnant ones. Comparable data for the >5 group were 138.5+26.4 vs. 103.5+41.9 (p=NS, ANOVA). The mean DHEA-s was 70.4+23.2 for the 10 lowest values vs. 243.2+64.4 for the 10 highest values (p=<.05, ANOVA). The clinical (ultrasound at 8 weeks) and live delivered PRs for the low group were 40.0 and 30.0% vs. 20 and 20% for the highest group (p=NS, Fisher's exact test). Given 3 cycles to conceive, 52 had positive pregnancy tests and 86 had negative tests. The mean DHEA-s levels were 140.7+57.3 for those who conceived vs. 154.1+91.4 for those not conceiving (p=NS, ANOVA). CONCLUSION: These data do not support the concept that low DHEA-s levels may produce fewer oocytes following IVF-ET or can negatively impact pregnancy rates.

Can immune parameters predict short-term symptomatic outcome of treatment in mood disorder out-patients? A review of the literature

healthy control group. Methods: The present study was part of the DELTA study, a randomised trial on the effectiveness of a preventive cognitive behavioral module in rMDD patients with at least two depressive episodes in the past. At baseline level mean morning cortisol and DHEA-S, mean evening cortisol and DHEA-S, mean morning and evening cortisol/DHEA-S ratio and mean morning–evening difference for both cortisol and DHEA-S were determined, in 127 patients. Steroid levels will be compared with those of an age and gender matched control group (n=75), free from medical illness, life time psychiatric disorders and life time psychiatric disorders in first degree relatives. Results: Data are currently analysed. Differences in steroid levels between the rMDD and the control group will be calculated. In rMDDassociationswill be calculated between steroid levels and the number of previous relapses, the use of antidepressants, gender and age. Discussion: This is the first large scale study in rMDD comparing the levels of salivary cortisol, DHEA-S and the cortisol/DHEA-S ratio, with the levels from an age and gender matched healthy control group. We will discuss the nature and severity of the steroid abnormalities found in rMDD and the implications for further study upon the prediction of clinical outcome.

Low circulating levels of dehydroepiandrosterone in histologically advanced nonalcoholic fatty liver disease

The biological basis of variability in histological progression of nonalcoholic fatty liver disease (NAFLD) is unknown. Dehydroepiandrosterone (DHEA) is the most abundant steroid hormone and has been shown to influence sensitivity to oxidative stress, insulin sensitivity, and expression of peroxisome proliferator-activated receptor alpha and procollagen messenger RNA. Our aim was to determine whether more histologically advanced NAFLD is associated with low circulating levels of DHEA. Serum samples were obtained prospectively at the time of liver biopsy in 439 patients with NAFLD (78 in an initial and 361 in validation cohorts) and in controls with cholestatic liver disease (n = 44). NAFLD was characterized as mild [simple steatosis or nonalcoholic steatohepatitis (NASH) with fibrosis stage 0-2] or advanced (NASH with fibrosis stage 3-4). Serum levels of sulfated DHEA (DHEA-S) were measured by enzyme-linked immunosorbent assay. Patients with advanced NAFLD had lower plasma levels of DHEA-S than patients with mild NAFLD in both the initial (0.25 +/- 0.07 versus 1.1 +/- 0.09 microg/mL, P < 0.001) and validation cohorts (0.47 +/- 0.06 versus 0.99 +/- 0.04 microg/mL, P < 0.001). A "dose effect" of decreasing DHEA-S and incremental fibrosis stage was observed with a mean DHEA-S of 1.03 +/- 0.05, 0.96 +/- 0.07, 0.83 +/- 0.11, 0.66 +/- 0.11, and 0.35 +/- 0.06 microg/mL for fibrosis stages 0, 1, 2, 3, and 4, respectively. All patients in both cohorts in the advanced NAFLD group had low DHEA-S levels, with the majority in the hypoadrenal range. The association between DHEA-S and severity of NAFLD persisted after adjusting for age. A relationship between disease/fibrosis severity and DHEA-S levels was not seen in patients with cholestatic liver diseases. More advanced NAFLD, as indicated by the presence of NASH with advanced fibrosis stage, is strongly associated with low circulating DHEA-S. These data provide novel evidence for relative DHEA-S deficiency in patients with histologically advanced NASH.

ARE DHEA AND/OR DHEA-S CONCENTRATIONS ASSOCIATED WITH REMISSION OF DEPRESSION OR IMPROVEMENTS IN MENTAL STATUS SCORES IN OLDER ADULTS?

