The Million Women Study

The Million Women Study is a study of women’s health analyzing data from more than one million women aged 50 and over conducted by UK researchers.^[1] It is a collaborative project between Cancer Research UK and the National Health Service (NHS), with additional funding from the Medical Research Council (UK). The study has abundantly fulfilled its aims of illuminating the answers to crucial questions about factors affecting the health of women in this age group, as its collaborators continue their frequent contribution to prestigious medical journals of what has become an impressive series of landmark medical papers.^[2]

One key focus of the study relates to the effects of hormone replacement therapy use on women's health. The study has confirmed the findings in the Women's Health Initiative (WHI) that women currently using HRT are more likely to develop breast cancer than those who are not using HRT.

Results from the Million Women Study, together with those of the WHI trial from the USA, have influenced national policy, including recent recommendations on the prescribing and use of hormone replacement therapy from the Royal College of Obstetricians and Gynaecologists and from the Commission on Human Medicines.

Study Design

The Million Women Study is a multi-centre, population-based prospective cohort study of women aged 50 and over invited to routine breast cancer screening in the UK. Between 1996 and 2001, women were invited to join the Million Women Study when they received their invitation to attend breast screening at one of 66 participating NHS Breast Screening Centres in the UK. At these centres, women received a study questionnaire with their invitation, which they were asked to complete and return at the time of screening. Around 70% of those attending the programme returned questionnaires and agreed to take part in the study, over 1 in 4 women in the UK in the target age group. The Million Women Study is the largest study of its kind in the world.

Aims

The Million Women Study was set up with the aim of recruiting 1,000,000 women in the UK into a cohort study, to provide answers to the following questions:

• What effects do combined oestrogen and progestagen hormone replacement therapy (HRT) preparations have on breast cancer risk?
• Are breast cancers detected at screening in women who have used HRT or oral contraceptives different in terms of size and invasiveness from the cancers detected in women who have never used these hormones?
• How does HRT use affect the efficacy of breast cancer screening?
• How does HRT use affect mortality from breast cancer and other conditions?

Findings

HRT and Breast Cancer

Follow-up of over 1 million women in the Million Women Study confirmed findings from other recent studies that women currently using HRT are more likely to develop breast cancer than those who are not using HRT.^[3][4][5] Past users are not at increased risk. The study was able to show that this effect is substantially greater for combined (oestrogen-progestagen) HRT than for oestrogen-only HRT; and that the effects were similar for all specific types and doses of oestrogen and progestagen, for oral, transdermal and implanted HRT, and for continuous and sequential patterns of use. Current users of oestrogen-progestagen HRT were at 2 fold increased risk of developing breast cancer, and current users of oestrogen-only HRT at 1.3 fold risk. Use of HRT by women aged 50–64 in the UK in the decade from 1993-2003 resulted in an estimated 20,000 extra breast cancers.

HRT and Endometrial (womb) Cancer

It is well known that post-menopausal women who have not had a hysterectomy are at increased risk of cancer of the endometrium (the lining of the womb) if they take oestrogen-only HRT. Follow up of over 700 000 women in the Million Women Study confirmed this and showed that the risk of endometrial cancer is also increased in women who take tibolone; but is not altered, or may even be reduced, in women taking combined oestrogen-progestagen HRT.^[6] These effects depend also on a woman’s body mass index (BMI, a measure of obesity) such that adverse effects of tibolone and oestrogen-only HRT are greatest in thinner women, and the beneficial effects of combined HRT are greatest in fatter women.

HRT and Ovarian Cancer

Results of the study show a small increase in risk of ovarian cancer in women taking HRT.^[7] Such an increased risk had been suspected from some previous studies, and has now been confirmed with the larger numbers available in this study. The findings come from analyses on 948,576 post-menopausal women in the study, followed up for about 5 years. Women currently taking HRT were at higher risk of developing and of dying from ovarian cancer than women not using HRT. Past users were not at increased risk. The risk in current users was increased about 1.2 fold; for every 1000 women using HRT, 2.6 developed ovarian cancer over 5 years, compared with 2.2 in those not taking HRT. The risk was the same for oestrogen-only, combined oestrogen-progestagen and other types of HRT (including tibolone) and did not vary by specific type of oestrogen or progestagen, or between oral and transdermal (patch) administration.

These results are equivalent to one extra case of ovarian cancer for every 2500 women taking HRT, and one extra death from ovarian cancer per 3300 women taking HRT, over 5 years. Publishers of these studies say that the results need to be looked at in the context of the other risks and benefits of HRT. In particular, an estimation of the overall effect of HRT use on three common cancers in women: breast cancer, endometrial (womb) cancer and ovarian cancer. Together, these cancers account for about 4 in 10 cancers in women in the UK. According to the findings, in women aged 50–69, about 19 of these cancers will develop over 5 years in every 1000 women not taking HRT. In women taking HRT the estimate is for the number of cancers to be increased to about 31. The overall increased risk is higher in women using combined oestrogen-progestagen HRT than in women using oestrogen-only HRT because most of the overall increase is due to an increase in breast cancer, and users of combined HRT have a higher risk of breast cancer than users of oestrogen-only HRT.

Public Health Implications: impact of the Million Women Study

Results from the Million Women Study, together with those from other studies such as the Women’s Health Initiative trial from the USA, have influenced national policy, including recent recommendations on the prescribing and use of hormone replacement therapy from the Royal College of Obstetricians and Gynaecologists and from the Commission on Human Medicines.

References

1. ^ http://www.millionwomenstudy.org/introduction/
2. ^ See, e.g., http://www.millionwomenstudy.org/publications/ http://www.millionwomenstudy.org/publications_other/ http://www.ncbi.nlm.nih.gov/pubmed?term=%22Million%20Women%20Study%20Collaborators%22
3. ^ Beral V, Banks E, Reeves G (August 2004). "Effects of estrogen-only treatment in postmenopausal women". JAMA 292 (6): 684; author reply 685–6. doi:10.1001/jama.292.6.684-a. PMID 15304460. 
4. ^ Banks E, Beral V, Reeves G (December 2004). "Published results on breast cancer and hormone replacement therapy in the Million Women Study are correct". Climacteric 7 (4): 415–6; author reply 416–7. doi:10.1080/13697130400014698. PMID 15799614. 
5. ^ Gray S (October 2003). "Breast cancer and hormone-replacement therapy: the Million Women Study". Lancet 362 (9392): 1332; author reply 1332. doi:10.1016/S0140-6736(03)14598-9. PMID 14575993. 
6. ^ Beral V, Bull D, Reeves G (2005). "Endometrial cancer and hormone-replacement therapy in the Million Women Study". Lancet 365 (9470): 1543–51. doi:10.1016/S0140-6736(05)66455-0. PMID 15866308. 
7. ^ Beral V, Bull D, Green J, Reeves G (May 2007). "Ovarian cancer and hormone replacement therapy in the Million Women Study". Lancet 369 (9574): 1703–10. doi:10.1016/S0140-6736(07)60534-0. PMID 17512855. 

External links

• The Million Women Study official website