HRT Use Research Articles

8622 The Severity of Vasomotor Symptoms Is Associated With Metabolic Dysfunction Associated Liver Disease (Masld) in Peri- AndPostmenopausal Women

Abstract Disclosure: E. Armeni: None. A. Augoulea: None. I. Karagkouni: None. I. Avgousti: None. M. Charamanta: None. S. Stergiotis: None. I. Lambrinoudaki: None. Introduction: Reproductive aging and ovarian senescence are associated with accelerated accumulation of cardiometabolic risk factors, but also progressively increasing risk for cardiovascular disease (CVD). Metabolic-dysfunction-associated steatotic liver disease (MASLD) is linked with a higher risk for CVD. The prevalence of MASLD with regards to reproductive aging, and the possible link with vasomotor symptoms has not been evaluated yet Methods: For the purpose of this cross-sectional study, we evaluated 106 peri- and postmenopausal women, retrieved from the outpatient Menopause clinic of the Second Department of Obstetrics and Gynecology, University of Athens, Aretaieio Hospital, Athens, Greece. The extent of steatotic liver disease (SLD) was estimated as values of the fatty liver index; using the known cut-off ≥ 60 for higher risk for SLD. MASLD was defined as the presence of ≥1 of the following risk factors in a woman with hepatic steatosis: 1) body mass index (BMI) ≥25 kg/m2 or waist circumference ≥85 cm; 2) fasting glucose ≥100 mg/dL or type 2 diabetes or hypoglycemic treatment; 3) blood pressure ≥130/85 mmHg or antihypertensive treatment; 4) triglycerides ≥150 mg/ dL or related treatment; and 5) high-density lipoprotein cholesterol ≤40 mg/dL or lipid-lowering treatment. The severity of vasomotor symptoms (VMS) was assessed using the Greene Climacteric Scale. Results: Moderate-to-severe VMS were evident in 42 women of our sample while 64 women had no-to-mild severity of VMS. Logistic regression analysis showed that moderate-to-severe VSM, as opposed to no-to-mild symptoms, were associated with MASLD (MASLD rates, moderate-to-severe VSM vs no-to-mild: 26.2% vs 12.5%, p-value=0.072; OR = 3.022, p-value =.041). This association became even stronger when we restricted the sample to early postmenopausal women (up to 5 years after the final menstrual period, N=57, VMS no-to-mild vs moderate-to-severe, 3.6% vs 24.1%, p-value = 0.025; OR=9.333, p-value=0.045). The models were adjusted for age, physical exercise, alcohol intake, current smoking, history of menstrual irregularity, and HRT use. Conclusion: The results of this study indicate that the severity of vasomotor symptoms is associated with the diagnosis of MASLD in midlife women, irrespective of the use of HRT. These observations underscore the importance of cardiovascular risk assessment in women with bothersome vasomotor symptoms. Presentation: 6/3/2024

Menopause and HRT (Use and Concerns) among Jordanian Women: A Cross Sectional Study

Menopause and HRT (Use and Concerns) among Jordanian Women: A Cross Sectional Study

Abstract P356: Women’s Reproductive Factors Are Associated With Future Risk of Hearing Loss

