Cancer risk after exposure to treatments for ovulation induction.
Uncertainty continues as to whether treatments for ovulation induction are associated with increased risk of cancer. The authors conducted a long-term population-based historical cohort study of parous women. A total of 15,030 women in the Jerusalem Perinatal Study who gave birth in 1974-1976 participated in a postpartum survey. Cancer incidence through 2004 was analyzed using Cox's proportional hazards models, controlling for age and other covariates. Women who used drugs to induce ovulation (n = 567) had increased risks of cancer at any site (multivariate hazard ratio (HR) = 1.36, 95% confidence interval (CI): 1.06, 1.74). An increased risk of uterine cancer was found among women treated with ovulation-inducing agents (HR = 3.39, 95% CI: 1.28, 8.97), specifically clomiphene (HR = 4.56, 95% CI: 1.56, 13.34). No association was noted between use of ovulation-inducing agents and ovarian cancer (age-adjusted HR = 0.61, 95% CI: 0.08, 4.42). Ovulation induction was associated with a borderline-significant increased risk of breast cancer (multivariate HR = 1.42, 95% CI: 0.99, 2.05). Increased risks were also observed for malignant melanoma and non-Hodgkin lymphoma. These associations appeared stronger among women who waited more than 1 year to conceive. Additional follow-up studies assessing these associations by drug type, dosage, and duration are needed.
Calderon-Margalit
R
R
Braun School of Public Health and Community Medicine, Hadassah-Hebrew University, Jerusalem, Israel. ronitc@ekmd.huji.ac.il
Friedlander
Y
Y
Yanetz
R
R
Kleinhaus
K
K
Perrin
M C
MC
Manor
O
O
Harlap
S
S
Paltiel
O
O
D000328:Adult; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000209:etiology; D015984:Causality; D015331:Cohort Studies; D005260:Female; D006801:Humans; D015994:Incidence; D007557:Israel / Q000453:epidemiology; D008228:Lymphoma, Non-Hodgkin / Q000453:epidemiology* / Q000209:etiology; D008545:Melanoma / Q000453:epidemiology* / Q000209:etiology; D010051:Ovarian Neoplasms / Q000453:epidemiology* / Q000209:etiology; D010062:Ovulation Induction / Q000009:adverse effects / Q000706:statistics & numerical data*; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012878:Skin Neoplasms / Q000453:epidemiology* / Q000209:etiology; D014594:Uterine Neoplasms / Q000453:epidemiology* / Q000209:etiology