Ronde, W.A. de

Aromatase inhibitors in men: Effects and therapeutic options (Article)

2011-06-21T00:00:00Z

Aromatase inhibitors effectively delay epiphysial maturation in boys and improve testosterone levels in adult men Therefore, aromatase inhibitors may be used to increase adult height in boys with gonadotropin-independent precocious puberty, idiopathic short stature and constitutional delay of puberty. Long-term efficacy and safety of the use of aromatase inhibitors has not yet been established in males, however, and their routine use is therefore not yet recommended.

Effects of oestradiol on gonadotrophin levels in normal and castrated men (Article)

2009-12-01T00:00:00Z

Context Testosterone inhibits gonadotrophin release in men either directly or after aromatization to oestradiol. We hypothesized that in males the androgen receptor-mediated effect of testosterone on LH release is negligible relative to that of oestradiol. Objective To compare the effect of experimentally induced variations of plasma oestradiol levels on LH levels in normal (physiological testosterone levels) and castrated men (very low testosterone levels). Design Prospective, open label, intervention. Subjects and interventions We suppressed endogenous oestradiol in 10 young men with letrozole 2·5 mg once daily. In these men and in 10 young healthy castrated men, we restored plasma oestradiol levels with oestradiol patches (first week 100 μg/day, second week 50 μg/day, third week 25 μg/day and fourth week no oestradiol patch). Measurements The effect of the intervention on plasma levels of LH were monitored and compared between the groups. Results With the intervention, the mean plasma oestradiol level in the two groups varied from supraphysiological to below the lower reference range. Levels of LH mirrored plasma oestradiol levels in both the groups, as did testosterone in the intact group. Despite similar oestradiol levels, mean levels of LH were significantly higher in the castrated group compared to the intact group for all doses of oestradiol, and supraphysiological levels of oestradiol were unable to suppress LH into the physiological range in the castrated group. Conclusions Physiological plasma oestradiol levels have a substantial suppressive effect on LH in men. However, low-normal testosterone levels are a prerequisite for suppression of LH into the normal range.

The association of sex hormone levels with quantitative ultrasound, bone mineral density, bone turnover and osteoporotic fractures in older men and women (Article)

2007-08-01T00:00:00Z

Objective: Sex steroids play an important role in the maintenance of bone health. Association studies on sex steroids and fractures are not consistent. Our objective was to examine whether serum oestradiol (E2) and testosterone (T) are associated with quantitative ultrasound (QUS), bone mineral density (BMD), bone turnover markers and fracture incidence. Design: The Longitudinal Ageing Study Amsterdam (LASA), an ongoing cohort study including 623 men and 634 women, aged 65-88 years. Measurements: Serum levels of E2, T, SHBG, albumin, bone turnover markers serum osteocalcin (OC) and urinary deoxypyridinoline (DPD/Cr) were measured. QUS of the heel and BMD of the hip were assessed, and a 6-year fracture follow-up was performed. Results: Men in the lowest quartile (Q1) of bioavailable E2 (bioE2) had higher levels of bone turnover and lower BMD (B = -0.09, P < 0.01) and QUS than men in the highest quartile (Q4). This also applied to Q1 of bioT. Women in Q1 of bioE2 had higher levels of bone turnover and lower BMD (B = -0.07, P < 0.01) and QUS than women in Q4. In men and women, levels of bioE2 below the median were associated with an increased risk of osteoporotic fractures after all adjustments [hazard ratio (HR) 1.53, 95% confidence interval (CI) 1.02-2.29]. In men, univariate analysis revealed that low bioT was associated with an increased fracture risk (HR 1.91, 95% CI 1.03-3.56), but after adjustment for age, this association was no longer significant. Conclusions: Low levels of bioE2 and bioT were found to be associated with high bone turnover, low QUS and BMD and high risk of osteoporotic fractures in both men and women.

Gender differences in vascular disease: Not a simple explanation (Article)

2007-06-01T00:00:00Z

A direct approach to the estimation of the origin of oestrogens and androgens in elderly men by comparison with hormone levels in postmenopausal women. (Article)

2005-02-01T00:00:00Z

OBJECTIVE: The origin of oestrogens in men is only partly understood. From infusion studies with radioactively labelled hormones, we know that oestradiol (E2) and oestrone (E1) are either directly secreted by the testes and adrenal glands or peripherally produced from testicular or adrenal androgens. DESIGN AND METHODS: We determined E2, E1, androstenedione, testosterone and dehydroepiandroster-one sulphate (DHEAS) in 292 elderly men and 367 postmenopausal women. We considered post-menopausal women as men without testes, assuming that the postmenopausal ovary is not endocrinologically active and that the testes do not contribute to circulating levels of DHEAS. Subjects were stratified by DHEAS levels to adjust for differences in DHEAS levels between sexes. For men and women separately, mean levels of E2, E1, androstenedione and testosterone were calculated per DHEAS stratum. The relative direct and indirect contributions of the testes to steroid levels in men were calculated by the formula [(C(m) - C(f))/C(m)] x 100%, in which C(m) and C(f) represent the mean concentrations of the steroid in men and women respectively. RESULTS: The relative contributions (%) of the testes to hormone levels per DHEAS stratum (<2, 2-4, 4-6 and >6 micromol/l) respectively were, for E2, 72%, 60%, 52% and 44%; for E1, 54%, 47%, 35% and 34%; for androstenedione, 14%, 4%, 12% and 0%; and, for testosterone, 88%, 88%, 87% and 83%. CONCLUSIONS: We conclude that in elderly men dependent on DHEAS levels, 44-72% of E2 and 34-54% of E1 originate directly or indirectly from the testes.