Introduction: The association between female reproductive factors and risk of hearing loss (HL) has been unclear. Hypothesis: Women’s reproductive factors have been associated with comorbidities such as cardiovascular disease and diabetes, which are all linked to hearing loss (HL). We thus hypothesized that reproductive factors might be associated with the risk of HL. Methods: We used data from the UK Biobank (UKB). Reproductive factors included number of children, age at the first/last birth, age at menarche, age at natural menopause, and reproductive period. HL was ascertained using the International Classification of Diseases 10th revision (ICD-10) codes H90 (conductive and sensorineural hearing loss) and H91 (other hearing loss). Cox proportional hazards models were used to examine the association between reproductive factors and hospital ascertained HL, considering death as a competitive event. In addition, we combined age at menopause with HRT status to see their joint effect on HL. All models were adjusted for age at baseline, ethnicity, education level, income, Townsend deprivation index, BMI, smoking status, drinking status, physical activities, cardiovascular disease, diabetes, and HRT use status. Results: Compared to women who had no child, women who had two, three and four or more children was linked to elevated risk of HL, with HR (95% CI) of 1.14 (1.04-1.25), 1.24 (1.11-1.38), and 1.35 (1.17-1.55), respectively. Compared to women who had first birth before age 25 years, women who had first birth greater than age 26 years had reduced risk of HL (0.84, 0.76-0.93). Women who gave last birth over age 40 years had elevated risk of HL (1.21, 1.01-1.45), compared to those who had last birth before age 35 years. Compared to women who had menopause at age 46-50 years, those who had early menopause less than age 45 years were associated with 24% higher risk of HL (1.24, 1.00-1.54). In addition, women with reproductive period less than 30 years had elevated risk of HL (1.19, 1.07-1.34), compared to women with reproductive period greater than 35 years. Women who had age at menopause greater than 50 years and used HRT had 25%-50% higher risk of HL, compared to their counterpart who did not use HRT. Conclusions: In conclusion, higher number of children, having first birth before age 25 years, having last birth after age 40 years, having menopause before age 45 years, and having reproductive period shorter than 30 years were associated with higher risk of hearing loss. In women with menopause age greater than 50 years, HRT use increased the risk of hearing loss.

Use of artificial intelligence to identify patients to be assessed in a breast clinic on 2-week wait: a retrospective cohort study

Background: The number of urgent referrals from primary care to specialist one stop breast clinics continues to rise beyond the capacity of the 2-week wait service. This study aims to use artificial intelligence (AI) to identify patients with new breast symptoms requiring a biopsy to identify those who should be prioritised for urgent breast clinic assessment. Methods: Data were collected retrospectively for patients attending one stop triple assessment breast clinic at Broomfield hospital between 1 June and 1 October 2021. PHP machine learning software was used to run AI on the data to identify patients who had a core biopsy in clinic. Results: A total of 794 cases were referred to one stop breast clinic for new breast symptoms—37 male (4.6%) and 757 female (95.3%). The average age of the patients included was 43.2 years. Five hundred thirty-six patients (67.5%) presented with a breast lump, 180 (22.7%) with breast pain, 61 (7.7%) with changes to shape or skin and 13 (1.6%) with a lump identified by their general practitioner. The patients who had a biopsy were of increased age [52.8 (SD 17.9) vs. 44.1 (SD 16.8), P<0.001], and had previous mammogram [n=21, (31.8%) vs. n=148 (20.3%), P 0.03], previous benign breast disease [n=9 (13.6%) vs. n=23 (3.1%), P<0.001], and increased use of HRT [n=13 (19.7%) vs. n=53 (6.4%), P<0.001]. The sensitivity and specificity of AI with neural network algorithms were 84% and 90%, respectively. Conclusion: AI was very effective at predicting the presenting symptoms that are likely to result in biopsy and can therefore be used to identify patients who need to be seen urgently in breast clinic.

Latin America and the Caribbean Code Against Cancer 1st Edition: Medical interventions including hormone replacement therapy and cancer screening

Prostate, breast, colorectal, cervical, and lung cancers are the leading cause of cancer in Latin America and the Caribbean (LAC) accounting for nearly 50% of cancer cases and cancer deaths in the region. Following the IARC Code Against Cancer methodology, a group of Latin American experts evaluated the evidence on several medical interventions to reduce cancer incidence and mortality considering the cancer burden in the region. A recommendation to limit the use of HRT was issued based on the risk associated to develop breast, endometrial, and ovarian cancer and on growing concerns related to the over-the-counter and without prescription sales, which in turn bias estimations on current use in LAC. In alignment with WHO breast and cervical cancer initiatives, biennial screening by clinical breast examination (performed by trained health professionals) from the age of 40 years and biennial screening by mammography from the age of 50 years to 74, as well as cervical screening by HPV testing (either self-sampling or provider-sampling) every 5–10 years for women aged 30–64 years, were recommended. The steadily increasing rates of colorectal cancer in LAC also led to recommend colorectal screening by occult blood testing every two years or by endoscopic examination of the colorectum every 10 years for both men and women aged 50–74 years. After evaluating the evidence, the experts decided not to issue recommendations for prostate and lung cancer screening; while there was insufficient evidence on prostate cancer mortality reduction by prostate-specific antigen (PSA) testing, there was evidence of mortality reduction by low-dose computed tomography (LDCT) targeting high-risk individuals (mainly heavy and/or long-term smokers) but not individuals with average risk to whom recommendations of this Code are directed. Finally, the group of experts adapted the gathered evidence to develop a competency-based online microlearning program for building cancer prevention capacity of primary care health professionals.

