Background

High risk prescribing can compromise independent wellbeing and quality of life in older adults. The aims of this project are to determine the prevalence, risk factors, clinical consequences, and costs of high risk prescribing, and to assess the impact of interventions on high risk prescribing in older people.

Methods

The proposed project will utilise data from the 45 and Up Study, a large scale cohort of 267,153 men and women aged 45 and over recruited during 2006–2009 from the state of New South Wales, Australia linked to a range of administrative health datasets. High risk prescribing will be assessed using three indicators: polypharmacy (use of five or more medicines); Beers Criteria (an explicit measure of potentially inappropriate medication use); and Drug Burden Index (a pharmacologic dose-dependent measure of cumulative exposure to anticholinergic and sedative medicines). Individual risk factors from the 45 and Up Study questionnaire, and health system characteristics from health datasets that are associated with the likelihood of high risk prescribing will be identified. The main outcome measures will include hospitalisation (first admission to hospital, total days in hospital, cause-specific hospitalisation); admission to institutionalised care; all-cause mortality, and, where possible, cause-specific mortality. Economic costs to the health care system and implications of high risk prescribing will be also investigated. In addition, changes in high risk prescribing will be evaluated in relation to certain routine medicines-related interventions. The statistical analysis will be conducted using standard pharmaco-epidemiological methods including descriptive analysis, univariate and multivariate regression analysis, controlling for relevant confounding factors, using a number of different approaches.

Discussion

The availability of large-scale data is useful to identify opportunities for improving prescribing, and health in older adults. The size of the 45 and Up Study, along with linkage to health databases provides an important opportunity to investigate the relationship between high risk prescribing and adverse outcomes in a real-world population of older adults.

In a prospective Australian population-based study linking questionnaire data from 2006–2009 with hospitalisation and death data to June 2010 for 95,038 men aged ≥45 years, Banks and colleagues found that more severe erectile dysfunction was associated with higher risk of cardiovascular disease.

Background

Erectile dysfunction is an emerging risk marker for future cardiovascular disease (CVD) events; however, evidence on dose response and specific CVD outcomes is limited. This study investigates the relationship between severity of erectile dysfunction and specific CVD outcomes.

Methods and Findings

We conducted a prospective population-based Australian study (the 45 and Up Study) linking questionnaire data from 2006–2009 with hospitalisation and death data to 30 June and 31 Dec 2010 respectively for 95,038 men aged ≥45 y. Cox proportional hazards models were used to examine the relationship of reported severity of erectile dysfunction to all-cause mortality and first CVD-related hospitalisation since baseline in men with and without previous CVD, adjusting for age, smoking, alcohol consumption, marital status, income, education, physical activity, body mass index, diabetes, and hypertension and/or hypercholesterolaemia treatment. There were 7,855 incident admissions for CVD and 2,304 deaths during follow-up (mean time from recruitment, 2.2 y for CVD admission and 2.8 y for mortality). Risks of CVD and death increased steadily with severity of erectile dysfunction. Among men without previous CVD, those with severe versus no erectile dysfunction had significantly increased risks of ischaemic heart disease (adjusted relative risk [RR] = 1.60, 95% CI 1.31–1.95), heart failure (8.00, 2.64–24.2), peripheral vascular disease (1.92, 1.12–3.29), “other” CVD (1.26, 1.05–1.51), all CVD combined (1.35, 1.19–1.53), and all-cause mortality (1.93, 1.52–2.44). For men with previous CVD, corresponding RRs (95% CI) were 1.70 (1.46–1.98), 4.40 (2.64–7.33), 2.46 (1.63–3.70), 1.40 (1.21–1.63), 1.64 (1.48–1.81), and 2.37 (1.87–3.01), respectively. Among men without previous CVD, RRs of more specific CVDs increased significantly with severe versus no erectile dysfunction, including acute myocardial infarction (1.66, 1.22–2.26), atrioventricular and left bundle branch block (6.62, 1.86–23.56), and (peripheral) atherosclerosis (2.47, 1.18–5.15), with no significant difference in risk for conditions such as primary hypertension (0.61, 0.16–2.35) and intracerebral haemorrhage (0.78, 0.20–2.97).

Conclusions

These findings give support for CVD risk assessment in men with erectile dysfunction who have not already undergone assessment. The utility of erectile dysfunction as a clinical risk prediction tool requires specific testing.

Please see later in the article for the Editors' Summary

Editors' Summary

Background

Erectile dysfunction is the medical term used when a man is unable to achieve or sustain an erection of his penis suitable for sexual intercourse. Although a sensitive topic that can cause much embarrassment and distress, erectile dysfunction is very common, with an estimated 40% of men over the age of 40 years experiencing frequent or occasional difficulties. The most common causes of erectile dysfunction are medications, chronic illnesses such as diabetes, and drinking too much alcohol. Stress and mental health problems can also cause or worsen erectile dysfunction. There is also increasing evidence that erectile dysfunction may actually be a symptom of cardiovascular disease—a leading cause of death worldwide—as erectile dysfunction could indicate a problem with blood vessels or poor blood flow commonly associated with cardiovascular disease.

Why Was This Study Done?

Although previous studies have suggested that erectile dysfunction can serve as a marker for cardiovascular disease in men not previously diagnosed with the condition, few studies to date have investigated whether erectile dysfunction could also indicate worsening disease in men already diagnosed with cardiovascular disease. In addition, previous studies have typically been small and have not graded the severity of erectile dysfunction or investigated the specific types of cardiovascular disease associated with erectile dysfunction. In this large study conducted in Australia, the researchers investigated the relationship of the severity of erectile dysfunction with a range of cardiovascular disease outcomes among men with and without a previous diagnosis of cardiovascular disease.

What Did the Researchers Do and Find?

