In spite of these results, however, this combination has been very rarely used to treat prostate cancer in the United States.The antigonadotropic as well as anticorticotropic effects of MGA may be involved in its effectiveness in the treatment of postmenopausal breast cancer via substantially decreasing gonadal and adrenal production of sex steroids and by extension circulating levels of estrogens, by about 80%. Androgenic and antiandrogenic activity
MGA is a weak partial agonist of the androgen receptor (AR). It has been reported to bind to this receptor with 5% of the affinity of the anabolic steroid metribolone. Despite its weak intrinsic activity at the AR, at clinical doses in humans, MGA appears to behave, for all intents and purposes, purely as an antiandrogen. This is based on the fact that no virilizing side effects have been observed with the use of MGA in patients of either sex at dosages up to as high as 1,600 mg per day, the highest that has been assessed. Furthermore, MGA produces detectable androgenic effects in animals only at a dose that is the equivalent of approximately 200 times that typically used for the treatment of prostate cancer in men. However, the medication does have moderate androgenic effects on serum lipids in humans, causing a significant reduction of HDL and LDL cholesterol levels and no change in triglyceride levels at a dosage of only 5 mg/day. Conversely, MGA does not decrease SHBG levels.
However, doses of 1 to 5 mg MGA were previously used in combined birth control pills in combination with the estrogen ethinylestradiol or mestranol. MGA is an effective contraceptive by itself at dosages of 0.35 to 0.5 mg/day, but is not effective at a dosage of 0.25 mg/day. MGA alone does not inhibit ovulation at a dosage of 0.5 mg/day, nor does it fully inhibit ovulation at a dosage of 0.7 mg/day or even at a dosage of 5 mg/day. The combination of 2 to 5 mg/day MGA and 100 μg/day mestranol has been found to consistently inhibit ovulation, whereas either medication alone did not completely inhibit ovulation in all women.Suppression of testosterone levels by MGA is responsible for its effectiveness in the treatment of conditions like prostate cancer and benign prostatic hyperplasia. In one study, 120 to 160 mg/day MGA suppressed testosterone levels in men by 72%. However, a recovery or "escape" of testosterone levels, gradually returning to near-normal values, has been observed in most men after 2 to 6 months of MGA therapy, and this has limited the usefulness of the medication. The combination of a lower dosage of MGA (40–80 mg/day) and a low oral dosage of an estrogen such as estradiol (0.5–1.5 mg/day), diethylstilbestrol (0.1–0.2 mg/day) or ethinylestradiol (50 µg/day) is able to suppress testosterone levels into the castrate range in men, maintain this suppression long-term, and achieve equivalent effectiveness to high-dosage estrogen monotherapy in the treatment of prostate cancer with comparatively greatly reduced toxicity and side effects.