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National Institutes of Health funding to address basic reproductive health for common female conditions remains disproportionately low, in part because of low success rates of grant applications by obstetrician-gynecologists. This study aimed to evaluate the scholarly productivity of individuals supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development Women's Reproductive Health Research K12 career development award, created to advance careers of obstetrician-gynecologist physician-scientists. We performed a cohort study of individuals who completed at least 2 years of Women's Reproductive Health Research training by June 30, 2015, and had at least 5-year follow-up. Earliest training start date was December 1, 1998. Primary outcomes from public data sources (National Institutes of Health RePORTER, PubMed, iCite) were (1) number of total and R01 National Institutes of Health grants as principal investigator; (2) numbers of total and first and last author publications; and (3) median and highest publication impact factor measured by the relative citation ratio. Secondary outcomes from an email survey subcohort were total number of research grants, federally funded grants, and number of National Institutes of Health grants as coinvestigator; institutional promotions and academic appointments, national and National Institutes of Health leadership roles; and career and mentorship satisfaction. Outcomes were recorded at 5, 10, and 15 years postgraduation, and aggregate anonymized data were divided into 3 groups using Women's Reproductive Health Research completion dates: June 30 of 2005, 2010, and 2015. Temporal trends were assessed. Results were stratified by gender, number of awarded grant cycles (1–2 vs 3–4), and specialty type. Analyses used Fisher exact or Pearson chi-square tests, and Mantel–Haenszel tests of trend. The distribution of the cohort (N=178) by graduation completion date was: on or before June 30, 2005 (57 [32%]); July 1, 2005 to June 30, 2010 (60 [34%]); and July 1, 2010 to June 30, 2015 (61 [34%]). Most participants were female (112 [64%]) and maternal–fetal medicine trained (53 [30%]), followed by no fellowship (50 [28%]). Of the 178 participants, 72 (40%) received additional National Institutes of Health funding as a principal investigator, 45 (25%) received at least 1 R01, and 23 (13%) received 2 to 5 R01s. There were 52 (31%) scholars with >10 first author publications, 66 (39%) with >10 last author publications, and 108 (63%) with ≥25 publications. The highest relative citation ratio was a median of 8.07 (interquartile range, 4.20–15.16). There were 121 (71%) scholars with relative citation ratio ≥5, indicating >5-fold greater publication impact than that of other National Institutes of Health–funded scientists in similar areas of research. No differences by gender, institution, or temporal trends were observed. Of the full cohort, 69 (45.7%) responded to the survey; most self-identified as women (50 [73%]) and White (51 [74%]). Our findings suggest that the infrastructure provided by an institutional K award is an advantageous career development award mechanism for obstetrician-gynecologists, a group of predominantly women surgeons. It may serve as a corrective for the known inequities in National Institutes of Health funding by gender. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome is the most common endocrine disorder in women of reproductive age, yet US incidence estimates do not exist, and prevalence estimates vary widely. A population-based US study estimated the incidence, prevalence, and trends of polycystic ovary syndrome by age, race and ethnicity, and diagnosing provider type. A retrospective cohort study of patients enrolled in Kaiser Permanente Washington from 2006 to 2019 was conducted. All members identified as female, aged 16 to 40 years with at least 3 years of enrollment and at least 1 healthcare encounter during that time, were eligible for inclusion. Individuals were excluded if they had a history of oophorectomy or hysterectomy. Polycystic ovary syndrome cases were identified using the International Classification of Diseases diagnosis codes (International Classification of Diseases, Ninth Revision, 256.4 or International Classification of Diseases, Tenth Revision, E28.2). Individuals with a polycystic ovary syndrome diagnosis before study entry were excluded from incidence rate estimations. The incidence rates were adjusted by age using direct standardization to the 2010 US census data. Temporal trends in incidence were assessed using weighted linear regression (overall) and Poisson regression (by age, race and ethnicity, and provider type). Prevalent cases were defined as patients with a polycystic ovary syndrome diagnosis at any time before the end of 2019. Medical record review of 700 incident cases diagnosed in 2011–2019 was performed to validate incident cases identified by International Classification of Diseases codes using the Rotterdam criteria. Among 177,527 eligible patients who contributed 586,470 person-years, 2491 incident polycystic ovary syndrome cases were identified. The mean age at diagnosis was 26.9 years, and the mean body mass index was 31.6 kg/m2. Overall incidence was 42.5 per 10,000 person-years; the rates were similar over time but increased in individuals aged 16 to 20 years from 31.0 to 51.9 per 10,000 person-years (P =.01) and decreased among those aged 26 to 30 years from 82.8 to 45.0 per 10,000 person-years (P =.02). A small decreasing temporal trend in incidence rates was only observed among non-Hispanic White individuals (P =.01). The incidence rates by diagnosing provider type varied little over time. Among the 58,241 patients who contributed person-time in 2019, 3036 (5.2%) had a polycystic ovary syndrome International Classification of Diseases diagnosis code; the prevalence was the highest among the Hawaiian and Pacific Islander group (7.6%) followed by Native American and Hispanic groups. Medical record review classified 60% as definite or probable incident, 14% as possible incident, and 17% as prevalent polycystic ovary syndrome. The overall positive predictive value of polycystic ovary syndrome International Classification of Diseases diagnosis code for identifying definite, probable, or possible incident polycystic ovary syndrome was 76% (95% confidence interval, 72%–79%). Among a cohort of nonselected females in the United States, we observed stable rates of incident polycystic ovary syndrome diagnoses over time. The incidence of polycystic ovary syndrome was 4- to 5-fold greater than reported for the United Kingdom. The prevalence of polycystic ovary syndrome (5.2%) was almost double before the published US estimates (2.9%) based on the International Classification of Diseases codes. Race and ethnicity and provider type did not seem to have a major impact on temporal rates. Incident diagnoses increased over time in younger and decreased in older age groups, perhaps related to shifting practice patterns with greater awareness among practitioners of the impact of polycystic ovary syndrome on long-term health outcomes and improved prevention efforts. Moreover, increasing obesity rates may be a factor driving the earlier ages at diagnosis. [ABSTRACT FROM AUTHOR]

