Correlation between fertility drugs use and malignant melanoma incidence: the state of the art
To explore further the relation between infertility and breast and female reproductive cancers, cancer incidence among 2,632 Israeli women treated for infertility between 1964 and 1974 was evaluated. Cancer incidence through December 1981 was determined by matching the study cohort to the Israel Cancer Registry. The observed number of cancers was compared with sex-age-ethnic and calendar-year, site-specific national cancer rates. There were 42 cancers observed compared with 37.4 expected, yielding a standardized incidence ratio of 1.1 (95% confidence interval (CI) = 0.8-1.5). Analysis by infertility diagnosis demonstrated no significant excess of total cancer incidence; the standardized incidence ratio was 1.3 (95% CI = 0.8-1.8) for infertility due to hormonal deficiency, 0.7 (95% CI = 0.3-1.4) for mechanical infertility, 1.6 (95% CI = 0.6-3.6) for infertility of the male partner, and 1.1 (95% CI = 0.5-2.2) for unclassified diagnosis. Site-specific analyses revealed a significantly increased risk (8.0; 95% CI = 2.5-19.3; four cases observed, 0.50 expected) of endometrial cancer for the hormonal group and a nonsignificant excess of breast cancer and melanoma. Although numbers were small, women with disorders causing unopposed estrogen production had a risk of 1.4 (95% CI = 0.8-2.2) for all cancer sites, which reached 10.3 (95% CI = 2.6-28.2; three cases observed, 0.29 expected) for endometrial cancer and 1.8 (95% CI = 0.8-3.4; eight cases observed, 4.43 expected) for breast cancer. Among women with nonhormonal infertility, there was a suggestion of increased risks of carcinoma of the ovary (3.2; 95% CI = 0.3-32.9; two cases observed, 0.63 expected) and thyroid (3.0; 95% CI = 0.3-24.6; two cases observed; 0.67 expected). No evidence of an association between ovulation-inducing drugs and cancer was found. This study supports the hypothesis that infertility caused by hormone deficiency is a risk factor for uterine cancer, but is inconclusive regarding breast cancer.