THE MILLION WOMEN STUDY

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Newsletter – December 2016

The Million Women Study- the first 20 years
In September we hosted collaborators and friends for the Million Women Study 20th anniversary celebrations. Talks by Cancer Epidemiology Unit and external researchers featured new results from the study and developments in breast cancer screening and treatments. The event also included an extended talk by Professor Dame Valerie Beral about AgeX, a randomised trial investigating the effect of adding an additional breast screen, either at age 47-49 or at 71-73 to the existing 7 invitations routinely offered at ages 50-70. So far 3 million women have been randomised, making this the largest randomised controlled trial ever undertaken.

Valerie Beral, Emily Banks and Julietta Patnick as they appeared on the front page of The Times when the Million Women Study was launched 20 years ago…

and at the 20th anniversary event in 2016.

Some Million Women Study results published since October 2015

Does happiness itself directly affect mortality?
Poor health can cause unhappiness. After allowing for this, and for lifestyle and behavioural factors which affect health, happiness and related measures of wellbeing do not appear to have any direct effect on mortality.
Liu et al. Lancet 2016; 387:874-81

Smoking, obesity increase risk of cataract
Using linked hospital admissions data, diabetes, smoking, and obesity were risk factors for cataract surgery in women in our study. Alcohol use, physical activity, and use of HRT were not associated with cataract surgery risk.
Floud et al. Ophthalmology 2016;123:1704-10

Tubal ligation (sterilisation) reduces risk of ovarian and other cancers
Women who have had their Fallopian tubes tied to prevent pregnancy have a reduced risk of developing cancers of the ovary and of the peritoneum lining the pelvis, as well as of the Fallopian tubes themselves. This may be because tying the tubes interrupts the passage of cancer-related cells or chemicals.
Gaitskell et al, Br J Cancer 2016;114:1033-7

Night shift work does not affect breast cancer risk
It has been suggested that working at night may affect the risk of breast cancer – but with substantial additional evidence from the Million Women Study and other UK studies we found no change in risk, once other factors (such as obesity) have been taken into account.
Travis et al, J Natl Cancer Inst. 2016;108(12).pii: djw169

For more about study results as they emerge, you can go to the study progress section of our web site: www.millionwomenstudy.org

If you have any comments or suggestions, please contact lynden.guiver@ceu.ox.ac.uk


Newsletter - December 2015

It is nearly 20 years since we started recruiting UK women to participate in the Million Women Study. With continued funding from the Medical Research Council and Cancer Research UK, the study is providing answers to many questions relating to women’s health. We are most grateful to our participants and collaborators for their continued support.

Million Women Study investigations published in scientific journals since October 2014
Information provided by the MWS participants has been instrumental in our research to help clarify some of the uncertainties about risk factors for cancers and vascular disease in women, and provide novel insights into potential causes of these diseases. Summaries of all published studies are available on the study website (www.millionwomenstudy.org), but here are a number of our recent findings:

Hormone replacement therapy (HRT), oral contraceptives, and cancers of the ovary and the endometrium
MWS investigators combined efforts with other scientists in a global collaboration. HRT use increases the risk of ovarian cancer, with use for five years from around age 50 years associated with about 1 extra ovarian cancer per 1000 users. In contrast, oral contraceptive use gives long term protection against endometrial cancer, and oral contraceptives may have prevented 200,000 cases worldwide in the last 10 years alone.
Beral V, et al. Lancet 2015;385:1835
Allen N, et al. Lancet Oncol 2015;16:1061.

Risk factors for ‘rare’ cancers
Our investigations into less common cancers suggest that oestrogen-only HRT use is associated with increased risks of brain tumours, but the risks are small (2 extra cases per 10,000 users over 5 years). We also identified factors associated with increased risk of anal cancer, including smoking, and a history of cervical precancer.
Benson VS, et al. Int J Cancer 2015;136:2369
Coffey K, et al. Br J Cancer 2015;112:1568.

Determinants of heart disease and stroke
Physical activity is known to be beneficial to health. We found that at moderate levels, it was associated with lower risks of heart disease and stroke; but among women who were already active, increasing its frequency does not seem to confer further reduction in risks. It has also been thought that participation in social activities may prevent heart disease. In the MWS, those who participated in social activities were more likely to be non-smokers, physically active, and have better self-rated health, which largely explained why they had a lower risk of heart disease than those who do not engage in social activities.
Armstrong ME, et al. Circulation 2015;131:721
Floud S, et al. Eur J Prev Cardiol 2015 (E-pub)

Risk factors for dementia
A new area of research for the study is dementia. With such a large, long term study we hope to add to what is known about lifestyle risk factors.