Objectives: Heart rate variability (HRV) reflects the integration of the parasympathetic nervous system with the rest of the body. Studies on the effects of yoga and exercise on HRV have been mixed but suggest that exercise increases HRV. We conducted a secondary analysis of the effect of yoga and exercise on HRV based on a randomized clinical trial of treatments for vasomotor symptoms in peri/post-menopausal women.Design: Randomized clinical trial of behavioral interventions in women with vasomotor symptoms (n=335), 40-62 years old from three clinical study sites.Interventions: 12-weeks of a yoga program, designed specifically for mid-life women, or a supervised aerobic exercise-training program with specific intensity and energy expenditure goals, compared to a usual activity group.Main Outcome Measures: Time and frequency domain HRV measured at baseline and at 12 weeks for 15min using Holter monitors.Results: Women had a median of 7.6 vasomotor symptoms per 24h. Time and frequency domain HRV measures did not change significantly in either of the intervention groups compared to the change in the usual activity group. HRV results did not differ when the analyses were restricted to post-menopausal women.Conclusions: Although yoga and exercise have been shown to increase parasympathetic-mediated HRV in other populations, neither intervention increased HRV in middle-aged women with vasomotor symptoms. Mixed results in previous research may be due to sample differences. Yoga and exercise likely improve short-term health in middle-aged women through mechanisms other than HRV. [ABSTRACT FROM AUTHOR]

Background: Intrauterine devices, including levonorgestrel-releasing and copper devices, are highly effective long-acting reversible contraceptives. The potential risks associated with intrauterine devices are low and include uterine perforation and device expulsion.Objective: This study aimed to evaluate the risk of perforation and expulsion associated with levonorgestrel-releasing devices vs copper devices in clinical practice in the United States.Study Design: The Association of Perforation and Expulsion of Intrauterine Device study was a retrospective cohort study of women aged ≤50 years with an intrauterine device insertion during 2001 to 2018 and information on intrauterine device type and patient and medical characteristics. Of note, 4 research sites with access to electronic health records contributed data for the study: 3 Kaiser Permanente-integrated healthcare systems (Northern California, Southern California, and Washington) and 1 healthcare system using data from a healthcare information exchange in Indiana (Regenstrief Institute). Perforation was classified as any extension of the device into or through the myometrium. Expulsion was classified as complete (not visible in the uterus or abdomen or patient reported) or partial (any portion in the cervix or malpositioned). We estimated the crude incidence rates and crude cumulative incidence by intrauterine device type. The risks of perforation and expulsion associated with levonorgestrel-releasing intrauterine devices vs copper intrauterine devices were estimated using Cox proportional-hazards regression with propensity score overlap weighting to adjust for confounders.Results: Among 322,898 women included in this analysis, the incidence rates of perforation per 1000 person-years were 1.64 (95% confidence interval, 1.53-1.76) for levonorgestrel-releasing intrauterine devices and 1.27 (95% confidence interval, 1.08-1.48) for copper intrauterine devices; 1-year and 5-year crude cumulative incidence was 0.22% (95% confidence interval, 0.20-0.24) and 0.63% (95% confidence interval, 0.57-0.68) for levonorgestrel-releasing intrauterine devices and 0.16% (95% confidence interval, 0.13-0.20) and 0.55% (95% confidence interval, 0.44-0.68) for copper intrauterine devices, respectively. The incidence rates of expulsion per 1000 person-years were 13.95 (95% confidence interval, 13.63-14.28) for levonorgestrel-releasing intrauterine devices and 14.08 (95% confidence interval, 13.44-14.75) for copper intrauterine devices; 1-year and 5-year crude cumulative incidence was 2.30% (95% confidence interval, 2.24-2.36) and 4.52% (95% confidence interval, 4.40-4.65) for levonorgestrel-releasing intrauterine devices and 2.30% (95% confidence interval, 2.18-2.44) and 4.82 (95% confidence interval, 4.56-5.10) for copper intrauterine devices, respectively. Comparing levonorgestrel-releasing intrauterine devices with copper intrauterine devices, the adjusted hazard ratios were 1.49 (95% confidence intervals, 1.25-1.78) for perforation and 0.69 (95% confidence intervals, 0.65-0.73) for expulsion.Conclusion: After adjusting for potential confounders, levonorgestrel-releasing intrauterine devices were associated with an increased risk of uterine perforation and a decreased risk of expulsion relative to copper intrauterine devices. Given that the absolute numbers of these events are low in both groups, these differences may not be clinically meaningful. [ABSTRACT FROM AUTHOR]

