Antiepileptic drugs (AEDs) are used increasingly in clinical practice to treat a number of conditions. However, the relationship between the use of these medications, particularly the newer AEDs, and fracture risk has not been well characterized. We used data from the Women's Health Initiative (WHI) to determine the relationship bewteen the use of AEDs and falls, fractures, and bone mineral density (BMD) over an average of 7.7 years of follow-up. We included 138,667 women (1,385 users of AEDs and 137,282 nonusers) aged 50 to 79 years in this longitudinal cohort analyses. After adjustment for covariates, use of AEDs was positively associated with total fractures [hazard ratio (HR) = 1.44, 95% confidence interval (CI) 1.30-1.61], all site-specific fractures including the hip (HR = 1.51, 95% CI 1.05-2.17), clinical vertebral fractures (HR = 1.60, 95% CI 1.20-2.12), lower arm or wrist fractures (HR = 1.40, 95% CI 1.11-1.76), and other clinical fractures (HR = 1.46, 95% CI 1.29-1.65) and two or more falls (HR = 1.62, 95% CI 1.50-1.74) but not with baseline BMD or changes in BMD (p > or = .064 for all sites). Use of more than one and use of enzyme-inducing AEDs were significantly associated with total fractures (HR = 1.55, 95% CI 1.15-2.09 and HR = 1.36, 95% CI 1.09-1.69, respectively). We conclude that in clinical practice, postmenopausal women who use AEDs should be considered at increased risk for fracture, and attention to fall prevention may be particularly important in these women.

OBJECTIVE:To examine associations of parental ages at childbirth with healthy survival to age 90 years among older women. STUDY DESIGN:This study included a racially and ethnically diverse sub-cohort of 8,983 postmenopausal women from the larger Women's Health Initiative population, recruited during 1993-1998 and followed for up to 25 years through 2018. MAIN OUTCOME MEASURES:The outcome was categorized as: 1) healthy survival, defined as survival to age 90 without major morbidities (coronary heart disease, stroke, diabetes, cancer, or hip fracture) or mobility disability; 2) usual survival, defined as survival to age 90 without healthy aging (reference category); or 3) death before age 90. Women reported their own and their parents' birth years, and parental ages at childbirth were calculated and categorized as <25, 25-29, 30-34, or ≥35 years. RESULTS:Women were aged on average 71.3 (standard deviation 2.7; range 65-79) years at baseline. There was no significant association of maternal age at childbirth with healthy survival to age 90 or death before age 90. Women born to fathers aged ≥35 compared with 30-34 years at their births were more likely to achieve healthy than usual survival (OR, 1.15; 95% CI, 1.00-1.32). There was no association of paternal age at childbirth with death before age 90. CONCLUSIONS:Findings suggest that being born to older fathers was associated with healthy survival to age 90 among women who had survived to ages 65-79 years at study baseline. There was no association of maternal age at childbirth with healthy survival to age 90 among these older women.

Objectives

To examine associations of maternal age at childbirth and parity with survival to age 90 years (longevity).

Methods

We performed a prospective study among a multiethnic cohort of postmenopausal US women in the Women's Health Initiative recruited from 1993 to 1998 and followed through August 29, 2014. We adjusted associations with longevity for demographic, lifestyle, reproductive, and health-related characteristics.

Results

Among 20 248 women (mean age at baseline, 74.6 years), 10 909 (54%) survived to age 90 years. The odds of longevity were significantly higher in women with later age at first childbirth (adjusted odds ratio = 1.11; 95% confidence interval = 1.02, 1.21 for age 25 years or older vs younger than 25 years; P for trend = .04). Among parous women, the relationship between parity and longevity was significant among White but not Black women. White women with 2 to 4 term pregnancies compared with 1 term pregnancy had higher odds of longevity.

Conclusions

Reproductive events were associated with longevity among women. Future studies are needed to determine whether factors such as socioeconomic status explain associations between reproductive events and longevity.

Objective:to examine the association of parental longevity with healthy survival to age 90 years. Methods:this was a prospective study among a racially and ethnically diverse cohort of 22,735 postmenopausal women from the Women's Health Initiative recruited from 1993 to 1998 and followed through 2017. Women reported maternal and paternal ages at death and current age of alive parents. Parental survival categories were <70, 70-79 (reference), 80-89 and ≥90 years (longevity). Healthy ageing was defined as reaching age 90 without major chronic conditions (coronary heart disease, stroke, diabetes, cancer, or hip fracture) or physical limitations. Results:women whose mothers survived to ≥90 years were more likely to attain healthy ageing (OR, 1.25; 95% CI, 1.11-1.42) and less likely to die before age 90 (OR, 0.75; 95% CI, 0.68-0.83). Women whose fathers survived to ≥90 years did not have significantly increased odds of healthy ageing but showed 21% (OR, 0.79; 95% CI, 0.70-0.90) decreased odds of death before age 90. Women whose mother and father both lived to 90 had the strongest odds of healthy ageing (OR, 1.38; 95% CI, 1.09-1.75) and decreased odds of death (OR, 0.68; 95% CI, 0.54-0.85). The proportion of healthy survivors was highest among women whose mother and father lived to 90 (28.6%), followed by those whose mother only lived to 90 (23.2%). Conclusions:parental longevity predicted healthy ageing in a national cohort of postmenopausal women, supporting the view that genetic, environmental, and behavioral factors transmitted across generations may influence ageing outcomes among offspring.

