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physical activity and fracture in postmenopausal women

371,279 postmenopausal women (mean age 59.8 years), who rated their health as good or excellent and reported participation in walking, cycling, gardening, doing housework, yoga, dance and sports club activities, were followed for  an average of 12 years for site-specific incident fracture (humerus, forearm, wrist, hip, femur (not neck) lower leg and ankle) through record linkage to national databases on day-case and overnight hospital admissions. For upper limb fractures there was significant heterogeneity across the 7 activity types, with gardening more than one hour/week associated with a lower risk, whereas cycling more than an hour/week was associated with an increased risk. For fractures of the lower limb including hip there was no significant heterogeneity by type of activity, with significant approximately 5-15% reductions in risk associated with most activities, except cycling. For hip fractures, there was no significant heterogeneity by type of activity, but with significant 15-20% reductions in risk associated with walking for 1 hour/day and participating in yoga and sporting activities. Physical activity is a modifiable risk factor for fracture, but the effects differ between different types of activities and different fracture sites. (Armstrong et al 2019)

Type and timing of menopausal hormone therapy and breast cancer risk: individual participant meta analysis of the worldwide epidemiological evidence  

Published findings on breast cancer risk associated with different types of menopausal hormone therapy (MHT) are inconsistent, with limited information on long-term effects. We reviewed published and unpublished epidemiological evidence on these associationsIf these associations are largely causal, then for women of average weight in developed countries, 5 years of MHT, starting at age 50 years, would increase breast cancer incidence at ages 50–69 years by about one in every 50 users of oestrogen plus daily progestagen preparations; one in every 70 users of oestrogen plus intermittent progestagen preparations; and one in every 200 users of oestrogen-only preparations. The corresponding excesses from 10 years of MHT would be about twice as great. (Beral et al, 2019)

lifestyle and colorectal cancers

Using data on 628,976 women screened using a guaiac-faecal occult blood test (gFOBt) between 2006 and 2012. relative risks and 95% confidence intervals were estimated by logistic and Cox regression for associations between individual lifestyle factors and risk of colorectal tumours. Current smoking was significantly associated with risk of interval cancer but not with risk of screen-detected cancer  and was the only factor of eight examined to show a significant difference in risk between interval and screen-detected cancers. Compared to screen-detected cancers, interval cancers tended to be sited in the proximal colon or rectum, to be of non-adenocarcinoma morphology, and to be of higher stage. (Blanks et al, 2019)

Association of gastrointestinal and other conditions with positivity to faecal occult blood testing

The Bowel Cancer Screening Programme (BSCP) in England offers biennial faecal occult blood testing (FOBt) at ages 60-69 years. This study found that FOBt positivity is associated with a substantially increased risk of colorectal neoplasms after screening. Adenoma, diverticular disease, inflammatory bowel disease, haemorrhoids, upper gastrointestinal cancer, oesophagitis, peptic ulcer, anaemia and other haematological disorders are also associated with FOBt positivity, both before and after screening. (He et al, 2019)

Bmi in midlife and risk of attempted suicide and suicide

1.2 million women, with a mean age 56 years, and no prior suicide attempts or other major illness, were followed by record linkage to national hospital admission and death databases. Being underweight was associated with a definite increase in the risk of suicidal behaviour, particularly death by suicide. Residual confounding could not be excluded for the small and inconsistent decreased risk of suicidal behaviour associated with being overweight or obese. (Geulayov et al, 2019)

cohort profile: The million Women Study 

Green et al 2019

BMI and use and costs of primary care services  

Among all women aged 55-79 years in England, excess weight accounted for an estimated 11% (£229 million/£2.2 billion) of all consultation costs and 20% (£384 million/£1.9 billion) of all prescription medication costs, of which 27% were for diabetes drugs, 19% for circulatory system drugs, and 13% for analgesics. (Kent et al, 2019)

Foods, macronutrients and breast cancer risk in postmenopausal women

Baseline diet was assessed in 2000-04 using a validated questionnaire in 691 571 postmenopausal UK women without previous cancer, who had not changed their diet recently. They were followed for 12 years by record linkage to national cancer and death databases. 29 005 were diagnosed with invasive breast cancer. By far the strongest association was between alcohol intake and an increased risk of breast cancer. Higher intakes of fruit and fibre were associated with lower risks of breast cancer, but it is unclear whether  these associations are causal. (Key et al 2019)

