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OBJECTIVE The aim of this study is to analyze the association between coronary artery vitamin D receptor (VDR) expression and systemic coronary artery atherosclerosis (CAA) risk factors. METHODS Female cynomolgus monkeys (n = 39) consumed atherogenic diets containing the women's equivalent of 1000 IU/day of vitamin D3. After 32 months consuming the diets, each monkey underwent surgical menopause. After 32 postmenopausal months, CAA and VDR expression were quantified in the left anterior descending coronary artery. Plasma 25OHD3, lipid profiles and serum monocyte chemotactic protein-1 (MCP-1) were measured. RESULTS In postmenopausal monkeys receiving atherogenic diets, serum MCP-1 was significantly elevated compared with baseline (482.2 ± 174.2 pg/ml vs. 349.1 ± 163.2 pg/ml, respectively; p

The objective of this study is to assess whether the presence of breast arterial calcifications (BACs) found on routine mammography is prospectively associated with the development of cardiovascular disease (CVD) events after 10 years of follow-up.Women presenting for screening mammography were enrolled in this prospective cohort. Baseline data were collected including history of CVD and CVD risk factors. Mammograms were assessed for the presence or absence of BAC. Participants completed questionnaires 10 years after baseline that assessed the development of CVD (coronary artery disease [CAD] and stroke) and CVD risk factors.Of the 1,995 participants who enrolled at baseline, complete 10-year follow-up data were available for 1,039; of those, 114 (11.0%) were BAC-positive and 925 (89.0%) were BAC-negative at baseline. After controlling for age, BAC-positive women were more likely to develop CAD (odds ratio, 3.14; 95% confidence interval, 1.86-5.27; P0.001) compared with BAC-negative women after 10 years of follow-up. After controlling for age, BAC-positive women were more likely to have had a stroke (odds ratio, 5.10; 95% CI, 1.82-14.30) compared with BAC-negative women after 10 years.The presence of BAC on routine screening mammography was associated with a significantly increased risk of developing CAD and stroke after 10 years of follow-up. Additional large prospective, population-based studies are needed to confirm BAC as a predictor of future CVD events and its utility in stratifying a woman's risk of CVD.

To assess the safety and serum estradiol (E2) and total testosterone (T) concentrations in postmenopausal women treated with Pellet Hormonal Therapy (PHT) and Food and Drug Administration approved Hormonal Therapy (FHT).A total of 539 postmenopausal women were identified, including 384 on PHT and 155 on FHT. Data extracted from medical records include demographics, indication for hormone therapy, treatment duration, side effects, serum E2 and T levels, and frequency of laboratory follow-up.The incidence of overall side effects was significantly higher in PHT compared with FHT (221 [57.6%] vs 23 [14.8%], P 0.00001, odds ratio [95% CI] =8.0[4.5-14.2]). When examining women with an intact uterus prior to hormone therapy initiation, 55.3% (136/246) on PHT vs 15.2% (12/79) on FHT had at least one episode of abnormal uterine bleeding (P 0.0001, odds ratio [95% CI] = 7.9[3.6-17.0]). Furthermore, a significantly higher proportion of women on PHT (20.3% [50/246]), compared with 6.3% (5/79) on FHT, had a hysterectomy (P = 0.036, odds ratio [95% CI] = 3.2[1.1-9.3]). Both mean (SD, Min-Max) peak E2 (pg/mL) and peak T (ng/dL) are significantly higher in the PHT group than those in the FHT group (E2: 237.70 [168.55, 10-1,111] vs 93.45 [130.77, 5.5-465.8], T: 194.04 [84.94, 4.3-599] vs 15.59 [19.52, 0.2-70], P 0.00001). Of those on PHT, four women had E2 level1,000 pg/mL and nine women with T level400 ng/dL.Women on PHT had a significantly higher incidence of side effects than FHT as well as a significantly higher supraphysiological level of peak E2 and T during the treatment.

Retroperitoneal (RP) hematoma is a rare complication of total vaginal hysterectomy. A 45-year-old female G4P3013 with a history of abnormal uterine bleeding refractory to treatment by endometrial ablation and stress urinary incontinence underwent total vaginal hysterectomy, bilateral salpingectomy, bilateral uterosacral ligament suspension, anterior colporrhaphy, and cystoscopy. After the hysterectomy the left uterine artery pedicle was hemostatic; however, the patient became hemodynamically unstable and anemic. Laparoscopy revealed a stable zone III RP hematoma. Intraoperative observation revealed no further expansion of the hematoma. Left iliac angiography and aortography revealed there was no extravasation from the uterine arteries and gonadal vessels. Four days post-operative abdominal CT showed a stable hematoma. Hemodynamic instability resolved over the post-operative course. RP hematoma must be included in the differential for the evaluation of acute intraoperative hemodynamic instability with an unclear source.

