Women's Health Initiative Study Research Articles

Premorbid predictors of death at initial presentation of coronary heart disease in the Women's Health Initiative study

Premorbid predictors of death at initial presentation of coronary heart disease in the Women's Health Initiative study

Proteome-wide association study using cis and trans variants and applied to blood cell and lipid-related traits in the Women's Health Initiative study.

In most Proteome-Wide Association Studies (PWAS), variants near the protein-coding gene (±1 Mb), also known as cis single nucleotide polymorphisms(SNPs), are used to predict protein levels, which are then tested for association with phenotypes. However, proteins can be regulated through variants outside of the cis region. An intermediate GWAS step to identify protein quantitative trait loci (pQTL) allows for the inclusion of trans SNPs outside the cis region in protein-level prediction models. Here, we assess the prediction of 540 proteins in 1002 individuals from the Women's Health Initiative (WHI), split equally into a GWAS set, an elastic net training set, and a testing set. We compared the testing r2 between measured and predicted protein levels using this proposed approach, to the testing r2 using only cis SNPs. The two methods usually resulted in similar testing r2, but some proteins showed a significant increase in testing r2 with our method. For example, for cartilage acidic protein 1, the testing r2 increased from 0.101 to 0.351. We also demonstrate reproducible findings for predicted protein association with lipid and blood cell traits in WHI participants without proteomics data and in UK Biobank utilizing our PWAS weights.

Association of clonal hematopoiesis and mosaic chromosomal alterations with solid malignancy incidence and mortality.

Understanding the impact of clonal hematopoiesis of indeterminate potential (CHIP) and mosaic chromosomal alterations (mCAs) on solid tumor risk and mortality can shed light on novel cancer pathways. The authors analyzed whole genome sequencing data from the Trans-Omics for Precision Medicine Women's Health Initiative study (n=10,866). They investigated the presence of CHIP and mCA and their association with the development and mortality of breast, lung, and colorectal cancers. CHIP was associated with higher risk of breast (hazard ratio [HR], 1.30; 95% confidence interval [CI], 1.03-1.64; p=.02) but not colorectal (p=.77) or lung cancer (p=.32). CHIP carriers who developed colorectal cancer also had a greater risk for advanced-stage (p=.01), but this was not seen in breast or lung cancer. CHIP was associated with increased colorectal cancer mortality both with (HR, 3.99; 95% CI, 2.41-6.62; p<.001) and without adjustment (HR, 2.50; 95% CI, 1.32-4.72; p=.004) for advanced-stage and a borderline higher breast cancer mortality (HR, 1.53; 95% CI, 0.98-2.41; p=.06). Conversely, mCA (cell fraction [CF] >3%) did not correlate with cancer risk. With higher CFs (mCA >5%), autosomal mCA was associated with increased breast cancer risk (HR, 1.39; 95% CI, 1.06-1.83; p=.01). There was no association of mCA (>3%) with breast, colorectal, or lung mortality except higher colon cancer mortality (HR, 2.19; 95% CI, 1.11-4.3; p=.02) with mCA >5%. CHIP and mCA (CF >5%) were associated with higher breast cancer risk and colorectal cancer mortality individually. These data could inform on novel pathways that impact cancer risk and lead to better risk stratification.

The 2017 Women’s Health Initiative study and use of hormone therapy: an emulated repeated cross-sectional study

BackgroundHormone therapy (HT) use among menopausal women declined after negative information from the 2002 Women’s Health Initiative (WHI) HT study. The 2017 post-intervention follow-up WHI study revealed that HT did not increase long-term mortality. However, studies on the effects of the updated WHI findings are lacking. Thus, we assessed the impact of the 2017 WHI findings on HT use in Taiwan.MethodsWe identified 1,869,050 women aged 50–60 years, between June and December 2017, from health insurance claims data to compare HT use in the 3 months preceding and following September 2017. To address the limitations associated with interval-censored data, we employed an emulated repeated cross-sectional design. Using logistic regression analysis, we evaluated the impact of the 2017 WHI study on menopausal symptom-related outpatient visits and HT use. In a scenario analysis, we examined the impact of the 2002 trial on HT use to validate our study design.ResultsStudy participants’ baseline characteristics before and after the 2017 WHI study were not significantly different. Logistic regressions demonstrated that the 2017 study had no significant effect on outpatient visits for menopause-related symptoms or HT use among women with outpatient visits. The scenario analysis confirmed the negative impact of the 2002 WHI trial on HT use.ConclusionsThe 2017 WHI study did not demonstrate any impact on either menopause-related outpatient visits or HT use among middle-aged women in Taiwan. Our emulated cross-sectional study design may be employed in similar population-based policy intervention studies using interval-censored data.

