Alison J. Huang

Sex Hormone Levels and Risks of Estrogen Receptor–Negative and Estrogen Receptor–Positive Breast Cancers

BACKGROUND Endogenous sex hormone levels are associated with risks of breast cancer overall and estrogen receptor (ER)-positive breast tumors; however, their associations with ER-negative tumors remain unclear. METHODS In a case-cohort study within the Womens Health Initiative Observational Study among postmenopausal women aged 50-79 years, we examined associations between endogenous testosterone and estradiol levels and the risks of ER-negative and ER-positive breast cancers. Serum levels of bioavailable testosterone and estradiol were assessed at the baseline visit in 317 invasive breast cancer case subjects and in a subcohort of 594 women. Bioavailable sex hormone levels were calculated using the total hormone level and the sex hormone-binding globulin concentration (measured by radioimmunoassays and a chemiluminescent immunoassay, respectively). Cox proportional hazards regression was used for statistical analysis. All statistical tests were two-sided. RESULT The unadjusted absolute rates of ER-negative breast cancer for testosterone quartiles 1-4 were 0.34, 0.20, 0.23, and 0.21 per 10,000 person-years, respectively. Compared with women in the lowest quartile of testosterone level, those in quartile 2 had a 56% lower risk of ER-negative cancer (hazard ratio [HR] = 0.44, 95% confidence interval [CI] = 0.23 to 0.85), those in quartile 3 had a 45% lower risk (HR = 0.55, 95% CI = 0.30 to 1.01), and those in quartile 4 had a 49% lower risk (HR = 0.51, 95% CI = 0.28 to 0.94), independent of other risk factors. Estradiol level was not associated with ER-negative breast cancer. ER-positive breast cancer risk increased with higher testosterone levels (P(trend) = .04), but this trend was not statistically significant after adjustment for estradiol (P(trend) = .15). ER-positive cancer risk was approximately twofold higher in women with estradiol levels in quartiles 2-4 compared with women in quartile 1, independent of risk factors. CONCLUSION Higher serum levels of bioavailable testosterone are associated with lower risks of ER-negative breast cancer in postmenopausal women.

Urinary incontinence in older community-dwelling women : The role of cognitive and physical function decline

OBJECTIVES: To examine the association between cognitive decline, physical function decline, and urinary incontinence in older community-dwelling women. METHODS: This was an observational study of 6,361 community-dwelling women aged 65 years and older participating in the Study of Osteoporotic Fractures. Clinical frequency and functional disruptiveness of incontinence were assessed by self-report questionnaires. Cognitive function was assessed at visits using the modified Mini-Mental State Examination, Trails B test, and Digit Symbol Substitution Test. Physical function was assessed by measuring walking speed over a 6-meter course and time needed to complete five chair stands. Women were considered to have recent, significant decline in cognitive or physical function if their cognitive or physical performance declined by greater than 1 standard deviation beyond the mean decline in the 6 years preceding assessment of incontinence. RESULTS: Women with recent physical function decline were more likely to report weekly incontinence (odds ratio [OR] 1.31, 95% confidence interval [CI] 1.09–1.56 for walking speed decline; OR 1.40, 95% CI 1.19–1.64 for chair stand decline), after adjusting for multiple characteristics. Women with recent cognitive decline were more likely to report incontinence that interfered with activities (OR 1.55, 95% CI 1.10–2.17 for modified Mini-Mental State Examination decline; OR 1.53, 95% CI 1.01–2.31 for Digit Symbol Substitution Test decline), after adjusting for multiple characteristics. CONCLUSION: Both cognitive and physical function decline are likely important contributors to incontinence in community-dwelling women aged 65 years and older. Although cognitive decline may not be associated with greater frequency of incontinence, women with cognitive decline may have more difficulty coping with incontinence symptoms. LEVEL OF EVIDENCE: II

