Military Sexual Trauma and Menopause Symptoms Among Midlife Women Veterans.

BACKGROUND: Sexual assault and/or sexual harassment during military service (military sexual trauma (MST)) can have medical and mental health consequences. Most MST research has focused on reproductive-aged women, and little is known about the long-term impact of MST on menopause and aging-related health. OBJECTIVE: Examine associations of MST with menopause and mental health outcomes in midlife women Veterans. DESIGN: Cross-sectional. PARTICIPANTS: Women Veterans aged 45-64 enrolled in Department of Veterans Affairs (VA) healthcare in Northern California between March 2019 and May 2020. MAIN MEASURES: Standardized VA screening questions assessed MST exposure. Structured-item questionnaires assessed vasomotor symptoms (VMS), vaginal symptoms, sleep difficulty, depressive symptoms, anxiety symptoms, and posttraumatic stress disorder (PTSD) symptoms. Multivariable logistic regression analyses examined associations between MST and outcomes based on clinically relevant menopause and mental health symptom thresholds. KEY RESULTS: Of 232 participants (age = 55.95 ± 5.13), 73% reported MST, 66% reported VMS, 75% reported vaginal symptoms, 36% met criteria for moderate-to-severe insomnia, and almost half had clinically significant mental health symptoms (33% depressive symptoms, 49% anxiety, 27% probable PTSD). In multivariable analyses adjusted for age, race, ethnicity, education, body mass index, and menopause status, MST was associated with the presence of VMS (OR 2.44, 95% CI 1.26-4.72), vaginal symptoms (OR 2.23, 95% CI 1.08-4.62), clinically significant depressive symptoms (OR 3.21, 95% CI 1.45-7.10), anxiety (OR 4.78, 95% CI 2.25-10.17), and probable PTSD (OR 6.74, 95% CI 2.27-19.99). Results did not differ when military sexual assault and harassment were disaggregated, except that military sexual assault was additionally associated with moderate-to-severe insomnia (OR 3.18, 95% CI 1.72-5.88). CONCLUSIONS: Exposure to MST is common among midlife women Veterans and shows strong and independent associations with clinically significant menopause and mental health symptoms. Findings highlight the importance of trauma-informed approaches to care that acknowledge the role of MST on Veteran women's health across the lifespan.

HOT FLASHES AND SLEEP DISRUPTION IN A RANDOMIZED TRIAL IN MENOPAUSAL WOMEN.

BACKGROUND: Hot flashes, common during menopause, affect up to 80% of Western menopausal women and are reported to contribute to sleep disturbances in midlife. Few prospective data are available to confirm the specific role of hot flashes in disrupting sleep in midlife women, however, or confirm whether changes in hot flashes in response to clinical therapies result in improvement in sleep. OBJECTIVE: To examine the effects of continuous nitroglycerin therapy on sleep quality in peri- and postmenopausal women with frequent hot flashes (pre-specified secondary trial endpoint), and to examine prospective associations between hot flashes and sleep disruption in this population. STUDY DESIGN: Sleep data were analyzed from a randomized, double-blinded, placebo-controlled trial of continuous transdermal nitroglycerin (NTG) therapy to suppress nitric oxide-mediated vasodilation in peri- or postmenopausal women with hot flashes. Participants were randomized to uninterrupted use of transdermal NTG (0.2-0.6 mg/hour) or placebo for 12 weeks. Nocturnal hot flashes awakening participants from sleep were evaluated using 7-day symptom diaries at baseline, 5 weeks, and 12 weeks. Sleep disruption (wake time after sleep onset, WASO) was assessed using validated sleep diaries, and global sleep quality was assessed by the validated Pittsburgh Sleep Quality Index (PSQI: range 0 [best] 21 [worst]) questionnaire. Mixed linear models examined changes in sleep quality and disruption, as well as the strength of associations between nocturnal hot flash frequency and sleep outcomes, over 5 and 12 weeks, adjusting for baseline values, age, race, and ethnicity. RESULTS: Among the 141 participants (70 to NTG and 71 to placebo, mean age 54.6 [±3.9] years), the mean baseline hot flash frequency was 10.8 (±3.5) per day, including 2.6 (±1.7) nocturnal hot flashes awakening participants. At baseline, hot flashes were the most commonly reported reason for nocturnal awakening, with 62.6% of participants reporting waking due to hot flashes at least twice nightly. Over 5 and 12 weeks, mean frequency of nocturnal hot flashes causing awakenings decreased in both groups (NTG: -0.9 episodes/night, placebo: -1.0 episodes/night). Sleep disruption as measured by average nightly WASO also decreased (NTG: -10.1 minutes, placebo: -7.3 minutes), and mean PSQI score improved (NTG: -1.3 points, placebo: -1.2 points). No significant between-group differences in change in sleep outcomes were detected from baseline to 5 and 12 weeks, including PSQI sleep quality score as a pre-specified secondary trial endpoint (P ≥ .05 for all). Greater improvement in nocturnal hot flash frequency over 5 and 12 weeks was associated with greater improvement in PSQI sleep quality score (ß= -0.30, P=.01) and sleep disruption reflected by WASO (ß= -1.88, P=.02) in the combined sample. CONCLUSION: Among menopausal women in a randomized trial of continuous NTG therapy for hot flashes, hot flashes were the most frequently reported cause of nocturnal awakenings. Compared to placebo, continuous NTG therapy did not result in greater improvements in sleep quality from baseline to 5 and 12 weeks. Based on night-by-night symptom diaries and questionnaires, however, greater improvement in nocturnal hot flash frequency in both groups was associated with greater improvement in sleep quality and disruption.