From cardiovascular protection to cardiovascular risk: the metamorphosis of menopausal hormone therapy.

Over the last 70years, oestrogen therapy for the management of menopausal symptoms has undergone a metamorphosis from perceived cardiovascular protection to perceived cardiovascular risk. The former perception is based on the convincing evidence from the Nurses' Health Study cohorts and the epidemiological data surrounding early menopause. The latter, and later, perception is based on the disquieting results from two randomised controlled studies, the Heart and Estrogen/Progestin Replacement Study (HERS) and the Women's Health Initiative study (WHI). The reality is probably more nuanced than the conclusions presented by any of these studies. When face to face with a patient, the clinician must negotiate the appropriate decision pathway around the interaction between cardiovascular risk, cardiovascular disease, menopause, and oestrogen +/-progestogen-containing hormone therapy.

Menopause hormone therapy prescribing in ambulatory care visits among midlife and older U.S. women from 2018 to 2019

The rates of prescription for menopause hormone therapy have been low in the U.S. since the 2002 Women's Health Initiative study, but no recent studies have assessed the prescribing of hormone therapy in the U.S. Using the National Ambulatory Medical Care Survey data from 2018 to 2019, we found that hormone therapy was prescribed in 3.8 % of U.S. visits by midlife and older women, with 60 % of these visits including estradiol-only prescriptions. Older age and Hispanic/Latina ethnicity were associated with decreased odds of prescribing, while White race and depression were associated with increased odds, indicating possible disparities in menopause care.

Abstract P400: Trajectories of Psychological Well-Being Are Associated With High Cardiovascular Health Late in Life: Findings From the Women’s Health Initiative

Introduction: Psychological well-being (PWB) may influence cardiovascular health (CVH) through what the American Heart Association has called the “mind-heart-body connection”. However, few studies have examined longitudinal relationships between positive PWB and CVH. We estimated associations between trajectories of PWB and Life’s Essential 8 (LE8) achievement. Hypothesis: We hypothesized that women who maintained high levels of PWB over time would have higher LE8 scores later in life. Methods: We conducted group-based trajectory modelling in the Women’s Health Initiative (WHI) to identify latent trajectories of PWB among those with ≥3 measurements of purpose in life (PIL, N=29,717) and personal growth (PG, N=12,148). PIL and PG scores were calculated according to participants’ responses to the FACIT-Sp Meaning Subscale and Ryff’s Scales of PWB, collected between 2000-2021. The selection of trajectory models was informed by statistical criteria and prior literature. Late life CVH (2018-2021) was summarized by LE8, with scoring adapted based on available data: self-reported treatment for hypertension, diabetes, and hypercholesterolemia, and historical food frequency questionnaires were used. Logistic regression was performed to estimate associations between PIL and PG trajectory group membership and high CVH (LE8≥80), summarized by odds ratios (OR) and 95% confidence intervals (CI). Logistic models adjusted for baseline age, WHI study arm, race, marital status, income, and education in those with complete data (PIL N=28,033; PG N=11,495). Results: On average, PIL trajectories spanned 17 years (age 66-83) and three latent groups were identified: high/decreasing (n=12,073; 47.4%), moderate/decreasing (n=12,096; 44.1%), and low/stable (n=2,548; 8.6%). Compared to those in the low/stable group, women in the moderate/decreasing and high/decreasing PIL groups had significantly higher odds of having high CVH (OR 1.47 [1.35, 1.61] and OR 2.09 [1.92, 2.28], respectively). These associations were robust to adjustment for demographics and social determinants of health: moderate/decreasing (aOR 1.40 [1.27, 1.53]), high/decreasing (aOR 1.88 [1.71, 2.07]). PG trajectories spanned 9 years (age 74-83) and high/stable (n=3,832, 31.5%), moderate/stable (n=5,692, 46.9%), and low/stable (n=2,624, 21.6%) latent groups were identified. Membership in moderate/stable (OR 1.53 [1.40, 1.69] and high/stable (OR 1.95 [1.75, 2.16]) PG trajectory groups was also significantly associated with odds of having high CVH. These associations remained significant after adjustment (moderate/stable aOR 1.40 [1.27, 1.55]; high/stable aOR 1.64 [1.46, 1.84]). Conclusions: Maintaining high levels of PIL and PG may contribute to better CVH late in life. Further research is needed to investigate how strategies to improve PWB may be integrated within cardiovascular care among older adults.