The researchers used information from the established 45 and Up Study, a large cohort study that includes 123,775 men aged 45 and over, selected at random from the general population of New South Wales, a large region of Australia. A total of 95,038 men were included in this analysis. The male participants completed a postal questionnaire that included a question on erectile functioning, which allowed the researchers to define erectile dysfunction as none, mild, moderate, or severe. Using information captured in the New South Wales Admitted Patient Data Collection—a complete record of all public and private hospital admissions, including the reasons for admission and the clinical diagnosis—and the government death register, the researchers were able to determine health outcomes of all study participants. They then used a statistical model to estimate hospital admissions for cardiovascular disease events for different levels of erectile dysfunction.

The researchers found that the rates of severe erectile dysfunction among study participants were 2.2% for men aged 45–54 years, 6.8% for men aged 55–64 years, 20.2% for men aged 65–74 years, 50.0% for men aged 75–84 years, and 75.4% for men aged 85 years and over. During the study period, the researchers recorded 7,855 hospital admissions related to cardiovascular disease and 2,304 deaths. The researchers found that among men without previous cardiovascular disease, those with severe erectile dysfunction were more likely to develop ischemic heart disease (risk 1.60), heart failure (risk 8.00), peripheral vascular disease (risk 1.92), and other causes of cardiovascular disease (risk 1.26) than men without erectile dysfunction. The risks of heart attacks and heart conduction problems were also increased (1.66 and 6.62, respectively). Furthermore, the combined risk of all cardiovascular disease outcomes was 1.35, and the overall risk of death was also higher (risk 1.93) in these men. The researchers found that these increased risks were similar in men with erectile dysfunction who had previously been diagnosed with cardiovascular disease.

What Do These Findings Mean?

These findings suggest that compared to men without erectile dysfunction, there is an increasing risk of ischemic heart disease, peripheral vascular disease, and death from all causes in those with increasing degrees of severity of erectile dysfunction. The authors emphasize that erectile dysfunction is a risk marker for cardiovascular disease, not a risk factor that causes cardiovascular disease. These findings add to previous studies and highlight the need to consider erectile dysfunction in relation to the risk of different types of cardiovascular disease, including heart failure and heart conduction disorders. However, the study's reliance on the answer to a single self-assessed question on erectile functioning limits the findings. Nevertheless, these findings provide useful information for clinicians: men with erectile dysfunction are at higher risk of cardiovascular disease, and the worse the erectile dysfunction, the higher the risk of cardiovascular disease. Men with erectile dysfunction, even at mild or moderate levels, should be screened and treated for cardiovascular disease accordingly.

Additional Information

Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001372.

Wikipedia defines erectile dysfunction (note that Wikipedia is a free online encyclopedia that anyone can edit)

MedlinePlus also has some useful patient information on erectile dysfunction

The Mayo Clinic has patient-friendly information on the causes of, and treatments for, erectile dysfunction, and also includes information on the link with cardiovascular disease

The National Heart Foundation of Australia provides information for health professionals, patients, and the general public about how to prevent and manage cardiovascular disease, including assessment and management of cardiovascular disease risk

Background

Large-scale population biobanks are critical for future research integrating epidemiology, genetic, biomarker and other factors. Little is known about the factors influencing participation in biobanks. This study compares the characteristics of biobank participants with those of non-participants, among members of an existing cohort study.

Methods

Individuals aged 45 and over participating in The 45 and Up Study and living ≤20km from central Wagga Wagga, New South Wales (NSW), Australia (rural/regional area) or ≤10km from central Parramatta, NSW (urban area) (n=2340) were invited to join a biobank, giving a blood sample and having additional measures taken, including height, weight, waist circumference, heart rate and blood pressure.

Results

The overall uptake of the invitation to participate was 33% (762/2340). The response rate was 41% (410/1002) among participants resident in the regional area, and 26% (352/1338) among those resident in the urban area. Characteristics associated with significantly decreased participation were being aged 80 and over versus being aged 45–64 (participation rate ratio: RR = 0.45, 95%CI 0.34-0.60), not being born in Australia versus being born in Australia (0.69, 0.59-0.81), having versus not having a major disability (0.54, 0.38-0.76), having full-time caregiving responsibilities versus not being a full-time carer (0.62, 0.42-0.93) and being a current smoker versus never having smoked (0.66, 0.50-0.89). Factors associated with increased participation were being in part-time work versus not being in paid work (1.24, 1.07-1.44) and having an annual household income of ≥$50,000 versus <$20,000 (1.50, 1.26-1.80).

Conclusions

A range of socio-economic, health and lifestyle factors are associated with biobank participation among members of an existing cohort study, with factors relating to health-seeking behaviours and access difficulties or time limitations being particularly important. If more widespread participation in biobanking is desired, particularly to ensure sufficient numbers among those most affected by these issues, specific efforts may be required to increase participation in certain groups such as migrants, the elderly, and those in poor health. Whilst caution should be exercised when generalising estimates of absolute prevalence from biobanks, estimates for many internal comparisons are likely to remain valid.

Objectives

This study aims to examine the association between self-reported heat stress interference with daily activities (sleeping, work, travel, housework and exercise) and three graded-holistic health and well-being outcomes (energy, emotions and life satisfaction).

Design

A cross-sectional study.

Setting

The setting is tropical and developing countries as Thailand, where high temperature and high humidity are common, particularly during the hottest seasons.

Participants

This study is based on an ongoing national Thai Cohort Study of distance-learning open-university adult students (N=60 569) established in 2005 to study the health-risk transition.

Primary and secondary outcome measures

Health impacts from heat stress in our study are categorised as physical health impacts (energy levels), mental health impacts (emotions) and well-being (life satisfaction). For each health and well-being outcome we report ORs and 95% CIs using multinomial logistic regression adjusting for a wide array of potential confounders.

