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OBJECTIVE: 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. METHODS: 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. RESULTS: 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; P < 0.001) 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. CONCLUSIONS: 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.

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OBJECTIVE: The aim of this study was to examine the association between common menopausal symptoms (MS) and long-term cardiovascular disease (CVD) and all-cause mortality. METHODS: In an observational cohort of 80,278 postmenopausal women with no known CVD at baseline from the Women's Health Initiative, we assessed individual MS severity (mild vs none; moderate/severe vs none) for night sweats, hot flashes, waking up several times at night, joint pain or stiffness, headaches or migraines, vaginal or genital dryness, heart racing or skipping beats, breast tenderness, dizziness, tremors (shakes), feeling tired, forgetfulness, mood swings, restless or fidgety, and difficulty concentrating. Outcomes included total CVD events (primary) and all-cause mortality (secondary). Associations between specific MS, their severity, and outcomes were assessed during a median of 8.2 years of follow-up. All results were multivariable adjusted, and individual associations were Bonferroni corrected to adjust for multiple comparisons. A machine learning approach (least absolute shrinkage and selection operator) was used to select the most parsimonious set of MS most predictive of CVD and all-cause mortality. RESULTS: The severity of night sweats, waking up several times at night, joint pain or stiffness, heart racing or skipping beats, dizziness, feeling tired, forgetfulness, mood swings, restless or fidgety, and difficulty concentrating were each significantly associated with total CVD. The largest hazard ratio (HR) for total CVD was found for moderate or severe heart racing or skipping beats (HR, 1.55; 95% confidence interval [CI], 1.29-1.86). The individual severities of heart racing or skipping beats, dizziness, tremors (shakes), feeling tired, forgetfulness, mood swings, restless or fidgety, and difficulty concentrating were associated with increased all-cause mortality. Moderate or severe dizziness had the largest HR (1.58; 95% CI, 1.24-2.01). Multiple symptom modeling via least absolute shrinkage and selection operator selected dizziness, heart racing, feeling tired, and joint pain as most predictive of CVD, whereas dizziness, tremors, and feeling tired were most predictive of all-cause mortality. CONCLUSION: Among postmenopausal women with no known CVD at baseline, the severity of specific individual MS was significantly associated with incident CVD and mortality. Consideration of severe MS may enhance sex-specific CVD risk predication in future cohorts, but caution should be applied as severe MS could also indicate other health conditions.

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OBJECTIVE: 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). METHODS: 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. RESULTS: 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 level > 1,000 pg/mL and nine women with T level > 400 ng/dL. CONCLUSION: 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.

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OBJECTIVE: 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. METHODS: 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. RESULTS: 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 trend < 0.001). CaD did not modify any association. CONCLUSION: 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.

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OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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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.

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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.

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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).

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OBJECTIVE: To assess adherence to management guidelines based on the terminology used to describe atypical glandular cells (AGC) on cytology reports. MATERIALS AND METHODS: We analyzed AGC pathology reports from Hartford Hospital, 2004-2007, and identified cases of AGC with the terminology atypical glandular cells or atypical endocervical cells (AEC). We calculated rates of clinical evaluations based on the terminology used to describe the AGC. Statistical analysis was performed using the χ test. RESULTS: Seventy-eight reports contained the terminology AEC and 97 reports contained the terminology AGC. The rate of histologic sampling in women with AEC was lower than in women with AGC (52.6% vs 83.5%; p < .01). Similarly, the rate of comprehensive evaluations was lower (33.3% vs 71.1%; p < .01). Fewer endocervical curettages (47.4% vs 77.3%; p < .01) and fewer endometrial biopsies in women 35 years or older were performed (26.9% vs 69.1%; p < .01) in women with AEC than in women with AGC. CONCLUSIONS: Women with AGC reports containing the term AEC were managed less optimally than those with AGC. These results suggest that the terminology used to describe the finding of atypical glandular cells may influence the clinical evaluation. Clinicians may not recognize AEC as AGCs. Ours results suggest that the terminology atypical endocervical cells should be avoided or accompanied by the terminology atypical glandular cells.

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OBJECTIVE: 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. METHODS: 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. RESULTS: 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) (P < 0.0001). 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) (P < 0.0001). CONCLUSIONS: 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.

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