Use Of Hormone Replacement Therapy Research Articles

Abstract 4138306: Impact of Early Menopause and Hormonal Replacement Therapy on Aortic Stenosis Progressio

Background: Early menopause is associated with an increased risk of cardiovascular disease and mortality in women. The present study aimed to examine the impact of early menopause and hormonal replacement therapy (HRT) on the progression of aortic stenosis (AS). Methods: Thirty-three postmenopausal women (mean age 65 ± 10 years) with mild or moderate AS prospectively recruited in the PROGRESSA study (NCT01679431) were included in this sub-analysis. All patients underwent multidetector computed tomography and Doppler-echocardiography at least twice during follow-up to assess both anatomic and hemodynamic AS severity, based on aortic valve calcification (AVC), mean pressure gradient (MG), and aortic valve area indexed to body surface area (AVA). Annualized changes in AVC, MG and AVAi were calculated between baseline and the last follow-up. Results: Over a median follow-up of 2 [1-4] years, early menopausal women had a faster progression rate of AVC, MG, and AVAi compared to other women: (100[58-130] vs. 23[2-71] AU/year, p=0.03); (2.37[0.82-3.61] vs. 0.31[0.01-1.78] mmHg/year, p=0.04); and (-0.12[-0.23-0.002] vs. -0.004[-0.07-0.08] cm 2 /m 2 /year, p=0.08) respectively. In multivariate analysis adjusted for age, AS severity at baseline, and comorbidities, early menopause remained significantly associated with faster AVC progression (p=0.003). Moreover, after comprehensive adjustment, women who received HRT (45%) had a slower progression rate of AVC (20[10-42] AU/year vs. 62[2-100], adjusted p=0.04). Conclusion: Early menopause is associated with faster progression of AS, both anatomically and hemodynamically. However, the use of HRT is associated with slower progression of AS. Integrating female-specific risk factors, particularly menopausal history and hormonal therapy status, into the clinical management of AS could enhance patient care.

Menopause Matters: Results of a National Survey of Rheumatoid Arthritis Patients in the UK.

The effects of the menopause have received a lot of attention in the press recently. Anecdotally, patients report changes in their arthritis around the menopause, either onset or aggravation of symptoms. Clearly, there are hormonal influences on arthritis with the female predominance, onset of RA around times of hormonal change and improvement during pregnancy. We were interested in exploring the patient perspective to inform future research and educational needs. A national survey was organised through the National Rheumatoid Arthritis Society (NRAS), using their database of people with RA and online community who self-selected as peri menopausal, menopausal or post-menopausal. A questionnaire was developed by the steering group seeking responses on the effects of the menopause, changes in the arthritis at the time, use of hormone replacement therapy (HRT) and any discussions they had had with their healthcare providers. Free text comments were analysed qualitatively. A total of 779 people responded during September/October 2023. Respondents were 95% Caucasian mainly in their 50s with onset of menopausal symptoms in their 40s. 80% responded that their arthritis was worse during the menopause with 10% being much worse. 47% had taken HRT. Of these, 80% experienced an improvement in their menopausal symptoms and 30% had a moderate or large improvement in their arthritis symptoms. A standout statistic was that 93% of respondents had had no medical discussion about the menopause. For those who did, this was most frequently with the GP in relation to HRT and osteoporosis. 84% of participants felt that the rheumatology team should receive more education and training about the menopause in relation to RA. The qualitative analysis revealed several themes: Discussion about the menopause only occurred if the patient raised it. There was conflicting advice about HRT. There is overlap and confusion of symptoms between RA and the menopause. Participants expressed a perceived link between menopause and onset or deterioration of their arthritis. This study was long overdue. Patients perceive a strong association between the menopause and onset or deterioration of their arthritis, with confusion over what is due to arthritis and what is being caused by the menopause. Patients would like much more discussion about the menopause, but this is not currently happening. They are getting conflicting advice on HRT. Further research is necessary to clarify the impact of the menopause on people with arthritis.

