Progesterone is a female hormone that plays an important role in the menstrual cycle and during pregnancy. It plays a balancing role with estrogen, and if not present in adequate amounts in the body, may predispose a woman to certain types of breast and uterine cancer. With the onset of menopause, the ovaries produce less progesterone.

Progesterone is not absorbed well when taken by mouth, but is absorbed reasonably well when applied to the skin. This has led to the development of a number of Progesterone Creams. Some contain synthetic progesterone, others contain natural Progesterone extracted from plants like the yam, and a third group of creams combines synthetic and natural progesterone. Natural Progesterone is widely thought to be safer than synthetic Progesterone compounds; however, scientists consider both natural and synthetic Progesterone to be equally safe and effective. Another fallacy is that natural Progesterone is effective in humans. Plant extracts contain a precursor of Progesterone called diosgenin, which can only be metabolized into active Progesterone by plants themselves. Many cream manufacturers combine plant extracts with synthetic progesterone, while still claiming their products contain natural progesterone. The exact amount of Progesterone in creams is not standardized, and women may end up applying fairly high doses over a period of time.

Although Progesterone Creams are widely available without a prescription in various dosages, data are lacking on their purported benefit in treating hot flashes in menopausal women. While no adverse effects are known to have occurred with Progesterone Creams, the North American Menopause Society does not recommend their use in treating hot flashes. Several studies have also shown that Progesterone Creams are ineffective in preventing osteoporosis. Other claims, such as increased sexual desire and prevention of endometrial and breast cancer, have also not been proven. The American College of Obstetricians and Gynecologists cautions against unsupervised use of hormone treatments with unproven benefits and unknown risks.