Plasma Dehydroepiandrosterone Sulfate Concentrations Research Articles

Oral Contraceptive Use Impairs Muscle Gains in Young Women

Riechman, SE and Lee, CW. Oral contraceptive use impairs muscle gains in young women. J Strength Cond Res 36(11): 3074-3080, 2022-Many active young women use oral contraceptives (OCs), yet their effects on the body composition and exercise performance have not been thoroughly studied. We examined the effects of OCs on muscle responses to a standardized resistance exercise training (RET) program. Two groups of young healthy women (18-29 years old, non-OC: n = 38, OC: n = 34) underwent 10 weeks of whole-body RET (3 days·wk -1 , 3 sets, 6-10 repetitions, at 75% of maximum strength, 13 exercises). Body composition was determined using hydrostatic weighing, and blood samples were taken before and after training to measure dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), IGF-1, and cortisol levels. There were significant differences in lean mass gains between the groups (non-OC: 3.5 ± 0.4% vs. OC: 2.1 ± 0.5% and non-OC: 1.6 ± 0.2 kg vs. OC: 1.0 ± 0.2 kg, p < 0.05). Plasma concentrations of DHEA, DHEAS, and IGF-1 were significantly lower, and cortisol levels were higher in the OC group before and after training ( p < 0.05). In addition, there were significant differences in lean mass gains depending on the androgenicity of progestin between the non-OC and medium-high groups (non-OC: 1.6 ± 0.2 kg, Low = 1.1 ± 0.2 kg, med-high = 0.3 ± 0.5 kg, p < 0.05). Oral contraceptive use impaired lean mass gains in young women after RET and was associated with lower DHEA, DHEAS, and IGF-1 and higher cortisol. The diminished lean mass gain may be related to the effect of OCs on anabolic and catabolic hormone levels or the androgenicity of progestin that may bind to androgen receptors and inhibit its function.

Comparative Evaluation of Dehydroepiandrosterone Sulfate Potential to Predict Hepatic Organic Anion Transporting Polypeptide Transporter-Based Drug-Drug Interactions.

Pharmacokinetic drug-drug interactions (DDIs) on hepatic organic anion transporting polypeptides (OATPs) are important clinical issues. Previously, we reported that plasma dehydroepiandrosterone sulfate (DHEAS) could serve as an endogenous probe to predict OATP-based DDIs in monkeys using rifampicin as an OATP inhibitor. Since the contribution of hepatic OATPs to the changes in plasma DHEAS by rifampicin remains unclear, however, we performed an in vivo pharmacokinetic study to explore this issue. Since plasma DHEAS concentrations were low in our rat model, the disposition of externally administered DHEAS was evaluated. Intravenously administered DHEAS was recovered mainly in bile (29.1%) and less in urine (2.95%). The liver tissue-to-plasma concentration ratio (Kpliver) decreased from 41.8 to 5.07 by rifampicin, and this decrement was consistent with the decrease in distribution volume from 247 to 59 ml/rat. Comparison of the in vitro IC50 of rifampicin for DHEAS uptake by isolated rat hepatocytes and in vivo plasma rifampicin concentration suggested that the effect of rifampicin on the plasma DHEAS concentration was explained mostly by the inhibition of hepatic OATPs, demonstrating that DHEAS could be a biomarker of hepatic OATP activity. Next, previously reported rifampicin-induced changes in plasma concentrations evaluated as an AUC ratio (AUCR) of possible probe compounds were compared on the basis of rifampicin dose/body surface area. The AUCR values of endogenous compounds and i.v. administered statins, for which possible DDIs in the intestinal absorption process can be excluded, increased proportionally to the rifampicin dose. Simultaneous measurement of these endogenous compounds could be effective biomarkers for the prediction of OATP-based DDIs.

Changes in maternal androgens and oestrogens in mares with experimentally-induced ascending placentitis.