DCIS and LCIS: Are the Risk Factors for Developing In Situ Breast Cancer Different?

Ductal carcinoma in situ (DCIS) is widely accepted as a precursor of invasive ductal carcinoma (IDC). Lobular carcinoma in situ (LCIS) is considered a risk factor for invasive lobular carcinoma (ILC), and it is unclear whether LCIS is also a precursor. Therefore, it would be expected that similar risk factors predispose to both DCIS and IDC, but not necessarily LCIS and ILC. This study examined associations with risk factors using data from 3075 DCIS cases, 338 LCIS cases, and 1584 controls aged 35-60, recruited from the UK-based GLACIER and ICICLE case-control studies between 2007 and 2012. Analysis showed that breastfeeding in parous women was protective against DCIS and LCIS, which is consistent with research on invasive breast cancer (IBC). Additionally, long-term use of HRT in post-menopausal women increased the risk of DCIS and LCIS, with a stronger association in LCIS, similar to the association with ILC. Contrary to findings with IBC, parity and the number of births were not protective against DCIS or LCIS, while oral contraceptives showed an unexpected protective effect. These findings suggest both similarities and differences in risk factors for DCIS and LCIS compared to IBC and that there may be justification for increased breast surveillance in post-menopausal women taking long-term HRT.

Withholding of Hormone Replacement Therapy Prior to Total Joint Arthroplasty Surgery to Reduce the Risk of Postoperative Thromboembolic Events: Is It Justified?—A Systematic Review of Clinical Practice Guidelines

BackgroundHormone replacement therapy (HRT), menopausal hormone therapy (MHT), and estrogen-containing medications are frequently withheld before elective lower limb arthroplasty, based on a perceived risk of venous thromboembolism (VTE). However, evidence linking HRT, MHT, and an increased VTE risk is equivocal. This systematic review evaluated the concordance of international clinical practice guidelines (CPGs) on the withholding of HRT or MHT. MethodsThe PubMed, Google Scholar, Cochrane, and Ovid databases were searched for CPGs for the preoperative, perioperative, and postoperative management of patients on HRT and MHT undergoing elective lower limb arthroplasty. This was supplemented by an internet search. There were 7 international CPGs in English, from Europe and North America, published between January 2000 and February 2023 reviewed against the Appraisal of Guidelines for Research & Evaluation Instrument (AGREE-II) criteria, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. ResultsThe guidelines reviewed revealed a mixed picture on HRT or MHT withdrawal and use in arthroplasty, with some featuring detailed advice on the preoperative and postoperative management of HRT or MHT (Scottish Intercollegiate Guidelines Network), while others featured no guidance (American College of Chest Physicians). The evidence referenced in these guidelines highlighted studies showing HRT or MHT to play a limited role in increasing VTE risk, with most studies from the 1990s and 2000s. ConclusionsBased on current evidence, non-estrogen-containing transdermal HRT or MHT should not be withheld in patients undergoing elective joint arthroplasty, though further evidence is required to justify withholding estrogen-containing forms.