Blood samples and genetic studies
We continue to collect blood samples for some women in the study, for genetic studies of breast cancer and of vascular disease.

Please let us know if you have any comments or suggestions. Contact: Lynden Guiver lynden.guiver@ceu.ox.ac.uk

Study website: www.millionwomenstudy.org


Newsletter - October 2014

We are grateful for the continued support of all our collaborators and study participants. In addition to the funding awarded to the Million Women Study in 2013 from the Medical Research Council, we are pleased to announce continued funding from Cancer Research UK. We now have more than 13 years of follow-up which will allow us to answer many questions about women’s health.

Million Women Study papers published since October 2013
Published papers include studies of organic food consumption in relation to risk of cancer, the link between birth weight and cancer risk in adulthood, and ethnic differences in the risk of breast cancer. We have also looked at risk factors for coronary heart disease, diverticular disease and hospital admissions for different conditions. Summaries of all publications are available on the study website:

Hospital admissions and excess weight
We estimated rates of admission to hospital according to body mass index. We found that one in eight of all admissions of women to hospital in the UK are linked to overweight or obesity. Hospital admissions for diabetes, knee-replacement, gallbladder disease and venous thromboembolism were most strongly associated with body mass index.

Reeves GK et al; Hospital admissions in relation to body mass index in UK women: a prospective cohort study. BMC Med 2014; 12:45.

Organic food and cancer
Organically produced foods are less likely than conventionally produced foods to contain pesticide residues. We found that there was little or no decrease in the risk of developing cancer associated with eating organic food, except possibly for non-Hodgkin lymphoma.

Bradbury KE et al; Organic food consumption and the incidence of cancer in a large prospective study of women in the United Kingdom. Br J Cancer 2014; 110:2321-6.

Blood Samples and the disease susceptibility study
We have been asking more study participants to provide blood samples to help us expand our understanding of the relationship between genetic and biochemical factors and disease susceptibility. The total number of blood samples collected is now 48,559.

The lab staff are always delighted to receive the gift of blood from a participant and look forward to reaching the 50,000 milestone next year.

Online diet questionnaire
To date, 96,000 online diet questionnaires have been completed. We’re still collecting data and hope to get even more participants involved now that our email list has been updated via the 4th general follow-up questionnaire.

4th General follow-up questionnaires
The mailing of the 4th general follow-up questionnaire was completed in March 2014 and around 600,000 responses have been received.

All of our questionnaires and publications can be viewed on the study website.
www.millionwomenstudy.org

Please let us know if you have any comments or suggestions. Contact: Barbara Crossley barbara.crossley@ceu.ox.ac.uk


Newsletter - October 2013

With more than 12 years of follow-up now available the Million Women Study continues to be an extremely valuable resource for the study of women’s health. With a new period of funding recently awarded by the Medical Research council to support the study until October 2018, we look forward to answering many new questions related to the health of our cohort. We are grateful for the continued support of all our collaborators and study participants.

We have published 23 MWS papers in 2012 and 2013. These include studies of body size, smoking, reproductive factors, alcohol consumption, pet ownership, mobile phone use, genetic and environmental factors, as they relate to cancers at specific sites. We have also looked at some risk factors for coronary heart disease, fractures, and motor neuron disease. All publications are available on the study website: www.millionwomen study.org.

Genes, the environment, and breast cancer
We found that in situ ductal breast cancers (DCIS) and invasive ductal breast cancers had similar genetic and environmental risk factor profiles, implying that they both share the same aetiology. However, while there was an association between BMI and invasive ductal breast cancer, there was no association of BMI with DCIS. This suggests that BMI may influence disease progression.

Reeves G.K., et al; Comparison of the effects of genetic and environmental risk factors on in situ and invasive ductal breast cancer. International Journal of Cancer 2012; 131:930-937

The 21st century hazards of smoking and benefits of stopping
Women born in developed countries during the early 1940s were the first generation in which a substantial number of women smoked throughout their adult life. We found that long term cigarette smokers lose at least 10 years of their lifespan. However, stopping smoking before the age of 40 years avoids more than 90% of this increased risk of death.

