Oral contraception and risk of endometrial cancer

Abstract

No placebo-controlled studies concerning hormonal contraception in general have been published, and only investigations on biological mechanisms and observational clinical studies are available. Thus, associations can be described but not their causality. Experimental studies strongly suggest protective effects of the progestagen component of hormonal contraception against development of estrogen-related (type 1) endometrial cancer. In light of this research, it seems biologically plausible that, in more than 20 published studies, a reduction in endometrial cancer risk was achieved in up to 50% of users of combined oral contraceptives (COC), compared with nonusers. Few data exist for progestin-only oral preparations. However, in view of the mechanisms involved, a reduction in cancer risk should also be expected. Whereas hormonal dose-dependency has been investigated in only a few studies, which showed a stronger risk reduction with increasing progestagenic potency, a decreased risk dependent on duration of use has been clearly demonstrated, and after stopping COC this effect has persisted for up to 20 years. Possible confounders, including family history, parity, and smoking, have been investigated in a few studies, with only a minor impact on hormonal effect of endometrial cancer risk, with the exception of obesity, which was a strong risk factor in most but not all studies. There are obvious differences in the incidence of endometrial cancer in women using COC when evaluated in absolute numbers for Western and Asian countries, being about 3-5-fold higher in the US than in Asia. Further research should include the noncontraceptive benefit of COC, especially in patients with a high risk of cancer, as in polycystic ovary disease, and should also include new contraceptive drugs using natural estradiol instead of ethinyl estradiol. Of importance is the question of the potency of hormonal intrauterine devices to protect against endometrial cancer. It can be concluded on the basis of biological plausibility and observational data that COC can strongly decrease the risk of estrogen-related endometrial cancer, with an effect persisting after withdrawal of the hormones, and a causal relationship for this protection against cancer seems reasonable.