Benefits of the Phytoestrogen Resveratrol for Perimenopausal Women

Endometriosis, characterized by macroscopic lesions in the ovaries, is a serious problem for women who desire conception. Damage to the ovarian cortex is inevitable when lesions are removed via surgery, which finally decreases the ovarian reserve, thereby accelerating the transition to the menopausal state. Soon after cessation of ovarian function, in addition to climacteric symptoms, dyslipidemia and osteopenia are known to occur in women aged >50 years. Epidemiologically, there are sex-related differences in the frequencies of dyslipidemia, hypertension, and osteoporosis. Females are more susceptible to these diseases, prevention of which is important for healthy life expectancy. Dyslipidemia and hypertension are associated with the progression of arteriosclerosis, and arteriosclerotic changes in the large and middle blood vessels are one of the main causes of myocardial and cerebral infarctions. Osteoporosis is associated with aberrant fractures in the spine and hip, which may confine the patients to the bed for long durations. Bone resorption is accelerated by activated osteoclasts, and rapid bone remodeling reduces bone mineral density. Resveratrol, a plant-derived molecule that promotes the function and expression of the sirtuin, SIRT1, has been attracting attention, and many reports have shown that resveratrol might exert cardiovascular protective effects. Preclinical reports also indicate that it can prevent bone loss and endometriosis. In this review, I have described the possible protective effects of resveratrol against arteriosclerosis, osteoporosis, and endometriosis because of its wide-ranging functions, including anti-inflammatory and antioxidative stress functions. As ovarian function inevitably declines after 40 years, intake of resveratrol can be beneficial for women with endometriosis aged <40 years.

Diabetes insipidus as the first manifestation of granulomatosis with polyangiitis: A case report

Background: Granulomatosis with Polyangiitis (GPA) is a necrotizing granulomatosis vasculitis that may influence most organs, but posterior pituitary involvement as the first manifestation is unusual. However, there are some case reports in this regard. Case presentation: A 49-year-old menopausal woman presented with polyuria, polydipsia and weight loss over time headache, purulent nasal discharge, malaise, ear pain developed. After right myringotomy due to secretory otitis media and nasal cavity biopsy, the symptoms exacerbated. Diabetes insipidus was documented by Deprivation test. Thus, 20 microgram nasal spray DDAVP was prescribed. Pituitary MRI +/- Gad demonstrated pituitary involvement. Pituitary axis hormone evaluation was consistent with menopausal state. Chest spiral CT scan showed speculated border soft tissue mass lesion. GPA confirmed with ACR criteria and C-ANCA positive. Therefore, corticosteroid and rituximab were started. Symptoms of DI responded well to the treatment and the spray dosage was decreased. Conclusion: DI can be the first manifestation of GPA; although it is rare, it is worth to be diagnosed early and serious treatment of vasculitis should be started to prevent irreversible damage to the hypophysis cell and unnecessary procedure. Keywords: GPA; granalomatosis vasculitis; diabetes insipidus.

How the Gut Microbiome Links to Menopause and Obesity, with Possible Implications for Endometrial Cancer Development

Background: Interest is growing in the dynamic role of gut microbiome disturbances in human health and disease. No direct evidence is yet available to link gut microbiome dysbiosis to endometrial cancer. This review aims to understand any association between microbiome dysbiosis and important risk factors of endometrial cancer, high estrogen levels, postmenopause and obesity. Methods: A systematic search was performed with PubMed as primary database. Three separate searches were performed to identify all relevant studies. Results: Fifteen studies were identified as highly relevant and included in the review. Eight articles focused on the relationship with obesity and eight studies focused on the menopausal change or estrogen levels. Due to the heterogeneity in patient populations and outcome measures, no meta-analysis could be performed. Both the menopausal change and obesity were noted to enhance dysbiosis by reducing microbiome diversity and increasing the Firmicutes to Bacteroidetes ratio. Both also incurred estrobolome changes, leading to increased systemic estrogen levels, especially after menopause. Furthermore, microbiome dysbiosis was reported to be related to systemic inflammation through toll-like receptor signaling deficiencies and overexpression of pro-inflammatory cytokines. Conclusions: This review highlights that the female gut microbiome is intrinsically linked to estrogen levels, menopausal state and systemic inflammation, which indicates gut microbiome dysbiosis as a potential hallmark for risk stratification for endometrial cancer. Studies are needed to further define the role the gut microbiome plays in women at risk for endometrial cancer.

Use of Hormone Therapy in Women with Early Menopause and Premature Ovarian Insufficiency

Women with early menopause or primary ovarian insufficiency (POI) experience a menopausal state a decade or more earlier than their peers. The health consequences for POI are vast and varied with detrimental effects seen on neurological, psychological, bone, and cardiovascular systems. The risk profile of POI patients requires special attention, as they differ from a typical menopausal population. This review will explore the health risks associated with POI and examine the various treatment options and also the risks associated with hormone therapy. Given the risks and benefits, POI patients should be strongly encouraged to start hormone therapy until the median age of menopause.