Service evaluation: HRT regimens prescribed for complex menopausal patient cases

Abstract Introduction With government and NHS drivers, there has been an increase in menopause awareness and management. The NHS Business Services Authority reported a 29% increase in hormone replacement therapy (HRT) prescribing between 2022-2023, with expectation that this would rise further with introduction of the new HRT prepayment certificate in April 20231. Partly due to celebrity sway and supported by national guidance2,3 there is patient expectation towards transdermal oestrogen with natural progesterone HRT. Older women, some years since undergoing natural menopause, are also seeking advice on HRT use (3) with referrals accepted by specialist menopause clinics. Aims This service evaluation project was undertaken to evaluate the prescribing of HRT regimens in complex patient cases seen within a specialist menopause clinic and included assessment of those advised to use natural progesterone as part of their HRT regimen, for endometrial protection2,3. Method 366 specialist menopause clinic appointments over 6 months (05.01.23-22.06.23) were retrospectively evaluated, with patients seen by a multidisciplinary team within an outpatient secondary care setting. Exclusion criteria included appointments not attended, those that were incorrectly booked or patients with inaccessible records. Data was collected using electronic patient records with results analysed using Microsoft Excel. Results Of 327 (89%) appointments evaluated, the patient age ranged between 30-84 years (median age 53). HRT was recommended for 288 (88%) patients. HRT was not recommended in cases such as antiphospholipid syndrome, breast cancer without genitourinary symptoms, in those of advanced age or in line with patient choice with patient decision not to take HRT after an individualised risk benefit evaluation. For 26 (9%) patients, only topical oestrogen treatment for localised genitourinary syndrome symptoms was advised. 171 (52%) patients were postmenopausal, 61 (19%) perimenopausal, 46 (14%) with premature ovarian insufficiency and 20 (6%) with surgical menopause. For 22 patients (7%) with Mirena intra-uterine system in situ, their menopause phase could not be accurately defined. 243 (88%) of those recommended HRT were advised a combined regime; 154 (53%) continuous combined; 67 (23%) sequential combined and 22 (9%) oestrogen with Mirena coil. For patients accepting combined HRT, one third (81) were recommended natural progesterone, with the other patients using progestogens for endometrial protection. Of these 81 patients, 77 (95%) were recommended transdermal oestrogen in combination with natural progesterone. For patients recommended natural progesterone, 68 (84%) were for doses in line with licensing and current British Menopause Society guidance. For 10 patients the off-label recommendation involved doubled doses of natural progesterone to help with control of unfavourable bleeding. Discussion For prescribing of natural progesterone, we assumed that our recommendations to the GP were enacted. With retrospective evaluation of patient letters as a limitation, this project identified that within our specialist clinic complex patient population, a recommendation for natural progesterone was made for one third of patients suitable for combined HRT use. When not prescribed in line with licensing, this was due to issues with vaginal bleeding. Acknowledgments Biranavi Kirupakaran, Sahil Misri, Hernani Almeida, Medical Students, Imperial College London for data collection.

Patient-reported sexual health outcomes of cervical cancer patients treated with definitive chemoradiation and MRI-guided brachytherapy

BackgroundSexual health is an important survivorship issue in cervical cancer. We assessed patient-reported sexual health outcomes and correlations with oncologist-assessed vaginal toxicity (VT). MethodsThis was a prospective, cross-sectional study of stage IB-IVA cervical cancer patients treated with definitive chemoradiation, who completed a socio-demographic questionnaire and the following patient-reported-outcomes (PROs): Female Sexual Function Index (FSFI), Female Sexual Distress Scale-Revised (FSDS-R), Menopause Rating Scale (MRS), Hospital Anxiety and Depression Scale (HADS). VT was assessed using the CTCAE v4.0. Sociodemographic, clinical data, PROs and VT were summarized using descriptive statistics; correlations were evaluated using linear regression analyses. ResultsBetween August 2018 and April 2022, 73 patients were analyzed. Median age was 49 (range 25–81), 57.5% had vaginal involvement at diagnosis and 76.9% were partnered. Sexual dysfunction (FSFI score ≤ 26), sexual distress (FSDS-R ≥ 11), severe menopausal symptoms (MRS ≥ 17), anxiety (HAD-Anxiety >7) and depression (HAS-Depression >7) were reported in 86.3%, 54.5%, 36.2%, 46.6% and 24.7%, respectively. Grade 2+ VT was reported in 27.4%. No significant associations were found between PROs and VT. On multivariable analysis, non-partnered status, use of hormone replacement therapy, and International Commission on Radiation Units and Measurements – rectovaginal dose (ICRU-RV) >65Gy were associated with worse sexual health (p < 0.005). ConclusionCervical cancer patients self-report high rates of sexual distress, dysfunction and menopause symptoms. Discordance between oncologist-assessed VT and PROs highlights the importance of evaluating the patient's experience. Proactive treatment of menopausal symptoms and attention to radiotherapy doses to the vagina should be considered.

Much more than a biological phenomenon: A qualitative study of women's experiences of brain fog across their reproductive journey.

Whilst 'brain fog' is mostly considered a biological problem little is understood about an individual's experience. This qualitative study explored women's experiences of brain fog focusing on those at the start (aged 18-25; n = 10) and end (aged 45-60; n = 10) of their reproductive journey. Descriptive thematic analysis described three themes: (i) 'daily disruptions' describing cognitive dysfunctions and the main triggers; (ii) 'the cycle of impact' with a focus on women's emotional experiences and how these can exacerbate brain fog; (iii) 'taking control' highlighting the use of self-care, physical prompts and Hormonal Replacement Therapy (HRT) to manage brain fog. Transcending these themes was the notion of 'crisis of identity' illustrating the negative impact of brain fog on the women's sense of self with some older women describing acceptance and finding it less challenging. Brain fog is much more than a biological phenomenon and has broader implications for a woman's sense of self.

Exploring hormone replacement therapy dynamics among menopausal women in Kuala Lumpur – a community based survey

BackgroundWomen may lack awareness of the existence of Hormone Replacement Therapy (HRT), its benefits, and potential drawbacks. Furthermore, they may be uninformed about the treatability of menopausal symptoms. Consequently, there is a need to evaluate the knowledge, attitudes, and practices related to HRT among menopausal women within the Malaysian population. Presently, no studies have reported on the inside, attitudes, and practices regarding HRT among menopausal women in Kuala Lumpur. This study sought to determine the prevalence, knowledge, attitude, and practice (KAP) towards HRT and its association with socio-demographic characteristics of the study population.MethodA cross-sectional study was conducted among menopausal women (n = 404) living in Kuala Lumpur, Malaysia. Data was collected using convenient sampling. This research consists of 5 major parts which are (A) Socio-demographic characteristics of participants, (B) HRT knowledge among respondents, (C) Attitudes towards HRT, (D) Practice of HRT, and (E) Menopausal symptoms. All appropriate data from the project was analyzed using IBM SPSS Statistics Ver 26.ResultsA total of 404 participants were recruited in this survey. Overall, participants had good knowledge (n = 254, 62.9%) and negative attitude (n = 213, 52.7%) towards HRT. The majority of them (83.4%) had never taken HRT. The common menopausal symptoms reported were hot flashes (35.4%), irritability/ mood swings (31.9%), and night sweats (29.2%). There was a significant association between knowledge of menopause and HRT and attitude towards HRT use. Participants (68.7%, n = 103) with poor knowledge of menopause and HRT showed a negative attitude towards HRT (p < 0.01).ConclusionsOverall, the prevalence of HRT use among the respondents is low. 83.4% of them have never taken HRT before. There was a positive correlation between knowledge and attitude towards HRT use. Healthcare systems should educate the public using various educational tools and social media.