Mixed Urinary Incontinence: Greater Impact on Quality of Life

PURPOSE We compared the impact of mixed, stress and urge urinary incontinence on quality of life in middle-aged or older women. MATERIALS AND METHODS We analyzed cross-sectional data from a population based cohort of 2,109 ethnically diverse middle-aged or older women. Among participants reporting weekly incontinence, clinical type of incontinence was assessed by self-reported questionnaires and disease specific quality of life impact was evaluated using the Incontinence Impact Questionnaire. Multivariable logistic regression was used to compare the odds of greater quality of life impact from incontinence, defined as an Incontinence Impact Questionnaire score in the 75th percentile or greater in women with stress, urge and mixed incontinence. RESULTS More than 28% (598) of women reported weekly incontinence, including 37% with stress, 31% with urge and 21% with mixed incontinence. Unadjusted Incontinence Impact Questionnaire scores were higher for women with mixed vs urge or stress incontinence (median score 29 vs 17 and 13, respectively, p <0.01). Adjusting for age, race/ethnicity, health status and clinical incontinence severity, women with mixed incontinence were more likely to report a greater overall quality of life impact compared to those with stress incontinence (OR 2.5, 95% CI 1.4-4.3), as well as a greater specific impact on travel (OR 2.2, 95% CI 1.3-3.7) and emotional (OR 1.8, 95% CI 1.0-3.4) Incontinence Impact Questionnaire domains. The overall impact of urge incontinence did not differ significantly from that of stress (urge vs stress OR 1.6, 95% CI 0.9-2.7) or mixed incontinence (mixed vs urge OR 1.6, 95% CI 0.9-2.8) in adjusted models. CONCLUSIONS In middle-aged or older women mixed incontinence is associated with a greater quality of life impact than stress incontinence independent of age, race, health or incontinence severity. Identification of women with mixed incontinence symptoms may be helpful in discovering which women are most likely to experience functional limitations and decreased well-being from incontinence.

An Intensive Behavioral Weight Loss Intervention and Hot Flushes in Women

BACKGROUND Higher body mass index is associated with worse hot flushes during menopause but the effect of weight loss on flushing is unclear. METHODS Self-administered questionnaires were used to assess bothersome hot flushes in a 6-month randomized controlled trial of an intensive behavioral weight loss program (intervention) vs a structured health education program (control) in 338 women who were overweight or obese and had urinary incontinence. Weight, body mass index, abdominal circumference, physical activity, calorie intake, blood pressure, and physical and mental functioning were assessed at baseline and at 6 months. Repeated-measures proportional odds models examined intervention effects on bothersome hot flushes and potential mediating factors. RESULTS Approximately half of participants (n = 154) were at least slightly bothered by hot flushes at baseline. Among these women, the intervention was associated with greater improvement in bothersome flushes vs control (odds ratio [OR] for improvement by 1 Likert category, 2.25; 95% confidence interval [CI], 1.20-4.21). Reductions in weight (OR, 1.32; 95% CI, 1.08-1.61; per 5-kg decrease), body mass index (1.17; 1.05-1.30; per 1-point decrease), and abdominal circumference (1.32; 1.07-1.64; per 5-cm decrease) were each associated with improvement in flushing, but changes in physical activity, calorie intake, blood pressure, and physical and mental functioning were not related. The effect of the intervention on flushing was modestly diminished after adjustment for multiple potential mediators (OR, 1.92; 95% CI, 0.95-3.89). CONCLUSION Among women who were overweight or obese and had bothersome hot flushes, an intensive behavioral weight loss intervention resulted in improvement in flushing relative to control. Trial Registration clinicaltrials.gov Identifier: NCT00091988.

Sexual function and aging in racially and ethnically diverse women.

OBJECTIVES: To examine factors influencing sexual activity and functioning in racially and ethnically diverse middle‐aged and older women.

Vaginal symptoms in postmenopausal women: self-reported severity, natural history, and risk factors.