Abstract P500: Proton Pump Inhibitor Use and Incident Cardiovascular Disease in Postmenopausal Women, Results From the Women’s Health Initiative

Introduction: Evidence from in-vitro and animal studies suggests that proton pump inhibitor (PPI) use is associated with incident cardiovascular disease (CVD). Observational studies in humans have shown conflicting results and didn’t account for relevant confounders such as diet and physical activity or confounding by indication. Methods: This study included 148,452 postmenopausal women without history of CVD at enrollment into the Women’s Health Initiative (WHI) observational study and clinical trials in 1993-1998. The primary exposure was PPI use (no, yes) determined by medication inventory conducted at baseline. The main outcome was incident primary CVD defined as a composite endpoint of physician-adjudicated myocardial infarction, coronary revascularization, stroke, and CVD mortality. Follow-up time was to September 2010. Cox proportional hazards regression was used to estimate hazards ratios (HR) and 95% confidence intervals (CI) for the association of PPI use and CVD. All models were adjusted for baseline age and stratified according to WHI study component. Additional models were further adjusted for demographics (education, income), lifestyle (smoking, alcohol, diet quality, physical activity, sleep duration), and major CVD risk factors (body mass index, family history of CVD, treated hypercholesterolemia, treated diabetes, treated hypertension). Results: Baseline prevalence of PPI use was 1.91%. After a mean follow-up of 11.3 years, there were 10,944 CVD events. PPI use was associated with a 28% higher risk of CVD compared to non-use in the age adjusted model (HR: 1.28, 95%CI: 1.13-1.45). The association was attenuated but remained significant after adjusting for potential confounders and was materially unchanged when using propensity score adjustment to better address confounding by indication (Table). Conclusions: PPI use was associated with higher risk of incident CVD in postmenopausal women. Further investigations are warranted to confirm this finding and identify potential mechanisms.

The evolving perspective of menopause management in the United Kingdom.

The use of menopausal hormone therapy (MHT) was significantly reduced following the publication of the Women's Health Initiative study results and has remained low ever since. However, from 2015 onwards, the UK has seen a substantial increase in MHT prescribing compared to other European countries. To evaluate the factors contributing to the shift in women's and healthcare professionals' (HCPs) perception of MHT in the United Kingdom and to provide learning points for other European countries. An exploratory, descriptive and qualitative study. An interactive virtual panel discussion in which seven UK-based HCPs with a special interest in the menopause discussed the evolution of its management in the United Kingdom. In the last 8 years, there has been a substantial increase in MHT prescriptions in the United Kingdom due to improved menopause awareness and acceptance of MHT. Accessibility to accurate, scientific, information and guidance from respected institutions is one of the main drivers of this change. Social media has increased that reach with 'influencers' empowering women to seek help. Women are demanding access to menopause health care so that they can receive holistic and individualized treatment based on their clinical conditions and needs. Standardized education of HCPs is an essential pillar to provide appropriate and equitable care to menopausal women and to guarantee safe prescribing of MHT. Furthermore, up to date and factually correct menopausal education would benefit all the population. Publication of new scientific data reporting a more favourable benefit/risk ratio with MHT, production of national guidance and an increased awareness via social media have led to the significant rise in MHT prescribing and improvement of menopause care in the United Kingdom. The lessons learned may benefit other European countries.