Results

Negative health and well-being outcomes (low-energy level, emotional problems and low life satisfaction) associated with increasing frequency of heat stress interfering with daily activities. Adjusted ORs for emotional problems were between 1.5 and 4.8 and in general worse than energy level (between 1.31 and 2.91) and life satisfaction (between 1.10 and 2.49). The worst health outcomes were when heat interfered with sleeping, followed by interference with daily travel, work, housework and exercise.

Conclusions

In tropical Thailand there already are substantial heat stress impacts on health and well-being. Increasing temperatures from climate change plus the ageing and urbanisation of the population could significantly worsen the situation. There is a need to improve public health surveillance and public awareness regarding the risks of heat stress in daily life.

Background

Various options exist for collecting biospecimens and biomarkers from cohort study participants, and these have important logistic, resource and scientific implications. Evidence on how different collection methods affect participation and data quality is lacking. This parallel-design randomised trial, the Link-Up Study, involved blood sample donation and other data collection among participants in an existing cohort study, The 45 and Up Study. It aimed to investigate the relation of fasting status, reminder letters and data collection site to response rates, data quality and biospecimen yield.

Methods

Individuals aged 45 and over participating in The 45 and Up Study and living ≤20 km from central Wagga Wagga, NSW (regional area) or ≤10 km from central Parramatta, NSW (urban area) (n = 2340) were randomised, stratified by area of residence, to be invited to give a blood sample and additional data by attending either a clinic established specifically for the trial, with an appointment time (“dedicated clinic”, n = 1336) or an existing local commercial pathology centre (n = 1004). Within dedicated clinic groups, participants were randomised into fasting (n = 668) or non-fasting (n = 668) and, at the Parramatta pathology centre site, reminder letter after two weeks (n = 336) or no reminder (n = 334).

Results

Overall, 33% (762/2340) of invitees took part in the Link-Up Study; 41% (410/1002) among regional and 26% (352/1338) among urban-area residents (p < 0.0001). At the dedicated clinics, response rates were 38% (257/668) not fasting and 38% fasting (257/668) (participation rate ratio (RR) = 1.00, 95%CI 0.91-1.08, p = 0.98). The response rate was 22% among individuals randomised to attend the Parramatta pathology centre without a reminder and 23% among those sent a reminder letter (RR = 1.01, 0.93-1.09, p = 0.74). In total, the response rate was 38% (514/1336) at the dedicated clinics and 25% (248/1004) at the pathology centres (RR = 0.67, 0.56-0.78, p < 0.01); measures of height, weight and systolic and diastolic blood pressure did not vary materially between these groups, nor did the median number of aliquots of plasma, buffy coat and red cells collected.

Conclusions

Among cohort study participants, response rates for an additional study involving biospecimen collection, but not data quality or average biospecimen yield, were considerably higher at dedicated clinics than at existing commercial pathology sites.

While increasing age, decreasing body mass index (BMI), and physical inactivity are known to increase hip fracture risk, whether these factors have similar effects on other common fractures is not well established. We used prospectively-collected data from a large cohort to examine the role of these factors on the risk of incident ankle, wrist and hip fractures in postmenopausal women. 1,155,304 postmenopausal participants in the Million Women Study with a mean age of 56.0 (SD 4.8) years, provided information about lifestyle, anthropometric, and reproductive factors at recruitment in 1996–2001. All participants were linked to National Health Service cause-specific hospital records for day-case or overnight admissions. During follow-up for an average of 8.3 years per woman, 6807 women had an incident ankle fracture, 9733 an incident wrist fracture, and 5267 an incident hip fracture. Adjusted absolute and relative risks (RRs) for incident ankle, wrist, and hip fractures were calculated using Cox regression models. Age-specific rates for wrist and hip fractures increased sharply with age, whereas rates for ankle fracture did not. Cumulative absolute risks from ages 50 to 84 years per 100 women were 2.5 (95%CI 2.2–2.8) for ankle fracture, 5.0 (95%CI 4.4–5.5) for wrist fracture, and 6.2 (95%CI 5.5–7.0) for hip fracture. Compared with lean women (BMI < 20 kg/m2), obese women (BMI ≥ 30 kg/m2) had a three-fold increased risk of ankle fracture (RR = 3.07; 95%CI 2.53–3.74), but a substantially reduced risk of wrist fracture and especially of hip fracture (RR = 0.57; 0.51–0.64 and 0.23; 0.21–0.27, respectively). Physical activity was associated with a reduced risk of hip fracture but was not associated with ankle or wrist fracture risk. Ankle, wrist and hip fractures are extremely common in postmenopausal women, but the associations with age, adiposity, and physical activity differ substantially between the three fracture sites.

Highlights

► Risk factors for ankle, wrist, and hip fractures differ by age, adiposity, and physical activity in postmenopausal women. ► Age-specific rates for wrist and hip fractures increased sharply with age, whereas rates for ankle fracture did not. ► Obese women had a three-fold increased risk of ankle fracture, when compared with lean women. ► Compared with lean women, obese women had a 43% and 77% reduced risk of wrist and hip fractures, respectively. ► Physical inactivity was associated with increased risk of hip fracture, but had little association with ankle or wrist fracture.

A case-control study conducted in South Africa provides new estimates of the risk of specific cancers of the female reproductive system associated with use of injectable and oral contraceptives.

Background

Oral contraceptives are known to influence the risk of cancers of the female reproductive system. Evidence regarding the relationship between injectable contraceptives and these cancers is limited, especially in black South Africans, among whom injectable contraceptives are used more commonly than oral contraceptives.