Historically, hormone therapy (HT) was the primary choice for the management of postmenopausal osteoporosis. Since the Women’s Health Initiative (WHI) study results were published in 2002, the safety concern about estrogen use in postmenopausal women led to a major paradigm shift in HT. With the reevaluation of the WHI study, by stratifying patients by age and time since menopause, it became evident that for healthy and recently postmenopausal women, the benefits of HT outweigh the risks. However, public misconceptions persist that HT should generally be avoided in postmenopausal women of all ages. We carefully examined the emerging evidence for efficacy and safety of estrogen and estrogen analogs use for osteoporosis management, in both general and special postmenopausal populations, and suggested that HT, with appropriate formulation, dosage, duration, and route of administration, may be considered an option for the primary prevention and treatment of osteoporosis in women with appropriate indications. In general, after 60 years of age or more than 10 years following menopause, the risk–benefit analysis for HT should be weighted toward avoidance.

This study evaluated whether vasomotor symptom (VMS) severity and number of moderate/severe menopausal symptoms (nMS) were associated with health outcomes, and whether calcium and vitamin D (CaD) modified the risks.The Women's Health Initiative CaD study was a double blind, randomized, placebo-controlled trial, which tested 400 IU of 25-hydroxyvitamin-D and 1,000 mg of calcium per day in women aged 50 to 79 years. This study included 20,050 women (median follow-up of 7 y). The outcomes included hip fracture, colorectal cancer, invasive breast cancer, all-cause mortality, coronary heart disease, stroke, cardiovascular death, and total cardiovascular disease (CVD). MS included: hot flashes, night sweats, dizziness, heart racing, tremors, feeling restless, feeling tired, difficulty concentrating, forgetfulness, mood swings, vaginal dryness, breast tenderness, migraine, and waking up several times at night. Associations between VMS severity and nMS with outcomes were tested.No association between VMS severity and any outcome were found. In contrast, nMS was associated with higher stroke (hazard ratio [HR] 1.40 95% confidence interval [CI] 1.04-1.89 for ≥ 2 MS vs none; HR 1.20 95% CI 0.89-1.63 for 1 MS vs none, P trend = 0.03) and total CVD (HR 1.35, 95% CI, 1.18-1.54 for ≥ 2 MS vs none; HR 0.99, 95% CI, 0.87-1.14 for 1 MS vs none P trend0.001). CaD did not modify any association.Severity of VMS was not associated with any outcome. Having ≥2 moderate or severe MS was associated with an increased risk for CVD. The number of moderate/severe MS may be a marker for higher CVD risk. : Video Summary:http://links.lww.com/MENO/A669.Video Summary:http://links.lww.com/MENO/A669.

Depression has been suggested as a risk factor for coronary heart disease (CHD). However, whether the risk may be affected by age is unknown. We seek to assess the difference in long-term CHD risk between younger (65) and older (≥65) women with depressive symptoms.Between June and August 2004, 1995 women presenting for routine mammography were enrolled to the primary study on breast arterial calcification. In 2005 (year 2), each woman completed a validated depression screening questionnaire. A similar questionnaire was mailed to each participant at year 4, 5, and 10 to obtain follow-up data (demographic and CHD risk factors) and record any change in CHD status.Of 1084 women who returned surveys at year 10, 998 had no history of CHD and answered depression screening questions at year 2 as well as questions about CHD events at year 10. Of 185 out of 998 (18.5%) who had positive depression screening at year 2, 24 (13.0%) developed ≥1 CHD events by year 10, which is significantly higher than the incidence of 6.5% (53/813) in control group (p 0.001). With CHD risk factors including age adjusted in a logistic regression model, depression was the only significant predictive factor for CHD in women aged65 (OR = 6.56, 95% CI 1.07-40.09, p = 0.042). However, in women aged ≥65, age was the only significant predictive factor for CHD.A history of depression may increase the risk of CHD over 9 years of follow-up, and more prominently in midlife women aged65 years.

Osteoporosis is one of the most common disorders around the world. Osteoporotic fracture especially hip fracture are associated with an increased mortality rate in elders. However, elders with osteoporosis or at high risk of fractures remain largely underdiagnosed and undertreated. The screening, diagnosis, and treatment of osteoporosis must be improved to maintain pace with its fast-growing prevalence. This review will cover risk factors of osteoporosis, screening and diagnosis tools, newfound advancements, current medical treatments including options for special populations of concern, and future research directions.