Managing the menopause during the pandemic

The structure of the presentation will be 1)Pandemic-Epidemiology 2)General Pandemic-Management 3)HRT and COVID 4)Different spectrum of menopausal symptoms (Europe/Asia) 5)Different risks lead to different HRT. 1)Pandemic-Epidemiology: SARS-COVID-19 has got to be a new disease, China was the first to suffer from the pandemic starting in December 2019 with spread all over the world. Diagnosis, treatment and protective measures have started in Europe in March 2020; up from autumn 2022 in Europe the pandemic changed to endemic, but protective measures still should be continued in risk patients like in hospitals and nursing homes. Rehabilitation will for long-time be an issue like treatment of "Post-" and "Long-COVID". China pursued a zero-COVID-policy until Dec 2022. The sudden stop of almost all measures led to a sharp increase in infections, which shows that the disease will remain a global risk. 2)General Pandemic-Management: Protective measures like vaccination, surgical masks, screening/testing, isolation management, travel/residence history in high-risk regions, education of patients and families had to be the first priority, ahead of other issues such as the management of menopause. 3)HRT and COVID: Already the first prelimary data assessed in Wuhan/China have shown that women with low estradiol-levels had more severe infections with COVID. An analysis of health records of 68,466 COVID-positive patients from 17 countries showed that the fatality risk for women > 50 years receiving HRT was reduced by more than 50% compared to those women not taking HRT (Seeland, 2020). Likewise from a case-control study analyzing the self-reported data of 1.6 million UK menopausal women through the COVID-Symptoms Study Smartphone application (control populations adjusted for age, body mass index, and smoking status) was concluded, that HRT not only can be used, but even can protect from COVID-infections and/or their sequelae (Costeira, 2021). 4)The different spectrum of menopausal symptoms (independent of COVID-infections) comparing data in Europe (showing more vasomotor symptoms) and China (more somatic symptoms) will be presented, including own data. 5)Different risks during HRT consequently lead to different use of HRT, especially more transdermal estrogen combined with progesterone in Europe due to much higher VTE-risk, but more management of the high bleeding-problems in China using individualized (mostly oral) estrogen/progestogen combinations.

Epidemiologic effectors on the breast tumor microenvironment: Results from the Cancer Prevention Study-II and -3 cohorts.

10530 Background: Despite breast cancer being the leading cancer among women, we have a poor understanding of the impact of epidemiologic risk factors on its tumor microenvironment (TME). We examined risk factors for TME favorability using a novel aggregate marker: the Histomic Prognostic Score (HiPS). Methods: Data were from whole slide image (WSI) scans of hematoxylin & eosin slides from women in the Cancer Prevention Studies CPS-II and -3, diagnosed with nonmetastatic breast cancer. Diagnoses occurred between enrollment and the last administrative date (1992/1993 to 2011 in CPS-II and 2006–2013 to 2018 in CPS-3). Median year of diagnosis was 2004 in CPS-II and 2014 in CPS-3. Using the WSI, a deep-learning model was trained to extract features and summarize the morphology of the epithelium, stroma, and tumor-infiltrating lymphocytes within the TME. These features, along with demographic, tumor biomarkers, and survival data, were then used to generate the HiPS, a novel measurement of “ prognostic favorability” of TME, ranging from 0 (favorable) to 10 (unfavorable). Multivariable linear models estimated associations between the HiPS score and epidemiologic risk factors: hormone replacement therapy use (HRT; current vs. former/never), cigarette smoking (current vs. former/never), alcohol intake (>1 drink vs. <1 drink/day), aspirin intake (daily vs. not daily) controlled for, age at diagnosis, body mass index (BMI), race, and cancer detection method (screen- vs. self-detected). Results: We included 1264 CPS-II and 651 CPS-3 participants in the analysis. Compared to CPS-II, CPS-3 participants were younger (mean (± sd) age 54.7 ± 7.6 vs. 72.2 ± 7, p<0.001), heavier (mean (± sd) BMI 27.1 ± 5.8 vs. 26 ± 4.8, p<0.001), and more diverse (7.4% vs. 2.1% non-White, p<0.001). Most breast cancers (69.9% of CPS-II and 64.1% of CPS-3) were screen-detected, p=0.206. Increasing age and BMI were associated with higher HiPS score in both cohorts, Table. Daily aspirin use and current HRT use were associated with lower HiPS scores in CPS-3 only. The inverse association for HRT use was lost in the following subgroups age < 50, ER-, HER2+, TNM stage-1, and screen-detected cancers. Conclusions: Increasing age and BMI have independent adverse effects on breast TME. Daily aspirin intake and current HRT use were only associated with a favorable TME in the younger, more contemporary cohort. Additional studies are needed to confirm these findings and better understand the role of these epidemiologic factors on the TME. [Table: see text]

Higher Lifetime Exposure to Gonadal Hormones is Associated With Lower White Matter Hyperintensities Burden: A UK Biobank Study in Post-Menopausal Women (P6-5.006)