Menopause Hormone Therapy: 2023 Update

The publication of the Women’s Health Initiative (WHI) study in 2002 caused a precipitous decline in use of menopause hormone therapy (MHT). Prior to publication, approximately 43% of women aged 45–74 used MHT; following publication, this number dropped to 11%. Fear of breast cancer was the largest motivator behind this decline. Since the WHI study, menopause medical education has been inadequate; it is estimated that 41% of medical schools do not include menopause education in their undergraduate curriculum. The same study highlighted significant knowledge gaps regarding menopause management among practicing physicians.&#x0D; Menopausal women are asking questions and expecting answers. Advocacy groups such as the Menopause Foundation of Canada are empowering women to acknowledge the impact of menopausal symptoms on the workplace, personal relationships and personal health. As MHT is considered first-line therapy (in the absence of contraindications), it behooves healthcare providers to have a working knowledge of MHT.

Reappraising 21years of the WHI study: Putting the findings in context for clinical practice.

Menopausal hormone treatment (MHT) is recommended for the management of menopause symptoms. The Women's Health Initiative (WHI) placebo-controlled randomised study examined the effects of continuous combined or estrogen-only MHT on the risk of non-communicable diseases (NCDs) in post-menopausal women. The study was terminated prematurely after an interim analysis showed an increased risk of breast cancer diagnosis, which led to a rapid decrease in MHT use worldwide. Subsequently, limitations of the study design and its interpretation in the context of other clinical studies has contributed to a more nuanced appreciation of the risk-benefit profile of differing MHT regimens regarding risk associated with the class of progestogen prescribed, its pattern of prescription, duration of use and timing of initiation related to menopause onset. This review provides a contextual interpretation of the WHI placebo-controlled study and evaluates the impact of bioidentical MHT, with a focus on combined therapies containing micronised progesterone, on the risk of chronic NCDs in post-menopausal women.

Racial and Ethnic Differences in Self-Reported COVID-19 Exposure Risks, Concerns, and Behaviors Among Diverse Participants in the Women's Health Initiative Study.

Racial and ethnic disparities in coronavirus disease 2019 (COVID-19) risk are well-documented; however, few studies in older adults have examined multiple factors related to COVID-19 exposure, concerns, and behaviors or conducted race- and ethnicity-stratified analyses. The Women's Health Initiative (WHI) provides a unique opportunity to address those gaps. We conducted a secondary analysis of WHI data from a supplemental survey of 48 492 older adults (mean age 84 years). In multivariable-adjusted modified Poisson regression analyses, we examined predisposing factors and COVID-19 exposure risk, concerns, and behaviors. We hypothesized that women from minoritized racial or ethnic groups, compared to non-Hispanic White women, would be more likely to report: exposure to COVID-19, a family or friend dying from COVID-19, difficulty getting routine medical care or deciding to forego care to avoid COVID-19 exposure, and having concerns about the COVID-19 pandemic. Asian women and non-Hispanic Black/African American women had a higher risk of being somewhat/very concerned about risk of getting COVID-19 compared to non-Hispanic White women and each was significantly more likely than non-Hispanic White women to report forgoing medical care to avoid COVID-19 exposure. However, Asian women were 35% less likely than non-Hispanic White women to report difficulty getting routine medical care since March 2020 (adjusted relative risk 0.65; 95% confidence interval 0.57, 0.75). We documented COVID-related racial and ethnic disparities in COVID-19 exposure risk, concerns, and care-related behaviors that disfavored minoritized racial and ethnic groups, particularly non-Hispanic Black/African American women.

Validation of a genome-wide polygenic score in improving fracture risk assessment beyond the FRAX tool in the Women's Health Initiative study.