While advanced stages of ascending placentitis can be diagnosed by transrectal ultrasonography and clinical signs, early stages can be missed. Thus, additional tools could enhance assessment of placental health. To characterise peripheral dehydroepiandrosterone sulphate (DHEA-S) and testosterone concentrations in mares carrying normal pregnancies (Study 1) and compare plasma concentrations of DHEA-S, testosterone, oestradiol 17-β (oestradiol) and oestrone sulphate (OES) in mares with or without placentitis (Study 2). Longitudinal cohort study of healthy mares (Study 1) and controlled experiment (Study 2). In Study 1, mares had serum samples collected from 100 days of gestation to term. In Study 2, pregnant mares (260-280 days gestation) were assigned to a control group or a group with placentitis. Placentitis was induced via intracervical inoculation of Streptococcus equi ssp. zooepidemicus. Blood was collected at inoculation/commencement for control mares (day = 0) and daily for 12 days post inoculation (DPI) or until abortion. Steroid concentrations were determined by immunoassays. Concentrations of steroids in Study 2 were also evaluated relative to days from abortion (DFA -8 days to 0). In Study 1, DHEA-S peaked by 180 days gestation, while testosterone concentrations were progressively increased from Days 100 to 180 with a plateau until ~240 days and a progressive decline until 290 days of gestation. In Study 2, concentrations of DHEA-S and testosterone were not significantly different between groups. There were significant effects of time (oestradiol P = 0.0008, OES P = 0.01) and time-by-group interactions (oestradiol P<0.001, OES P<0.0001) for oestrogen concentrations. For mares with experimental placentitis, concentrations of oestradiol were significantly reduced at -6, -2, -1 and 0 DFA, while OES concentrations were significantly reduced on the day before abortion (0 DFA). Testosterone and DHEA-S were increased and varied through pregnancy. Oestrogens but not androgens decreased significantly in mares with experimentally-induced ascending placentitis.

Investigation of dermatology life quality index and serum prolactin and serum dehydroepiandrosterone sulphate levels in patients with chronic urticaria.

Chronic urticaria (CU) is known to be one of the most disturbing diseases which significantly affect the quality of life. Prolactin (PRL) and DHEA-S (dehydroepiandrosterone sulfate) are stress-associated hormones in chronic urticaria. In the present study, we measured DHEA-S and prolactin levels of CU patients, compared them with healthy subjects and evaluated the association between disease status and serum levels. Plasma DHEA-S and serum PRL concentrations were measured in 48 CU patients and 31 healthy subjects. CU activity was assessed with the use of the symptom scores recommended with EAACI/GALEN/EDF guidelines. All the patients participating in this study were evaluated by means of Dermatology Life Quality Index (DLQI). With respect to DLQI and clinical activity scores, plasma DHEA-S and serum prolactin levels were compared. Median plasma concentration of DHEA-S was significantly lower in CU patients as compared with healthy subjects (p = 0.026). DHEA-S levels of females were significantly lower than males (p = 0.001). Mean PRL values of the patients were higher than the controls, but not statistically significant (p = 0.619) and there was a statistically signifcant inverse correlation with DHEA-S levels (p = 0.04, r = -0.298). Therewas a significant correlation between DLQI and clinical disease activity (p < 0.001, r = 0.748). The exact relation of hormones to CU pathogenesis remains to be determined by further clinical studies. In addition, therapies aiming to increase DHEA-S and decrease PRL may be subject to trial in CU.

