Routes of delivery for progesterone and progestins.

The trends in postmenopausal hormonal therapy (HT) seem to favor the non-oral delivery routes for both the estrogen and the progestin for women with an intact uterus. Targeting the lowest possible dose of the progestin or of the natural hormone progesterone to be delivered directly to the uterus, the target organ for which it is designed, would avoid the possible drawbacks of systemic effects of progestins on other targets. Several delivery systems are either available or in development including vaginal gels and vaginal rings delivering the physiological hormone progesterone or intrauterine systems delivering very low doses of levonorgestrel. In addition, transdermal gels and spray are under development and can deliver very low doses of Nestorone a 19-norprogesterone derivative, not active orally but with high progestational activity when given via non-oral routes. The assumption that these new delivery systems should lead to an improved risk/benefit ratio in HT will need to be demonstrated in larger randomized controlled studies.