<h3>Objective:</h3> The aim of this study was to examine the relationship between lifetime exposure to endogenous and exogenous gonadal hormones on white matter hyperintensities (WMH) in post-menopausal women. <h3>Background:</h3> The onset of menopause accelerates the development of brain biomarkers of small vessel disease, such as WMH, supporting the cerebrovascular-protective effects of hormones. However, whether this effect is influenced by lifetime exposure to hormones is unclear. <h3>Design/Methods:</h3> Two measures of lifetime endogenous hormone exposure (ENHE) were explored: 1) cumulative number of years with a natural menstrual cycle and 2) cumulative number of live childbirths in women having never received hormone replacement therapy (HRT, n=6039). For exogenous hormone exposure (EXHE): 1) the use of oral HRT and 2) topical HRT (n=246). WMH volume was obtained from preprocessed T2-FLAIR images. <h3>Results:</h3> In a linear model adjusted for intracranial volume, age, oral contraceptive use, socio-demographics, and cardiovascular risk factors, both ENHEcycle and EMNHEparity were negatively associated with WMH (R2 = 0.30, F = 241, DF = 6027, p&lt;0.0001; βparity = −0.025, p = 0.006; βcycle = −0.003 p = 0.017). For EXHE, women who received topical HRT had significantly lower WMH volume than oral HRT (t=1.99, p= 0.048) after correcting for intracranial volume, age, socio-demographics, cardiovascular risk factors, ENHEcycle and ENHEparity. <h3>Conclusions:</h3> Our results provide further evidence that lifetime exposure to endogenous hormones appears to have an independent protective effect on WMH burden, and extending this with exogenous topical HRT may confer additional protection. The stronger effect of parity may be due to prolonged exposure to elevated estrogen resulting in long-lasting structural or functional changes in the small cerebral vessels. <b>Disclosure:</b> Dr. Perron has nothing to disclose. Miss Cote has nothing to disclose. Prof. Lepage has nothing to disclose. Dr. Bocti has nothing to disclose. Kevin Whittingstall has nothing to disclose.

Bone mineral density, vertebral fractures and trabecular bone score in primary ovarian insufficiency.

Bone health in primary ovarian insufficiency (POI) is under-investigated. We assessed patients with spontaneous POI for vertebral fractures (VFs) and related parameters of bone health. 70 cases with spontaneous POI (age 32.5 ± 7.0years) and an equal number of controls were assessed for BMD, TBS, and VFs. BMD at the lumbar-spine (L1-L4), left hip, non-dominant forearm, and TBS (iNsight software) were measured on a dual-energy X-ray absorptiometry (DXA) machine. VFs were assessed by Genant's classification. Serum FSH, LH, estradiol, T4, TSH, iPTH, serum 25(OH)D, total calcium, and inorganic phosphorus were measured. BMD at the lumbar-spine, hip and forearm was reduced by 11.5%, 11.4% and 9.1% in POI as compared to controls (P < 0.001). Degraded or partially degraded microarchitecture on TBS was observed in 66.7% of patients and 38.2% of controls (P = 0.001). 15.7% of the POI patients had VFs, compared to 4.3% of controls (P = 0.045). Age, duration of amenorrhea and duration of HRT use were the significant predictors of TBS (P < 0.01). Serum 25(OH)D was the significant determinant of VFs. TBS abnormalities were higher in patients with POI and VFs. BMD was not significantly different in patients with and without VFs. Thus, lumbar-spine osteoporosis, impaired TBS and VFs were present in 35.7%, 66.7% and 15.7% of patients with spontaneous POI in their early third decade. This indicates need for rigorous investigations for impaired bone health in these young patients and management with HRT, vitamin-D, and possible need for bisphosphonate therapy.

Association of lifespan reproductive duration with depression in Swedish twins: The role of hormone replacement therapy.

