Postmenopausal Status Research Articles

High-fat diet promotes coagulation and endothelial activation in Sprague Dawley rats: Short-term effects of combined oral contraceptives

BackgroundCombined oral contraceptives (COCs), use in individuals are associated with increased risk of thrombotic events. This highlights the significance of assessing the impact of COC on promoting coagulation and endothelial activation in high-fat diet (HFD)-fed Sprague Dawley rats. MethodsTwenty (20) five-weeks-old female Sprague Dawley rats weighing between 150 and 200g were subjected to both LFD and HFD-feeding for 8-weeks to determine its influence on basic metabolic status, hemostatic profile, hemodynamic parameters (blood pressure and heart rate), as well as selected biomarkers of coagulation (tissue factor and D-dimer) and endothelial activation (Von Willebrand factor and nitric oxide). Thereafter HFD-fed animals were treated with receive high dose combined oral contraceptive (HCOC) and low dose combine oral contraceptive (LCOC) for 6 weeks. ResultsOur results showed that beyond weight gain, HFD-feeding was associated with hyperglycemia, increased mean arterial pressure, and reduced nitric oxide levels when compared with LFD group (p<0.05). Interestingly, treatment with high dose of COC for 6-weeks did not significantly alter atherothrombotic markers (p>0.05). However, this study is not without limitation as regulation of these markers remains to be confirmed within the cardiac tissues or endothelial cells of these animals. ConclusionHFD-feeding orchestrate the concomitant release of pro-coagulants and endothelial activation markers in rats leading to haemostatic imbalance and endothelial dysfunction. Short-term treatment with COC shows no detrimental effects in these HFD-fed rats. Although in terms of clinical relevance, our findings depict the notion that the risk of CVD in association with COC may depend on the dosage and duration of use among other factors especially in certain conditions. However, additional studies are required to confirm these findings, especially long-term effects of this treatment within the cardiac tissues or endothelial cells of these animals in certain conditions relating to postmenopausal state.

The impact of menopause and serum DHEA-S level on the severity of Covid-19

ObjectivesWe aimed to demonstrate the difference between premenopausal and postmenopausal women in respect of the clinical course and outcomes of Covid-19. We investigated the epidemiological and hormonal factors which influence the severity of the disease. Study designThis observational cross-sectional study included the female patients admitted to a Covid-19 outpatient clinic between July 2020 and June 2021 and diagnosed with a positive polymerase chain reaction test. Blood samples were obtained to determine the serum levels of follicle stimulating hormone, luteinizing hormone, estradiol, total testosterone and dehydroepiandrosterone sulfate. Main outcome measureOur primary outcome was the poor clinical course of the disease in postmenopausal women. Our secondary outcome was the contribution of hormonal status to the clinical course of the disease. ResultsOur cohort consisted of 253 female patients (85 with mild, 125 with moderate and 43 with severe disease; 101 at the premenopausal and 152 at the postmenopausal stage). There was a statistically significant difference between the patients in different severity groups regarding clinical data and serum levels of luteinizing hormone, follicle stimulating hormone, estradiol and dehydroepiandrosterone sulfate. Being one year younger decreased the odds of having severe Covid-19 0.338-fold relative to the group with mild disease. A decrease in the serum dehydroepiandrosterone sulfate level was associated with a 2.604-fold increase in the odds of having severe Covid-19 relative to the group with mild disease. Being postmenopausal increased the odds of having severe disease compared with mild disease by 2.687-fold. ConclusionsThe prognosis of Covid-19 is more favorable in premenopausal women compared with postmenopausal women. Age, postmenopausal status and serum levels of dehydroepiandrosterone sulfate are important predictors of the severity of Covid-19 for women.

Transgender Women on Estrogen Have a Lower Burden of Thrombotic Events Compared to Cisgender Men: A Nationwide Hospital-Based Survey