To analyze the treatment effect of calcium+vitamin D supplementation, hormone therapy, both, and neither on cardiovascular disease risk factors.We conducted a prospective, randomized, double-blind, placebo-controlled trial among Women's Health Initiative (WHI) participants. The predefined primary outcome was low-density lipoprotein cholesterol (LDL-C).Between September 1993 and October 1998, a total of 68,132 women aged 50-79 years were recruited and randomized to the WHI-Dietary Modification (n=48,835) and WHI-Hormone Therapy trials (n=27,347). Subsequently, 36,282 women from WHI-Hormone Therapy (16,089) and WHI-Dietary Modification (n=25,210) trials were randomized in the WHI-Calcium+Vitamin D trial to 1,000 mg elemental calcium carbonate plus 400 international units vitamin D3 daily or placebo. Our study group included 1,521 women who participated in both the hormone therapy and calcium+vitamin D trials and were in the 6% subsample of trial participants with blood sample collections at baseline and years 1, 3, and 6. The average treatment effect with 95% confidence interval, for LDL-C, compared with placebo, was -1.6, (95% confidence interval [CI] -5.5 to 2.2) mg/dL for calcium+vitamin D alone, -9.0 (95% CI -13.0 to -5.1) mg/dL for hormone therapy alone, and -13.8 (95% CI -17.8 to -9.8) mg/dL for the combination. There was no evidence of a synergistic effect of calcium+vitamin D+hormone therapy on LDL-C (P value for interaction=.26) except in those with low total intakes of vitamin D, for whom there was a significant synergistic effect on LDL (P value for interaction=.03).Reductions in LDL-C were greater among women randomized to both calcium+vitamin D and hormone therapy than for those randomized to either intervention alone or to placebo. The treatment effect observed in the calcium+vitamin D+hormone therapy combination group may be additive rather than synergistic. For clinicians and patients deciding to begin calcium+vitamin D supplementation, current use of hormone therapy should not influence that decision.ClinicalTrials.gov, https://clinicaltrials.gov, NCT00000611.

Data in humans and nonhuman primates have suggested a possible synergistic effect of vitamin D and calcium (CaD) and estrogen on the cardiovascular disease (CVD) risk factors. Using randomized trial data we explored whether the effect of menopausal hormone therapy (HT) on CVD events is modified by CaD supplementation.A prospective, randomized, double-blind, placebo-controlled trial was implemented among postmenopausal women in the Women's Health Initiative. A total of 27,347 women were randomized to the HT trials (0.625 mg/d of conjugated equine estrogens [CEE] alone for women without a uterus vs placebo; or 0.625 mg of CEE in addition to 2.5 mg of medroxyprogesterone acetate daily [CEE + MPA] for women with a uterus vs placebo). After 1 year, 16,089 women in the HT trial were randomized to the CaD trial and received either 1,000 mg of elemental calcium carbonate and 400 IU of vitamin D3 daily or placebo. The mean (SD) duration of follow-up after CaD randomization was 6.2 (1.3) years for the CEE trial and 4.6 (1.1) years for the CEE + MPA trial. CVD and venous thromboembolism events evaluated in this subgroup analysis included coronary heart disease, stroke, pulmonary embolism, all-cause mortality, plus select secondary endpoints (total myocardial infarction, coronary revascularization, deep venous thrombosis, cardiovascular death, and all CVD events). Time-to-event methods were used and models were fit with a Cox proportional hazards regression model.In the CEE trial, CaD significantly modified the effect of CEE on stroke (P interaction = 0.04). In the CaD-placebo group, CEE's effect on stroke was harmful (hazard ratio [95% confidence interval] = 2.19[1.34-3.58]); however, it was neutral in the CaD-supplement group (hazard ratio [95% confidence interval] = 1.07[0.66-1.73]). We did not observe significant CEE-CaD interactions for coronary heart disease, total CVD events, or any of the remaining endpoints. In the CEE + MPA trial, there was no evidence that the effect of CEE + MPA on any of CVD endpoints was modified by CaD supplementation.CaD did not consistently modify the effect of CEE therapy or CEE + MPA therapy on CVD events. However, the increased risk of stroke due to CEE therapy appears to be mitigated by CaD supplementation. In contrast, CaD supplementation did not influence the risk of stroke due to CEE + MPA.

Consensus on when to initiate DXA screening for early postmenopausal women (65 years of age) is lacking. Low body mass index (BMI) has been proposed as one of the major risk factors for osteoporosis. This study sought to compare the predictive performance of BMI alone with 5 screening modalities (the U.S. Preventive services task force [USPSTF] FRAX threshold of 9.3%, a risk factor based approach [≥ 1 risk factors], the osteoporosis self-assessment tool [OST2], the osteoporosis risk assessment instrument [ORAI ≥ 9], and the simple calculated osteoporosis risk estimation [SCORE ≥ 6]) in identifying early postmenopausal women with osteoporosis.Postmenopausal women aged 50-64 years presenting for a DXA test were recruited between January 1, 2007, and March 1, 2009. Demographic data and osteoporosis risk factors were obtained through a telephone survey. The performance of each screening tool in predicting osteoporosis was compared.Of 445 study participants, 95% were White, 38 had osteoporosis (T-score ≤ -2.5). BMI (28) was associated with the highest Sensitivity (95%), the lowest Negative Likelihood Ratio (LR-) of 0.14, an AUC of 0.73, and the number needed to scan (NNS) of 8. The USPSTF approach had the lowest sensitivity (24%), highest LR- (0.91), lowest AUC (0.62), and highest NNS (9). Among 5 established modalities, SCORE (≥ 6) appears to be the best (sensitivity: 92%, LR-: 0.24, AUC: 0.75, NNS: 9).BMI (28) had a comparable numerical screening performance overall to the current screening modalities. BMI (28) could be considered a potential indicator when screening early postmenopausal White women for osteoporosis. However, a better osteoporosis screening tool remains to be developed.

