Urine and Serum Sex Steroid Profile in Testosterone-Treated Transgender and Hypogonadal and Healthy Control Men.

Background: The impact of testosterone (T) treatment on antidoping detection tests in female-to-male (F2M) transgender men is unknown. We investigated urine and serum sex steroid and luteinizing hormone (LH) profiles in T-treated F2M men to determine whether and, if so, how they differed from hypogonadal and healthy control men. Method: Healthy transgender (n = 23) and hypogonadal (n = 24) men aged 18 to 50 years treated with 1000 mg injectable T undecanoate provided trough urine and blood samples and an additional earlier postinjection sample (n = 21). Healthy control men (n = 20) provided a single blood and urine sample. Steroids were measured by mass spectrometry-based methods in urine and serum, LH by immunoassay, and uridine 5'-diphospho-glucuronosyltransferase 2B17 genotype by polymerase chain reaction. Results: Urine LH, human chorionic gonadotropin, T, epitestosterone (EpiT), androsterone (A), etiocholanolone (Etio), A/Etio ratio, dehydroepiandrosterone (DHEA), dihydrotestosterone (DHT), and 5α,3α- and 5ß,3α-androstanediols did not differ between groups or by time since last T injection. Urine T/EpiT ratio was <4 in all controls and 12/68 (18%) samples from T-treated men, but there was no difference between T-treated groups. Serum estradiol, estrone, and DHEA were higher in transgender men, and serum T and DHT were higher in earlier compared with trough blood samples, but serum LH, follicle-stimulating hormone, and 3α- and 3ß,5α-diols did not differ between groups. Conclusion: Urine antidoping detection tests in T-treated transgender men can be interpreted like those of T-treated hypogonadal men and are unaffected by time since last T dose. Serum steroids are more sensitive to detect exogenous T administration early but not later after the last T dose.

Effect of long-term administration of cross-sex hormone therapy on serum and urinary uric acid in transsexual persons.

BACKGROUND: Transsexual persons afford a very suitable model to study the effect of sex steroids on uric acid metabolism. DESIGN: This was a prospective study to evaluate the uric acid levels and fractional excretion of uric acid (FEUA) in a cohort of 69 healthy transsexual persons, 22 male-to-female transsexuals (MFTs) and 47 female-to-male transsexuals (FMTs). The subjects were studied at baseline and 1 and 2 yr after starting cross-sex hormone treatment. RESULTS: The baseline levels of uric acid were higher in the MFT group. Compared with baseline, uric acid levels had fallen significantly after 1 yr of hormone therapy in the MFT group and had risen significantly in the FMT group. The baseline FEUA was greater in the FMT group. After 2 yr of cross-sex hormone therapy, the FEUA had increased in MFTs (P = 0.001) and fallen in FMTs (P = 0.004). In MFTs, the levels of uric acid at 2 yr were lower in those who had received higher doses of estrogens (P = 0.03), and the FEUA was higher (P = 0.04). The FEUA at 2 yr was associated with both the estrogen dose (P = 0.02) and the serum levels of estradiol-17beta (P =0.03). In MFTs, a correlation was found after 2 yr of therapy between the homeostasis model assessment of insulin resistance and the serum uric acid (r = 0.59; P = 0.01). CONCLUSIONS: Serum levels of uric acid and the FEUA are altered in transsexuals as a result of cross-sex hormone therapy. The results concerning the MFT group support the hypothesis that the lower levels of uric acid in women are due to estrogen-induced increases in FEUA.

Serum and urine tissue kallikrein concentrations in male-to-female transsexuals treated with antiandrogens and estrogens.

BACKGROUND: The expression of human tissue kallikrein genes is regulated by steroid hormones, but most studies have been conducted with cancer cell lines. Our purpose was to examine serum and urinary tissue kallikrein concentration changes in male-to-female transsexuals before and after treatment with antiandrogens and estrogens. METHODS: Thirty-five male-to-female transsexuals receiving cyproterone acetate and estrogens (orally or transdermally) were included in this study. Serum and urine samples were collected before initiation of therapy and 4 and 12 months post therapy. ELISAs were used to measure multiple kallikreins in serum and urine. RESULTS: After antiandrogen and estrogen therapy, serum testosterone concentrations decreased dramatically, as did serum and urinary concentrations of human glandular kallikrein (hK2) and prostate-specific antigen (PSA; hK3). Statistically significant but relatively small changes in serum and urinary concentrations of many other kallikreins were also seen. Kallikreins in serum and urine were correlated before and after treatment. CONCLUSIONS: The concentrations of hK2 and hK3, but not of any other kallikreins, decrease dramatically after combined antiandrogen and estrogen treatment in male-to-female transsexuals. The smaller responses of the other kallikreins presumably reflect their expression in multiple tissues.

