Changes In Dehydroepiandrosterone Sulfate Research Articles

"Ferula assa-foetida L" or "Foeniculum vulgare"? Which one is more effective in the management of polycystic ovarian syndrome? A randomized, placebo controlled, triple-blinded.

There are few evaluation about the effects of Fennel and Ferula on human polycystic ovary syndrome (PCOS). The goals of this study were to evaluate and compare the effectiveness of two medicinal plants of the Apiaceae family (Fennel and Ferula) in management of PCOS. The sample size was 47 participants with PCOS who were randomly divided into 3 groups. The Ferula assa-foetida L group received 100 mg of Ferula (n=14), the Foeniculum vulgare group received 46 mg of Fennel (n=15), and the placebo group received placebo twice daily for 3 months (n=14). Before the intervention, there were no significant differences between groups in terms of clinical parameters, endometrial thickness, or ovarian volume. After the interventions, the number of ovarian follicles was decreased in the Ferula and Fennel groups as compared to the placebo group (p<0.05). The number of ovarian follicles in both ovaries in the Ferula and Fennel group decreased and this decrease was significant in the right side as compared to placebo group. Our findings showed significant changes in dehydroepiandrosterone sulfate (DEHAS) and thyroid-stimulating hormone (TSH) levels after the intervention (p<0.03) between the Ferula and Placebo groups. Since use of Ferula could make significant changes in TSH and DEHAS levels and decrease the number of right and left ovarian follicles compared to Fennel and placebo, it can be concluded that this herbal medicine is more effective than Fennel in managing PCOS.

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.

Relationship between bone density of paranasal sinuses and adrenal steroids pattern in women during menopausal transition

The course of menopause transition (MT) is associated with peculiarities of alterations occurring in a woman’s body, in particular, in the structure of bone tissue. Considering that bones of the paranasal sinuses (BPNSs) play a natural defense role against the spread of dental infection, their structure is important in dentistry. However, no information was found pertaining to changes of BPNSs during MT – a time when dental maladies increase in many women.&#x0D; The aim of our study was to collate density of BPNSs with status of adrenal steroids in women during MT, since the pattern of their changes determines the course of MT.&#x0D; Cross-sectional associations were examined between bone density of PNSs assessed by Spiral Computed Tomography and Serum content of testosterone (T), sex hormone binding globulin (SHBG), free androgen index (FAI), insulin, dehydroepiandrosterone sulfate (DHEAS), Adione, and Adiol in 113 women of per­imenopausal age (age range from 45 to 55 years) who had already experienced premenopausal menstrual decline (amenorrhea less than 2 years).&#x0D; Strong positive (r = 0.73) correlation between minimal bone density of maxillary sinus in women with level of DHEAS was detected. It is important to note, that the correlation between minimal density of the lower wall of frontal sinus is a weak positive (0.3). Therefore , it can be suggested that bone tissue of the maxillary sinus is more sensitive to changes in DHEAS.&#x0D; The study showed that the level of male steroids, in particular DHEAS, affected the state of bone tissue in participants older than 50 years of age.

Plasma Dehydroepiandrosterone Sulfate and Cardiovascular Disease Risk in Older Men and Women.