Diet and risk of glioma

Available evidence on diet and glioma risk comes mainly from studies with retrospective collection of dietary data. To minimise possible differential dietary recall between those with and without glioma, this study presents findings from three large prospective studies: participants included 692,176 from  the Million Women Study, (UK) 470,780 from the NIH-AARP Study (US), and 99,148 from the PLCO Study (US). The largest prospective evidence to date suggests little, if any, association between major food groups, nutrients, or common healthy dietary patterns, and glioma incidence. (Kuan et al, 2019)

Alcohol drinking patterns and liver cirrhosis risk

In middle-aged women, cirrhosis incidence increases with total alcohol intake, even at moderate levels of consumption. For a given weekly intake of alcohol, this excess incidence of cirrhosis is higher if consumption is usually without meals, or with daily drinking. (Simpson et al, 2019)

oral bisphosphonates and risk of osteonecrosis of the jaw

About 1 in 10 postmenopausal UK women are prescribed oral bisphosphonates to treat osteoporosis. Osteonecrosis of the jaw is a recognised uncommon but important side effect of intravenous bisphosphonates, but epidemiological evidence on risk of osteonecrosis of the jaw associated with oral bisphosphonate use is less conclusive. The incidence of hospital admission with osteonecrosis of the jaw was examined among 521,695 Million Women Study participants, aged 64.7 years at baseline. In this  population, use of oral bisphosphonates was associated with a 6-fold increased risk of hospital admission with osteonecrosis of the jaw, accounting for around one-third of cases, with an excess risk of about 0.6/1000 users over 5 years. (Wotton et al, 2018)

cancer risk in women who were breastfed as infants

548,741 women without prior cancer reported whether they had been breastfed and were followed by record-linkage to national cancer registration, hospital admission and death databases. Of eight cancers examined one association was highly statistically significant: an increase in colorectal cancer incidence among women who had been breastfed. Eight other gastro-intestinal conditions, were studied and increased risks in women who had been breastfed versus not were found for benign colorectal polyps and for appendicitis.  (Yang et al, 2018)

Coffee and pancreatic cancer risk in women who have never smoked

Reported associations between coffee consumption and an increased risk of pancreatic cancer could be due to residual confounding by smoking and/or biased recall of coffee consumption in retrospective studies. Studying associations prospectively in never smokers should minimise these problems. 309,797 never-smoking women self-reported typical daily coffee consumption at a mean age of 59.5 years and were followed up for a median of 13.7 years through record linkage to national health cancer and death registries. A meta-analysis of results from this cohort and three smaller prospective studies found little or no statistically significant association between coffee consumption and pancreatic cancer risk in never smokers. (Zhou et,al, 2019)


Histological subtypes of ovarian cancer associated with parity and breastfeeding

Ovarian cancer risk is known to be reduced amongst women who have had children, but reported associations with breastfeeding are varied. Few studies have had sufficient power to explore reliably these associations by tumour histotype. In a prospective study of 1.1 million UK women, 8719 developed ovarian cancer during follow-up. Women  who had not given birth had a 24% greater ovarian cancer risk than women with one child, with significant heterogeneity by histotype. There was no significant increase in serous tumours, a modest increase in mucinous tumours, but a substantial increase in endometrioid and clear-cell tumours. Each additional birth was associated with an overall 6% reduction in ovarian cancer risk; this association also varied by histotype, with the largest reduction in risk for clear-cell tumours and weak, if any, effect for endometrioid, high-grade serous, or mucinous tumours. The results showed little association with age at first or last birth. There was about a 10% risk reduction per 12-months breastfeeding, with no significant heterogeneity by histotype, but statistical power was limited. (Gaitskill et al, 2018)

participation in colorectal cancer screening in Australia

The Australian Government’s National Bowel Cancer Screening Program (NBCSP) provides free home-based immunochemical faecal occult blood test to eligible Australians turning 55 and 65 in that year. This study investigated factors associated with self-reported ever-uptake of the NBCSP and of any CRC screening using follow-up questionnaire data from 105,897 Australians aged ≥45years enrolled in the 45 and Up Study in New South Wales, Australia. The study found that smokers, disadvantaged groups and those with lower levels of education and non-English speaking backgrounds are less likely to have ever-participated in organised screening through the NBCSP or in any form of CRC screening. (He et al , 2018