Background: Intrauterine devices are effective instruments for contraception, and 1 levonorgestrel-releasing device is also indicated for the treatment of heavy menstrual bleeding (menorrhagia).Objective: To compare the incidence of intrauterine device expulsion and uterine perforation in women with and without a diagnosis of menorrhagia within the first 12 months before device insertion STUDY DESIGN: This was a retrospective cohort study conducted in 3 integrated healthcare systems (Kaiser Permanente Northern California, Southern California, and Washington) and a healthcare information exchange (Regenstrief Institute) in the United States using electronic health records. Nonpostpartum women aged ≤50 years with intrauterine device (eg, levonorgestrel or copper) insertions from 2001 to 2018 and without a delivery in the previous 12 months were studied in this analysis. Recent menorrhagia diagnosis (ie, recorded ≤12 months before insertion) was ascertained from the International Classification of Diseases, Ninth and Tenth Revision, Clinical Modification codes. The study outcomes, viz, device expulsion and device-related uterine perforation (complete or partial), were ascertained from electronic medical records and validated in the data sources. The cumulative incidence and crude incidence rates with 95% confidence intervals were estimated. Cox proportional hazards models estimated the crude and adjusted hazard ratios using propensity score overlap weighting (13-16 variables) and 95% confidence intervals.Results: Among 228,834 nonpostpartum women, the mean age was 33.1 years, 44.4% of them were White, and 31,600 (13.8%) had a recent menorrhagia diagnosis. Most women had a levonorgestrel-releasing device (96.4% of those with and 78.2% of those without a menorrhagia diagnosis). Women with a menorrhagia diagnosis were likely to be older, obese, and have dysmenorrhea or fibroids. Women with a menorrhagia diagnosis had a higher intrauterine device-expulsion rate (40.01 vs 10.92 per 1000 person-years) than those without, especially evident in the first few months after insertion. Women with a menorrhagia diagnosis had a higher cumulative incidence (95% confidence interval) of expulsion (7.00% [6.70-7.32] at 1 year and 12.03% [11.52-12.55] at 5 years) vs those without (1.77% [1.70-1.84] at 1 year and 3.69% [3.56-3.83] at 5 years). The risk of expulsion was increased for women with a menorrhagia diagnosis vs for those without (adjusted hazard ratio, 2.84 [95% confidence interval, 2.66-3.03]). The perforation rate was low overall (<1/1000 person-years) but higher in women with a diagnosis of menorrhagia vs in those without (0.98 vs 0.63 per 1000 person-years). The cumulative incidence (95% confidence interval) of uterine perforation was slightly higher for women with a menorrhagia diagnosis (0.09% [0.06-0.14] at 1 year and 0.39% [0.29-0.53] at 5 years) than those without it (0.07% [0.06-0.08] at 1 year and 0.28% [0.24-0.33] at 5 years). The risk of perforation was slightly increased in women with a menorrhagia diagnosis vs in those without (adjusted hazard ratio, 1.53; 95% confidence interval, 1.10-2.13).Conclusion: The risk of expulsion is significantly higher in women with a recent diagnosis of menorrhagia. Patient education and counseling regarding the potential expulsion risk is recommended at insertion. The absolute risk of perforation for women with a recent diagnosis of menorrhagia is very low. The increased expulsion and perforation rates observed are likely because of causal factors of menorrhagia. [ABSTRACT FROM AUTHOR]

Abstract: Background: Women have higher rates of depression and often experience depression symptoms during critical reproductive periods, including adolescence, pregnancy, postpartum, and menopause. Collaborative care intervention models for mood disorders in patients receiving care in an OB-GYN clinic setting have not been evaluated. Study design and methodology for a randomized controlled trial of collaborative care depression management versus usual care in OB-GYN clinics and the details of the adapted collaborative care intervention and model implementation are described in this paper. Methods: Women over age 18years with clinically significant symptoms of depression, as measured by a Patient Health Questionnaire-9 (PHQ-9) score ≥10 and a clinical diagnosis of major depression or dysthymia, were randomized to the study intervention or to usual care and were followed for 18months. The primary outcome assessed was change over time in the SCL-20 depression scale between baseline and 12months. Baseline Results: Two hundred five women were randomized: 57% white, 20% African American, 9% Asian or Pacific Islander, 7% Hispanic, and 6% Native American. Mean age was 39years. 4.6% were pregnant and 7.5% were within 12months postpartum. The majority were single (52%), and 95% had at least the equivalent of a high school diploma. Almost all patients met DSM IV criteria for major depression (99%) and approximately 33% met criteria for dysthymia. Conclusions: An OB-GYN collaborative care team, including a social worker, a psychiatrist, and an OB-GYN physician, who met weekly and used an electronic tracking system for patients was the essential element of the proposed depression care treatment model described here. Further study of models that improve quality of depression care that are adapted to the unique OB-GYN setting is needed. [Copyright &y& Elsevier]

Abstract: Background: Women ages 35 years and older have the greatest proportion of contraceptive nonuse and unintended pregnancies ending in abortion. Study Design: We conducted a population-based case-control study among women ages 35–44 years at risk of unwanted pregnancy using the National Survey of Family Growth (NSFG) data to investigate risk factors for contraceptive nonuse. Results: At last intercourse, 9.8% of women reported not using any contraceptive method. Contraceptive nonusers, as compared to users, were more likely to be ages 40–44 years (OR=2.0, 95% CI 1.1–3.7), foreign-born (OR=4.3, 95% CI 1.9–9.7), black (OR=2.8, 95% CI 1.1–7.0), with household incomes 100–249% of the federal poverty level (FPL) (OR=2.5, 95% CI 1.1–5.8). Women who received contraceptive counseling in the past year had an 80% decreased risk of nonuse (95% CI 0.1–0.5). Conclusion: Public health strategies to reduce unintended pregnancy, particularly among women ages 35 years and older, should focus on addressing disparities in contraceptive use and promoting contraceptive counseling. [Copyright &y& Elsevier]

Abstract: Objective: The goal of this study was to assess whether menopausal symptoms were more common and/or more severe among women with depressive symptoms. Methods: A cross-sectional survey of 1358 women, ages 45–70, at two large integrated health plans (Seattle; Boston) was performed. Information on demographics, medical and reproductive history, medication use, menopausal experience and depressive symptoms (PHQ-8) were collected. Women taking HT were excluded. Logistic regression models adjusted for age and body mass index tested the associations between menopausal symptoms (hot flushes, night sweats, vaginal dryness and dyspareunia) and presence of moderate/severe depressive symptoms. Results: 770 women were included; 98 (12.7%) had moderate/severe depressive symptoms and 672 (87.3%) had no/mild depressive symptoms. Women with moderate/severe depressive symptoms were almost twice as likely to report recent vasomotor symptoms (hot flashes and or night sweats) vs. women with no/mild depressive symptoms (adjusted odds ratio (aOR) 1.67, 95%CI 1.04–2.68), and to report them as severe (aOR 1.63, 95%CI 0.95–2.83). A higher symptom burden was observed despite the fact that 20% of women with moderate/severe depressive symptoms (vs. 4.6% no/mild depressive symptoms) were using an SSRI or SNRI, medications known to improve vasomotor symptoms. The percentage of women with menopausal symptoms, and the percentage with severe vasomotor symptoms were linearly associated with the depressive symptom score. Conclusions: Depressive symptoms “amplified” the menopausal experience, or alternatively, severe vasomotor symptoms worsened depressive symptoms. [Copyright &y& Elsevier]