Hormone Replacement Therapy and Alzheimer's Disease: Current State of Knowledge and Implications for Clinical Use.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder responsible for over half of dementia cases, with two-thirds being women. Growing evidence from preclinical and clinical studies underscores the significance of sex-specific biological mechanisms in shaping AD risk. While older age is the greatest risk factor for AD, other distinct biological mechanisms increase the risk and progression of AD in women including sex hormones, brain structural differences, genetic background, immunomodulation and vascular disorders. Research indicates a correlation between declining estrogen levels during menopause and an increased risk of developing AD, highlighting a possible link with AD pathogenesis. The neuroprotective effects of estrogen vary with the age of treatment initiation, menopause stage, and type. This review assesses clinical and observational studies conducted in women, examining the influence of estrogen on cognitive function or addressing the ongoing question regarding the potential use of hormone replacement therapy (HRT) as a preventive or therapeutic option for AD. This review covers recent literature and discusses the working hypothesis, current use, controversies and challenges regarding HRT in preventing and treating age-related cognitive decline and AD. The available evidence indicates that estrogen plays a significant role in influencing dementia risk, with studies demonstrating both beneficial and detrimental effects of HRT. Recommendations regarding HRT usage should carefully consider the age when the hormonal supplementation is initiated, baseline characteristics such as genotype and cardiovascular health, and treatment duration until this approach can be more thoroughly investigated or progress in the development of alternative treatments can be made.

Female hormonal and reproductive factors and the risk of subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH), primarily caused by rupture of intracranial aneurysm, has a high incidence rate in women. We aimed to evaluate the association between female hormonal and reproductive factors and SAH. A prospective cohort of 226,469 participants from the UK Biobank was followed for a median period of 14.75 years. Cox proportional hazards models and restricted cubic splines were used to explore the associations between 13 major factors and SAH, including menarche age, menopausal status, age at menopause, reproductive lifespan, pregnancy history, age at first and last live births, number of live births, adverse fertility outcomes, history of oral contraception or hormone-replacement therapy (HRT) use, and surgical history of hysterectomy or bilateral oophorectomy. SAH occurred in 769 of participants during the follow-up period. Both women with a younger age at menarche (< 12 years) and post-menopausal women had a higher SAH risk (hazard ratio (HR), 1.28; 95% confidence interval (CI), 1.06-1.54) and (HR, 1.48; 95% CI, 1.10-1.99), respectively. A higher risk of SAH was identified in those with an earlier age at menopause (< 40 years: HR, 2.09; 95% CI, 1.43-3.06; 40-44 years: HR, 1.68; 95% CI, 1.23-2.29). A shorter reproductive lifespan (< 30 years) was associated with increased SAH risk (HR, 1.64; 95% CI, 1.28-2.11), while a longer reproductive lifespan (> 42 years) showed a protective effect (HR, 0.65; 95% CI, 0.55-0.77). Younger age at first live birth (< 24 years) was associated with SAH (HR, 1.39; 95% CI, 1.13-1.72). Hysterectomy (HR, 2.55; 95% CI, 2.12-3.05) or bilateral oophorectomy (HR, 1.51; 95% CI, 1.14-2.01) also predisposed women to SAH. Age at last live birth, number of live births, pregnancy history, adverse fertility outcomes, and HRT or oral contraceptive use were not associated with SAH. Female hormonal and reproductive factors are important for evaluating SAH risk in women. In particular, earlier menopause is associated with an increased risk of SAH. The data utilized in this study were sourced from a third party and are not publicly accessible. The UK Biobank data that support the findings of this research are available from the UK Biobank (www.ukbiobank.ac.uk), subject to review and approval by the UK Biobank.

