Discontinuation of hormone replacement therapy or oral contraceptive pill

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Non-systematic review evidence

A non-systematic literature search review was performed to answer the following question: Should hormone replacement therapy or oral contraceptive pill be discontinued upon development of melanoma?

Most of the data regarding the risk of melanoma associated with use of the oral contraceptive pill (OCP) or hormone replacement therapy (HRT) is based on epidemiological studies.

One cohort study found there was an increased risk of melanoma in women taking the OCP, and but no increase in the risk of melanoma in those who were not currently taking the OCP, but had done so in the past. However this study did not control for confounding factors such as sun exposure.[1] In contrast, a case-control study found that there was no association between OCP use and melanoma, but an increased risk of melanoma in those who had used HRT[2] and another large cohort study found no association between use of the OCP and melanoma.[3]

A randomised controlled trial involving over 27,000 women that compared the incidence of melanoma in post-menopausal women in those taking HRT and those who did not take HRT, found that the use of HRT did not affect the incidence of melanoma[4] and, furthermore, several meta-analyses and literature reviews found that use of the OCP or HRT was not associated with an increased risk of melanoma.[5][6][7][8][9][10]

The use of HRT and the OCP does not influence the prognosis of melanoma.[11]

Evidence regarding the use of the OCP and HRT and the risk of melanoma is insufficient to demonstrate an association.

There is no convincing evidence that either hormone replacement therapy (HRT) or the use of the oral contraceptive pill (OCP) affects the natural history of melanoma.[12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30]

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Evidence summary and practice points

Evidence summary Level References
The use of HRT or the OCP does not affect the natural history of melanoma. III-3 [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30]
The use of HRT or the OCP does not increase the risk of melanoma III-3 [4], [5], [6], [7], [8], [9], [10]
The use of HRT or the OCP does not influence the prognosis of melanoma III-3 [11]

Practice pointQuestion mark transparent.png

HRT and the OCP are not contraindicated in women who currently have or have had melanoma.

