Histology of genital tract and breast tissue after long-term testosterone administration in a female-to-male transsexual population.

Growing evidence indicates that androgens play a positive role in follicle proliferation and growth. Hence, many authors have assumed that androgen supplementation in women with poor ovarian reserve might improve the number of antral follicles available for ovarian stimulation. As androgen administration may become more frequently used in reproductive medicine, this study aimed at describing the histological changes observed in the genital tract and the breast of female-to-male (FTM) transsexuals. A pathological analysis of the genital tract of 112 FTM subjects who were given androgen for at least 6 months before hystero-salpingo-oophorectomy was performed. In addition, 100 bilateral mastectomies were performed, allowing a study of the breast tissue. Mean ovarian volume was increased, with histological characteristics of polycystic ovaries (PCO), defined as >12 antral follicles per ovary, observed in 89 patients (79.5%). Endometrial atrophy was observed in 45%. Breast examination revealed marked reduction of glandular tissue and increase of fibrous connective tissue in 93%, without atypical hyperplasia or carcinoma. The present data confirms and expands the putative associations between long-term androgen administration and abnormalities in ovarian architecture with macroscopic and microscopic characteristics of PCO, increased risk of endometrial atrophy and fibrotic breast tissue with marked glandular reduction.

Expression of progesterone and estradiol receptors in normal adrenal cortex, adrenocortical tumors, and primary pigmented nodular adrenocortical disease.

Adrenal tumors occur more frequently in women and are the leading cause of Cushing's syndrome during pregnancy. We aimed to evaluate the potential role of sex steroids in the susceptibility of women to adrenocortical tumors. We evaluated the presence of the progesterone receptor (PR), estradiol receptors (ERs), and aromatase in 5 patients with primary pigmented nodular adrenal disease (PPNAD), 15 adrenocortical adenomas (ACAs) and adjacent normal tissues, 12 adrenocortical carcinomas (ACCs), and 3 normal adrenal glands (NA). The expression of PR and ERalpha was evaluated by enzyme immunoassays, real-time RT-PCR, immunohistochemistry, and cytosol-based ligand-binding assays. ERbeta and aromatase levels were evaluated by real-time RT-PCR. ERalpha concentrations were low in NA, in adrenal tissues adjacent to ACA (51+/-33), in ACC (53+/-78), and lower in ACA (11+/-11 fmol/mg DNA). Conversely, PR concentrations were high in NA and adrenal tissues adjacent to ACA, at 307+/-216 fmol/mg DNA, and were even higher in tumors - 726+/-706 fmol/mg DNA in ACA and 1154+/-1586 fmol/mg DNA in ACC - and in isolated PPNAD nodules. Binding study results in four tumors were compatible with binding to a steroid receptor. In patients with PPNAD, a strong positive immunohistochemical signal was associated with the sole isolated nodular regions. ERbeta transcript levels were very high in all samples except those for two ACCs, whereas aromatase levels were low. PR and ERbeta are clearly present in normal adrenal glands and adrenal tumors. Further studies may shed light on the possible pathogenic role of these receptors in adrenal proliferation.