Intimate Partner Violence, Mental Health, and Aging-Related Health Among Men and Women Veterans Across the Lifespan.

BACKGROUND: A growing body of evidence suggests adverse health outcomes related to intimate partner violence (IPV), including traumatic brain injury (TBI). However, most research in this area has focused on reproductive-aged women. OBJECTIVE: To examine relationships between IPV (with and without TBI), mental health, and aging-related health outcomes among men and women Veterans across the lifespan. DESIGN: Cross-sectional analysis of Department of Veterans Affairs (VA) administrative data from fiscal years 2000-2019. Descriptive statistics and chi-square analyses were used to compare key comorbidities in matched samples of Veterans with and without IPV (gender-stratified and matched 1:3 based on demographics and index date). Comparisons between those with IPV and TBI relative to IPV alone were also examined. SUBJECTS: Veterans aged 18 + with and without documented IPV in Department of Veterans Affairs (VA) electronic health records (n = 4108 men, 2824 women). MAIN MEASURES: ICD codes were used to identify IPV, TBI, and aging-related medical (sleep disorder, hypertension, diabetes, dementia) and common psychiatric (depression, posttraumatic stress disorder, alcohol use disorder, and substance use disorder) diagnoses. KEY RESULTS: Demographic characteristics were reflective of VA-enrolled Veterans (men: mean age 66, SD 16; 72% non-Hispanic White; women: mean age 47, SD 13; 64% non-Hispanic White). Relative to Veterans without IPV, both men and women with IPV had higher rates of all examined medical (e.g., sleep disorders, men: 33% vs. 52%; women: 45% vs. 63%) and psychiatric diagnoses (e.g., depression, men 32% vs. 74%; women 59% vs. 91%; all ps < .001), with evidence of an additive effect of TBI on some psychiatric outcomes. CONCLUSIONS: IPV is broadly associated with aging-related and mental health, and TBI is a common correlate that may further contribute to psychiatric outcomes. Findings highlight the importance of trauma-informed care and recognizing the potential role of these exposures on men and women Veterans' health across the lifespan.

Factors Associated with Military Sexual Trauma (MST) Disclosure During VA Screening Among Women Veterans.

BACKGROUND: Capturing military sexual trauma (MST) exposure is critical for Veterans' health equity. For many, it improves access to VA services and allows for appropriate care. OBJECTIVE: Identify factors associated with nondisclosure of MST in VA screening among women. DESIGN: Cross-sectional telephone survey linked with VA electronic health record (EHR) data. PARTICIPANTS: Women Veterans using primary care or women's health services at 12 VA facilities in nine states. MAIN MEASURES: Survey self-reported MST (sexual assault and/or harassment during military service), socio-demographics and experiences with VA care, as well as EHR MST results. Responses were categorized as "no MST" (no survey or EHR MST), "MST captured by EHR and survey," and "MST not captured by EHR" (survey MST but no EHR MST). We used stepped multivariable logistic regression to examine "MST not captured by EHR" as a function of socio-demographics, patient experiences, and screening method (survey vs. EHR). KEY RESULTS: Among 1287 women (mean age 50, SD 15), 35% were positive for MST by EHR and 61% were positive by survey. Approximately 38% had "no MST," 34% "MST captured by EHR and survey," and 26% "MST not captured by EHR". In fully adjusted models, odds of "MST not captured by EHR" were higher among Black and Latina women compared to white women (Black: OR = 1.6, 1.2-2.2; Latina: OR = 1.9, 1.0-3.6). Women who endorsed only sexual harassment in the survey (vs. sexual harassment and sexual assault) had fivefold higher odds of "MST not captured by EHR" (OR = 4.9, 3.2-7.3). Women who were screened for MST in the EHR more than once had lower odds of not being captured (OR = 0.3, 0.2-0.4). CONCLUSIONS: VA screening for MST may disproportionately under capture patients from historically minoritized ethnic/racial groups, creating inequitable access to resources. Efforts to mitigate screening disparities could include re-screening and reinforcing that MST includes sexual harassment.

Long-term Psychoactive Medications, Polypharmacy, and Risk of Suicide and Unintended Overdose Death Among Midlife and Older Women Veterans.

