1. ¹Cancer Research UK Epidemiology and Genetics Group, Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK
2. ²Reproductive Medicine Unit, University College London Hospitals, Rowland Hill Street, London NW3 2PF, UK
3. ³Department of Gynaecology, Royal Free Campus, Royal Free and University College Medical School, Huntley Street, London WC1E 6DH, UK

Correspondence: Professor I dos Santos Silva, E-mail: isabel.silva@lshtm.ac.uk

⁴Current addresses – PA Wark: Imperial College London, Department of Epidemiology and Public Health, St Mary's Campus, London W2 1PG, UK; VAM: International Agency for Research on Cancer, 150 cours Albert-Thomas, 69372 Lyon, France; CO: St Michael's University Hospital Bristol, Southwell Street, Bristol BS2 8 UG; JN: Norfolk and Norwich University Hospital, Colney Lane, Norwich NR4 7UY

Received 20 February 2009; Revised 15 April 2009; Accepted 15 April 2009; Published online 12 May 2009.

Abstract

To assess long-term health effects of ovarian-stimulation drugs we followed-up for over 20 years a British cohort of 7355 women with ovulatory disorders, 43% of whom were prescribed ovarian-stimulation drugs, and identified a total of 274 deaths and 367 incident cancers. Relative to the general population, the cohort experienced lower mortality from most causes, including from all neoplasms combined, and lower incidence of cervical cancer, but higher incidence of cancers of the breast (relative risk: 1.13; 95% CI 0.97, 1.30) and corpus uteri (2.02; 1.37, 2.87). There were, however, no significant differences in the risk of cancers of the breast, corpus uteri, ovary, or of any other site, between women who had been prescribed ovarian-stimulation drugs and those who had not. Further analyses by type of drug and dose revealed a dose–response gradient in the risk of cancer of the corpus uteri (P for linear trend=0.03), with women given 2250 mg of clomiphene having a 2.6-fold (2.62; 0.94, 6.82) increase in risk relative to those who were not treated. These findings do not support strong associations between ovulation-stimulation drugs and cancer risks, but they indicate the need for continued monitoring to establish whether risks are elevated in certain subgroups of users.