Lower dehydroepiandrosterone-sulfate (DHEA-S) levels have been inconsistently associated with coronary heart disease (CHD) and mortality. Data are limited for heart failure (HF) and association between DHEA-S change and events. Assess associations between low DHEA-S/DHEA-S change and incident HF hospitalization, CHD, and mortality in older adults. DHEA-S was measured in stored plasma from visits 4 (1996-1998) and 5 (2011-2013) of the Atherosclerosis Risk in Communities study. Follow-up for incident events: 18 years for DHEA-S level; 5.5 years for DHEA-S change. General community. Individuals without prevalent cardiovascular disease (n = 8143, mean age 63 years). Associations between DHEA-S and incident HF hospitalization, CHD, or mortality; associations between 15-year change in DHEA-S (n = 3706) and cardiovascular events. DHEA-S below the 15th sex-specific percentile of the study population (men: 55.4 µg/dL; women: 27.4 µg/dL) was associated with increased HF hospitalization (men: hazard ratio [HR] 1.30, 95% confidence interval [CI], 1.07-1.58; women: HR 1.42, 95% CI, 1.13-1.79); DHEA-S below the 25th sex-specific percentile (men: 70.0 µg/dL; women: 37.1 µg/dL) was associated with increased death (men: HR 1.12, 95% CI, 1.01-1.25; women: HR 1.19, 95% CI, 1.03-1.37). In men, but not women, greater percentage decrease in DHEA-S was associated with increased HF hospitalization (HR 1.94, 95% CI, 1.11-3.39). Low DHEA-S and change in DHEA-S were not associated with incident CHD. Low DHEA-S is associated with increased risk for HF and mortality but not CHD. Further investigation is warranted to evaluate mechanisms underlying these associations.

Developmental changes in the endocrine stress response in orangutans (Pongo pygmaeus)

Non-invasive measures of stress are crucial for captive and conservation management programs. The adrenal hormone dehydroepiandrosterone-sulfate (DHEAS) has recently been adopted as a stress marker, but there is little investigation of its relationship to glucocorticoids (GC), well-known indicators of stress. This study examined the influence of age, reproductive state and environment on GC and DHEAS levels in orangutans, to test whether the GC/DHEAS ratio can provide an index of stress response in primates. We measured fecal GC (fGC) and fecal DHEAS (fDHEAS) concentrations in 7 captive orangutans from zoological parks in Japan and 22 wild orangutans from Danum Valley Conservation Area, Malaysia. We found that in a stressful condition (transportation), fDHEAS levels increased 2days after the fGC response, which occurred 1day after the stressor. One pregnant female had elevated levels of both hormones, and a higher fGC/fDHEAS ratio than baseline. Females in the first year of lactation had fGC levels and the fGC/fDHEAS ratio significantly higher than both baseline and females in the second and subsequent years of lactation. There was no effect of age on fGC levels, but the fGC/fDHEAS ratio was higher in infants than adults and adolescents. fDHEAS concentrations were lower in infants than juveniles, adolescents and adults, a phenomenon known as adrenarche, shared with humans and other great apes. We suggest that changes in DHEAS during orangutan life history are associated with changes in the dynamics of maintaining homeostasis that vary with age and reproductive state. The GC/DHEAS ratio index is useful to evaluate age-related abilities of responding to stressful challenges.

Changes in androstenedione, dehydroepiandrosterone, testosterone, estradiol, and estrone over the menopausal transition

BackgroundPrevious reports have noted that dehydroepiandrosterone-sulfate (DHEAS) increases prior to the final menstrual period (FMP) and remains stable beyond the FMP. How DHEAS concentrations correspond with other sex hormones across the menopausal transition (MT) including androstenedione (A4), testosterone (T), estrone (E1), and estradiol (E2) is not known. Our objective was to examine how DHEAS, A4, T, E1, and E2 changed across the MT by White vs. African-American (AA) race/ethnicity.MethodsWe conducted a longitudinal observational analysis of a subgroup of women from the Study of Women’s Health Across the Nation observed over 4 visits prior to and 4 visits after the FMP (n = 110 women over 9 years for 990 observations). The main outcome measures were DHEAS, A4, T, E1, and E2.ResultsCompared to the decline in E2 concentrations, androgen concentrations declined minimally over the MT. T (β 9.180, p < 0.0001) and E1 (β 11.365, p < 0.0001) were higher in Whites than in AAs, while elevations in DHEAS (β 28.80, p = 0.061) and A4 (β 0.2556, p = 0.052) were borderline. Log-transformed E2 was similar between Whites and AAs (β 0.0764, p = 0.272). Body mass index (BMI) was not significantly associated with concentrations of androgens or E1 over time.ConclusionThis report suggests that the declines in E2 during the 4 years before and after the FMP are accompanied by minimal changes in DHEAS, A4, T, and E1. There are modest differences between Whites and AAs and minimal differences by BMI.

