Decrease In Dehydroepiandrosterone Sulfate Levels Research Articles

Glucocorticoid-induced adrenal insufficiency after therapy with intravenous methylprednisolone in patients with moderate-to-severe and active Graves' orbitopathy: assessment with a low-dose corticotropin test.

We aimed to assess adrenal function following treatment of moderate-to-severe and active Graves' orbitopathy (GO) with intravenous methylprednisolone (IVMP) in weekly pulses in a cumulative dose of 4.5 or 7.5g. We evaluated the impact of IVMP pulses on adrenal reserve using a low-dose (1μg) ACTH stimulation test (LDT) for the first time. In this prospective study we evaluated adrenal function in 21 patients with moderate-to-severe and active GO treated with 12 weekly IVMP pulses according to the European Group on Graves' Orbitopathy (EUGOGO) recommendations. We assessed serum cortisol, plasma adrenocorticotropic hormone (ACTH), and dehydroepiandrosterone sulfate (DHEA-S) levels before the 1st and 12th IVMP pulse. We performed dynamic testing using LDT before the 12th IVMP pulse in all patients. In those who failed LDT, adrenal function was reassessed with LDT and the overnight metyrapone test after 4-7weeks. Two patients failed to achieve serum cortisol levels ≥ 18.1μg/dL at 30 and 60min in LDT and were diagnosed with glucocorticoid-induced adrenal insufficiency (GC-induced AI). They were recommended to take hydrocortisone in situations of acute stress. Both patients were reassessed within 4-7weeks after treatment cessation and showed an adequate response in LDT and overnight metyrapone test. We observed a statistically significant decrease in DHEA-S levels (p = 0.004) before the 12th IVMP pulse compared to baseline in all patients. For the first time, our research shows that administering IVMP in 12 weekly pulses can result in GC-induced AI. We suggest that patients should undergo careful evaluation for GC-induced AI, including LDT, after therapy with IVMP according to EUGOGO guidelines. Screening for altered adrenal reserve could prevent life-threatening complications, particularly during acute stress situations.

A comparison of the effects of oral contraceptives on the clinical and biochemical manifestations of polycystic ovary syndrome: a crossover randomized controlled trial.

Do oral contraceptives (OCs) containing progestins with low androgenic or antiandrogenic activities have different effects to those containing levonorgestrel (LNG) on clinical, androgenic and metabolic manifestations of polycystic ovarian syndrome (PCOS)? The three OCs tested had similar effects on clinical findings of hyperandrogenism (HA), whereas products containing LNG were less effective on androgenic profiles and had detrimental effects on lipid profiles. Despite data available on the effects of OCs, the superiority of products with low androgenic or antiandrogenic progesterone components in comparison with older products used in women with PCOS has not been clarified. This study is a crossover randomized controlled six-arm trial, with all six arms including two 6-month treatment periods, one period with OCs containing LNG, and the other with one of three OCs containing desogestrel (DSG), cyproterone acetate (CPA) or drospirenone (DRSP). The trial was conducted between February 2016 and January 2018 and enrolled 200 patients with PCOS. Two hundred women with PCOS (ages 18-45years) were recruited at the endocrine outpatient clinic of the Research Institute for Endocrine Sciences (RIES) of the Shahid Beheshti University of Medical Sciences, Tehran, Iran. A blocking or stratification random allocation (block size = 6) using a computer-based random number generator was prepared to assign participants to treatment groups. Both the clinical examiner and data analyst were blinded to participants during the trial. Outcomes of interest, including anthropometric and clinical manifestations and hormonal, and biochemical parameters were assessed at baseline, after 3 and 6months of each treatment and after the washout period. This study detected a higher decrease in free-androgen index (FAI) levels after 3months of treatment with OCs containing DSG (95% CI: -2.3, -1.0), CPA (95% CI: -2.4, -1.1) and DRSP (95% CI: -2.6, -1.4), compared with products containing LNG (P< 0.001). Use of OCs containing DSG (95% CI: -3.6, -1.5), CPA (95% CI: -3.1, -0.8) and DRSP (95% CI: -3.4, -1.1) for 6months was associated with more decrease in FAI, compared with products containing LNG (P< 0.001). The study showed that use of OCs containing DSG, CPA and DRSP for 3-6months was associated with a higher increase of sex hormone-binding globulin (SHBG), compared with products containing LNG (P< 0.001). We also observed more decrease in dehydroepiandrosterone sulfate levels after use of OCs containing DSG (P= 0.003), CPA (P= 0.012) and DRSP (P< 0.001) for 6months, compared with products containing LNG. Our results showed that the use of OCs containing DRSP for 6months was associated with more improvement in acne, compared with products containing LNG (P= 0.007). Women treated with OCs containing CPA, and DRSP for 3months had higher TG and HDL levels and lower LDL levels, compared with those treated with products containing LNG (P< 0.05). After 6months of treatment, patients treated with OCs containing DRSP had a sharper decline in LDL levels and more increase in HDL levels, compared to those treated with products containing LNG (P= 0.001). Considering this trial was conducted in women diagnosed with Androgen Excess Society criteria, the results may not be generalizable for mild phenotypes diagnosed using Rotterdam criteria. Other limitations of the study include the high dropout rate, the lack of a gold standard androgen assay and the multiple end points. Our results support the views of clinicians, who suggest an OC with a low androgenic or antiandrogenic progestin, if available, to treat PCOS. This study was supported by the RIES, Shahid Beheshti University of Medical Sciences, Tehran, Iran. There are no conflicts of interest. IRCT201702071281N2. 21 February 2017. 21 March 2017.