Relationship between polymorphisms in the sulfotransferase SULT2A1 gene and dehydroepiandrosterone sulfate concentration in children

Dehydroepiandrosterone sulfate (DHEA-S) is the most abundant circulating steroid hormone in humans, and has important physiological effects. A relationship has been suggested between variations of DHEA-S concentration and polymorphisms in the gene encoding sulfotransferase (SULT2A1), an enzyme that catalyzes the formation of DHEA-S from DHEA. We have investigated the relationship between the single nucleotide polymorphisms (SNPs) rs2637125 and rs182420 in the SULT2A1 gene and plasma DHEA-S concentration in children at two different ages. The sample population comprised 981 healthy 6-8-year-olds and 792 12-16-year-old children. In total, 12-16-year-old boys homozygous for the rare allele of rs182420 (CC) showed significantly lower DHEA-S concentration than TC boys, and both (TC and CC) had lower levels than TT boys. In all, 12-16 -year-old boy carriers of the rare allele for the rs2637125 polymorphism also showed lower levels of DHEA-S than GG carriers. No differences were observed in DHEA-S concentrations across genotypes in 6-8-year-old children. Our data show an age-related association of polymorphisms in the SULT2A1 gene with lower DHEA-S, suggesting that these polymorphisms may affect DHEA-S concentration in adults.

The effect of treatment with ketoconazole on central CRH systems of depressed patients

Steroid-synthesis inhibitors are reported to reduce psychopathology in treatment-resistant depressed patients. We studied the effect of a 3-week treatment with ketoconazole on the evening plasma concentrations of cortisol, corticosteroid-binding globulin (CBG), dehydroepiandrosterone-sulfate (DHEA-S) and adrenocorticotrope hormone (ACTH) as well as morning cerebrospinal fluid (CSF) concentrations of cortisol, corticotropin-releasing hormone (CRH) and arginine-vasopressin (AVP) in six elderly treatment-resistant depressed patients. While we found plasma cortisol concentrations to be unchanged, a decline in plasma DHEA-S concentrations indicated effective steroid-synthesis inhibition. In morning CSF we found CRH concentrations that did not change. Our preliminary observations indicate that the treatment of depressed patients with the steroid-synthesis inhibitor ketoconazole does not lead to a major increase in CSF CRH secretion.

Changes in Plasma Sex Hormone Levels in Women with Severe Concomitant Injury

Objective: to perform a complex study of the plasma levels of 11 sex hormones and their functional values in women with severe concomitant injury (SCI). Subjects and methods. The study enrolled 16 women aged 18—45 years who had SCI. Admission APACHE II scores were 18.9±1.3. According to the outcome of a posttraumatic period, all the patients were divided into 2 groups: A) survivors; B) deceased subjects. The normal values were used to comparatively analyze the concentrations of reproductive hormones. The time course of changes in hormone concentration was studied on postoperative days 1, 3, and 7. The hormone profile was examined by BSL test kits (USA) on a STAT Fax 2100 enzyme immunoanalyzer (Awareness Technology Inc., USA). The content of prolactin, luteinizing hormone, follicle-stimulating hormone, progesterone, 17-hydroxyprogesterone, dehydroepiandrosterone sulfate (DHEA-S), androstendione (A), testosterone (T), dihydrotestosterone, estrone, and estradiol (E) were measured. Results. The complex study of changes in the profile of 11 plasma sex hormones was first conducted in women in the posttraumat-ic period. Moreover, the typical plasma hormonal changes were elevated prolactin levels, a decrease in the concentrations of gonadotropins, and increases in some androgens, A, T, and E. The deceased women showed lower concentrations of DHEA-S and T. Analysis revealed an inverse correlation between the plasma concentration of DHEA-S and the injury severity. This change seems to suggest that an adrenal adaptation reaction is exhausted. The changes revealed in hormonal levels are of significance in understanding the pathogenesis of SCT. This may serve as a basis for the development of new therapy modalities using reproductive hormones in the postresuscitative period. Key words: severe concomitant injury, sex hormones, prolactin, luteinizing hormone, follicle-stimulating hormone, progesterone, 17-hydroxyprogesterone, androgens, estrogens.

