Progesterone is a natural hormone which is produced by the ovary during the second half of the menstrual cycle. Its biological function is to change the lining of the uterus so that the cells which line the uterus can provide nutrition to the developing embryo during the earliest phases of development after conception. If conception fails to occur, the drop in progesterone and estrogen levels in the blood lead to menstruation which is a shedding of the lining of the uterus. This periodic shedding is an important prevention of the development of uterine cancer. Women who lack progesterone and who produce or are exposed to persistent levels of estrogen are at greater risk for this form of cancer. Other biological effects of progesterone include assisting in the final development of the female breast during puberty. Progesterone had mild sedative effects. Many clinicians feel that Premenstrual Syndrome (PMS) is related to progesterone although this is poorly understood. Side effects from progesterone administration may include fluid retention, irritability, depression, and hypoglycemic attacks.

There are two general forms of progesterone available pharmacologically in the United States–progesterone and progestins. Progesterone has 21 carbon atoms. Progestins are derived from testosterone, a powerful male hormone, which has 19 carbon atoms. Their chemical structure is very similar. By changing the testosterone molecule, one can get more progesterone-like effects and few androgenic (or male-directed) effects. There were two reasons why it was necessary to develop these synthetic progestins: First, natural progesterone has unpredictable absorption as well as side effects such as sedation and second, it was more expensive to produce than synthetic progestins. Today, however, the progesterone molecule is manufactured from many plant sources such as Mexican wild yam and soy.

The progesterone most commonly used in the United States for menopause management is Medroxyprogesterone acetate (Provera®, Amen®, Cycrin®) which comes in 2.5 mg, 5.0 mg, and 10.0 mg tablets. Unfortunately, many women have side effects to this preparation— particularly the 10mg dose which is now felt to be unnecessary for most women and probably an overdose. There are other progestins including Norethindrone acetate (Aygestin®) 5 mg which is a bit too potent for most women and Norethindrone (NorQD®, Micronor®) 0.35 mg and dl-Norgestrel (Ovrette®) 0.075 mg which are birth control pills and are not potent enough to reverse the effects of estrogen on the uterus. Megestrol acetate (Megace®) 20 – 40 mg is also progesterone used in the treatment of cancer and endometriosis. Published studies have demonstrated the use of dosages of 2.5-7.5mg daily will protect the uterus. The formulations available in the United States are probably too potent for menopause management.

Other forms of progesterone include micronized progesterone capsules (Promethium®) and vaginal suppositories (manufactured by pharmacists (25 mg, 50 mg, 100 mg, 200 mg), progesterone in oil injection 50 mg/ml, depo-medroxyprogesterone acetate, and progesterone creams (manufactured by pharmacists) in varying concentrations. A 10% concentration is fairly typical. Crinoline® vaginal gel is manufactured in an 8% concentration.

Recent studies have shown that 100mg of micronized progesterone (Promethium®) twice a day for 14 days or daily for 28 days is adequate for menopause management. There is some data to suggest that this form might have fewer side effects such as depression, bloating, and weight gain than synthetic progestins. Recent clinical trials (HERS), WHI) have suggested that the use of medroxyprogesterone (Provera) may increase the risk of heart disease, stroke and breast cancer. There is some evidence to suggest that so called “natural progesterone” has less of these effects than some synthetic progestins. There are no long term epidemiological studies on the biological effects of so called “natural progesterone”.

The use of natural progesterone for the management of PMS remains very controversial. Studies in the 1980s could not demonstrate any effectiveness but other people claim they feel better. Newer theories suggest that PMS may be due to estrogen deficiency, not progesterone deficiency.

One can purchase progesterone creams and gels in health food stores. These preparations have not bee reviewed by the FDA for safety, purity or effectiveness. They range in potency from 5mg / tsp. to 1000mg / tsp.!! Absorption through the skin is very variable depending upon the type of vehicle (ointment, gel, cream) the medicine is placed in and where on the skin it is applied. So be careful with these!!! Depending on which preparation you use, you may experience no effects or an overdose with all of the problems mentioned above. If you are using topical hormones, it is important to let your health provider know. There are no long term epidemiological studies on the effectiveness of these preparations in menopause.