Use Of Hormone Replacement Therapy Research Articles

Abstract B083: The associations of breast density, hormone use, family history, reproductive and lifestyle factors with triple negative breast cancer: a systematic review and meta-analysis

Abstract Background: Triple negative breast cancer (TNBC) has poor prognosis compared to other breast cancer subtypes. Objectives: This systematic review and meta-analysis examines whether established breast cancer risk factors are associated with TNBC in adult females.Data Sources: Studies were searched on EMBASE, Medline, SCOPUS and grey literature with no limit on the date of publication. The search string included MeSH terms of the exposures of interest and TNBC. References of included studies were also searched. Study Selection: The exposures of interest included parity, breastfeeding, duration of breastfeeding, age at menarche, age at first live birth, oral contraceptive (OCP) use, duration of OCP use, use of hormone replacement therapy (HRT), family history, body mass index (BMI), alcohol use, smoking and breast density. Studies that compared exposures of interest between women diagnosed with TNBC versus cancer-free women.Main outcomes and Measures: The main outcome of interest was TNBC. The effect measures, weighted odds ratios, were estimated from random effects models. Sensitivity analyses stratified by menopausal status and using the leave one out meta-analysis (LOOM) method were performed.Data Extraction and Synthesis: Data extraction and synthesis was performed as per PRISMA guidelines. Four reviewers independently screened the search results in a blinded manner and conflicts were resolved by discussion. Study quality was determined using the Newcastle-Ottawa scale for case control studies and cohort studies. Data extraction was performed independently by four reviewers and one reviewer checked 30% of work of each other reviewer. Odds ratios were extracted and data were meta-analyzed using a random effects model. Results: Thirty-three studies were included. Family history, longer duration of oral contraceptive use, and higher breast density were significantly associated with increased risk for TNBC, and later age at menarche and breastfeeding were protective against TNBC. Later age at first birth was protective against TNBC. Parity, HRT, alcohol, smoking, and BMI were not significantly associated with risk for TNBC. Conclusion: These findings further clarify differences in etiology between ER/PR+HER2- and TNBC, highlighting the need to identify additional actionable risk factors for TNBC to improve prevention and early detection of these poor prognosis breast tumors. Citation Format: Nitya Kumar, Sarah Ehsan, Shahana Banerjee, Claudia Fernandez Perez, Isabelle Lhuilier, Jilian Neuner, Tara-Friebel Klinger, Bindhu Nair, Sara Anjum Niinuma, Shivangi Nampoothiri, Anne Marie McCarthy. The associations of breast density, hormone use, family history, reproductive and lifestyle factors with triple negative breast cancer: a systematic review and meta-analysis [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr B083.

Investigating the synergistic effects of hormone replacement therapy, apolipoprotein E and age on brain health in the UK Biobank.

Global prevalence of Alzheimer's Disease has a strong sex bias, with women representing approximately two-thirds of the patients. Yet, the role of sex-specific risk factors during midlife, including hormone replacement therapy (HRT) and their interaction with other major risk factors for Alzheimer's Disease, such as apolipoprotein E (APOE)-e4 genotype and age, on brain health remains unclear. We investigated the relationship between HRT (i.e., use, age of initiation and duration of use) and brain health (i.e., cognition and regional brain volumes). We then consider the multiplicative effects of HRT and APOE status (i.e., e2/e2, e2/e3, e3/e3, e3/e4 and e4/e4) via a two-way interaction and subsequently age of participants via a three-way interaction. Women from the UK Biobank with no self-reported neurological conditions were included (N = 207,595 women, mean age = 56.25 years, standard deviation = 8.01 years). Generalised linear regression models were computed to quantify the cross-sectional association between HRT and brain health, while controlling for APOE status, age, time since attending centre for completing brain health measure, surgical menopause status, smoking history, body mass index, education, physical activity, alcohol use, ethnicity, socioeconomic status, vascular/heart problems and diabetes diagnosed by doctor. Analyses of structural brain regions further controlled for scanner site. All brain volumes were normalised for head size. Two-way interactions between HRT and APOE status were modelled, in addition to three-way interactions including age. Results showed that women with the e4/e4 genotype who have used HRT had 1.82% lower hippocampal, 2.4% lower parahippocampal and 1.24% lower thalamus volumes than those with the e3/e3 genotype who had never used HRT. However, this interaction was not detected for measures of cognition.No clinically meaningful three-way interaction between APOE, HRT and age was detected when interpreted relative to the scales of the cognitive measures used and normative models of ageing for brain volumes in this sample. Differences in hippocampal volume between women with the e4/e4 genotype who have used HRT and those with the e3/e3 genotype who had never used HRT are equivalent to approximately 1-2 years of hippocampal atrophy observed in typical health ageing trajectories in midlife (i.e., 0.98%-1.41% per year). Effect sizes were consistent within APOE e4/e4 group post hoc sensitivity analyses, suggesting observed effects were not solely driven by APOE status and may, in part, be attributed to HRT use. Although, the design of this study means we cannot exclude the possibility that women who have used HRT may have a predisposition for poorer brain health.

