Effects of training and protein/carbohydrate supplementation by food on strength, body composition and bone metabolism in postmenopausal women

Background: Menopause is associated with impairments of health, e.g. cardiovascular disease, changes in body composition, decrease in bone density. Physical activity and nutrition strategies have been demonstrated to counteract some of these disabilities. Aim of the present study was to analyze the impact of 3 months of strength and endurance training combined with protein/carbohydrate supplementation on strength, body composition and bone metabolism in postmenopausal women. Method(s): 62 postmenopausal women were recruited. Measurements: Body composition by BIA. Strength of leg, chest and handgrip. delta44Ca/42Ca in blood and urine as proxies for bone metabolism, samples were analyzed by mass spectrometry. Participants completed 2/week endurance training (walking) for 60 minutes (60-75% km/h of 4mmol threshold) and a whole-body strength training 1/week for 60 minutes (online). In addition, the intervention group (IG) received 100g of sour milk cheese and 76g of white bread (35.3 g carbohydrate, 36.1 g protein, 3.5 g fat, 321 kcal) after each training. Result(s): Training results in an anabolic effect on bone metabolism, here protein/carbohydrate supplementation does not show additive effects. Training resulted in an increase of leg and hand grip strength. For hand grip strength an additive effect could be demonstrated after protein/carbohydrate supplementation. Both groups increased muscle mass and reduced fat mass, although the results were not significant. Discussion(s): Training was effective, showing an increase in strength. Additive effects of the nutritional intervention could be only observed for hand grip strength. This may be due to a weak compliance of the protein/carbohydrate supplementation by a meal while corona pandemic. Also, because of the endurance parts, the training was not specifically designed to increase strength. Nevertheless, even this mild training has a remarkably strong impact on bone metabolism. Conclusion(s): Even if the effects are faint, the data of this study provide evidence that protein/carbohydrate supplementation, also by food, supports the events of training on strength. Training has a strong impact on bone metabolism in postmenopausal women. The subjects respond very individually to training and nutrition interventions. Training consequentially is to be personalized.Copyright © 2023

Premenopausal women recover from COVID-19 disease better than postmenopausal women: the Role of DHEA-S

Objectives: We aimed to demonstrate the difference between the premenopausal and postmenopausal women in respect of the clinical course and outcome of the Covid-19 disease. In addition, we investigated the epidemiological and hormonal factors which may have an influence on the progression, severity and mortality of the disease. Study design: A cross-sectional study. Main Outcome Measure(s): Our primary outcome was to demonstrate the poor clinical course and outcome of the Covid-19 disease in the postmenopausal women. Our secondary outcome was to establish the contribution of the hormonal status of the patients to the clinical course of the Covid-19 disease. Result(s): In our cohort, 86 women had mild, 128 women had moderate and 53 women had severe Covid-19 disease. 101 women were at premenopausal state while 152 women were at postmenopausal state. There was a statistically significant difference between the patients with mild, moderate and severe Covid-19 disease with respect to age, BMI, gravidity, parity, smoking, co-morbidities, being in pre-menopausal period, O2 saturation, diastolic blood pressure, parameters of complete blood count, biochemical tests, LH, FSH, E2, DHEA-S, length of hospital stay, body temperature, and the percentage of patients with dyspnea. In the total group, being one year younger decreased the odds of having severe Covid-19 disease 0.338 fold relative to the mild disease (CI: 0.164-0.697, p=0.003). Even though statistically less significant, younger age has a positive impact for the postmenopausal group (OR: 0.378, CI: 0.157-0.910, p=0.030). In the total group, the decrease in the serum DHEA-S level was associated with a 2.604 fold increase in the odds of having severe Covid-19 disease relative to the mild disease (CI:1.254-5.410, p=0.010). For the pre-menopausal group of patients, the decrease in serum DHEA-S level increased the odds of having severe disease by 3.864 fold (CI: 1.269-11.764, p=0.017). In the total group, 1 unit increase in the level of serum LH increased the odds of having mild disease compared to severe disease by 2.821 fold (CI:1.002-5.410, p=0.050). Conclusion(s): The prognosis of Covid-19 disease is more favorable in the premenopausal women with higher serum E2 levels compared to the postmenopausal women. The age and serum levels of DHEA-S and LH are important predictors of the severity of Covid-19 infection for women.Copyright © 2023

Presentation of Takotsubo Cardiomyopathy in a Patient with Coronavirus-19 Disease