Purpose: We sought to examine the relationship between recent use of oral contraceptives and hormone therapy and endometrial hyperplasia (EH) risk. Methods: Cases comprised women diagnosed with complex EH (n = 289) or atypical EH (n = 173) between 1985 and 2003. One age-matched control was selected for each case; excluded were women with a prior hysterectomy or diagnosis of EH or endometrial cancer. Hormone use in the 6 months prior to the date of the case''s first symptoms was ascertained using a pharmacy database and medical records. Odds ratios (OR) and 95% confidence intervals (CI) were calculated. Results: Three (1.1%) cases had used oral contraceptives, compared to 16 (6.0%) controls (OR = 0.2, 95% CI: 0.0–0.6). Fifty-one (16.8%) cases had taken estrogen-only hormone therapy, in contrast to two (0.7%) controls (OR = 37.6, 95% CI: 8.8–160.0). The risk of EH among estrogen plus progestin hormone users did not differ from that of non-users (OR = 0.7, 95% CI: 0.4–1.1). Conclusions: This study suggests that previous findings of the association of estrogen-only hormone therapy with increased risk of EH and the lack of an association between estrogen plus progestin hormone therapy and EH risk are likely to apply to both complex EH and atypical EH. Further examination of the association between oral contraceptives and EH, with greater numbers of OC users, is warranted. [Copyright &y& Elsevier]

We designed a randomized double-blind randomized trial to examine the short and long-term effects of alternative approaches commonly used to manage menopause symptoms. Women were randomly assigned to: (1) black cohosh 160 mg daily; (2) multibotanical (50 mg black cohosh, alfalfa, chaste tree, dong quai, false unicorn, licorice, oats, pomegranate, Siberian ginseng, boron) four capsules daily; (3) multibotanical plus telephone counseling to increase dietary soy; (4) conjugated equine estrogen 0.625 mg +/- 2.5 mg medroxyprogesterone acetate; or (5) placebo. Working with a skilled CAM provider helped us choose interventions that reflected naturopathic practices worthy of study. Mass mailing, with careful tracking and rapid responses to recruitment rates, was an effective and cost-effective recruitment strategy. Creativity was necessary to construct methods for blinding capsules and the dietary soy intervention. Independent testing of herbal products was vital to confirming their constituents. The Data and Safety and Monitoring Committee, and project officers at the funding agency, were critical partners in designing responses to unanticipated Women's Health Initiative findings published during the HALT trial. Careful monitoring of adverse events may provide much needed information about side effects of herbal products and supplements. Despite inherent challenges, the study of alternative therapies for menopause symptoms is a rewarding and important area deserving of further inquiry. [ABSTRACT FROM AUTHOR]

Abstract: We designed a randomized double-blind randomized trial to examine the short and long-term effects of alternative approaches commonly used to manage menopause symptoms. Women were randomly assigned to: (1) black cohosh 160mg daily; (2) multibotanical (50mg black cohosh, alfalfa, chaste tree, dong quai, false unicorn, licorice, oats, pomegranate, Siberian ginseng, boron) four capsules daily; (3) multibotanical plus telephone counseling to increase dietary soy; (4) conjugated equine estrogen 0.625mg±2.5mg medroxyprogesterone acetate; or (5) placebo. Working with a skilled CAM provider helped us choose interventions that reflected naturopathic practices worthy of study. Mass mailing, with careful tracking and rapid responses to recruitment rates, was an effective and cost-effective recruitment strategy. Creativity was necessary to construct methods for blinding capsules and the dietary soy intervention. Independent testing of herbal products was vital to confirming their constituents. The Data and Safety and Monitoring Committee, and project officers at the funding agency, were critical partners in designing responses to unanticipated Women''s Health Initiative findings published during the HALT trial. Careful monitoring of adverse events may provide much needed information about side effects of herbal products and supplements. Despite inherent challenges, the study of alternative therapies for menopause symptoms is a rewarding and important area deserving of further inquiry. [Copyright &y& Elsevier]

Increasing epidemiological evidence supports the view that dietary flavonoids have protective roles in oral diseases, including cancer. However, the dietary forms of flavonoids, the flavonoid glycosides, must first be hydrolyzed to the aglycones, which is thought to occur mainly in the intestine. In the present study we tested whether this hydrolytic activity occurs in the oral cavity. Saliva was collected from human subjects, incubated with flavonoid glycosides, and analyzed for aglycone formation by HPLC. When quercetin 4'-glucoside or genistein 7-glucoside was incubated with human saliva, hydrolysis to quercetin and genistein, respectively, was detected within minutes. Studies of additional flavonoid glycosides demonstrated that glucose conjugates were rapidly hydrolyzed, but not conjugates with other sugars, i.e., rutin, quercitrin, and naringin. In a limited study of 17 subjects, the interindividual variability in the hydrolysis of genistein 7-glucoside was >20-fold. This supports the contention that salivary hydrolysis of certain flavonoid glucosides may be important in some individuals but not in others. Support for a bacterial contribution to this hydrolysis was obtained from the inhibitory effect of antibacterials in vivo and in vitro and from experiments with subcultured oral bacterial colonies. However, cytosol isolated from oral epithelial cells was also capable of effective hydrolysis. Dietary flavonoid glucosides may thus be hydrolyzed in the oral cavity by both bacteria and shedded epithelial cells to deliver the biologically active aglycones at the surface of the epithelial cells. The aglycones quercetin and genistein both potently inhibited proliferation of oral cancer cells. The large interindividual variability in this hydrolytic activity may be a factor that should be taken into consideration in future studies. [ABSTRACT FROM AUTHOR]