Should hormone replacement therapy (any route of administration) be considered in all postmenopausal women with lower urinary tract symptoms? Report from the ICI-RS 2023.

This International Consultation on Incontinence-Research Society report aims to summarize the evidence and uncertainties regarding the use of hormone replacement therapy by any route in the management of lower urinary tract symptoms (LUTS) including recurrent urinary tract infections (rUTI), with a review of special considerations for the elderly. Research question proposals to further this field have been highlighted. An overview of the existing evidence, guidelines, and consensus regarding the use of topical or systemic estrogens in the management of LUTS. There are currently evidence and recommendations to offer topical estrogens to postmenopausal women with overactive bladder symptoms as well as postmenopausal women with rUTIs. Systemic estrogens however have been shown in a meta-analysis to have a negative effect on LUTS and, therefore are not currently recommended. Although available evidence and recommendations exist for the use of topical estrogens, few women are commenced on these in primary care. There remain large gaps still within our knowledge of the use of estrogens within the management of LUTS, particularly on when it should be commenced, the length of time treatment should be continued for, and barriers to prescribing.

Explaining variability in early stages of [18F]-flortaucipir tau-PET binding: Focus on sex differences.

Female sex is associated with increased [18F]-flortaucipir signal, which may be affected by amyloid pathology, age, and off-target binding in skull and meninges. In this cross-sectional study comprising 52 females and 52 matched males, we examined sex-related differences in regional tau-positron emission tomography (PET) with and without considering off-target binding. We assessed the respective contributions of sex, age, amyloid-PET burden, and off-target binding to tau-PET signal. We explored associations between age at menopause and hormone replacement therapy (HRT) use with regional tau-PET signals. Female sex was associated with increased regional tau both independently and interactively with amyloid, but amyloid-independent associations were largely reduced when controlling for off-target binding. Age but not age*sex interactions explained a small but significant amount of tau-PET signal in temporoparietal regions. Considering the sample size and limited range of amyloid-PET burden, no clear associations between regional tau-PET signals and age at menopause or HRT use could be found. Female sex is associated with increased [18F]-flortaucipir signal mainly through its interaction with amyloid.

Hormone replacement therapy in gynecological cancer survivors and BRCA mutation carriers: a MITO group survey.

Early iatrogenic menopause in gynecological cancer survivors and BRCA mutation (BRCAm) carriers undergoing risk-reducing salpingo-oophorectomy (RRSO) is a major health concern. Hormone replacement therapy (HRT) is the most effective remedy, but remains underused in clinical practice. The Multicenter Italian Trials in Ovarian cancer and gynecologic malignancies (MITO) group promoted a national survey to investigate the knowledge and attitudes of healthcare professionals regarding the prescription of HRT. The survey consisted of a self-administered, multiple-choice 45-item questionnaire, available online to all MITO members for 2 months starting from January 2022. A total of 61 participants completed the questionnaire (47 out of 180 MITO centers; compliance: 26.1%). Most respondents were female (73.8%), younger than 50 years (65.6%), and gynecologic oncologists (55.7%), working in public general hospitals (49.2%). An 84.4% of specialists actively discuss HRT with patients and 51.0% of patients ask the specialist for an opinion on HRT. The rate of specialists globally in favor of prescribing HRT was 22.9% for ovarian cancer, 49.1% for cervical cancer, and 8.2% for endometrial cancer patients. Most respondents (70.5%) believe HRT is safe for BRCA-mutated patients after RRSO. Nearly 70% of physicians prescribe systemic HRT, while 23.8% prefer local HRT. Most specialists recommend HRT for as long as there is a benefit and generally for up to 5 years. Real-world data suggest that many healthcare professionals still do not easily prescribe HRT for gynecological cancer survivors and BRCA mutation carriers after RRSO. Further efforts are required to implement the use of HRT in clinical practice and to support both clinicians in recommending HRT and patients in accepting it.

Does exogenous hormonal therapy affect the risk of glioma among females: A systematic review and meta-analysis.

