Researchers have known ever since the 1970s that estrogen therapy increases the risk of endometrial cancer, or cancer of the lining of the uterus. To counteract this possibility, women with a uterus are advised to add a progestin, which is the synthetic version of another female hormone called progesterone. But there is little long-term information to confirm the safety and efficacy of combining progestins (or progesterone) with estrogen. Furthermore, doctors are experimenting with dosage to minimize exposure to progestin and its most annoying side effect, monthly bleeding, without compromising the drug's ability to reduce the risk of endometrial cancer. A new study sheds some light on one of the many unanswered questions surrounding progestin.

In the U.S., progestin is most often prescribed either continuously or cyclically. The latter describes the practice of taking progestin only 5-15 days each monthly cycle. Thus far studies indicate that there are variations in progestin's ability to protect against endometrial cancer, depending on how the drug is taken. The most recent study was conducted by Swedish and American research team and published in the Journal of the National Cancer Institute (JNCI, 7/7/99). It showed that the risk of endometrial cancer increased after five or more years of use in women taking progestins cyclically. The best way to minimize the risk of endometrial cancer, according to this study, may be to take progestins continuously. A 1997 American study published in the same journal (JNCI, 8/6/97) found "nearly a twofold increased risk for endometrial cancer associated with cyclic regimens used for fewer than 10 days per month but no increased risk among women who took cyclic therapy for 10 or more days per month."

Definitive answers regarding hormone therapy are expected from an ongoing government-funded clinical trial in which postmenopausal women were randomly assigned to receive estrogen and progestin in one of a variety of combinations. One treatment group in this trial, called the Postmenopausal Estrogen/Progestin Intervention (PEPI) trial, is taking estrogen and micronized progesterone (see below). Early results (three years) indicate that 100 mg of oral micronized progesterone daily can protect the uterus.

As for the so-called natural progesterone cream, available at health food stores and through mail-order catalogues, the product is unlikely to provide protection from endometrial cancer for women on estrogen therapy. A 1998 British study compared an oral progestin with the popular topical cream called Pro-Gest, sold in North America and Europe. Blood tests showed that systemic absorption of the progesterone was minimal. While Pro-Gest contains many natural ingredients, such as almond oil and grapefruit seed, no claim is made on the product that the hormone itself is natural (see HealthFacts, 6/98).

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