Due to public recognition and acceptance, more transgender women are being prescribed gender-affirming estrogen therapy. Traditionally, sexual dimorphism has been shown to play a significant role in the pathophysiology of thrombotic phenomena. While genetic factors remain the key players in the divergent male and female phenotypes, limited information is available regarding the thrombo-vascular effects of estrogen therapy in transgender women. Furthermore, available data has been conflicting with respect to vascular outcomes in this specific population. Therefore, more evidence is required to understand the long-term effects of gender-affirming estrogen therapy. In the current study, we investigated the thrombotic outcomes of estrogen therapy in transgender women (male sex assigned at birth), in comparison to cisgender men and cisgender women. We performed retrospective analyses using the TriNetX database that includes de-identified data for over 250 million patients across 76 certified healthcare organizations. We included all adults over the age of 18 years and excluded those with the presence of documented prothrombotic risk factors such as obesity, diabetes, hyperlipidemia, smoking, and cancer. Within the cohort of cisgender women, we excluded pregnancy and post-menopausal status. The thrombotic outcomes within the transgender cohort were recorded after the start of hormone replacement therapy. To account for thrombotic events, we used search terms such as acute myocardial infarction (MI), cerebral infarcts, pulmonary embolism (PE), and deep vein thrombosis (DVT). We found 12,369 transgender women, 29,746,302 cisgender men, and 32,591,972 cisgender women that were eligible for our study. The transgender women had lower incidences of MI (0.14% vs. 0.38%, P&amp;lt;0.0001), cerebral infarcts (0.21% vs. 0.49%, P&amp;lt;0.0001), and DVT (0.33% vs. 0.47%, P&amp;lt;0.022) compared to cisgender men. The incidence of PE was comparable in both these groups (P=0.85). Furthermore, we observed that transgender women also experienced significantly lower incidences of cerebral infarcts (0.21% vs. 0.42%, P=0.0003) and a moderately decreased incidence of MI (0.14% vs 0.22%, P=0.062) compared to cisgender women. The incidence of venous thrombosis was similar in these two groups. Overall, we observed a paradoxical decrease in rates of thrombotic events, suggesting that estrogen may play a protective role against the development of acute MI, cerebral infarction, and DVT in transgender women. Further investigation is required to understand the downstream targets that offer these cardioprotective effects. Importantly, our data may provide clinicians with reassurance that traditional vascular risks associated with estrogen may be less pronounced in males.

3 The Menopause Transition in Women with Traumatic Brain Injury

Objective:All premenopausal women who survive traumatic brain injury (TBI) will eventually experience menopause. Challenges experienced by women with TBI are superimposed on challenges associated with hormonal changes in midlife. Some women with stressful life contexts such as TBI are more vulnerable to the added burdens of the menopause transition, potentiating its effects. Although it may be argued that TBI research correctly overrepresents the male experience given disparities in injury rates (4:1), there are important differences in how females and males age, their specific health needs, and the psychosocial context of midlife. Development of evidence-based interventions begins with understanding the experience of menopause after TBI, including where and when key problems may emerge.Participants and Methods:All participants were women 40-60 years old, not taking hormones (i.e., replacement therapy or other systematic hormones), with intact ovaries. Women with TBI were &gt; 2 years post injury, whose menstrual period returned after injury, and were living in the community. Severity of injury ranged from complicated-mild to severe TBI. Pre/peri and postmenopausal status was determined by presence/absence of menstrual period in previous 6 months, respectively. Eighteen common menopause symptoms (vasomotor, somatic, psychological, and cognitive) were assessed for presence and frequency (rarely-always), along with Quality of Life in Neurological Disorders (Neuro-QOL) Sleep Disturbance and Traumatic Brain Injury Quality of Life (TBIQOL) Anxiety, Depression, and Fatigue scales.Results:Overall, women with TBI (n = 68) showed greater presence and frequency of symptoms than women without TBI (n = 153), with fewer within-group differences by menopausal status. Among pre/peri-menopausal women, TBI and non-TBI groups did not significantly differ and showed small effect sizes on symptoms associated with changes in estrogen during menopause, including hot flashes, night sweats, bowel and bladder sequelae, and breast tenderness. However, pre/peri-menopausal women with TBI also endorsed body aches and headaches, as well as troubles with memory, focus, fatigue, cognitive concerns, sleep, and anxiety significantly more than their pre/peri-menopausal counterparts (all medium effect sizes). Among postmenopausal women, those with TBI had significantly greater frequency of hot flashes, crying spells, poor memory, worry, moodiness, panic attacks, sleep disturbance, and anxiety than women without TBI. Within TBI, only hot flashes and breast tenderness were greater in postmenopausal versus pre/peri-menopausal women. Within non-TBI, postmenopausal status was associated with significantly greater hot flashes, night sweats, restlessness, poor memory, irritability, sleep disturbance, and anxiety, with greater fatigue but not significantly.Conclusions:The findings support a model of TBI and menopause in which symptoms most closely associated with estrogen decline in pre/peri-menopause are generally similar between women with and without TBI, and symptoms that overlap with common TBI sequelae were generally more often present and frequently experienced among women with TBI versus non-TBI. We did not observe a synergistic or potentiating effect of TBI on menopause symptoms in post-menopause. These findings offer insight that contextualizes the experience of menopause symptoms among women with TBI. Such insights are essential for the development of treatment approaches that maximize health and wellbeing during the menopause transition for women with TBI.

The impact of 4R Care Delivery Model on timing and sequence of bone density screening among patients with breast cancer.