BACKGROUND: Rates of suicide and unintended overdose death are high among midlife and older women, yet there is paucity of data identifying women at greatest risk. Psychoactive medications, commonly prescribed and co-prescribed in this population, may serve as salient indicators of risk for these outcomes. OBJECTIVE: To determine whether long-term psychoactive medications and psychoactive polypharmacy predict risk of suicide and unintended overdose death among midlife and older women Veterans above and beyond other recognized factors. DESIGN: Longitudinal cohort study PARTICIPANTS: Women Veterans aged ≥ 50 with at least one Veterans Health Administration (VHA) clinical encounter in FY2012-2013. MAIN MEASURES: Long-term psychoactive medications (opioids, benzodiazepines, sedative-hypnotics, antidepressants, antipsychotics, and antiepileptics, prescribed for ≥ 90/180 days) and psychoactive polypharmacy (overlapping for ≥ 1 day) from VHA pharmacy records; suicide and unintended overdose death through December 31, 2018. KEY RESULTS: In this national sample of 154,558 midlife and older women Veterans (mean age 63.4, SD 9.3 years), 130 died by suicide and 175 died from unintentional overdose over an average of 5.6 years. In fully adjusted models, long-term opioids (hazard ratio (HR) 2.01, 95% CI 1.21-3.35) and benzodiazepines (HR 2.99, 95% CI 1.82-4.91) were associated with death by suicide; opioids (HR 3.62, 95% CI 2.46-5.34), benzodiazepines (HR 2.77, 95% CI 1.73-4.42), sedative-hypnotics (HR 1.87, 95% CI 1.06-3.29), antidepressants (HR 1.47, 95% CI 1.03-2.12), antipsychotics (HR 1.81, 95% CI 1.02-3.22), and antiepileptics (HR 2.17, 95% CI 1.48-3.19) were associated with unintended overdose death. Women who were co-prescribed ≥ 3 psychoactive medications had over 2-fold increased risk of suicide (HR 2.83, 95% CI 1.65-4.84) and unintended overdose death (HR 2.60, 95% CI 1.72-3.94). CONCLUSIONS: Long-term psychoactive medications and psychoactive medication polypharmacy were important indicators of risk for death by suicide and death by unintended overdose among midlife and older women Veterans, even after accounting for psychiatric and substance use disorders.

Interpersonal violence and painful bladder symptoms in community-dwelling midlife to older women.

BACKGROUND: Women are more likely to present with genitourinary complaints immediately after exposure to interpersonal violence, but little is known about the long-term effects of violence on women's urologic health, including their susceptibility to bladder pain and infections. OBJECTIVE: To determine whether lifetime interpersonal violence exposure and current posttraumatic stress disorder (PTSD) symptoms are associated with the prevalence or severity of painful bladder symptoms and a greater lifetime history of antibiotic-treated urinary tract infections in community-dwelling midlife and older women. STUDY DESIGN: We examined the cross-sectional data from a multiethnic cohort of community-dwelling women aged 40 to 80 years enrolled in a northern California integrated healthcare system. Women completed structured self-report questionnaires about their past exposure to physical and verbal/emotional intimate partner violence and sexual assault. The symptoms of PTSD were assessed using the PTSD checklist for the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition, Civilian version. Additional structured self-report measures assessed the current bladder pain, other lower urinary tract symptoms, and the history of antibiotic-treated urinary tract infections. Multivariable logistic regression models examined self-reported interpersonal violence exposure history and current PTSD symptoms in relation to current bladder pain and antibiotic-treated urinary tract infection history. RESULTS: Among 1974 women (39% non-Latina White, 21% Black, 20% Latina, and 19% Asian), 22% reported lifetime interpersonal violence exposure, 22% reported bladder pain, and 60% reported a history of ever having an antibiotic-treated urinary tract infection. Lifetime experiences of sexual assault (odds ratio, 1.39; [95% confidence interval, 1.02-1.88]) and current PTSD symptoms (odds ratio, 1.96; [95% confidence interval, 1.45-2.65]) were associated with current bladder pain. A lifetime experience of physical intimate partner violence was associated with having a urinary tract infection at any time in life previously (odds ratio, 1.38; [95% confidence interval, 1.00-1.86]), as was emotional intimate partner violence (odds ratio, 1.88; [95% confidence interval, 1.43-2.48]), sexual assault (odds ratio, 1.44; [95% confidence interval, 1.09-1.91]), and current PTSD symptoms (odds ratio, 1.54; [95% confidence interval, 1.16-2.03]). CONCLUSION: In this ethnically diverse, community-based cohort, lifetime interpersonal violence exposures and current PTSD symptoms were independently associated with current bladder pain and the lifetime history of antibiotic-treated urinary tract infections in midlife to older women. The findings suggest that interpersonal violence and PTSD symptoms may be underrecognized markers of risk for urologic pain and infections in women, highlighting a need for trauma-informed care of these issues.

Menopausal Hormone Therapy and Suicide in a National Sample of Midlife and Older Women Veterans.