To explore (1) long-acting reversible contraception (LARC) use and (2) future contraceptive preferences in Sub-Saharan African adolescents as undesired pregnancies in Sub-Saharan African adolescents are associated with significant maternal/neonatal morbidity.Nationally-representative Demographic and Health Surveys (USAID) obtained informed consent and interviewed 45,054 adolescents, including 19,561 (43.4% of total) sexually active adolescents (aged 15-19) from 18 least developed Sub-Saharan African nations regarding contraception (years 2005-2011, response rate 89.8-99.1% for all women interviewed). Frequencies and percentages of contraceptive use, prior pregnancies, and unwanted births were reported. Categorical variables were analyzed through χA majority of sexually active adolescents were not using contraception (n = 16,165 non-users; 82.6% of all sexually active adolescents). Many (n = 8465, 43.3% of sexually active adolescents) interviewed already had at least one child, with 31.5% (n = 2646) of those with previous children reporting the pregnancy was not wanted at the time it occurred. Sexually active adolescents using contraception (n = 3384) used LARCs (injectable contraception, implants, or intrauterine devices; 29.8%, n = 1007) barrier contraceptives (31.9%), oral contraceptives (10.9%), and other methods (27.4%). Adolescents using LARCs were more likely to be urban [OR 1.76 (95% CI 1.39-2.22)], to have been visited by a family planning worker in the last 12 months [OR1.62 (95% CI 1.24-2.11)], and to have visited a health facility in the past 12 months [OR1.84 (95% CI 1.53-2.21)]. Injectable contraception was the most preferred (39.9%, n = 3036) future method by sexually-active non-contracepting adolescents who were asked about future methods (n = 7605) compared to other methods. An unfortunate percentage of adolescents surveyed cannot read (35.7%, n = 16,084).A majority of sexually-active adolescents in Sub-Saharan Africa are not using contraception and are desirous of doing so. Offering LARCs during post-abortive or postpartum care with particular focus on rural adolescents may reduce undesired pregnancy and subsequent morbidity/mortality. Educational materials should limit printed information as many teens are unable to read.

OBJECTIVE Hormone therapy (HT) prescription patterns have varied enormously over time and across specialties. The present study attempts to look at practice variation in specific controversial scenarios and to determine if attendance at The North American Menopause Society (NAMS) 2016 Annual Meeting, where the draft of the 2017 NAMS HT Position Statement was presented, had any impact on members' HT prescribing patterns. METHODS An anonymous survey with 11 case scenarios was sent to all NAMS members before and after the 2016 NAMS Annual Meeting. Pre- and postmeeting responses were pooled into a single cohort. For those who responded to both surveys, only the postmeeting survey responses were included in the cohort. The impact of attendance at the 2016 NAMS Annual Meeting was investigated by comparing paired responses with "controversial questions" between pre- and postmeeting surveys in the matched population who either attended the 2016 NAMS Annual Meeting (intervention arm) or did not (control arm). "Controversial questions" were defined as those where 25% to 75% of responders answered "YES" to a question. McNemar's test was applied to analyze paired responses using SAS statistical software, with P ≤ 0.05 being considered statistically significant. RESULTS A total of 1,786 NAMS members were surveyed before and after the 2016 NAMS meeting, 234 (13%) completed the premeeting survey, 166 (9%) completed the postmeeting survey, and 52 completed both surveys. Of the 52, 27 attended the 2016 NAMS Annual Meeting and 25 did not. The pooled cohort contains 348 responses which represents a 20% response rate. Six complex case scenarios with "controversial questions" were identified from the pooled cohort and reexamined in the intervention and control arm, respectively. In the intervention arm, significant changes toward being more likely to prescribe HT in guideline-consistent cases were noted in four out of six cases, whereas significant changes in HT use were not seen in any of six complex cases in the control arm. CONCLUSIONS NAMS members' prescribing patterns of HT vary in complex clinical scenarios. After the 2016 NAMS Annual Meeting where a draft of the 2017 NAMS HT Position Statement was presented and discussed, in four challenging and complex clinical situations a significant number of practitioners changed their prescription patterns toward prescribing HT which was consistent with the new guideline.