553 Background: Bone loss is common in patients with breast cancer and can impact treatment decisions related to endocrine therapy. Hence, bone density assessment prior to starting endocrine therapy is highly important, especially because endocrine therapy is the first line adjuvant treatment for patients with ER+ breast cancer. Implementing timely bone density assessment is challenging, particularly in the early care trajectory when there are many tests and procedures taking place. We conducted a care delivery optimization in a large health system to implement bone density testing and referral for bone health consultation prior to endocrine therapy. The optimization was conducted as part of implementing the 4R Oncology model (Right Info, Right Care, Right Patient, at the Right Time), a novel approach to improving patient-facing care planning, team-based delivery and patient self-management. Here we describe the impact of this intervention. Methods: A cohort of 278 women with breast cancer who were in the 4R intervention (the 4R cohort) was compared to a historical control cohort of 201 women who received care pre-4R. Demographic, bone health history, and oncologic care data were abstracted from chart review and clinical databases. The prevalence of bone loss and timing of bone density consultation request was compared between the 4R and historical control cohorts. Results: The age, race/ethnicity and rate of ER+ cancer were similar between cohorts. Patients in the 4R cohort were significantly more likely to have received a consultation for bone density screening prior to the start of endocrine therapy (see Table). They were also more likely to receive a bone density test result during their care (Table). These findings remained significant when data were restricted to those ≥ 50 years (as a proxy for postmenopausal status) and those with ER-positive breast cancer. The rates of osteopenia and osteoporosis were similar between the cohorts: control 47%, 24%; 4R cohort: 46%, 23% respectively (data not shown). Conclusions: Care optimization using the 4R Oncology Model was associated with a significant improvement in the timing of bone density testing before initiation of endocrine therapy. The 4R Oncology Model can lead to more informed decision making in adjuvant endocrine therapy for patients with breast cancer. Additional optimizations to improve the rates of bone density tests and referrals will be beneficial.[Table: see text]

Menopause Status and Within-Group Differences in Chronological Age Affect the Functional Neural Correlates of Spatial Context Memory in Middle-Aged Females.

Reductions in the ability to encode and retrieve past experiences in rich spatial contextual detail (episodic memory) are apparent by midlife-a time when most females experience spontaneous menopause. Yet, little is known about how menopause status affects episodic memory-related brain activity at encoding and retrieval in middle-aged premenopausal and postmenopausal females, and whether any observed group differences in brain activity and memory performance correlate with chronological age within group. We conducted an event-related task fMRI study of episodic memory for spatial context to address this knowledge gap. Multivariate behavioral partial least squares was used to investigate how chronological age and retrieval accuracy correlated with brain activity in 31 premenopausal females (age range, 39.55-53.30 years; mean age, 44.28 years; SD age, 3.12 years) and 41 postmenopausal females (age range, 46.70-65.14 years; mean age, 57.56 years; SD age, 3.93 years). We found that postmenopausal status, and advanced age within postmenopause, was associated with lower spatial context memory. The fMRI analysis showed that only in postmenopausal females, advanced age was correlated with decreased activity in occipitotemporal, parahippocampal, and inferior parietal cortices during encoding and retrieval, and poorer spatial context memory performance. In contrast, only premenopausal females exhibited an overlap in encoding and retrieval activity in angular gyrus, midline cortical regions, and prefrontal cortex, which correlated with better spatial context retrieval accuracy. These results highlight how menopause status and chronological age, nested within menopause group, affect episodic memory and its neural correlates at midlife.SIGNIFICANCE STATEMENT This is the first fMRI study to examine how premenopause and postmenopause status affect the neural correlates of episodic memory encoding and retrieval, and how chronological age contributes to any observed group similarities and differences. We found that both menopause status (endocrine age) and chronological age affect spatial context memory and its neural correlates. Menopause status directly affected the direction of age-related and performance-related correlations with brain activity in inferior parietal, parahippocampal, and occipitotemporal cortices across encoding and retrieval. Moreover, we found that only premenopausal females exhibited cortical reinstatement of encoding-related activity in midline cortical, prefrontal, and angular gyrus, at retrieval. This suggests that spatial context memory abilities may rely on distinct brain systems at premenopause compared with postmenopause.

Information Support Provided by Specialized Nurses via Mobile Healthcare App May Improve Treatment Adherence of Breast Cancer Patients: An Observational Study

ObjectivesMobile devices facilitate the healthcare management of breast cancer. Meanwhile, specialist nurses play an important role in disease management. We established a smartphone-based app that enables patients to raise questions to specialist nurses. We aimed to evaluate whether the information support provided by specialist nurses via smartphone app could improve the treatment adherence of breast cancer patients. Data SourceBreast cancer patients who received surgery and registered for the app between March 2013 and April 2020 were included. Data related to the use of the app, the number of raised questions, and the specific content of each question were retrieved. Overall, 2675 patients were included, with 560 patients raising questions to specialist nurses via the app. Patients with higher educational levels, postmenopause status, and more advanced diseases were more likely to seek informational support via a smartphone app. The treatment adherence was 86.4%. Multivariate analysis demonstrated that raising questions was associated with better compliance. Regarding the distribution of questions, 78.8% of patients had questions about the treatment schedule and procedure, 65.9% of patients had questions during the adjuvant treatment, and only 19.6% of patients raised questions about follow-up and rehabilitation. After a median follow-up of 44 months, there was no survival difference between patients who raised questions and those who did not. ConclusionSeeking information support from specialist nurses was associated with better treatment adherence. The smartphone-based healthcare app enables specialist nurses to provide more conducive service for patients, and validation of this finding in further studies is warranted. Implications for Nursing PracticeBreast cancer patients were more interested in problems with treatment procedures and schedules. Those who asked questions had better treatment adherence. The smartphone-based app could not only provide patients with a platform to seek information support but also help specialist nurses understand the needs of patients.