Objective: This study aimed to examine factors other than estrogen deficiency influencing the development and persistence of vaginal dryness, itching, and painful sexual intercourse after menopause. Methods: We analyzed data from a 2-year, population-based cohort of 1,017 postmenopausal women aged 55 to 75 years. Vaginal symptoms were assessed by interviewer-administered questionnaire, and vaginal swabs were performed to assess vaginal pH and microbial flora at baseline, 12 months, and 24 months. Generalized estimating equations were used to identify characteristics associated with symptoms. Results: Half of the women (n = 471) reported problematic vaginal dryness, a third (n = 316) reported itching, and 40% of sexually active women (n = 166) reported painful intercourse at baseline. Of women not taking estrogen, half of those reporting baseline symptoms were symptomatic after 24 months. Vaginal dryness was associated with younger age (odds ratio [OR], 0.81; 95% CI, 0.69-0.94, per 5-y increase), nonwhite race (ie, African American, Hispanic, Asian or Pacific Islander, or American Indian [OR, 1.53; 95% CI, 1.04-2.27]), diabetes (OR, 1.51; 95% CI, 1.07-2.12), lower 36-item Short-Form Health Survey physical functioning scores (OR, 0.90; 95% CI, 0.85-0.97, per 10-point increase), lower body mass index (OR, 0.81; 95% CI, 0.71-0.93, per 5 kg/m2 increase), recent sexual activity (OR, 1.14; 95% CI, 1.08-1.21), and vaginal colonization with enterococci (OR, 1.25; 95% CI, 1.04-1.51). Vaginal itching was also associated with lower physical functioning scores (OR, 0.86; 95% CI, 0.80-0.92, per 10-point increase). Risk factors for painful intercourse included younger age (OR, 0.72; 95% CI, 0.56-0.93, per 5-y increase), diabetes (OR, 3.48; 95% CI, 1.93-6.27), lower body mass index (OR, 0.76; 95% CI, 0.61-0.95, per 5 kg/m2 increase), and higher vaginal pH (OR, 1.10; 95% CI, 1.00-1.21, per 0.5 units). Conclusions: Vaginal symptoms affect a large proportion of postmenopausal women, particularly those with diabetes and those with lower body mass index, but may resolve for up to half of women without estrogen therapy.

Diabetes Mellitus and Sexual Function in Middle-Aged and Older Women

OBJECTIVE: Diabetes mellitus is an established risk factor for sexual dysfunction in men, but its effect on female sexual function is poorly understood. We examined the relationship of diabetes to sexual function in middle-aged and older women. METHODS: Sexual function was examined in a cross-sectional cohort of ethnically diverse women aged 40–80 years using self-administered questionnaires. Multivariable regression models compared self-reported sexual desire, frequency of sexual activity, overall sexual satisfaction, and specific sexual problems (difficulty with lubrication, arousal, orgasm, or pain) among insulin-treated diabetic, non–insulin-treated diabetic, and nondiabetic women. Additional models assessed relationships between diabetic end-organ complications (heart disease, stroke, renal dysfunction, and peripheral neuropathy) and sexual function. RESULTS: Among the 2,270 participants, mean±standard deviation age was 55±9.2 years, 1,006 (44.4%) were non-Latina white, 486 (21.4%) had diabetes, and 139 (6.1%) were taking insulin. Compared with 19.3% of nondiabetic women, 34.9% of insulin-treated diabetic women (adjusted odds ratio [OR] 2.04, 95% confidence interval [CI] 1.32–3.15) and 26.0% of non–insulin-treated diabetic women (adjusted OR 1.42, 95% CI 1.03–1.94) reported low overall sexual satisfaction. Among sexually active women, insulin-treated diabetic women were more likely to report problems with lubrication (OR 2.37, 95% CI 1.35–4.16) and orgasm (OR 1.80, 95% CI 1.01–3.20) than nondiabetic women. Among all diabetic women, end-organ complications such as heart disease, stroke, renal dysfunction, and peripheral neuropathy were associated with decreased sexual function in at least one domain. CONCLUSION: Compared with nondiabetic women, diabetic women are more likely to report low overall sexual satisfaction. Insulin-treated diabetic women also appear at higher risk for problems such as difficulty with lubrication and orgasm. Prevention of end-organ complications may be important in preserving sexual activity and function in diabetic women. LEVEL OF EVIDENCE: II