BACKGROUND: Among midlife and older women, menopause symptoms and menopausal hormone therapy have been linked to mental health disorders and other comorbidities related to suicide. However, the role of hormone therapy as a prognostic factor of suicide risk is largely unknown. OBJECTIVES: To examine associations between menopausal hormone therapy, suicide attempts, and suicide among midlife and older women Veterans. RESEARCH DESIGN: In this longitudinal analysis of national Veterans Health Administration data from women Veterans aged 50 years and above, we used Fine-Gray proportional hazards models to examine associations between menopausal hormone therapy (prescribed in 2012-2013) and incident suicide attempts and suicide (index date-2016). MEASURES: Menopausal hormone therapy and psychoactive medications from pharmacy records; suicide attempts and suicide from national suicide data repositories; demographic variables, medical and psychiatric diagnoses, and substance use disorders from electronic medical record data and International Classification Diagnoses-9-CM codes. RESULTS: In this national sample of 291,709 women Veterans (mean age 60.47, SD 9.81), 6% were prescribed menopausal hormone therapy at baseline. Over an average of 4.5 years, 2673 had an incident suicide attempt (93%) or death by suicide (7%). Adjusting for age, race, and medical diagnoses, menopausal hormone therapy was associated with increased risk of suicide attempt (hazard ratio 1.41; 95% confidence interval, 1.22-1.64) and over 2-fold increased risk of death by suicide (hazard ratio 2.47; 95% confidence interval, 1.58-3.87). Associations with death by suicide remained significant after accounting for psychiatric comorbidity and psychoactive medications. CONCLUSIONS: Menopausal hormone therapy may be an important indicator of suicide risk among midlife and older women.

Women Veterans' Experiences with Integrated, Biopsychosocial Pain Care: A Qualitative Study.

OBJECTIVES: Biopsychosocial, integrated pain care models are increasingly implemented in the Veterans Health Administration to improve chronic pain care and reduce opioid-related risks, but little is known about how well these models address women veterans' needs. DESIGN: Qualitative, interview-based study. SETTING: San Francisco VA Health Care System Integrated Pain Team (IPT), an interdisciplinary team that provides short-term, personalized chronic pain care emphasizing functional goals and active self-management. SUBJECTS: Women with chronic pain who completed ≥3 IPT sessions. METHODS: Semistructured phone interviews focused on overall experience with IPT, perceived effectiveness of IPT care, pain care preferences, and suggested changes for improving gender-sensitive pain care. We used a rapid approach to qualitative thematic analysis to analyze interviews. RESULTS: Fourteen women veterans (mean age 51 years; range 33-67 years) completed interviews. Interviews revealed several factors impacting women veterans' experiences: 1) an overall preference for receiving both primary and IPT care in gender-specific settings, 2) varying levels of confidence that IPT could adequately address gender-specific pain issues, 3) barriers to participating in pain groups, and 4) barriers to IPT self-management recommendations due to caregiving responsibilities. CONCLUSIONS: Women veterans reported varied experiences with IPT. Recommendations to improve gender-sensitive pain care include increased provider training; increased knowledge of and sensitivity to women's health concerns; and improved accommodations for prior trauma, family and work obligations, and geographic barriers. To better meet the needs of women veterans with chronic pain, integrated pain care models must be informed by an understanding of gender-specific needs, challenges, and preferences.

Opioid Reduction and Risk Mitigation in VA Primary Care: Outcomes from the Integrated Pain Team Initiative.

BACKGROUND: National guidelines advise decreasing opioids for chronic pain, but there is no guidance on implementation. OBJECTIVE: To evaluate the effectiveness of an Integrated Pain Team (IPT) clinic in decreasing opioid dose and mitigating opioid risk. DESIGN: This study prospectively compared two matched cohorts receiving chronic pain care through IPT (N = 147) versus usual primary care (UPC, N = 147) over 6 months. Patients were matched on age, sex, psychiatric diagnoses, and baseline opioid dose. PATIENTS: Veterans receiving care at a VA medical center or VA community-based clinics. INTERVENTION: Interdisciplinary IPT, consisting of a collocated medical provider, psychologist, and pharmacist embedded in VA primary care providing short-term biopsychosocial management of veterans with chronic pain and problematic opioid use. MAIN MEASURES: Change in opioid dose expressed as morphine equivalent daily dose (MEDD) and opioid risk mitigation evaluated at baseline, 3 months, and 6 months. KEY RESULTS: Compared with veterans receiving UPC, those followed by IPT had a greater mean MEDD decrease of 42 mg versus 8 mg after 3 months and 56 mg versus 17 mg after 6 months. In adjusted analysis, compared with UPC, veterans in IPT achieved a 34-mg greater mean reduction at 3 months (p = 0.002) and 38-mg greater mean reduction at 6 months (p = 0.003). Nearly twice as many patients receiving care through IPT versus UPC reduced their daily opioid dose by ≥50%, representing more than a two-fold improvement at 3 months, which was sustained at 6 months [odds ratio = 2.03; 95% CI = 1.04-3.95, p = 0.04]. Significant improvements were also demonstrated in opioid risk mitigation by 6 months, including increased urine drug screen monitoring, naloxone kit distribution, and decreased co-prescription of opioids and benzodiazepines (all p values < 0.001). CONCLUSIONS: Interdisciplinary biopsychosocial models of pain care can be embedded in primary care and lead to significant improvements in opioid dose and risk mitigation.

Early Life Sexual Trauma and Later Life Genitourinary Dysfunction and Functional Disability in Women.