FEATURES OF MENOPAUSE MANAGEMENT AS AN AGING PREVENTION (review article)

Menopause is a physiological transition period in a woman’s life from the reproductive phase with regular ovulatory cycles and corresponding cyclic changes in the reproductive system to the postmenopausal state. The modern concept of female reproductive aging is to recognize the leading role of depletion of the ovarian follicular apparatus. Climacteric syndrome (CS) is the earliest and most common complication of the menopausal period. Most of the pathological manifestations that occur during peri- and postmenopausal periods are associated with an estrogen deficiency state and are subject to correction by hormone replacement therapy (HRT). In addition, in postmenopause the frequency of many diseases that reflect the biological aging of the body increases. Therefore, in order to develop optimal HRT regimens and understand the role of a rational lifestyle in the correction of these manifestations, it is necessary to consider the evolution of views on the menopause in general and HRT in particular. Until now, there has been no consensus regarding the tactics of a differentiated approach when prescribing HRT, taking into account existing systemic disorders in women with a history of “diseases of civilization.” Individualization of HRT in patients with a history of impaired reproductive function should be determined not only by the clinical variability of the manifestations of CS, but also taking into account the presence of extragenital pathology, which requires the implementation of our proposed diagnostic algorithm and the basis for the development of such a HRT strategy.

Breast cancer risk factors and mammographic density among 12518 average-risk women in rural China

BackgroundMammographic density (MD) is a strong risk factor for breast cancer. We aimed to evaluate the association between MD and breast cancer related risk factors among average-risk women in rural China.MethodsThis is a population-based screening study. 12518 women aged 45–64 years with complete MD data from three maternal and childcare hospitals in China were included in the final analysis. ORs and 95%CIs were estimated using generalized logit model by comparing each higher MD (BI-RADS b, c, d) to the lowest group (BI-RADS a). The cumulative logistic regression model was used to estimate the ORtrend (95%CI) and Ptrend by treating MD as an ordinal variable.ResultsOlder age (ORtrend = 0.81, 95%CI: 0.79–0.81, per 2-year increase), higher BMI (ORtrend = 0.73, 95%CI: 0.71–0.75, per 2 kg/m2), more births (ORtrend = 0.47, 95%CI: 0.41–0.54, 3 + vs. 0–1), postmenopausal status (ORtrend = 0.42, 95%CI: 0.38–0.46) were associated with lower MD. For parous women, longer duration of breastfeeding was found to be associated with higher MD when adjusting for study site, age, BMI, and age of first full-term birth (ORtrend = 1.53, 95%CI: 1.27–1.85, 25 + months vs. no breastfeeding; ORtrend = 1.45, 95%CI: 1.20–1.75, 19–24 months vs. no breastfeeding), however, the association became non-significant when adjusting all covariates. Associations between examined risk factors and MD were similar in premenopausal and postmenopausal women except for level of education and oral hormone drug usage. Higher education was only found to be associated with an increased proportion of dense breasts in postmenopausal women (ORtrend = 1.08, 95%CI: 1.02–1.15). Premenopausal women who ever used oral hormone drug were less likely to have dense breasts, though the difference was marginally significant (OR = 0.54, P = 0.045). In postmenopausal women, we also found the proportion of dense breasts increased with age at menopause (ORtrend = 1.31, 95%CI: 1.21–1.43).ConclusionsIn Chinese women with average risk for breast cancer, we found MD was associated with age, BMI, menopausal status, lactation, and age at menopausal. This finding may help to understand the etiology of breast cancer and have implications for breast cancer prevention in China.

THU643 Hyperandrogenism Caused By A Steroid Cell Tumor Of The Ovary In A Postmenopausal Woman

