Higher Dehydroepiandrosterone Sulfate Levels Research Articles

Gonadotropin, Prolactin and Thyrotropin Pituitary Secretion after Exogenous Dehydroepiandrosterone-Sulfate Administration in Normal Women

The effect of exogenous dehydroepiandrosterone-sulfate (DHAS) on luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (PRL) and thyroid-stimulating hormone (TSH) pituitary secretion was studied in 8 normal women during the early follicular phase. The plasma levels of these hormones were evaluated after gonadotropin-releasing hormone (GnRH)/thyrotropin-releasing hormone (TRH) stimulation performed after placebo or after 30 mg DHAS i.v. administration. The half-life of DHAS was also calculated on two subjects; two main components of decay were detected with half-times of 0.73-1.08 and 23.1-28.8 h. The results show an adequate response of all hormones to GnRH or TRH tests which was not significantly modified, in the case of LH, FSH and PRL, when performed in the presence of high levels of DHAS. However, the TSH response to TRH was significantly less suppressed (p less than 0.05) (39%) after DHAS administration than during repeated TRH stimulation without DHAS (51%). The data support the hypothesis that DHAS does not affect LH, FSH and PRL secretion, while TSH seemed to be partially influenced.

The influence of body weight on lipoprotein lipids in patients with polycystic ovary syndrome

Lipoprotein lipid and androgen profiles were compared after a 12-hour fast that involved 13 women with polycystic ovary syndrome and 13 who did not have the syndrome. All women were matched for percent ideal body weight. As expected, patients with polycystic ovary syndrome had significantly higher luteinizing hormone--to--follicle-stimulating hormone ratios, higher testosterone levels, higher free testosterone levels, higher dehydroepiandrosterone sulfate levels, and lower testosterone-estradiol-binding globulin binding capacity than the other women. Patients with polycystic ovary syndrome had significantly higher mean serum triglyceride levels, very-low-density lipoprotein cholesterol levels, and lower high-density lipoprotein cholesterol levels. Differences in body weight do not explain the male pattern of lipoprotein lipid concentrations in women with polycystic ovary syndrome. The association of hyperandrogenism with lipoprotein lipid abnormalities should be evaluated in regard to the influence of endogenous sex steroids on differences between the sexes in incidence of cardiovascular disease.

Blood pressure, body fat, and dehydroepiandrosterone sulfate variation in adolescence.

Several significant interrelations among variation in blood pressure, body fat, and adrenal androgen levels, as assessed by serum dehydroepiandrosterone sulfate concentrations, were found in black male and female adolescents, aged 12 to 16 years. In girls, high levels of dehydroepiandrosterone sulfate were associated with significantly higher levels of blood pressure (alpha = 0.05), even after adjusting for the significant association between increased levels of dehydroepiandrosterone sulfate and body fat. The increased body fat (i.e., body mass index) found with higher levels of dehydroepiandrosterone sulfate in girls was related to significantly greater (alpha = 0.05) accumulations of fat in the upper trunk, as opposed to the limb. In boys, high levels of serum dehydroepiandrosterone sulfate, low body mass index, and significantly higher blood pressure were interrelated (alpha = 0.05). In addition to the interaction of increased body mass index or body fat and increased levels of dehydroepiandrosterone sulfate in association with higher blood pressure, high levels of the adrenal androgen, even in boys with low body mass index, were associated independently with relatively higher blood pressure. Body proportion analyses for these boys indicated that they were tall and thin, in contrast to the other boys with low body mass index, who were generally short and thin.

Abnormal androgen and oestrogen metabolism in men with steroid sulphatase deficiency and recessive X-linked ichthyosis.

