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Exogenous hormones and cancer in the UK

Hormone levels may explain differences in risk for some of the most commonly diagnosed female cancers and could be responsible for as many as 15% of cancers in the UK1.

The lifestyle choices that determine hormone levels are not as straightforward as stopping smoking or eating healthily and are largely dictated by reproductive or genetic factors, over which individuals may have little or no control.This page presents information on cancer risk and hormones including oral contraceptives and hormone replacement therapy.

Table 5.1 shows a summary of what we know about hormones and cancer risk.

Download this table (14KB)

Studies assessing serum levels of testosterone and other male sex hormones in men and risk of prostate cancer suggest a more than two-fold increase in risk in men with the highest testosterone levels2.

Risk of ovarian, endometrial and breast cancers increases with earlier age at menarche and later menopause, and reduces with each full-term pregnancy (the first full-term pregnancy providing more protection than successive ones)3,4. There is a transient increase in risk of breast cancer with each full-term pregnancy after the age of 25, and this is most marked with a woman’s first pregnancy. Uniparous women with a first full-term pregnancy after the age of 30 have a higher breast cancer risk than childless women until their late 50s5.

Breast cancer risk is reduced by around 4% for each year a woman breastfeeds4. It has also been reported that the risk of endometrial cancer is reduced by as much as 50%6 and the risk of ovarian cancer by 40%7 in women who breastfeed. Today around 70% of mothers breastfeed initially, compared with only 50% in the 1970s, but less than half of these women breastfeed for more than four months and only a third for more than six months8.

Oral contraceptives and cancer

A meta-analysis of European case-control studies indicates that use of OCs for five or more years results in a 50% reduction in risk of ovarian cancer which remains for more than 20 years9. Case-control studies have consistently reported a 40 to 60% reduction in risk of endometrial cancer, increasing with duration of use, among users of combination OCs10. There is a slight transient increase in risk of breast cancer while OCs are taken11,12.

Use of OCs for more than five years results in a duration-dependent increased risk for cervical cancer after adjustment for potential confounders including human papillomavirus (HPV) status (see infections section below), smoking and use of barrier contraceptives. Risk falls once use of OCs is stopped13.

Hormone replacement therapy (HRT) and cancer

Women taking oestrogen-only HRT are at an increased risk of endometrial and ovarian cancers14. The risk of uterine cancer is approximately doubled after five years, while the risk of ovarian cancer increases by about 25% for the same duration of use3,10. Combined oestrogen-progestagen HRT does not increase risk of ovarian cancer, and may even protect against endometrial cancer 3,10,14.

The UK ‘Million Women Study’ reported breast cancer RRs for current use of oestrogen-progestagen therapy or oestrogen only of 2 and 1.3, respectively. Risk increased with duration of use, with risk ratios of 2.3 for 10 or more years of combined HRT, compared with 1.5 for less than one year. There was a marginally increased risk in women who stopped HRT less than a year before entering the study, but no difference in risk between never users and women as a group who stopped therapy at some point in the previous five years15.

It is estimated that over the past decade, use of HRT by UK women aged 50-64 has resulted in an extra 20,000 breast cancers, oestrogen-progestagen therapy accounting for 15,000 of these15.

References

1. Doll, R. and P.J. Fau, Epidemiology of Cancer, in Oxford Textbook of Medicine. 4th ed, D. Warrell, et al., Editors. 2003, OUP.
2. Shaneyfelt, T., et al., Hormonal predictors of prostate cancer: a meta-analysis. J Clin Oncol, 2000. 18(4): p. 847-53.PubMed
3. Pike, M.C., C.L. Pearce, and A.H. Wu, Prevention of cancers of the breast, endometrium and ovary. Oncogene, 2004. 23(38): p. 6379-91.PubMed
4. Collaborative Group on Hormonal Factors in Breast Cancer, Breast cancer and breastfeeding: collaborative reanalysis of individual data from 47 epidemiological studies in 30 countries, including 50302 women with breast cancer and 96973 women without the disease. Lancet, 2002. 360(9328): p. 187-95.PubMed
5. Albrektsen, G., et al., Breast cancer risk by age at birth, time since birth and time intervals between births: exploring interaction effects. Br J Cancer, 2005. 92(1): p. 167-75.PubMed
6. Newcomb, P.A. and A. Trentham-Dietz, Breast feeding practices in relation to endometrial cancer risk, USA. Cancer Causes Control, 2000. 11(7): p. 663-7.PubMed
7. Tung, K.H., et al., Effect of anovulation factors on pre- and postmenopausal ovarian cancer risk: revisiting the incessant ovulation hypothesis. Am J Epidemiol, 2005. 161(4): p. 321-9.PubMed
8. Department of Health, Infant Feeding 2000. 2002: London.Link
9. Bosetti, C., et al., Long-term effects of oral contraceptives on ovarian cancer risk. Int J Cancer, 2002. 102(3): p. 262-5.PubMed
10. Schottenfeld D and Fraumeni J, Cancer Epidemiology and Prevention. 1996, Oxford: Oxford University Press.
11. Boyle, P., et al., European Code Against Cancer and scientific justification: third version (2003). Ann Oncol, 2003. 14(7): p. 973-1005.PubMed
12. Collaborative Group on Hormonal Factors in Breast Cancer, Breast cancer and hormonal contraceptives: collaborative reanalysis of individual data on 53 297 women with breast cancer and 100 239 women without breast cancer from 54 epidemiological studies. Collaborative Group on Hormonal Factors in Breast Cancer. Lancet, 1996. 347(9017): p. 1713-27.PubMed
13. Smith, J.S., et al., Cervical cancer and use of hormonal contraceptives: a systematic review. Lancet, 2003. 361(9364): p. 1159-67.PubMed
14. Lacey, J.V., Jr., et al., Menopausal hormone replacement therapy and risk of ovarian cancer. Jama, 2002. 288(3): p. 334-41.PubMed
15. Beral, V., Breast cancer and hormone-replacement therapy in the Million Women Study. The Lancet, 2003. 362(9382): p. 419-427.PubMed