Methods and Findings

We analysed data from a South African hospital-based case–control study of black females aged 18–79 y, comparing self-reported contraceptive use in patients with breast (n = 1,664), cervical (n = 2,182), ovarian (n = 182), and endometrial (n = 182) cancer, with self-reported contraceptive use in 1,492 control patients diagnosed with cancers with no known relationship to hormonal contraceptive use. We adjusted for potential confounding factors, including age, calendar year of diagnosis, education, smoking, alcohol, parity/age at first birth, and number of sexual partners. Among controls, 26% had used injectable and 20% had used oral contraceptives. For current and more recent users versus never users of oral or injectable contraceptives, the odds ratios (ORs) for breast cancer were significantly increased in users of oral and/or injectable contraceptives (OR 1.66, 95% CI 1.28–2.16, p<0.001) and separately among those exclusively using oral (1.57, 1.03–2.40, p = 0.04) and exclusively using injectable (OR 1.83, 1.31–2.55, p<0.001) contraceptives; corresponding ORs for cervical cancer were 1.38 (1.08–1.77, p = 0.01), 1.01 (0.66–1.56, p = 0.96), and 1.58 (1.16–2.15, p = 0.004). There was no significant increase in breast or cervical cancer risk among women ceasing hormonal contraceptive use ≥10 y previously (p = 0.3 and p = 0.9, respectively). For durations of use ≥5 y versus never use, the ORs of ovarian cancer were 0.60 (0.36–0.99, p = 0.04) for oral and/or injectable contraceptive use and 0.07 (0.01–0.49, p = 0.008) for injectable use exclusively; corresponding ORs for endometrial cancer were 0.44 (0.22–0.86, p = 0.02) and 0.36 (0.11–1.26, p = 0.1).

Conclusions

In this study, use of oral and of injectable hormonal contraceptives was associated with a transiently increased risk of breast and cervical cancer and, for long durations of use, with a reduced risk of ovarian and endometrial cancer. The observed effects of injectable and of oral contraceptives on cancer risk in this study did not appear to differ substantially.

Please see later in the article for the Editors' Summary

Editors' Summary

Background

Hormonal contraceptives are among the most commonly used medications. Globally, more than 210 million women currently use either hormonal contraceptive pills or injectable contraceptives. Contraceptive pills usually contain manmade versions of the female sex hormones estrogen and progesterone (the combined oral contraceptive, or “pill”); most injectable hormonal contraceptives contain only manmade progesterone preparations. Hormonal contraceptives, which prevent pregnancy by disrupting the cyclical changes in estrogen and progesterone levels that prepare the body for pregnancy, have revolutionized birth control since they first became available in the early 1960s. However, it is now known that taking the pill also influences women's risk of developing cancers of the female reproductive system. Current and recent users have an increased risk of developing breast and cervical cancer (the cervix is the structure that connects the womb to the vagina) compared to never users, although this increased risk quickly disappears when women stop taking the pill. By contrast, women who have used the pill have a reduced risk of developing ovarian cancer and cancer of the womb (endometrial cancer) compared to never users that increases with the duration of pill use and persists for many years after use ceases. These effects on reproductive system cancers are thought to occur because these cancers depend on naturally occurring sex hormones for their development and growth.

Why Was This Study Done?

Although the evidence that the pill influences the risk of developing cancers of the female reproductive system is extensive, much less is known about how injectable hormonal contraceptives affect cancer risk. In this hospital-based case–control study (a study that compares the characteristics of people with and without a specific condition), the researchers investigate the relationship between the use of oral and injectable hormonal contraceptives and cancers of the breast, cervix, ovary, and endometrium among black South African women. Injectable contraceptives have been used for longer in South Africa than elsewhere and are used more commonly than oral contraceptives among black South African women.

What Did the Researchers Do and Find?

As part of the Johannesburg Cancer Case Control Study, which recruits black patients attending Johannesburg public referral hospitals for cancer treatment, the researchers compared hormonal contraceptive use in women with breast, cervical, ovarian, or endometrial cancer with contraceptive use in women diagnosed with other cancers such as lung, colon, and rectal cancers, which are not known to be influenced by hormonal contraceptives. Among the controls, a quarter had used injectable contraceptives and a fifth had used oral contraceptives. After adjusting for other factors that might influence cancer risk such as age, smoking, and number of sexual partners, the odds ratio (OR) of breast cancer among current and recent users of oral and/or injectable contraceptives compared to never users was 1.66. That is, the risk of developing breast cancer among current and recent users of hormonal contraceptives was 1.66 times that among never users. For women using oral contraceptives exclusively or injectable contraceptives exclusively, the ORs of breast cancer were 1.57 and 1.83, respectively. There were also increases in cervical cancer risk among current and recent users of hormonal contraceptives compared to never users, but no significant increase in breast or cervical cancer risk among women who had ceased hormonal contraceptive use more than ten years previously. Finally, the use of hormonal contraceptives for more than five years reduced the risk of both ovarian and endometrial cancer.

What Do These Findings Mean?

These findings indicate that, among black women in South Africa, the use of oral or injectable hormonal contraceptives is associated with a transiently increased risk of breast and cervical cancer, and that extended use of these contraceptives is associated with a reduced risk of ovarian and endometrial cancer. Moreover, they suggest that the effects of oral versus injectable contraceptives on cancer risk do not differ substantially, although for endometrial and ovarian cancer the small number of cases exposed to injectable contraceptives limits the accuracy of the risk estimates. Other limitations of this study include the possibility that the findings may be affected by uncontrolled confounding. That is, women who used hormonal contraceptives may have shared other unidentified characteristics that affected their cancer risk. Nevertheless, these findings provide new information about the effects of oral and injectable hormonal contraceptives on cancer risk that should help women make informed decisions about their choice of contraceptive method.

Additional Information

Please access these web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001182.