The effect of exogenous hormone replacement therapy (HRT) and oral contraceptive pills (OCPs) on glioma risk in females is unclear despite numerous studies; hence, we conducted a meta-analysis to evaluate this relationship. Studies investigating the impact of exogenous female hormones on glioma risk were retrieved by searching 4 databases from inception until September 2022. Articles of any design, such as case-control and cohort studies, proving the relative risk (RR), odds ratio (OR), or hazard ratio were included. Summary OR values were calculated using a random effects model. Both HRT and OCP use of any duration decreased the risk of developing glioma [HRT OR = 0.78, 95% CI 0.66-0.91, P = .00; OCP: OR = 0.80, 95% CI 0.67-0.96, P = .02]. When stratified by duration of use, HRT use >1 year significantly reduced glioma risk (<1 year: OR = 0.82, 95% CI 0.63-1.07, P = 0.15; 1-5 years: OR = 0.79, 95% CI 0.67-0.92, P = .00; 5-10 years: OR = 0.80, 95% CI 0.66-0.97, P = .02; >10 years: OR = 0.69, 95% CI 0.54-0.88, P = .00). In contrast, only OCP use for >10 years significantly reduced glioma risk (<1 year: OR = 0.72, 95% CI 0.49-1.05, P = .09; 1-5 years: OR = 0.88, 95% CI 0.72-1.02, P = .09; 5-10 years: OR = 0.85, 95% CI 0.65-1.1, P = 0.21; >10 years: OR = 0.58, 95% CI 0.45-0.74, P = .00). Our pooled results strongly suggest that sustained HRT and OCP use is associated with reduced risk of glioma development.

Effect of baseline oestradiol serum concentration on the efficacy of anastrozole for preventing breast cancer in postmenopausal women at high risk: a case-control study of the IBIS-II prevention trial

An increased risk of breast cancer is associated with high serum concentrations of oestradiol and testosterone in postmenopausal women, but little is known about how these hormones affect response to endocrine therapy for breast cancer prevention or treatment. We aimed to assess the effects of serum oestradiol and testosterone concentrations on the efficacy of the aromatase inhibitor anastrozole for the prevention of breast cancer in postmenopausal women at high risk. In this case-control study we used data from the IBIS-II prevention trial, a randomised, controlled, double-blind trial in postmenopausal women aged 40-70 years at high risk of breast cancer, conducted in 153 breast cancer treatment centres across 18 countries. In the trial, women were randomly assigned (1:1) to receive anastrozole (1 mg/day, orally) or placebo daily for 5 years. In this pre-planned case-control study, the primary analysis was the effect of the baseline oestradiol to sex hormone binding globulin (SHBG) ratio (oestradiol-SHBG ratio) on the development of all breast cancers, including ductal carcinoma in situ (the primary endpoint in the trial). Cases were participants in whom breast cancer was reported after trial entry and until the cutoff on Oct 22, 2019, and who had valid blood samples and no use of hormone replacement therapy within 3 months of trial entry or during the trial. For each case, two controls without breast cancer were selected at random, matched on treatment group, age (within 2 years), and follow-up time (at least that of the matching case). For each treatment group, we applied a multinominal logistic regression likelihood-ratio trend test to assess what change in the proportion of cases was associated with a one-quartile change in hormone ratio. Controls were used only to determine quartile cutoffs. Profile likelihood 95% CIs were used to indicate the precision of estimates. A secondary analysis also investigated the effect of the baseline testosterone-SHBG ratio on breast cancer development. We also assessed relative benefit of anastrozole versus placebo (calculated as 1 - the ratio of breast cancer cases in the anastrozole group to cases in the placebo group). The trial was registered with ISRCTN (number ISRCTN31488319) and completed recruitment on Jan 31, 2012, but long-term follow-up is ongoing. 3864 women were recruited into the trial between Feb 2, 2003, and Jan 31, 2012, and randomly assigned to receive anastrozole (n=1920) or placebo (n=1944). Median follow-up time was 131 months (IQR 106-156), during which 85 (4·4%) cases of breast cancer in the anastrozole group and 165 (8·5%) in the placebo group were identified. No data on gender, race, or ethnicity were collected. After exclusions, the case-control study included 212 participants from the anastrozole group (72 cases, 140 controls) and 416 from the placebo group (142 cases, 274 controls). A trend of increasing breast cancer risk with increasing oestradiol-SHBG ratio was found in the placebo group (trend per quartile 1·25 [95% CI 1·08 to 1·45], p=0·0033), but not in the anastrozole group (1·06 [0·86 to 1·30], p=0·60). A weaker effect was seen for the testosterone-SHBG ratio in the placebo group (trend 1·21 [1·05 to 1·41], p=0·011), but again not in the anastrozole group (trend 1·18 [0·96 to 1·46], p=0·11). A relative benefit of anastrozole was seen in quartile 2 (0·55 [95% CI 0·13 to 0·78]), quartile 3 (0·54 [0·22 to 0·74], and quartile 4 (0·56 [0·23 to 0·76]) of oestradiol-SHBG ratio, but not in quartile 1 (0·18 [-0·60 to 0·59]). These results suggest that serum hormones should be measured more routinely and integrated into risk management decisions. Measuring serum hormone concentrations is inexpensive and might help clinicians differentiate which women will benefit most from an aromatase inhibitor. Cancer Research UK, National Health and Medical Research Council (Australia), Breast Cancer Research Foundation, and DaCosta Fund.