Pirie K, et al; The 21st century hazards of smoking and benefits of stopping: a prospective study of one million women in the UK. Lancet 2013; 381: 133-141.

Blood Samples and the disease susceptibility study
We have been asking more study participants to provide blood samples to help us expand our understanding of the relationship between genetic and biochemical factors, and disease susceptibility. This phase of blood collection is due to be completed by the end of 2014.

4th General follow-up questionnaires
Mailing of the 4th general follow-up questionnaire began in June 2013 and will finish in March 2014.

Online diet questionnaire
To date, 27 500 women have completed at least one online 24-hour dietary recall questionnaire.

What do you think of our website? Please let us know if you have any comments or suggestions. Contact: Barbara Crossley barbara.crossley@ceu.ox.ac.uk


Newsletter - August 2011

Thank you to all who attended our collaborators’ meeting in April last year – we hope you enjoyed the day. With more than 10 years’ follow-up and a huge amount of data collected this is an exciting time for the study: we are very grateful for the continued support from women in the study and from all our collaborators.

Timing of HRT use affects breast cancer risk
We have updated and extended our results on HRT and breast cancer (first published in 2003). A new finding is that the increased risk of breast cancer in HRT users is greater when HRT is started around the menopause than if it is started later.

Beral V, Reeves G, Bull D, Green J; for the Million Women Study Collaborators. Breast Cancer Risk in Relation to the Interval Between Menopause and Starting Hormone Therapy J.Natl Cancer Inst 2011 Feb 16;103(4):296-305. Epub 2011 Jan 28.

Genes and breast cancer risk
Our first publications on genetic factors came out in 2010. Several common genes for breast cancer have recently been identified, each of which carries only a small increased risk. We showed that these genes affect risk separately from non-genetic factors such as HRT and obesity; and that, even in combination, they have only a modest effect on breast cancer risk.

Reeves GK, et al; Incidence of breast cancer and its subtypes in relation to individual and multiple low-penetrance genetic susceptibility loci. JAMA. 2010 Jul 28;304(4):426-34

Travis RC, et al; Gene–environment interactions in 7610 women with breast cancer: prospective evidence from the Million Women Study Lancet 2010;375(9732):2143-51. Epub 2010 Jun 3.

The 15 other MWS papers published since our last newsletter in 2009 include studies of height and cancer, fluid intake and kidney cancer, and obesity in relation to liver cirrhosis and to hip fracture. All publications are available on the study website: www.millionwomen study.org.

Another data entry milestone
In March 2011 we finished entering data from the 2nd general follow up questionnaire. Approximately 700,000 questionnaires were returned from the mail out of 1.3 million sent out in 2006-7. To mark this occasion we had a small celebration in the unit, with a suitable cake.

The 3rd follow-up questionnaire
Mailing of the 3rd general follow-up questionnaire began in 2010 and will finish in early 2012. We are also investigating online questions to supplement postal questionnaires. Since July 2010 11,000 women have completed a diet questionnaire.

What do you think of our website?
Please let us know if you have any comments or suggestions. Contact: Barbara Crossley barbara.crossley@ceu.ox.ac.uk


Newsletter - June 2009

A DIARY DATE
Collaborators’ meeting: Wednesday April 28th 2010

The next Collaborators’ meeting will be in Oxford on the above date. We will be sending out details at a later stage. We will be delighted to see you all again at the Richard Doll Building for the meeting.

Publications since the last newsletter in December 2007

The most recent publication was the ‘Moderate Alcohol Intake and Cancer Incidence in Women’ paper.

The conclusions were that low to moderate alcohol consumption in women increases the risk of certain cancers. For every additional drink regularly consumed per day, the increase in incidence up to age 75 years per 1000 for women in developed countries is estimated to be about 11 for breast cancer, 1 for cancers of the oral cavity and pharynx, 1 for cancer of the rectum, and 0.7 each for cancers of the oesophagus, larynx and liver, giving a total excess of about 15 cancers per 1000 women up to age 75.