skin carcinoma and smoking

1,223,626 women without prior cancer were followed using electronic linkage to national cancer registration data for 14 years. Questionnaire information about smoking and other factors was recorded at recruitment (1996-2001) and every 3-5 years subsequently. In current versus never-smokers, cutaneous squamous cell carcinoma (SCC) incidence was increased but basel cell carcinoma (BCC) incidence was decreased. The study concluded that smoking-associated risks for SCC and BCC are in the opposite direction to each other and appear to vary by anatomical site. (Pirie et al, 2018)

Differences in risk factors for three types of stroke

A 12.9 year follow-up study found that classic risk factors for stroke such as diabetes, obesity and smoking have considerably different effects on the three main types of stroke: subarachnoid hemorrhage and intracerebral hemorrhage and ischemic stroke. (Price et al, 2018)

alcohol drinking patterns and cirrhosis risk

Over 15 years of follow-up of 401806 women with a mean age of 60, without previous cirrhosis or hepatitis, and who reported drinking at least one alcoholic drink per week, 1560 had a hospital admission with cirrhosis or died from the disease. Cirrhosis incidence increased with amount of alcohol consumed per week. About half of the participants reported usually drinking with meals and, after adjusting for amount consumed, cirrhosis incidence was lower for usually drinking with meals than not. Among 175618 women who consumed seven or more drinks per week, cirrhosis incidence was greater for daily consumption than non-daily consumption. Daily consumption, together with not drinking with meals, was associated with more than a doubling of cirrhosis incidence. (Simpson et al 2018)


Night shift work and breast cancer  

Using information from nearly 800,000 women we found no evidence for an association between night shift work and development of breast cancer even amongst women who had worked nights for over 20 years. other large UK studies, EPIC-Oxford and UK Biobank, This lack of association was confirmed when we combined our results with those of 10 other studies. (Travis et al, 2016)

Women with disabilities less likely to take part in breast or bowel cancer screening 

Around a quarter of 500,000 women in England who answered the 8-year re-survey reported some form of disability. Women with a disability were 40% less likely than women without a disability to have attended for recent breast screening, and 25% less likely to have taken part in bowel cancer screening. Disabled women without access to a car were particularly unlikely to have had breast screening, which requires attendance at a clinic, while the bowel cancer screening test is done at home. Our findings suggest that women with disabilities may not have equitable access to the free NHS cancer screening programmes. (Floud et al, 2017)

Antidepressants, depression and risk of blood clots

Seven percent of the 730,000 women in our study, reported using antidepressants. Previous studies reported that depression and the use of antidepressants may be linked to risk of blood clots in the veins (venous thromboembolism, VTE, most commonly seen as clots in the legs, or lungs.) We found that women taking antidepressants had about a 40% increased risk of VTE compared with those not taking antidepressants, but there was no increased risk in women with depression or anxiety who were not taking antidepressants. It is not clear whether this higher risk is due to the antidepressant medications, or to other factors associated with depression or anxiety. (Parkin et al, 2017)


Height and Fracture Risk

We confirmed that the risk of a hip fracture rose with increasing height, with about a 50% higher risk with each additional 10cm of height. An increased risk was also found for other fracture sites but to a lesser extent. Possible explanations for this higher risk in taller women are larger distance when falling, the greater force on the bones of taller or heavier women when they fall and perhaps differences in bone shape and structure between shorter and taller women. (Armstrong et al, 2016)

Explaining social inequalities in heart disease risk

Research suggests that the higher rates of coronary heart disease in those living in more deprived areas and with less education could be explained by differences in health-related behaviours. We found that at least 70% of the differences in heart disease risk by education and deprivation group could be explained by differences in four health-related behaviours. The larger proportion of smokers in poorer and less educated groups explained the greatest part of the difference in risk. Higher levels of physical inactivity and of overweight and obesity and differences in levels of alcohol consumption also played an important role. (Floud et al, 2016)

