ESTROGEN-PROGESTIN REPLACEMENT THERAPY AND ENDOMETRIAL CANCER

Background: It has been known for more than 20 years that estrogen rep lacement therapy substantially increases a woman's risk of developing endometrial cancer. To reduce this increased risk, progestins have bee n added to estrogen replacement therapy for between 5 and 15 days (usu ally 7 or 10 days) per ''month'' in a sequential fashion (sequential e strogen-progestin replacement therapy) or with each dose of estrogen r eplacement therapy (continuous combined replacement therapy). At the p resent time, however, little is known about the effects of varying the number of days that progestin is used in sequential estrogen-progesti n replacement therapy. Purpose: We sought to determine the effects of sequential estrogen-progestin replacement therapy and continuous combi ned replacement therapy on a woman's risk of developing endometrial ca ncer. Methods: A population-based, case-control study of 833 ease subj ects and 791 control subjects was conducted. Women mere postmenopausal , white, and aged 50-74 years when first diagnosed with invasive endom etrial cancer or were aged 50-74 Sears at the matching date for contro l subjects. All subjects were interviewed in person with the aid of a month-by-month calendar. Relative risks were estimated by odds ratios (ORs); ORs were adjusted simultaneously for the different forms of hor mone replacement therapy and for the known endometrial cancer risk fac tors. Results: The adjusted OR was 2.17 (95% confidence interval [CI] = 1.91-2.47) per 5 rears of estrogen replacement therapy use (based on 422 users among the case subjects and 262 users among the control sub jects), For women who received sequential estrogen-progestin replaceme nt therapy with the progestin given for less than 10 days (effectively 7 days) per month, the adjusted OR was only slightly reduced to 1.87 (95% CI = 1.32-2.65) per 5 years of use (74 case subjects and 47 contr ol subjects). However, when progestin was given for 10 or more days (e ffectively 10 days), there was essentially no increased risk (adjusted OR = 1.07 per 5 years of use; 95% CI = 0.52-1.41) (79 case subjects a nd SS control subjects). Continuous combined replacement therapy was a lso associated with essentially no increased risk (adjusted OR = 1.07 per 5 years of use; 95% CI = 0.50-1.43) (94 case subjects and 81 contr ol subjects), Conclusions: The progestin in sequential estrogen-proges tin replacement therapy needs to be given for at least 10 days to bloc k effectively any increased risk of endometrial cancer. Continuous com bined estrogen-progestin therapy is similarly effective. Neither regim en reduces a woman's underlying risk of endometrial cancer, The sharp distinction between the effects of less than 10 days (effectively 7 da ys) and 10 or more days (effectively 10 days) of progestin use in sequ ential estrogen-progestin replacement therapy suggests that the extent of endometrial sloughing may play a critical role in determining endo metrial cancer risk.