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Which Systemic Feature Is Related To The Effects Of Menopause

Assessment Of Breast Wati And Adipocyte Diameters

The effect of estrogen on the brain

Breast WATi was assessed by measuring the number of CLS-B as previously described . Briefly, immunohistochemistry for CD68 was performed on five sections of breast white adipose tissue per case. The study pathologist assessed cases as CLS-B-positive or negative and recorded the number of CLS-B per case. To determine the total WAT area examined, exclusive of epithelial and fibrotic tissue, digital photographs of each slide were generated and measured with Image J Software . In cases where CLS-B were detected, those with #CLS-B/cm2 above the median value were defined as having severe inflammation, whereas those with values below the median were defined as having mild inflammation.

Adipocyte diameter measurements were performed as previously described . Briefly, breast WAT hematoxylin and eosinstained sections were photographed at 20× using an Olympus B ×50 microscope and MicroFire digital camera . Mean diameters were then calculated from the digitized images by measuring 30 or more individual adipocytes for each patient using the linear dimensional tool in the Canvas 11 Software .

Why Menopause Is Relevant To The Rheumatologist

  • Zoe McLaren, Olivia Hum, Why menopause is relevant to the rheumatologist, Rheumatology, 2021 , keab848,

  • All women who live beyond middle age will go through the menopause. Some with symptoms all with potential long-term health consequences related to cardiovascular disease and bone health. On average women will have 32years of life post-menopause. For many this can mean reaching the peak of career, while balancing responsibilities of childcare and ageing parents, at a time when oestrogen deficiency is beginning to manifest.

    It is important that we break down silos of expertise, arm ourselves with the knowledge to recognize the potential symptoms of the menopause and perimenopause, and consider how that might be contributing to the picture before us. Rheumatology teams provide care for patients with chronic rheumatic diseases through the life course. The data concerning the interaction of these conditions and menopause are incomplete and requires further study. In the same way that we consider contraception, pregnancy and breast feeding in our female patients, we should also be mindful of the effects of the menopause, and consider adding this to our holistic assessment of patients.

    Funding: No specific funding was received from any bodies in the public, commercial or not-for-profit sectors to carry out the work described in this article.

    Disclosure statement: The authors have declared no conflicts of interest.

    Covariates And Exposure Of Interest

    We obtained information on baseline characteristics including race/ethnicity , age at disease onset, and disease duration , as well as time-varying covariates recorded at each annual visit, including menopausal status, disease subtype , smoking , and medications. Medication exposures were collected by physicians and included information on exposure to oral contraceptive pills , hormone replacement therapy , disease-modifying antirheumatic drugs , and exposure to cyclophosphamide. Of note, bosentan was categorized a priori as a DMARD because observational studies have shown a potential beneficial effect on skin thickening , and cyclophosphamide was evaluated independently because of its well-known association with premature gonadal failure . The exposure of interest, menopausal status, was assessed through self-report, by asking the subject if they had reached menopause at baseline or since the last follow-up visit if they were previously premenopausal.

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    Postmenopausal Women Had Significantly Higher Bmi More Severe Wati And Higher Breast Expression Of Aromatase

    One hundred sixty-one women who underwent mastectomy for breast cancer treatment or prevention were included in the study: 102 were premenopausal and 59 were postmenopausal. Clinicopathological features are presented in . Compared with premenopausal women, postmenopausal women were significantly older and had a higher BMI . Women in the postmenopausal group were also more likely to have type II diabetes mellitus, hypertension, dyslipidemia, and more severe breast WATi, measured as the number of CLS-B/cm2, compared with premenopausal women. There were no differences in breast cancer subtypes that developed in pre- vs postmenopausal women.

    Table 1.

    Aromatase messenger RNA levels were significantly higher in postmenopausal compared with premenopausal women . Similarly, aromatase activity was also higher in the postmenopausal group . Moreover, in the multivariable linear regression model including both age and menopausal status, only menopausal status was significantly associated with aromatase expression. There was a significant positive correlation between aromatase and BMI in both pre- and postmenopausal women . In the postmenopausal group, being overweight or obese was associated with higher levels of aromatase mRNA compared with having a healthy weight , whereas the same comparison in premenopausal women did not achieve statistical significance. In women with a BMI 25, menopause was associated with higher aromatase .

    Menopause May Modify The Strength Of The Correlation Between Aromatase And Systemic Markers

    Menopause

    To determine whether systemic factors that reflect metabolic health are associated with aromatase expression, correlative analyses between blood markers and breast aromatase mRNA, in relation to menopausal status, were performed. Results are summarized in . Overall, there was a significant positive correlation between aromatase mRNA and levels of IL-6, insulin, glucose, leptin, hsCRP, HOMA2-IR, and triglycerides. A significant inverse correlation was observed between breast aromatase transcript expression and systemic levels of adiponectin and HDL cholesterol. When the study population was segregated based on menopausal status, associations between aromatase mRNA and glucose remained significant in both groups. However, correlations between aromatase transcript expression and IL-6, leptin, adiponectin, hsCRP, HOMA2-IR, and HDL cholesterol were only significant in the postmenopausal group. The strength of associations between aromatase and blood markers in pre- and postmenopausal groups was then assessed . Findings demonstrate that aromatase mRNA levels are more strongly associated with leptin, hsCRP, adiponectin, and HDL cholesterol after menopause.

