Norethisterone

Norethisterone and its acetate and enantate are progestogens. Norethisterone was the first orally active progestogen synthesized, and as such, it has been referred to as a first generation progestogen. Norethisterone is derived from nortestosterone. This means that it has some androgenic activity, unlike natural progesterone and its other derivatives (dydrogesterone and medroxyprogesterone). Norethisterone is used in the combined oral contraceptive and to oppose the effect of estrogen on the endometrium in hormone replacement regimens. Norethisterone exerts its effects by binding to steroid receptors in the reproductive tract, breast, liver, and in the brain. The affinity of norethisterone for endometrial progesterone receptors is similar to that of the natural ligand and so it can produce secretory changes in the estrogen-primed endometrium. Like endogenous progesterone, in the second half of the menstrual cycle, norethisterone also exerts a central thermogenic effect. However, in some animal tests for progestogenic activity norethisterone acts as a competitive antagonist to progesterone. Norethisterone can influence reproductive behaviors, during estrus and mating in animals, but similar effects are less obvious in humans.