The US National Cancer Institute provides information on breast cancer (including personal stories from breast cancer survivors), cervical cancer, ovarian cancer, and endometrial cancer for patients and health professionals, and a fact sheet on oral contraceptives and cancer risk (in English and Spanish)

Cancer Research UK also provides information on breast cancer, cervical cancer, ovarian cancer, and endometrial cancer and information about the birth control pill and cancer risk

Eyes on the Prize, an online support group for women who have had cancers of the female reproductive system, has personal stories; further personal stories about breast, cervical, and ovarian cancer are provided by the charity Healthtalkonline

Background

Patterns of physical activity (PA), domestic activity and sedentary behaviours are changing rapidly in Asia. Little is known about their relationship with obesity in this context. This study investigates in detail the relationship between obesity, physical activity, domestic activity and sedentary behaviours in a Thai population.

Methods

74,981 adult students aged 20-50 from all regions of Thailand attending the Sukhothai Thammathirat Open University in 2005-2006 completed a self-administered questionnaire, including providing appropriate self-reported data on height, weight and PA. We conducted cross-sectional analyses of the relationship between obesity, defined according to Asian criteria (Body Mass Index (BMI) ≥25), and measures of physical activity and sedentary behaviours (exercise-related PA; leisure-related computer use and television watching ("screen-time"); housework and gardening; and sitting-time) adjusted for age, sex, income and education and compared according to a range of personal characteristics.

Results

Overall, 15.6% of participants were obese, with a substantially greater prevalence in men (22.4%) than women (9.9%). Inverse associations between being obese and total weekly sessions of exercise-related PA were observed in men, with a significantly weaker association seen in women (p(interaction) < 0.0001). Increasing obesity with increasing screen-time was seen in all population groups examined; there was an overall 18% (15-21%) increase in obesity with every two hours of additional daily screen-time. There were 33% (26-39%) and 33% (21-43%) reductions in the adjusted risk of being obese in men and women, respectively, reporting housework/gardening daily versus seldom or never. Exercise-related PA, screen-time and housework/gardening each had independent associations with obesity.

Conclusions

Domestic activities and sedentary behaviours are important in relation to obesity in Thailand, independent of exercise-related physical activity. In this setting, programs to prevent and treat obesity through increasing general physical activity need to consider overall energy expenditure and address a wide range of low-intensity high-volume activities in order to be effective.

OBJECTIVE

To examine the effect of childbearing and maternal breastfeeding on a woman's subsequent risk of developing type 2 diabetes.

RESEARCH DESIGN AND METHODS

Using information on parity, breastfeeding, and diabetes collected from 52,731 women recruited into a cohort study, we estimated the risk of type 2 diabetes using multivariate logistic regression.

RESULTS

A total of 3,160 (6.0%) women were classified as having type 2 diabetes. Overall, nulliparous and parous women had a similar risk of diabetes. Among parous women, there was a 14% (95% CI 10–18%, P < 0.001) reduced likelihood of diabetes per year of breastfeeding. Compared to nulliparous women, parous women who did not breastfeed had a greater risk of diabetes (odds ratio 1.48, 95% CI 1.26–1.73, P < 0.001), whereas for women breastfeeding, the risk was not significantly increased.

CONCLUSIONS

Compared with nulliparous women, childbearing women who do not breastfeed have about a 50% increased risk of type 2 diabetes in later life. Breastfeeding substantially reduces this excess risk.

Substantial reductions in breast cancer incidence in women 50 years old or older have been observed recently in many developed countries, and falling use of menopausal hormone therapy (HT) remains the most plausible explanation. In keeping with recent observations from the Women's Health Initiative, a report from the California Teachers Study cohort in this issue of Breast Cancer Research adds to this growing evidence. The investigators found a 26% reduction in invasive breast cancer in the cohort from 2000-2002 to 2003-2005, which accompanied an estimated 64% drop in HT use between 2000-2001 and 2005-2006. By collating individual data on the use of HT and breast cancer incidence, they also demonstrated that the decline in incidence was concentrated in women who had ceased HT use. The decline reflected a decrease predominantly in oestrogen receptor-positive tumours in the context of stable screening patterns over the study period. Millions of women continue to use HT, and these findings support carefully targeted short duration use as an important ongoing strategy to minimise breast cancer risk.

Background

Vitamin D supplementation for fracture prevention is widespread despite conflicting interpretation of relevant randomised controlled trial (RCT) evidence. This study summarises quantitatively the current evidence from RCTs and observational studies regarding vitamin D, parathyroid hormone (PTH) and hip fracture risk.

Methods

We undertook separate meta-analyses of RCTs examining vitamin D supplementation and hip fracture, and observational studies of serum vitamin D status (25-hydroxyvitamin D (25(OH)D) level), PTH and hip fracture. Results from RCTs were combined using the reported hazard ratios/relative risks (RR). Results from case-control studies were combined using the ratio of 25(OH)D and PTH measurements of hip fracture cases compared with controls. Original published studies of vitamin D, PTH and hip fracture were identified through PubMed and Web of Science databases, searches of reference lists and forward citations of key papers.

Results

The seven eligible RCTs identified showed no significant difference in hip fracture risk in those randomised to cholecalciferol or ergocalciferol supplementation versus placebo/control (RR = 1.13[95%CI 0.98-1.29]; 801 cases), with no significant difference between trials of <800 IU/day and ≥800 IU/day. The 17 identified case-control studies found 33% lower serum 25(OH)D levels in cases compared to controls, based on 1903 cases. This difference was significantly greater in studies with population-based compared to hospital-based controls (χ21 (heterogeneity) = 51.02, p < 0.001) and significant heterogeneity was present overall (χ216 (heterogeneity) = 137.9, p < 0.001). Serum PTH levels in hip fracture cases did not differ significantly from controls, based on ten case-control studies with 905 cases (χ29 (heterogeneity) = 149.68, p < 0.001).