Abstract Disclosure: M.S. Myint: None. A. Pinero-Pilona: None. Introduction Steroid cell tumor-not otherwise specified (SCT-NOS) is a subtype of steroid cell tumors which, in turn, is a subtype of sex cord-stroma tumors of the ovary. SCTs are exceedingly rare, account for less than 0.1% of all ovarian tumors, can secrete androstenedione, α-hydroxyprogesterone, and testosterone, and cause hyperandrogenism. We present a case of SCT-NOS, which was revealed postoperatively and was associated with breast cancer. Clinical Case A 74-year-old postmenopausal woman presented approximately a year after the onset of hirsutism, frontal alopecia and an elevated serum total testosterone (TTST) 341 ng/dl (reference range 3 to 41 ng/dL) and free testosterone (FRTST) 10.5 pg/mL (reference range 0.0 to 4.2 pg/mL). She has no clitoromegaly, acne, striae, or changes in voice and no history of infertility or PCOS. Physical examination was significant for cushingoid appearance, frontal alopecia, and hirsutism on the face. Her estradiol level was 213 pg/mL (reference range 0 to 30 pg/mL), FSH and LH levels were in the postmenopausal range, 17-hydroxyprogesterone, DHEA-sulfate, androstenedione, and morning cortisol were normal. Pelvic ultrasonography and CT of the abdomen and pelvis did not reveal an adrenal or ovarian abnormality. We suspected an ovarian source and thus recommended bilateral oophorectomy due to the markedly elevated testosterone level and postmenopausal status. We also started spironolactone. Before setting up for surgery, she was diagnosed with invasive lobular left breast cancer and underwent surgery and radiotherapy. Then, she had bilateral salpingo-oophorectomy. After surgery, TTST dropped to 4 ng/dL and FRTST to 2 pg/mL. Her hyperandrogenic symptoms significantly subsided. Pathology revealed a 1.5 cm red-brown nodule within the left ovary. The nodule contains polygonal cells with vacuolated cytoplasm arranged in nests, cords, and sheets. Cells were positive in calretinin and inhibin and negative in Reinke crystal. A steroid cell tumor, NOS was confirmed. Pathologic features associated with aggressive clinical behavior were not present. Conclusion The incidence of SCT-NOS is highest in women of childbearing age but rare in postmenopausal women. There were only a few case reports of SCT-NOS, most of which are relatively larger and revealed on imaging. In our case, the imaging did not localize the tumor. Sex cord-stromal tumors are often not visualized on imaging. Failure to identify a tumor on imaging does not rule out the presence of a tumor. One should always rule out androgen-secreting tumors in cases of significantly high testosterone. When imaging fails to reveal a tumor, bilateral oophorectomy should be considered in postmenopausal women and an ovarian and adrenal venous sampling in women of childbearing age. It is worth doing so because hyperandrogenism is associated with an increased risk of endometrial and breast cancer. Presentation: Thursday, June 15, 2023

Urinary Tract Infections After Urogynecologic Surgery: Risk Factors, Timeline, and Uropathogens

ABSTRACT Postoperative urinary tract infection (PO-UTI) is seen in 6.4%–32% of stress urinary incontinence (SUI) and/or pelvic organ prolapse (POP) surgeries despite perioperative antibiotic prophylaxis. Postoperative complications associated with PO-UTI include increased mortality and longer hospitalization. Increasing prevalence of resistance to antibiotics and antibiotic stewardship principles necessitate both the improvement of infection prevention strategies and judicious antibiotic prescriptions. Four factors are known to increase PO-UTI risk: (1) recurrent UTI (RUTI) history, (2) preoperative UTI, (3) day-of-surgery UTI, and (4) prolonged postoperative catheterization. This study intended to determine (1) risk factors of PO-UTI and PO-RUTI, (2) preoperative and postoperative UTI temporal distribution, and (3) detected uropathogens in a large database. The study used medical record data of all SUI/POP surgical procedures performed in the Kaiser Southern California Hospital system from January 1, 2008 to December 31, 2016 for women 18 years of age or older. Procedures used Current Procedural Terminology codes for identifying and subcategorizing surgical procedures and their route (SUI or POP; abdominal or vaginal, respectively). The study-wide definition of UTI was as follows: (1) positive standard urine culture of greater than 105 CFU/mL of ≤2 uropathogens, or (2) prescription of urinary antibiotics prescribed for the indication of UTI symptoms. The analysis consisted of 21,063 urogynecologic surgical procedures performed on 20,051 women (33,626 POP and/or SUI procedures), with 22,641 UTI events being diagnosed in 10,091 women. Mean age was 56.9 years, and mean BMI was 29.1. The cohort underwent surgery for only SUI (35.4%), only POP (32.7%), or POP/SUI combined (31.9%). In the 13.5 months postoperatively, 11,976 UTIs were diagnosed in 6733 women. The first month experienced a sharp increase compared with the preoperative year, the second month increased further, and the third month showed leveling of PO-UTI incidence. Prescribed antibiotics captured most UTI events (13,337 or 58.3%). Prescribed antibiotics, in order of most-prescribed to least-prescribed, were as follows: ciprofloxacin (33.7%), cephalexin (21.4%), nitrofurantoin (20.4%), and sulfamethoxazole-trimethoprim (17.6%). The study determined that most PO-UTIs occurred within the first 2 months, with many of these being diagnosed within 2 weeks of surgery. For those patients already having a history of RUTI, RUTI significantly increases in postoperative year 1 when compared with the preoperative year. All patients undergoing SUI procedures had increased PO-RUTI risks compared with their POP-only group peers. Escherichia coli was the most common pathogen found. Risk and event timing were affected by surgical indication: although surgery for only SUI had a lower 6-week PO-UTI risk, it was counterintuitively associated with a higher PO-RUTI risk. Multivariate regression revealed predictable risk factors for PO-UTI: OAB, history of diabetes, history of preoperative UTI within 6 weeks of surgery, history of RUTI, stent and catheter placement. A more confusing finding was the association of a vaginal estrogen prescription with increased short-term PO-UTI risk, possibly related to its use in women with a history of RUTI, but more probably related to the postmenopausal status of many of the women in the dataset. The study recommends preoperative assessment with the purpose of identifying and eliminating UTIs within 6 weeks before surgery, as well as development of protocols for enhanced prophylaxis for women at increased risk such as diabetics and women with preoperative RUTI.

