Effect of Testosterone Administration on Serum and Urine Kallikrein Concentrations in Female-to-Male Transsexuals

Abstract

Background: Concentrations of human tissue kallikreins (hKs), a group of 15 secreted serine proteases found in many tissues, are modulated by steroid hormones in cancer cell lines. To gain insight into in vivo kallikrein regulation we measured kallikrein concentrations in serum and urinary tissue in female-to-male transsexuals before and after testosterone administration. Methods: We collected blood and urine samples before treatment and after 4 and 12 months from 28 female-tomale transsexuals who received 250 mg of testosterone esters intramuscularly every 2 weeks. We used ELISA assays to measure multiple kallikreins in serum and urine. Results: After testosterone administration, serum testosterone concentrations increased by ϳ15-fold. Serum kallikrein concentrations increased dramatically for hK3 (prostate-specific antigen) and increased moderately for hK2, hK5, hK6, hK7, hK8, hK10, and hK11. In urine, we noted major increases for hK3 and hK2 only. For all other kallikrein concentrations, we observed no considerable changes. Conclusions: We conclude that, in serum and urine of female-to-male transsexuals after testosterone adminis-

Prostate-Specific Antigen as a Marker of Hyperandrogenism in Women and Its Implications for Antidoping

“…Urinary concentrations of PSA increased from 5.4 ng/L before treatment to 1604 ng/L after treatment, suggesting that this parameter is even more sensitive than serum PSA as a marker of hyperandrogenism. Increases of urinary and serum PSA in these patients were similar after 4 and 12 months of treatment (34 ). These preliminary data, generated exclusively by our group over the last 20 years, suggest that (a) serum and urinary PSA is a highly sensitive marker of integrated endogenous androgenic activity in females and (b) serum and urinary PSA is a highly sensitive marker of exogenous androgen administration in females.…”

Androgens Inhibit the Stimulatory Action of 17β-Estradiol on Normal Human Breast Tissue in Explant Cultures

“…Studies on nonhuman primates with similarities to humans in terms of the mammary gland, reproductive physiology, and peripheral steroid hormone metabolism showed that the administration of testosterone markedly reduced estrogeninduced proliferation and estrogen receptor (ER)-␣ gene expression (6,11). Female-to-male transsexuals treated with androgens exhibited involutionary changes similar to those observed in the breasts of menopausal women, including marked reduction of glandular tissue, involution of the lobuloalveolar structures, prominence of fibrous connective tissue, and the presence of only small amounts of adipose tissue (12). However, the doses of androgens used in those treatments were notably high.…”

Serum complexed and free prostate-specific antigen (PSA) for the diagnosis of the polycystic ovarian syndrome (PCOS)

“…Vural et al reported serum PSA elevations in patients with PCOS (13), a finding confirmed by others (14–18). We have further documented that serum and urine PSA levels are highly elevated in female-to-male transsexuals after testosterone treatment, thereby demonstrating that androgens regulate PSA synthesis in female tissues in vivo (19, 20). …”

“…Indeed, it seems plausible that the increased levels of both cPSA and fPSA in the female circulation of PCOS patients is driven by testosterone, as it has been shown in in vitro systems such as breast carcinoma cell lines (8). In vivo , PSA is increased in both serum and urine after the administration of testosterone to young female-to-male transsexuals (19, 20). Although we did not characterize the tissue source of PSA in this study, we have previously demonstrated that the major site of production of PSA in female tissues is the breast, and that PSA could be upregulated in this tissue by steroid hormones (11).…”