Serum levels of sex hormone binding globulin (SHBG), testosterone, free testosterone, dihydrotestosterone, androstenedione, dehydroepiandrosterone sulphate, oestradiol, oestrone, oestrone sulphate, FSH, and LH were measured in 20 steroid sulphatase-deficient men with recessive X-linked ichthyosis and in normal men. The serum oestrone sulphate level was significantly higher than normal in the patients (P less than 0.0001). In affected men, there was a tendency towards higher dehydroepiandrosterone sulphate levels and no decline with age was seen in the patients as opposed to normal men (interaction: P less than 0.025). Serum androstenedione, and oestradiol levels were lower than normal in the patients (P less than 0.0005 and P = 0.055, respectively), while their LH level was higher than normal (P less than 0.0005). The serum levels of SHBG, total and free testosterone, dihydrotestosterone, oestrone, and FSH were not significantly different from normal in the icthyotic patients. We suggest that the observed abnormalities in these patients are a consequence of the enzyme deficiency which severely impairs the ability of tissues to hydrolyse steroid sulphates.

123 LATE ONSET 21-OH-DEFICIENCY (21-OHD) CAN BE MISDIAGNOSED AS “TYPICAL PREMATURE PUBARCHE” (PP) IN CHILDHOOD

The isolated and early growth of pubic hair (PH) is often associated with slight advance in bone age (BA) and statural age (SA). Diagnosis of PP is classically made on high levels of dehydroepiandrosterone sulfate (DS). In this context, measuring only DS can be misleading, as we observed in 5 girls. The first 3 were seen at 5.5 yr for PP with normal SA ; their basal levels of DS (μg/dl) were indeed very high for age (135, 40 and 73 respectively). The last 2 girls were seen at 6-8 yr for early onset of PH (5-7 yr) and tall stature ; DS levels (63-94 and 86-158) were also very high. BA was advanced but not so drastically when reported to SA, except in girl n° 3. 21-OHD, suspected only in girl n° 5, was recognized in all girls on the systematic or retrospective (n° 1) measurement of 17-OH-progesterone (OHP) levels (ng/dl) which were variably elevated between girls (287 to 5372), but even more variable between days in each of them (ex: 87 to 2731 in n° 4). In girls n° 1, 3 and 4, OHP as well as DS were normally suppressed with Dexamethasone. Girl n° 1, misdiagnosed as PP until 16 yr, had normal menses from 12.7 yr onwards, still had high DS (362) and OHP (1246) levels at 18 yr but refused Rx. In girls n° 4 and 5, now treated for 2-3 yr, DS returned slowly to normal for age. In both girls, HLA-typing revealed the B14 antigen. In conclusion: 1) DS levels are high from a very young age in children with late onset or partial 21-OHD, in contrast to what observed in CAH newborns (Ped. Res., 1982, 16, 10); 2) Because 21-OHD can mimic the clinical and biological symptoms of “classical” PP, OHP should be measured systematically in children with PP.

Multiple androgenic abnormalities, including elevated free testosterone, in hyperprolactinemic women.

To investigate the basis of the hirsutism and elevated plasma dehydroepiandrosterone (DHA) and/or DHA sulfate (DHAS) in hyperprolactinemic women, we measured androgen binding parameters and an extensive profile of plasma androgens in normal (NL) and hyperprolactinemic women (HYPRL). ACTH tests and dexamethasone (dex) suppression tests were performed in subgroups. Free testosterone levels were higher in HYPRL (13.1 +/- 23.3 vs. 7.18 +/- 0.72 pg/ml; P less than 0.025), although total testosterone was comparable. This disparity was related to plasma testosterone-estradiol-binding globulin (TEBG) levels being one third lower in HYPRL (mean +/- SE, 27.4 +/- 4.0 nM) than in NL (41.2 +/- 3.7 nM; P less than 0.0125). Less striking elevations of plasma DHAS, androstenedione, and 11-deoxycortisol were found in HYPRL. Plasma total dihydrotestosterone [17 beta-hydroxy-5 alpha-androstan-3-one (tDHT)] was nearly 30% lower in HYPRL (11.2 +/- 2.6 ng/dl) than in NL (15.6 +/- 1.3 ng/dl; P less than 0.025), whereas free DHT was normal. Ratios of tDHT to precursors were lower in HYPRL (P less than 0.005). After ACTH stimulation, hyperresponsiveness of 17-hydroxyprogesterone and androstenedione were observed. Apparent adrenal enzyme efficiencies, judged from post-ACTH product to precursor ratios, were normal in HYPRL with one exception: the ratio of tDHT to total testosterone at 4 h was lower (P less than 0.05). Dex suppression normalized androgens and obliterated the abnormal tDHT to precursor ratios. These findings suggest an ACTH dependency of the abnormalities. In summary, we find that about 40% of HYPRL have an androgenic abnormality, and the most characteristic abnormality is an elevated free testosterone level (abnormal in 43%). Depressed TEBG and high DHAS levels were found with lesser frequency (19-21%). The plasma tDHT concentration was low, both in absolute terms and relative to its precursors. Dex suppressibility of the hyperandrogenemia was also observed. We postulate that PRL may exert multiple effects on steroid secretion and metabolism. Possibilities include the inhibition of the TEBG level.

