Hum. Reprod. Advance Access originally published online on December 6, 2007
Human Reproduction 2008 23(2):451-456; doi:10.1093/humrep/dem381
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Risk of thyroid cancer after exposure to fertility drugs: results from a large Danish cohort study
1 Department of Viruses, Hormones and Cancer, Institute of Cancer Epidemiology, Danish Cancer Society, Strandboulevarden 49,2100 Copenhagen, Denmark 2 The Juliane Marie Centre, Copenhagen University Hospital, Blegdamsvej 9,2100 Copenhagen, Denmark
3 Correspondence address. Tel: +45-3525-7693; Fax: +45-3525-7731; E-mail: allan{at}cancer.dk
BACKGROUND: Findings from the few epidemiological studies that have investigated thyroid cancer risk after fertility drugs have been inconclusive. Using data from the largest cohort of infertile women to date, we examined the effects of fertility drugs on thyroid cancer risk.
METHODS: A cohort of 54 362 women with infertility problems referred to Danish fertility clinics in the period 1963–1998 was established. A detailed data collection including information about type and amount of treatment was conducted. Using case-cohort techniques, we calculated rate ratios (RRs) of thyroid cancer associated with different fertility drugs after adjustment for age at first live birth.
RESULTS: A total of 29 thyroid cancers were identified during follow-up through 2000. Use of clomiphene [RR = 2.28; 95% confidence interval (CI): 1.08–4.82] or progesterone (RR = 10.14; 95% CI: 1.93–53.33) was associated with an increased thyroid cancer risk, although the latter estimate was based on few cases. When stratifying for parity status, the risk was primarily associated with clomiphene (RR = 3.09; 95% CI: 1.21–7.88) in parous women. No significantly increased risk was found after use of gonadotrophins, hCG or GnRH. We observed no association with number of cycles of use or years since first use (latency).
CONCLUSIONS: Clomiphene and possibly progesterone may increase thyroid cancer risk, particularly among parous women. Longer follow-up is needed to confirm our findings.
Key words: thyroid cancer/infertility/fertility drugs/clomiphene/gonadotrophins
Submitted on June 29, 2007; resubmitted on September 13, 2007; accepted on November 2, 2007.
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