The effects of the aromatase inhibitor anastrozole on bone metabolism and cardiovascular risk indices in ovariectomized, androgen-treated female-to-male transsexuals.

OBJECTIVE: Cases of men with estrogen resistance and aromatase deficiency have highlighted the effects of estrogens on bone metabolism, the cardiovascular system and biochemical variables of the metabolic syndrome. In eugonadal men, administration of an aromatase inhibitor induces a substantial elevation of LH and testosterone due to the decreased negative-feedback signal of estrogen and may thwart the interpretation of results. As there is no gonad for LH to act on, no increase of serum testosterone concentration will be seen in female-to-male transssexuals. The aim of this study was to investigate the effects of estrogen deprivation on bone metabolism and vascular parameters without the interference of counter-regulatory effects as seen in eugonadal men. DESIGN: Thirty ovariectomized female-to-male transsexuals participated in this double-blind, randomized trial. During 3 months, subjects received the aromatase inhibitor anastrozole 1 mg/day (n = 16) or a placebo (n = 14) in addition to parenteral testosterone esters (Sustanon 250 every 2 weeks). RESULTS: Serum 17beta-estradiol (E(2)) concentration fell significantly from 134.0 +/- 78.8 to 77.7 +/- 130.6 pmol/l compared with placebo (P < 0.01). LH and FSH levels rose without the rise of testosterone levels observed in eugonadal men. Within the placebo group, E(2) remained at baseline levels. Of the endpoint variables measured (bone metabolism and vascular parameters) no significant changes were observed compared with placebo, or within the anastrozole-treated group. CONCLUSIONS: These results may indicate that the negative effects of estrogen deprivation in men only become manifest when the concentration falls below the levels induced by our intervention with anastrozole (77 pmol/l). This assumption is supported by the observation in the anastrozole group that, although effects of the reduction of serum E(2) on vascular parameters could not be demonstrated in subjects as a group, there was a correlation between individual serum E(2) and several vascular parameters.

Docosahexaenoic acid concentrations are higher in women than in men because of estrogenic effects.

BACKGROUND: During pregnancy there is a high demand for docosahexaenoic acid (DHA), which is needed for formation of the fetal brain. Women who do not consume marine foods must synthesize DHA from fatty acid precursors in vegetable foods. OBJECTIVE: We studied sex differences in DHA status and the role of sex hormones. DESIGN: First, DHA status was compared between 72 male and 103 female healthy volunteers who ate the same rigidly controlled diets. Second, the effects of sex hormones were studied in 56 male-to-female transsexual subjects, who were treated with cyproterone acetate alone or randomly assigned to receive oral ethinyl estradiol or transdermal 17beta-estradiol combined with cyproterone acetate, and in 61 female-to-male transsexual subjects, who were treated with testosterone esters or randomly assigned for treatment with the aromatase inhibitor anastrozole or placebo in addition to the testosterone regimen. RESULTS: The proportion of DHA was 15 +/- 4% (x +/- SEM; P < 0.0005) higher in the women than in the men. Among the women, those taking oral contraceptives had 10 +/- 4% (P = 0.08) higher DHA concentrations than did those not taking oral contraceptives. Administration of oral ethinyl estradiol, but not transdermal 17beta-estradiol, increased DHA by 42 +/- 8% (P < 0.0005), whereas the antiandrogen cyproterone acetate did not affect DHA. Parenteral testosterone decreased DHA by 22 +/- 4% (P < 0.0005) in female-to-male transsexual subjects. Anastrozole decreased estradiol concentrations significantly and DHA concentrations nonsignificantly (9 +/- 6%; P = 0.09). CONCLUSION: Estrogens cause higher DHA concentrations in women than in men, probably by upregulating synthesis of DHA from vegetable precursors.

Estimating the contribution of the prostate to blood dihydrotestosterone.

The prostate strongly expresses type 2 5 alpha-reductase, which avidly converts on entry most testosterone (T) to 5 alpha-dihydrotestosterone (DHT). However, the quantitative contribution of the prostate to blood DHT is uncertain. We evaluated prostatic contribution to blood DHT by comparing the blood DHT concentrations in androgen-deficient patients with or without a prostate while they were receiving standard dose of T replacement. Androgen-deficient males (ADM) and female to male (F2M) transsexuals were studied in 2 centers, with both groups receiving either testosterone ester injections (250 mg mixed T esters) every 1 wk (Amsterdam) or 800 mg subdermal T implantation (Sydney). Among 39 Dutch patients, F2M (n = 21) were younger and smaller in physique than ADM (n = 18). One week (+/-1 d) after an injection, plasma DHT concentrations were 1.6 +/- 0.2 (F2M) vs. 1.4 +/- 0.2 (ADM) nmol/liter (P = 0.47), but the postinjection time interval to blood sampling was shorter in F2M (5.9 +/- 0.4 vs. 7.2 +/- 0.3 d; P = 0.01). Covariance adjustment for time since last injection, age, and physique did not change the lack of significant difference in postinjection plasma DHT concentration. The rapid and wide excursions in plasma T concentrations after an im T ester injection make the timing of blood sampling critical. To remove confounding by this variable, the experiment was repeated at a second site in similar patients, but using a depot T that achieves steady-state delivery for prolonged periods. Among 29 Australian patients, before and 1 month after subdermal implantation of 800 mg T, plasma DHT concentrations were not significantly different between groups [F2M, 1.1 +/- 0.1 (n = 14); ADM, 1.3 +/- 0.1 (n = 15); P = 0.28]. Correction for covariates, including age, height, weight, body surface area, and body mass index, did not influence the lack of significant difference between treated groups. As both modes of T administration yielded similar plasma DHT concentrations regardless of the presence of a prostate, this study indicates that the normal human prostate is not a major contributor to circulating blood DHT concentrations.

Atypical MEN type 2B associated with two germline RET mutations on the same allele not involving codon 918.

A kindred was diagnosed with atypical MEN type 2B characterized by medullary thyroid cancer and mucosal neurilemmomas in multiple family members. Mutation analysis revealed a double RET germline mutation, Val804Met and Ser904Cys, in affected individuals. The clinical phenotype, the functional effect of the mutations, and the clinical implications of our findings are discussed.