Objective The aim of the study was to promote the importance of providing gynecologic screening for transgender men (TGM) who desire to keep their female organs. Materials and methods In June 2015, the Women's Health Center (WHC) at Reading Hospital was approached to become a resource for transgender (TG) patients in our community. This also presented the opportunity to develop an educational program for OBGYN residents/providers in TG healthcare. From June 2015 to August 2016, we educated ourselves, established standards of care, collaborated with other services, and reached out to the community we represent. We present our experience in creating this specialty clinic as well as our first 16 months of experiential data to help other facilities meet the needs of this community. Results The primary outcome was the establishment of a comprehensive service for TG patients in our community. From August 2016 to December 2017, a total of 27,516 patient visits were conducted in WHC, 67 (0.2%) were TG patient visits with an average age of 33 years. Of 67, 16 (23.9%) were TGM and 51 (76.1%) were transgender women (TGW) visits, representing a total of 20 new TG patients including 9 (45%) TGM and 11 (55%) TG women. A total of 5 (55.6%) of 9 TGM received vaginal/cervical cytology screening. Sexually transmitted infection screenings were performed in 14 (70%) TG patients versus 6,689 (40.7%) in a non-TG WHC population. Conclusions Servicing the transgender community is an important aspect of care for OBGYN providers. Our data suggest that TGM have similar gynecologic needs to the rest of our clinic population.

PURPOSE Residents in obstetrics and gynecology are deemed to be proficient in transvaginal ultrasound (TVUS) upon graduation, although TVUS education in residency is not standardized. The objective of this study is to assess for improvement in TVUS knowledge among residents after viewing an educational DVD. METHODS This is a multisite prospective randomized controlled trial using an educational DVD ("Gynecology: Beginners Only"), compared to routine education. All participants completed a pretest on TVUS images and principles. The intervention group repeated the test after DVD viewing. During the trial, performing and logging TVUS examinations were encouraged. All enrolled residents repeated the test 6-10 months later. RESULTS Fifty-seven residents completed the study with a mean pretest score of 9.7 (1st year resident 9.8, 2nd year resident 9.6, 3rd year resident 10.1, 4th year resident 9.4, P = .763), with a mean of 31.5 TVUS examinations logged prior to intervention. The mean score in the intervention group (n = 34) improved significantly after viewing (11.2, P

Osteoporosis is a prevalent and po- tential debilitating disease. Characterized by archi- tectural modifications in bone matrix, osteoporosis ultimatelyincreases the propensity forbones to frac- ture, especially at the hip and spine. Fortunately, osteoporosis can be treated effectively if detected at an early stage. While recognizing an increased risk offracture inwomen with osteoporosis, mostcases of fracture occur in women with osteopenia orlowbone mass. A good fracture risk assessment tool would be more clinically meaningful than an accurate osteo-. porosis screening or diagnostic tool. Here we present a concise review ofthe existing modalities which may be utilized to screen for osteoporosis or predict risk of oteonorotic fractures.

OBJECTIVE Cardiovascular disease (CVD) is the leading cause of death among American postmenopausal women and all adult Americans. The medical community and the lay community have recently become intrigued with vitamin D and its potential role in reducing the risk of CVD. Research findings from multiple retrospective studies, few prospective studies, and recent nonhuman primate studies have been inconsistent and conflicting. The objective of this study is to review what is known about the topic, what questions remain unanswered, and where the research community should be focusing. METHODS A literature search was conducted through PubMed and Google Scholar up to August 1, 2014. One hundred six articles, including 18 double-blind, placebo-controlled, randomized clinical trials, relevant to the study topic were identified. All studies were stratified based on study design and primary outcome. The effects of vitamin D on CVD were reviewed and summarized. RESULTS Although there is an abundance of observational studies suggesting an association with CVD protection, the most well-controlled randomized human trial data available show no benefit of vitamin D on CVD. However, highly controlled nonhuman primate studies indicate a beneficial relationship. CONCLUSIONS Well-designed research, with CVD as primary outcome, is needed to help bridge the gap in our knowledge on this topic. In the meantime, caution should be applied to avoid overdiagnosis and overtreatment of vitamin D deficiency.

We conducted a meta-analysis of the current literature to deduce the strength of association between breast arterial calcification (BAC) and coronary artery disease (CAD) and/or stroke.PubMed, Google Scholar, ClinicalTrials.gov, and Ovid were searched for English-language literature up to August 2013 using the terms "breast arterial calcification," "breast vascular calcification," "coronary artery disease," "coronary heart disease," "cardiovascular disease," "abnormal coronary angiography," and "stroke." A hand search of the reference lists of key articles was performed to supplement the literature search. Our literature search revealed 75 articles for further abstract review. Limiting our search to articles that quantitatively assessed the correlation between BAC and stroke or angiographically proven CAD, we reviewed 35 full manuscripts. Of these articles, 14 were included in the final analysis.We analyzed 10 cross-sectional studies (n = 3,952) with CAD as the primary outcome (diagnosed by coronary angiography). The odds ratio (95% CI) for CAD in those with BAC versus those without BAC is 3.86 (3.25-4.59) (P0.0001). For stroke, six cross-sectional studies were analyzed (n = 18,888). The odds ratio (95% CI) for stroke in those with BAC versus those without BAC is 1.54 (1.25-1.90) (P0.0001).These results suggest that BAC is significantly associated with both CAD and stroke. Although more prospective studies are warranted to clarify whether BAC is truly a predictor of the future development of CAD and stroke, the concept that BAC is a benign finding is waning.