Objective

The aim of the study was to examine the association of long-term oral bisphosphonate use, compared with short-term use, with fracture risk among postmenopausal women with breast cancer.

Methods

We studied 887 postmenopausal women who were enrolled to the Women's Health Initiative from 1993 to 1998, diagnosed with breast cancer after enrollment, and reported current oral bisphosphonate use of 2 years or more on a medication inventory administered in 2008 to 2009. The outcome of any clinical fracture was ascertained by self-report on an annual study form; a subset of fractures was confirmed with medical records. Women were followed from completion of the medication inventory until 2014. The association between duration of bisphosphonate use reported on the medication inventory and fracture was estimated using multivariate Cox proportional hazards survival models that compared 4 to 7 years and 8 or more years of bisphosphonate use with 2 to 3 years of use.

Results

On average, women were 76 years of age and were followed for 3.7 (SD 1.1) years. There were 142 clinical fractures. In the multivariate-adjusted analysis for fracture risk factors, 8 or more years of bisphosphonate use was associated with higher risk of fracture compared with 2 to 3 years of use (hazard ratio, 1.67 [95% CI, 1.06-2.62]). There was no significant association of 4 to 7 years of use with fracture.

Conclusions

Bisphosphonate use of 8 or more years was associated with higher risk of any clinical fracture compared with 2 to 3 years of use. Our findings raise concern about potential harm or decreased effectiveness of long-term bisphosphonate use on fracture risk. The findings warrant confirmatory studies.

Background

The Women's Health Initiative (WHI) clinical trial of conjugated equine estrogens (CEEs), involving 10,739 postmenopausal women with hysterectomy, aged 50 to 79 years, was stopped early owing to lack of overall health benefit and increased risk of stroke. Because CEE is still prescribed for treatment of menopausal symptoms and prevention of osteoporosis, it is important to understand the overall impact of this therapy on health-related quality of life (HRQOL).

Methods

All participants completed 6 specific measures of quality of life at baseline and 1 year, and a subsample (n = 1189) also completed the questions 3 years after randomization. Changes in scores were analyzed for treatment effect.

Results

Randomization to CEE was associated with a statistically significant but small reduction in sleep disturbance at year 1 compared with baseline (mean benefit, 0.4 points on a 20-point scale) and a statistically significant but small negative effect on social functioning (mean effect, -1.3 points on a 100-point scale). There were no significant improvements due to CEE in the areas of general health, physical functioning, pain, vitality, role functioning, mental health, depressive symptoms, cognitive function, or sexual satisfaction at year 1. A subgroup examined 3 years after baseline had no significant benefits for any HRQOL outcomes. Among women aged 50 to 54 years with moderate to severe vasomotor symptoms at baseline, CEE did not improve any of the HRQOL variables at year 1.

Conclusion

In this trial of postmenopausal women with prior hysterectomy, oral CEE did not have a clinically meaningful effect on HRQOL.

Objective

The aim of the present study was to investigate associations between reproductive factors and survival to age 90 years.

Methods

This was a prospective study of postmenopausal women from the Women's Health Initiative recruited from 1993 to 1998 and followed until the last outcomes evaluation on August 29, 2014. Participants included 16,251 women born on or before August 29, 1924 for whom survival to age 90 during follow-up was ascertained. Women were classified as having survived to age 90 (exceptional longevity) or died before age 90. Multivariable logistic regression models were used to evaluate associations of ages at menarche and menopause (natural or surgical) and reproductive lifespan with longevity, adjusting for demographic, lifestyle, and reproductive characteristics.

Results

Participants were on average aged 74.7 years (range, 69-81 y) at baseline. Of 16,251 women, 8,892 (55%) survived to age 90. Women aged at least 12 years at menarche had modestly increased odds of longevity (odds ratio [OR], 1.09; 95% CI, 1.00-1.19). There was a significant trend toward increased longevity for later age at menopause (natural or surgical; Ptrend = 0.01), with ORs (95% CIs) of 1.19 (1.04-1.36) and 1.18 (1.02-1.36) for 50 to 54 and at least 55 compared with less than 40 years, respectively. Later age at natural menopause as a separate exposure was also significantly associated with increased longevity (Ptrend = 0.02). Longer reproductive lifespan was significantly associated with increased longevity (Ptrend = 0.008). The odds of longevity were 13% (OR 1.13; 95% CI, 1.03-1.25) higher in women with more than 40 compared with less than 33 reproductive years.