Factors associated with the combination of general and abdominal obesity in middle-aged and older Korean women: a cross-sectional study.

To identify factors associated with general and abdominal obesity in middle-aged and older Korean women based on the biopsychosocial model. Data from 4,076 women aged ≥45 years who participated in the Korea National Health and Nutrition Examination Survey from 2015 to 2020 were analyzed. Complex sampling analysis was performed using IBM SPSS ver. 26.0. The combination of general and abdominal obesity was positively associated with age ≥65 years, postmenopausal status, and without breastfeeding experience among biomedical factors; depressive symptoms and prolonged (≥8 hours a day) sedentary behavior among psychosocial factors; and an educational level lower than middle or high school graduation and the first and second income quantiles among biosocial factors. Healthcare providers in communities and public societies should screen for risk factors for the combination of general and abdominal obesity while considering non-modifiable biomedical (e.g., age) and biosocial factors (e.g., educational level). In addition, intervention strategies should be developed by considering modifiable psychosocial factors such as sedentary behavior.

Impact of estrogen on IgG glycosylation and serum protein glycosylation in a murine model of healthy postmenopause.

The glycosylation of immunoglobulin (Ig) G regulates IgG interaction capability with Fc gamma receptors found in all immune cells. In pathogenic conditions, estrogen can impact IgG levels and glycosylation. Following menopause, when estrogen levels decline affecting the immune system and potentially leading to a heightened susceptibility of immune activation. In this study, we aim to determine if estrogen levels can regulate IgG glycosylation in postmenopausal healthy situations. Mice were ovariectomized to simulate an estrogen-deficient postmenopausal status and then treated with 17-beta-estradiol (E2) at different doses and different administration strategies. Using a highly sensitive liquid chromatography-tandem mass spectrometry (MS/MS) glycoproteomic method, we demonstrated that E2 treatment increased the degree of glycosylation on IgG-Fc with both galactosylation and sialylation in the position required for interaction with Fc gamma receptors. We also observed that only long-term estrogen deficiency reduces IgG levels and that estrogen status had no impact on total IgG sialylation on both Fab and Fc domains or general glycoprotein sialylation evaluated by ELISA. Furthermore, E2 status did not affect the total sialic acid content of total cells in lymphoid organs and neither B cells nor plasma cells. The study concluded that E2 treatment does not affect total serum glycoprotein sialylation but alters IgG glycosylation, including IgG sialylation, implying that estrogen functions as an intrinsic modulator of IgG sialylation and could thereby be one pathway by which estrogen modulates immunity.

Role of Female Sex Hormones and Immune Response in Salt-Sensitive Hypertension Development: Evidence from Experimental Models.

Female sex hormones have systemic effects unrelated to their reproductive function. We describe experiences of different research groups and our own, on aspects related to the importance of female sex hormones on blood pressure (BP) regulation and salt-sensitivity-mediated BP response and salt sensitivity without alterations in BP, as well as renal sodium handling and interactions with the immune system. Changes in sodium intake in normotensive premenopausal women cause more BP variations than in men. After menopause, women often develop arterial hypertension (HT) with a profile of sodium sensitivity. Besides, experimental results have shown that in adult rat models resembling the postmenopausal hormonal state induced by ovariectomy, controlling BP is not enough to avoid renal and other tissue infiltration with immune cells, which does not occur when sodium intake is low or normal. Therefore, excess sodium promotes an inflammatory state with the involvement of immune cells. The evidence of activation of adaptive immunity, besides changes in T cell subpopulations, includes changes in sodium transporters and receptors. More studies are needed to evaluate the particular sodium sensitivity of women and its meaning. Changes in lifestyle and sodium intake reduction are the main therapeutic steps. However, to face the actual burden of salt-sensitive HT in postmenopausal women and its associated inflammatory/immune changes, it seems reasonable to work on immune cell activity by considering the peripheral blood mononuclear cell phenotypes of molecules and transport proteins related to sodium handle, both to screen for and treat cell activation.

Association between Estrogen Exposure and Idiopathic Subglottic Stenosis.