BACKGROUND: Past research has examined the health outcomes of early sexual trauma in reproductive age women, but little is known about potential long-term effects in older age. OBJECTIVE: To examine associations between early life sexual trauma and later life sexual/genitourinary dysfunction and general functional disability in women. DESIGN: Cross-sectional analysis of nationally representative observational data from the National Social Life, Health, and Aging Project (2010-2011) PARTICIPANTS: One thousand seven hundred forty-five US women aged ≥ 50 years MAIN MEASURES: Two forms of early life sexual trauma (childhood sexual abuse and unwanted first sexual experience), sexual/genitourinary dysfunction (pain during sex, lack of pleasure during sex, urinary incontinence, other urinary symptoms), and general functional disability (difficulty performing 7 activities of daily living (ADLs) or 8 instrumental activities of daily living (IADLs)), assessed by interview and questionnaire. KEY RESULTS: Of 1745 women, 11% reported a history of childhood sexual abuse and 39% an unwanted first sexual experience. Childhood sexual abuse was associated with later life sexual/genitourinary dysfunction (pain during sex [OR 1.9, 95% CI 1.1-3.3], other urinary problems [OR 1.9, 95% CI 1.2-3.1]), and difficulty with multiple ADLs/IADLs (walking across the room [OR 1.9, 95% CI 1.2-3.1], getting in or out of bed [OR 2.0, 95% CI 1.2-3.3], bathing [OR 2.0, 95% CI 1.2-3.5], prepping meals [OR 2.4, 95% CI 1.5-3.8], shopping for food [OR 1.6, 95% CI 1.0-2.4], and completing light work [OR 1.6, 95% CI 1.0-2.4]), after adjusting for age, race, and education. Unwanted first sexual experience was associated with later life lack of pleasure with sex (OR 1.7, 95% CI 1.1-2.5) and difficulty with ADLs/IADLs (walking one block [OR 1.5, 95% CI 1.1-2.1], completing light work [OR 1.6, 95% CI 1.1-2.1]) in adjusted analyses. CONCLUSIONS: Early sexual trauma may be an under-recognized marker of risk of aging-related functional decline in women. Findings underline the importance of providing trauma-informed care for women across the aging spectrum.

Military Sexual Trauma in Older Women Veterans: Prevalence and Comorbidities.

BACKGROUND: Recent attention has highlighted the common occurrence and health consequences of military sexual trauma (MST) in younger women veterans. However, almost nothing is known about MST in older veterans. OBJECTIVE: To describe MST among older women veterans, including prevalence and common comorbidities. DESIGN: Cross-sectional observational study, using data from national Department of Veterans Affairs medical records. PARTICIPANTS: Population-based sample of women Veterans aged 55+ with at least one documented MST screen response and at least one clinical encounter in fiscal years 2005-2015. MAIN MEASURES: MST screen: medical diagnoses (diabetes, hypertension, hyperlipidemia, myocardial infarction, cerebrovascular disease, congestive heart failure, obesity, chronic pain conditions, back pain, dementia, insomnia, sleep apnea, menopause symptoms) and mental health diagnoses (anxiety, depression, posttraumatic stress disorder, tobacco use, alcohol use disorder, substance use disorder, opioid use disorder, suicidal ideation) from International Classification of Diseases, Ninth Revision Clinical Modification codes in the medical record. KEY RESULTS: In this cohort of older women veterans (n = 70,864, mean age 65.8 ± 10.4 years), 13% had a positive MST screen. In multivariable regression analyses adjusted for age, race/ethnicity, and marital status, MST was strongly associated with most mental health diagnoses, particularly posttraumatic stress disorder (OR 7.25, 95% CI 6.84-7.68), depression (OR 2.39, 95% CI 2.28-2.50), and suicidal ideation (OR 2.42, 95% CI 2.08-2.82). MST was also associated with multiple medical conditions, particularly sleep disorders (insomnia OR 1.61, 95% CI 1.43-1.82; sleep apnea OR 1.48, 95% CI 1.37-1.61) and pain (chronic pain OR 1.58, 95% CI 1.50-1.67; back pain OR 1.40, 95% CI 1.34-1.47). CONCLUSIONS: A history of MST is common among older women veterans and associated with a range of medical and mental health diagnoses. These findings call attention to the need for additional research in this understudied population, and the importance of trauma-informed care approaches for women across the lifespan.

Patient-centered change in the day-to-day impact of postmenopausal vaginal symptoms: results from a multicenter randomized trial.