Case Report: It is well documented that Coronavirus Disease 19 (COVID-19) patients who suffer cardiac injury have a higher mortality rate, however the exact mechanism of cardiac injury and potential complications are still unknown. Takotsubo Cardiomyopathy (TCM), which was first described in 1990 in Japan, is characterized by a transient systolic and diastolic left ventricular dysfunction with a range of wall motion abnormalities predominantly affecting women often following an emotional or physical trigger. Though TCM is seen less commonly as a cardiac complication of COVID-19, with increasing rates of cardiovascular events due to COVID-19, TCM should be taken into consideration as a potential diagnosis for a COVID-19 positive patient. Case Description: The case of a 75-year old female with a history significant for hypertension, type 2 diabetes mellitus, hyperlipidemia, and gastroesophageal reflux disease presented to the Emergency Department after a ground level fall and subsequent left hip pain. Upon primary survey, EKG showed persistent sinus tachycardia in the 130-150s, with intermittent borderline dynamic changes and a troponin that was mildly elevated at 0.10, and an initial false negative COVID-19 test. Preoperative echocardiogram showed normal left ventricle size, no regional wall abnormalities, and a left ventricular ejection fraction (LVEF) of 60-65%. In post-operative care, EKG illustrated dynamic changes in the form of ST elevation in the lateral precordial leads, as well as an increase in the cardiac troponins, from 0.07 to 3.51. A subsequent echocardiogram illustrated a drop in her ejection fraction from 60-65% to 30-35%, with evidence of left ventricular systolic dysfunction that was not noted on previous echocardiograms. Following the Mayo clinic diagnostic criteria, this patient met the diagnostic criteria for TCM, as evident by new electrocardiograph findings, non-obstructive cardiac catherization findings, echocardiogram findings illustrating transient left ventricular systolic dysfunction, modest elevations in cardiac troponins as well as the patient being a post-menopausal female. Subsequent echocardiogram on 2 week follow up showed a rebound in her ejection fraction to 50-55%. Discussion(s): Possible outcomes of TCM include cardiogenic shock, respiratory failure, and death. It is imperative that clinicians consider TCM as a possible diagnosis when treating COVID-19 patients that may be exhibiting cardiac complications. Frequent ECG monitoring and a vigilant differential should include TCM in patients presenting with COVID-19.

27th Asia and Oceania Federation of Obstetrics and Gynecology Congress

The proceedings contain 358 papers. The topics discussed include: role of early prophylactic aspirin on Covid-19 outcome in antenatal patients - an audit of a hospital in India;partial intestinal obstruction complicating pregnancy: diagnostic dilemma and management;a case report of uterine rupture recognized during cesarean section at the site of a previous hysteroscopy-related perforation;menstrual characteristics and its related morbidities among adolescent girls living in North Borneo, Malaysia: a questionnaire-based study;the volume of posterior cervical varicose correlates with intraoperative blood loss in placenta previa;implications of large fibroids in pregnancy: a multidisciplinary approach;unexpected ovarian malignancy in postmenopausal women following laparoscopic surgery for adnexal masses - a review of 5 years;post radiotherapy outcome on cervical cancer stage IIIB patients with and without paraaortic lymph nodes enlargement;and evaluation of the relationship between thrombocytosis and clinico-pathological factors of patients with epithelial ovarian cancer.

Is Treating Post-Menopausal Women With Symptomatic Hand Osteoarthritis With Hormone Replacement Therapy Feasible?: Results From The Hope-E Randomised, Placebo-Controlled Feasibility Study

Purpose: Hand osteoarthritis (OA) is more common in women. Hand OA incidence increases further in females around the age of 50, the typical age of menopause. Estrogen-deficient states are associated with increased musculoskeletal pain and inflammation and with increased rates of symptomatic OA. Estrogen replacement and selective estrogen receptor modulators (SERMs) can improve pain and structure in some pre-clinical models of OA associated with estrogen loss, and in exploratory analysis from hormone replacement therapy (HRT) trials. However, no randomised clinical trials (RCTs) of HRT had been performed in symptomatic OA populations, specifically hand OA. By carrying out a RCT feasibility study of a form of HRT (conjugated estrogens (CE)-bazedoxifene) in post-menopausal women with painful hand OA, we set out to determine the feasibility and acceptability of this. We also aimed to generate proof-of concept data on likely outcomes, calculate a sample size and refine methods for a full trial. Method(s): We recruited females aged 40-65 years and 1-10 years after final menstrual period with definite hand OA and >=2 painful hand joints across three primary/secondary care sites and from the community. Medical exclusions included those typical for clinical HRT use. Design was parallel group, double-blind 1:1 randomisation of CE-bazedoxifene or placebo, taken orally once daily for 24 weeks, then tapering for 4 weeks before study end at Week 28. Primary feasibility outcomes were rates of eligible participant identification, recruitment, randomisation, retention, compliance, and likelihood of unblinding. Adverse events (AEs) were collected. Secondary clinical outcomes included the anticipated primary outcome in a full trial of mean hand pain over 14 days prior to each visit, scored on a 0-10 numerical rating scale (NRS) where 10 is worst pain possible, as well as hand function, appearance and menopause symptoms. Progression criteria to a full RCT were: (i) recruitment >=30 participants across all sites in 18 months (or proportionate to time open);(ii) a drop-out rate of <=30% of randomised individuals;and (iii) acceptability to the majority of participants, including acceptable AE rates. All clinical outcomes were analysed on an intention-to-treat basis. Though not powered to detect a treatment difference, change and treatment effects (the difference in the outcome between the two groups) were indicated with 95% CIs, with all models adjusted for clinical subtype of painful hand joint, study site, and baseline values. The sample size for a full trial was estimated using the standard deviation (SD) of week 24 mean hand pain. Result(s): Due to the COVID-19 pandemic, the recruitment window was reduced to 12-15 months. From May 2019 to December 2020, 434 enquiries/referrals were received. Of 96 telephone pre-screens, 35 individuals were potentially eligible and of these, 33 gave consent to participate. Of the remaining, 250/401 (62%) were ineligible, whilst 55/401 (14%) chose not to proceed, with the most common reason being not wanting to take HRT. 28/35 (80% (95%CI 63%,92%)) eligible participants were randomised to study medication. All 28 participants completed all follow-ups with high compliance (100% active, 13/14[93%] placebo) and outcome measure completeness (100%, mean hand pain). All three AE-related treatment withdrawals were on placebo when unblinded. No serious AEs occurred. Participants/investigators were well blinded (participant blinding index 0.50[95%CI 0.25 to 0.75]). All three prespecified progression criteria were therefore met for a full trial. The treatment effect difference over 24 weeks in mean hand pain between active and placebo was -0.71 (95% CI -2.20 to 0.78) (Fig 1A). During tapering/stopping medication, mean hand pain increased by 1.31 points in the active arm compared with 0.17 in the placebo arm, indicating a possible effect of cessation of medication (Fig 1A). Furthermore, 6/13 (46%) participants in the active group reported worsening pain at week 28 compared with week 24, but only 2/12 (17%) were worse on withdrawing placebo (Fig 1B). The sample size for a full trial was estimated as 296 (based on MCID 0.8 on NRS, SD 2.0, 90% power, 10% drop-out, alpha 5%). Conclusion(s): This first study of a RCT of HRT for painful hand OA met its progression criteria, indicating that a full trial of an HRT in this population is feasible and acceptable. Although not powered to detect an effect, there was a trend towards improvement in hand pain on treatment and worsening of hand pain on tapering in the active arm only. This adds to proof-of-concept data in this area, justifying more work.ISRCTN12196200. Funded by Research for Patient Benefit programme, National Institute for Health Research (UK) PB-PG-0416-20023 [Formula presented]Copyright © 2023

