THE ANDROGENICITY OF PROGESTINS

All steroid hormones are structurally similar, but relatively minor di fferences cause profound alterations in biochemical activity. The 21-c arbon series (pregnane nucleus) includes the corticoids and the true p rogestins (e.g., medroxyprogesterone acetate). The 19-carbon series (a ndrostane nucleus) includes all the androgens, among them the progesti ns used in most oral and parenteral contraceptives. The removal of car bon 19 from testosterone changes the major hormonal effect from androg enic to progestogenic, but these ''19-nor'' steroids retain varying de grees of androgenic activity. (They can also have limited estrogenic a ctivity, but this is insignificant at the low doses used for contracep tion.) Some of the 19-nortestosterone progestins are metabolized to ot her compounds (e.g., norethynodrel, ethynodiol diacetate, and lynestre nol to norethindrone), and some (levonorgestrel, desogestrel) are acti ve unchanged. The Lingering androgenic effects of 19-nor progestins ar e 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 lipopro teins prompted the development of less androgenic compounds, but the o bvious benefit of the new progestins (desogestrel, gestodene, norgesti mate) is a reduction in the symptoms associated with the androgenicity of the older compounds. Mitigation of androgenic effects on lipoprote in and carbohydrate metabolism could have long-term benefits, especial ly for women who are at risk of arteriosclerotic vascular disease; how ever, these effects remain to be epidemiologically demonstrated.