A Case-Control Study of Cancer of the Endometrium

Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 86%

Endometrial cancer following treatment for breast cancer: A case-control study in Denmark

Ewertz¹,

Machado²,

Boice³

et al. 1984

“…Because of the possibility of risk of melanoma being related to endogenous hormonal factors, the data was analysed for age at first birth and numbers of livebirths; variables which are important in the aetiology of other hormone related tumours such as breast and ovarian cancer (Brinton et al, 1979;Kelsey et al, 1982;Hildreth et al, 1981). Univariate analysis demonstrated a significant negative association between risk of melanoma and number of live births (Table II), which persisted for superficial spreading melanomas even after adjustment for host factors, educational status and age at first birth.…”

Section: Methodsmentioning

confidence: 99%

Reproductive factors, oral contraceptives and risk of malignant melanoma: Western Canada Melanoma Study

Gallagher¹,

Elwood²,

Hill³

et al. 1985

100

“…Table I shows the results of seven studies which have considered the effect of the daily dose of CEE. All except one (Kelsey et al, 1982) found that the risk was greater for doses of 1.25 mg day-1 (and above) than for doses of 0.625mg day-1 (and below), although in two studies this trend was not adjusted for duration of use. Table II shows the effect of the two doses, 0.625 mg and 1.25 mg, of CEE on plasma E2, SHBG and estimated E2 binding.…”

mentioning

confidence: 90%

The dose-effect relationship between 'unopposed' oestrogens and endometrial mitotic rate: its central role in explaining and predicting endometrial cancer risk

Key¹,

Pike²

1988

485

333

Summary The 'unopposed oestrogen hypothesis' for endometrial cancer maintains that risk is increased by exposure to endogenous or exogenous oestrogen that is not opposed simultaneously by a progestagen, and that this increased risk is due to the induced mitotic activity of the endometrial cells. Investigation of the mitotic rate during the menstrual cycle shows that increases in plasma oestrogen concentration above the relatively low levels of the early follicular phase do not produce any further increase in the mitotic rate of endometrial cells. A modification of the unopposed oestrogen hypothesis which includes this upper limit in the response of endometrial cells to oestrogen is consistent with the known dose-effect relationships between endometrial cancer risk and both oestrogen replacement therapy and postmenopausal obesity; it also suggests that the mechanism by which obesity increases risk in premenopausal women involves progesterone deficiency rather than oestrogen excess, and that the protective effect of cigarette smoking may be greater in postmenopausal than in premenopausal women.Detailed analysis of the age-incidence curve for endometrial cancer in the light of this hypothesis suggests that there will be lifelong effects of even short duration use of exogenous hormones. In particular, 5 years of combination-type oral contraceptive use is likely to reduce a woman's lifetime risk of endometrial cancer by some 60%; whereas 5 years of unopposed oestrogen replacement therapy is likely to increase her subsequent lifetime risk by at least 90%; and even 5 years of 'adequately' opposed therapy is likely to increase subsequent lifetime risk by at least 50%.Epidemiological studies have shown that the risk of developing endometrial cancer increases markedly with increasing weight and with use of oestrogen replacement therapy (ERT) or sequential-type oral contraceptives, and decreases markedly with use of combination-type oral contraceptives (COCs) (Weiss et al., 1980;Henderson et al., 1983). These risk factors can all be explained in terms of the 'unopposed oestrogen hypothesis' for endometrial cancer (Siiteri, 1978;Henderson et al., 1982).In essence the unopposed oestrogen hypothesis maintains that endometrial cancer risk is increased by exposure to endogenous or exogenous oestrogen which is not opposed by progesterone or a synthetic progestagen, and that this increased risk is caused by the increased mitotic activity of the endometrium induced by such exposure. It has, however, not been clear that this hypothesis can explain the high relative risk associated with obesity in premenopausal women.In this paper we first argue, on the basis of studies of premenopausal hormone levels and of endometrial mitotic rates, that endometrial cell division is not increased by increases in plasma oestrogen concentration above early follicular levels. We show that epidemiological studies of the effects of different doses of ERT on endometrial cancer risk are consistent with the existence of such an upper limit, as are studies...