Objectives The aim of this study was to conduct a systematic review and meta-analysis on the performance of the WHO's Fracture Risk Assessment (FRAX) instrument in predicting 10-year risk of Major Osteoporotic Fractures (MOF) and Hip Fractures (HF), using the USA treatment thresholds, in populations other than their derivation cohorts. Design EMBASE and MEDLINE database were searched with search engine PubMed and OVID as well as Google Scholar for the English-language literature from July 2008 to July 2016. Limiting our search to articles that analyzed only MOF and/or HF as an outcome, 7 longitudinal cohorts from 5 countries (USA, Poland, France, Canada, New Zealand) were identified and included in the meta-analysis. SAS NLMIXED procedure (SAS v 9.3) was applied to fit the Hierarchical Summary Receiver Operating Characteristics (HSROC) model for meta-analysis. Forest plot and HSROC plot was generated by Review Manager (RevMan v 5.3). Results Seven studies (n = 57,027) were analyzed to assess diagnostic accuracy of FRAX in predicting MOF, using 20% as the 10-year fracture risk threshold for intervention, the mean sensitivity, specificity, and diagnostic odds ratio (DOR) along with their 95% confidence intervals (CI) were 10.25% (3.76%–25.06%), 97.02% (91.17%–99.03%) and 3.71 (2.73–5.05), respectively. For HF prediction, using 3% as the 10-year fracture risk threshold, six studies (n = 50,944) were analyzed. The mean sensitivity, specificity, and DOR along with their 95% confidence intervals (CI) were 45.70% (24.88%–68.13%), 84.70% (76.41%–90.44%) and 4.66 (2.39–9.08), respectively. Conclusions Overall, using the 10 year intervention thresholds of 20% for MOF and 3% for HF, FRAX performed better in identifying patients who will not have a MOF or HF within 10 years, than those who will. A substantial number of patients who developed fractures, especially MOF within 10 years of follow up, were missed by the baseline FRAX assessment.

Most clinicians are not prepared to provide integrated personal care to address all the clinical needs of women with primary ovarian insufficiency. Design thinking is an engineering methodology used to develop and evaluate novel concepts for systems operation. Here we articulate the need for a seamlessly integrated mobile health system to support genomic research as well as patient care. We also review the pathophysiology and management of primary ovarian insufficiency. Molecular understanding regarding the pathogenesis is essential to developing strategies for prevention, earlier diagnosis, and appropriate management of the disorder. The syndrome is a chronic disorder characterized by oligo/amenorrhea and hypergonadotropic hypogonadism before age 40 years. There may be significant morbidity due to: 1) depression and anxiety related to the loss of reproductive hormones and infertility; 2) associated autoimmune adrenal insufficiency or hypothyroidism; and 3) reduced bone mineral density and increased risk of cardiovascular disease related to estrogen deficiency. Approximately 5% to 10% of women with primary ovarian insufficiency conceive and have a child. Women who develop primary ovarian insufficiency related to a premutation in FMR1 are at risk of having a child with fragile X syndrome, the most common cause of inherited intellectual disability. In most cases of spontaneous primary ovarian insufficiency no environmental exposure or genetic mechanism can be identified. As a rare disease, the diagnosis of primary ovarian insufficiency presents special challenges. Connecting patients and community health providers in real time with investigators who have the requisite knowledge and expertise would help solve this dilemma.

A 55-year-old Caucasian postmenopausal woman with BMI of 22.5 kg/m2 presents to the clinic for follow-up to discuss the results of her recent dual-energy X-ray absorptiometry (DXA) bone mineral density (BMD) scan. She has a personal history of premenopausal early-stage hormone receptor-positive breast cancer at age 47 and a family history of parental hip fracture. Following her initial breast cancer treatment, she received tamoxifen for 5 years (Age 47–52) followed by anastrozole (an aromatase inhibitor) until the current time. The DXA scan reports T-scores of −1.8 at the total hip and −1.6 at the lumbar spine. What would be your preferred management?

ObjectiveThe objective of this study was to evaluate whether increased serum 25-hydroxyvitamin D3 (25OHD3) concentrations, in response to calcium/vitamin D (CaD) supplementation, are associated with improved lipids in postmenopausal women.MethodsThe parent trial was a double-blind, randomize

This chapter provides a summary of the literature including results from large trials, meta-analyses, and recent major recommendations. Two well-accepted and recent recommendations include those from the Agency for Health Research and Quality on calcium and vitamin D supplementation and from the Institute of Medicine's dietary reference intakes for calcium and vitamin D. This review suggests that there is strong evidence for synergistic roles of calcium and vitamin D in maintaining bone health in postmenopausal women, but the correlation between vitamin D alone and bone health is overall inconclusive.