The effects of exogenous estrogen in women with SAR-CoV-2 infection: a systematic review and meta-analysis.

STUDY QUESTION: Does exogenous estrogen use affect COVID-19-related mortality in women? SUMMARY ANSWER: Menopausal hormone therapy (MHT) was associated with a lower likelihood of all-cause fatality related to COVID-19 in postmenopausal women (odds ratio (OR) 0.28, 95% CI 0.18, 0.44; 4 studies, 21 517 women) but the combined oral contraceptive pill in premenopausal women did not have a significant effect (OR 1.00, 95% CI 0.42-2.41; 2 studies, 5099 women). WHAT IS KNOWN ALREADY: Men are much more likely to die from COVID-19 than women. STUDY DESIGN, SIZE, DURATION: In this systematic meta-analysis, a literature search was conducted using the following search terms related toCOVID-19 and estrogen, sex hormones, hormonal replacement, menopause, or contraception. The PubMed, Scopus, Cochrane Library, and EMBASE databases were searched to identify relevant studies published between December 2019 and December 2021. We also searched MedRxiv as a preprint database and reviewed the reference lists of all included studies and clinical trial registries for ongoing clinical studies until December 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: All comparative studies that compared the rates mortality and morbidity (hospitalization, intensive care unit (ICU) admission, and ventilation support) due to COVID-19 in women using exogenous estrogen to a control group of women (nonusers) were included. A review of the studies for inclusion, extraction of data, and assessment of the risk of bias was performed independently by two reviewers. The ROBINS-I tool and the RoB 2 tool were used for bias assessment of the included studies. Pooled odds ratios (ORs) with 95% CIs were calculated using Review Manager V5.4.1. The I2 statistic was used to quantify heterogeneity. The quality of the evidence was assessed using GRADE criteria. MAIN RESULTS AND THE ROLE OF CHANCE: After searching the databases, we identified a total of 5310 studies. After removing duplicate records, ineligible studies, and ongoing studies, a total of four cohort studies and one randomized controlled trial comprising 177 809 participants were included in this review. There was a moderate certainty of evidence that MHT was associated with a lower likelihood of all-cause fatality related to COVID-19 (OR 0.28, 95% CI 0.18, 0.44; I2 = 0%; 4 studies, 21 517 women). The review indicated a low certainty of evidence for other outcomes. The mortality rate of premenopausal women in the combined oral contraceptive pill group did not differ significantly from the control group (OR 1.00, 95% CI 0.42-2.41; 2 studies, 5099 women). MHT marginally increased the rate of hospitalization and ICU admission (OR 1.37, 95% CI 1.18-1.61; 3 studies, 151 485 women), but there was no significant difference in the need for respiratory support between MHT users and nonusers (OR 0.91, 95% CI 0.52-1.59; 3 studies, 151 485 women). Overall, the tendency and magnitude of the effects of MHT in postmenopausal women with COVID-19 were consistent across the included studies. LIMITATIONS, REASONS FOR CAUTION: The certainty of the evidence for other outcomes of this review may be limited, as all included studies were cohort studies. In addition, the dosages and durations of exogenous estrogen used by postmenopausal women varied from study to study, and combined progestogen administration may have had some effect on the outcomes. WIDER IMPLICATIONS OF THE FINDINGS: The findings of this study can aid in counseling postmenopausal women taking MHT when they are diagnosed with COVID, as they have a lower chance of death than those not taking MHT. STUDY FUNDING/COMPETING INTEREST(S): Khon Kaen University provided financial support for this review and had no involvement at any stage of the study. The authors have no conflicts of interest to declare. REGISTRATION NUMBER: PROSPERO, CRD42021271882.

