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Malignant melanoma risk after exposure to fertility drugs: results from a large Danish cohort study

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Abstract

Objective

The aim was to examine the effects of fertility drugs on malignant melanoma risk using data from the largest cohort of infertile women to date.

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 malignant melanoma associated with different fertility drugs after adjustment for parity status.

Results

112 malignant melanomas were identified during follow-up through 2000. Use of clomiphene, gonadotrophins, hCG or GnRH did not affect risk of malignant melanoma significantly. When stratifying for parity, however, use of gonadotrophins (RR = 2.29; CI: 1.16–4.52) or GnRH (RR = 3.26; 95% CI: 1.50–7.09) among parous women was associated with a significant increased risk. For all groups of fertility drugs, we found no association with number of cycles of use or years since first use (latency).

Conclusions

Our findings showed no strong association between malignant melanoma risk and use of fertility drugs, although the results indicated that use of gonadotrophins or GnRH might increase risk in parous women. Longer follow-up is needed to confirm our findings.

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References

  1. Titus-Ernstoff L (2000) An overview of the epidemiology of cutaneous melanoma. Clin Plast Surg 27:305–316

    PubMed  CAS  Google Scholar 

  2. National Board of Health (2007) The cancer registry 2007, Copenhagen

  3. Green A, Trichopoulos D (2002) Skin cancer. In: Adami HO, Hunter D, Trichopoulos D (eds) Textbook of cancer epidemiology. New York: Oxford University Press, Inc., pp 281–300

    Google Scholar 

  4. Neale RE, Darlington S, Murphy MF, Silcocks PB, Purdie DM, Talback M (2005) The effects of twins, parity and age at first birth on cancer risk in Swedish women. Twin Res Hum Genet 8:156–162

    Article  PubMed  Google Scholar 

  5. Wyshak G, Frisch RE, Albright NL, Albright TE, Schiff I (1989) Reproductive factors and melanoma of the skin among women. Int J Dermatol 28:527–530

    Article  PubMed  CAS  Google Scholar 

  6. Lambe M, Thorn M, Sparen P, Bergstrom R, Adami HO (1996) Malignant melanoma: reduced risk associated with early childbearing and multiparity. Melanoma Res 6:147–153

    Article  PubMed  CAS  Google Scholar 

  7. Karagas MR, Zens MS, Stukel TA et al (2006) Pregnancy history and incidence of melanoma in women: a pooled analysis. Cancer Causes Control 17:11–19

    Article  PubMed  Google Scholar 

  8. Holly EA, Weiss NS, Liff JM (1983) Cutaneous melanoma in relation to exogenous hormones and reproductive factors. J Natl Cancer Inst 70:827–831

    PubMed  CAS  Google Scholar 

  9. Westerdahl J, Olsson H, Masback A, Ingvar C, Jonsson N (1996) Risk of malignant melanoma in relation to drug intake, alcohol, smoking and hormonal factors. Br J Cancer 73:1126–1131

    PubMed  CAS  Google Scholar 

  10. Beral V, Evans S, Shaw H, Milton G (1984) Oral contraceptive use and malignant melanoma in Australia. Br J Cancer 50:681–685

    PubMed  CAS  Google Scholar 

  11. Beral V, Ramcharan S, Faris R (1977) Malignant melanoma and oral contraceptive use among women in California. Br J Cancer 36:804–809

    PubMed  CAS  Google Scholar 

  12. Fathalla MF (1971) Incessant ovulation—a factor in ovarian neoplasia? Lancet 2:163

    Article  PubMed  CAS  Google Scholar 

  13. Henderson BE, Ross RK, Judd HL, Krailo MD, Pike MC (1985) Do regular ovulatory cycles increase breast cancer risk? Cancer 56:1206–1208

    Article  PubMed  CAS  Google Scholar 

  14. Sovino H, Sir-Petermann T, Devoto L (2002) Clomiphene citrate and ovulation induction. Reprod Biomed Online 4:303–310

    Article  PubMed  CAS  Google Scholar 

  15. Mosgaard B, Lidegaard O, Andersen AN (1995) Use of fertility drugs in Denmark 1973–1993. An analysis based on sale statistics. Acta Obstet Gynecol Scand 74:614–618

    Article  PubMed  CAS  Google Scholar 

  16. Ministry of the Interior and Health (2006) The Danish medicines agency 2006, Copenhagen

  17. Wysowski DK (1993) Use of fertility drugs in the United States, 1973 through 1991. Fertil Steril 60:1096–1098

    PubMed  CAS  Google Scholar 

  18. Fuller PN (1999) Malignant melanoma of the ovary and exposure to clomiphene citrate: a case report and review of the literature. Am J Obstet Gynecol 180:1499–1503

    Article  PubMed  CAS  Google Scholar 

  19. Kuppens E, Bergman W, Welvaart K, Bruijn JA, Scheffer E (1992) Multiple primary melanomas in a patient with familial-type DNS during clomiphene-induced pregnancy. Melanoma Res 2:71–74