Hormonal status of cortisol and dehydroepiandrosterone sulfate in an elderly Tunisian population

Adrenal function and aging have been the object of intense interest recently, especially as regards dehydroepiandrosterone sulfate (DHEA-S), which is of major importance, since it is distinct from cortisol and aldosterone in declining with age. In a group of healthy old Tunisians, we investigated the association between cortisol and DHEA-S, on the one hand, and age, sex, lifestyle, physical health, including the body mass index (BMI), physical activity, and smoking indicators, on the other hand. We observed that cortisol concentrations did not change with aging, while DHEA-S concentrations decrease with age in both sexes. Cortisol/DHEA-S ratio, however, increases with aging. Our results revealed that DHEA-S levels are affected neither by physical activity nor by weight. It appears also that current smoking could not affect the level of DHEA-S. Relationships were found between DHEA-S concentrations and BMI, then between DHEA-S levels and serum cholesterol, triglycerides and calcium. No modification in the morning serum cortisol was found to be associated with aging. Decrease in DHEA-S levels is, however, clearly associated with this phenomenon. High cortisol/DHEA-S ratio accelerates the occurrence of some adult diseases, such as diabetes mellitus, atherosclerosis, dementia, and osteoporosis. Generally, the adrenal insufficiency marked by a cognitive impairment, immune disorders, sexual dysfunction, and scores for depression and anxiety can be corrected by a replacement of deficient DHEA-S. To cite this article: O. Chehab et al., C. R. Biologies 330 (2007).

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.

Growth and hormone characteristics of pubertal development in the hamadryas baboon.

The semi-longitudinal collection of growth measurements in male and female hamadryas baboons has enabled documentation of the timing of puberty and the development of sexually dimorphic growth patterns in body weight, crown-rump length (CRL), limb lengths, and muscle mass. In addition, another sexually dimorphic characteristic appears to be the presence of a pubertal growth spurt in body weight, and possibly CRL, in male but not female baboons. Serum testosterone levels rose during male development; however, there was a progressive decrease in dehydroepiandrosterone sulfate levels indicating the absence of adrenarche. Insulin-like growth factor-I (IGF-I) and its major binding protein, IGFBP-3, both rose during pubertal development; however, a simultaneous rise in the IGF-I:IGFBP-3 molar ratio suggests other factors may enhance the bioactivity of IGF-I during puberty. A distinct rise in serum osteocalcin levels was also associated with puberty in male baboons. These growth and hormonal changes during puberty in the hamadryas baboon indicate that this species provides a close primate model for human puberty.