Effects of a Single-Dose Interscalene Block on Pain and Stress Biomarkers in Patients Undergoing Arthroscopic Rotator Cuff Repair: A Randomized Controlled Trial

To compare the effects of a single-dose interscalene block and general anesthesia (SISB/GA) with the effects of GA only in the early postoperative period after arthroscopic rotator cuff repair by evaluating subjective pain visual analog scale scores and objective pain-related stress biomarkers. Patients refractory to conservative treatment of the affected shoulder were enrolled in this prospective, randomized endpoint study. Patients diagnosed with a rotator cuff tear (1-4cm) based on magnetic resonance imaging were included. Exclusion criteria were small (<1cm) and massive (>4cm) rotator cuff tears. Thirty-one patients each were randomized into the SISB/GA and GA treatment groups. Preoperative pain scores were measured at 6:00 AM on the day of surgery, measured again at 1 and 6hours postoperatively, and then every 6hours until 3days postoperatively. Blood sampling was performed to evaluate the stress biomarkers insulin, dehydroepiandrosterone sulfate, and fibrinogen preoperatively at 6:00 AM on the day of surgery and postoperatively at 18, 42, and 66hours (6:00 AM on postoperative days 1-3). Pain scores were significantly decreased in the SISB/GA group (2.50 ± 0.94) versus the GA group (3.82 ± 1.31) on the day of surgery (P < .001), and especially at 6hours postoperatively (SISB/GA: 2.42 ± 1.43; GA: 4.23 ± 2.17; P < .001). Insulin was decreased significantly in the SISB/GA group (10.55 ± 7.92 μU/mL) versus the GA group (20.39 ± 25.60 μU/mL) at 42hours postoperatively (P= .048). There was no significant change in dehydroepiandrosterone sulfate or fibrinogen over time (P> .05). After arthroscopic rotator cuff repair, an SISB effectively relieved pain on the day of surgery without any complications. In addition, insulin levels were significantly reduced at 42hours postoperatively. Level I, prospective randomized controlled trial.

Coordination of cortisol response to social evaluative threat with autonomic and inflammatory responses is moderated by stress appraisals and affect

Recent approaches to stress regulation have emphasized coordination among multiple biological systems. This study builds on evidence that hypothalamic-pituitary-adrenal (HPA) axis activity should be considered in coordination with other stress-sensitive biological systems to characterize healthy responses. Healthy African-Americans (n=115) completed the Trier Social Stress Test, and biological responses were assessed through salivary cortisol, dehydroepiandrosterone-sulfate (DHEA-S), alpha amylase (sAA), and C-reactive protein (sCRP). Multilevel modeling demonstrated that cortisol responses typically aligned with changes in DHEA-S, sAA, and sCRP across the session. At the same time, the degree of cortisol coordination with sAA and sCRP varied by participants’ subjective stress following the task; participants with higher secondary stress appraisals showed greater cortisol-sAA alignment, whereas those experiencing more negative affect showed greater cortisol-sCRP alignment. Results highlight the importance of a multisystem approach to stress and suggest that positive HPA axis coordination with the autonomic response, but not with the immune/inflammatory response, may be adaptive.

