The medication was introduced for medical use in combination with ethinylestradiol (EE) as an oral contraceptive in 1963 by British Drug Houses in the United Kingdom under the brand name Volidan (4 mg MGA and 50 μg EE tablets), and this was followed by Serial 28 (1 mg MGA and 100 μg EE tablets) and Volidan 21 (4 mg MGA and 50 μg EE tablets) in 1964 and Nuvacon (2 mg MGA and 100 μg EE tablets) in 1967, all by British Drug Houses also in the United Kingdom. It was also marketed under the brand name Delpregnin (5 mg MGA and 100 μg mestranol tablets) by 1965, among others. MGA-containing birth control pills were withdrawn after reports in the early 1970s of a high incidence of venous thromboembolism with the preparations.In the early 1970s, MGA was found to be associated with mammary tumors in beagle dogs, and along with several other progestogens, was withdrawn as an oral contraceptive from several markets including the United Kingdom, Canada, and Germany. It was also under investigation for use as a contraceptive in the United States, but development was discontinued in 1972 following the mammary toxicity findings in dogs, and MGA was never marketed as an oral contraceptive in the United States. Subsequent research, such as monkey studies, revealed that there is no similar risk in humans. Following its withdrawal from the market, MGA was eventually reintroduced for the treatment of hormone-sensitive cancers.
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.