Anastrozole dose escalation for optimal estrogen suppression in postmenopausal early stage breast cancer: A prospective trial

Introduction: We performed matched case-control studies utilizing cohorts of postmenopausal women with ER+ breast cancer receiving adjuvant aromatase inhibitors (AI) on MA.27 [anastrozole, exemestane] or PreFace [letrozole] to assess the association between estrogen suppression after 6 months of treatment and an early breast cancer (EBC) event within 5 years of AI initiation (Clin Cancer Res 2020;26:2986-98). We found a significant 3.0-fold increase in risk of an EBC event for those taking anastrozole with levels of estrone (E1) >=1.3 pg/mL and estradiol (E2) >=0.5 pg/mL, but not for exemestane or letrozole. Given these findings we designed a prospective pharmacodynamic (PD) study to evaluate the impact of anastrozole (1 mg/day: ANA1) on E1 and E2 levels, and among those with inadequate estrogen suppression (IES: E1 >=1.3 pg/mL and E2 >=0.5 pg/mL), to evaluate the safety and PD efficacy of high-dose anastrozole (10 mg/day: ANA10), which has been found to be safe in prior clinical trials (Cancer 1998;83:1142-52). Method(s): Post-menopausal women with stage I-III, ER >=1% positive/HER2-negative breast cancer who were candidates for anastrozole were eligible after completion of locoregional therapy and chemotherapy, as clinically indicated. Women who were pre-menopausal at diagnosis were not eligible. All patients received 8-10 weeks of ANA1, after which those with adequate estrogen suppression (AES: E1< 1.3 pg/mL or E2< 0.5 pg/mL) came off study. Those with IES went on to receive ANA10 for 8-10 weeks, followed by letrozole (2.5 mg/day: LET) for 8-10 weeks. All patients were managed at their treating oncologist's discretion following study discontinuation. E1 and E2 blood levels were measured pre-treatment and after completion of each treatment cycle by a CLIA-approved liquid chromatography with tandem mass spectrometry in the Immunochemical Core Laboratory at Mayo Clinic. With a sample size of 29 patients with IES after ANA1, a one-sided binomial test of proportions with a significance level of 0.05 will have an 87% chance of rejecting the proportion with AES after ANA10 is at most 25% (Ho) when the true proportion is at least 50%. Specifically, the null hypothesis is rejected if the number of women with AES after ANA10 is 12 or more. Data lock was July 6, 2022. Result(s): Of the 161 women enrolled from April 2020 through May 2022, 3 withdrew consent prior to start of ANA1 and 2 were ineligible;thus, 156 women comprised the study cohort. Median patient age was 64 years (range 44-86), 10% of patients were of Hispanic ethnicity and/or non-white race, and 15% received chemotherapy. Six patients remain on ANA1, and 10 discontinued ANA1 due to refusal (7), adverse event (AE) (2), or COVID-19 (1). Forty-one of the remaining 140 patients (29.3% 95%CI: 21.9- 37.6%) had IES with ANA1. Nine of these 41 patients did not go on to ANA10 due to refusal (6) or AE (3). Of the 32 patients who started ANA10, 8 remain on treatment, 5 discontinued due to refusal (3) or AE (1-grade 2 urinary tract infection;1-grade 1 palpitations), and 19 had a blood draw 45 days or more after starting ANA10. No grade 3-5 AEs or grade 2 hot flashes or arthralgias were reported. Of these 19 patients, 14 achieved AES with ANA10 (73.7% 95%CI: 48.8-90.9%). All 19 patients switched to LET of which 3 remain on treatment, 1 is missing E1/E2 data, and 15 had a blood draw 45 days or more after starting LET. Of these 15 patients, 10 maintained AES, 2 acquired AES with LET, and 3 no longer had AES. Anastrozole and letrozole drug levels will be reported at the meeting. Conclusion(s): Approximately 29% of postmenopausal women with ER+/HER2- BC receiving adjuvant anastrozole 1 mg/daily had IES. A majority of these patients achieved AES with dose escalation to ANA10 without tolerability issues. E1 and E2 levels are logical biomarkers given the mechanism of action of anastrozole, and further study utilizing them to determine the optimal dose of anastrozole for a given patient should be performed.

Premenopausal and postmenopausal women during the COVID-19 pandemic.

The current global COVID-19 mortality rate is estimated to be around 3.4%; however, it is dependent on age, sex, and comorbidities. Epidemiological evidence shows gender disparities in COVID-19 severity and fatality, with non-menopausal females having milder severity and better outcomes than age-matched males. However, the difference vanishes when comparing postmenopausal women with age-matched men. It has been suggested that, to some extent, this is due to the protective role of female hormones, such as anti-Müllerian hormone and oestradiol (E2), in non-menopausal women. Oestrogens have been hypothesized to be crucial in modulating viral infection and the progression of the disease via an action on immune/inflammatory responses and angiotensin-converting enzyme type 2 expression. Hence, the most likely explanation is that, because the levels of oestrogen in females after menopause decrease, oestrogen no longer offers a beneficial effect as seen in younger females. The COVID-19 pandemic has highlighted the serious negative effects arising from the state of E2 deficiency. Therefore, hormone replacement therapy gains further support as the damaging effect of the decline in ovarian function affects many biological systems, and recently with the COVID-19 pandemic, oestrogen's vital role within the immune system has become quite clear. However, additional clinical investigations regarding hormone replacement therapy are urgently needed to further verify the protective and therapeutic effects of E2 on menopausal women with COVID-19.