Neuroprotective–neurotrophic effect of endogenous dehydroepiandrosterone sulfate during intense stress exposure

Recent reports demonstrate neurotrophic properties of dehydroepiandrosterone sulfate (DHEAS) in men at rest, as well as profound neurotrophic responses to stress in both men and women. Little is known of neuroprotective–neurotrophic effects of DHEAS during stress exposure, either in men or women. This translational study was designed to examine neuroprotective–neurotrophic effects of DHEAS throughout intense stress exposure in healthy men and women. The study took place within a stressful 12-day military survival course. Utilizing a longitudinal cross-sectional repeated measures design, One hundred sixteen healthy active-duty military personnel (80% male) were studied before, during, and 24h after the course. The dependent variable was the neurotrophin salivary nerve growth factor (sNGF). In terms of total hormone output, the effect of DHEAS on sNGF was mediated by testosterone. Unlike testosterone or cortisol, DHEAS reliably predicted sNGF at each time point, and change in DHEAS predicted change in sNGF across time points. Baseline DHEAS predicted total sNGF output across the stress trajectory. Consistent with preclinical as well as cross-sectional human research, this study demonstrates neuroprotective–neurotrophic effects of DHEAS in healthy men and women exposed to intense stress. Results are evaluated in relation to established criteria for causation.

Concurrent Change in Dehydroepiandrosterone Sulfate and Functional Performance in the Oldest Old: Results From the Cardiovascular Health Study All Stars Study

The correlation between dehydroepiandrosterone sulfate (DHEAS) decline and age led to the hypothesis that DHEAS might be a marker of primary aging, though conflicting data from observational studies of mortality do not support this. We evaluated concurrent DHEAS and functional decline in a very old cohort to test if DHEAS change tracks with functional change during aging. DHEAS and functional performance (gait speed, grip strength, Modified Mini-Mental State Examination [3MSE] score, and digit symbol substitution test [DSST] score) were measured in 1996-1997 and 2005-2006 in 989 participants in the Cardiovascular Health Study All Stars study (mean age 85.2 years in 2005-2006, 63.5% women and 16.5% African American). We used multivariable linear regression to test the association of DHEAS decline with functional decline. After adjustment, each standard deviation decrease in DHEAS was associated with greater declines in gait speed (0.12 m/s, p = .01), grip strength (0.09 kg, p = .03), 3MSE score (0.13 points, p < .001), and DSST score (0.14 points, p = .001) in women only. Additional adjustment for baseline DHEAS attenuated the association with grip strength but did not alter other estimates appreciably, and baseline DHEAS was unassociated with functional decline. In this cohort of very old individuals, DHEAS decline tracked with declines in gait speed, 3MSE score, and DSST score, but not grip strength, in women independent of baseline DHEAS level. DHEAS decline might be a marker for age-associated performance decline, but its relevance is specific to women.

Cardiovascular Disease Is Associated with Greater Incident Dehydroepiandrosterone Sulfate Decline in the Oldest Old: The Cardiovascular Health Study All Stars Study

To describe cross-sectional and longitudinal associations with dehydroepiandrosterone sulfate (DHEAS) and change in DHEAS with age. Longitudinal cohort study. Pittsburgh, Pennsylvania. Cardiovascular Health Study All Stars study participants assessed in 2005/06 (N=989, mean age 85.2, 63.5% women, 16.5% African American). Health characteristics were assessed in 2005/06 according to DHEAS level, mean DHEAS and DHEAS change across age categories were tested, and linear and logistic regression was used to identify factors present in 1996/97 associated with continuous and categorical DHEAS change. Mean +/- standard deviation DHEAS was 0.555 +/- 0.414 microg/mL in 1996/97 and 0.482 +/- 0.449 microg/mL in 2005/06 for women and 0.845 +/- 0.520 microg/mL in 1996/97 and 0.658 +/- 0.516 microg/mL in 2005/06 for men. In 2005/06, DHEAS was lower in women and subjects with cardiovascular disease (CVD) and chronic pulmonary disease and higher for African Americans and subjects with hypertension and high cholesterol. Mean DHEAS change was greater in men (-0.200 microg/mL) than in women (-0.078 microg/mL) (P<.001). Each 1-year increase in age attenuated the effect of male sex by 0.01 microg/mL (P=.009), abolishing the sex difference in DHEAS change by age 79. Presence of CVD before the study period was associated with greater absolute DHEAS change (beta=-0.04 microg/mL, P=.04) and with the fourth quartile of DHEAS change versus the first to third quartiles (odds ratio=1.46, 95% confidence interval=1.03-2.05). DHEAS change continues into very old age, is not homogenous, is affected by sex, and is associated with prevalent CVD. Future studies should investigate factors that might accelerate DHEAS decline.