Conclusions

Neither higher nor lower dose vitamin D supplementation prevented hip fracture. Randomised and observational data on vitamin D and hip fracture appear to differ. The reason for this is unclear; one possible explanation is uncontrolled confounding in observational studies. Post-fracture PTH levels are unrelated to hip fracture risk.

Background

There is little empirical evidence regarding the generalisability of relative risk estimates from studies which have relatively low response rates or are of limited representativeness. The aim of this study was to investigate variation in exposure-outcome relationships in studies of the same population with different response rates and designs by comparing estimates from the 45 and Up Study, a population-based cohort study (self-administered postal questionnaire, response rate 18%), and the New South Wales Population Health Survey (PHS) (computer-assisted telephone interview, response rate ~60%).

Methods

Logistic regression analysis of questionnaire data from 45 and Up Study participants (n = 101,812) and 2006/2007 PHS participants (n = 14,796) was used to calculate prevalence estimates and odds ratios (ORs) for comparable variables, adjusting for age, sex and remoteness. ORs were compared using Wald tests modelling each study separately, with and without sampling weights.

Results

Prevalence of some outcomes (smoking, private health insurance, diabetes, hypertension, asthma) varied between the two studies. For highly comparable questionnaire items, exposure-outcome relationship patterns were almost identical between the studies and ORs for eight of the ten relationships examined did not differ significantly. For questionnaire items that were only moderately comparable, the nature of the observed relationships did not differ materially between the two studies, although many ORs differed significantly.

Conclusions

These findings show that for a broad range of risk factors, two studies of the same population with varying response rate, sampling frame and mode of questionnaire administration yielded consistent estimates of exposure-outcome relationships. However, ORs varied between the studies where they did not use identical questionnaire items.

The effect of pregnancy on survival and the best time to conceive are uncertain, so consideration of individual priorities is essential

Using data from the UK Million Women Study, Emily Banks and colleagues investigate the relationships between the incidence of hip fracture and a woman's age, menopausal status, and age at menopause.

Background

Bone mineral density is known to decrease rapidly after the menopause. There is limited evidence about the separate contributions of a woman's age, menopausal status and age at menopause to the incidence of hip fracture.

Methods and Findings

Over one million middle-aged women joined the UK Million Women Study in 1996–2001 providing information on their menopausal status, age at menopause, and other factors, which was updated, where possible, 3 y later. All women were registered with the UK National Health Service (NHS) and were routinely linked to information on cause-specific admissions to NHS hospitals. 561,609 women who had never used hormone replacement therapy and who provided complete information on menopausal variables (at baseline 25% were pre/perimenopausal and 75% postmenopausal) were followed up for a total of 3.4 million woman-years (an average 6.2 y per woman). During follow-up 1,676 (0.3%) were admitted to hospital with a first incident hip fracture. Among women aged 50–54 y the relative risk (RR) of hip fracture risk was significantly higher in postmenopausal than premenopausal women (adjusted RR 2.22, 95% confidence interval [CI] 1.22–4.04; p = 0.009); there were too few premenopausal women aged 55 y and over for valid comparisons. Among postmenopausal women, hip fracture incidence increased steeply with age (p<0.001), with rates being about seven times higher at age 70–74 y than at 50–54 y (incidence rates of 0.82 versus 0.11 per 100 women over 5 y). Among postmenopausal women of a given age there was no significant difference in hip fracture incidence between women whose menopause was due to bilateral oophorectomy compared to a natural menopause (adjusted RR 1.20, 95% CI 0.94–1.55; p = 0.15), and age at menopause had little, if any, effect on hip fracture incidence.

Conclusions

At around the time of the menopause, hip fracture incidence is about twice as high in postmenopausal than in premenopausal women, but this effect is short lived. Among postmenopausal women, age is by far the main determinant of hip fracture incidence and, for women of a given age, their age at menopause has, at most, a weak additional effect.

Please see later in the article for the Editors' Summary

Editors' Summary

Background

Anyone can break a hip but most hip fractures occur in elderly people. As people age, their bones gradually lose minerals and become less dense, which weakens the bones and makes them more susceptible to fracture. Because women lose bone density faster than men as they age and because women constitute the majority of the elderly, three-quarters of hip fractures occur in women. Hip fractures can cause long-term health problems and premature death. Thus, although surgical repair of a broken hip usually only requires a hospital stay of about a week, a quarter of elderly people who were living independently before their fracture have to stay in a nursing home for at least a year after their injury and a fifth of elderly people who break a hip die within the year. Most hip fractures are caused by falls. Regular exercise to improve strength and balance combined with review of medicines (to reduce side effects and interactions), regular eye examinations, and the removal of fall hazards from the home can help to prevent hip fractures in elderly people.

Why Was This Study Done?

Bone density decreases very rapidly in women immediately after menopause—the time when menstruation permanently stops—and then continues to decrease more slowly with age. Most women have their menopause in their early 50s but menopause can occur in younger women. Early menopause is thought to be a risk factor for osteoporosis (thinning of the bones) and fractures later in life but little is known about how menopause influences hip fracture risk as women age. In this prospective study (a type of study in which a group of people is followed for several years to see whether they develop a particular condition), the researchers investigate the incidence of hip fractures in relation to age, menopausal status, and age at menopause among the participants of the Million Women Study. This study, which recruited 1.3 million women aged 50–64 years who attended UK breast cancer screening clinics between 1996 and 2001, has been investigating how reproductive and lifestyle factors affect women's health.

What Did the Researchers Do and Find?

