Effects of transdermal application of DHEA on the levels of steroids, gonadotropins and lipids in men. (57/529)

In order to ascertain the kinetics of absorption and metabolism of transdermally administered dehydroepiandrosterone (DHEA), 10 men 29-72 years old (mean 52.4+/-14.5) received 50 mg DHEA/day in a gel applied onto the skin of the abdomen for 5 consecutive days. The objective was to establish the extent to which DHEA influences the levels of gonadotropins, sex hormone-binding globulin and lipids. It was found that DHEA is well absorbed and rapidly metabolized to its sulfate (DHEAS), androstenedione, and consequently to testosterone and estradiol. The DHEA levels that markedly increased after the first doses gradually declined already during the application, and this decline proceeded even after it was discontinued, reaching levels significantly lower than the original ones. On the other hand, the levels of DHEA metabolites (with the exception of DHEAS) rose during the application and reached values significantly higher than the basal ones within 5 weeks. This effect was accompanied by significantly decreased levels of LH. The serum levels of lipids, namely of cholesterol (both HDL and LDL cholesterol), triglycerides, apolipoproteins A-I and B and lipoprotein(a) after DHEA application were not changed significantly, and the atherogenic index (AI) remained unaltered. However, some correlations between hormones and lipids were found. Negative correlations concerned the following indices: DHEA/Lp(a); DHEAS/cholesterol; DHEA, DHEAS, testosterone/TG; testosterone/AI. On the other hand, LH, FSH/cholesterol, FSH, SHBG/LDL cholesterol, FSH/Apo B, Lp(a) correlated positively. It can be concluded that transdermal short-time application of DHEA results in a decrease of endogenous DHEA after finishing the treatment, with a parallel marked increase in the levels of sex hormones. Using this application protocol, exogenous DHEA neither altered the lipid spectrum, nor did it influence the atherogenic index.  (+info)

Functional analysis and androgen-regulated expression of mouse organic anion transporting polypeptide 1 (Oatp1) in the kidney. (58/529)

Mouse Oatp1 was recently identified as a new murine member of the organic anion transporting polypeptide (Oatp) family and suggested to represent the counterpart of rat Oatp1. Northern blot analysis detected expression of several mouse Oatp-transcripts predominantly in liver and kidney. In the present study we describe the strict androgen-dependent expression of mouse Oatp1 mRNA in kidney and obtained further information about its substrate specificity using Xenopus oocytes. In addition to the previously reported estrone-3-sulfate, we demonstrate that mouse Oatp1 mediates sodium-independent uptake of the anionic steroid conjugates dehydroepiandrosterone sulfate (K(m) approximately 8 microM) and estradiol-17-glucuronide (K(m) approximately 5 microM) and also of the prostaglandin PGE(2).  (+info)

Age-related changes of the hypothalamic-pituitary-adrenal axis: pathophysiological correlates. (59/529)

The aim of this review was to examine the evidence for age-related changes of the hypothalamic-pituitary-adrenal (HPA) axis in both physiological and pathological aging, on the basis of the many data in the literature, as well as of our personal findings. A statistically significant circadian rhythmicity of serum cortisol was maintained in elderly subjects, even if with a reduced amplitude of the 24 h fluctuations and a trend to an increase of the serum levels in the evening and at night-time, in comparison with young controls. Furthermore, an age-related impairment of HPA sensitivity to steroid feedback was present in elderly people. The occurrence of senile dementia amplified the changes already present in physiological aging. While the cortisol secretion was generally well maintained in aging, the adrenal production of dehydroepiandrosterone and of its sulfate (DHEAS) exhibited an age-related decline. Therefore, the cortisol/DHEAS molar ratio was significantly higher in elderly subjects and even more in demented ones, than in young controls. Due to the opposite effects of cortisol and DHEAS on the brain and particularly on the hippocampal region, the imbalance between glucocorticoids and androgens occurring in physiological and even more in pathological aging, may have adverse effects on the function of this region, whose key role in learning and memory is well known.  (+info)

Hyposecretion of the adrenal androgen dehydroepiandrosterone sulfate and its relation to clinical variables in inflammatory arthritis. (60/529)