BACKGROUND: Vulvovaginal symptoms, which include dryness, irritation, and pain with intercourse, are common among postmenopausal women and are associated with impaired sexual functioning and quality of life. Previous assessment of treatment strategies for these symptoms has been limited by a lack of sensitive patient-centered outcome measures that assess symptom impact on functional and quality-of-life domains. OBJECTIVE: We aimed to (1) examine change in the impact of postmenopausal vulvovaginal symptoms on multiple aspects of well-being and functioning in relation to vaginal estradiol and moisturizer treatment and (2) guide meaningful interpretation of scores on a structured-item questionnaire measure of condition-specific impact. STUDY DESIGN: Data were drawn from postmenopausal women who were enrolled in the Menopause Strategies: Finding Lasting Answers for Symptoms and Health Vaginal Health Trial (a 12-week, double-blind, placebo-controlled randomized trial of treatment for vulvovaginal symptoms) who were assigned to vaginal 10-µg estradiol tablet plus placebo gel (n=98), vaginal moisturizer plus placebo tablet (n=97), or dual placebo (n=94). At baseline and 12-week follow up, participants completed the Day-to-Day Impact of Vaginal Aging questionnaire to assess the impact of vaginal symptoms on 4 domains (activities of daily living, emotional well-being, sexual functioning, and body image), each on a 0-4 point scale. Day-to-Day Impact of Vaginal Aging sensitivity to change was assessed by the examination of the associations between change in Day-to-Day Impact of Vaginal Aging domain scores and vulvovaginal symptom severity from baseline to 12 weeks with analysis of covariance. Within-woman and between-group minimal clinically important improvement was assessed with the use of an anchor-based approach that relates change in Day-to-Day Impact of Vaginal Aging domain scores with self-reported benefit from treatment. RESULTS: Participants in all treatment arms (n=289) demonstrated reduced impact of vulvovaginal symptoms on all domains of well-being and functioning as assessed by Day-to-Day Impact of Vaginal Aging at 12-week follow up, with no significant differences in improvement between women who were assigned to either estradiol tablet or vaginal moisturizer compared with placebo. For all Day-to-Day Impact of Vaginal Aging domains, mean impact scores were reduced when participants reported symptom improvement (-0.3 to -0.8 point change in Day-to-Day Impact of Vaginal Aging scores for <2-point symptom severity change vs -0.4 to -1.6 point change in Day-to-Day Impact of Vaginal Aging scores for 2+ point symptom severity change; all P<.001). Minimal clinically important change in Day-to-Day Impact of Vaginal Aging domain scale scores, which are anchored to self-reported meaningful benefit from treatment at 12 weeks, ranged from -0.4 to -1.3 (within-woman) and -0.2 to -0.7 (between-group). Observed change and minimal clinically important difference were largest for the sexual functioning domain. CONCLUSION: The impact of vulvovaginal symptoms on day-to-day activities, sexual function, emotional well-being, and body image may be improved with low-dose vaginal estradiol, moisturizer, or topical placebo. The Day-to-Day Impact of Vaginal Aging questionnaire demonstrates sensitivity to change with treatment of vulvovaginal symptoms, particularly Day-to-Day Impact of Vaginal Aging scales that focus on symptom impact on sexual functioning and body image. Minimal clinically important improvement in the impact of vulvovaginal symptoms as measured by the Day-to-Day Impact of Vaginal Aging can be defined with the use of these measures.

An Integrated Pain Team Model: Impact on Pain-Related Outcomes and Opioid Misuse in Patients with Chronic Pain.

OBJECTIVE: Biopsychosocial integrated pain team (IPT) care models are being implemented in Veterans Health Administration (VA) and other health care systems to address chronic pain and reduce risks related to long-term opioid therapy, with little evaluation of effectiveness to date. We examined whether IPT improves self-reported pain-related outcomes and opioid misuse. DESIGN: Single-group quality improvement study. SETTING: Large VA health care system. SUBJECTS: Veterans with chronic pain (N = 99, 84% male, mean age [SD] = 60 [13] years). METHODS: Using paired t tests and Wilcoxon matched-pairs signed-ranks tests, we examined pain experience (Brief Pain Inventory, Pain Catastrophizing Scale), opioid misuse (Current Opioid Misuse Measure), treatment satisfaction (Pain Treatment Satisfaction Scale), and pain management strategies among patients with chronic pain before and after three or more IPT encounters. RESULTS: After an average (SD) of 14.3 (9) weeks engaged in IPT, patients reported improvement in pain interference (mean [SD] = 46.0 [15.9] vs 40.5 [16.2], P < 0.001), pain catastrophizing (mean [SD] = 22.9 [13.0] vs 19.3 [14.1], P = 0.01), treatment satisfaction (i.e., "very satisfied" = 13.1% at baseline vs 25.3% at follow-up, P = 0.01), and reduced opioid misuse (mean [SD] = 11.0 [7.5] vs 8.2 [6.1], P = 0.01). Patients reported increased use of integrative (i.e., acupuncture, 11% at baseline vs 26% at follow-up, P < 0.01) and active pain management strategies (i.e., exercise, 8% at baseline vs 16% at follow-up, P < 0.01) and were less likely to use only pharmacological pain management strategies after IPT engagement (19% at baseline vs 5% at follow-up, P < 0.01). CONCLUSIONS: Biopsychosocial, integrated pain care may improve patient-centered outcomes related to opioid misuse and the subjective experience and nonpharmacological self-management of chronic pain.

Whole Health Options and Pain Education (wHOPE): A Pragmatic Trial Comparing Whole Health Team vs Primary Care Group Education to Promote Nonpharmacological Strategies to Improve Pain, Functioning, and Quality of Life in Veterans-Rationale, Methods, and Implementation.