The primary aim of this 36-month prospective cohort study was to evaluate the association between use of oral contraceptives (OCs) and bone mineral density in reproductive-age women. The 36-month bone density (g/cm2) at the spine, hip and whole body and percent change from baseline (measured at 6-month intervals) were evaluated among 245 women 18–39 years of age; 89 were using OCs (median duration: 3.7 years at study entry) and 156 were not using any hormonal contraception. Before and after adjustment for covariates (baseline bone density, age, race, ever pregnant, exercise, body mass and calcium intake), women using OCs did not differ significantly from comparison women in percent change in bone density over 36 months or in absolute bone density at 36 months. All p-values for between-group differences were >0.55. In conclusion, within the limitations of this study, OCs did not appear to impact bone density over time in this cohort of reproductive-age women. [Copyright &y& Elsevier]

Background: Accurate estimates of incidence and prevalence of endometriosis among nonselected cohorts are lacking in the United States, and earlier reports have produced varying results.Objective: This study aimed to define endometriosis incidence and prevalence in a US population and evaluate factors influencing these estimates over time.Study Design: A 10-year retrospective cohort study using Kaiser Permanente Washington electronic health records database was completed. The primary analysis included women enrollees aged 16 to 60 years, from January 2006 to December 2015, who had a uterus, were continuously enrolled for at least 2 years before cohort entry and had at least 1 healthcare utilization. Secondary analysis included all women enrollees aged 16 to 60 years during this time. Incident endometriosis was identified using the International Classification of Diseases, Ninth Revision and Tenth Revision, diagnosis codes. Annual incidence rates were age-adjusted by direct standardization to the 2015 study population. Secular trends in incidence overall and by 5-year age group, race and ethnicity, diagnosis modality, and practitioner type were assessed using Poisson regression analyses. Prevalent cases were defined as women enrolled in 2015 and had an endometriosis diagnosis before the end of 2015. The prevalence rates of chronic pelvic pain and dysmenorrhea defined by the International Classification of Diseases, Ninth Revision and Tenth Revision, diagnosis codes in 2006-2015 were estimated.Results: Among 332,056 eligible women who contributed 1,176,329 person-years during the 10-year study period, 2863 incident endometriosis cases were identified for an average incidence of 24.3 cases per 10,000 person-years. In our primary analysis, incidence rates declined over the study interval from a high of 30.2 per 10,000 person-years in 2006 to 17.4 per 10,000 person-years in 2015 and were highest among women aged 36 to 45 years in most years. Incidence rates were similar across race and ethnicity groups. The distribution of the 2863 incident cases by the diagnosis modality was as follows: 45.5% surgical, 5.7% imaging, and 48.8% clinical. Endometriosis incidence rates per 10,000 person-years were similar in women who were surgically and clinically diagnosed and decreased significantly from 2006 to 2015 (surgically diagnosed endometriosis dropped from 13.4 to 7.4 and clinically diagnosed endometriosis dropped from 16.1 to 8.9; P value of <.001 for linear trend over time for each). Incident case distribution by diagnosing provider was as follows: 73.6% obstetrician and gynecologist, 15.7% primary care provider, and 10.7% "other." Incidence of endometriosis diagnosed by an obstetrician and gynecologist and primary care provider decreased over the study interval (P<.001 for linear trend over time for each). Method of diagnosis and provider type did not differ by race and ethnicity. Among 135,162 women who contributed person-time in 2015, 2521 women were diagnosed with endometriosis, a prevalence rate of 1.9%. In our secondary analysis, the frequency of chronic pelvic pain diagnosis increased over the study interval from 3.0% in 2006 to 5.6% in 2015.Conclusion: The incidence rates of endometriosis declined over the 10-year study interval and did so uniformly across age groups, races and ethnicities, and the main diagnosing modalities and providers. Declining rates may reflect a shift in practice patterns in the United States away from the diagnosis of endometriosis both clinically and surgically, rather than favoring more general diagnoses of chronic pelvic pain. The prevalence of endometriosis in 2015 in the United States is in keeping with data from recent studies outside the United States using health record data. [ABSTRACT FROM AUTHOR]

Article Title and Bibliographic Information Comparison of the prevalence of human papilloma virus infection in histopathologically confirmed premalignant oral lesions and healthy oral mucosa by brush smear detection. Dalla Torre D, Burtscher D, Edlinger M, Sölder E, Widschwendter A, Rasse M, Puelacher W. Oral Surg Oral Med Oral Pathol Oral Radiol 2015;119(3):333–9. Reviewers Susan G. Reed, DDS, MPH, DrPH, Amy E. Wahlquist, MS Purpose/Question Is the risk for oral HPV higher in patients with potentially premalignant oral lesions (leukoplakia or erythroplakia) compared to patients without those oral lesions? Source of Funding Information not available Type of Study/Design Case-control study Level of Evidence Level 2: Limited-quality, patient-oriented evidence Strength of Recommendation Grade Not applicable [ABSTRACT FROM AUTHOR]