To examine the association between reproductive duration and postmenopausal depression (taking the use of hormone replacement therapy [HRT] into account). In this population-based cohort study, 11 320 postmenopausal women (mean age 63.6 years) were followed for up to 18 years. Reproductive duration was categorized into three groups: short (≤34 years), average (35-39 years), and long (≥40 years). Depression was ascertained from the Sweden National Patient Registry. During the follow up, 593 (5.24%) women developed depression. In the multi-adjusted generalized estimating equation model, the odds ratios (ORs) of depression were 1.28 (95% confidence interval [CI] 1.05-1.55) and 1.25 (95% CI 1.01-1.55) for women with short and long reproductive durations, respectively, compared with those women with average reproductive duration. Women with a non-typical reproductive duration (≤34 or ≥40 years) who received HRT were at a higher risk of depression (OR 1.82, 95% CI 1.42-2.33). There was a significant additive interaction between non-typical reproductive duration and the use of HRT on depression (attributable proportion 0.26, 95% CI 0.03-0.50). Women with a short or long reproductive duration, especially those with a history of HRT use, have a higher risk of depression after menopause compared with those with an average reproductive duration.

Reproductive Factors and Colorectal Cancer Risk: A Population-Based Case-Control Study.

BackgroundHormone-replacement therapy (HRT) is associated with lower colorectal cancer (CRC) risk among postmenopausal women. However, little is known about the effects of lifetime exposure of women to varying levels of estrogen and progesterone through reproductive factors such as parity, use of oral contraceptives (OC), breastfeeding, and menstruation on CRC risk.MethodsWe assessed associations between reproductive factors and CRC risk among 2650 female CRC patients aged 30+ years and 2175 matched controls in a population-based study in Germany, adjusting for potential confounders by multiple logistic regression.ResultsInverse associations with CRC risk were found for numbers of pregnancies (odds ratio [OR] per pregnancy = 0.91, 95% confidence interval [CI] = 0.86 to 0.97), breastfeeding for 12 months and longer (OR = 0.74, 95% CI = 0.61 to 0.90), and use of either OC or HRT (OR = 0.75, 95% CI = 0.64 to 0.87) or both (OR = 0.58, 95% CI = 0.48 to 0.70). Similar results were found for postmenopausal women only and when adjusting for number of pregnancies and for all reproductive factors analyzed together. Breastfeeding duration of 12 months and longer was associated with lower risk of cancer only in the proximal colon (OR = 0.58, 95% CI = 0.45 to 0.74).ConclusionsSeveral reproductive factors were associated with lower CRC risk in women, including number of pregnancies, breastfeeding duration, and use of OC and HRT. This suggests that women’s exposure to female reproductive hormones plays a key role in the difference in CRC risk between women and men and in site-specific CRC risk.

Reproductive factors and breast arterial calcification: a systematic review and meta-analysis

Background Breast arterial calcification (BAC) is a common incidental finding on screening mammography. Recent evidence suggests that BAC is associated with cardiovascular disease (CVD). We systematically reviewed the associations between BAC and reproductive factors (menopausal status, hormone replacement therapy [HRT] use, oral contraceptive [OC] use and parity). Methods MEDLINE and EMBASE databases, references of relevant papers and Web of Science were searched up to February 2020 for English-language studies that evaluated these associations. Study quality were determined and a random effects model was used to assess these associations. Results Nineteen observational studies (n = 47,249; three cohort studies, seven case–control studies, nine cross-sectional studies) were included. BAC was associated with menopause (nine studies; n = 15,870; odds ratio [OR] 2.67; 95% confidence interval [CI] 1.50–4.77) and parity (seven studies; n = 27,728; OR 2.50; 95% CI 1.68–3.71) and inversely with HRT use (10 studies; n = 33,156; OR 0.57; 95% CI 0.40–0.80). No association was found with OC use. Eleven studies were considered good in quality. Marked heterogeneity existed across all analyses. Conclusions BAC is associated with HRT use, menopause and parity. However, careful interpretation is required as marked heterogeneity existed across all analyses. Traditional cardiovascular risk factors may need to be taken into account in future investigations of associations between BAC and reproductive factors. PROSPERO CRD42020141644.