Previous study has established two polygenic scores (PGSs) related to femoral neck bone mineral density (BMD) (PGS_FNBMDldpred) and total body BMD (PGS_TBBMDldpred) that are associated with fracture risk. However, these findings have not yet been externally validated in an independent cohort. This study aimed to validate the predictive performance of the two established PGSs and to investigate whether adding PGSs to the Fracture Risk Assessment Tool (FRAX) improves the predictive ability of FRAX in identifying women at high risk of major osteoporotic fracture (MOF) and hip fractures (HF). The study used the Women's Health Initiative (WHI) cohort of 9,000 postmenopausal women of European ancestry. Cox Proportional Hazard Models were used to assess the association between each PGS and MOF/HF risk. Four models were formulated to investigate the effect of adding PGSs to the FRAX risk factors: (1) Base model: FRAX risk factors; (2) Base model + PGS_FNBMDldpred; (3) Base model + PGS_TBBMDldpred; (4) Base model + metaPGS. The reclassification ability of models with PGS was further assessed using the Net Reclassification Improvement (NRI) and the Integrated discrimination improvement (IDI). The study found that the PGSs were not significantly associated with MOF or HF after adjusting for FRAX risk factors. The FRAX base model showed moderate discrimination of MOF and HF, with a C-index of 0.623 (95% CI, 0.609 to 0.641) and 0.702 (95% CI, 0.609 to 0.718), respectively. Adding PGSs to the base FRAX model did not improve the ability to discriminate MOF or HF. Reclassification analysis showed that compared to the model without PGS, the model with PGS_TBBMDldpred (1.2%, p = 0.04) and metaPGS (1.7%, p = 0.05) improve the reclassification of HF, but not MOF. The findings suggested that incorporating genetic information into the FRAX tool has minimal improvement in predicting HF risk for elderly Caucasian women. These results highlight the need for further research to identify other factors that may contribute to fracture risk in elderly Caucasian women.

Predicting All-Cause Mortality in Women With and Without Breast Cancer Using the Schonberg Index: A Women's Health Initiative Study.

When treating older women with breast cancer, life expectancy is an important consideration. ASCO recommends calculating 10-year mortality probabilities to inform treatment decisions. One useful tool is the Schonberg index, which predicts risk-based all-cause 10-year mortality. We investigated the use of this index in women aged ≥65 years with breast cancer in the Women's Health Initiative (WHI). We calculated 10-year mortality risk scores for 2,549 WHI participants with breast cancer ("cases") and 2,549 age-matched breast cancer-free participants ("controls") using Schonberg index risk scoring. Risk scores were grouped into quintiles for comparisons. Risk-stratified observed mortality rates and 95% confidence intervals were compared across cases and controls. Observed 10-year mortality rates in cases and controls were also compared with Schonberg index-based predicted 10-year mortality rates. Compared with controls, cases were more often white (P=.005), had higher income and education levels (P<.001 for both), more often lived with their husband/partner (P<.001), scored higher on subjective health/happiness (P<.001), and needed less assistance in activities of daily living (P<.001). Participants with breast cancer had similar risk-stratified 10-year mortality rates compared with controls (34% vs 33%, respectively). Stratified results showed that cases had slightly higher mortality rates than controls in the lowest risk quintile and lower mortality rates in the 2 highest risk quintiles. Observed mortality rates in cases and controls were similar to Schonberg index-predicted mortality, with model c-indexes of 0.71 and 0.76, respectively. Among women aged ≥65 years with incident breast cancer, the Schonberg index-based risk-stratified 10-year mortality rates were similar to those in women without breast cancer, demonstrating a similar performance of the index among both populations. Along with other health measures, prognostic indexes can help predict survival among older women with breast cancer and support geriatric oncology guidelines that promote using life expectancy calculation tools for shared decision-making.

Advancing menopause care in Australia: barriers and opportunities.

Advancing menopause care in Australia: barriers and opportunities.

Factors associated with long-term gastrointestinal symptoms in colorectal cancer survivors in the women's health initiatives (WHI study).