The effectiveness of estrogen therapy and aerobic exercise combined with resistance training therapy in postmenopausal womens osteoporosis

Postmenopausal osteoporosis (PMOP) usually happens five to ten years following a womans menopause, and some women over 50 in China suffer from PMOP. Hormone replacement therapy (HRT) and aerobics combined with resistance training are the two promising osteoporosis interventions, but few studies have compared their efficacy. The mechanisms by which exercise treatment and hormone replacement therapy affect bone mineral density (BMD) are examined in this review and other health parameters in postmenopausal osteoporosis patients. As studied in this paper, estrogen improves osteoporosis. However, risks such as venous thromboembolism limit the long-term use of HRT. In terms of exercise therapy, a direct comparison of aerobic exercise combined with resistance exercise and HRT showed that supervised exercise improved BMD more than HRT and that exercise also boosted metabolism and avoided the risks of HRT. In conclusion, aerobic and resistance training provides a safer alternative to HRT for managing postmenopausal osteoporosis, and further studies should optimize exercise regimens.

The effect of APOEƐ4 on neurocognitive decline is accentuated by female sex and menopause: Identification of mitigating interventions

AbstractBackgroundTwo thirds of those living with AD are female. Age‐standardised AD prevalence is consistently higher at all ages over 70 years in women versus men. The aetiology of the accelerated neurophysiological decline in females is poorly understood. Here we investigate the independent and interactive impact of APOE4 carrier status and menopause.MethodTargeted replacement (APOE3‐TR and APOE4‐TR) rodent models and human cohort studies (European Prevention of Alzheimer’s Dementia (EPAD) and UK Biobank (UKB)) were used to investigate the impact of APOE4, menopause and hormone replacement therapy (HRT) on cognition, brain volumes (assessed by MRI), omega‐3 fatty acid status and synaptic function. In rodents, menopause is elicited by the administration of 4‐vinylcyclohexene diepoxide (VCD), which induces a human‐like “perimenopausal” phenotype, whilst maintaining ovarian tissue integrity.ResultsIn EPAD, using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) test battery, HRT use in APOE4 only was associated with higher overall cognition and (delayed) memory scores and larger entorhinal and amygdala volumes in APOE4 only. Earlier HRT introduction was associated with larger hippocampal volumes. In UKB, HRT use was associated with improved memory in APOE4/E4. In mice, VCD administration reduced recognition memory, brain docosahexaenoic acid (DHA, omega‐3 fatty acid) levels, and altered synaptic plasticity biomarkers in APOE4‐TR animals, which was mitigated by DHA supplementation (1).ConclusionAn increased penetrance of the APOE4 genotype during the menopausal transition is likely to contribute to the higher incident AD in females, and in APOE4 females versus non‐carriers. HRT and DHA intervention during the menopausal transition, as a critical window of opportunity, may represent effective strategies to support cognitive health into older age in this ‘at‐risk’ (APOE4 female) group, which typically represent 12% of Caucasian populations compared and 33‐50% of AD.1. Pontifex MG et al., FASEB J. 2021 May;35(5):e21583

The impact of female reproductive period length, parity, and hormonal replacement therapy on cognitive performance