Hormone replacement therapy in relation to the risk of colorectal cancer in women by BMI: a multicentre study with propensity score matching

Epidemiological evidence about hormone replacement therapy and colorectal carcinogenesis by demographic and clinical traits remains unclear. We aimed to assess this postulated association in a large multicentre study and further explore the modification effect by BMI and others. We retrospectively collected records of women diagnosed with colorectal cancer (CRC) at the age of 50years and older during 2014-2017 and their HRT dispensing prior to CRC diagnosis in three tertiary hospitals in China. CRC cases were matched with controls at a ratio of 1:3 using nearest neighbour propensity scores matching to better control for the remaining imbalance between groups, which generated a total of 824 cases with 2472 controls. Our study confirmed the inversed association between colorectal cancer risk and hormone replacement therapy (OR, 0.62; 95% CI, 0.54-0.75), which was more prominent among women having multiple HRT dispenses (OR, 0.60; 95% CI, 0.52-0.76). Furthermore, significant associations were consistently observed for the short-term (OR, 0.69; 95% CI, 0.57-0.88), middle-term (OR, 0.51; 95% CI, 0.41-0.66), and long-term HRT users (OR, 0.70; 95% CI, 0.43-0.90). Estrogen-related regimen reduced CRC risk more than progestogen-only. We, for the first time, found that the modifying effect of BMI on HRT use and CRC risk was in different ways when BMI was categorized by a medium level of 27. Our findings mainly suggest that there might be a different mechanism for the reversed association between HRT and colorectal tumorigenesis by BMI level, providing thoughts on clinical treatment of CRC.

Extending the Cultivation Period of Undaria pinnatifida by Using Regional Strains with Phenotypic Differentiation along the Sanriku Coast in Northern Japan

The Sanriku district is one of the largest Undaria pinnatifida (Wakame) cultivation areas in Japan. However, the production has steadily declined in recent years due to the high retirement rate among fishers. Extending the cultivation period is a potential way to improve productivity by decentralizing the workforce through the production process. We aimed to investigate the phenotypic differentiation between regional strains of U. pinnatifida collected from Matsushima Bay (MAT) and Hirota Bay (HRT) in the Sanriku district through a cultivation trial to verify the application for the purpose of extending the cultivation period. The growth of MAT was better than that of HRT when the cultivation started earlier (i.e., 9 and 19 October 2014); in contrast, HRT outperformed MAT when the cultivation started later (6 November and 12 December 2014). The yield of MAT reached over the standard amount in the Sanriku district in February. On the other hand, the yield of HRT reached over this value in April. Furthermore, the photosynthetic performance and nutrient uptake rates differed between MAT and HRT, indicating that the differences may result in maturation characteristics. According to these results, the combined use of MAT and HRT would be a valuable strategy by which to extend the cultivation period.

Female reproductive factors and risk of joint replacement arthroplasty of the knee and hip due to osteoarthritis in postmenopausal women: a nationwide cohort study of 1.13 million women

Previous studies of the relationships between female reproductive factors and osteoarthritis (OA) have shown conflicting results. In this study, we aimed to explore the relationships between reproductive factors and joint replacement arthroplasty of the knee (TKRA) and hip (THRA) in a large nationwide population-based cohort of postmenopausal Korean women. We included 1,134,680 subjects who participated in national health examinations in 2009 in the study. The study outcomes were incident THRA or TKRA due to severe hip or knee OA. The relationships between reproductive factors and THRA or TKRA were evaluated using a multivariable-adjusted proportional hazards model. During a mean follow-up duration of 8.2 years, 1,610 incident THRA cases and 60,670 incident TKRA cases were observed. Later age at menarche, longer breastfeeding, HRT and OC use were associated with increased risk of TKRA for severe knee OA, while later age at menopause and longer reproductive span were associated with decreased risk. With regard to THRA for severe hip OA, later menarche, longer breastfeeding, HRT more than 5 years, and OC use more than 1 year were associated with higher risk. The associations between reproductive factors and severe OA were more pronounced in underweight and younger subjects. We found that shorter estrogen exposure was associated with higher risk of TKRA due to severe knee OA, and such associations were more pronounced in underweight and younger subjects. The association between shorter estrogen exposure and THRA was not robust.