    Article  PubMed  CAS  Google Scholar 

  20. Brinton LA, Melton LJ III, Malkasian GD Jr, Bond A, Hoover R (1989) Cancer risk after evaluation for infertility. Am J Epidemiol 129:712–722

    PubMed  CAS  Google Scholar 

  21. Modan B, Ron E, Lerner-Geva L et al (1998) Cancer incidence in a cohort of infertile women. Am J Epidemiol 147:1038–1042

    PubMed  CAS  Google Scholar 

  22. Ron E, Lunenfeld B, Menczer J et al (1987) Cancer incidence in a cohort of infertile women. Am J Epidemiol 125:780–790

    PubMed  CAS  Google Scholar 

  23. Venn A, Watson L, Lumley J, Giles G, King C, Healy D (1995) Breast and ovarian cancer incidence after infertility and in vitro fertilisation. Lancet 346:995–1000

    Article  PubMed  CAS  Google Scholar 

  24. Rossing MA, Daling JR, Weiss NS, Moore DE, Self SG (1995) Risk of cutaneous melanoma in a cohort of infertile women. Melanoma Res 5:123–127

    Article  PubMed  CAS  Google Scholar 

  25. Holly EA, Cress RD, Ahn DK (1995) Cutaneous melanoma in women. III. Reproductive factors and oral contraceptive use. Am J Epidemiol 141:943–950

    PubMed  CAS  Google Scholar 

  26. Althuis MD, Scoccia B, Lamb EJ et al (2005) Melanoma, thyroid, cervical, and colon cancer risk after use of fertility drugs. Am J Obstet Gynecol 193:668–674

    Article  PubMed  Google Scholar 

  27. Young P, Purdie D, Jackman L, Molloy D, Green A (2001) A study of infertility treatment and melanoma. Melanoma Res 11:535–541

    Article  PubMed  CAS  Google Scholar 

  28. International Agency for Research on Cancer (2007) GLOBOCAN 2002, France

  29. Jensen A, Sharif H, Svare EI, Frederiksen K, Kjaer SK (2007) Risk of breast cancer after exposure to fertility drugs: results from a large Danish cohort study. Cancer Epidemiol Biomarkers Prev 16:1400–1407

    Article  PubMed  CAS  Google Scholar 

  30. Hannibal CG, Jensen A, Sharif H, Kjaer SK (2007) Risk of thyroid cancer after exposure to fertility drugs: results from a large Danish cohort study. Hum Reprod 23(2):451–456

    Google Scholar 

  31. National Board of Health (2007) The national patient registry 2007, Copenhagen

  32. Danish Civil Registration System. (2007) The registry of civil registration 2007, Copenhagen

  33. National Board of Health (2007) The medical birth registry 2007, Copenhagen

  34. Prentice RL (1986) A case–cohort design for epidemiologic cohort studies and disease prevention trials. Biometrika 73:1–11

    Article  Google Scholar 

  35. Venn A, Watson L, Bruinsma F, Giles G, Healy D (1999) Risk of cancer after use of fertility drugs with in-vitro fertilisation. Lancet 354:1586–1590

    Article  PubMed  CAS  Google Scholar 

  36. Beral V (1983) Parity and susceptibility to cancer. Ciba Found Symp 96:182–203

    PubMed  CAS  Google Scholar 

  37. Smith MA, Fine JA, Barnhill RL, Berwick M (1998) Hormonal and reproductive influences and risk of melanoma in women. Int J Epidemiol 27:751–757

    Article  PubMed  CAS  Google Scholar 

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Acknowledgment

We thank Nick Martinussen for helping with the data management, and all participating hospital departments and private fertility clinics for their contributions to the data collection.

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Authors and Affiliations

  1. Department of Viruses, Hormones and Cancer, Institute of Cancer Epidemiology, Danish Cancer Society, Strandboulevarden 49, 2100, Copenhagen, Denmark

    Charlotte Gerd Hannibal, Allan Jensen, Heidi Sharif & Susanne Krüger Kjaer

  2. The Juliane Marie Centre, Copenhagen University Hospital, Blegdamsvej 9, 2100, Copenhagen, Denmark

    Susanne Krüger Kjaer

Authors
  1. Charlotte Gerd Hannibal
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  2. Allan Jensen
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  3. Heidi Sharif
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  4. Susanne Krüger Kjaer
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Corresponding author

Correspondence to Allan Jensen.

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Hannibal, C.G., Jensen, A., Sharif, H. et al. Malignant melanoma risk after exposure to fertility drugs: results from a large Danish cohort study. Cancer Causes Control 19, 759–765 (2008). https://doi.org/10.1007/s10552-008-9138-5

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  • DOI: https://doi.org/10.1007/s10552-008-9138-5

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