6700 Risk Of Dementia According To The Reproductive Factors In Postmenopausal Women With Diabetes

Abstract Disclosure: J. Yu: None. K. Han: None. J. Yun: None. S. Lee: None. Risk of dementia according to the reproductive factors in postmenopausal women with diabetes Jin Yu[1], Kyungdo Han[2], Jae-Seung Yun[3], Seung-Hwan Lee[1],[4] [1]Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea[2]Department of Statistics and Actuarial Science, Soongsil University[3]Division of Endocrinology and Metabolism, Department of Internal Medicine, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea[4]Department of Medical Informatics, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea Background: Previous studies have suggested a possible association between endogenous estrogen exposure and decreased risk of cognitive impairment or dementia. We aimed to investigate the impact of reproductive factors on the risk of dementia in women with diabetes. Methods:166,245 postmenopausal women with type 2 diabetes aged over 40 who underwent health examination in 2009 were identified from the National Health Information Database. Information regarding reproductive factors were collected through self-administered questionnaires. Incident dementia was defined using diagnosis codes and anti-dementia drug prescription. Cox proportional hazards regression analyses were performed to evaluate the risk of all-cause dementia, Alzheimer’s disease, and vascular dementia according to reproductive factors including age at menarche, age at menopause, reproductive lifespan, parity, and use of hormone replacement therapy (HRT). Results: The mean age and reproductive lifespan were 64.5 ± 8.0 and 33.4 ± 4.7 years, respectively. During the median follow-up of 8.3 years, 25,330 cases of any dementia, including 20,817 cases of Alzheimer's disease and 2,756 cases of vascular dementia were developed. The hazard ratios (95% CI) of all-cause dementia were 1.28 (1.06-1.56) for age at menarche &amp;gt;16 years compared with ≤12 years, 0.71 (0.66-0.77) for age at menopause ≥55 years compared with &amp;lt;40 years, and 0.72 (0.68-0.76) for reproductive lifespan ≥40 years compared with &amp;lt;30 years, respectively. The risk of all-cause dementia was decreased by 11% in women with parity ≥2 compared with 0, and by 16% in women with HRT for more than 5 years compared without HRT. Similar findings were observed for Alzheimer’s disease and vascular dementia. Conclusion: Longer reproductive lifespan was associated with lower risk of dementia in postmenopausal women with diabetes. Presentation: 6/2/2024

7407 Normosmic Idiopathic Hypogonadotropic Hypogonadism in Women: A Case Report and Comprehensive Review

Abstract Disclosure: E.G. Bustamante: None. M. Sulehri: None. I. Patoli: None. A. Karunakaran: None. Normosmic Idiopathic Hypogonadotropic Hypogonadism (nIHH) in Women: A Case Report and Literature ReviewIntroduction: IHH is a rare genetic disorder affecting gonadotropic-releasing hormone (GnRH) production and/or action, resulting in diminished sex steroid levels. Characterized by the absence of spontaneous pubertal development. In women, it manifests with normal adrenarche but absent thelarche and menarche. Our case highlight a late diagnosis of IHH in a 34-year-old woman with primary amenorrhea. Case report: A 34 year old lady with a history of primary amenorrhea sought evaluation. At age 16, she underwent assessment for short stature and primary amenorrhea, denying anosmia, headache, visual disturbances. Evaluation revealed bone age concordant with chronological age and normal MRI Brain. Pelvic ultrasound (US) showed small premenarchal uterus and ovaries. She initiated oral contraceptive pills (OCP) and experienced regular menses. Seeking fertility assistance at age 24, a normal Hysterosalpingogram was followed by successful delivery of twins after ovarian stimulation. Post-delivery menses did not resume and OCP was not restarted. Family history revealed a sister with irregular periods requiring OCP.Subsequently workup at age 30 showed Estradiol 22 pg/ml, FSH/LH 4.1/2.3 mUI/mL; normal PRL, TFT, DHEAS, 17OHP. Repeat Pelvic US showed normal uterus, endometrial stripe normal at 0.24 cm and non-visualized ovaries. PCOS testing negative for hyperandrogenism. Progesterone challenge resulted in no withdrawal bleeding. Brain MRI demonstrated a 2.2 x 1.3 mm hypoenhancing ovoid mass in the pars Intermedia of the pituitary gland suggestive of pituitary microadenoma. Pituitary axis hormonal testing was normal. Karyotype revealed 46 XX (normal female). Genetic evaluation identified a pathogenic variant (p.R35C) in GNRH1 gene. Her final diagnosis: nIHH. Discussion HH is diagnosed in 5% of all women with primary amenorrhea and is divided into 2 major categories: Kallmann syndrome and nIHH. The majority of known causes of HH can be attributed to mutations in KAL1, FGFR1, or GNRHR. The p.R35C variant has been associated with autosomal dominant nIHH. Diagnosis involves clinical suspicious, low LH/FSH and sex steroid levels, normal hypothalamic–pituitary imaging, and exclusion of differentials.Treatment goal for female focus on regular breast and uterine development, as well as the capability to conceive. Use of hormonal replacement therapy and/or gonadotropins or pulsatile GnRH for ovarian stimulation are essential. ConclusionWhile IHH predominantly affects men, limited literature explores its manifestation in women and its impact on fertility. The identification of a GNRH1-related nIHH variant highlights the role of genetic testing in specific HH diagnoses. Failure to diagnose in adolescence may compromise women overall well-being Presentation: 6/1/2024

The Impact of Hormone Replacement Therapy on the Riskof Heart Failure in Postmenopausal Women: A Meta-Analysis of Clinical and Observational Studies.

The relationship between heart failure (HF) and hormone replacement therapy (HRT) in postmenopausal women remains unclear. This paper aimed to elucidate the association between HRT and HF outcomes in postmenopausal women by scrutinizing evidence from clinical trials and observational studies. The meta-analysis was systematically executed following the PRISMA guidelines to include studies identified from the electronic databases, including PubMed, EMBASE, EBSCO, ICTRP, and NIH clinical trials. The primary endpoint of the effect comprised risk ratios (RR) for HF incidence and mortality, attended by 95% confidence intervals (CIs). The risk of bias was assessed employing the Cochrane Risk of Bias 2 (RoB2) tool for clinical trials and the Newcastle-Ottawa Scale (NOS) for observational studies. The search yielded a total of eight reports, originating from six individual studies, for inclusion in the current study, and 25 047 participants were included. The meta-analysis demonstrated no remarkable association between HRT and the incidence of HF in postmenopausal women (RR: 1.07, 95% CI: 0.91-1.25, p = 0.37). However, a significant reduction in all-cause mortality was observed among post-menopausal HF patients who received HRT (RR: 0.65, 95% CI: 0.49-0.87, p = 0.003). In age-related subgroup analyses, no significant change in the risk of HF was noticed among participants on HRT. The findings of this paper demonstrate that HRT use is not associated with a significant increase in the risk of incident HF. This meta-analysis also suggests a benefit in all-cause mortality when HRT is administered to postmenopausal women with HF.