Circulating Dehydroepiandrosterone Sulfate Concentrations during the Menopausal Transition

A previous report from the Study of Women Across the Nation indicated a rise in dehydroepiandrosterone sulfate (DHEAS) during the menopausal transition using data from three annual visits. Our objective was to examine changes in DHEAS with chronological and ovarian aging, expanding the original analyses to include 10 yr of annual data. A longitudinal observational study and cross-sectional analyses of baseline data were conducted. OUTCOME MEASURES AND SUBJECTS: DHEAS, age, menopause status, ethnicity, smoking, weight, and height were assessed in 2886 women from five ethnic groups aged 42-52 yr at entry. Hysterectomy, bilateral oophorectomy, and hormone use were excluded. Cross-sectional analysis at baseline showed a linear decline in circulating log-transformed DHEAS with increasing age for either the entire cohort (2.81% per year) or for individual ethnicities. A similar negative association with baseline age (2.44% decline per year) was seen in longitudinal linear mixed modeling including observations from premenopause through late postmenopause, an additional 0.33% decline/year. In contradistinction, a late-transition rise in DHEAS was detected when the same women were analyzed by ovarian status. The average increase in mean circulating DHEAS level between early and late menopause transition, beyond changes predicted by aging, was 3.95%, followed by an average decline of 3.96% during the late postmenopause. Approximately 84.5% of the women had an estimated within-woman increase in DHEAS from premenopause/early perimenopause to late perimenopause/early postmenopause. These observations underscore differences between cross-sectional and longitudinal studies and the importance of considering ovarian status. Additional investigations regarding adrenal contribution to sex steroids in mid-aged women are warranted.

Stressful Military Training: Endocrine Reactivity, Performance, and Psychological Impact

We examined the responsiveness of both cortisol and dehydroepiandrosterone sulfate (DHEAS) to the stress of survival training in military men and evaluated relationships to performance, peritraumatic dissociation, and the subsequent impact of stressful events. Baseline salivary cortisol samples were self-collected by 19 men at 0900 and 1930 in a free-living (FL) environment. DHEAS samples were also collected in a subset of this sample (N = 12). Samples were subsequently taken at similar time points during a stressful captivity (SC) phase of training. Repeated-measures analyses of variance with follow-up paired t-tests examined differences across time and conditions. Significant increases were observed at both time points (0900 and 1930) from FL to SC in both cortisol (0900: 9.2 +/- 3.4 nmol x L(-1) vs. 18.4 +/- 10.5 nmol x L(-1); 1930: 3.5 +/- 3.0 nmol x L(-1) vs. 27.7 +/- 10.9 nmol x L(-1)) and DHEAS (0900: 1.7 +/- 1.3 ng x ml(-1) vs.6.7 +/- 3.5 ngx ml(-1); 1930: 1.5 0.84 ng x ml(-1) vs. 4.5 +/- 3.0 ng x ml(-1)). Also, overall performance during a high-intensity captivity-related challenge was inversely related to the DHEAS-cortisol ratio; conversely, overall performance during a low-intensity captivity-related challenge was positively related to DHEAS at the 0900 time point during SC. Dissociation was unrelated to endocrine indices measured during SC, while total impact of events was inversely related to percent change in DHEAS from FL to SC. Cortisol and DHEAS increase in response to allostatic load, and may relate to human performance during SC as well as PTSD symptoms.