At-risk patient and healthcare provider perspectives on clinical trial participation for ductal carcinoma in situ

Background: Significant challenges exist in recruiting newly diagnosed ductal carcinoma in situ (DCIS) patients to participate in presurgical intervention trials. Perceived motivators and barriers to participation have not been formally studied from the patient or healthcare provider (HCP) perspective. Based on our experience in the Promise Study (NCT02694809), we hypothesized that delaying surgery and concern for side effects are barriers to trial participation and that access to new treatments and financial benefits are motivators. To improve recruitment, we conducted focus groups to better understand barriers and motivators for trial participation in our patient population. Methods: Three focus groups with post-menopausal women (PMW) without history of DCIS, one focus group with patients previously treated for DCIS, and two HCP focus groups were conducted. Due to COVID-19, the focus groups took place online via videoconferencing and included participants from across the United States. A thirdparty facilitator generated discussion on predetermined topics including knowledge of DCIS, clinical trial recruitment materials, hormone replacement therapy, healthcare delivery and clinical trials during COVID-19, and perceived motivators and barriers to trial participation in general and specifically for women with DCIS. Here, we focus on comparing perceived influential factors for patient participation in DCIS clinical trials in PMW and HCP focus groups. Qualitative thematic analysis was completed on focus group transcripts in NVivo. Results: PMW had no knowledge of DCIS prior to the focus groups and believed DCIS should be removed promptly. PMW believed barriers to DCIS clinical trial participation included the potential for the study drug to cause harm, distrust of medicine, and the fact that DCIS is not life-threatening. PMW identified helping future DCIS patients, accessing better treatment, and easing anxiety as motivators for DCIS trial participation. HCPs believed patients were motivated by increased monitoring by the medical team, financial incentive, and access to newer treatment. HCPs believed that delays in DCIS surgery, the potential for the intervention to be harmful or ineffective, and the trial causing patient anxiety were barriers. Neither group emphasized time commitment as a barrier to DCIS trial participation. PMW were not motivated by financial incentives. Conclusions: Knowledge about DCIS is lacking in PMW. PMW and HCPs agreed that the risk of harm caused by study interventions is a deterrent to trial participation and that access to superior treatment is a motivator. However, PMW and HCPs did not agree on other motivators and barriers which could lead to missed recruitment opportunities. Providing educational materials on DCIS and addressing motivators and barriers to clinical trial participation may increase recruitment to presurgical DCIS trials.

REGRESSIVE BONE MINERAL DENSITY TRENDS SEEN with DELAY in FOLLOW UP of DENOSUMAB TREATMENT DUE to the PANDEMIC INDUCED LOCKDOWN-A SINGLE CENTRE INDIAN EXPERIENCE

Background: Denosumab (Dmab), a fully human monoclonal antibody that inhibits receptor activator of nuclear factor kappa-β ligand (RANKL), which selectively inhibits osteoclastogenesis can be used for a long period unlike the relatively short period with Teriparatide.1-2 However the effects of Dmab can quickly regress if the treatment is delayed.3 Objectives: The pandemic led to multiple prolonged lockdowns since March 2020 to Jan 2022 in India. This resulted in follow up Dmab treatment delays. The retrospective study was aimed to look for the effect of the delays. Methods: The bone mineral density (BMD) trends from the central dual-energy X-ray absorptiometry (DXA) at our centre were studied. The trends of patients under Dmab for one year and delay in follow up for 10-12 months for the forth dose were evaluated. 21 postmenopausal women who had been under treatment with Dmab 60 mg subcutaneous injection at 6 monthly interval for one year followed up with such delays. 6 were excluded because of history of sars-cov-2 infection and glucocorticoid use. In the study group of 15 (n=15), the mean BMD at L2, L3 & L4 (sp BMD) and Right and Left Hip (hip BMD) were studied from before treatment (a BMD), 6 months after 1st and at the time of 2nd injection (b BMD), 6 months of the 2nd and at the time of 3 rd injection of Dmab (c BMD), and that due to delay in follow up of 10-12 months (d BMD). The mean percentage trend change between a-b, b-c, and c-d BMDs was evaluated. The least signifcant change (LSC) 4 from a single centre DXA was used to validate the fndings. Results: The mean percentage change after the treatment for the 1st 6 months of Dmab (a-b BMD) was 4.08% and 3.60% and the second injection resulted in a further change (b-c BMD) of 5.98% and 4.52% in the sp BMD & hip BMD respectively. The delay in follow up of 10-12 months resulted in a change (c-d BMD) of-7.81% in the sp BMD and-2.96% in the hip BMD. The LSC from a single centre DXA is 2.6% and 3.6% for sp BMD and hip BMD respectively. A p>0.05 was considered statistically signifcant. Table 1 shows the BMD changes. Conclusion: These fndings suggest that regressive trend in BMD are seen when the treatment with Dmab is delayed even as early as 10 to 12 months. It was seen much faster in the spine compared to the hip. It is therefore advised that short term treatment with Dmab without follow up could lead to loss of all gains and may also worsen the osteoporosis.