Colorectal cancer (CRC) survivors often experience long-term symptoms after cancer treatments. But gastrointestinal (GI) symptom experiences are under-investigated in CRC survivors. We described persistent GI symptoms after cancer treatments in female CRC survivors and assessed GI symptoms' risk and life-impact factors. A cross-sectional study utilized data from the Women's Health Initiative (WHI) Life and Longevity After Cancer (LILAC) study that recruited postmenopausal women. Correlation analyses and multivariable linear regression models were used. CRC survivors after cancer treatments were included (N = 413, mean age 71.2 years old, mean time since diagnosis = 8.1 years). 81% of CRC survivors experienced persistent GI symptoms. Bloating/gas was the most prevalent (54.2%± 0.88) and severe GI symptom, followed by constipation (44.1%±1.06), diarrhea (33.4%±0.76), and abdominal/pelvic pain (28.6%±0.62). Significant risk factors for GI symptoms include time since cancer diagnosis (<5 years), advanced cancer stage, high psychological distress, poor dietary habits, and low physical activity. Fatigue and sleep disturbance were the most significant risk factors for long-term GI symptoms (β = 0.21, t = 3.557; β = 0.20, t = 3.336, respectively, Ps < .001). High severity of GI symptoms was positively associated with poor quality of life (QOL), increased daily life interferences (social and physical functions), and low body image satisfaction (Ps < .001). Women CRC survivors experience a high GI symptom burden, highlighting the need to inform policy and improve the QOL of cancer survivors. Our findings will aid in identifying those more vulnerable to symptoms, and inform future survivorship care interventions (i.e., community-based cancer symptom management) by considering multiple risk factors (e.g., psychological distress).

Oral estradiol/micronized progesterone may be associated with lower risk of venous thromboembolism compared with conjugated equine estrogens/medroxyprogesterone acetate in real-world practice

ObjectivesThe Women's Health Initiative study reported an increased risk of venous thromboembolism among menopausal women treated with conjugated equine estrogens/medroxyprogesterone acetate (CEE/MPA) versus placebo. Newer hormone therapies may have a lower venous thromboembolism risk. The study compared the risk of venous thromboembolism between women treated with the combined oral product 17β-estradiol/micronized progesterone (E2/P4) and those treated with oral CEE/MPA regimens. Study designIn a retrospective longitudinal study using real-world claims data from April 2019 to June 2021, women aged 40 years or more treated with oral E2/P4 or oral CEE/MPA who did not have a venous thromboembolism diagnosis before first dispensing claim of CEE/MPA or E2/P4 identified on or after May 1st 2019 (index date) were observed for 6 months or more after the index date. Oral E2/P4 and oral CEE/MPA had been prescribed by the treating physician in real-world practice and were observed through pharmacy dispensing records. Main outcome measuresVenous thromboembolism risk was compared between women receiving oral E2/P4 versus oral CEE/MPA. ResultsThe study included 36,061 women treated with oral E2/P4 or oral CEE/MPA. In the analyses weighted by the inverse probability of treatment for control of potential confounding factors, the incidence of venous thromboembolism was significantly lower for oral E2/P4 compared with oral CEE/MPA (37/10,000 women-years for oral E2/P4 vs 53/10,000 women-years for oral CEE/MPA; incidence rate ratio 0.70, 95 % confidence interval: 0.53–0.92). ConclusionsReal-world evidence suggests that the risk of venous thromboembolism is significantly lower among women treated with oral E2/P4 compared with oral CEE/MPA.

Menopausal hormone therapy and the risk of type 2 diabetes mellitus: Health Insurance Database in South Korea-based retrospective cohort study.

Menopausal hormone therapy (MHT) is known to reduce the incidence of type 2 diabetes mellitus (T2DM); however, since the Women's Health Initiative study, the types and doses of female hormones used for MHT have changed considerably. Therefore, this study was conducted to determine whether MHT, which is currently widely prescribed, increases the risk of T2DM. We performed a retrospective cohort study based on national health insurance data and cancer screening data from 2002 to 2019. We included the MHT group as postmenopausal women older than 40 years who used at least one MHT for at least 6 months between 2003 and 2011. We subclassified the MHT group into five categories; tibolone, combined estrogen plus progestin by the manufacturer (CEPM), oral estrogen, combined estrogen plus progestin by the physician (CEPP), and transdermal estrogen. We selected the non-MHT group as postmenopausal women who had never been prescribed MHT from 2002 to 2019. We compared the incidence of T2DM between the MHT group and the non-MHT group. We enrolled 330,771 women in the MHT group and 798,550 women in the control group. T2DM was diagnosed in 15.2% of the non-MHT group, 16.6% of the tibolone group, 12.1% of the CEPM group, 16.6% of the oral estrogen group, 15.4% of the CEPP group, and 17% of the transdermal estrogen group. In Cox proportional hazard analysis adjusted for variable factors, tibolone, oral estrogen, CEPP, and transdermal estrogen increased the incidence of T2DM. In contrast, there was no change in the risk of T2DM in the CEPM group. MHT, including tibolone, which is currently the most prescribed agent, increased the risk of T2DM; however, CEPM did not increase the risk of T2DM. Only tibolone increased the risk of T2DM in participants older than 70 years.