Differential response to adrenocorticotropin hormone stimulation in polycystic ovarian disease with high and low dehydroepiandrosterone sulfate levels

The relative contributions of the ovary and the adrenal gland to androgen overproduction in polycystic ovarian disease (PCOD) remain controversial. In this investigation, patients with proven PCOD were divided into two groups, (1) those with low dehydroepiandrosterone sulfate (DHEAS) levels and (2) those with high DHEAS levels, and compared with controls for their response to adrenocorticotropin hormone (ACTH) stimulation. Significant differences in weight, degree of menstrual disturbance, and basal progesterone levels distinguished the two groups with PCOD. Although no discrete enzyme block was unmasked by ACTH, marked differences in steroid production ratios were apparent between the low and high DHEAS PCOD groups. These results suggest that in PCOD with high DHEAS (1) substantial differences in adrenal steroidogenesis pathways occur, (2) increased progesterone as well as inappropriate estrogen feedback may contribute to chronic anovulation, and (3) serum DHEAS levels may be a helpful screen in discerning those patients who have a significant adrenal component to their hyperandrogenism and may benefit from adrenal suppression alone or in combination.

Prenatal diagnosis of X-linked ichthyosis

Prenatal diagnosis of X-linked ichthyosis in a case of steroid sulfatase deficiency was made at 16 weeks by the demonstration of (1) high levels of dehydroepiandrosterone sulfate in amniotic fluid; (2) gross deficiency of steroid sulfatase activity in cultured amniotic fluid cells; (3) very low estriol concentrations in maternal blood and urine; (4) increased maternal plasma dehydroepiandrosterone sulfate; and (5) a characteristic maternal urinary steroid profile with greatly increased levels of 16α-hydroxydehydroepiandrosterone. The latter method is particularly useful since it requires no invasive procedures for the patient and is very specific.

The modulating role of obesity and 17 beta-estradiol (E2) on bound and unbound E2 and adrenal androgens in oophorectomized women.

17 beta-Estradiol (E2) pellet replacement therapy for oophorectomized women has been shown to be safe and effective. Some investigators have advocated the addition of testosterone (T) pellets for oophorectomized women. This study was carried out to measure the level of androgens in oophorectomized women with and without E2 pellets. The possible modulating role of E2 upon adrenal androgens was investigated as well as the effects of obesity on bound and unbound serum levels of E2 and T. Seven obese patients and eight nonobese normal patients with E2 pellets were compared to nine oophorectomized age- and weight-matched control women not receiving estrogen. Obese patients had higher levels of androstenediol (Adiol) and androstenedione (A) than nonobese patients, yet compared to oophorectomized controls, nonobese patients had higher levels of dehydroepiandrosterone sulfate (DHEA-S) and Adiol. As a group, patients with E2 pellets had higher levels of DHEA-S, Adiol A, and unbound T compared to oophorectomized controls, and their Adiol and total and unbound T levels were similar to those of premenopausal females. Obese patients had lower levels of total E2, yet a higher percentage of unbound E2, resulting in unbound E2 levels which were similar to those of the nonobese women. Unbound T was higher in obese patients compared to the nonobese women and oophorectomized controls. In conclusion, these data suggest that 1) there may be a modulating role of E2 on adrenal androgens exemplified by an increased serum level of delta 5-3 beta-ol androgens in women with E2 pellets, 2) supplemental T implants for oophorectomized women may not be necessary, and 3) obese women with pellets have higher levels of Adiol, A, and unbound T then nonobese women and therefore have a higher ratio of androgen to estrogen.