BACKGROUND: The Whole Health model of the U.S. Department of Veterans Affairs (VA) emphasizes holistic self-care and multimodal approaches to improve pain, functioning, and quality of life. wHOPE (Whole Health Options and Pain Education) seeks to be the first multisite pragmatic trial to establish evidence for the VA Whole Health model for chronic pain care. DESIGN: wHOPE is a pragmatic randomized controlled trial comparing a Whole Health Team (WHT) approach to Primary Care Group Education (PC-GE); both will be compared to Usual VA Primary Care (UPC). The WHT consists of a medical provider, a complementary and integrative health (CIH) provider, and a Whole Health coach, who collaborate with VA patients to create a Personalized Health Plan emphasizing CIH approaches to chronic pain management. The active comparator, PC-GE, is adapted group cognitive behavioral therapy for chronic pain. The first aim is to test whether the WHT approach is superior to PC-GE and whether both are superior to UPC in decreasing pain interference in functioning in 750 veterans with moderate to severe chronic pain (primary outcome). Secondary outcomes include changes in pain severity, quality of life, mental health symptoms, and use of nonpharmacological and pharmacological therapies for pain. Outcomes will be collected from the VA electronic health record and patient-reported data over 12 months of follow-up. Aim 2 consists of an implementation-focused process evaluation and budget impact analysis. SUMMARY: This trial is part of the Pain Management Collaboratory, which seeks to create national-level infrastructure to support evidence-based nonpharmacological pain management approaches for veterans and military service personnel.

Menopausal Symptoms and Higher Risk Opioid Prescribing in a National Sample of Women Veterans with Chronic Pain.

BACKGROUND: The greatest increases in long-term opioid use and opioid-related overdose mortality in recent years have been among women in midlife. Common menopausal symptoms broadly affect health and health care utilization in midlife, but their contribution to chronic pain management during this period is unknown. OBJECTIVE: To examine relationships between menopausal symptoms and long-term opioid prescription patterns among midlife women with chronic pain. DESIGN: Cross-sectional analysis of national Veterans Health Administration medical and pharmacy records (2014-2015). PARTICIPANTS: Women Veterans aged 45-64 with ≥ 1 outpatient visit and chronic pain diagnoses spanning ≥ 90 days. MAIN MEASURES: Long-term opioids (prescribed oral opioids for ≥ 90 days), high-dose long-term opioids (> 50 mg average morphine equivalent daily dose), and long-term opioids co-prescribed with central nervous system depressants (benzodiazepine and non-benzodiazepine sedative-hypnotics, gabapentin/pregabalin, muscle relaxants). Multivariable logistic regression models were used to examine associations between outcomes and menopausal symptoms (menopausal symptom-related diagnoses (i.e., "symptomatic menopausal states") on ≥ 2 encounters and/or menopausal hormone therapy, adjusting for race, age, body mass index, and mental health and substance use disorder diagnoses. KEY RESULTS: In this national sample of 104,984 midlife women Veterans with chronic pain (mean age 54.5, SD 5.4 years), 17% had evidence of menopausal symptoms, 51% were prescribed long-term opioids, 13% were prescribed high-dose long-term opioids, and 35% were co-prescribed long-term opioids and central nervous system depressants. In multivariable analyses, women with menopausal symptoms had increased odds of long-term opioids (OR 1.21, 95% CI 1.18-1.26), high-dose long-term opioids (OR 1.08, 95% CI 1.02-1.13), and long-term opioids co-prescribed with central nervous system depressants (sedative-hypnotics OR 1.25, 95% CI 1.22-1.30; gabapentin/pregabalin OR 1.23, 95% CI 1.20-1.27; muscle relaxants OR 1.24, 95% CI 1.20-1.28). CONCLUSIONS: Among midlife women Veterans with chronic pain, evidence of menopausal symptoms was associated with potentially risky long-term opioid prescription patterns, independent of known risk factors.

Interpersonal trauma and aging-related genitourinary dysfunction in a national sample of older women.

BACKGROUND: Among reproductive-aged women, exposure to interpersonal trauma is associated with genitourinary symptoms. Little is known about the relationship between these exposures and the genitourinary health of older women, who tend to experience different and more prevalent genitourinary symptoms because of menopause and aging. OBJECTIVES: In this study, we examined relationships between common types of interpersonal trauma and aging-related genitourinary dysfunction among older women. STUDY DESIGN: We analyzed data from the National Social Life, Health, and Aging Project, a national area probability sample of older community-dwelling adults born between 1920 and 1947. We used cross-sectional data from home-based study visits conducted in 2005-2006 to examine interpersonal violence exposures (any lifetime sexual assault, past-year emotional and physical abuse), and past-year genitourinary symptoms (urinary incontinence, other urinary problems, and vaginal pain/lubrication problems with sexual intercourse) among women participants. Multivariable logistic regression models were used to relate interpersonal violence and genitourinary symptoms, adjusting for age, race/ethnicity, body mass index, education, marital status, parity, hormone therapy, depressive and anxiety symptoms, and self-reported health. In exploratory models, we further adjusted for vaginal maturation, a tissue-specific marker of aging-related urogenital atrophy obtained from vaginal self-swabs. RESULTS: In this national sample of 1551 older women (mean age 69 ± 2 years), 9% reported sexual assault, 23% reported emotional abuse, and <1% reported physical abuse. Urinary incontinence and other urinary problems were reported by 42% and 17%, respectively, and 42% of sexually active women (n = 527) reported vaginal symptoms with intercourse. In multivariable regression analyses adjusted for age, race/ethnicity, education, marital status, parity, hormone therapy, anxiety, depressive symptoms, and self-reported health, women with any lifetime history of sexual assault had 2.5 times the odds (95% confidence interval, 1.0-6.3) of vaginal symptoms, while women who reported past-year emotional abuse had higher odds of urinary incontinence (odds ratio, 1.7, 95% confidence interval, 1.2-2.4) and other urinary problems (odds ratio, 1.8, 95% confidence interval, 1.2-2.8). Among women who provided vaginal self-swabs (n = 869), adjustment for vaginal maturation-attenuated associations with other urinary problems (odds ratio, 1.6, 95% confidence interval, .9-2.6) and vaginal symptoms (odds ratio, 2.2, 95% confidence interval, 0.8-5.8). CONCLUSION: Sexual assault and emotional abuse may play a role in the development or experience of aging-related genitourinary dysfunction in older women. Clinicians caring for older women should recognize the prevalence and importance of traumatic exposures in health related to menopause and aging.