Sex Hormones and Androgen Receptor: Risk Factors of Coronary Heart Disease in Elderly Men

To investigate the variation of sex hormone and its receptor level in elderly male patients with coronary heart disease (CHD) and to evaluate the correlations between CHD and sex hormone as well as sex hormone receptor. Altogether 139 male CHD patients (CHD group) aged 60-92 years and 400 healthy men (control group) aged 60-90 years were included in this cross sectional study. The plasma concentrations of dehydroepiandrosterone sulfate (DHEAS), total testosterone (TT), free testosterone (FT), estradiol (E2), sex hormone binding globulin (SHBG), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were measured. The androgen receptor (AR) was tested by flow cytometry. Correlations between CHD and levels of sex hormones and AR were analyzed. Compared with the control group, the levels of DHEAS, TT, FT, SHBG, and the fluorescence intensity of AR in the CHD group significantly reduced (P < 0.05), while the levels of FSH and E2 significantly increased (P < 0.01). Age was negatively correlated with TT (r = -0.28, P = 0.00) and FT (r = -0.17, P = 0.01), while it was positively correlated with SHBG (r = 0.14, P = 0.04) and E2 (r = 0.33, P = 0.00). AR fluorescence intensity was negatively correlated with systolic blood pressure (r = -0.12, P = 0.01). Binary logistic regression analysis showed that TT, SHBG, and AR were all negatively correlated with CHD (P < 0.05). Elderly male patients with CHD are found to have low levels of DHEAS, TT, FT, SHBG, and AR, while high concentrations of E2 and FSH. Low levels of TT and SHBG may be the potential risk factors of CHD in elderly men.

Chronic insulin treatment, but not chronic ACTH administration increases plasma dehydroepiandrosterone sulfate levels in adolescent male rats.

The chronic effect of daily i. m. administration of ACTH (1 U/kg bodyweight (BW), group A) and of insulin (15/kg BW, group B) on circulating dehydroepiandrosterone sulfate (DHEA-S) and testosterone was investigated in postpubertal male Wistar rats. NaCl-injected animals served as controls (group C). After at least 8 days under the respective hormone or NaCl treatment "basally" circulating testosterone levels were slightly suppressed in insulin- (1.56 +/- 0.86 ng/ml) and markedly reduced (0.54 +/- 0.21 ng/ml) in ACTH-treated rats vs. controls (2.33 +/- 0.69 ng/ml). DHEA-S levels, however, nearly doubled under chronic insulin administration (0.4 +/- 0.18 ng/ml) in comparison to the groups A (0.22 +/- 0.11 ng/ml) and C (0.23 +/- 0.09 ng/ml). Food intake and weight gain were also elevated (vs. groups A and C) as were the basal plasma corticosterone levels (vs. group C) in insulin treated rats. Following an acute ACTH stimulation test (12 U/kg BW i.m.) performed in all three treatment groups, plasma DHEA-S showed a further increase in the animals receiving insulin (0.75 +/- 0.32 ng/ml), whereas no response was detectable in rats from group A (0.27 +/- 0.13 ng/ml) or C (0.24 +/- 0.11 ng/ml). Further measurements of corticosterone or testosterone responses following endocrinological stimulation tests with supraphysiological doses of either ACTH or human chorionic gonadotropin (hCG) indicated that a lowering in the catabolism (metabolic clearance) of corticosteroids or androgens could not be the cause for the elevated DHEA-S levels seen after daily insulin injections.(ABSTRACT TRUNCATED AT 250 WORDS)

Link Between Psychological Resilience And Dehydroepiandrosterone Sulfate Against Competition Outcome In Golfers

