Breast development extension adrenocorticotropic hormone (ACTH)), and thyroid hormones such as thyroxine (and by extension thyroid-stimulating hormone (TSH) and thyrotropin-releasing hormone (TRH)) also play permissive but less well-understood/poorly-characterized roles in breast development during both puberty and pregnancy, and are required for full functional development. Leptin has also been found to be an important factor in mammary gland development, and has been found to promote mammary epithelial cell proliferation. In contrast to the female-associated sex hormones, estrogen and progesterone, the male-associated sex hormones, the androgens, such as testosterone and dihydrotestosterone (DHT), powerfully suppress the action of estrogen in the breasts. At least one
Transgender hormone therapy (male-to-female) suggesting a protective role of the male sex-determination chromosome. On the other hand, men with Klinefelter's syndrome (two X chromosomes and one Y chromosome), which causes hypoandrogenism, hyperestrogenism, and a very high incidence of gynecomastia (80%), have a dramatically (20- to 58-fold) increased risk of breast cancer compared to men with one X chromosome, closer to the rate of homogametic females. The incidences of breast cancer in karyotypical men (46,XY karyotype), men with Klinefelter's syndrome (47,XXY karyotype), and karyotypical women (46,XX karyotype) are approximately 0.1%, 3%, and 12.5%, respectively. Individuals with the 46,XY karyotype affected by complete androgen insensitivity syndrome