antiandrogen in both women and men. It mediates its antiandrogenic effects by 1) stimulating the production of sex hormone-binding globulin (SHBG) in the liver, which decreases free and thus bioactive concentrations of testosterone in the blood; and by 2) suppressing luteinizing hormone (LH) secretion from the pituitary gland, which decreases production of testosterone by the gonads. Birth control pills that contain EE are useful in the treatment of androgen-dependent conditions like acne and hirsutism by virtue of their antiandrogenic effects. Birth control pills containing EE have been found to increase circulating SHBG levels by 2- to 4-fold in women and to reduce free testosterone concentrations by 40 to 80%. Birth control pills containing high doses of EE can increase SHBG levels in women by as much as 5- to 10-fold. This is similar to the 5- to 10-fold increase in SHBG levels that occurs during pregnancy. Due to the marked increase in SHBG levels, free testosterone levels become very low during treatment with EE-containing birth control pills. In men, a study found that treatment with a relatively low dosage of 20 μg/day EE for five weeks increased circulating SHBG levels by 150% and, due to the accompanying decrease in free testosterone levels, increased total circulating levels of testosterone by 50% (via upregulation of gonadal testosterone production due to reduced negative feedback by androgens on the hypothalamic–pituitary–gonadal axis). The stimulation of hepatic SHBG production by EE is far stronger than with other estrogens like estradiol, owing to the high resistance of EE to inactivation in the liver and hence its disproportionate effects in this part of the body. Estrogens are antigonadotropins and are able to suppress the secretion of LH and FSH from the pituitary gland and by extension gonadal testosterone production. High-dose estrogen therapy, including with EE, is able to suppress testosterone levels in men by around 95%, or into the castrate/female range. The dosage of EE required for use as a component of hormone therapy for preoperative transgender women is 50 to 100 µg/day. This high dosage is associated with a high incidence of VTE, particularly in those over the age of 40 years, and it has been said that it should not be used. The dosage of EE used in the treatment of prostate cancer in men is 150 to 1,000 µg/day (0.15–1.0 mg/day). A dosage of EE of 50 μg twice daily (100 μg/day total) has been