Circulating nitric oxide levels increase after anti-androgen treatment in male-to-female transsexuals.
Circulating nitric oxide is produced by the vascular endothelium under the influence of the sex steroid milieu and shows gender difference. Since data on hormonal manipulation in males are scant, the present study was designed to evaluate nitric oxide levels before and after anti-androgen treatment in young male-to-female (MF) transsexuals. Fifteen MF transsexuals aged 23.7 +/- 1.3 yr, with normal testicular volume and normal body mass index were studied. Twenty adult males aged 28.2 +/- 2.4 yr served as controls. A low nitrate diet was administered to all subjects throughout the study, starting 15 days before the beginning. Blood samples were drawn from all subjects on day 0; flutamide 750 mg/day was then administered to transsexuals for 30 days, and another sample was taken on day 30. In all subjects the concentration of nitrite plus nitrate (NOx), two stable compounds into which nitric oxide spontaneously decomposes, was determined; also total testosterone (T) and free testosterone (fT), 17(beta)estradiol (E2), SHBG, delta4-androstenedione (A), DHEAS, 17-hydroxy-progesterone (OHP), LH, FSH and PRL were assayed. All hormones determined in controls and transsexuals were comparable at the beginning of the study. NOx was also comparable in controls (11.0 +/- 1.0 microM/l) and transsexuals (11.1 +/- 1.2 microM/l) and did not significantly correlate with any of the hormones assayed. After 30 days of flutamide administration, LH, T, fT, A and E2 increased; DHEAS decreased, while FSH, SHBG and PRL were unchanged; NOx rose significantly (18.7 +/- 1.7 microM/l; p < 0.05), and its percentage increase with respect to pre-treatment levels correlated with that of E2 (R = 0.77; p < 0.01). Healthy males and MF transsexuals do not differ in terms of sex hormones and NOx levels. In neither group is NOx significantly correlated to any sex hormone assayed. Treatment with flutamide in MF transsexuals elicits an increase in androgens, which are not biologically active because of the androgen receptor blockade, and an increase in the estrogenic milieu, which correlates with the increase in NOx.
Valenti
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DiSEM, Chair of Endocrinology, University of Genoa, Genoa, Italy.
Fazzuoli
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Giusti
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D000293:Adolescent; D000328:Adult; D000726:Androgen Antagonists / Q000627:therapeutic use*; D005260:Female; D005485:Flutamide / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000097:blood*; D009573:Nitrites / Q000097:blood; D014189:Transsexualism / Q000097:blood* / Q000188:drug therapy*
D000726:Androgen Antagonists; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D005485:Flutamide