The androgenicity of progestins

Abstract

All steroid hormones are structurally similar, but relatively minor differences cause profound alterations in biochemical activity. The 21-carbon series (pregnane nucleus) includes the corticoids and the true progestins (e.g., medroxyprogesterone acetate). The 19-carbon series (androstane nucleus) includes all the androgens, among them the progestins used in most oral and parenteral contraceptives. The removal of carbon 19 from testosterone changes the major hormonal effect from androgenic to progestogenic, but these "19-nor" steroids retain varying degrees of androgenic activity. (They can also have limited estrogenic activity, but this is insignificant at the low doses used for contraception.) Some of the 19-nortestosterone progestins are metabolized to other compounds (e.g., norethynodrel, ethynodiol diacetate, and lynestrenol to norethindrone), and some (levonorgestrel, desogestrel) are active unchanged. The lingering androgenic effects of 19-nor progestins are dose-related, opposed by estrogen, and are manifested metabolically (e.g., glucose tolerance, lipoprotein synthesis) and symptomatically (e.g., acne, weight gain). The effect of 19-nortestosterones on lipoproteins prompted the development of less androgenic compounds, but the obvious benefit of the new progestins (desogestrel, gestodene, norgestimate) is a reduction in the symptoms associated with the androgenicity of the older compounds. Mitigation of androgenic effects on lipoprotein and carbohydrate metabolism could have long-term benefits, especially for women who are at risk of arteriosclerotic vascular disease; however, these effects remain to be epidemiologically demonstrated.

PIP: This paper reports the results of a review of current literature on progestin androgenicity and any progress made to reduce androgenicity. Structurally synthetic, steroid hormones are similar. The 19-carbon structure series includes all the androgens, including the progestins used in most oral and parenteral OC formulations. Some 19-nortestosterone progestins are metabolized to other compounds and some are active as they are. Androgenic effects of 19-nor progestins are dose-related, opposed by estrogen, and are manifested metabolically or symptomatically. Effects on lipoprotein and carbohydrate metabolism may play a role in the development of vascular disease. This has lead researchers to develop safer, less androgenic compounds characterized by fewer androgenic side effects.