Correlation between bone mineral density and endometrial thickness over time in women with breast cancer history

As the efficacy of chemotherapy and adjuvant endocrine therapy for breast cancer increase, the quality-of-life to cancer survivors could be more important issue in strategies of breast cancer treatment. Bone health has become more compelling in care of breast cancer survivor than ever before. This retrospective study was aimed to evaluate factors relating to the change in BMD and to ascertain the correlation between changes in BMD and EMT of women with breast cancer in follow-up. Records of 164 women who underwent surgery for breast cancer were reviewed in this study. The basal characteristics included parity, menopausal state, medication with vitamin D, bisphosphonate, selective estrogen modulator (SERM), aromatase inhibitor (AI), gonadotrophin releasing hormone agonist (GnRHa), chemotherapy, radiotherapy, cancer type including positivity of estrogen receptor, progesterone receptor and HER2, combined the other gynecologic disease or the other origin cancer. At initial and follow-up visit, all subjective were checked with BMD, endometrial thickness (EMT). The mean age was 52.1 ± 8.5 years old and overall interval between initial and follow-up visits were 17.6 ± 7.5 month in this study. The BMDs of L1–4 (1.040 ± 0.166 g/cm2 vs 1.070 ± 0.181 g/cm2, p < 0.001), femur neck (0.850 ± 0.121 g/cm2 vs 0.870 ± 0.136 g/cm2, p < 0.001), and femur total (0.902 ± 0.132 g/cm2 vs 0.915 ± 0.138 g/cm2, p < 0.001) at follow-up visit were significantly lower than those at initial visit. The change in BMDs of L1–4 ( ΔBMDL1–4, r = 0.353, p < 0.001, and r = 0.228, p = 0.003), femur neck ( ΔBMDNeck, r = 0.198, p = 0.011, and r = 0.282, p < 0.001), femur total ( ΔBMDTotal, r = 0.294, p < 0.001, and r = 0.327, p < 0.001) had positive correlation with age and the change in EMT ( ΔEMT). After age correction, ΔEMT had positive correlation with ΔBMDNeck ( r = 0.245, p = 0.002) and ΔBMDTotal ( r = 0.273, p < 0.001). ΔBMDL1–4 and ΔBMDNeck differed according to menopausal state ( p < 0.001 and p = 0.035), bisphosphonate ( p < 0.001 and p < 0.001), and GnRHa ( p < 0.001 and p < 0.001). In follow-up of women with history of breast cancer, ΔEMT could be an alternative screening marker for BMD decrease.

Musculoskeletal Pain during the Menopausal Transition: A Systematic Review and Meta-Analysis

Musculoskeletal pain (MSP) is one of the most severe complaints in women undergoing menopause. The prevalence of MSP varied when taking the menopausal state and age factor into consideration. This study investigated the prevalence of MSP in perimenopausal women and its association with menopausal state. The MEDLINE, Embase, Web of Science, and PubMed databases were searched from inception to July 2020, and 16 studies were retrieved for the current meta-analysis. The primary outcome measure was the MSP Odds Ratio (OR). The estimated overall prevalence of MSP among perimenopausal women was 71% (4144 out of 5836, 95% confidence interval (CI): 64%-78%). Perimenopausal women demonstrated a higher risk for MSP than premenopausal ones (OR: 1.63, 95% CI: 1.35-1.96, P = 0.008 , I 2 = 59.7 % ), but similar to that in postmenopausal ones (OR: 1.07, 95% CI: 0.95–1.20, P = 0.316 , I 2 = 13.4 % ). The postmenopausal women were at a higher risk of moderate/severe MSP than the premenopausal ones (OR: 1.45, 95% CI: 1.21-1.75, P = 0.302 , I 2 = 16.5 % ) or the perimenopausal ones (OR: 1.40, 95% CI: 1.09–1.79, P = 0.106 , I 2 = 55.4 % ). In conclusion, the perimenopause is a state during which women are particularly predisposed to develop MSP. As to moderate to severe degrees of MSP, the odds increase linearly with age, from premenopause to peri- and then to postmenopause.

Sex Differences in the Clinical Profile Among Patients With Gout: Cross-sectional Analyses of an Observational Study

Objective Research findings in gout result predominantly from studies about men and might not be generalizable to women. To improve insight into sex differences in gout, our study compared clinical characteristics and comorbidities of female and male patients with gout, and explored the influence of menopause on these differences. Methods Data from patients referred to 2 rheumatology clinics and diagnosed with gout were used. Clinical characteristics and comorbidities of each sex were compared univariately. Sex difference in comorbidities were further explored in multivariate logistic regression analyses adjusting for age, BMI, smoking, and alcohol consumption in both the total group and in those with gout onset ≥ 55 years (as a surrogate for menopausal state). Results There were 954 patients, including 793 (83%) men, included. Women were on average older (65 vs 62 yrs), were more often obese (54% vs 36%), had a higher serum uric acid (sUA) level (0.53 vs 0.49 mmol/L), used diuretics more often (60% vs 30%), and consumed alcohol less frequently (47% vs 72%). Additionally, women more frequently had reduced renal function (64% vs 31%), hypertension (78% vs 56%), heart failure (23% vs 12%), and type 2 diabetes (39% vs 17%; all P < 0.05). In those with gout onset ≥ 55 years, differences in comorbidities were less pronounced and disappeared after adjusting for lifestyle. Conclusion Our study confirmed sex differences in clinical characteristics and comorbidities among newly diagnosed patients with gout, and revealed that sex differences in comorbidities among those with gout onset beyond the age of female menopause were strongly attenuated and fully explained by lifestyle.

