Reproductive factors and risk of endometrial cancer. The Iowa Women's Health Study.

Gravidity and parity have strong inverse relations with endometrial cancer occurrence. To determine whether gravidity masks an association with other reproductive factors, the authors analyzed data from a cohort study of 24,848 postmenopausal Iowa women aged 55-69 years who were cancer free at baseline in 1986 and who had not had a hysterectomy. During 5 years of follow-up, 167 incident endometrial cancer cases were documented. As expected, the mean gravidity of cases was lower than that of noncases (2.6 vs. 3.5, p < 0.0001). Endometrial cancer occurrence was associated positively with early age at menarche, late age at natural menopause, and total length of ovulation span, but history of infertility and ages at first and last pregnancy were unrelated to risk after adjustment for gravidity. Two additional factors remained statistically significant independent of gravidity: a history of ever (vs. never) having had an induced abortion (relative risk = 2.5, 95% confidence interval 1.1-5.7) and timing of spontaneous abortions (miscarriages). Results suggest that a miscarriage late in reproductive life, followed by lack of a subsequent full-term pregnancy, may be a marker for progesterone deficiency. If so, the findings support the "unopposed" estrogen hypothesis for the etiology of endometrial cancer.