Background: Half of all postmenopausal women report symptoms of vulvar, vaginal, or urinary discomfort with substantial impact on sexual function and quality of life; underlying mechanisms leading to symptoms are poorly understood.Objective: To examine the possibility that the vaginal microbiota and/or mucosal immune response contributes to the severity of bothersome vaginal symptoms, we conducted a substudy of samples from a randomized trial of vaginal treatment for genitourinary syndrome of menopause to compare these features between women whose symptoms improved and women whose symptoms did not improve.Study Design: This is a secondary analysis of samples collected in a 12-week randomized trial of treatment with vaginal estradiol or moisturizer vs placebo for moderate-severe postmenopausal symptoms of vaginal discomfort. We randomly selected 20 women in each arm with ≥2-point decrease in most bothersome symptom severity (responders) and 20 matched controls with ≤1-point decrease (nonresponders). At 0, 4, and 12 weeks, we characterized vaginal microbiota (16S ribosomal RNA gene sequencing), vaginal fluid metabolites (broad-based metabolomic profiling), vaginal fluid-soluble immune markers (Meso Scale Discovery), pH, and vaginal maturation index. We compared responders with nonresponders at baseline and across all visits using linear mixed models to evaluate associations with microbiota, metabolites, and immune markers, incorporating visit and participant-specific random effects while controlling for treatment arm.Results: Here, the mean age of women was 61 years (n=120), and most women (92%) were White. At enrollment, no significant differences were observed between responders and nonresponders in age, most bothersome symptom type or severity, microbiota composition or diversity, Lactobacillus dominance, metabolome, or immune markers. There was a significant decrease in diversity of the vaginal microbiota in both responders and nonresponders (P<.001) over 12 weeks. Although this change did not differ by responder status, diversity was associated with treatment arm: more women in the estradiol arm (63%) had Lactobacillus-dominant, lower diversity bacterial communities than women in the moisturizer (35%) or dual placebo (23%) arms (P=.001) at 12 weeks. The metabolome, vaginal maturation index, and measured immune markers were not associated with responder status over the 12 weeks but varied by treatment arm.Conclusion: Postmenopausal vaginal symptom severity was not significantly associated with vaginal microbiota or mucosal inflammatory markers in this small study. Women receiving vaginal estradiol experienced greater abundance of lactobacilli and lower vaginal pH at end of treatment. [ABSTRACT FROM AUTHOR]

Background: Intrauterine devices are effective and safe, long-acting reversible contraceptives, but the risk of uterine perforation occurs with an estimated incidence of 1 to 2 per 1000 insertions. The European Active Surveillance Study for Intrauterine Devices, a European prospective observational study that enrolled 61,448 participants (2006-2012), found that women breastfeeding at the time of device insertion or with the device inserted at ≤36 weeks after delivery had a higher risk of uterine perforation. The Association of Uterine Perforation and Expulsion of Intrauterine Device (APEX-IUD) study was a Food and Drug Administration-mandated study designed to reflect current United States clinical practice. The aims of the APEX-IUD study were to evaluate the risk of intrauterine device-related uterine perforation and device expulsion among women who were breastfeeding or within 12 months after delivery at insertion.Objective: We aimed to describe the APEX-IUD study design, methodology, and analytical plan and present population characteristics, size of risk factor groups, and duration of follow-up.Study Design: APEX-IUD study was a retrospective cohort study conducted in 4 organizations with access to electronic health records: Kaiser Permanente Northern California, Kaiser Permanente Southern California, Kaiser Permanente Washington, and Regenstrief Institute in Indiana. Variables were identified through structured data (eg, diagnostic, procedural, medication codes) and unstructured data (eg, clinical notes) via natural language processing. Outcomes include uterine perforation and device expulsion; potential risk factors were breastfeeding at insertion, postpartum timing of insertion, device type, and menorrhagia diagnosis in the year before insertion. Covariates include demographic characteristics, clinical characteristics, and procedure-related variables, such as difficult insertion. The first potential date of inclusion for eligible women varies by research site (from January 1, 2001 to January 1, 2010). Follow-up begins at insertion and ends at first occurrence of an outcome of interest, a censoring event (device removal or reinsertion, pregnancy, hysterectomy, sterilization, device expiration, death, disenrollment, last clinical encounter), or end of the study period (June 30, 2018). Comparisons of levels of exposure variables were made using Cox regression models with confounding adjusted by propensity score weighting using overlap weights.Results: The study population includes 326,658 women with at least 1 device insertion during the study period (Kaiser Permanente Northern California, 161,442; Kaiser Permanente Southern California, 123,214; Kaiser Permanente Washington, 20,526; Regenstrief Institute, 21,476). The median duration of continuous enrollment was 90 (site medians 74-177) months. The mean age was 32 years, and the population was racially and ethnically diverse across the 4 sites. The mean body mass index was 28.5 kg/m2, and of the women included in the study, 10.0% had menorrhagia ≤12 months before insertion, 5.3% had uterine fibroids, and 10% were recent smokers; furthermore, among these women, 79.4% had levonorgestrel-releasing devices, and 19.5% had copper devices. Across sites, 97,824 women had an intrauterine device insertion at ≤52 weeks after delivery, of which 94,817 women (97%) had breastfeeding status at insertion determined; in addition, 228,834 women had intrauterine device insertion at >52 weeks after delivery or no evidence of a delivery in their health record.Conclusion: Combining retrospective data from multiple sites allowed for a large and diverse study population. Collaboration with clinicians in the study design and validation of outcomes ensured that the APEX-IUD study results reflect current United States clinical practice. Results from this study will provide valuable information based on real-world evidence about risk factors for intrauterine devices perforation and expulsion for clinicians. [ABSTRACT FROM AUTHOR]