Happiness, health and mortality 

Women who reported feeling unhappy were no more likely to die from any cause, or specifically from cancer or from heart disease, than women who reported feeling happy most of the time. Poor health may cause unhappiness, and poor health increases the risk of dying: but we found no evidence to relate happiness itself to mortality. (Liu et al, 2016)

Lung cancer in never smokers 

A small proportion of lung cancers develop in people who have never smoked. Approximately half the women in the Million Women Study have never smoked. We looked at 34 possible risk factors in over 600,000 of these never smokers and found three factors associated with risk of lung cancer: height (taller women at higher risk), ethnicity (non-White women at higher risk), and asthma (higher risk in women with asthma requiring treatment). The increased risks associated with these three factors are small compared with the risk associated with smoking. (Pirie et al, 2016)

Tubal ligation and risk of ovarian and other cancers 

Many studies have linked cutting, clipping or tying the Fallopian tubes to prevent pregnancy to a lower risk of developing ovarian cancer. Comparing women who had been sterilised to those had not we found that risk of some types of ovarian cancer was reduced, and of others unchanged. The Fallopian tubes provide a passage between the ovary/abdominal cavity and the womb; it is thought that with the tubes tied, cancer-causing cells or other substances are less able to travel along the tubes. (Gaitskell, Coffey et al, 2016)

Diabetes, smoking and obesity increase the risk of cataract surgery

Using linkage to hospital admissions records, we studied potential risk factors for having cataract surgery. We confirmed that increasing age and diabetes are the strongest risk factors (women with diabetes have 3 times the risk of cataract as women without diabetes) and found that risk of cataract surgery was also modestly increased in smokers, and in obese women. There was no link with HRT use as had been previously suggested.  (Floud et al, 2016)


HRT and ovarian cancer

A collaborative analysis confirmed that current HRT use is associated with a 40% increased risk of ovarian cancer, or one extra case of ovarian cancer per 1000 women using HRT for 5 years from age 50.  We found similar risks for oestrogen-only and combined oestrogen-progestagen therapy, and the risk remained increased for many years after HRT use stops. (Beral et al, 2015

Oral contraceptives and endometrial cancer

This study found that 10 years’ use of the oral contraceptive pill reduces later risk of endometrial cancer by half, from 2.3 to 1.3 cases per 100 women and this is a long-lasting effect. Use of the pill is estimated to have prevented 400,000 cases of endometrial cancer worldwide over the past 50 years. (Collaborative Group on Epidemiological Studies on Endometrial Cancer, 2015)

Eating organic foods does not affect cancer risk

Of 630,000 women who provided information on their diet; 7% usually or always ate organic food, and 30% never did.  Over 53,000 women developed cancer during a nine-year period and the risk was the same in women who ate organic food and in those who never did. Of the 16 most common types of cancer our results suggested a possible reduced risk only for one, non-Hodgkin lymphoma.  (Bradbury 2015)

Smoking, obesity and bowel cancer screening 

The NHS bowel cancer screening programme uses a postal Faecal Occult Blood (FOB) test to pick up blood hidden in the stool, which may come from an undetected cancer or potentially precancerous growth. Men and women aged 60-74 are invited to complete the test every two years. Screening programme records show that uptake is lower for people in more deprived socio-economic groups, and higher for older age groups. We confirmed this for the women in our study, and also showed  a lower uptake in screening by women who smoke, by obese women and by non-white ethnic women. The same factors were associated with a higher risk of testing positive on the FOB test, and of having a bowel polyp (a potentially pre-cancerous growth) detected, among women who were screened. (Blanks et al, 2015)

Frequent physical activity may not reduce vascular disease risk as much as moderate activity

We found that the lowest risks of vascular disease (heart disease, stroke and blood clots) were in women who do some physical activity such as walking, cycling and gardening, on two to six days a week. Risks were around 20% higher in women who do no physical activity, and were no lower (and possibly higher) in women who reported exercising every day. (Armstrong et al, 2015)