The neurosteroid dehydroepiandrosterone sulfate (DHEA-S) has been implicated to play a role in stress coping and recovery. The role of DHEA-S in the mood adjustment against negative outcome for athletic competition has not previously been investigated in athletes. PURPOSE: To determine the link between mood adjustment and circulating DHEA-S level following a competition for elite golfers. METHODS: 14 elite golfers participated in a major national golf tournament, were subsequently divided into two groups according to their competition outcomes: made the cut (N= 8) and failed (N=6) groups. Profile of Mood States (POMS) inventory and plasma concentrations of DHEA-S and cortisol were measured 1 day before beginning of competition (baseline) and 1, 3, 5 days after their final competitions, in the morning (0800-0830) under fasted condition. RESULTS: Total mood disturbance scores and DHEA-S were not changed for the made the cut group throughout the entire observation period. DHEA-S for the failed group was significantly dropped below baseline on day 1 and remained lower for 5 days. Depression subscale of POMS for the failed group was increased only on day 1 post-competition, reflecting a situational reaction on the event. Cortisol for the made the cut group was significantly dropped only on day 1 after competition and no change was observed for the failed group. CONCLUSIONS: Although the post-competition overall mood state was well-maintained for those golfers who received negative competition outcome, plasma DHEA-S concentration was declined for 5 days, suggesting its role in the coping mechanism against psychological challenge.

The role of DHEA-S in the mood adjustment against negative competition outcome in golfers

Several lines of evidence suggest that dehydroepiandrosterone sulphate (DHEA-S) is invariably consumed following different types of acute stress, implicating its role in stress coping and recovery. The role of DHEA-S in the mood adjustment against negative outcome for athletic competition has not previously been investigated. In the current study, 14 elite golfers participating in a major national golf tournament were subsequently divided into two groups according to their competition outcomes: made the cut (n = 8) and failed to make the cut (n = 8). The Profile of Mood States (POMS) inventory and plasma concentrations of DHEA-S and cortisol were measured 1 day before the beginning of competition (baseline) and 1, 3, and 5 days after the players' final competition, in the morning (08.00–08.30 h) under fasted conditions. Results showed that the total mood disturbance scores and DHEA-S were not changed for the group that made the cut throughout the entire observation period. DHEA-S concentration for the group that failed to make the cut fell significantly below baseline values on day 1 and remained lower for 5 days. The Depression subscale of the POMS for the group that failed to make the cut was increased only on day 1 post-competition, reflecting a situational reaction to the event. Cortisol concentration for the group that made the cut fell significantly below baseline values on day 1 only after competition and no change was observed for the group that failed to make the cut. In conclusion, although the overall mood state post-competition was well-maintained for those golfers who had a negative competition outcome, plasma DHEA-S concentration was reduced for 5 days, suggesting that it has a role in the coping mechanism against psychological challenge.

Estrogen receptor alpha gene polymorphisms are associated with estradiol levels in postmenopausal women

Postmenopausal estradiol (E(2)) levels vary widely between individuals and this variation is an important determinant of diseases such as osteoporosis. It has been suggested that the estrogen receptor alpha (ESR1) gene may influence peripheral E(2) levels, but the role of common sequence variations in the ESR1 gene is unclear. In 631 postmenopausal women and 528 men from the Rotterdam Study, a population-based, prospective cohort study of individuals aged 55 years and over, ESR1 PvuII-XbaI haplotypes were determined and correlated with plasma E2 levels. In women, haplotype 1 (T-A) was significantly associated with an allele-dose-dependent decrease in E(2). After adjusting for age, body mass index, years since menopause and testosterone levels, plasma E(2) levels decreased by 1.90 pmol/l per allele copy of this haplotype (P < 0.05). Extreme genotypes, representing 23 and 27% of the population, varied by 3.93 pmol/l. No association with plasma testosterone was observed. In a subset of 446 women, no association of genotype with plasma concentrations of dehydroepiandrosterone sulfate, androstenedione or estrone was seen. In men, none of the sex hormone levels was associated with the ESR1 PvuII-XbaI haplotypes. We have demonstrated a role for genetic variations in the ESR1 gene in determining post-menopausal E(2) levels in women.

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.

Effect of caloric restriction on the 24-hour plasma DHEAS and cortisol profiles of young and old male rhesus macaques.