THU0359 GENDER IMPACT ON LOWER URINARY TRACT INVOLVEMENT IN SYSTEMIC SCLEROSIS PATIENTS

Background:Lower urinary tract symptoms (LUTS) are an underdiagnosed but frequent manifestation in systemic sclerosis (SSc) [1]. LUTS pathogenesis in SSc is undetermined, mainly involving dysautonomia, fibrosis and a possible antibody-mediated damage [2]. Divergently from general population, female sex and advanced age are not reported to significantly impact LUTS in SSc [2].Objectives:To evaluate the potential influence of gender and hormone-related factors in LUTS prevalence and severity among SSc patients (Pts).Methods:A population of 42 SSc Pts and 50 age- and sex-matched healthy subjects (HSs) was evaluated. SSc diagnosis was based on 2013 ACR/EULAR criteria. Demographic data, medications interfering with pelvic floor dynamics and general comorbidities commonly associated with LUTS – diabetes mellitus, chronic heart failure, chronic obstructive pulmonary disease, peripheral neuropathy, pelvic organ prolapse, fecal incontinence – were recorded. Validated self-reported questionnaires derived from the International Conference on Incontinence were used to assess prevalence and severity of LUTS, namely of urinary incontinence (UI) and overactive bladder (OAB) [3]. Data were analysed using non-parametric tests. Apvalue <0.05 and a confidence interval (CI) of 95% were considered statistically significant.Results:There were no significant differences in main demographic data between SSc Pts and HSs. Specifically, median age was 61 years (IQR 21-85)vs57 years (IQR 28-93) and female prevalence 83%vs84% in SSc PtsvsHSs, respectively. Amongst the female population, 83% of SSc Ptsvs84% of HSs was in post-menopausal state, with a median of 1 (IQR 0-3)vs1 (IQR 0-4) pregnancy by natural route, respectively. No woman of the study had received hormone replacement therapy or local hormonal therapies prior to the study. Similarly, there were not any significant differences in analysed comorbidities, while ongoing treatment was significantly different between the two populations, SSc patients more frequently receiving calcium channel blockers and glucocorticoids than healthy subjects (p< 0.001). In SSc Pts, statistically significant correlation was observed between stress UI and sex, with an increased female-to-male ratio (p< 0.005), but any significant difference was observed in US distribution depending on parity and menopausal state, nor on other analysed variables. Interestingly, female dominance has not resulted as a significant predictive factor for LUTS prevalence or severity in SSc Pts. In fact, in the regression analysis, SSc disease was the only significant predictor for LUTS (OR 3.45, 95% CI 1.41-7.95; p< 0.01), independently of other analysed variables, particularly of gender and hormone-related factors.Conclusion:This study confirms the absence of pathogenic female-gender participation in LUTS prevalence among SSc Pts. However, consistently with findings on general population, a significant increased prevalence of urinary symptoms, particularly of stress UI, in SSc female Pts has emerged [4]. It is therefore conceivable that hormonal factors may act as a catalytic circumstance rather than pathogenic players in LUTS progression during SSc disease.References:[1]John G et al. Arthritis Care Res (Hoboken) 2018;70(8):1218–27.[2]John G. Clin Rheumatol. 2020;39(1):5–8[3]Abrams P et al, J Urol. 2006;175:1063–6[4]Abelson B et al. Biol Sex Differ. 2018;9(1):45Disclosure of Interests:Greta Pacini: None declared, Sabrina Paolino: None declared, Federica Goegan: None declared, Pietro Francesco Bica: None declared, Elisa Alessandri: None declared, Carmen Pizzorni: None declared, Alberto Sulli Grant/research support from: Laboratori Baldacci, Emanuele Gotelli: None declared, Francesco Cattelan: None declared, Vanessa Smith Grant/research support from: The affiliated company received grants from Research Foundation - Flanders (FWO), Belgian Fund for Scientific Research in Rheumatic diseases (FWRO), Boehringer Ingelheim Pharma GmbH & Co and Janssen-Cilag NV, Consultant of: Boehringer-Ingelheim Pharma GmbH & Co, Speakers bureau: Actelion Pharmaceuticals Ltd, Boehringer-Ingelheim Pharma GmbH & Co and UCB Biopharma Sprl, Maurizio Cutolo Grant/research support from: Bristol-Myers Squibb, Actelion, Celgene, Consultant of: Bristol-Myers Squibb, Speakers bureau: Sigma-Alpha