Allen NE, Beral V, Casabonne D, Kan SW, Reeves GK, Brown A, Green J. J Natl Cancer Inst 2009;101:296-305

There have been 12 other papers published since 2007. These include:

Reeves GK, Pirie K, Green J, Bull D, Beral V; Million Women Study Collaborators. Reproductive factors and specific histological types of breast cancer: prospective study and meta-analysis. Br J Cancer. 2009 Feb 10;100(3):538-44.

Liu B, Balkwill A, Roddam A, Brown A, Beral V on behalf of the Million Women study Collaborators. Separate and joint effects of alcohol and smoking on the risk of cirrhosis and gallbladder disease in middle-aged women. Am J Epidemiol 2009 Jan 15;169(2):153-60.

Reeves G, Pirie K, Beral V, Green J, Spencer E, Bull D for the Million Women Study Collaborators. Cancer incidence and mortality in relation to body mass index in the Million Women Study: cohort study. British Medical Journal; 2007 Dec 1;335(7630):1134.

All the papers are described, with a summary of each paper in the Publications section of this website.

The lilac follow-up questionnaire

The whole cohort of 1.3 million women were sent lilac follow-up questionnaires in 2006-7. Approximately 700K were returned. and 42% are now scanned and verified. This questionnaire will provide us with additional information that will inform us of any incident illnesses and diet/medication changes.
A copy of the lilac questionnaire is also available on our website in the questionnaires section.

The next follow-up questionnaire

This questionnaire is still on the drawing board and the colour has yet to be decided but it will be ready to go out in 2010. We are also investigating online questions to supplement postal questionnaires

Blood collection for genetics

With the help of participants, general practitioners and practice nurses throughout the UK we have collected almost 34,000 blood samples. This year we have also asked practice staff in selected areas of England to help with a body measurements validation exercise. This involves taking a participant’s height, weight, waist and hip measurements, in addition to collecting a blood sample. To date, we have received body measurements taken in general practices for over 2,300 women, which will be used to validate those reported on our questionnaires.

In addition, we have kept abreast of recent national changes to the government’s health research strategy by registering the study on the Clinical Research Network Portfolio of the National Institute for Health Research. This entitles the study to support from the NHS Service Support Fund for research activity undertaken in the NHS, which is now managed by the new Comprehensive Local Research Networks.


Newsletter - December 2007

Ovarian Cancer and HRT

Our third major paper on hormone replacement therapy and cancer was published in April this year. This means we have analysed data on three major cancers in women – breast (published 2003), endometrial (published 2005) and now ovarian cancer – and we are beginning to build up a picture of the overall effects of different types of HRT on cancer risk.

We found a small increase in risk of incident and fatal ovarian cancer in women taking HRT – equivalent to about 1 extra cancer per 2500 women over 5 years – and no increased risk in past users. There was no difference between combined and oestrogen-only HRT for ovarian cancer; but because breast cancer is much more common, and is more strongly related to combined than to oestrogen-only HRT, overall women taking combined HRT are at higher risk for breast, endometrial and ovarian cancers combined than women taking oestrogen-only HRT.

Million Women Collaborators. Ovarian cancer and hormone-replacement therapy in the Million Women Study. Lancet 2007;369: 1703-10

New publications

As well as the paper on ovarian cancer, we have published 3 other papers using MWS data; on obesity and cancer:

Reeves G, Pirie K, Beral V, Green J, Spencer E, Bull D for the Million Women Study Collaborators. Cancer incidence and mortality in relation to body mass index in the Million Women Study: cohort study. British Medical Journal; DOI:10.1136/bmj.39367.495995.AE

(This paper can be found on line)

on height and weight and joint replacements:

Liu B, Balkwill A, Banks E, Cooper C, Green J, Beral V on behalf of the Million Women Study Collaborators. Relationship of height, weight and body mass index to the risk of hip and knee replacements in middle-aged women. Rheumatology May 2007; 46: 861-867

and a methodological paper comparing hospital records and self-reported disease incidence:

Liu B, Sweetland S, Beral V, Green J, Balkwill A, Casabonne D on behalf of the Million Women Study Collaborators. Self-reported information on joint replacement and cholecystectomy agrees well with that in medical records. Journal of Clinical Epidemiology 2007;60:1190-1194

Data from the Million Women Study has also been included in several collaborative publications on cervical cancer. Details of these publications can be found in the publications section of this website.