Although dietary caloric restriction (CR) can retard aging in laboratory rats and mice, it is unclear whether CR can exert similar effects in long-lived species, such as primates. Therefore, we tested the effect of CR on plasma levels of dehydroepiandrosterone sulfate (DHEAS), a reliable endocrine marker of aging. The study included six young (approximately 10 years) and ten old (approximately 25 years) male rhesus macaques, approximately half of the animals in each age group having undergone >4 years of 30% CR. Hourly blood samples were collected remotely for 24 hours, through a vascular catheter, and assayed for DHEAS and cortisol. Both of these adrenal steroids showed a pronounced diurnal plasma pattern, with peaks occurring in late morning, but only DHEAS showed an aging-related decline. More importantly, there was no significant difference in plasma DHEAS concentrations between the CR animals and age-matched controls. These data fail to support the hypothesis that CR can attenuate the aging-related decline in plasma DHEAS concentrations, at least not when initiated after puberty.

Estrogens in Intrahepatic Cholestasis of Pregnancy

In Brief Objective To determine whether estrogen production and excretion are impaired in gravidas with intrahepatic cholestasis. Methods Plasma and urine samples were collected from 13 women from the United States and Chile at 35–38 weeks' gestation with mild (n = 9) or severe (n = 4) intrahepatic cholestasis of pregnancy. Urinary and plasma steroid levels from women with cholestasis were compared with levels from 27 normal pregnant women within the same gestational age range. Urinary concentrations of dehydroepiandrosterone (DHEA), estrone (E1), estradiol (E2), estriol (E3), estetrol, progesterone, and 16-hydroxy-pregnenolone were measured by gas chromatography mass spectrometry, and plasma concentrations of DHEA sulfate, progesterone, unconjugated E1, unconjugated E2, unconjugated E3, sulfated E3 derivatives, glucuronidated E3 derivatives, and total E3 were measured by radioimmunoassay. Results Compared with normal pregnant women, women with cholestasis had significantly lower plasma levels of estrogens and DHEA sulfate, the precursor to placental estrogen production synthesized by the fetal adrenal gland (Hotelling-Lawley trace = 0.81; F4,19= 3.9; P = .02). The mean plasma DHEA sulfate, unconjugated E2, unconjugated E3, and total E3 concentrations were 0.271, 10.21, 9.80, and 99.53 ng/mL, respectively, in women with cholestasis compared with 0.802, 18.98, 16.28, and 145.07 ng/mL for controls. Conclusion Fetal adrenal production of DHEA sulfate, and in response, downstream placental production of estrogens, was compromised by intrahepatic cholestasis of pregnancy. Intrahepatic cholestasis of pregnancy is associated with decreased maternal plasma levels of estrogens and the estrogen precursor dehydroepiandrosterone sulfate.

Estrogens in intrahepatic cholestasis of pregnancy

Objective: To determine whether estrogen production and excretion are impaired in gravidas with intrahepatic cholestasis. Methods: Plasma and urine samples were collected from 13 women from the United States and Chile at 35–38 weeks’ gestation with mild ( n = 9) or severe ( n = 4) intrahepatic cholestasis of pregnancy. Urinary and plasma steroid levels from women with cholestasis were compared with levels from 27 normal pregnant women within the same gestational age range. Urinary concentrations of dehydroepiandrosterone (DHEA), estrone (E1), estradiol (E2), estriol (E3), estetrol, progesterone, and 16-hydroxy-pregnenolone were measured by gas chromatography mass spectrometry, and plasma concentrations of DHEA sulfate, progesterone, unconjugated E1, unconjugated E2, unconjugated E3, sulfated E3 derivatives, glucuronidated E3 derivatives, and total E3 were measured by radioimmunoassay. Results: Compared with normal pregnant women, women with cholestasis had significantly lower plasma levels of estrogens and DHEA sulfate, the precursor to placental estrogen production synthesized by the fetal adrenal gland (Hotelling-Lawley trace = 0.81; F 4,19 = 3.9; P = .02). The mean plasma DHEA sulfate, unconjugated E2, unconjugated E3, and total E3 concentrations were 0.271, 10.21, 9.80, and 99.53 ng/mL, respectively, in women with cholestasis compared with 0.802, 18.98, 16.28, and 145.07 ng/mL for controls. Conclusion: Fetal adrenal production of DHEA sulfate, and in response, downstream placental production of estrogens, was compromised by intrahepatic cholestasis of pregnancy.