Idiopathic subglottic stenosis (iSGS) is a rare, recurrent, fibroinflammatory disease affecting the larynx and proximal trachea. Given it occurs primarily in adult females, estrogen is speculated to play a central pathophysiological role. This study aimed to evaluate relationships between estrogen exposure, disease progression, and recurrence. North American Airway Collaborative (NoAAC) data of adults with iSGS obstructive airway lesions, who underwent index endoscopic airway dilation, were used to identify associations between estrogen exposure, disease characteristics, and time to recurrence (TTR), and interventions were analyzed using Kruskal-Wallis test and Pearson coefficient. Cox proportional hazards regression models compared hazard ratios by estrogen exposure. Kaplan-Meier curves were plotted for TTR based on menopausal status. In all, 533 females had complete estrogen data (33% premenopausal, 17% perimenopausal, 50% postmenopausal). Median estrogen exposure was 28 years. Overall, there was no dose-response relationship between estrogen exposure and disease recurrence. Premenopausal patients had significantly shorter time from symptom manifestation to diagnosis (1.17 vs. 1.42 years perimenopausal vs. 2.08 years postmenopausal, p < 0.001), shorter time from diagnosis to index endoscopic airway dilation (1.90 vs. 2.50 vs. 3.76 years, p = 0.005), and higher number of procedures (1.73 vs. 1.20 vs. 1.08 procedures, p < 0.001). We demonstrate premenopausal patients may have a more aggressive disease variant than their peri- and postmenopausal counterparts. However, it is unclear as to whether this is related to reduced estrogen in the peri- and postmenopausal states or the age-related physiology of wound healing and inflammation, regardless of estrogen. 3 Laryngoscope, 134:825-830, 2024.

Dietary quality index and the risk of breast cancer: a case-control study

BackgroundDiet quality is a significant determinant in the etiology of breast cancer (BrCa), but further studies are required to explore this relationship. Therefore, we tried to assess if diet quality, assessed using the Diet Quality Index-International (DQI-I), was related to BrCa among the Iranian population.MethodsIn the present case-control research, 134 women with a recent diagnosis of BrCa and 267 without BrCa were selected as case and control groups. Individual food intake data from a food frequency questionnaire was used to compute DQI-I. Also, the multivariable logistic regression models were utilized to evaluate the association between DQI-I and BrCa odds .ResultsWe found a significant association between the last tertile of DQI-I and BrCa odds in the fully adjusted model (odds ratio (OR) = 0.30; 95% confidence interval (CI): 0.15–0.56). The subgroup analysis based on menopausal status also showed a significant decrease in BrCa odds in pre-and post-menopausal women (pre-menopausal: OR = 0.27; 95% CI: 0.10–0.70 – post-menopausal status: OR = 0.35; 95% CI: 0.13–0.92).ConclusionsOur findings indicated that a higher DQI-I score was related to a lower chance of BrCa. According to our research, a healthy diet pattern is crucial for BrCa prevention.

Factors related to bone mineral density in female patients receiving TSH-suppressive doses of levothyroxine for thyroid cancer

Background: Patients with thyroid cancer receive a high-dose thyroid hormone therapy after total thyroidectomy for suppression of thyroid stimulating hormone (TSH); this may affect bone mineral density (BMD). Identifying the common factors that affect BMD (including the duration of a high dose of thyroid hormone treatment) may, therefore, aid the delivery of appropriate and comprehensive care in such cases. Objective: To identify the factors related to BMD in female patients with thyroid cancer. Materials and Methods: This cross-sectional study evaluated data pertaining to the BMD and demographic characteristics of female patients with thyroid cancer. The patients were aged at least 40 years and received a high-dose thyroid hormone replacement therapy after total thyroidectomy at the Rajavithi Hospital between January 2004 and December 2019. The relationships between BMD and associated factors were analyzed using Pearson’s correlation and multiple linear regression. A p-value of less than 0.05 was considered statistically significant. Results: A total of 100 female patients with a mean age of 55.37 ± 11.36 (40-82) years and mean body mass index (BMI) of 24.8 ± 4.96 (15-40) were included; 60 and 56 of them were postmenopausal and coffee drinkers, respectively. High-dose thyroid hormone replacement therapy was received for a mean duration of 94.59±50.36 (3-210) months and 13 patients had a history of fractures; 60%, 30%, and 10% had normal BMD, osteopenia, and osteoporosis, respectively. The factors affecting BMD included the BMI (p-value &lt;0.001) and postmenopausal status(p-value &lt;0.001). Subgroup analyses showed the BMI to be the factor affecting BMD in the premenopausal group (p-value &lt;0.001). Age, BMI, and calcium supplement intake were found to have an effect on the BMD in the postmenopausal group (p-value= 0.003, 0.002, and 0.020, respectively). The duration of high-dose thyroid hormone intake had no effect on the BMD in both the overall population (p-value= 0.558) and the subgroups based on the menopausal status (p-value = 0.437 and 0.380 in premenopausal and postmenopausal groups, respectively). Conclusion: In female patients who were treated for thyroid cancer, the factors affecting the BMD included the BMI in the premenopausal group and the age, BMI, and calcium supplementation in the postmenopausal group.