Conclusions

Reproductive characteristics were associated with late-age survival in older women.

Purpose of the study

Women's military roles, exposures, and associated health outcomes have changed over time. However, mortality risk-within military generations or compared with non-Veteran women-has not been assessed. Using data from the Women's Health Initiative (WHI), we examined all-cause and cause-specific mortality by Veteran status and military generation among older women.

Design and methods

WHI participants (3,719 Veterans; 141,802 non-Veterans), followed for a mean of 15.2 years, were categorized into pre-Vietnam or Vietnam/after generations based on their birth cohort. We used cox proportional hazards models to examine the association between Veteran status and mortality by generation.

Results

After adjusting for sociodemographic characteristics and WHI study arm, all-cause mortality hazard rate ratios (HRs) for Veterans relative to non-Veterans were 1.16 (95% CI: 1.09-1.23) for pre-Vietnam and 1.16 (95% CI: 0.99-1.36) for Vietnam/after generations. With additional adjustment for health behaviors and risk factors, this excess mortality rate persisted for pre-Vietnam but attenuated for Vietnam/after generations. After further adjustment for medical morbidities, across both generations, Veterans and non-Veterans had similar all-cause mortality rates. Relative to non-Veterans, adjusting for sociodemographics and WHI study arm, pre-Vietnam generation Veterans had higher cancer, cardiovascular, and trauma-related morality rates; Vietnam/after generation Veterans had the highest trauma-related mortality rates (HR = 2.93, 1.64-5.23).

Implications

Veterans' higher all-cause mortality rates were limited to the pre-Vietnam generation, consistent with diminution of the healthy soldier effect over the life course. Mechanisms underlying Vietnam/after generation Veteran trauma-related mortality should be elucidated. Efforts to modify salient health risk behaviors specific to each military generation are needed.

Background

Calcium and vitamin D (CaD) supplementation trials including the Women's Health Initiative (WHI) trial of CaD have shown nonsignificant reductions in total mortality. This report examines intervention effects on total and cause-specific mortality by age and adherence.

Methods

The WHI CaD trial was a randomized, double-blind, placebo-controlled trial that enrolled 36,282 postmenopausal women aged 51-82 years from 40 U.S. clinical centers. Women were assigned to 1,000 mg of elemental calcium carbonate and 400 IU of vitamin D(3) daily or placebo with average follow-up of 7.0 years.

Results

The hazard ratio (HR) for total mortality was 0.91 (95% confidence interval [CI], 0.83-1.01) with 744 deaths in women randomized to CaD versus 807 deaths in the placebo group. HRs were in the direction of reduced risk but nonsignificant for stroke and cancer mortality, but near unity for coronary heart disease and other causes of death. HRs for total mortality were 0.89 in the 29,942 women younger than 70 years (95% CI, 0.79-1.01) and 0.95 in the 6,340 women aged 70 and older (95% CI, 0.80-1.12; p value for age interaction = .10). No statistically significant interactions were observed for any baseline characteristics. Treatment effects did not vary significantly by season.

Conclusions

In the WHI CaD trial, supplementation did not have a statistically significant effect on mortality rates but the findings support the possibility that these supplements may reduce mortality rates in postmenopausal women. These data can neither support nor refute recommendations for higher dose vitamin D supplementation to reduce cancer or total mortality.

Purpose

Menopausal hormone therapy (MHT) use induces alterations in circulating estrogens/estrogen metabolites, which may contribute to the altered risk of reproductive tract cancers among current users. Thus, the current study assessed associations between circulating estrogens/estrogen metabolites and ovarian and endometrial cancer risk among MHT users.

Methods

We conducted a nested case-control study among postmenopausal women using MHT at baseline in the Women's Health Initiative Observational Study (179 ovarian cancers, 396 controls; 230 endometrial cancers, 253 controls). Multivariable logistic regression was utilized to estimate odds ratios and 95% confidence intervals overall and by subtype.

Results

Estrogen/estrogen metabolite levels were not associated with overall or serous ovarian cancer risk, examined separately. However, unconjugated estradiol was positively associated with non-serous ovarian cancer risk [quintile 5 vs. quintile 1: 3.01 (1.17-7.73); p-trend = 0.03; p-het < 0.01]. Endometrial cancer risk was unrelated to estrogen/estrogen metabolite levels among women who took combined estrogen/progestin therapy (EPT).

Conclusions

These findings provide novel evidence that may support a heterogeneous hormonal etiology across ovarian cancer subtypes. Circulating estrogens did not influence endometrial cancer risk among women with EPT-induced high-estrogen levels. Larger studies are needed to delineate the relationship between ovarian/endometrial cancer subtypes and estrogen levels in the context of MHT use.