Adrenarche and the evolution of human life history

Adrenarche, the prepubertal onset of adrenal production of dehydroepiandrosterone sulfate (DHEAS), is a distinctive aspect of the human life course. Yet its evolutionary origins remain unexplained. Production of DHEAS is associated with the development of the zona reticularis, a novel histological layer within the adrenal gland, derived from the fetal adrenal gland, and associated with primates more generally. Evidence that DHEAS is a neurosteroid, together with the fact that increases in DHEAS parallel patterns of cortical maturation from approximately age 6 years to the mid-20s, suggests that DHEAS may play an important role in extended brain maturation among humans. DHEAS has demonstrated effects on mood in humans, and acts at neuron receptor sites. I suggest three ways in which DHEAS may play a role in human brain maturation: 1) increasing activity of the amgydala; 2) increasing activity of the hippocampus; and 3) promoting synaptogenesis within the cortex. I propose that associated changes in fearfulness and anxiety, and memory, could act to increase social interaction with nonfamiliar individuals and shape cognitive development. Comparison with the African apes suggests that the timing of adrenarche in chimpanzees may be similar to that in humans, though the full course of age-related changes in DHEAS and their relationship to reproductive and brain maturation are not clear. The role of DHEAS as a physiological mechanism supporting increased brain development, extended life span, and decreased sexual dimorphism is most compatible with Kaplan et al.'s (2000) theory of the evolution of human life history and intergenerational transfers.

Aging and season affect plasma dehydroepiandrosterone sulfate (DHEA-S) levels in a primate

In humans, plasma concentration of dehydroepiandrosterone sulfate (DHEA-S) declines with age and is considered as a potential predictor of longevity. DHEA-S is apparently unique to primates but few species of nonhuman primates have been studied for age-related changes in DHEA-S. In a short living primate, the grey mouse lemur (longevity 10–13 years), metabolic and physiological parameters exhibit high seasonal changes with age-related decrease in amplitude. From 8 month- to 11-year-old males ( N=175), plasma DHEA-S levels were measured either during the breeding season or during the winter sexual rest. Plasma DHEA-S levels show high significant changes according to season and age. During winter, DHEA-S levels were maintained low and constant over lifetime. During the summer breeding season, a decline of DHEA-S levels occurred after the age of 3 years and accelerated after the age of 6 years. DHEA-S level was about 30–40% of its adult value with age over 6 years, a stepwise pattern most closely resembling to human pattern. In mouse lemur, DHEA-S met the criteria for a biomarker of aging. When correlated to other age-related changes, the results give the opportunity to consider the mouse lemur as a promising primate model to study aging processes.

A longitudinal study of dehydroepiandrosterone sulphate (DHEAS) change in older men and women: the Rancho Bernardo Study

To examine the age-related and sex-specific rates and determinants of change in endogenous dehydroepiandrosterone sulphate (DHEAS) levels in older community-dwelling adults, taking into account regression to the mean. Prospective cohort study from Rancho Bernardo, California, USA. Plasma for DHEAS was collected at baseline and 10-14 years later from 242 men and 207 postmenopausal women (age range, 60-77 years), who were not taking hormone therapy or corticosteroids. Age-related and sex-specific changes in DHEAS were calculated according to four different definitions of change: absolute change, annual percentage change, change exceeding 10% of baseline and change exceeding that expected from statistical regression to the mean. Determinants of DHEAS change were assessed using regression analyses. Baseline DHEAS levels were higher for men than women (age-adjusted means, 1.37+/-0.73 microg/ml (3.72+/-1.98 micromol/l) vs 0.73+/-0.48 microg/ml (1.98+/-1.30 micromol/l) respectively, P<0.0001), with more pronounced declines observed in men (-4.0%/year) compared with women (-2.1%/year; P<0.001). Some 28% of women and 5% of men had DHEAS levels that increased or stayed the same according to a 10% definition of change. When regression to the mean artifact was accounted for, only 15% of women and 5% of men showed true increases in DHEAS. In both sexes, baseline DHEAS levels accounted for three-quarters of the variability in absolute DHEAS change over time, with higher baseline levels resulting in greater loss. Sex, baseline weight, age and smoking status were significantly associated with DHEAS change in univariate models; only sex remained independently associated with DHEAS change in multivariate analyses, with men showing greater annual declines than women (estimated coefficient=0.006, P=0.008). In this sample, over 30% of the observed changes in DHEAS could be attributed to regression to the mean. Potential underlying mechanisms of change in DHEAS levels, and sex differences, are discussed.