Colorectal Cancer in Egypt: Clinical, Life-Style, and Socio-Demographic Risk Factors

Background: Colorectal cancer (CRC) is cancer of the colon and rectum. It arises from the mucosa that lining the colon, rectum or both. Aim of the work: Determination of the clinical, lifestyle, and socio-demographic risk factors of colorectal cancer in Egypt. Patients and Methods: A hospital-based, case-control study design was performed. 160 cases with CRC and 300 healthy subjects were recruited in this study. An endoscopic, radiological and pathological methods and clinical examinations had been done for the collection of data. Results: The most significant risk factors for medical and family were obesity, DM, bowel habit change, inflammatory bowel disease (IBD), precancerous colonic lesions, no NSAIDs use, no HRT use, cholecystectomy, and family history of CRC (ORs=2.12, 2.13, 1.97, 4.91, 5.46, 3.69, 6.3, 3.84, and 8.88; respectively). Conclusion: The most important risk factors of CRC were obesity, DM, IBD, precancerous colonic lesions, and family history of CRC. Risk factors of CRC are commonly controllable.

Risk-reducing salpingo-oophorectomy and breast cancer incidence among BRCA-mutation carriers.

10548 Background: Uncertainty exists with regard to the role of bilateral salpingo-oophorectomy in altering the risk of breast cancer in BRCA-mutation carriers. Methods: Included were 1645 healthy Jewish Israeli BRCA1/2 -mutation carriers from a single center without prophylactic mastectomy. Carriers with and without risk-reducing bilateral salpingo-oophorectomy (RRBSO) were matched according to BRCA-mutation type (BRCA1 vs. BRCA2) and year of birth (±1 year). Hormonal and reproductive variables were compared and incidence of breast cancer recorded. Association between RRBSO and breast cancer was studied. Results: Seventy-seven and 50 matched-pairs had BRCA1 and BRCA2 mutation respectively. Fifty-two carriers had breast cancer, 21 in RRBSO-group and 31 in no- RRBSO group, with no statistically significant difference. When analysing each mutation group separately, stratified by age at surgery, no association between RRBSO and breast cancer incidence was found among BRCA1-mutation carriers. However, in BRCA2 mutation carriers, RRBSO was associated with a statistically significant decreased overall incidence of breast cancer, HR = 0.2 (confidence interval 0.44-0.913, p = 0.038). Breast cancer incidence was lower after 5, 10,15 and 20 years in BRCA2-mutation carriers with RRBSO compared to no-RRBSO. Age at menarche, age at surgery, parity and oral contraceptive use were not significant risk factors for breast cancer. Hormone replacement therapy was used by 62 mutation carriers, 52 in the RRBSO group and 10 in the no-RRBSO group, and its use did not alter breast cancer risk (p = 0.463). Conclusions: According to our findings, RRBSO is associated with a reduced risk of breast cancer only in BRCA2 mutation carriers, regardless of HRT use.

Hormone replacement therapy in women with cancer and risk of cancer-specific mortality and cardiovascular disease: a protocol for a cohort study from Scotland and Wales

BackgroundHormone replacement therapy (HRT) is widely used and has proven benefits for women with menopausal symptoms. An increasing number of women with cancer experience menopausal symptoms but the safety of HRT use in women with cancer is unclear. There are particular concerns that HRT could accelerate cancer progression in women with cancer, and also that HRT could increase the risk of cardiovascular disease in such women. Therefore, our primary aim is to determine whether HRT use alters the risk of cancer-specific mortality in women with a range of common cancers. Our secondary objectives are to investigate whether HRT alters the risk of second cancers, cardiovascular disease, venous thromboembolism and all-cause mortality.MethodsThe study will utilise independent population-based data from Wales using the SAIL databank and Scotland based upon the national Prescribing Information System. The study will include women newly diagnosed with common cancers from 2000 to 2016, identified from cancer registries. Women with breast cancers will be excluded. HRT will be ascertained using electronic prescribing in Wales or dispensing records in Scotland. The primary outcome will be time to cancer-specific mortality from national mortality records. Time-dependent cox regression models will be used to calculate hazard ratios (HR) and 95% confidence intervals (95% CIs) for cancer specific death in HRT users compared with non-users after cancer diagnosis after adjusting for relevant confounders, stratified by cancer site. Analysis will be repeated investigating the impact of HRT use immediately before cancer diagnosis. Secondary analyses will be conducted on the risk of second cancers, cardiovascular disease, venous thromboembolism and all-cause mortality. Analyses will be conducted within each cohort and pooled across cohorts.DiscussionOur study will provide evidence to inform guidance given to women diagnosed with cancer on the safety of HRT use and/or guide modifications to clinical practice.