At enrollment and three years later, the study participants provided information about their menopausal status and other health and lifestyle factors likely to affect their fracture risk. From these data, the researchers identified more than half a million women who had never used hormone replacement therapy (which reduces fracture risk) and who had given complete information about their menopausal status. They then looked for statistical associations between the occurrence of a first hip fracture in these women over the next few years and their age, menopausal status, and age at menopause. Among women aged 50–54 years, postmenopausal women were twice as likely to have a hip fracture as premenopausal women. Among postmenopausal women, the incidence of hip fractures increased steeply with age and was seven times higher in 70–74-year olds than in 50–54-year olds. Women who had their menopause before age 45 had a slightly increased risk of hip fracture but any effect of age at menopause on the risk of hip fracture was small compared to the effect of age itself, and the slightly increased risk may have been due to other factors that could not be fully accounted for in the analysis.

What Do These Findings Mean?

These findings indicate that around the time of menopause, although hip fractures are rare, the risk of a fracture in postmenopausal women is twice that in premenopausal women. The findings also show that among postmenopausal women, age is the major determinant of hip fracture risk and that for women of a given age, their age at menopause has little effect on hip fracture risk. Women attending breast cancer screening clinics and completing questionnaires about their health may not be representative of the general population. Furthermore, these findings rely on women self-reporting their menopausal status accurately. Nevertheless, the results of this study suggest that clinicians advising women about hip fracture prevention should probably base their advice on the woman's age and on age-related factors such as frailty rather than on factors related to menopause. Clinicians can also now reassure elderly women who had an early menopause that their risk of hip fracture is unlikely to be higher than that of similar women who had a later menopause.

Additional Information

Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000181.

The American Academy of Orthopaedic Surgeons has detailed information about hip fractures

The US National Institute of Arthritis and Muscoloskeletal and Skin Diseases has an interactive feature called “Check up on your bones and provides detailed information about osteoporosis, including advice on fall prevention

The US Centers for Disease Control and Prevention has a fact sheet about hip fractures among older adults

MedlinePlus has links to resources about hip fracture, osteoporosis, and menopause (in English and Spanish)

More information on the Million Women Study is available

Breast cancer incidence may be increasing in Thailand but very little research has assessed core breast cancer risk factors in this country.

We used baseline questionnaire data from a national cohort study of Thai Open University students in an exploratory case-control study of breast cancer. The study included 43 female cases and 860 age-matched controls selected from the remaining 47,271 female cohort participants. Odds ratios and 95% confidence intervals were calculated using conditional logistic regression.

The women were predominantly premenopausal. Taller women had an increased risk of breast cancer (OR = 2.3, 95% CI 1.1–4.8, for height ≥160 cm vs ≤154 cm) as did women with non-insulin dependent diabetes mellitus (OR = 8.4, 95% CI 1.7–41). Women with older siblings had a reduced risk of breast cancer compared to those firstborn (OR = 0.3, 95% CI0.2–0.7).

Although limited by small case numbers, our findings suggest substantial increases in breast cancer rates in Thailand could be expected in the future.

Correction to Banks E, Jorm L, Lujic S, Rogers K. Health, ageing and private health insurance: baseline results from the 45 and Up Study cohort. ANZ Health Policy 2009; 6: 16.

Background

This study investigates the relationships between health and lifestyle factors, age and private health insurance (PHI) in a large Australian population-based cohort study of people aged 45 years and over; the 45 and Up Study. Unlike previous Australian analyses of relationships between health, lifestyle and PHI, it incorporates adjustment for multiple confounding socioeconomic and demographic factors. Recruitment into the 45 and Up Study began in February 2006 and these analyses relate to the first 103,042 participants who joined the study prior to July 2008.

Results

The proportion with PHI decreased with increasing age. The factors independently and most strongly associated with having PHI were: higher income; higher educational attainment; not holding a health care concession card; not being of Aboriginal/Torres Strait Islander origin; being a non-smoker; high levels of self-rated health and functional capacity; and low levels of psychological distress. These factors increased the probability of having PHI by 16% to 125%, compared to individuals without these characteristics. PHI coverage was significantly but only marginally higher in people reporting non-melanoma skin cancer (adjusted RR 1.04, 95%CI 1.03–1.05), prostate cancer (1.09, 1.06–1.11) or an enlarged prostate (1.07, 1.06–1.09), those reporting a family history of a range of conditions (e.g. 1.02, 1.01–1.03 for a family history of heart disease; 1.03, 1.02–1.04 for a family history of prostate cancer) and lower in people reporting diabetes (0.92, 0.91–0.94) or stroke (0.91, 0.88–0.94), compared to people who did not have these medical or family histories. PHI was higher in those reporting certain surgical procedures with RRs (95%CI) of 1.12 (1.09–1.15) for hip replacement, 1.10 (1.08–1.13) for knee replacement and 1.12 (1.09–1.15) for prostatectomy, compared to those not reporting these interventions.

Conclusion

Compared to the rest of the study population, those with PHI are richer, better educated, more health conscious, in better health and more likely to use certain discretionary health services. Hence, PHI use is generally highest among those with the least need for health care. Whether or not people have PHI is more strongly associated with demographic and lifestyle factors than with health status.

Background

Limited evidence suggests that people from non-English speaking backgrounds in Australia have lower than average rates of participation in cancer screening programs. The objective of this study was to examine the distribution of bowel, breast and prostate cancer test use by place of birth and years since migration in a large population-based cohort study in Australia.

Methods

In 2006, screening status, country of birth and other demographic and health related factors were ascertained by self-completed questionnaire among 31,401 (16,126 women and 15,275 men) participants aged 50 or over from the 45 and Up Study in New South Wales.