Blood collection for genetics

With the help of participants, GPs and practice nurses throughout the UK we have already collected over 24,000 blood samples and first genetic analyses are underway. This part of the study will continue for at least another 3 years (see Disease Susceptibility Study on the website).

Medical Research Council: continued funding

We are delighted to have been awarded a further 5 year grant from the MRC: this will fund further data collection and storage of blood samples and analyses of cardiovascular disease and other non-cancer outcomes

Collaborators’ meeting

The next collaborators’ meeting will be held in 2009 and not in 2008 as stated in our last newsletter.

End of the yellow era

In September 2007, we finished entering data from the first follow up questionnaires of the study. 862,035 women responded to the follow up questionnaire or yellow questionnaire, as it is known in the unit. These questionnaires were mailed initially in mid 1999 and the last mailing was in early 2005.

To mark this occasion we held a small celebration in the unit, this party also marked the semi-retirement of Barbara Crossley, one of our longest serving members of staff who manages our data entry staff and questionnaire entry in Oxford. A cake moulded and decorated in the shape of a questionnaire was made by two of the team. Barbara will continue to work on a part-time basis and can be contacted as usual on 01865 289625.

We have now moved onto entering data from the second follow up phase with the lilac questionnaires. All these questionnaires are displayed on this website.


Newsletter - October 2006

Collaborators’ meeting: Wednesday May 10th 2006

We were delighted to welcome many of you to our collaborators’ meeting in May. We hope that you enjoyed the opportunity to see our new building and to hear how the study is progressing. As in previous years, the meeting was chaired by Martin Vessey and Julietta Patnick; presentations included talks on HRT and histological types of breast cancer, on surgical management of breast cancer, on smoking and cancer, on pancreatic and ovarian cancers and on gallbladder disease. We hope to publish many of these results soon. The next collaborators’ meeting will be held in 2008.

New publications

Since our last Newsletter three Million Women Study papers have been published. Two deal with methodological issues: a paper by Toral Gathani comparing the classification of Breast Cancer in screening clinic records and in ONS:

and a comparison of self reported cervical smear histories from one of our follow up questionnaires and NHS records by Karen Canfell.

Emily Banks has also published a further paper on false positive recall following mammography.

Blood collection in the Million Women Study

We are in the process of collecting blood samples from over 20 000 women in the Million Women Study. The aim is to extract and store DNA so we can include genetic factors in our analyses. We have begun collection in England, and will proceed to Scotland later on this year. Selected women are sent an invitation to provide a blood sample and a further questionnaire to complete; they then go to their GP to have the sample taken. We are indebted to the GPs and practice nurses throughout the country who have agreed to help; without them we would not be able to collect blood from such a widespread study population. Samples are posted back to our laboratory where they are processed prior to DNA extraction.We hope that the results from this part of our study will provide us with a greater insight into the separate and joint effects (eg with other factors such as use of HRT) of genetic factors on susceptibility to disease within the Million Women Study.

Second general follow-up questionnaire

The whole cohort of 1.3 million women is being sent a second general follow-up questionnaire this year, on average 6 years since the first general follow-up (yellow). This new questionnaire (lilac) will provide us with updated and additional information on factors such as diet,exercise and general well being. It will also inform us of any incident illnesses and changes in diet or medication. A copy of the new questionnaire is available on our website in the questionnaires section.


Newsletter - July 2005

The Richard Doll Building

The Million Women Study now comes to you from our splendid new offices in the Richard Doll Building at the Churchill Hospital site in Headington, Oxford. Much more space and light, as well as the benefits of closer liaison with colleagues, including Julietta Patnick of the NHS Cancer Screening Programme, who will have a research office in this building.

Next collaborators’ meeting: Wednesday May 10th 2006

The next meeting for collaborators will be held here in the Richard Doll Building on Wednesday May 10th 2006. Details and an invitation form will be sent out nearer the time.

New Publications

Two papers have recently been published from the Million Women Study: a major paper on endometrial cancer (Lancet 2005; 365:1543-51) and an assessment of the validity of the dietary questions in the first follow-up (yellow) questionnaire (Public Health Nutrition 2005;8:201-13).