TiN nanopowder was synthesized by carbothermal reduction method by using a (TiO 2 + C) precursor derived from titanyl nitrate, urea, glucose, ammonium nitrate, and citric acid mixed solution. The results revealed that the obtained precursor consisted of flake particles with a uniform dispersion of amorphous TiO 2 and C. The precursor powders were subsequently calcined under nitrogen at 900–1300 °C for 2 h. The initial transformation of TiO 2 to TiN, by adopting this route, occurred at 900 °C. Moreover, TiO x N y , TiO 2 , and carbon below 1200 °C, and TiC x N y , TiO x N y , TiO 2 , and carbon at (or above 1200 °C) were found to be as impurities with the calcined products. The lattice parameter of TiN synthesized at 1100 °C (α = 4.240 A) agrees well with the theoretical value (α = 4.241 A). TiN powder, synthesized at 1100 °C, exhibited well-distributed spherical particles ranging from 80 to 100 nm. The nitrogen, oxygen, and residual carbon contents of TiN powder synthesized at 1100 °C were found to be 20.37 wt.%, 1.91 wt.%, and 3.36 wt.%, respectively.

The in-training examination (ITE) offers formative assessments of residents' developing medical knowledge. Identification of an ITE performance level associated with success on the specialty board examination allows identification of “at risk” residents.Background This study sought to identify a threshold score for obstetrics and gynecology residents' performance on the Council on Resident Education in Obstetrics and Gynecology (CREOG) ITE that predicts successful performance on the American Board of Obstetrics and Gynecology (ABOG) written examination.Objective We analyzed ITE and ABOG results of 80 residents who completed 4 years of CREOG ITEs at 2 institutions between 2002 and 2012. We assessed the level of performance associated with successful performance on the ABOG written examination.Methods Data analyzed included scores for 71 of 80 residents (89%), with an overall pass rate of 82%. A postgraduate year (PGY) 4 score of 200 on the CREOG ITE or twice in any of the PGY training years was associated with a 100% ABOG pass rate. Scoring ≥ 205 in any PGY also was associated with a 100% pass rate. Residents who did not attain a score of 200 had a 35% to 45% chance of failing the ABOG written examination, depending on the PGY of the ITE performance.Results Our findings suggest that a CREOG ITE score of at least 200 twice, or as a PGY-4, offers assurance of successful performance on the ABOG examination. Scores lower than this threshold may be used to identify “at risk” residents for added learning and provide program elements in need of improvement.Conclusions

Objective The aim of this study was to identify the potential relationships between plasma 25-hydroxyvitamin D(3) (25OHD(3)), C-reactive protein (CRP), coronary artery atherosclerosis (CAA), and coronary artery remodeling in monkeys consuming atherogenic diets. Methods Female cynomolgus monkeys (n = 74) were fed a casein-lactalbumin (C/L)-based, moderately atherogenic diet for 12 months. They then consumed either a soy-based (n = 35) or C/L-based (n = 39) diet for 32 months. CRP concentrations were then determined, and monkeys underwent surgical menopause. Each diet group was then rerandomized to receive soy (n = 36) or C/L (n = 38). After 32 postmenopausal months, 25OHD(3), CRP, CAA, and coronary artery remodeling were determined. All monkeys received a woman's equivalent of 1,000 IU/day of vitamin D(3) and 1,200 mg/day of calcium throughout the study. Results The premenopausal and postmenopausal dietary protein sources had no effect on postmenopausal 25OHD(3) concentrations (P = 0.6). Across treatment groups, there was a statistically significant inverse relationship between 25OHD(3) concentrations and CRP at necropsy (r = -0.35, P = 0.003). A significant inverse correlation between 25OHD(3) concentration and the change in CRP from premenopause to postmenopause was observed (r = -0.32, P = 0.007). The significant associations identified between plasma 25OHD(3) and CRP remained after controlling for postmenopausal diet. Those monkeys with a greater increase in CRP also had significantly more CAA and less ability to maintain normal lumens by remodeling. Conclusions Higher plasma concentrations of 25OHD(3) were associated with lower CRP. Lower CRP was associated with less coronary atherosclerosis and improved coronary artery remodeling. These findings suggest that 25OHD(3) concentrations are associated with an anti-inflammatory state and may support an association between oral vitamin D3 and cardioprotection.