Insulin sensitivity and antiandrogenic therapy in women with polycystic ovary syndrome

Polycystic ovary (PCO) syndrome is strongly associated with insulin resistance and the accompanying adverse metabolic profile. To distinguish the mechanisms of this association, we determined the interactions of PCO with obesity and the influence of ameliorating direct androgenic actions via short-term treatment with the antiandrogen flutamide. Insulin sensitivity was determined by the hyperinsulinemic eugiycemic clamp in groups of lean and obese PCO women and weight-matched controls. Compared with control values, insulin-mediated glucose utilization in PCO women was significantly lower in lean (1.96 ± 0.17 v 1.24 ± 0.10, P < .01) and obese (1.23 ± 0.18 v 1.03 ± 0.09 mmol/m 2/min, P < .01) subjects. ANOVA indicated that the effects of obesity and androgenicity are independent and additive. In both lean and obese PCO women, treatment with flutamide for 1 or 3 months markedly improved the clinical and biochemical androgenic features, but did not significantly influence the overall insulin sensitivity. A large disparity between individuals in the response to treatment correlated significantly with a simultaneous reduction in plasma levels of dehydroepiandrosterone sulfate (DHEA-S). Thus in women, PCO and obesity exert synergistic effects on insulin resistance. The decreased insulin sensitivity is mediated via indirect androgenic actions or nonandrogenic mechanisms. In some individuals, a direct effect of androgens might have been masked by a decrease in DHEA-S levels.

Dehydroepiandrosterone Sulfate in a Long-term Care Aged Population

Ninety-four institutionalized subjects (mean age 82.9 years; 13 men and 81 women) were assessed for serum dehydroepiandrosterone sulfate (DHEAS) levels. The mean value was 457 ng/ml (SD = 426) in this cross-sectional study. There was a significant decrease in DHEAS levels with age. There was no difference among demented patients with Alzheimer's disease (n = 46), other dementia cases (n = 16), and other individuals (n = 32). The subjects treated for arterial hypertension had significantly lower DHEAS levels. No correlation was found between DHEAS and cortisol values. After age adjustment, no association was observed between DHEAS and chronic diseases, medications, several biochemical or hematological parameters, or 3-year mortality.

A Prospective Study of Dehydroepiandrosterone Sulfate (DHEAS) and Bone Mineral Density in Older Men and Women

The purpose of this study was to prospectively examine the relation of dehydroepiandrosterone sulfate (DHEAS) to bone mineral density in a community-based sample of 260 men and 162 women who were residents of Rancho Bernardo, California. DHEAS levels had been measured in plasma obtained in 1972-1974 when the men were 50-74 years of age and the women were 55-74. In 1988-1991, bone mineral density was measured at the lumbar spine and hip using dual x-ray absorptiometry, and at the mid-radius and ultradistal radius using single photon absorptiometry. Among men, there was a significant decrease in DHEAS levels and bone mineral density at the hip, ultradistal radius, and midshaft radius with increasing age. However, for both men and women, there was no significant association of DHEAS levels with bone mineral density at any site, both before and after adjustment for age, obesity, cigarette smoking, and use of antihypertensive medications. These data do not support the hypothesis of DHEAS having a causal role in senile osteoporosis.

Dehydroepiandrosterone Sulfate Levels Are not Suppressible by Glucocorticoids before Adrenarche*

We measured dehydroepiandrosterone sulfate (DHEA-S) levels in children before and after high dose prednisone therapy. In older children (postadrenarchal), there was a 70% decrease in DHEA-S levels after 1 week. However, even after a month of therapy, DHEA-S was detectable in serum. In contrast, in younger (preadrenarchal) children, the low initial DHEA-S levels were not decreased by prednisone therapy. These findings suggest that there are two distinct regulatory pathways leading to DHEA-S, one of which is independent of ACTH.

Decreased serum level of dehydroepiandrosterone sulfate in postmenopausal women with ovarian cancer.

Serum levels of dehydroepiandrosterone sulfate (DHEAS) were measured in 41 postmenopausal women with ovarian tumor (16 with ovarian cancer, 6 with borderline malignant and 19 with benign ovarian tumor) and in 21 postmenopausal women without ovarian neoplasm. Circulating DHEAS levels were significantly lower in patients with ovarian cancer than in women with benign ovarian tumor and in control subjects. Women with advanced ovarian cancer had lower DHEAS levels than those with local ovarian cancer. An age-related decrease in DHEAS levels was noted in the control group, while circulating DHEAS levels were independent of age in the ovarian cancer group. The results indicate the effect of ovarian cancer on this adrenal androgen and the possible presence of ovarian factor in malignant ovarian neoplasm.