Reproductive factors and mammographic density within the International Consortium of Mammographic Density: A cross-sectional study

BackgroundElevated mammographic density (MD) for a woman’s age and body mass index (BMI) is an established breast cancer risk factor. The relationship of parity, age at first birth, and breastfeeding with MD is less clear. We examined the associations of these factors with MD within the International Consortium of Mammographic Density (ICMD).MethodsICMD is a consortium of 27 studies with pooled individual-level epidemiological and MD data from 11,755 women without breast cancer aged 35–85 years from 22 countries, capturing 40 country-& ethnicity-specific population groups. MD was measured using the area-based tool Cumulus. Meta-analyses across population groups and pooled analyses were used to examine linear regression associations of square-root (√) transformed MD measures (percent MD (PMD), dense area (DA), and non-dense area (NDA)) with parity, age at first birth, ever/never breastfed and lifetime breastfeeding duration. Models were adjusted for age at mammogram, age at menarche, BMI, menopausal status, use of hormone replacement therapy, calibration method, mammogram view and reader, and parity and age at first birth when not the association of interest.ResultsAmong 10,988 women included in these analyses, 90.1% (n = 9,895) were parous, of whom 13% (n = 1,286) had ≥ five births. The mean age at first birth was 24.3 years (Standard deviation = 5.1). Increasing parity (per birth) was inversely associated with √PMD (β: − 0.05, 95% confidence interval (CI): − 0.07, − 0.03) and √DA (β: − 0.08, 95% CI: − 0.12, − 0.05) with this trend evident until at least nine births. Women who were older at first birth (per five-year increase) had higher √PMD (β:0.06, 95% CI:0.03, 0.10) and √DA (β:0.06, 95% CI:0.02, 0.10), and lower √NDA (β: − 0.06, 95% CI: − 0.11, − 0.01). In stratified analyses, this association was only evident in women who were post-menopausal at MD assessment. Among parous women, no associations were found between ever/never breastfed or lifetime breastfeeding duration (per six-month increase) and √MD.ConclusionsAssociations with higher parity and older age at first birth with √MD were consistent with the direction of their respective associations with breast cancer risk. Further research is needed to understand reproductive factor-related differences in the composition of breast tissue and their associations with breast cancer risk.

Correlation between Hearing Impairment and the Triglyceride Glucose Index in Middle-Aged Female Based on a Korean National Health and Nutrition Examination Survey

Background and Objectives: This study aimed to investigate the association between insulin resistance, as measured by the triglyceride–glucose index (TyG index), and hearing impairment in middle-aged women in Korea. Materials and Methods: This cross-sectional survey utilized data from the Korea National Health and Nutrition Examination Survey (KNHANES) IV (2007–2009), specifically from the period after July 21, 2009, when hearing test results became available, and from the KNHANES V (2010–2012). This study was conducted on 5416 women aged 40 to 69 who had completed both the health examination survey and audiometric tests, excluding those with missing data on menopausal status and the use of hormone replacement therapy. Results: In the study group, the prevalence of high-frequency hearing loss according to the TyG index was significantly higher in the mild hearing loss group (OR = 1.29; 95% CI: 1.12, 1.49, p &lt; 0.001) and the moderate hearing loss group (OR = 1.27; 95% CI: 1.09, 1.48, p = 0.002). Conversely, the prevalence of low-frequency hearing loss did not show a significant difference in either the mild hearing loss group (OR = 1.17; 95% CI: 0.99, 1.37, p = 0.065) and the moderate hearing loss group (OR = 1.13; 95% CI: 0.94, 1.35, p = 0.199) Conclusions: Since diabetes can induce hearing impairment in women, it is recommended that women with a high TyG index undergo early hearing tests