Associations of sex-hormone-binding globulin (SHBG) with non-SHBG-bound levels of testosterone and estradiol in independently living men. (Article)

2005-01-01T00:00:00Z

Results of in vitro experiments indicate that with increasing concentrations of SHBG, testosterone (T) is preferentially bound to SHBG in comparison with estradiol (E2). In these studies, the ratio of non-SHBG-bound E2 (non-SHBG-E2) to non-SHBG-T increased with increasing levels of SHBG. SHBG has consequently been regarded as an estrogen amplifier. In this cross-sectional study in 399 men aged between 40 and 80 yr we tested whether higher levels of SHBG are associated with a higher estrogen/androgen ratio in vivo. The mean T level of these men was in the eugonadal range [536 +/- 152 ng/dl (18.6 +/- 5.26 nmol/liter), mean +/- sd]. With increasing SHBG levels the non-SHBG-bound fraction of T decreased from 80 to 36% and that of E2 from 89 to 53%. Higher levels of SHBG were associated with higher levels of both total T [regression coefficient (beta) after adjustment for age and body mass index, 286 +/- 15.8; P < 0.001] and total E2 (beta = 4.47 +/- 0.90; P < 0.001). However, SHBG levels were negatively related with levels of non-SHBG-E2 (beta = -1.78 +/- 0.69; P < 0.001), whereas there was a positive association between levels of SHBG and non-SHBG-T (beta = 32.0 +/- 9.78; P = 0.001). Furthermore, we observed a negative relationship between SHBG levels and the E2/T ratio of either total (beta = -0.016 +/- 0.002; P < 0.001) or non-SHBG-bound (beta = -0.011 +/- 0.002; P < 0.001) hormone. Therefore, we conclude that in eugonadal men, higher SHBG levels are associated with lower levels of non-SHBG-E2 but slightly higher levels of non-SHBG-T. This means that SHBG cannot be regarded as an estrogen amplifier in eugonadal men.

Endogenous sex hormones, sex hormone-binding globulin, and the risk of incident vertebral fractures in elderly men and women: the Rotterdam Study. (Article)

2004-07-01T00:00:00Z

In an age-matched, case-control study, we investigated the association between endogenous sex steroid hormones and incident vertebral fractures in both elderly men and women (aged 67.7 +/- 6.8 yr). Drawn from the Rotterdam Study, participants required radiographs of the lumbar spine at both baseline and follow-up (average time of follow-up, 6.5 yr) and frozen blood samples, taken at baseline. One hundred and seventy-eight men (45 cases) and 454 women (115 cases) were thus selected. Serum estradiol, SHBG, testosterone, and insulin were measured, along with bone mineral density at both spine and hip. Women in the lowest tertile of serum estradiol (< or =15.5 pmol/liter) had a 2.1 times increased risk (95% confidence interval, 1.3-3.5) of incident vertebral fractures, independently of bone mineral density measured at either site. SHBG levels in the lowest two tertiles were associated with a 50% reduction in incident vertebral fracture risk. Women with a combination of both low estradiol and high SHBG had a 7.8 times higher risk of an incident vertebral fracture (95% confidence interval, 2.7-22.5; P < 0.001), adjusted for age and weight. This increased risk did not change when non-SHBG-bound estradiol was used instead of total estradiol. For men, no clear association was found, possibly due to insufficient power. No clear association between testosterone and incident vertebral fractures was observed in either men or women.

Hemodynamic and biochemical effects of the AT1 receptor antagonist irbesartan in hypertension (Article)

1995-01-01T00:00:00Z

We studied the hemodynamic, neurohumoral, and biochemical effects of the novel angiotensin type 1 (AT1) receptor antagonist irbesartan in 86 untreated patients with essential hypertension on a normal sodium diet. According to a double-blind parallel group trial, patients were randomized to a once-daily oral dose of the AT1 receptor antagonist (1, 25, or 100 mg) or placebo after a placebo run-in period of 3 weeks. Randomization medication was given for 1 week. Compared with placebo, 24-hour ambulatory blood pressure did not change with the 1-mg dose, and it fell (mean and 95% confidence interval) by 7.0 (4.2-9.8)/6.1 (3.9-8.1) mm Hg with the 25-mg dose and by 12.1 (8.1-16.2)/7.2 (4.9-9.4) mm Hg with the 100-mg dose. Heart rate did not change during either dose. With the 25-mg dose, the antihypertensive effect was attenuated during the second half of the recording, and with the 100-mg dose, it was maintained for 24 hours. Baseline values of renin and the antihypertensive response to the 25- and 100-mg doses were well correlated (r = .68, P < .01). Renin did not change with the 1-mg dose, but it rose threefold to fourfold with the 25-mg dose and fourfold to fivefold with the 100-mg dose 4 to 6 hours after administration. With the 100-mg dose, renin was still elevated twofold 24 hours after dosing. The changes in renin induced by the AT1 receptor antagonist were associated with parallel increments in angiotensin I and angiotensin II. Aldosterone, despite AT1 receptor blockade, did not fall.