Subjective Sleep Related to Post Traumatic Stress Disorder Symptoms among Trauma-Exposed Men and Women.

Objective/Background: Sleep difficulty is both a common symptom of posttraumatic stress disorder (PTSD) and a risk factor for the development and maintenance of PTSD symptomatology. Gender differences in sleep following trauma exposure have been posited to contribute to the increased risk for the development of PTSD among women, but the persistence and long-term contributions of these potential differences to the maintenance and severity of PTSD symptoms is unclear. Participants: Men and women reporting a history of trauma exposure (n = 112, 63% female) participated in this study. Methods: Subjective sleep complaints and PTSD symptom severity were assessed using well-validated measures (Pittsburgh Sleep Quality Index, PTSD Symptom Checklist). Multivariable regression models (full sample and gender-stratified) were used to predict PTSD symptom severity from global, subscale, and individual item sleep parameters, adjusted for gender, age, race/ethnicity, education, and body mass index. Results: In the full sample, traditional measures of sleep quality and sleep disturbance were associated with PTSD symptom severity. Difficulty falling asleep, poor sleep quality, and sleep disturbance from a variety of sources were related to higher PTSD symptom severity in men, while self-reported sleep disturbance related to nightmares and emotional regulation were associated with PTSD symptom severity among women. Conclusions: These findings add to the limited literature on gender-specific risk factors related to sleep and PTSD, and may inform intervention development and implementation related to PTSD severity among vulnerable adults.

Amelogenin X impacts age-dependent increase of frequency and number in labial incisor grooves in C57BL/6.

Labial grooves in maxillary incisors have been reported in several wild-type rodent species. Previous studies have reported age-dependent labial grooves occur in moderate prevalence in C57BL/6 mice; however, very little is known about the occurrence of such grooves. In the present study, we observed age-dependent groove formation in C57BL/6 mice up to 26 months after birth and found that not only the frequency of the appearance of incisor grooves but also the number of grooves increased in an age-dependent manner. We examined the molecular mechanisms of age-dependent groove formation by performing DNA microarray analysis of the incisors of 12-month-old (12M) and 24-month-old (24M) mice. Amelx, encoding the major enamel matrix protein AMELOGENIN, was identified as a 12M-specific gene. Comparing with wild-type mice, the maxillary incisors of Amelx-/- mutants indicated the increase of the frequency and number of labial grooves. These findings suggested that the Amelx gene impacts the age-dependent appearance of the labial incisor groove in C57BL/6 mice.

Gender Differences in Cardiovascular Risk Related to Diabetes and Posttraumatic Stress Disorder.

OBJECTIVES: To examine relationships between posttraumatic stress disorder (PTSD), diabetes, and cardiovascular disease (CVD) among older men and women. METHODS: In a national retrospective cohort study of Veterans aged ≥55 (n=2,789,264, 6% female), associations between PTSD and diabetes (2008-2011) and incident CVD (2012-2015) were assessed with gender-stratified Fine-Gray proportional hazard models, adjusted for demographics and medical comorbidities. RESULTS: Incident CVD was observed in 22% of men and 12% of women, and related to PTSD (men HR=1.05, 95% CI=1.04-1.06, Wald χ2=80.46, df=1, p<.001; women HR=1.47, 95% CI=1.38-1.57, Wald χ2=148.60, df=1, p<.001), diabetes (men HR=1.34, 95% CI=1.34-1.35, Wald χ2=9177.64, df=1, p<.001; women HR=1.49, 95% CI=1.44-1.55, Wald χ2=419.02, df=1, p<.001), and comorbid PTSD-diabetes (men HR=1.50, 95% CI=1.48-1.52, Wald χ2=4180.92, df=1, p<.001; women HR=1.96, 95% CI=1.80-2.12, Wald χ2=257.28, df=1, p<.001). CONCLUSIONS: CVD risk was increased with PTSD and diabetes, and strongly increased with comorbid PTSD-diabetes. Among women, PTSD and diabetes conferred equivalent CVD risk.