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  1. Bhupathiraju SN, Grodstein F, Stampfer MJ, Willett WC, Hu FB, Manson JE. Exogenous Hormone Use: Oral Contraceptives, Postmenopausal Hormone Therapy, and Health Outcomes in the Nurses' Health Study. Am J Public Health 2016 Sep;106(9):1631-7 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/27459451.
  2. Lea CS, Holly EA, Hartge P, Lee JS, Guerry D 4th, Elder DE, et al. Reproductive risk factors for cutaneous melanoma in women: a case-control study. Am J Epidemiol 2007 Mar 1;165(5):505-13 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17158470.
  3. Hannaford PC, Selvaraj S, Elliott AM, Angus V, Iversen L, Lee AJ. Cancer risk among users of oral contraceptives: cohort data from the Royal College of General Practitioner's oral contraception study. BMJ 2007 Sep 29;335(7621):651 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17855280.
  4. 4.0 4.1 Tang JY, Spaunhurst KM, Chlebowski RT, Wactawski-Wende J, Keiser E, Thomas F, et al. Menopausal hormone therapy and risks of melanoma and nonmelanoma skin cancers: women's health initiative randomized trials. J Natl Cancer Inst 2011 Oct 5;103(19):1469-75 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21878677.
  5. 5.0 5.1 Gandini S, Iodice S, Koomen E, Di Pietro A, Sera F, Caini S. Hormonal and reproductive factors in relation to melanoma in women: current review and meta-analysis. Eur J Cancer 2011 Nov;47(17):2607-17 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21620689.
  6. 6.0 6.1 Driscoll MS, Martires K, Bieber AK, Pomeranz MK, Grant-Kels JM, Stein JA. Pregnancy and melanoma. J Am Acad Dermatol 2016 Oct;75(4):669-678 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/27646737.
  7. 7.0 7.1 Bataille V, de Vries E. Melanoma--Part 1: epidemiology, risk factors, and prevention. BMJ 2008 Nov 20;337:a2249 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19022841.
  8. 8.0 8.1 Roh MR, Eliades P, Gupta S, Grant-Kels JM, Tsao H. Cutaneous melanoma in women. Int J Womens Dermatol 2017 Mar;3(1 Suppl):S11-S15 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/28492033.
  9. 9.0 9.1 Kuhle CL, Kapoor E, Sood R, Thielen JM, Jatoi A, Faubion SS. Menopausal hormone therapy in cancer survivors: A narrative review of the literature. Maturitas 2016 Oct;92:86-96 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/27621244.
  10. 10.0 10.1 La Vecchia C, Bosetti C. Oral contraceptives and neoplasms other than breast and female genital tract. Eur J Cancer Prev 2009 Sep;18(5):407-11 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19609214.
  11. 11.0 11.1 Jhaveri MB, Driscoll MS, Grant-Kels JM. Melanoma in pregnancy. Clin Obstet Gynecol 2011 Dec;54(4):537-45 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/22031244.
  12. 12.0 12.1 Holly EA, Weiss NS, Liff JM. Cutaneous melanoma in relation to exogenous hormones and reproductive factors. J Natl Cancer Inst 1983 May;70(5):827-31 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/6573527.
  13. 13.0 13.1 Karagas MR, Stukel TA, Dykes J, Miglionico J, Greene MA, Carey M, et al. A pooled analysis of 10 case-control studies of melanoma and oral contraceptive use. Br J Cancer 2002 Apr 8;86(7):1085-92 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/11953854.
  14. 14.0 14.1 Holman CD, Armstrong BK, Heenan PJ. Cutaneous malignant melanoma in women: exogenous sex hormones and reproductive factors. Br J Cancer 1984 Nov;50(5):673-80 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/6498065.
  15. 15.0 15.1 Gallagher RP, Elwood JM, Hill GB, Coldman AJ, Threlfall WJ, Spinelli JJ. Reproductive factors, oral contraceptives and risk of malignant melanoma: Western Canada Melanoma Study. Br J Cancer 1985 Dec;52(6):901-7 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/4074642.
  16. 16.0 16.1 Green A, Bain C. Hormonal factors and melanoma in women. Med J Aust 1985 Apr 15;142(8):446-8 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/3982348.
  17. 17.0 17.1 Zanetti R, Franceschi S, Rosso S, Bidoli E, Colonna S. Cutaneous malignant melanoma in females: the role of hormonal and reproductive factors. Int J Epidemiol 1990 Sep;19(3):522-6 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/2262243.
  18. 18.0 18.1 Beral V, Ramcharan S, Faris R. Malignant melanoma and oral contraceptive use among women in California. Br J Cancer 1977 Dec;36(6):804-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/597478.
  19. 19.0 19.1 Hannaford PC, Villard-Mackintosh L, Vessey MP, Kay CR. Oral contraceptives and malignant melanoma. Br J Cancer 1991 Mar;63(3):430-3 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/2003986.
  20. 20.0 20.1 Adam SA, Sheaves JK, Wright NH, Mosser G, Harris RW, Vessey MP. A case-control study of the possible association between oral contraceptives and malignant melanoma. Br J Cancer 1981 Jul;44(1):45-50 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/7259960.
  21. 21.0 21.1 Palmer JR, Rosenberg L, Strom BL, Harlap S, Zauber AG, Warshauer ME, et al. Oral contraceptive use and risk of cutaneous malignant melanoma. Cancer Causes Control 1992 Nov;3(6):547-54 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/1420858.
  22. 22.0 22.1 Lê MG, Cabanes PA, Desvignes V, Chanteau MF, Mlika N, Avril MF. Oral contraceptive use and risk of cutaneous malignant melanoma in a case-control study of French women. Cancer Causes Control 1992 May;3(3):199-205 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/1610966.
  23. 23.0 23.1 Osterlind A, Tucker MA, Stone BJ, Jensen OM. The Danish case-control study of cutaneous malignant melanoma. III. Hormonal and reproductive factors in women. Int J Cancer 1988 Dec 15;42(6):821-4 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/3192324.
  24. 24.0 24.1 Helmrich SP, Rosenberg L, Kaufman DW, Miller DR, Schottenfeld D, Stolley PD, et al. Lack of an elevated risk of malignant melanoma in relation to oral contraceptive use. J Natl Cancer Inst 1984 Mar;72(3):617-20 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/6583445.
  25. 25.0 25.1 Bain C, Hennekens CH, Speizer FE, Rosner B, Willett W, Belanger C. Oral contraceptive use and malignant melanoma. J Natl Cancer Inst 1982 Apr;68(4):537-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/6951070.
  26. 26.0 26.1 Holly EA, Cress RD, Ahn DK. Cutaneous melanoma in women. III. Reproductive factors and oral contraceptive use. Am J Epidemiol 1995 May 15;141(10):943-50 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/7741124.
  27. 27.0 27.1 Westerdahl J, Olsson H, Måsbäck A, Ingvar C, Jonsson N. Risk of malignant melanoma in relation to drug intake, alcohol, smoking and hormonal factors. Br J Cancer 1996 May;73(9):1126-31 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/8624275.
  28. 28.0 28.1 Beral V, Evans S, Shaw H, Milton G. Oral contraceptive use and malignant melanoma in Australia. Br J Cancer 1984 Nov;50(5):681-5 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/6498066.
  29. 29.0 29.1 Holly EA, Cress RD, Ahn DK. Cutaneous melanoma in women: ovulatory life, menopause, and use of exogenous estrogens. Cancer Epidemiol Biomarkers Prev 1994 Dec;3(8):661-8 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/7881339.
  30. 30.0 30.1 Persson I, Yuen J, Bergkvist L, Schairer C. Cancer incidence and mortality in women receiving estrogen and estrogen-progestin replacement therapy--long-term follow-up of a Swedish cohort. Int J Cancer 1996 Jul 29;67(3):327-32 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/8707404.

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