Hypothalamic-pituitary-adrenal underactivity has been reported in rheumatoid arthritis (RA). This phenomenon has implications with regard to the pathogenesis and treatment of the disease. The present study was designed to evaluate the secretion of the adrenal androgen dehydroepiandrosterone sulfate (DHEAS) and its relation to clinical variables in RA, spondyloarthropathy (Spa), and undifferentiated inflammatory arthritis (UIA). Eighty-seven patients (38 with RA, 29 with Spa, and 20 with UIA) were studied, of whom 54 were women. Only 12 patients (14%) had taken glucocorticoids previously. Age-matched, healthy women (134) and men (149) served as controls. Fasting blood samples were taken for determination of the erythrocyte sedimentation rate (ESR), serum DHEAS and insulin, and plasma glucose. Insulin resistance was estimated by the homeostasis-model assessment (HOMAIR). DHEAS concentrations were significantly decreased in both women and men with inflammatory arthritis (IA) (P < 0.001). In 24 patients (28%), DHEAS levels were below the lower extreme ranges found for controls. Multiple intergroup comparisons revealed similarly decreased concentrations in each disease subset in both women and men. After the ESR, previous glucocorticoid usage, current treatment with nonsteroidal anti-inflammatory drugs, duration of disease and HOMAIR were controlled for, the differences in DHEAS levels between patients and controls were markedly attenuated in women (P = 0.050) and were no longer present in men (P = 0.133). We concluded that low DHEAS concentrations are commonly encountered in IA and, in women, this may not be fully explainable by disease-related parameters. The role of hypoadrenalism in the pathophysiology of IA deserves further elucidation. DHEA replacement may be indicated in many patients with IA, even in those not taking glucocorticoids.  (+info)

The effect of early postnatal treatment with a gonadotropin-releasing hormone agonist on the developmental profiles of testicular steroid hormones in the intact male pig. (61/529)

Three studies examined the effects of early postnatal treatment with a GnRH agonist on plasma concentrations of testosterone, dehydroepian-drosterone sulfate, 16-androstene steroids in fat and salivary glands, androstenone in fat and plasma, and testicular development of intact male pigs. The first study involved 45 7-d-old pigs assigned to three treatment groups: 1) boars administered 100 microg/kg of Lupron depot, 2) boars administered 200 microg/kg of Lupron depot, and 3) control boars receiving a saline carrier. The second study involved 20 7-d-old pigs assigned to two treatments: daily injection of 200 microL of 0.5 mg/mL Lupron from d 7 to 35 and controls treated with saline. The third study involved a total of 100 animals assigned to 10 groups of 10 based on their age at slaughter. These groups were subdivided into one of two treatments: 1) boars injected with 200 microL of 0.5 mg/mL of Lupron from d 3 to 35 and 2) control boars injected with saline. Testicular steroid hormone concentrations in plasma decreased (P < 0.01) within 7 d of GnRH agonist treatment. Following cessation of treatment, steroid levels increased to control levels and remained constant until the final rise at 5 mo. Plasma testosterone levels in the 100 microg/kg depot treatment group were higher (P < 0.05) than that of the 200 microg/kg and control group at 164 d of age. There were no differences between treatments (P > 0.05) in testicular steroid hormone levels at the end of study 2 or 3. There were no differences (P > 0.05) in concentrations of 16-androstene steroids in salivary glands between any of the treatment groups at market weight in studies 1 and 2. Fat androstenone levels measured in the third study ranged between 0.6 microg/g and 4.2 microg/g at 7 to 28 d of age. Treatment with GnRH agonist decreased plasma steroid levels and testicular development; however, by d 60 testicular size and weight were at control levels and remained similar until 180 d of age. The results of these studies indicate that daily administration of a GnRH agonist significantly decreased testicular development and steroidogenesis only during treatment, but testis growth and steroidogenesis had returned to control levels by 60 d of age in male pigs. Suppression of the early postnatal rise in testicular steroid hormones did not affect growth performance or steroid hormone levels at 5 to 6 mo of age.  (+info)

Serum hormones and the alcohol-breast cancer association in postmenopausal women. (62/529)