Ethnic differences in breast cancer incidence in the UK 

In the UK, breast cancer incidence is 15-20% lower in South Asian and black women than in white women. While the majority of women in the Million Women Study are white, the study includes about 6,000 women of South Asian ethnicity and 5,000 black women. We compared the patterns of known risk factors for breast cancer such as childbearing history, body size, HRT use, and alcohol consumption, between ethnic groups and found that differences in these factors could explain most if not all of the differences in rates of breast cancer. For example, South Asian and black women were less likely than white women to drink alcohol or to use HRT, and on average had more children and were more likely to breastfeed their children, all factors which are linked to lower risk of breast cancer. Risk factors for breast cancer act similarly in women from different ethnic groups, and most differences between ethnic groups in the incidence of breast cancer reflect differences in these risk factors. (Gathani et al 2014)

Women who are married or living with a partner have the same risk of developing heart disease as unmarried women, but are less likely to die from heart disease.

We compared the risks of developing heart disease (incident ischaemic heart disease; heart attack or angina) and of dying from heart disease in women who were married or living with a partner, and in those who were not. The risk of developing heart disease was the same for both groups, but married or partnered women were 20-30% less likely to die from heart disease than unmarried women. The reason for this difference is not clear but may reflect social circumstances, such as the presence or absence of another person to raise the alarm, or to encourage a partner to seek early medical help. (Floud et al, 2014)

Measuring the impact of overweight and obesity on hospital admissions

In the 1.25 million women in the study there were nearly three million admissions to hospital and women with a higher body mass index (BMI) were more likely to be admitted. We estimated that one in eight admissions was likely to be due to overweight or obesity. The conditions most strongly associated with BMI were diabetes, knee replacement, blood clots and gallbladder disease but admission for conditions for which a link with obesity has not been so clearly recognised (such as carpal tunnel syndrome, diverticulitis, and cataracts) was also related to BMI. (Reeves et al 2014)


The influence of having children on body size 

Women who have children tend to have a higher body mass index in later life than women who have no children. On average, women in our study each had 2 children, and by their late fifties have an average BMI of 26. Women who had 3 children have an average BMI in their fifties of 26.5, and women who have not had children have an average BMI of 25.6. Breastfeeding for 6 months was associated with lower average BMI in middle age than in women with the same number of children who had not breastfed. Although the differences are small, they are important, because risk of many common diseases in middle and old age (including heart disease, stroke and cancer) is closely related to small differences in BMI. (Bobrow et al, 2013)

What body size means for heart disease risk

The risk of developing coronary heart disease increased smoothly with increasing body mass index across a wide range, from low weight (BMI <20 kg/m2) to obese (BMI 30+ kg/m2), whereas risk of dying from coronary heart disease is higher both in very lean and in very obese women. Risk of coronary heart disease was also, separately, related to waist measurement, so that at any given BMI, women with larger waist had higher risk (Canoy 2013b). Our results suggest that having a BMI of 30 compared to a BMI of 20 is equivalent in terms of heart disease risk to adding 5 years of age. These heart disease analyses are possible because women in the Million Women Study gave permission for us to use their NHS medical records, and we have access to information on hospital admissions for all women in the study. We have shown that this information is accurate and reliable for use in our analyses (Wright et al, 2012) (Canoy 2013a).

Mobile phones and cancer

Most previous studies of a possible link between use of mobile phones and risk of brain tumours involved patients who had been diagnosed with a brain tumour before they were asked about their mobile phone use. Our questionnaires included questions about mobile phone use, and we studied brain tumours and other cancers which developed after we had collected the information on mobile phone use. We found no association between use of mobile phones for many years and risk of brain or other cancer, or of the most common types of benign brain tumour. We found a possible increased risk of acoustic neuroma, (a rare benign tumour of the acoustic nerve which carries impulses from the ear) in women who had used a mobile phone for at least 5 years compared with women who have never used a phone but view this finding with caution because acoustic neuroma is so rare, it could be due to chance. It may be that women using mobile phones were more likely to be investigated for the tumour, because acoustic neuroma can cause hearing loss. (Benson et al, 2013)


