Short-Term and Long-Term Histologic Effects of Castration and Estrogen Treatment on Breast Tissue of 14 Male-to-Female Transsexuals in Comparison With Two Chemically Castrated Men

Abstract

The histologic changes induced in the mammary gland of male-to-female transsexuals have not yet been reported in the literature. We studied the histologic changes induced by chemical and surgical castration and estrogen therapy in the breasts of 14 such patients, with particular reference to acinar and lobular formation. To objectify the influence of cross-sex treatment, the histologic findings were compared with those in two men treated hormonally for prostate cancer. The slight increase in the plasma estrogen-to-androgen ratio seen in idiopathic gynecomastia usually does not induce acinar and lobular formation in the male breast. In men treated with nonprogestative antiandrogens for prostate cancer, only moderate acinar and lobular formation occurs. Only in male-to-female transsexuals in whom progestative chemical castration is combined with feminizing estrogen therapy will full acinar and lobular formation occur with hormonally stimulated nuclei and pseudolactational changes. Hence, combined progestative antiandrogens and estrogens are necessary for genetically male breast tissue to mimic the natural histology of the female breast. Orchidectomy does not contribute to this. Apocrine metaplasia may occur in breasts of male-to-female transsexuals, but so far, only four cases of breast cancer in male-to-female transsexuals have been documented.

Fibroadenoma in the male breast: Truth or Myth?

“…In idiopathic pre-pubertal or senile gynecomastia, the increase in the plasma estrogen-to-androgen ratio usually will not induce acinar and lobular formation in the male breast. However, in transsexuals, in whom progestagenic antiandrogens, such as cyproterone acetate, are combined with feminizing estrogen therapy, then acini and lobular formation will occur (9,13). The use of a luteinizing hormone-releasing hormone agonist to decrease testosterone levels for the treatment of advanced prostate cancer has contributed to the development of gynecomastia and fibroadenoma (9).…”

Fibroadenoma of the breast in a man associated with adenocarcinoma of the rectum and polyposis coli

“…However, in transsexuals, in whom progestagenic antiandrogens, such as cyproterone acetate, are combined with feminizing estrogen therapy, acini and lobular formation will occur (6,14). The use of a luteinizing hormone-releasing hormone agonist to decrease testosterone levels for the treatment of advanced prostate cancer has contributed to the development of gynecomastia and fibroadenoma (6).…”

Lobular Breast Cancer in a Male Patient with a Previous History of Irradiation Due to Hodgkin’s Disease

“…Analysis of the histological features of male breast cancer as compared to female breast cancer indicates the presence of only 1 difference: lobular (also known as small-cell) cancer is extremely rare in men due to hormonal factors and the lack of acini and lobules [3][4][5]. However, although true lobule formation is not usually present, lobules are sometimes seen, but there is disagreement as to whether this feature occurs only in cases with a known endocrine etiology [20][21][22].…”