HAND OSTEOARTHRITIS: INVESTIGATING PAIN EFFECTS in A RANDOMISED PLACEBO-CONTROLLED FEASIBILITY STUDY of ESTROGEN-CONTAINING THERAPY (HOPE-E): REPORT on the PRIMARY FEASIBILITY OUTCOMES

Background: There is an unmet need for new treatments for hand osteoarthri-tis (OA). Symptomatic hand OA is more common in women and its incidence increases round the age of menopause. Pre-clinical, epidemiological and post hoc studies in Hormone Replacement Therapy (HRT) trials implicate estrogen defciency as of likely importance in OA aetiopathogenesis. No clinical trials of HRT have been carried out in hand OA to date. The licensed HRT Duavive (conjugated estrogens + SERM bazedoxifene) was selected on its potential for efficacy and tolerability. Objectives: We set out to determine the feasibility and acceptability of this form of HRT in post-menopausal women with hand OA, to generate proof of concept data and refne methods for a full study. Methods: ISRCTN12196200. Females aged 40-65 yrs and 1-10yrs after fnal menstrual period with hand OA fulflling ACR criteria and 2+ painful hand joints were recruited. Eligibility incorporated best practice for HRT prescription but did not require menopausal symptoms. Recruitment was at 3 sites in primary/secondary care, including directly from the community. Design was parallel group, double-blind 1:1 randomisation of Duavive or placebo, orally once daily for 24 weeks, then weaning for 4 weeks before stopping. Routes and rates of recruitment and the acceptability of randomisation, medication (compliance, retention), and proposed outcomes were measured, and the likelihood of unblinding. Measures related to hand pain and function, menopause symptoms and joint appearance. Patient and Public Involvement actively informed study rationale, design and materials. An end of study questionnaire and 2 participant focus groups provided further acceptability data. Results: Recruitment was for 12/possible 18 months, interrupted due to COVID-19. Some study procedures were modifed to allow reopening whilst collecting all primary outcomes. 434 enquiries/referrals were received, leading to 96 telephone pre-screens, of which 33 gave written informed consent and attended face to face screening. 28/33 screened (85%) were eligible and randomised. The highest number of randomisations was from study web presence (n=7) followed by SMS text from GP surgeries (n=5). Of 401 not proceeding, 250 (62%) were ineligible, most commonly due to contraindicated medication, followed by medical contraindication, whilst 55 (14%) decided not to take part, for reasons including not wanting to take a hormone-based drug or difficulty attending study visits. Retention and compliance were excellent. All 28 participants completed all study follow ups, with only 3 withdrawals from treatment due to AEs, 2 of these at week 24 and all in the placebo arm. There were no serious AEs. High levels of completeness of all study outcome measures were achieved. Bang's blinding index suggested that participants/investigators were well blinded. There were overall high/good levels of satisfaction with taking part in the study. 26/28 (92%) would recommend taking part to others with hand OA (irrespective of study arm). Many found the fexibility offered by a combination of remote and face to face visits (due to the pandemic) attractive. Additional insights from focus groups were to include hand stiffness as well as pain measures but to reduce the overall number of questions. Conclusion: Despite COVID-19 and a reduced recruitment period, this study recruited sufficient numbers to assess feasibility outcomes. Randomisation of eligible people and retention rates were high. A mixture of remote and face to face visits due to COVID-19 probably improved recruitment and retention and was supported by participants, who were generally satisfed with the study design and medication. The study provided useful insight and improvements that would be incorporated into a future study. Overall, this feasibility study showed that with clear messaging on eligibility and a defned recruitment strategy, recruitment and retention to a study testing this treatment is possible.

LONGITUDINAL STUDY ASSESSING THE EFFECTS OF METHENAMINE HIPPURATE ON THE URINARY MICROBIOME OF POSTMENOPAUSALWOMEN WITH RECURRENT UTI

