• Endometrial cancer (cancer of the lining of the uterus) and
• Epithelial ovarian cancer.

Combined OCs probably help protect against these cancers by reducing the rate of cell division in the endometrial lining and the ovaries. In the case of the uterine endometrium, the progestin component in the pill is thought to counteract the effects of estrogen, which would otherwise encourage cell division. OCs may protect against ovarian cancer by reducing gonadotropin production by the pituitary gland, thus reducing the effects of gonadotropin stimulation of the surface cells of the ovaries (62, 359).

Endometrial cancer. Even as little as one year's use of combined OCs cuts the risk of endometrial cancer substantially, and protection lasts long after women stop using OCs. A combined analysis of eight case-control studies and two cohort studies found that longer use significantly increased protection (409, 535). One year of OC use reduced risk to 77% of that among nonusers, 2 years to 62%, 4 years to 49%, 8 years to 36%, and 12 years to 30%. Earlier studies reported protection persisting from 3 to 10 years (195, 210, 234, 516.)

It is uncertain whether the degree of protection against endometrial cancer varies with estrogen and/or progestin dose. The 1985 US Centers for Disease Control's Cancer and Steroid Hormone (CASH) study found no relationship between progestin dose and the degree of protection (58). Although the number of women using any one formulation in the CASH study was too small to allow an analysis by formulation, both high- and low-dose pills had a protective effect. In contrast, a 1991 WHO study suggested that protection was greater for users of formulations containing high doses of progestins (393, 460). Although there are no studies on whether progestin-only OCs protect against endometrial cancer, studies of the effects of progestins on the endometrium suggest that it is progestin rather than estrogen that confers the protective effect (243, 297, 360). Moreover, a 1991 WHO study of the progestin-only injectable contraceptive depot medroxyprogesterone acetate (DMPA) found that it protected against endometrial cancer as well as combined OCs (461). Therefore progestin-only OCs may have at least some protective effect (297).

Epithelial ovarian cancer. Combined OCs help protect against epithelial ovarian cancer (12, 59, 62, 92, 200, 299, 325, 391, 474, 515, 524). This finding from the large 1985 CASH study and many earlier, smaller studies has been confirmed over the past decade (180, 345, 386, 390).

In the CASH study women using OCs for 10 years or more reduced their risk of ovarian cancer to 20% of that among nonusers. The CASH study also found that protection against epithelial ovarian cancer persists long after women stop using OCs. Even women who had stopped using OCs 15 or more years earlier faced just half the risk that never-users faced. Each of the 11 pill formulations studied offered similar protection, whether the formulation was high- or low-dose (59).

The protective effect of OCs against epithelial ovarian cancer may grow in importance in the coming years. All studies to date have focused on women younger than 55, since most OC users and former users are in this age group. Ovarian cancer is more common in women over age 60, however. Since the protective effect of OC use apparently persists for many years, widespread OC use may eventually result in a decline in the incidence of this frequently fatal disease. Epithelial ovarian cancer is by far the most common type of ovarian cancer (59).