Background: Adenomyosis symptoms are disabling. Population-based data on incidence and prevalence of adenomyosis are lacking that could guide future evidence-based treatments and clinical management.Objective: To evaluate the incidence, 10-year secular trends, and prevalence of adenomyosis diagnoses and to describe symptoms and treatment patterns in a large U.S. cohort.Study Design: We performed a retrospective population-based cohort study of women aged 16-60 years in 2006-2015, enrolled in Kaiser Permanente Washington, a mixed-model health insurance and care delivery system. Adenomyosis diagnoses identified by ICD codes from the International Classification of Diseases 9th and 10th editions and potential covariates were extracted from computerized databases. Women with prior hysterectomy, and for incidence estimates women with prior adenomyosis diagnoses, were excluded. Linear trends in incidence rates over the 10-year study period were evaluated using Poisson regression. Rates and trend tests were examined for all women adjusting for age using direct standardization to the 2015 study population, by age groups, and by race/ethnicity. Chart reviews were performed to validate diagnostic accuracy of ICD codes in identifying adenomyosis incidence. Symptoms and treatment patterns at diagnosis and in the following 5 years were assessed.Results: A total of 333,693 women contributed 1,185,855 woman-years (2006-2015) for incidence calculations. Associated symptom-related codes (menorrhagia or abnormal uterine bleeding, dysmenorrhea or pelvic pain, dyspareunia, and infertility) were observed in 90.8%; 18.0% had co-occurrent endometriosis codes and 47.6% had co-occurrent uterine fibroid codes. The overall adenomyosis incidence was 1.03% or 28.9 per 10,000 woman-years, with a high of 30.6 in 2007 and a low of 24.4 in 2014. Overall age-adjusted estimated incidence rates declined during the 10-year study interval (linear trend P < .05). Incidence was highest for women aged 41-45 years (69.1 per 10,000 woman-years in 2008) and was higher for black (highest 44.6 per 10,000 woman-years in 2011) vs white women (highest 27.9 per 10,000 woman-years in 2010). Overall prevalence in 2015 was 0.8% and was highest among women aged 41-45 years (1.5%). Among the 624 potential adenomyosis cases identified by diagnostic codes in 2012-2015 and with sufficient information in the medical record to determine true case status, 490 were confirmed as incident cases, yielding a 78.5% (95% confidence interval, 75.1%, 81.7%) positive predictive value of adenomyosis ICD-9/ICD-10 codes for identifying an incident adenomyosis case. Health care burden was substantial: 82.0% of women had hysterectomies, nearly 70% had imaging studies suggestive of adenomyosis, and 37.6% used chronic pain medications.Conclusion: Adenomyosis burden to the individual and the health care system is high. Incidence rates are disproportionately high among black women. These findings are of concern, as currently available long-term medical therapies remain limited beyond hysterectomy. Our data and methodologies are novel and could serve as a foundation to guide clinicians and health care systems to develop clinical management plans and track outcomes for women with adenomyosis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Despite considerable public health burden, uterine fibroid population-based incidence estimates are few. Secular trends over time are even more limited.Objective: We sought to evaluate the incidence, 10-year secular trends, and prevalence of uterine fibroid diagnoses and describe the proportion of symptomatic women.Study Design: We performed a retrospective population-based cohort study of women, aged 18-65 years, enrolled 2005 through 2014 in Kaiser Permanente Washington. Uterine fibroid diagnoses identified by International Classification of Diseases, Ninth Revision codes and potential covariates were extracted from computerized databases. Women with prior hysterectomy and, for incidence estimates, women with prior fibroid diagnoses were excluded. Linear trends in incidence rates over the 10-year study period were evaluated using Poisson regression models. Rates and trend tests were examined for all women, by age groups, and by race/ethnicity.Results: Associated International Classification of Diseases, Ninth Revision symptom-related codes were observed in 90% of incident cases. Incidence rates for fibroid diagnoses were highest for the age group 45-49 years, 240.3 per 10,000 woman-years in 2014, and for black women across all years. Overall age-adjusted estimated incidence rates declined during the 10-year study interval, from 139.4 per 10,000 woman-years in 2005 to 101.4 in 2014 (P value trend .0008). Overall prevalence in 2014 was 9.6%, and was highest among women aged 50-54 years (15.9%). Black women had higher prevalence (18.5%) than other racial/ethnic groups.Conclusion: We found a decreasing trend of new uterine fibroid diagnoses among predominantly symptomatic women ages 18-65 years in a recent 10-year interval. This finding was due, perhaps in part, to secular trends of decreasing hysterectomies. Nonetheless, uterine fibroids remain a common health burden, with a prevalence of nearly 10%. Rates are disproportionately high and occur at younger ages for black women, and possibly for other non-white racial/ethnic groups. These findings are of concern, as current available long-term medical therapies remain limited. [ABSTRACT FROM AUTHOR]

Article Title and Bibliographic Information: The possible premalignant character of oral lichen planus and oral lichenoid lesions: a prospective five-year follow-up study of 192 patients. van der Meiji, E.H., H. Mast and I. van der Waal (2007). Oral Oncol 43(8):742-8. Level of Evidence: Level 2 (Limited-quality, patient-oriented evidence) Strength of Recommendation Grade: Not applicable Purpose/Question: What is the premalignant character of oral lichenoid lesions (OLL) and oral lichen planus (OLP) for oral squamous cell carcinoma? Source of Funding: Information not available Type of Study/Design: Cohort study [Copyright &y& Elsevier]

Objective: We investigated the effect of interpregnancy body mass index (BMI) change on success of term vaginal birth after cesarean (VBAC) among normal, overweight and obese women. Study Design: Using 1992-2009 Washington State birth certificate data linked with hospitalization records, we conducted a population-based retrospective cohort study of nulliparous women (BMI ≥18.5 kg/m2) with a primary cesarean in their first birth and a term trial of labor in their second. Interpregnancy weight change (difference between first and second prepregnancy BMIs) was categorized as maintenance (<1 BMI unit change), loss (≥1 unit), moderate gain (≥1 and <2 units), high gain (≥2 units). We estimated relative risks of VBAC success using generalized linear models with a log-link function, adjusting for maternal age, race/ethnicity, nativity, marital status, education, smoking, primary cesarean indication, interpregnancy interval, birth year for second birth, and prenatal care adequacy. Results: Among 8302 women who attempted a term trial of labor, 65% had a successful VBAC. Women with normal BMI before their first pregnancy experienced an 8% decrease in VBAC success with moderate gain (relative risk [RR], 0.92; 95% confidence interval [CI], 0.87–0.98) and a 12% decrease in success with high gain (RR, 0.88; 95% CI, 0.83–0.93), compared with normal weight women who maintained weight. Weight loss increased VBAC success in women who were overweight (RR, 1.12; 95% CI, 1.01–1.25) or obese before their first delivery (RR, 1.24; 95% CI, 1.04–1.49), compared with overweight and obese women, respectively, who maintained weight. Conclusion: Women can improve their chance of successful VBAC through interpregnancy weight management. [Copyright &y& Elsevier]