THE IMPACT OF HOP EXTRACT ACTIVE COMPONENTS ON METABOLIC DISTURBANCES IN ESTROGEN DEFICIENT FEMALE RATS WITH PREDIABETES

A number of studies have shown a greater cardiovascular risk in women with type 2 diabetes compared to men. The latter may be due to more excessive manifestations of metabolic disorders in women, in particular postmenopausal, that develop even at the stage of prediabetes. Since the use of hormone replacement therapy in women after menopause had adverse results on the progression of cardiovascular events, an alternative method of reducing cardiovascular risk in postmenopausal women with prediabetes may be the use of phytoestrogens, which possess estrogen-like activity without negative side effects specific to exogenous estrogens. The aim of our study was to evaluate the effect of hop extract on metabolic disturbances in female rats with prediabetes under estrogen deficiency. Materials and methods. The study was conducted on three-month-old intact and ovariectomized Wistar rats with metabolic syndrome (MS) induced by high calorie diet (15% lard, 25% sucrose, 1% bile salts, 59% standard feed) for eight weeks. The test substances were administered intragastrically once per day in a dose of 20 μg/kg or 200 μg/kg b.w. in recalculation on 8-prenylnaringenin for hop extract and 200 μg/kg b.w. in recalculation on estradiol for the reference drug, from the fifth week after induction of metabolic syndrome. Results. It was revealed that administration of hop extract in a dose of 200 μg/kg, similar to estradiol, led to improvement in glucose tolerance and decrease in insulin resistance (p˂0.05) in estrogen deficient rats with MS. In contrast to estradiol, hop extract had no effect on the mass of uterus in ovariectomized animals. The use of hop extract only in the dose of 200 μg/kg, similar to estradiol, was accompanied by a significant decrease in body weight gain and visceral fat, as well as normalization of the total lipids content in serum of experimental animals (p˂0.05). It is of note, that hop extract resulted in decrease of hypertriglyceridemia (p˂0.05), but did not affect the level of total cholesterol, while estradiol reduced the concentration of total cholesterol (p˂0.05), and had no effect on the level of triglycerides. Hop extract in a dose of 200 μg/kg, as well as estradiol, led to a decrease in the intensity of lipid peroxidation induced by MS under estrogen deficiency, as evidenced by reduced concentration of conjugated dienes in serum (p˂0.05). At the same time, the total antioxidant activity of serum in these animals remained elevated compared to intact group. In rats with MS and hypoestrogenia, hop extract in the highest dose and estradiol resulted in complete normalization (p˂0.05) of the decreased level of NO stable metabolites in serum and the reduced activity of NO-synthase in heart. Conclusions. The revealed cardioprotective effect of hop extract that is realized due to the improved lipid profile and reduced insulin resistance, visceral obesity, oxidative stress and endothelial dysfunction in estrogen deficient female rats with MS indicates the prospects of its use for prevention and treatment of cardiovascular complications in postmenopausal women with prediabetes.

P225 RISK FACTORS FOR CEREBROVASCULAR DISEASE IN WOMEN ADMITTED TO THE INTERNAL MEDICINE SERVICE OF THE EMERGENCY DEPARTMENT OF THE CENTRAL HOSPITAL IN SAN CRISTOBAL (TACHIRA, VENEZUELA)

Background and objective: Cerebrovascular disease is a leading cause of mortality and disability worldwide. Research has focused on determining the risk factors for cerebrovascular disease independent of gender; however, it has been important to differentiate between men and women due to the variety of causes that occur in the latter. Therefore, the aim was to determine the risk factors for cerebrovascular disease in women admitted to the internal medicine service of the Central Hospital of San Cristóbal (Táchira, Venezuela). Methods: A case-control study was performed. Cases were female patients diagnosed with acute cerebrovascular disease (24 to 72 hours after symptom onset). Controls were hospitalized or community-based female subjects without pathologies associated with cardiovascular disorders. The case-control ratio was 1:2, of equal age or ± 5 years. All participants signed the informed consent form and completed the data collection form. Odds ratios (OR) were calculated, with 95% confidence intervals. Results: In the period between February 2 to July 15, 2020, 111 female participants entered the study, 37 cases (26 with ischemic cerebrovascular disease and 11 with hemorrhagic cerebrovascular disease) and 74 controls. Of the risk factors studied: arterial hypertension, diabetes mellitus, dyslipidemia, physical inactivity, smoking, alcohol consumption, overweight, obesity, atrial fibrillation, use of oral contraceptives, use of hormone replacement therapy, autoimmune diseases, only association was found between atrial fibrillation (OR 9.1736, 95% CI 3.3638-25.0173), autoimmune diseases (OR 9.1736, 95% CI 3.3638-5.0173) and ischemic cerebrovascular disease. No association was found with any risk factor and hemorrhagic cerebrovascular disease. Conclusions: The risk factors for cerebrovascular disease in the female population are modifiable and treatable, being pertinent to determine their presence and carry out the necessary actions to reduce morbimortality in this population group.

Disease Activity and Bone Microarchitectural Phenotype in Patients With Axial Spondyloarthritis

Background: Axial spondyloarthritis (AxSpA) is a chronic rheumatic disease characterized by spine inflammation, abnormal bone growth, and paradoxically osteoporosis and vertebral fractures. The pathogenesis of skeletal deficits in this disease is poorly understood. Purpose: We sought to evaluate volumetric bone mineral density (vBMD) and bone microarchitecture in patients with AxSpA and to identify disease-related factors associated with skeletal abnormalities. Methods: We enrolled patients between 2018 and 2021 as part of a 2-year prospective study at a single institution investigating skeletal health and the skeletal effects of interleukin-17 (IL-17) treatment. Patients with AxSpA who met Assessment in SpondyloArthritis International Society (ASAS) classification criteria by X-ray or had evidence of active inflammation on magnetic resonance imaging suggestive of sacroiliitis were referred to the study by their rheumatologists. We excluded those with a history of fragility fracture, multiple myeloma, Cushing’s disease, primary hyperparathyroidism, osteomalacia, untreated vitamin D deficiency, secondary osteoporosis, or other systemic rheumatic diseases, as well as use of oral steroids for 2 or more weeks in the 6 months prior or current use of hormone replacement therapy, current oral bisphosphonate, past or current intravenous bisphosphonate, teriparatide, or denosumab therapies. A total of 1606 patients were screened for eligibility. Of these, 30 participants were enrolled (mean age 43 years, 50% male). Patients with AxSpA had dual-energy X-ray absorptiometry (DXA) measurements of areal BMD (aBMD) and high-resolution peripheral quantitative computed tomography (HR-pQCT) measurements of vBMD microarchitecture and failure load by finite element analysis. Standardized disease assessment tools used included the Bath Ankylosing Spondylitis Disease Activity (BASDAI), Metrology Index (BASMI), and Functional Index (BASFI). Results: In the 30 included patients, mean DXA and HR-pQCT Z-scores were within 1 standard deviation (SD) of normal for all indices, except for total vBMD in males (–1.2 SD below mean). Mean symptom duration was 11.7 years and mean scores for BASDAI, BASFI, and BASMI were 4.6, 3.6, and 2.7, respectively (range 1–10, 10 = severe limitation). Longer disease duration was associated with more severe skeletal deficits at the hip and tibia—specifically, lower hip aBMD, lower meta- and inner-trabecular vBMD, lower trabecular number, and higher trabecular separation and heterogeneity. Conclusion: This study of 30 patients with AxSpA found that abnormalities in bone density and microarchitecture at weightbearing sites were associated with longer disease duration. Because of its small sample size, larger studies are needed to better characterize the pathogenic disease factors that govern skeletal damage in AxSpA.