Purpose: DHEA and DHEA-S concentrations decline with advancing age and are thought to be related to mood and cognitive function. Recently, the authors reported that alprazolam-induced acute increases in DHEA concentrations were associated with improved psychomotor function. Others have reported low morning concentrations of DHEA in adolescents and adults diagnosed with depression. Therefore, the authors evaluated DHEA and DHEA-S concentrations in an ongoing double-blind comparative trial of antidepressants in older depressed adults. A secondary purpose was to evaluate concentrations of these steroids relative to cognitive function of these depressed patients. Methods: Subjects were 40 in- and out-patients (8 men, 32 women; 63 to 88 years of age) who met DSM-IV criteria for major depression and who were enrolled in a 12-week, double-blind treatment study at the University of Pittsburgh. Ten patients were cognitively impaired based on their Mattis Dementia Rating Scale score (MDRS), but did not meet NINCDS-ADRDA criteria for a diagnosis of probable or possible Alzheimer's disease or DSM-IV criteria for dementia. Subjects underwent thorough medical, psychiatric and cognitive assessments at week 0, which was prior to randomization to 12 weeks of treatment with either nortriptyline (n=17) or paroxetine (n=23). All 40 subjects experienced remission of depression symptoms following 12 weeks of either nortriptyline or paroxetine, as indicated by Ham-D scores at Week 0 (22.4) and at Week 12 (6.7; P<0.001). Global Assessment of Functioning (GAF) scores were 45.3 at Week 0 and 76.2 at Week 12 (P<0.001). The Folstein MMSE and the MDRS were assessed at Week 0 and after 12 weeks of treatment. For analysis of steroid concentrations, morning blood samples were obtained at Week 0, and at 6 and 12 weeks. Serum samples were assayed for DHEA, DHEA-S, and cortisol using an 125I-radioimmunoassay method. Results: The differences between pre- and post-treatment scores on both Ham-D and GAF were significant (P<0.001), reflecting the successful treatment of depressed mood and consequent gain in functioning. At Week 0, the range of concentrations was wide for DHEA (0.6 1/n – 17.2 ng/ml), DHEA-S (41.0–4116 ng/ml), and cortisol (2.1–34.6 μg/dl). Mean DHEA and DHEA-S concentrations decreased with the remission of depression, as indicated in Table 1, although increases relative to Week 0 were observed in some subjects at Week 6 (DHEA, n=10; DHEA-S, n=11), and Week 12 (DHEA, n=5; DHEA-S, n=8). There were no differences in DHEA or DHEA-S concentrations between the nortriptyline and paroxetine treatment groups. There was a significant correlation between the change in cortisol and change in GAF score from Week 0 and Week 12 (P=0.01). The cognitively impaired (CI) patients tended to have higher DHEA and DHEA-S concentrations at Week 0 than the nonimpaired group (NI) (P>0.2). During therapy, the decreases in concentrations also tended to be greater in the CI group; the change from Week 0 at Weeks 6 and 12, respectively, expressed as CI:NI ratios of the means were 0.75 and 1.5 (DHEA), 1.6 and 1.2 (DHEA-S), and 2.2 and 32.3 (cortisol). There were no correlations between cognitive and psychosocial functioning and concentrations of DHEA or DHEA-S. Conclusions: Data from these older depressed patients indicate that DHEA and DHEA-S concentrations decrease during successful treatment with nortriptyline or paroxetine. Mean DHEA and DHEA-S concentrations decreased within 6 weeks of therapy, remained relatively unchanged through 12 weeks of treatment, and were independent of drug treatment group. Whether the changes in hormone concentrations are a consequence of remission of depression or of a specific drug effect cannot be determined. In the subset of 10 CI patients, no significant correlation was identified between the changes in either DHEA or DHEA-S concentrations and improvement in cognitive function assessed by the MDRS. The decrease in DHEA and DHEA-S concentrations in the majority of subjects was not anticipated. The source of variability in DHEA and DHEA-S concentrations in response to remission from depression needs to be further evaluated. P38

Elevated serum progesterone levels during pituitary suppression may signify adrenal hyperandrogenism

Objective: To investigate whether elevated serum P levels after pituitary down-regulation signify adrenal enzyme defects or hyperandrogenism. Design: Prospective study. Setting: Assisted reproduction unit in a university medical center. Patient(s): Two hundred twenty-seven IVF patients treated by the long down-regulation protocol. Intervention(s): Oral dexamethasone (DEX) administration if P level exceeded 0.8 ng/mL (conversion factor to SI unit, 3.180) after pituitary suppression. Main Outcome Measure(s): Serum concentrations of P, E 2, LH, DHEAS, and 17α-hydroxy progesterone and ACTH stimulation tests. Result(s): In eight patients (3.5%), serum P levels exceeded 0.8 ng/mL and E 2 and LH levels confirmed pituitary down-regulation. Mean DHEAS levels in the patients in this group were significantly higher than in the other patients. All eight patients demonstrated a significant decrease in serum P level after DEX administration. In five patients the ACTH stimulation test suggested an adrenal defect. Five pregnancies were achieved after the addition of DEX to the treatment protocol. Conclusion(s): High serum P levels after pituitary down-regulation appear to be of adrenal origin and may be the first indication of an adrenal enzyme defect. Further investigation such as an ACTH stimulation test is recommended, followed by treatment with DEX if indicated.