Serum and urinary prostate-specific antigen and urinary human glandular kallikrein concentrations are significantly increased after testosterone administration in female-to-male transsexuals.

BACKGROUND: The genes that encode prostate-specific antigen (PSA) and human glandular kallikrein (hK2) are up-regulated by androgens and progestins in cultured cells, but no published studies have described the effect of androgen administration in women on serum and urinary PSA or hK2. METHODS: We measured serum and urinary PSA and hK2 before, and 4 and 12 months post testosterone treatment by immunofluorometric methods in 32 female-to-male transsexuals. RESULTS: Mean serum PSA increased from 1.1 ng/L to 11.1 ng/L and then to 22 ng/L by 4 and 12 months post treatment, respectively; the corresponding mean values in urine were 17, 1420, and 18 130 ng/L, respectively. Serum hK2, another kallikrein closely related to PSA, remained undetectable at the three time points. However, urinary hK2 concentration rose from below the detection limit (<6 ng/L) before treatment to 18 and 179 ng/L by the 4th and the 12th month of treatment, respectively. All changes were statistically significant (P <0.001) at 4 months. CONCLUSIONS: Testosterone administration increases serum and urinary PSA and urinary hK2 in women. These measurements may be useful as indicators of androgenic stimulation in women.

Dramatic suppression of plasma and urinary prostate specific antigen and human glandular kallikrein by antiandrogens in male-to-female transsexuals.

PURPOSE: Prostate specific antigen (PSA) and human glandular kallikrein (hK2) are mainly produced by the prostate and their genes are regulated by androgens through the androgen receptor. We determine whether PSA and hK2 change significantly in plasma and urine after antiandrogen treatment in male-to-female transsexuals. MATERIALS AND METHODS: Plasma and urine PSA and hK2 were measured with highly sensitive immunofluorometric procedures capable of detecting within 1 or 6 ng./l. PSA or hK2, respectively. Study groups consisted of 10 men treated with cyproterone acetate only (group 1), 15 transdermal estradiol plus cyproterone acetate (group 2) and 31 ethinyl estradiol plus cyproterone acetate (group 3). Plasma and urine samples were collected before initiation of treatment as well as after 4 months of hormonal therapy. For a subset of group 3 patients blood and urine samples were also obtained after 12 months of treatment. RESULTS: Cyproterone acetate, a steroidal antiandrogen, alone or with estradiol was able to suppress greater than 90% of plasma and urinary PSA and hK2 concentration after 4 or 12 months of therapy. CONCLUSIONS: Cyproterone acetate therapy causes dramatic suppression of plasma and urinary PSA and hK2 in men without prostate cancer. Since cyproterone acetate is used for prostate cancer treatment, suppression of PSA after hormonal therapy may not accurately reflect therapy success in reducing tumor burden.

Effects of sex steroid hormones on regional fat depots as assessed by magnetic resonance imaging in transsexuals.

We investigated prospectively the effect of sex steroids on regional fat depots and thigh muscle mass in adult transsexuals. Ethinyl estradiol in combination with cyproterone acetate, a progestational antiandrogen, was given to 20 male-to-female (M-F) transsexuals, and parenteral testosterone esters were given to 17 female-to-male (F-M) transsexuals. Before and after 12 mo of cross-sex hormone administration, several anthropometric measurements (weight, skinfolds, body circumferences, and bioimpedance) were performed, and transverse magnetic resonance images were obtained at the level of the abdomen, hip, and thigh to quantify fat depots (subcutaneous and visceral) and muscle areas. We observed that treatment with ethinyl estradiol in M-F transsexuals induced a significant increase in all subcutaneous fat depots, with a lesser but proportional and significant increase in the visceral fat depot and a decrease in thigh muscle area. Testosterone administration in F-M transsexuals markedly increased thigh muscle area, reduced subcutaneous fat deposition at all levels measured, but slightly increased the visceral fat area. We conclude that sex steroid hormones are important determinants of the sex-specific localization of body fat.