Results

35% of women and 39% of men reported having a bowel cancer test and 57% of men reported having a prostate specific antigen (PSA) test, in the previous 5 years. 72% of women reported having screening mammography in the previous 2 years. Compared to Australian-born women, women from East Asia, Southeast Asia, Continental Western Europe, and North Africa/Middle East had significantly lower rates of bowel testing, with odds ratios (OR; 95%CI) ranging from 0.5 (0.4–0.7) to 0.7 (0.6–0.9); migrants from East Asia (0.5, 0.3–0.7) and North Africa/Middle East (0.5, 0.3–0.9) had significantly lower rates of mammography. Compared to Australian-born men, bowel cancer testing was significantly lower among men from all regions of Asia (OR, 95%CI ranging from 0.4, 0.3–0.6 to 0.6, 0.5–0.9) and Continental Europe (OR, 95%CI ranging from 0.4, 0.3–0.7 to 0.7, 0.6–0.9). Only men from East Asia had significantly lower PSA testing rates than Australian-born men (0.4, 0.3–0.6). As the number of years lived in Australia increased, cancer test use among migrants approached Australian-born rates.

Conclusion

Certain migrant groups within the population may require targeted intervention to improve their uptake of cancer screening, particularly screening for bowel cancer.

Introduction

Current and recent users of hormone replacement therapy (HRT) have an increased risk of being recalled to assessment at mammography without breast cancer being diagnosed ('false positive recall'), but there is limited information on the effects of different patterns of HRT use on this. The aim of this study is to investigate in detail the relationship between patterns of use of HRT and false positive recall.

Methods

A total of 87,967 postmenopausal women aged 50 to 64 years attending routine breast cancer screening at 10 UK National Health Service Breast Screening Units from 1996 to 1998 joined the Million Women Study by completing a questionnaire before screening and were followed for their screening outcome.

Results

Overall, 399 (0.5%) participants were diagnosed with breast cancer and 2,629 (3.0%) had false positive recall. Compared to never users of HRT, the adjusted relative risk (95% CI) of false positive recall was: 1.62 (1.43–1.83), 1.80 (1.62–2.01) and 0.76 (0.52–1.10) in current users of oestrogen-only HRT, oestrogen-progestagen HRT and tibolone, respectively (p (heterogeneity) < 0.0001); 1.65 (1.43–1.91), 1.49 (1.22–1.81) and 2.11 (1.45–3.07) for current HRT used orally, transdermally or via an implant, respectively (p (heterogeneity) = 0.2); and 1.84 (1.67–2.04) and 1.75 (1.49–2.06) for sequential and continuous oestrogen-progestagen HRT, respectively (p (heterogeneity) = 0.6). The relative risk of false positive recall among current users appeared to increase with increasing time since menopause, but did not vary significantly according to any other factors examined, including duration of use, hormonal constituents, dose, whether single- or two-view screening was used, or the woman's personal characteristics.

Conclusion

Current use of oestrogen-only and oestrogen-progestagen HRT, but not tibolone, increases the risk of false positive recall at screening.

Objectives To examine how lifestyle, hormonal, and other factors influence the sensitivity and specificity of mammography.

Methods Women recruited into the Million Women Study completed a questionnaire about various personal factors before routine mammographic screening. A sample of 122 355 women aged 50-64 years were followed for outcome of screening and incident breast cancer in the next 12 months. Sensitivity and specificity were calculated by using standard definitions, with adjustment for potential confounding factors.

Results Breast cancer was diagnosed in 726 (0.6%) women, 629 in screen positive and 97 in screen negative women; 3885 (3.2%) were screen positive but had no subsequent diagnosis of breast cancer. Overall sensitivity was 86.6% and specificity was 96.8%. Three factors had an adverse effect on both measures: use of hormone replacement therapy (sensitivity: 83.0% (95% confidence interval 77.4% to 87.6%), 84.7% (73.9% to 91.6%), and 92.1% (87.6% to 95.0%); specificity: 96.8% (96.6% to 97.0%), 97.8% (97.5% to 98.0%), and 98.1% (98.0% to 98.2%), respectively, for current, past, and never use); previous breast surgery v no previous breast surgery (sensitivity: 83.5% (75.7% to 89.1%) v 89.4% (86.5% to 91.8%); specificity: 96.2% (95.8% to 96.5%) v 97.4% (97.3% to 97.5%), respectively); and body mass index < 25 v ≥ 25 (sensitivity: 85.7% (81.2% to 89.3%) v 91.0% (87.5% to 93.6%); specificity: 97.2% (97.0% to 97.3%) v 97.4% (97.3% to 97.6%), respectively). Neither sensitivity nor specificity varied significantly according to age, family history of breast cancer, parity, past oral contraceptive use, tubal ligation, physical activity, smoking, or alcohol consumption.

Conclusions The efficiency, and possibly the effectiveness, of mammographic screening is lower in users of hormone replacement therapy, in women with previous breast surgery, and in thin women compared with other women.

Background

Information regarding the characteristics and health of women who do and do not attend for breast cancer screening is limited and representative data are difficult to obtain.

Methods

Information on age, deprivation and prescriptions for various medications was obtained for all women at two UK general practices who were invited to breast cancer screening through the National Health Service Breast Screening Programme. The characteristics of women who attended and did not attend screening were compared.

Results

Of the 1064 women invited to screening from the two practices, 882 (83%) attended screening. Screening attenders were of a similar age to non-attenders but came from significantly less deprived areas (30% of attenders versus 50% of non-attenders came from the most deprived areas, P < 0.0001) and were more likely to have a current prescription for hormone replacement therapy (32% versus 19%, P < 0.0001). No significant differences in recent prescriptions of medication for hypertension, heart disease, hypercholesterolaemia, diabetes mellitus, asthma, thyroid disease or depression/anxiety were observed between attenders and non-attenders.

Conclusion

Women who attend the National Health Service Breast Screening Programme come from less deprived areas and are more likely to have a current prescription for hormone replacement therapy than non-attenders, but do not differ in terms of age or recent prescriptions for various other medications.