Introduction: Postmenopausal women with recurrent urinary tract infections (RUTI) are repeatedly exposed to antibiotics and therefore at risk for colonization by multi-drug resistant organisms. Methenamine hippurate (MH) is FDAapproved for the prevention of RUTI;however, the mechanism of action of MH or, more specifically, the role of MH in the alteration of the urobiome is not known. Since preliminary data has shown that MH may be effective against some bacteria (e.g., Escherichia coli), but not others (e.g., Enterococcus faecalis), we hypothesize that resident bladder microbiota will be altered by administration of MH. Objective: Our objective is to determine the longitudinal effect of MH on the urobiome of postmenopausal women with RUTI. Methods: A longitudinal study with a convenient sample of 10 postmenopausal women with a clinical history of RUTI was conducted (Figure 1). UDI6 questionnaires, voided urine, catheterized urine, and peri-urethral swabs were obtained at baseline and three months after daily MH use. Expanded quantitative urine culture (EQUC) was performed on these specimens. In addition, during the 3-month timeframe, four self-collection windows were completed (windows A-D): (A) prior to initiating MH (baseline urobiome), (B) one week after starting MH, (C) two weeks before the 3-month follow-up, and (D) one week before the 3-month follow-up. Voided urine and peri-urethral swabs were collected daily for one week during windows A-D to determine how the urobiome changed. Sequencing of samples from these collection windows is pending. Results: Ten participants enrolled;however, three participants were not able to complete the study due to allergic reaction, improper handling of samples, and COVID infection. Six participants have completed the study;microbiological studies for one participant are still in process. There were no episodes of acute cystitis for any participant during the length of the study. UDI6 results suggested a trend towards a decrease in frequency, leakage with urgency, and abdominal pain;however, none of these were statistically significant (Table 1). Of the six remaining participants, the average baseline urine pH was 5.8 ± 0.8. For the completed participants, an initial microbiological comparison of EQUC results at baseline and 3-month visits show differences in sample diversity. Specifically, the number of species detected (richness) in catheterized urine increased for all but one participant (Figures 2A and 2B) though there was little or no changes in overall diversity (Shannon Index, Figure 2B) or evenness (Pielou's Index, Figure 2C) for any sample type. Exposure to MH did not result in the loss of uropathogenic species present in catheterized urine at baseline;instead, additional uropathogenic and commensal microbiota were detected at the 3-month visit. Conclusions: UDI6 trended towards symptom improvement in frequency, urge incontinence, and pain, consistent with RUTI prevention and symptoms control. Microbiological results suggest that MH increases the richness of the bladder urobiome. This consistent trend suggests MH may reduce RUTI events by altering the urobiome community richness instead of eliminating uropathogenic microbiota from the bladder. Further studies are needed to understand the interaction between MH and a host that is susceptible to uropathogen overgrowth (Table Presented).

Pulmonary benign metastasizing leiomyoma (PBML) - A rare cause of lung tumor

Introduction: Benign metastasizing leiomyoma (BML) is a rare disorder that usually occur in premenopausal women with uterine leiomyoma. The commonest metastasis site is the lungs. Diagnosis and treatment are challenging and there is no standardized treatment for BML. Case Description: We report a case of a 66-year-old menopausal lady who presented to Sarawak General Hospital in October 2021 for Covid-19 infection, with incidental finding of pulmonary benign metastasizing leiomyoma (PBML). She experienced one-year history of weight loss. Chest X-ray on admission revealed a solitary right lung nodule (2 x 2cm). CT thorax revealed a right perihilar lesion with multiple smaller lung nodules. Tuberculosis was excluded. The histopathology result of lung biopsy surprisingly showed spindle cell neoplasm with smooth muscle differentiation. There was no palpable abdominal mass. Ultrasound showed irregular endometrial mass about 3.9 x2 cm. Repeated CT thorax and abdomen in April 2022 showed the lung lesion has enlarged to 4 x 4 cm. Patient is planned for a hysterectomy and bilateral salpingo-oophorectomy following a multidisciplinary meeting among Respiratory Physician, Oncologist and Gynae-oncologist. Discussion: Benign metastasizing leiomyoma is rare and not well understood. It usually occurs in premenopausal women with history of myomectomy or hysterectomy. Only few cases have been reported among postmenopausal women without prior history of leiomyoma. Lung biopsy is crucial in excluding serious causes such as malignancy and achieving the correct diagnosis. As there is no established treatment and monitoring guideline, treatment should be individualized and guided by a multidisciplinary team.

INVESTIGATING IDA: LARGE-SCALE DATA SHOWING PERSISTENT GAPS AT THE FRONT DOOR

Introduction Iron deficiency anaemia (IDA) can be a sign of serious underlying disease but often overlooked. Recently updated guidelines of the British Society of Gastroenterology (BSG) recommend male and postmenopausal female patients with IDA should be screened for coeliac disease and undergo dual endoscopy (or CT). Aims This project looked to assess current adherence to these guidelines at the Queen Elizabeth Hospital in Birmingham. Methods A retrospective audit was performed using health informatics for patients who attended AMU/CDU from April 2018 to March 2021. The number of patients with IDA in this time frame was identified. A further analysis of this group was made to determine the proportion of patients with IDA who had IgA TTG measured as well as those who had OGD and colonoscopy/CT colonoscopy requested. Results There were 67797 patients in this study period. 32422 (47.8%) were anaemic (Hb < 120g/dl for women, <130g/dl for men as per WHO guidelines) of which 6357 (19.6%;9.38% of total) had a microcytic anaemia (MCV <83 as per University Hospitals Birmingham laboratory reference range). Ferritin was tested in 3337 (52.5%) of this group, and of those, 1041 (31.2%) were found to have overt IDA (ferritin <30 mg/mL). Rate of investigation The patient cohort with confirmed IDA comprised 334 males (32.0%), 556 post-menopausal females (53.4%, defined as age ≥45) and 151 pre-menopausal females (14.5%). A further analysis was made to explore how male and postmenopausal female cases were investigated, and if the rate of investigation was affected by the COVID-19 pandemic from 1st March 2020 onwards in this subgroup. Results are shown in the table below. In general, only a minority of patients underwent further investigation with males more likely to undergo OGD than females. Surprisingly, apart from increased TTG check latterly, little difference was seen after onset of the COVID-19 pandemic. Conclusions This large-scale study found that only a small minority of patients with IDA underwent further investigation. Whilst the study period includes the pandemic era, our results don't suggest this made a significant impact on practice. Nevertheless, these findings indicate a strong need for increased awareness and quality improvement about optimising IDA investigation according to BSG guidelines.