AbstractBackgroundSome evidence suggests that Alzheimer’s disease and cognitive decline are more prevalent in women and that risk factors specific to the female sex could be involved. The aim of this study is to estimate the association between the length of female reproductive period, parity, hormonal replacement therapy (HRT) and later life cognition in a large cohort of Brazilian older adults.MethodWe analyzed cross‐sectional data from 4,558 women and 3,799 men. Cognitive function was measured through a global cognitive score composed of orientation, verbal fluency, and memory tests. Age at menarche and menopause, parity and use of HRT were self‐reported. Multiple linear regression analyses were performed to identify hormone related factors associated with current cognitive functioning in women, adjusting for relevant covariates. Afterwards, we performed an analysis among men for number of children.ResultHigher parity was associated with worse cognitive functioning (β = ‐0.01, p &lt; 0.001), while lengthier reproductive life (β = 0.00, p = 0.001) and HRT use (β = 0.04, p = 0.023) were associated with better cognitive performance. We performed a sensitivity analysis, after dividing women into parity groups. When compared with 0 births, the group with 1‐5 had better cognition (β = 0.08, p = 0.001), while the other groups displayed no differences. After excluding nulliparous women, compared to women with 1‐5 births, women with 6‐10 (β = ‐0.1, p &lt; 0.001) and 11+ births (β = ‐0.16, p &lt; 0.001) had an increasingly worse cognitive performance. We also analyzed number of children data for men, which had no impact on cognition (β = ‐0.00, p = 0.688).ConclusionResults indicate a protective effect on cognition of longer reproductive life, HRT use and 1‐5 childbirths, when compared to being nulliparous or having 6+ births. Among men, number of children was not associated with cognitive performance. These findings indicate a positive effect of estrogen on the brain, unrelated to current offspring. This effect might be mitigated by frequent pregnancies, but a smaller number of childbirths may not be enough to exert an impact, while bringing positive psychological effects that are protective for cognition.

Abstract B145: Validation of a colorectal cancer risk prediction model in US Black women

Abstract Background: The National Cancer Institute’s Colorectal Cancer Risk Assessment Tool (NCI-CCRAT) estimates an individual's five-year risk of developing colorectal cancer. It was developed by estimating relative risks from a population of US White women and men and incorporating race, gender, and age-specific incidence data from population-based cancer registries. However, the model performance has not been assessed for Black Americans, who have the highest colorectal cancer incidence and mortality rates of any US racial/ethnic group. Methods: The NCI-CCRAT estimates the absolute risk of colorectal cancer based on an individual’s age, sex, family history of colorectal cancer, sigmoidoscopy/colonoscopy, polyps, smoking, physical activity, regular aspirin/nonsteroidal anti-inflammatory drug (NSAID) use, vegetable intake, body mass index, and hormone replacement therapy use. Validation of the NCI-CCRAT was performed using prospective data from 57,558 participants ages 40 to 84 years in the Black Women's Health Study (BWHS). We predicted 5-year absolute risk using data from 2001 through 2015 in three 5-year prediction periods: 2001-2005, 2006-2010, and 2011-2015. To assess model performance, we computed calibration by comparing the expected number of colorectal cancer cases predicted by the model to the observed number of cases (E/O) in the BWHS overall and in subgroups of the population. We assessed discriminatory accuracy by calculating the area under the curve (AUC). Results: During follow-up from 2001 through 2015 (634,512 person-years), 433 BWHS participants developed invasive colorectal cancer. Based on the NCI-CCRAT, 543 cases were expected. The NCI-CCRAT was well-calibrated in the first 5-year prediction period (2001-2005 E/O=1.03, 95% CI: 0.88–1.21), but the model overestimated risk in the subsequent 5-year prediction periods, with E/O=1.30 for 2006-2010 and E/O=1.44 for 2011-2015. The overall E/O ratio was 1.25 (95% confidence interval: 1.14–1.38), indicating that NCI-CCRAT overestimated the number of cases in this population of Black women. Of note, associations with colorectal cancer were weaker in the BWHS than in the development cohort for vigorous physical activity, aspirin/NSAID use, vegetable intake, and body mass index. We estimated discriminatory accuracy only for the first 5-year prediction period (2001-2005, N cases=151) for which the model was well calibrated, and obtained an age-adjusted AUC of 0.61 (95% CI: 0.57–0.66). Conclusions: The NCI-CCRAT overestimated the overall number of colorectal cancer cases by 25% in this prospective cohort of Black women, possibly due to population-specific differences in the relative risks of key factors driving colorectal cancer incidence. Discriminatory accuracy was similar to measures from the original validation cohort of White women and men. Impact: This study suggests that further research is needed to determine the most important predictors of colorectal cancer etiology in Black women and to develop and test a colorectal cancer risk prediction model for Black Americans. Citation Format: Jessica L. Petrick, Nelsy Castro-Webb, Gary R. Zirpoli, Kerrie P. Nelson, Julie R. Palmer, Ruth M. Pfeiffer. Validation of a colorectal cancer risk prediction model in US Black women [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B145.