Endometriyal Kanserde Delta Nötrofil İndeksinin Öngörücü Potansiyeli: Tanı için Yeni Bir Biyobelirteç

Aim: This study aimed to explore the potential of delta neutrophil index (DNI) as a predictive biomarker for the development of endometrial cancer (EC) in women with endometrial intraepithelial neoplasia (EIN). Material and Methods: This retrospective study included 139 women diagnosed with EIN who underwent surgery between 2019 and 2022. Demographic data, medical history, and laboratory parameters, including DNI, were collected from the patients' medical records. Patients with other types of cancer, a history of steroid use, inflammatory, hematologic, or autoimmune diseases, or missing data were excluded. The patients' pathology reports were reviewed, and patients were divided into three groups by the final pathological diagnosis, benign (n=64), EIN (n=66), and EC (n=39). Results: The mean DNI level of the EC group was found to be significantly higher than the EIN and benign groups (4.85±2.31, 2.31±0.89, 1.48±1.03, p&amp;lt;0.001, respectively). The optimal cut-off value of DNI was determined as 2.75% with 82.1% sensitivity and 73.8% specificity. DNI levels &amp;gt;2.75% were found to be associated with an 11.56-fold (95% CI: 4-59-29.09, p&amp;lt;0.001) increased risk of EC. Smoking and postmenopausal status were also identified as independent risk factors for EC. Patients with smoking had a 4.13-fold (95% CI: 1.54-11.01, p=0.005), and postmenopausal status had a 2.8-fold (95% CI: 1.87-9.04, p=0.034) increased risk of EC. Conclusion: The results of this study suggest that DNI may be a useful biomarker for predicting the risk of EC. The results also confirm that smoking and postmenopausal status are independent risk factors for EC.

Extensive lesions and a positive cone margin are strong predictors of residual disease in subsequent hysterectomy following conization for squamous intraepithelial lesion grade 2 or 3 study design

BackgroundThis study aimed to determine the predictive factors for post-conization of residual disease in subsequent hysterectomy for cervical intraepithelial neoplasia grade 2 or 3.MethodsThis retrospective study included 267 patients with histologically confirmed cervical intraepithelial neoplasia grade 2 or 3 who underwent hysterectomy within 7 months after conization. Clinical data (e.g., age, menopausal status, gravidity, parity, type of transformation zone, conization method) as well as pathological data pertaining to conization and hysterectomy were collected from medical records. A logistic regression model was used to analyze the relationship between the variables and risk of residual lesions in hysterectomy samples.ResultsOverall, 70 (26.2%) patients had residual lesions in their hysterectomy specimens. Univariate analyses revealed that age ≥ 50 years (p=0.019), endocervical gland involvement(p=0.013), positive margin(p < 0.001), and involvement of 3–4 quadrants(p < 0.001) were risk factors for residual lesions. Conversely, postmenopausal status, gravidity ≥ 3, parity ≥ 2, loop electrosurgical excision procedure, and type III transformation zone were not risk factors for residual lesions. A positive margin(p < 0.001) and multiple-quadrant involvement(p < 0.001) were identified as independent risk factors for residual lesions on multivariate analysis.ConclusionsMultiple-quadrant involvement and a positive cone margin were reliable predictive factors for residual disease. Total hysterectomy or repeated cervical conization should be considered for patients with these two risk factors. The identification of high-risk patients with extensive lesions by colposcopic examination before conization is indispensable, as it will enable surgeons to perform conization with consideration of risk factors and possibly improve the approach used for the excisional procedure. For high-risk patients, colposcope-guided cold-knife conization is preferred when resources permit.

Prevalence of PIK3CA mutations in Taiwanese patients with breast cancer: a retrospective next-generation sequencing database analysis.

Breast cancer is the most common cancer type that affects women. In hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) is the most frequently mutated gene associated with poor prognosis. This study evaluated the frequency of PIK3CA mutations in the Taiwanese breast cancer population. This is a retrospective study; patient data were collected for 2 years from a next-generation sequencing database linked to electronic health records (EHRs). The primary endpoint was the regional prevalence of PIK3CA mutation. The secondary endpoints were to decipher the mutation types across breast cancer subtype, menopausal status, and time to treatment failure after everolimus (an mTOR inhibitor) or cyclin-dependent kinase 4/6 (CDK4/6) inhibitor treatment. PIK3CA mutations were identified in 278 of 728 patients (38%). PIK3CA mutations were reported in 43% of patients with HR-/HER2+ subtype and 42% of patients with HR+/HER2- postmenopausal status. A lower prevalence of PIK3CA mutations was observed in triple-negative (27%) and HR+/HER2- premenopausal patients (29%). The most common mutation was at exon 20 (H1047R mutation, 41.6%), followed by exon 9 (E545K mutation, 18.9% and E542K mutation, 10.3%). Among patients treated with CDK4/6 inhibitors, the median time to treatment failure was 12 months (95% CI: 7-21 months) in the PIK3CA mutation cohort and 16 months (95% CI: 11-23 months) in the PIK3CA wild-type cohort, whereas patients receiving an mTOR inhibitor reported a median time to treatment failure of 20.5 months (95% CI: 8-33 months) in the PIK3CA mutation cohort and 6 months (95% CI: 2-9 months) in the PIK3CA wild-type cohort. A high frequency of PIK3CA mutations was detected in Taiwanese patients with breast cancer, which was consistent with previous studies. Early detection of PIK3CA mutations might influence therapeutic decisions, leading to better treatment outcomes.