Stability of Adrenocortical Steroidogenesis over Time in Healthy Women and Women with Polycystic Ovary Syndrome

Adrenocortical secretion is up-regulated in women with polycystic ovary syndrome (PCOS), and absolute adrenal androgen (AA) excess is evident in approximately 25% of these patients. We hypothesized that AA biosynthesis is an inherited trait and that, as for other inherited traits, AA biosynthesis remains stable over time. To test this hypothesis, we prospectively studied 23 off-treatment PCOS patients and seven age- and body mass index-matched control women on two separate occasions 3-5 yr apart (45.0 +/- 19.0 months and 47.4 +/- 21.3 months, respectively; P > 0.05). All subjects underwent an acute adrenal stimulation using 0.25 mg ACTH-(1-24), and dehydroepiandrosterone (DHEA), androstenedione, and cortisol (F) were measured 0 and 60 min post ACTH; basal levels of total and free testosterone (T), SHBG, and DHEA sulfate (DHEA-S) were also assessed. Among PCOS patients, the mean DHEA-S levels during the repeat study were significantly lower when compared with the initial assessment (170 +/- 107 microg/dl vs. 134 +/- 79 microg/dl, respectively; P = 0.02). However, only patients with initial DHEA-S levels above the median (high DHEA-S) experienced a net decrease in the levels of this metabolite (252.5 +/- 99.2 microg/dl vs. 174.3 +/- 82.5 microg/dl; P = 0.001) over the time of the study; patients with initial DHEA-S levels in the lower half (low DHEA-S) did not experience a change in DHEA-S (94.6 +/- 28.9 microg/dl vs. 97.7 +/- 56.5 microg/dl; P = 0.85). In patients, the total T levels tended to be higher at the second study, although SHBG levels were also higher, resulting in unchanged free T levels over time. Among controls, no significant changes in basal androgens were observed over the time of the study. There were no significant differences in either the basal or ACTH-stimulated levels of DHEA, androstenedione, or F over the time of the study in either PCOS or control women. We conclude that the adrenocortical secretion of AAs or F in PCOS and control women remains stable over time, supporting the hypothesis that the adrenal response to ACTH may be an inherited trait. Alternatively, a decrease in DHEA-S levels over time was observed but only among PCOS patients whose initial levels of this metabolite were above the group median, suggesting that the activity of sulfotransferase in these patients may be up-regulated by factors other than those affecting adrenocortical biosynthesis and that such regulatory influences attenuate over time.

Mindfulness-based stress reduction in relation to quality of life, mood, symptoms of stress and levels of cortisol, dehydroepiandrosterone sulfate (DHEAS) and melatonin in breast and prostate cancer outpatients