Does Health & Her app use improve menopausal symptoms? A longitudinal cohort study

ObjectivesThe Health & Her app provides menopausal women with a means of monitoring their symptoms, symptom triggers and menstrual periods, and enables them to engage in a variety of digital...

The Relationship Between Mood and Sleep in Different Female Reproductive States.

Mood and sleep are tightly interrelated. Mood and sleep symptoms and disorders are more common in women than in men and often associated with reproductive events. This article reviews the current literature on the reciprocal relationships between mood and sleep across reproductive phases in women, such as menstrual cycle and related disorders, pregnancy, climacteric, and use of hormonal contraception and hormone replacement therapy. Mood and sleep symptoms seem to covary in relation to physiologic and pathologic reproductive conditions, although the relationship seems more clear for subjective than objective sleep.

Reproductive Factors Linked With Myocardial Fibrosis: MESA (Multi-Ethnic Study of Atherosclerosis)

BackgroundRecent evidence has shown that reproductive factors are associated with an increased risk of heart failure with preserved ejection fraction in women. However, the pathogenic pathways underlying this relationship are unclear. Subclinical myocardial fibrosis has been found to be a common pathway in a large proportion of patients with heart failure with preserved ejection fraction. ObjectivesThis study examined the relationship between vital reproductive factors (parity, pregnancy, age at menopause, and use of hormone replacement therapy [HRT]) with interstitial myocardial fibrosis (IMF) and myocardial scar measured by cardiac magnetic resonance imaging (CMR) T1 mapping and late gadolinium enhancement, respectively. MethodsThere were 596 female participants (mean age 67 ± 8 years) enrolled in MESA (Multi-Ethnic Study of Atherosclerosis) who had complete parity data and underwent CMR. Parity was categorized as 0 live births, 1 to 2, 3 to 4, and ≥5 live births. Multivariable regression models were constructed to assess the associations of parity status, history of null gravidity, age at menopause and HRT with CMR obtained measures of IMF (extracellular volume [ECV], native-T1 time) and myocardial scar. ResultsWomen with a history of nulliparity had greater ECV% (β = 0.95 ± 0.28, P = 0.001) and native-T1 ms (β = 10.6 ± 4.9, P = 0.03) than those who had 1 to 2 live births. These associations were independent of age, traditional cardiovascular risk factors, and interim cardiovascular events. Similar associations were found for women with a history of null gravidity compared to those with a history of pregnancy (ECV% [β = 0.7 ± 0.3, P = 0.02] and native-T1 ms [β = 10.6 ± 5.2, P = 0.04]). There was no association between age at menopause and HRT with markers of IMF. There were no associations between parity status, null gravidity, and age of menopause with the presence of myocardial scar; however, those who used HRT were independently associated with a lesser risk of myocardial scar (OR: 0.20; 95% CI: 0.05-0.82). ConclusionsIn a multiethnic cohort, women with a history of nulliparity or null gravidity had greater IMF defined by CMR, while those who used HRT were less likely to have myocardial scar.

Age at menopause and the risk of stroke: observational and mendelian randomisation analysis in 204,244 postmenopausal women

Abstract Background Observational studies have shown that women with an early menopause are at higher risk of stroke compared to women with a later menopause. However, associations with stroke subtypes are inconsistent and the causality is unclear. Purpose We conducted a large-scale analysis to investigate the observational association between age at menopause and different types of stroke accompanied by a Mendelian Randomisation analysis to evaluate causality. Methods We analysed data of the UK Biobank and EPIC-CVD study. Postmenopausal women without a history of stroke at baseline were eligible for inclusion. The study endpoints were total stroke and stroke subtypes (i.e., ischaemic stroke, haemorrhagic stroke, intracerebral haemorrhage, and subarachnoid haemorrhage). We investigated the observational association between age at menopause and risk of stroke using Cox-regression analysis in each study separately before combining effect sizes using random-effects meta-analysis. Cox-regression analyses were progressively adjusted for (1) age, (2) smoking status, body mass index, glycated haemoglobin, total cholesterol, and hypertension, and (3) ever use of hormone replacement therapy and age at menarche. We used two-sample Mendelian Randomisation analysis to study whether there is a causal relationship between genetically proxied age at menopause and risk of stroke. Results A total of 204,244 women were included (7,883 from EPIC-CVD [5,292 from the sub-cohort]; 196,361 from the UK Biobank). Pooled mean baseline age was 58.9 years (SD 5.8) and pooled mean age at menopause was 47.8 years (SD 6.2). Natural menopause occurred in 77.6% of all women. Over a median follow-up of 12.6 years (IQR 11.8, 13.3), 6,770 women experienced a stroke. In multivariable adjusted observational analyses, the pooled hazard ratios per five years younger age at menopause were 1.09 (95% CI: 1.07, 1.12) for stroke, 1.09 (1.06, 1.13) for ischaemic stroke, 1.10 (1.04, 1.16) for haemorrhagic stroke, 1.14 (1.08, 1.20) for intracerebral haemorrhage, and 1.00 (0.84, 1.20) for subarachnoid haemorrhage. The Mendelian Randomization analysis found no evidence for a causal relationship between genetically proxied age at menopause and risk of any type of stroke. Conclusion Earlier age at menopause is associated with, but no causally related to the risk of stroke.