Clinical Significance of Postvoid Residual Volume in Older Ambulatory Women

OBJECTIVES: To examine the prevalence, natural history, and clinical significance of high postvoid residual (PVR) volume in ambulatory older women.

Endogenous Estrogen Levels and the Effects of Ultra-Low-Dose Transdermal Estradiol Therapy on Bone Turnover and BMD in Postmenopausal Women†

In a randomized controlled trial of a 0.014 mg/d transdermal estradiol patch, serum bone turnover markers decreased to a greater degree in postmenopausal women with lower versus higher endogenous estradiol levels. This suggests that the protective effects of ultra‐low‐dose estrogen therapy on the postmenopausal skeletal health may depend critically on womens endogenous estrogen levels before treatment.

Urinary Incontinence Before and After Bariatric Surgery

IMPORTANCE Among women and men with severe obesity, evidence for improvement in urinary incontinence beyond the first year after bariatric surgery-induced weight loss is lacking. OBJECTIVES To examine change in urinary incontinence before and after bariatric surgery and to identify factors associated with improvement and remission among women and men in the first 3 years after bariatric surgery. DESIGN, SETTING, AND PARTICIPANTS The Longitudinal Assessment of Bariatric Surgery 2 is an observational cohort study at 10 US hospitals in 6 geographically diverse clinical centers. Participants were recruited between February 21, 2005, and February 17, 2009. Adults undergoing first-time bariatric surgical procedures as part of clinical care by participating surgeons between March 14, 2006, and April 24, 2009, were followed up for 3 years (through October 24, 2012). INTERVENTION Participants undergoing bariatric surgery completed research assessments before the procedure and annually thereafter. MAIN OUTCOMES AND MEASURES The frequency and type of urinary incontinence episodes in the past 3 months were assessed using a validated questionnaire. Prevalent urinary incontinence was defined as at least weekly urinary incontinence episodes, and remission was defined as change from prevalent urinary incontinence at baseline to less than weekly urinary incontinence episodes at follow-up. RESULTS Of 2458 participants, 1987 (80.8%) completed baseline and follow-up assessments. At baseline, the median age was 47 years (age range, 18-78 years), the median body mass index was 46 kg/m2 (range, 34-94 kg/m2), and 1565 of 1987 (78.8%) were women. Urinary incontinence was more prevalent among women (49.3%; 95% CI, 46.9%-51.9%) than men (21.8%; 95% CI, 18.2%-26.1%) (P < .001). After a mean 1-year weight loss of 29.5% (95% CI, 29.0%-30.1%) in women and 27.0% (95% CI, 25.9%-28.6%) in men, year 1 urinary incontinence prevalence was significantly lower among women (18.3%; 95% CI, 16.4%-20.4%) and men (9.8%; 95% CI, 7.2%-13.4%) (P < .001 for all). The 3-year prevalence was higher than the 1-year prevalence for both sexes (24.8%; 95% CI, 21.8%-26.5% among women and 12.2%; 95% CI, 9.0%-16.4% among men) but was substantially lower than baseline (P < .001 for all). Weight loss was independently related to urinary incontinence remission (relative risk, 1.08; 95% CI, 1.06-1.10 in women and 1.07; 95% CI, 1.02-1.13 in men) per 5% weight loss, as were younger age and the absence of a severe walking limitation. CONCLUSIONS AND RELEVANCE Among women and men with severe obesity, bariatric surgery was associated with substantially reduced urinary incontinence over 3 years. Improvement in urinary incontinence may be an important benefit of bariatric surgery.