Objectives: This study investigated the relationships between a mindfulness-based stress reduction meditation program for early stage breast and prostate cancer patients and quality of life, mood states, stress symptoms, and levels of cortisol, dehydroepiandrosterone-sulfate (DHEAS) and melatonin. Methods: Fifty-nine patients with breast cancer and 10 with prostate cancer enrolled in an eight-week Mindfulness-Based Stress Reduction (MBSR) program that incorporated relaxation, meditation, gentle yoga, and daily home practice. Demographic and health behavior variables, quality of life, mood, stress, and the hormone measures of salivary cortisol (assessed three times/day), plasma DHEAS, and salivary melatonin were assessed pre- and post-intervention. Results: Fifty-eight and 42 patients were assessed pre- and post-intervention, respectively. Significant improvements were seen in overall quality of life, symptoms of stress, and sleep quality, but these improvements were not significantly correlated with the degree of program attendance or minutes of home practice. No significant improvements were seen in mood disturbance. Improvements in quality of life were associated with decreases in afternoon cortisol levels, but not with morning or evening levels. Changes in stress symptoms or mood were not related to changes in hormone levels. Approximately 40% of the sample demonstrated abnormal cortisol secretion patterns both pre- and post-intervention, but within that group patterns shifted from “inverted-V-shaped” patterns towards more “V-shaped” patterns of secretion. No overall changes in DHEAS or melatonin were found, but nonsignificant shifts in DHEAS patterns were consistent with healthier profiles for both men and women. Conclusions: MBSR program enrollment was associated with enhanced quality of life and decreased stress symptoms in breast and prostate cancer patients, and resulted in possibly beneficial changes in hypothalamic-pituitary-adrenal (HPA) axis functioning. These pilot data represent a preliminary investigation of the relationships between MBSR program participation and hormone levels, highlighting the need for better-controlled studies in this area.

The relationship of circulating dehydroepiandrosterone, testosterone, and estradiol to stages of the menopausal transition and ethnicity.

In this report, 3029 women between the ages of 42 and 54 yr from five ethnic groups were studied for 2 yr. Log circulating dehydroepiandrosterone sulfate (DHEAS) concentrations were highest among Chinese and Japanese and lowest among African Americans and Hispanics, and this pattern persisted after adjustment for age, smoking, and log body mass index (BMI). With the exception of Japanese women, log BMI was negatively related to log circulating DHEAS. The magnitude of this association varied by ethnic group, and the decline in log circulating DHEAS levels with higher log BMI was steepest for Chinese and least steep for Hispanics. The relationship between log DHEAS and log BMI was positive for Japanese. DHEAS levels did not decline at a steady rate during the menopausal transition and transiently increased in some women and increased, on average, during the transition to late perimenopause. These increases tended to be larger for Chinese, Hispanic, and Japanese than for African Americans and Caucasians, although the interactions were not statistically significant. Changes in circulating testosterone and, to a lesser extent, estradiol were correlated to changes in DHEAS. These data have importance in understanding the endocrinology of the menopausal transition, defining the relationship of adrenal steroid production during declining ovarian function and determining a rationale regarding DHEAS supplementation for older women.

Diurnal rhythm and effects of oral contraceptives on serum dehydroepiandrosterone sulfate (DHEAS) are related to alterations in serum albumin rather than to changes in adrenocortical steroid secretion

Dehydroepiandrosterone sulfate (DHEAS), which is of almost exclusive adrenal origin, is important for the androgen status in women and prepubertal children, and DHEAS assays are used in the investigation of hyperandrogenism. There are conflicting reports concerning a diurnal variation in serum DHEAS. Although of adrenocortical origin, serum DHEAS levels are decreased by oral contraceptives (OCs). DHEAS is strongly bound to serum albumin and has a very low metabolic clearance rate. The present study was performed in order to investigate whether a diurnal variation in serum DHEAS exists and, if so, whether this diurnal variation and the decreased DHEAS levels following OC use are related to alterations in adrenocortical steroids or to changes in serum albumin. Serum concentrations of DHEAS, dehydroepiandrosterone (DHEA), cortisol and albumin were determined in blood samples taken every half hour over a 24-h period in 10 healthy women before and during use of combined OCs. Significant and frequently synchronous diurnal variations in serum DHEAS and albumin were found before as well as during OC use. These variations were not synchronous with the diurnal variation in DHEA. OCs significantly decreased serum DHEAS and albumin levels. A multiple regression analysis showed changes in albumin to be the most decisive factor for the diurnal variation as and for OC-induced changes in DHEAS. Changes in serum DHEAS during the day and following OC use are related to alterations in its main binding protein, serum albumin, rather than to changes in adrenocortical steroid secretion.