Diet questions at follow up

The first follow-up questionnaire included a set of questions about diet. Dr Andrew Roddam and Million Women Study colleagues looked at how reproducible and how accurate the answers to these questions were, by comparing the same set of questions answered at different times by a subgroup of 12 000 women in the study, and by comparing the answers to questions with more precise answers from 7-day diet diaries. The diet questions were answered consistently over time and provided a reasonably good assessment of nutrients such as carbohydrate, fat, cholesterol, sugars, alcohol,fibre and vitamins. This work will help us to use diet information from the questionnaires in future analyses.

Endometrial Cancer

Analysis based on 3-4 year follow-up of over 716 000 post-menopausal women, of whom 1320 were diagnosed with incident endometrial cancer, showed that different types of hormone replacement therapy had very different effects on the risk of endometrial cancer. Compared with never users of HRT, risk was increased with use of oestrogen-only HRT (1.5 times the risk of never users) and of tibolone (1.8 times); was not changed with use of cyclic combined HRT, and was reduced (0.7 times) with use of continuous combined HRT. These effects were significantly affected by a woman’s body mass index, so that the adverse effects of oestrogen and tibolone were greatest in lean women and the beneficial effects of combined HRT greatest in obese women. The increased risk of endometrial cancer with oestrogen-only HRT is of course well known and is the reason why women with a uterus are generally prescribed combined HRT preparations. The increased risk with tibolone was not previously clear, nor were the details of the effects of combined HRT and the joint effects with body mass index.

The Million Women Study is the only large HRT study with data on both breast and endometrial cancer and it is clear that overall, the increased risk of breast cancer with combined HRT outweighs any benefit there may be from combined therapy in terms of endometrial cancer. These results therefore have major implications for clinical practice.


Newsletter - November 2004

Million Women Study Publications

Three more papers have been published this year: one on fractures, and two on the efficiency and effectiveness of mammography in hormone replacement therapy (HRT) users.

Fractures and HRT

Based on nearly 3 years’ follow-up of 140 000 postmenopausal women recruited between 1996 and 1998, Million Women Study findings published in May 2004 (JAMA 2004; 291: 2212-2220) confirmed that current users of HRT have fewer new fractures than women not taking HRT. We were able to show that protection against fractures was similar for different types of HRT (oestrogen only, combined oestrogen-progestagen, and other types including tibolone) and different doses of hormones, but that protection disappeared within a year of stopping HRT use. For most women the increased risk of breast cancer and stroke will outweigh this benefit of HRT.

Mammography is less sensitive and less specific in HRT users

Two papers (BMJ May 2004;328:1291-1292 and BMJ Aug 2004;329:477-479), based on mammographic screening in the Million Women Study, have confirmed that mammography is both less sensitive and less specific for detection of breast cancer in women taking HRT. Similar results were found for different types and doses of HRT. This effect of HRT is probably related to increased breast density, and seems to last for some years after HRT use has stopped. One result is an increased risk of false positive recall within the Breast Screening Programme; another is that cancers are less likely to be detected at screening, and more likely to present as interval cancers.

New premises: the Richard Doll Building

The Million Women Study will be moving to brand new premises next year as the Radcliffe Infirmary closes. The Richard Doll Building, at the Churchill Hospital site in Oxford, will bring the Cancer Research UK Epidemiology Unit together with the Clinical Trial Service Unit and other public health and epidemiology departments of Oxford University. Work on the building, by Nicholas Hare Architects, is nearing completion.

Dark blue banner
The Richard Doll Building

2005: Next Collaborator’s meeting

We hope to be settled in the new building by summer 2005, ready to host the next Collaborators’ meeting in the autumn. We will send out details nearer the time.

Thank you to screening clinic staff

Moya Simmonds, Elizabeth Hilton and Barbara Crossley would like to thank screening clinic staff for their help during the collection of data for 2002-2003, giving details of breast cancers that have developed in the ladies who returned our questionnaires in those long ago days when you were all kind enough to send them out. We were very grateful then to be treated so well when we were causing you extra work, and even happier this year when you made us so welcome in spite of again causing work for the Office Managers and disruption for the rest of the offices. We enjoyed meeting familiar faces, and some new ones, and thank you for all your help.

Impact of the Million Women Study

Our paper on breast cancer and HRT was the most downloaded paper in the Lancet for 2003 and is much quoted. The results of the Million Women Study have already influenced prescribing policy in the UK; we hope that future results will continue to help inform the debate on HRT use.


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