Severe Hypertriglyceridemia as a Cause of Arterial Thrombosis with Peripheral Embolic Complications

Lead Author's Financial Disclosures: Nothing to disclose. Study Funding: None. Background/Synopsis: Extensive evidence exists in support of a causal association of elevated triglyceride-rich lipoprotein (TRL) levels with the risk of atherosclerosis progression. Hypertriglyceridemia has been established as a risk factor for venous thrombosis, including a 2- fold increase in the risk of venous thrombosis in postmenopausal women. However, there is limited data on the role of hypertriglyceridemia in the arterial thrombosis. Objective/Purpose: Not Applicable. Methods: Case description: A 51-year-old white female with hypertension and type 2 diabetes (hemoglobin A1C, 7.4%) was transferred for further management of newly diagnosed bilateral renal and splenic infarcts. No risky habits were elicited except for the use of combined hormonal contraceptives over the past two years to control menorrhagia. Family history was significant for hypertriglyceridemia. Her physical exam was unremarkable. Testing for COVID-19 was negative. An extensive hypercoagulable and autoimmune work-up was unremarkable. Fasting lipid profile was significant for elevated levels of triglycerides, 1,274 mg/dL (replicated on two separate occasions), very low-density lipoprotein-cholesterol, 255 mg/dL, and non-high-density lipoprotein-cholesterol, 214 mg/dL, directly measured low-density lipoprotein cholesterol, 39 mg/dL and lipoprotein(a), 6 mg/dL. There was no structural pathology on the echocardiogram, including no interatrial shunt or intracardiac thrombus. Her whole-body computed tomography angiography revealed a focal calcified protruding thrombus in the distal thoracic aorta. No significant plaque was seen elsewhere in the aorta. Results: Decision-making. The posterior thrombus in the distal thoracic and proximal abdominal aorta was determined as a culprit for the visceral organ infarcts. Over the course of the hospital stay her abdominal pain gradually resolved. Treatment with low dose aspirin and therapeutic dose of low-molecular weight heparin was initiated followed by apixaban and aspirin on discharge. She was started on atorvastatin 40 mg, fenofibrate 145 mg, icosapent ethyl 4 g, resulting in a 70% reduction in the triglycerides levels (306 mg/dL). In 3 months, her repeat CT angiography showed significant resolution of the aortic atherothrombosis with no signs of aortic wall inflammation. At the 6-month follow-up visit she was switched to dual antiplatelet therapy with a plan to repeat imaging in 6 months. Conclusions: This case illustrates challenges in managing patients with arterial thrombosis in the setting of familial hypertriglyceridemia. Apart from severely elevated triglycerides no other etiology was evident. We propose further investigation of the prothrombotic properties of TRL and the role of targeted triglyceride-lowering therapies on atherothrombotic outcomes.

Correction of menopausal disorders: New possibilities of menopausal hormone therapy

Determining the role of menopausal hormone therapy in the era of covid infection is an urgent task. The reasons for the lower rate of severe outcomes in women against the background of covid infection compared to men are currently being discussed. This is suggestive of the idea that the female body has the protection that accounts for this advantage. that Scientific literature data were reviewed to select the best combination of estrogen and progesterone when used as menopausal hormone therapy in the present setting. During the analysis of the literature on the use of estrogens and progestins as menopausal hormone therapy published in recent years, we used the following sources: PubMed, E-libary, Scopus. The body of material, which we studied, led us to a conclusion about the preference for the gestagen component when menopausal hormone therapy was prescribed. Gestagen should have the lowest risks in the development of thrombosis, as well as level the pronounced symptoms of peri- and postmenopause. According to the sources we studied and the authors’ own clinical experience, levonorgestrel-containing menopausal hormone therapy preparations have a high safety profileImproving physicians’ literacy about the criteria for prescribing menopausal hormone therapy, including drugs containing two components, estrogen and levonorgestrel in a cyclic regimen, will allow the use of hormone therapy in a wider range of patients in the perimenopausal and postmenopausal periods. © 2022, Remedium Group Ltd. All rights reserved.

Characteristics of COVID-19 in peri-and postmenopausal women. Role of hormone replacement therapy

A literature review on the effect of peri-and postmenopausal period on the course of novel coronavirus infection and post-COVID-19 syndrome was performed. The aspects of hormone replacement therapy against the background of therapy for COVID-19 and post-COVID-19 syndrome were studied. The postmenopausal period in women was found to be a risk factor for a more severe course of COVID-19. Estradiol may act as a protective factor for women with COVID-19 by regulating cellular and humoral immunity factors such as interleukin-2,-6,-8, tumor necrosis factor-α and C3. Prolonged course of COVID-19, persistence of its symptoms and development of severe post-COVID-19 syndrome are associated with female sex, with women in peri-and postmenopausal period being most vulnerable. Symptoms of estrogen deficiency and menopause may be similar to the manifestations of post-COVID-19 syndrome, and these conditions can coexist and aggravate each other. According to international experts, the use of hormone replacement therapy will help to improve the well-being of women, their quality of life, and relieve the symptoms typical of menopause and post-COVID-19 syndrome.