O-313 Increased risk of preterm deliveries in long term survivors of children, adolescent, and young adult exposure to chemotherapy or chemo-radiotherapy: a systematic review and meta-analysis

Abstract Study question What is the long-term impact on pregnancy outcomes of a childhood adolescent, and young adult (AYA) exposure to chemotherapy or chemo-radiotherapy? Summary answer Whereas preterm delivery and pregnancy loss were significantly increased in chemotherapy and chemo-radiotherapy groups compared to control group, live birth rate was not affected. What is known already The impact of radiotherapy on the uterus has been widely described. Lately, studies have underlined the potential negative effect of chemotherapy on the womb. Indeed, three recent publications have reported that adult females treated with hematopoietic stem cell transplantation (HSCT) in childhood had a reduced uterus volume, both after conditioning by total body irradiation (TBI) and after alkylating agents-based regimen. The pregnancy outcome will depend in part on the uterine volume and its vascularization. Therefore, a history of chemotherapy or chemo-radiotherapy may be associated to an increased risk of obstetrical complications. Study design, size, duration A systematic review and meta-analysis were performed on comparative studies. Searches were conducted on Medline, Embase and the Cochrane Library from 1990 to April 2023, using the main following search terms: cancer survivors, bone marrow transplantation, chemotherapy, radiotherapy, pregnancy outcome, pregnancy complications, preterm delivery, and pregnancy loss. All studies reporting live birth rate (LBR) in adult females who have received chemotherapy and/or chemo-radiotherapy during childhood and AYA &amp;lt; 25 years were included. Participants/materials, setting, methods Two independent reviewers carried out the study selection, the bias assessment using the ROBINS-I tool and data extraction. The primary outcome was the LBR. The main secondary outcomes were preterm delivery and pregnancy loss rates. For each outcome, a random-effect frequentist network meta-analysis (NMA) was carried out to estimate risk ratios with their 95% confidence intervals. Sensitivity analyses were conducted by excluding studies at high risk of bias and leave-one out method. Main results and the role of chance After reviewing 2,328 abstracts, 25 studies were retained for review. Eight studies were included in the meta-analysis on LBR: 3,997 females became pregnant leading to 2,878 live births. The NMA shows a moderate heterogeneity/inconsistency (τ²= 0.012, I²=58% [11%; 80%]) and did not show any significant impact of treatments on LBR. Sensitivity analyses lead to the same conclusions. Six studies reported a total of 125 preterm deliveries out of 1,976 started pregnancies and were included in the NMA (τ²= 0.07, I²=19% [0%; 62%]). Chemo-radiotherapy was significantly associated with higher risk of preterm delivery compared to the control group (3.44 [1.94; 6.09]) and chemotherapy group (1.93 [1.19; 3.15]). The chemotherapy group was associated with a statistically higher risk of preterm delivery than the control group (1.78 [1.01; 3.13]). Eight studies including 606 pregnancy loss out of 3,653 started pregnancies were entered in the NMA (τ²= 0, I²=0% [0%; 65%]). Chemo-radiotherapy was associated with significantly higher risk of pregnancy loss compared to the control group (1.80 [1.34; 2.43]) and chemotherapy group (1.68 [1.26; 2.25]). No statistical difference was shown in the risk of pregnancy loss between the chemotherapy and the control groups (1.07 [0.87; 1.32]). Limitations, reasons for caution Study selection was focused on live birth rate; therefore, the research was probably not exhaustive for the secondary outcomes. Adjustment on parity or history of hormonal replacement therapy (HRT) was not performed because of a lack of data. Subgroup analysis on the type of chemotherapy was not possible. Wider implications of the findings This meta-analysis reports a negative impact of chemotherapy or chemo-radiotherapy on obstetric outcomes. Further studies including clear information on parity and use of HRT are needed. Moreover, a description on the type of chemotherapy could help to refine these conclusions. Trial registration number Not applicable

O-083 Sexual function in women with Premature Ovarian Insufficiency (POI): systematic review and meta-analysis