The risks of smoking and the benefits of giving up

In many countries, including the UK, women did not begin smoking in large numbers until the 1940s and 50s, while many men started smoking earlier in the century. About half the women in the Million Women Study started smoking, on average, at the age of 19 years, and those still smoking now have smoked for over 50 years. We found that women who had smoked throughout their adult life were three times as likely as those who had never smoked to die prematurely, losing on average 11 years of life. The effects of long-term smoking on risk of death, and risk of smoking-related diseases, such as lung cancer, heart attack and chronic lung disease, were similar to those seen in men with equivalent smoking histories. A woman who starts smoking at 19 and continues until she is 60 is three times as likely to die by the age of 80 as a woman who has never smoked; but stopping smoking at age 30 avoids almost all (97%) of the extra risk in older age. Giving up at age 40 avoids 90% of the extra risk, and smoking for 30 years and stopping at age 50 avoids two-thirds of the extra risk of death that a woman would have had in her 60s and 70s, if she had continued to smoke. (Pirie et al, 2012)

Body size, exercise and fractures: different effects for hip, ankle and wrist

We had already shown that hip fractures are less common in women who take regular exercise, and in fatter women. Fractures of the wrist were also less common in fatter women, but fractures of the ankle were more likely to occur in fatter than in thinner women; and the amount of exercise a woman took did not affect risk of fracture of either wrist or ankle. It is likely that these patterns reflect different effects of exercise and body size on bone health and on risk of falling, or of injury on falling. (Armstrong et al, 2011)

Different types of HRT have different effects on risk of blood clots

Venous thromboembolism includes blood clots in the deep veins of the legs (deep vein thrombosis  or DVT and the less common, but more serious, blood clots in the lungs (pulmonary embolism). Women taking HRT are known to have an increased risk of blood clots in the veins. We looked at the effects of different types of HRT on the risk of serious blood clots causing hospital admission or death. We found women taking oral forms of combined oestrogen-progestagen HRT have about a 2-fold risk, compared with women not taking HRT  [is this about double the risk of women not taking HRT??] , women taking oral oestrogen-only HRT have about a 40% increase in risk; and women using HRT gels or patches have no increased risk. We think that HRT absorbed through the skin, has less effect on the liver, and on chemicals involved in blood clotting, than HRT taken orally.

We also showed that blood clot risk was different for different types of progestagen used in combined HRT. Risks were higher for combined HRT including MPA (medroxyprogesterone acetate) than for combined HRT with norethisterone or norgestrel. Risk of blood clots was raised equally for the two main types of oestrogen-only HRT (equine oestrogen and oestradiol ) used by women in the study.

In women at normal background risk of developing blood clots, our results suggest that over 5 years, about 1 in 700 middle-aged UK women not taking HRT will be admitted to hospital with pulmonary embolism. In women taking oral oestrogen-only HRT this figure rises to 1 in 500, and in women taking oral combined HRT containing norethisterone or norgestrel to 1 in 400. The risk rises to 1 in 250 for women taking HRT containing medroxyprogesterone acetate (MPA).  (Sweetland, Beral et al 2012)


Timing of HRT influences breast cancer risk

The increased risk of breast cancer is greater when HRT is started around the time of menopause than later. We found a higher risk of breast cancer in HRT users compared with those who had never used HRT, with the risk greater for combined oestrogen-progestagen HRT than for oestrogen-only HRT, and a rapid fall in risk after HRT is stopped. Women taking combined HRT had an increase in breast cancer risk of about 50% if they started HRT five years or more after menopause, but of 100% if HRT use started close to menopause.  Women starting oestrogen–only HRT five or more years after menopause had no increased risk of breast cancer, while the risk increased by about 40% for those starting treatment closer to the menopause. (Beral et al, 2011) (Beral et al, 2003)

Body size and physical activity both affect hip fracture risk

We investigated how body mass index (BMI) and levels of physical activity are linked to risk of hip fractures using linkage to NHS records on hospital admissions. We found that women with a BMI of 30 or more were about half as likely as thinner women to have a hip fracture, and that the risk was about 30% lower for women who took any regular exercise compared with those who took no exercise. The effects of body size and exercise were independent of each other: physical activity was linked to a lower risk of hip fracture and a higher BMI was also linked to lower fracture risk. Fatter women may benefit both from stronger bones and from cushioning when they fall; exercise is thought to help to strengthen bones and improve balance and coordination, reducing the likelihood of serious falls. (Armstrong et al, 2011)