Abstract 14112: Reproductive Risk Factors and Pulmonary Arterial Hypertension in Women

Introduction: Pulmonary arterial hypertension (PAH) is a devastating disease that affects women more often than men. The female predominance has increased over time; recent U.S. cohorts demonstrate a female:male ratio of nearly 4:1. The role of women-specific risk, such as reproductive exposures, is poorly understood in the pathophysiology of PAH. Hypothesis/Goals: We hypothesize that reproductive exposures influence the development and/or severity of PAH in women. We sought to investigate the role of reproductive factors and contribution of exogenous estrogen exposures to PAH onset and severity. Methods: Using reproductive history/exposure questionnaires from 390 women with PAH, enrolled in both the PAH Biobank and United States Pulmonary Hypertension Scientific Registry, we conducted linear regression analyses to assess the association between individual disease severity variables, as well as REVEAL Lite 2.0 scores, and patient reported reproductive variables as the predictors (Table 1). We adjusted for potential confounders including age, race, BMI, and PAH sub-group (idiopathic, heritable, or associated). Results: We found that younger menopause age, less than or equal to 40 years old, associates with a lower cardiac index (CI) at diagnosis [β -0.57, p 0.02]. The association persisted when controlling for use of hormone replacement therapy (HRT). There was a trend toward lower CI in those with menopause age of 41 to 50 years old, but not statistically significant [p 0.10]. Ever use of HRT was associated with a higher pulmonary vascular resistance [β 1.6, p 0.05] and lower CI [β -0.28, p 0.01] at diagnosis. Conclusion: Premature menopause (age less than 40 years) and ever use of HRT associate with worse hemodynamics at diagnosis in women with PAH, including lower cardiac index. Further investigations into reproductive exposures may offer an opportunity for more comprehensive risk factor screening and modification by physicians treating PAH patients.

Abstract 18381: Long-Term Coronary Artery Disease Risk in Female Adults With Surgically-Induced Menopause : A Systematic Review

Introduction: Coronary artery disease (CAD) is a leading cause of morbidity and mortality in female adults. Prior studies have suggested an association between surgically-induced menopause (SIM) and long-term CAD risk. Yet, the pathophysiology and clinical significance of this relationship remains unclear. As SIM causes a premature cessation of potentially cardioprotective hormones, this review aimed to further investigate if SIM is a risk factor for CAD. Methods: SCOPUS, Web of Science, Cochrane Library, OVID/Embase, SciELO, and LILACS were searched from inception to April 2023 for observational studies reporting the effects of hysterectomy, oophorectomy, and/or salpingectomy prior to age fifty on long-term CAD risk. Results: Among 3056 identified records, nineteen studies were included with a combination of benign and malignant surgical indications. The studies reported on coronary heart disease (n=6), CAD (n=4), ischemic heart disease (n=3), and myocardial infarction (n=7). Sixteen articles with an average of 106,433 participants per study demonstrated a significantly increased risk of CAD following SIM (Table 1). In particular, hysterectomy with or without bilateral oophorectomy, and bilateral oophorectomy alone were found to have the most profound influence. Unilateral oophorectomy or hysterectomy with salpingo-oophorectomy did not appear to increase CAD risk. Average follow-up duration after SIM ranged from six to twenty-four years. Five studies adjusted for post-menopausal hormone replacement therapy use. Conclusions: SIM may elevate long-term CAD risk following hysterectomy and/or bilateral oophorectomy. Given that the majority of SIM are performed pre- or peri-menopausal for benign indications, understanding the associated cardiovascular risks is vital for informed decision-making, early detection, and prevention.