Abstract Study question What is the impact of idiopathic premature ovarian insufficiency (POI) on sexual function in women? Summary answer Women with POI exhibit significant reduced sexual function and a higher risk of sexual dysfunction than healthy control women. What is known already POI is a life-changing diagnosis with profound physical and psychological consequences. The impact of POI on sexual complaints, seems multifaceted. Many women report vaginal dryness, dyspareunia (painful intercourse), and diminished libido, but also psychosexual function could be impaired, with potential effects on sexual identity, sexual function, and sexual relationships. Furthermore, the POI diagnosis can have a significant impact on a woman's self-esteem and body image, which could result in problems with sexual function. The ESHRE Guideline emphasizes the importance of providing psychological support and counseling to address the emotional and psychosexual impact of POI. Study design, size, duration This systematic review and meta-analysis is reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The following online databases were systematically searched: EMBASE, Medline(Ovid), Web of Science, Coachrane, PsychInfo and Google Scholar up to January 2023. Participants/materials, setting, methods A total of ten studies were included in the systematic review and five studies involving 352 women with POI were included in the meta-analysis. Random effects models were used for analyses, with data reported as Hedges’ g and 95% confidence interval, and the risk of heterogeneity was evaluated. Main results and the role of chance Eight of the ten studies concluded that women with POI have a reduced sexual function. An overall medium Hedges’ g effect size of −0.72 was found (ranging between −0.20 to −1.29) in favor of control women, with moderate heterogeneity (I2 = 64%). When we stratified studies in which women were using hormone replacement therapy (HRT) we calculated an even higher Hedges’ g effect size of −0.82 (95% CI −1.18, −0.47). Pooled data from the different FSFI domains, revealed that women with POI scored significantly lower on all domains. Especially the domain ‘dyspareunia’ exhibited the greatest dissimilarity (Hedges g of −0.63, 95%CI −0.86, −0.39) in women with POI compared to control. Limitations, reasons for caution We have reported a moderate heterogeneity which may be caused by differences in age, duration of diagnosis, infertility status, and socioeconomic background in the various studies. Additionally, limitations such as selection bias, data duplication, and questionnaire variation were identified. Wider implications of the findings The results show that women with POI have reduced sexual function, and HRT use did not improve sexual function. This suggest that oral HRT is less effective for sexual dysfunction. There could be an important role for psychological factors in improving sexual well-being among women with POI. Trial registration number CRD42023437203 (PROSPERO)

Hormone replacement therapy and cancer mortality in women with 17 site-specific cancers: a cohort study using linked medical records

BackgroundThere is limited evidence on the safety of Hormone Replacement Therapy (HRT) in women with cancer. Therefore, we systematically examined HRT use and cancer-specific mortality in women with 17 site-specific cancers.MethodsWomen newly diagnosed with 17 site-specific cancers from 1998 to 2019, were identified from general practitioner (GP) records, hospital diagnoses or cancer registries in Scotland, Wales and England. Breast cancer patients were excluded because HRT is contraindicated in breast cancer patients. The primary outcome was time to cancer-specific mortality. Time-dependent Cox regression models were used to calculate adjusted hazard ratios (HR) and 95% confidence intervals (95% CIs) for cancer-specific mortality by systemic HRT use.ResultsThe combined cancer cohorts contained 182,589 women across 17 cancer sites. Overall 7% of patients used systemic HRT after their cancer diagnosis. There was no evidence that HRT users, compared with non-users, had higher cancer-specific mortality at any cancer site. In particular, no increase was observed in common cancers including lung (adjusted HR = 0.98 95% CI 0.90, 1.07), colorectal (adjusted HR = 0.79 95% CI 0.70, 0.90), and melanoma (adjusted HR = 0.77 95% CI 0.58, 1.02).ConclusionsWe observed no evidence of increased cancer-specific mortality in women with a range of cancers (excluding breast) receiving HRT.

Does the use of double hormone replacement therapy for trauma patient organ donors improve organ recovery for transplant.

With an ongoing demand for transplantable organs, optimization of donor management protocols, specifically in trauma populations, is important for obtaining a high yield of viable organs per patient. Endocrine management of brain-dead potential organ donors (BPODs) is controversial, leading to heterogeneous clinical management approaches. Previous studies have shown that when levothyroxine was combined with other treatments, including steroids, vasopressin, and insulin, BPODs had better organ recovery and survival outcomes were increased for transplant recipients. To determine if levothyroxine use in combination with steroids in BPODs increased the number of organs donated in trauma patients. A retrospective review of adult BPODs from a single level 1 trauma center over ten years was performed. Exclusion criteria included patients who were not solid organ donors, patients who were not declared brain dead (donation after circulatory death), and patients who did not receive steroids in their hospital course. Levothyroxine and steroid administration, the number of organs donated, the types of organs donated, and demographic information were recorded. Univariate analyses were performed with P < 0.05 considered to be statistically significant. A total of 88 patients met inclusion criteria, 69 (78%) of whom received levothyroxine and steroids (ST/LT group) vs 19 (22%) receiving steroids without levothyroxine (ST group). No differences were observed between the groups for gender, race, pertinent injury factors, age, or other hormone therapies used (P > 0.05). In the ST/LT group, 68.1% (n = 47) donated a high yield (3-5) of organ types per donor compared to 42.1% (n = 8) in the ST group (P = 0.038). There was no difference in the total number of organ types donated between the groups (P = 0.068). This study suggests that combining levothyroxine and steroid administration increases high-yield organ donation per donor in BPODs in the trauma patient population. Limitations to this study include the retrospective design and the relatively small number of organ donors who met inclusion criteria. This study is unique in that it mitigates steroid administration as a confounding variable and focuses specifically on the adjunctive use of levothyroxine.