Phthalates are suspect environmental endocrine disruptors that may affect male reproduction and development by disturbing androgen synthesis and cell-cell interactions in the seminiferous epithelium. The in vivo metabolites, monophthalates, are thought to be the active agents, and toxicant effects including testicular damage and decreased sperm motility have been described previously. In this study, the aim was to investigate the effect of monophthalates on Sertoli cells using a two-compartment cell culture model, asking whether tight junction protein structures are affected, compromising the blood-testis barrier and contributing to male-mediated toxicity. Sertoli cells were isolated from Sprague Dawley rat testes and seeded onto the filters of two-compartment wells. A Sertoli cell monolayer was allowed to form, whereupon the cultures were treated with 0, 10, 30, 150, and 600 micromol/L monobutyl phthalate (MBP) or mono-2-ethylhexyl phthalate (MEHP) for 24 h. Effects on the tight junctions between adjacent Sertoli cells were studied by light and transmission electron microscopy, the transepithelial electrical resistance (TEER) assay, and immunofluorescence localization. Results showed that exposures to monophthalates destroyed tight junctional structure in Sertoli cell monolayers in a dose-depended manner, as evidenced by a loss of single-cell layer organization in the cultures, decline of TEER value, and decreased expression of proteins associated with tight junctions such as zonula occludens-1 (ZO-1), F-actin, and Occludin. The changes were observed at doses of 150 and 600 micromol/L, which is 10-100 times higher relative to estimated human exposures from the environment. These results are consistent with monophthalate-induced damage to tight junctions between adjacent Sertoli cells, suggesting that damage to Sertoli cell tight junctions induced by monophthalates may be an underlying mechanism of their male-mediated reproductive toxicity.

OBJECTIVES To assess the risk of endometrial cancer (EC) associated with atypical glandular cells of endometrial origin (AGC-EM) in 2 age groups (age younger than 51 vs 51 years or older). METHODS A retrospective case series was assembled identifying AGC from a pathology database between January 1, 2005 and January 1, 2009. Demographics, cervical cytology results, and final diagnoses (including clinically significant diseases and cancers) were recorded from the initial AGC diagnosis until August 30, 2011. Data were analyzed using the χ test to compare rates of disease between age groups. RESULTS Among the 444 patients with AGC, 41% (183/444) had AGC-EM. Women younger than 51 years, compared to those 51 years or older, had significantly lower rates of AGC-EM (35% [105/296] vs 53% [78/148]; p < .001; odds ratio, 0.49; 95% confidence interval, 0.33-0.74). The rate of EC was significantly lower in those younger than 51 years, compared to those aged 51 or older (5% [8/158] vs 19% [18/95]; p < .001; odds ratio, 0.23; 95% confidence interval, 0.09-0.55) in women who underwent endometrial biopsy. In women younger than 51 years who underwent an endometrial biopsy, the rate of EC had a stepwise increase across 3 subclasses of AGC (from AGC of endocervical origin [AGC-EC] to AGC not otherwise specified to AGC-EM) (p = .04). CONCLUSIONS Women aged 51 years or older who have AGC are more likely to have AGC-EM and EC than women younger than 51 years. In women younger than age 51, AGC-EM is the subclass most associated with EC while compared to 2 other subclasses (AGC not otherwise specified and AGC-EC).

Introduction: Heterotopic pregnancy is the coexistence of intrauterine pregnancy (IUP) and extrauterine gestation. It is a rare and dangerous life-threatening situation that is difficult to diagnose and easily missed. The incidence in the general population is estimated to be 1 in 30,000. Risk factors for ectopic pregnancy are pelvic inflammatory disease (PID), tubo-ovarian abscess (TOA), previous ectopic pregnancies, or previous surgery. Case: A 22 year old gravida 2 para 1-0-0-1 presented to the emergency department (ED) and was diagnosed with heterotopic pregnancy despite lack of any notable risk factors. Transvaginal ultrasound showed live IUP and right ovarian/adnexal ectopic pregnancy with heartbeat, along with moderate hemoperitoneum. She underwent operative laparoscopy and right salpingectomy, being discharged home on post-operative day 1 with a stable hemoglobin concentration. She delivered the IUP at 38 weeks 5 days gestation via spontaneous vaginal delivery. Discussion: This case represents a spontaneous heterotopic pregnancy in a 22-year-old patient with no previous risk factors identified and demonstrates laparoscopy as a successful treatment modality for heterotopic pregnancy.

OBJECTIVE: The purpose of this study was to assess the effectiveness of a menopause clinic to enhance trainees' medical knowledge. METHODS: Between July 2004 and May 2007, 73 resident physicians completed a rotation that included a weekly menopause clinic and completion of a pretest and posttest examination. Each test contained questions on topics covering menopause, perimenopause, and general women's health. At the end of each testing session, a total score and a menopause score were given. RESULTS: The mean (SD) pretest menopause score and total score were 63.2% (13.3%) and 63.7% (11.3%), respectively. The mean posttest increase in the menopause score was 14%, with a median score increase of 10.2% (P < 0.0001). The posttest results ranged from a maximum decrease of 7.8% to a maximum increase of 47.1%. The mean increase in the total score was 13%, with a median increase of 10.7% (P < 0.0001). For the posttest total score, the range went from -7.2% to 39.3%. There was no correlation between the score changes and the number of clinic sessions attended, the resident specialties (obstetrics/gynecology vs non-obstetrics/gynecology), the level of training (postgraduate year 1 or 2), or the examination order (test A vs test B taken first). CONCLUSION: Menopause clinics can add to resident physician knowledge about menopause-related matters. Menopause clinics may help educate future physicians in their ability to care for postmenopausal women.