Follow-up analysis of sex hormone levels and prognosis in women after hematopoietic stem cell transplantation

Objective: To investigate the levels of sex hormone and fertility in female patients after hematopoietic stem cell transplantation (HSCT), as well as their correlation with conditioning regimens, and analyse the effect of hormone replacement therapy (HRT) in young women after HSCT. Methods: Retrospective case series study. The clinical data of 147 women who underwent HSCT in the First Affiliated Hospital of Soochow University from January 2010 to January 2021 were retrospectively analyzed. The sex hormone levels were measured and followed-up, and the survival, menstrual fertility and the use of HRT of the patients were also followed-up. The sex hormone levels were measured after transplantation, and the ovarian function was evaluated. Independent sample t test and χ2 test were used for comparison between the two groups. Results: The median age of the 147 patients was 26 (range, 10-45) years. Of them, 135 patients received allogeneic HSCT and 12 patients received autologous HSCT. Furthermore, 129 patients received myeloablative conditioning, and 18 patients received reduced conditioning dose. The median follow-up time was 50 months (range, 18-134 months). Five patients died of disease recurrence during follow-up. Of the 54 patients with subcutaneous injection of zoladex, three recovered menstruation spontaneously after transplantation, and all of them were myeloablative conditioning patients, one patient gave birth to twins through assisted reproductive technology. Ninety-three patients did not use zoladex before conditioning, two patients with aplastic anemia with non-myeloablative transplantation resumed menstruation spontaneously, and conceived naturally. The level of follicle stimulating hormone after transplantation in patients receiving myeloablative conditioning regimen was significantly higher than that in patients receiving reduced-dose conditioning regimen [(95.28±3.94) U/L vs. (71.85±10.72) U/L, P=0.039]. Among 147 patients, 122 patients developed premature ovarian failure, 83 patients received sex hormone replacement therapy after transplantation, and 76 patients recovered menstruation and improved endocrine function. Conclusions: The incidence of premature ovarian failure is high in female patients after HSCT, and patients have a chance at natural conception. Reducing the dose of conditioning regimen and the application of zoladex before transplantation can reduce ovarian of conditioning drugs. HRT after transplantation can partially improve the endocrine function of patients.

Migraine in perimenopausal women

Sex hormones have a significant influence on the course of migraine in women. Perimenopause is accompanied by unstable cycle length, vasomotor, urogenital and other symptoms, while the course of migraine usually worsens. In postmenopause ovarian follicular function decreases, and the course of migraine improves in most cases. However, a number of studies have shown that the course of migraine does not change or even worsen after menopause. Perimenopausal and postmenopausal migraine patients are also more likely to suffer from vasomotor symptoms. Hormone replacement therapy is prescribed to relieve vasomotor symptoms, which may worsen the course of migraine. In this review, the influence of perimenopause and postmenopause on the course of migraine, the use of hormone replacement therapy, and methods to relieve and prevent attacks in patients with migraine are examined in detail.

Establishment of a Labile Bound Copper Reference Interval in a Healthy Population via an Inductively Coupled Plasma Mass Spectrometry Dual Filtration-Based Assay.

Clinical testing for Wilson disease (WD) is potentially challenging. Measuring the fraction of labile bound copper (LBC) to total copper may be a promising alternative diagnostic tool with better sensitivity and specificity than some current biomarker approaches. A dual filtration-based inductively coupled mass spectrometry (ICP-MS) assay to measure LBC in serum was developed. To establish a reference interval for LBC and LBC to total copper (LBC fraction) in a healthy adult population, and to examine associations between total copper, LBC, and LBC fraction with age, sex, menopausal status, hormone replacement therapy, and supplement use. Serum samples were collected from healthy male (n = 110) and female (n = 104) patients between the ages of 19 and 80 years. Total copper and LBC were analyzed using ICP-MS. Results were used to calculate the LBC fraction. Reference intervals were calculated for the 2.5th and 97.5th percentiles for both LBC and LBC fraction. The reference intervals for LBC were determined to be 13 to 105 ng/mL and 12 to 107 ng/mL for female and male patients, respectively. The reference intervals for the LBC fraction were 1.0% to 8.1% and 1.2% to 10.5% for female and male patients, respectively. No significant associations were found regarding age, menopausal status, hormone replacement therapy, or vitamin and supplement use. Sex-specific reference intervals have now been established for LBC and LBC fraction. These data in conjunction with further testing of WD populations can be used to assess the sensitivity and specificity of LBC fraction in screening, monitoring, and diagnosis.