Association of Exogenous Estrogen and Endometrial Carcinoma

Abstract

To determine the association between the incidence of endometrial cancer and the use of estrogen in menopausal and post-menopausal women, we retrospectively compared 317 patients with adenocarcinoma of the endometrium with an equal number of matched controls having other gynecologic neoplasms; 152 patients used estrogen, as compared to 54 of 317 controls. Thus, the risk of endometrial cancer was 4.5 times greater among women exposed to estrogen therapy. When estrogen use was adjusted for concomitant variables such as obesity, hypertension, diabetes, parity, referral pattern, age at diagnosis, year of diagnosis and other gynecologic neoplasms, the magnitude of the increased relative risk was associated with several of these variables, and was highest in patients without obesity and hypertension. Exogenous estrogen therapy is associated with an increased risk of endometrial carcinoma, but this increased relative risk is less apparent in patients with physiologic characteristics previously associated with an increased risk.

Declines in breast cancer after the WHI: apparent impact of hormone therapy

“…In that circumstance, a population-based cancer surveillance system detected a rapid increase in cancer incidence rates, and strongly linked it to increasing prevalence of estrogen use on the basis of knowledge of exposure trends (e.g., prescription data) and biologic plausibility. The link subsequently was confirmed by case-control studies [27]. Physicians stopped prescribing estrogen to women with intact uteri, in some cases by adding a second pill, a progestin, to the regimen, and endometrial cancer rates declined substantially [28].…”

Therapeutic Progress—review Xvii: Oral Contraception and Cancer of the Female Reproductive System

“…Although national incidence rates have been generally stable, an increasing incidence has been recorded in North America during the last decade. This worrying trend may reflect widespread use of oestrogen replacement therapy post-menopausally, which has been shown in a number of case-control studies to increase risk of endometrial cancer (36,37). T h e excess risk may be reduced by the use of cyclical combinations of oestrogen and progestogen, but information on this is incomplete.…”

Fallout from the Women’s Health Study: A Short-lived Vindication for Feminists and the Resurrection of Hormone Therapies

“…Seaman and Seaman's (1977) famous quote "promise her anything but give her cancer" (p. 377), was prophetic. Instead of estrogen protecting a woman's uterus from cancer, estrogen was characterized as a "carcinogen" (Smith et al, 1975;Ziel & Finkle, 1975). As expected, rebuttals to the estrogen-cancer connection, similar to what is now being discussed about the WHI findings, were forthcoming.…”

“…Arm 2 consisted of 10,739 women who met the inclusion criterion of not having a uterus. The rationale for the inclusion criterion is the estrogen-cancer of the uterus connection that has been known for decades (Smith, Prentice, Thompson, & Herrmann, 1975;Ziel & Finkle, 1975). Specifically, a woman who does not have a uterus can take unopposed estrogen safely because one cannot develop cancer of the uterus if the uterus has been removed.…”