Insulin resistance and advancing age: What role for dehydroepiandrosterone sulfate?

The relationship between insulin resistance and aging is still debated. This study aims to investigate the role that age-related differences in plasma dehydroepiandrosterone sulfate (DHEAS) concentration may have on insulin action. For this reason, 75 subjects (42 men and 33 women) with a wide age range (21 to 106 years) were studies. In all subjects, plasma DHEAS and total testosterone concentrations were measured and a euglycemic clamp was used, but substrate oxidation was not determined in centenarians (n = 15). Plasma DHEAS correlated with age ( r = −.77, P < .001) and whole-body glucose disposal (WBGD) ( r = .57, P < .001). After controlling for age, sex, body fat, and waist to hip ratio (WHR), the association between plasma DHEAS and WBGD was still observed ( r = .31, P < .005). Comparing subjects at the third tertile versus those at the first and second tertiles of plasma age-adjusted DHEAS concentration, the former group showed a weaker association between WBGD and age ( r = −.38, P < .05) that the latter group ( r = −.43, P < .002). The difference between the two regression lines was also significant ( P < .03). After controlling for sex, body fat, and WHR, the association between plasma DHEAS and WBGD was dependent on the age of the subjects, being strong in adults (n = 30, age < 50 years, r = .69, P < .001), weak in old subjects throughout the different age groups, the univariate association between plasma DHEAS and WBGD was present in females ( r = .43, P < .01) but not in males ( r = .17, P < .32). Plasma total testosterone and insulin-like growth factor-1 (IGF-1) concentrations declined with advancing age and were significantly correlated with DHEAS and WBGD. In a multivariate analysis with WBGD as the dependent variable, a model including age, sex, body fat, WHR, DHEAS, total testosterone, and IGF-1 explained 66% of WBGD variability, with DHEAS significantly and independently associated with WBGD ( P < .004). In conclusion, the negative relationship between advancing age and insulin action seems related to plasma DHEAS concentration. Differences in plasma total testosterone and IGF-1 concentrations may provide a further contribution to the relationship between DHEAS and WBGD.

Signs of testicular insufficiency in adrenomyeloneuropathy and neurologically asymptomatic X‐linked adrenoleukodystrophy: a retrospective study

X-linked adrenoleukodystrophy (X-ALD) is characterized by central nervous system demyelination, and impaired steroidogenesis in the adrenal cortex and testis. Most patients develop adrenocortical insufficiency. We studied retrospectively the frequency and severity of testicular dysfunction in 26 men with X-ALD. Twenty-one had adrenomyeloneuropathy and five patients were neurologically asymptomatic. In addition to obtaining a routine history and physical examination, we studied plasma levels of testosterone, sex hormone binding globulin, the free androgen index, and the plasma concentrations of dehydroepiandrosterone-sulphate, LH and FSH. In a subset of patients, the testosterone response to hCG and the LH and FSH responses to GnRH were also determined. Clinical signs of gonadal dysfunction were manifested by diminished libido (46%), largely overlapping with erectile dysfunction (58%), and failure of the testes to descend (15%). Physical examination revealed diminished body sexual hair (50%), gynaecomastia (35%), and small testes (12%). Laboratory studies showed low plasma total testosterone levels in 12%, and an insufficient increase after stimulation with hCG in 88% (15 of 17 patients tested). Plasma LH concentration was increased in 16%, and the plasma FSH level was elevated in 32%. The response of LH concentrations to GnRH stimulation was abnormally high in 47% (nine of 19 patients studied), and the response of FSH levels was too low in 16% (three of 19 patients tested). In conclusion, in a retrospective study of 26 men' with X-ALD, in 20 some signs of clinical hypogonadism were found. Plasma testosterone values were generally in the normal range, but upon testing of the hypothalamo-pituitary-testis axis some abnormalities became apparent.