BACKGROUND: Alcohol ingestion is associated with an increased risk of breast cancer in most epidemiologic studies. Results, however, are heterogeneous at lower levels of alcohol intake, and a biologic mechanism for the association has not been clearly identified. To determine whether alcohol consumption by postmenopausal women elevates serum levels of hormones associated with an increased risk of breast cancer, we performed a controlled feeding study. METHODS: Participants were 51 healthy postmenopausal women not using hormone replacement therapy. Each participant rotated through three 8-week dietary periods in which she consumed 15 or 30 g of alcohol per day or an alcohol-free placebo beverage. The order of assignment to the three alcohol levels was random. During the dietary periods, all food and beverages were supplied by the study, and energy intake was adjusted to keep body weight constant. Levels of estradiol, estrone, estrone sulfate, testosterone, androstenedione, progesterone, dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), and androstenediol were measured by radioimmunoassays in serum collected at the end of each dietary period. All statistical tests are two-sided. RESULTS: When women consumed 15 or 30 g of alcohol per day, respectively, estrone sulfate concentrations increased by 7.5% (95% confidence interval [CI] = -0.3% to 15.9%; P =.06) and 10.7% (95% CI = 2.7% to 19.3%; P =.009) and DHEAS concentrations increased by 5.1% (95% CI = 1.4% to 9.0%; P =.008) and 7.5% (95% CI = 3.7% to 11.5%; P<.001) relative to levels when women consumed placebo. None of the other hormones measured changed statistically significantly when women consumed alcohol. CONCLUSIONS: Results suggest a possible mechanism by which consumption of one or two alcoholic drinks per day by postmenopausal women could increase their risk of breast cancer.  (+info)

Body composition characteristics and body fat distribution in lean women with polycystic ovary syndrome. (63/529)

Body composition, fat distribution and bone mineral density were examined in lean women suffering from polycystic ovary syndrome (PCOS) and compared with body composition and fat distribution characteristics of weight-matched lean controls. Ten women with PCOS and a body mass index (BMI) below 25.00 (kg/m(2)) and 10 healthy women with a BMI below 25.00 (kg/m(2)) matched for age and weight and BMI as controls were enrolled in this study. Body composition and bone density were measured by dual-energy- x-ray-absorptiometry and fat distribution patterns were calculated. Although matched for age, weight and BMI, lean PCOS patients showed a significantly higher amount of body fat and lower amount of lean body mass than the controls. The majority of PCOS patients showed an intermediate or android kind of fat distribution. Only 30% of the lean PCOS patients corresponded to the definition of gynoid fat distribution while this was true of all lean controls.  (+info)

Prospective measurements of dehydroepiandrosterone sulfate in a cohort of elderly subjects: relationship to gender, subjective health, smoking habits, and 10-year mortality. (64/529)

The decrease with age of the adrenal-secreted dehydroepiandrosterone sulfate (DHEAS) in serum has suggested that it may be causally related to longevity. For the PAQUID [People (Personnes) Aged (Agees) About What (Quid, in Latin)] cohort of elderly subjects, we have previously reported higher DHEAS in men than in women, a decrease with age and, among men, a negative correlation between the DHEAS level and mortality at 2 and 4 years. Here, with an 8-year followup in 290 subjects, we show a global decrease of 2.3% per year for men and 3.9% per year for women. However, in approximately 30% of cases, there was an increase of DHEAS. We observed no relationship between the evolution of DHEAS level and functional, psychological, and mental status, possibly because of selection by death. In women, no association was found between mortality and DHEAS level. In men, the relative risk (RR) of death was higher for the lowest levels of DHEAS (RR = 1.9, P = 0.007), with RR = 6.5, P = 0.003 for those under 70 years old, a result indicating heterogeneity of the population. There was an effect of subjective health on mortality that disappeared after adjustment of DHEAS levels, suggesting its relation with these DHEAS levels. Death RR was much higher in smokers with a low DHEAS level than in nonsmokers with high DHEAS (RR = 6.7, P = 0.001). We submit that the involvement of DHEAS is possibly different according to gender, that association between low DHEAS level and mortality only for men under 70 years old possibly reflects heterogeneity of the population, and that DHEAS level is a reliable predictor of death in male smokers.  (+info)