Objective: The purpose of this study was to determine the efficacy of 3 nonhormonal therapies for the improvement of menopause-related quality of life in women with vasomotor symptoms. Study Design: We conducted a 12-week 3 × 2 randomized, controlled, factorial design trial. Peri- and postmenopausal women, 40-62 years old, were assigned randomly to yoga (n = 107), exercise (n = 106), or usual activity (n = 142) and also assigned randomly to a double-blind comparison of omega-3 (n = 177) or placebo (n = 178) capsules. We performed the following interventions: (1) weekly 90-minute yoga classes with daily at-home practice, (2) individualized facility-based aerobic exercise training 3 times/week, and (3) 0.615 g omega-3 supplement, 3 times/day. The outcomes were assessed with the following scores: Menopausal Quality of Life Questionnaire (MENQOL) total and domain (vasomotor symptoms, psychosocial, physical and sexual). Results: Among 355 randomly assigned women who average age was 54.7 years, 338 women (95%) completed 12-week assessments. Mean baseline vasomotor symptoms frequency was 7.6/day, and the mean baseline total MENQOL score was 3.8 (range, 1–8 from better to worse) with no between-group differences. For yoga compared to usual activity, baseline to 12-week improvements were seen for MENQOL total –0.3 (95% confidence interval, –0.6 to 0; P = .02), vasomotor symptom domain (P = .02), and sexuality domain (P = .03) scores. For women who underwent exercise and omega-3 therapy compared with control subjects, improvements in baseline to 12-week total MENQOL scores were not observed. Exercise showed benefit in the MENQOL physical domain score at 12 weeks (P = .02). Conclusion: All women become menopausal, and many of them seek medical advice on ways to improve quality of life; little evidence-based information exists. We found that, among healthy sedentary menopausal women, yoga appears to improve menopausal quality of life; the clinical significance of our finding is uncertain because of the modest effect. [ABSTRACT FROM AUTHOR]

Summary Cancer-related fatigue (CRF) is a commonly reported and debilitating side effect of cancer and/or cancer treatment. Sleep disorders are also highly reported in the cancer population; however it is unknown if sleep is associated with fatigue. In the general population, exercise has been shown to improve sleep, however in the cancer population this idea is under investigation. The primary purposes of this review were to: (i) review the prevalence and causes of sleep disorders in cancer patients and survivors, (ii) examine the relationship between sleep and CRF and (iii) review the impact of exercise interventions on sleep in cancer patients and survivors. A scoping review of the literature was conducted regarding exercise interventions in cancer patients and survivors with sleep as at least one outcome measure. A search of the literature revealed limited studies ( n = 21) assessing the effect of exercise on sleep disorders in the cancer population. Methodological issues are evident because assessing sleep is often not the main outcome of interest. The reviewed studies revealed that exercise positively impacts sleep quality and quantity. There seems to be possible relationship between sleep disorders, exercise and CRF. Further investigation of this relationship is necessary, specifically using objective measurement tools, in large, controlled studies, focusing on sleep as the primary outcome. [ABSTRACT FROM AUTHOR]

Objective: We sought to identify biomarkers associated with progestin therapy resistance and persistence/progression of endometrial hyperplasia. Study Design: We performed a nested case-control study among women with complex (n = 73) and atypical (n = 41) hyperplasia treated with oral progestin, followed up 2-6 months for persistence/progression. We evaluated index endometrial protein expression for progesterone receptor isoform A, progesterone receptor isoform B (PRB), PTEN, Pax-2, and Bcl-2. Odds ratios and 95% confidence intervals (CIs) were estimated. Results: Among women with atypical hyperplasia, high PRB expression was associated with 90% decreased risk of persistence/progression (95% CI, 0.01–0.8). High expression of progesterone receptor A and PRB suggested decreased risk of persistence/progression (odds ratio, 0.1; 95% CI, 0.02–1.0). These findings were not observed among women with complex hyperplasia. No associations were found with PTEN, Pax-2, and Bcl-2 protein expression. Conclusion: PRB expression shows promise as a biomarker of progestin response. Further research is warranted to understand how PRB expression may guide treatment decisions. [ABSTRACT FROM AUTHOR]

Objective: The objective of the study was to estimate the age-specific incidence of endometrial hyperplasia: simple, complex, and atypical, in order of increasing likelihood of progression to carcinoma. Study Design: Women aged 18-90 years with endometrial pathology specimens (1985-2003) at a large integrated health plan were identified using automated data. Incidence rates were obtained by dividing the number of cases by the estimated number of female health plan enrollees who retained a uterus. Results: Endometrial hyperplasia peak incidence was: simple, 142 per 100,000 woman-years, complex, 213 per 100,000 woman-years, both in the early 50s; and atypical, 56 per 100,000 woman-years in the early 60s. Age-adjusted incidence decreased over the study period, especially for atypical hyperplasia. Conclusion: Endometrial hyperplasia incidence without and with atypia peaks in the early postmenopausal years and in the early 60s, respectively. Given that some cases of endometrial hyperplasia likely go undiagnosed, the figures provided should be viewed as minimum estimates of the true incidence. [Copyright &y& Elsevier]