Effects of castration on early postnatal development of male accessory sex glands in the domestic pig.

In the neonatal pig there is a remarkable production of steroids by the testes for the first few weeks after birth. Several androgens and estrogens reach a peak at about one month of age. In order to gain an understanding of the significance of this early steroid secretion we examined the effect on accessory sex glands of removal of the testes before the peak in these compounds would have occurred. Pigs were castrated (n = 38) at 2-3 weeks of age, with littermates serving as intact controls (n = 33). Animals were killed at ages ranging from 4-12 weeks. Blood samples were taken and both bulbourethral (BU) and vesicular glands (VG) were removed, as well as the testes of intact males. Organ pairs were weighted and samples fixed for histological examination. Plasma samples were stored at -20 degrees C until assayed, without extraction, for testosterone, dehydroepiandrosterone sulfate (DHEAS) and estrone sulfate (E1S) by radioimmunoassay. Of the hormones measured, plasma DHEAS concentrations were highest, but variable over the time period (304.2 and 75.6 nmol/l; 87.7 and 21.8 ng/ml at 5 and 12 weeks respectively). E1S declined steadily from 76.6 to 5.8 nmol/l (20.7 to 1.56 ng/ml). Testosterone levels were lowest but rose from 2.67 to 9.54 nmol/l (0.77 to 2.75 ng/ml). No steroids were clearly detectable in samples from castrated males. Testes weights (wt) increased fourfold, as did body wt for both intact and castrate males. Both BU and VG showed absolute increase in wt (3.5x and 5x respectively) in intact males, and each was about 2.8x greater than in castrates (mg/kg body wt). Histological sections were markedly distinctive for both BU and VG between intact and castrate animals, and a lack of developmental changes in both glands was noted in the castrates. Our findings provide clear evidence of an influence of the testes on accessory sex glands in the early postnatal life of the pig.

Longitudinal study of adrenal steroids in a cohort of HIV-infected patients with hemophilia

The objective of the study was to relate plasma dehydroepiandrosterone sulfate (DHEA-S) concentrations to the progression of HIV infection in individual HIV-infected men with hemophilia and to obtain information on the cause of DHEA-S alterations. Blood samples were obtained from 16 men with hemophilia; in 9 men serial samples were available for up to 11 years after HIV-1 infection. Control samples were obtained from men of comparable ages without hemophilia or HIV infection. Measurements were made of CD4 + cell counts, plasma adrenocorticotropic hormone (ACTH), cortisol, DHEA, DHEA-S, and prolactin. Before HIV infection, men with hemophilia had significantly lower plasma levels of DHEA-S than control men. After infection, 3 of 9 subjects studied serially had little or no change in plasma DHEA-S levels or in CD4 + cell counts over 11 years. Four of the 9 in whom AIDS developed had progressive decreases in plasma DHEA-S concentrations that, in some cases, preceded a precipitous fall in CD4 + cell counts. Major decreases in plasma DHEA-S levels before falls in CD4 + counts were observed in 2 other subjects who had other severe illnesses. None of the decreases in DHEA-S levels were associated with decreased concentrations of plasma cortisol, ACTH, or prolactin. We conclude that plasma DHEA-S is an indicator of general health rather than a specific indicator for progression of HIV. The decrease in plasma DHEA-S is not related to ACTH stimulation of the adrenal gland or to cortisol secretion, but it may be related to cytokines that can inhibit 17-hydroxylation of DHEA-S precursors.