Impact of an Expanded Definition of Family History on Outcomes of Active Surveillance for Prostate Cancer.

Despite family history being an established risk factor for prostate cancer, the role of a broader definition of family history inclusive of not just prostate cancer but other genetically related malignancies has not been investigated in the active surveillance population. Here, we evaluate the impact of an expanded definition of family history on active surveillance outcomes. Patients undergoing active surveillance for prostate cancer at Massachusetts General Hospital from 1997-2019 with detailed data available on family cancer history were identified. Primary outcome was biopsy progression-free survival, and secondary outcomes were treatment-free survival, adverse pathological features at prostatectomy, and biochemical recurrence after treatment. Statistical analyses were conducted using the Kaplan-Meier method and Cox regression. Among 855 evaluable patients, 300 (35.1%) patients had any family history of prostate cancer, and 95 (11.1%) had a family history of related malignancies suggestive of a hereditary cancer syndrome. Family history of prostate cancer alone was not associated with biopsy progression, whereas family history suggestive of a hereditary cancer syndrome was associated with a significantly increased risk of biopsy progression (HR 1.43, 95%CI 1.01-2.02), independent of other known clinicopathological risk factors in multivariable analysis. Similarly, family history suggestive of a hereditary cancer syndrome was associated with significantly lower treatment-free survival (HR 1.58, 95%CI 1.14-2.18) in multivariable analysis. No significant association was found between family history and adverse features on surgical pathology or biochemical recurrence. An expanded family history suggestive of a hereditary cancer syndrome is an independent predictor of biopsy progression during active surveillance. Men with such a family history may still be offered active surveillance but should be counseled regarding the higher risk of disease progression.

Air pollution and decreased bone mineral density among Women's Health Initiative participants.

Osteoporosis heavily affects postmenopausal women and is influenced by environmental exposures. Determining the impact of criteria air pollutants and their mixtures on bone mineral density (BMD) in postmenopausal women is an urgent priority. We conducted a prospective observational study using data from the ethnically diverse Women's Health Initiative Study (WHI) (enrollment, September 1994-December 1998; data analysis, January 2020 to August 2022). We used log-normal, ordinary kriging to estimate daily mean concentrations of PM10, NO, NO2, and SO2 at participants' geocoded addresses (1-, 3-, and 5-year averages before BMD assessments). We measured whole-body, total hip, femoral neck, and lumbar spine BMD at enrollment and follow-up (Y1, Y3, Y6) via dual-energy X-ray absorptiometry. We estimated associations using multivariable linear and linear mixed-effects models and mixture effects using Bayesian kernel machine regression (BKMR) models. In cross-sectional and longitudinal analyses, mean PM10, NO, NO2, and SO2 averaged over 1, 3, and 5 years before the visit were negatively associated with whole-body, total hip, femoral neck, and lumbar spine BMD. For example, lumbar spine BMD decreased 0.026 (95% CI: 0.016, 0.036) g/cm2/year per a 10% increase in 3-year mean NO2 concentration. BKMR suggested that nitrogen oxides exposure was inversely associated with whole-body and lumbar spine BMD. In this cohort study, higher levels of air pollutants were associated with bone damage, particularly on lumbar spine, among postmenopausal women. These findings highlight nitrogen oxides exposure as a leading contributor to bone loss in postmenopausal women, expanding previous findings of air pollution-related bone damage. US National Institutes of Health.