A progestin is a medication that mimics the action of progesterone. Progesterone is an ovarian hormone produced by the corpus luteum, the structure that forms from the ovarian follicle after ovulation and prepares the uterus for implantation. Unless a pregnancy intervenes, the corpus luteum has a finite lifespan of 10 to14 days. As it fails, progesterone levels fall. Menses, which is the bleeding accompanying the loss of the uterine lining, is the consequence of the withdrawal of progesterone support. As such, it is not the progestin, but its withdrawal, which results in menstruation. In the absence of ovulation, minimal progesterone is produced form the ovary and the interval between menses is lengthened (oligomenorrhea). While progestins may be used to regulate the menstrual cycle and blood levels of LH may be reduced by progestins, they appear to be of little use in reduction of hair growth, or possibly metabolic derangements.

The most commonly used agent is medroxyprogesterone acetate (MPA) (Cycrin, Amen, and Provera). A regimen of 5 to 10 mg for 10-14 days monthly is used for normalization of cyclic bleeding. Some prefer therapy every three months. It is unclear whether this is effective in reducing the risk of hyperplasia. Alternatively, norethindrone acetate (Aygestin) can be used at 5 mg. daily in a similar regimen. Some patents report better tolerance of norethindrone. In 1998, a standardized oral progesterone preparation (Prometrium) was introduced. While progesterone therapy is not new, it has required a compounding chemist, has been relatively difficult to obtain and expensive. While less potent, a natural preparation may have theoretical benefits over the synthetic progestins. Prometrium may be given in the same fashion as the progestins with 100 mg equal to approximately 2.5 mg. of MPA.

For a progestin to work, the uterus must first be “primed” with estrogen. In some PCOS patients the estrogen levels are not sufficient for the progestin to have an effect. If a progestin alone does not induce bleeding, a regimen first using estrogen then progestin may be tried.

Because of the nature of PCOS, there are the early stages of follicle development, but ovulation does not occur. The small follicles (cysts) of PCOS, while not producing near the amount of a pre-ovulatory follicle, do usually produce enough estrogen to stimulate the proliferation of the uterine lining. In absence of ovulation, the uterus is subject to unopposed estrogen stimulation. Left unchecked, this can lead to an overgrowth of the lining of the uterus (endometrial hyperplasia) and if unchecked, even uterine cancer. While uterine cancer is rare under age 40, most cases will occur in associations with PCOS. Progestins do little for the overall body health, but are used to cause regular withdrawal uterine bleeding and prevention of hyperplasia. Some patients report depression with the synthetic progestins that may be lessened with the progesterone.