    Table 3.

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    Whats The Difference Between Vaginal Atrophy And A Yeast Infection

    Both vaginal atrophy and yeast infections can have symptoms of dryness, itching, redness and pain. However, vaginal atrophy is caused by a lack of estrogen while a vaginal yeast infection is caused by a fungal infection. Consult with your healthcare provider regarding symptoms so that you, together, can determine what condition you have.

    Measurement Of Systemic Factors

    Glucose , insulin , leptin, adiponectin, hsCRP, and IL-6 were measured in plasma using an enzyme-linked immunosorbent assay. Fasting serum levels of triglycerides, as well as total, low-density, and high-density lipoprotein cholesterol were measured by the clinical chemistry laboratory at MSKCC. Quality control was ensured, with intra-assay coefficients of variation being less than 7%.

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    The Epidemiology Of Common Pelvic Floor Disorders

    Pelvic floor disorders traditionally refer to irritative lower urinary tract symptoms and/or overactive bladder dry , urinary incontinence , pelvic organ prolapse , and anal/fecal incontinence . Epidemiologic studies indicate that approximately one in three to four community-dwelling women are affected by PFDs, with the highest rates in menopausal women., The overall prevalence increases with age from 6% in young women between 20 and 29 years, 32% between 50 and 59 years, to 53% in older women aged 80+ years. Key risk factors are well-recognized and include increasing parity, vaginal delivery, increasing age, obesity, and hysterectomy. To date, a significant body of knowledge has accumulated, consistently demonstrating the detrimental quality of life effect of these common conditions. Astoundingly, 69% of hospitalized patients with serious illnesses who were asked to evaluate different health states as compared with death, considered urinary and fecal incontinence same or worse than death, which was higher than the number of people who rated relying on a ventilator to survive.

    In addition to the negative impact of these conditions on the individuals, PFDs impart a substantial economic and societal burden with over 1.2 million estimated new patient visits in the United States in 2010. Recent studies predict that the demand for PFDs care will further increase by 35%, with over 1.6 million visits expected in 2030.

    Treatment Options For Menopauserelated Sexual Dysfunctions

    Pre Menopause Symptoms | Signs And Symptoms Of Menopause | Postmenopausal Symptoms

    3.1. Hormonal Treatment

    3.1.1. Hormonal Replacement Therapy

    3.1.2. Local Estrogen Therapy

    3.1.3. Ospemifene and Tissue-Selective Estrogen Complex

    3.1.4. Androgens: Systemic and Local Treatment

    3.2. Non-Hormonal Treatment

    3.2.1. Central Nervous System Agents for HSDD

    3.2.2. Vaginal Moisturizers and Lubricants

    3.2.3. Laser Therapies

    3.2.4. Future Options

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    Menopause And Urinary Tract Infections

    Urinary tract infection represents a leading cause of bacterial infections in women, across the lifespan. In women, UTI is nearly always treated with antibiotics. These infections have a significant negative impact on health-related QOL and high impact on health care, with an estimated annual social cost of 1.6 billion dollars and 11.3 million prescriptions. The growing concerns about collateral effects and antibiotics resistance are propelling research into new therapies and strategies for prevention.

    Recurrent UTIs , defined as three or more UTIs in 12 months or two UTIs in 6 months, occurs commonly after menopause. While up to 15% of women over 60 will develop frequent UTIs, this percentage increases to 20% for women aged > 65 years. Approximately 25% to 50% of women aged > 80 years have detectable bacteruria on the standard urine culture.

    The presumed etiology of rUTI relates to the reservoir of potential uropathogens within the gut these microbes increase vaginal colonization with enteric bacteria, increasing UTI risk. The pathogenesis of rUTIs in menopausal women may, in part, be related to the microbial changes in vagina associated with menopause. Lower systemic and local estrogen levels raise the vaginal pH and decrease the lactobacillus dominant vaginal flora typical for premenopausal women. Together, these factors increase the chance that microbes with uropathogenic capability establish residence in the vagina.

    Why Is Oestrogen Important For Vaginal Health

    • The vaginal area needs adequate levels of oestrogen to maintain tissue integrity.
    • The vaginal epithelium contains oestrogen receptors which, when stimulated by the hormone, keep the walls thick and elastic.
    • When the amount of oestrogen in the body decreases this is commonly associated with dryness of the vulva and vagina.
    • A normal pre-menopausal vagina is naturally acidic, but with menopause it may become more alkaline, increasing susceptibility to urinary tract infections. A number of factors, including low oestrogen levels, have been implicated in the development of UTIs4-7 and vaginitis8-9 in postmenopausal women.
    • The vulval area changes with ageing as fatty tissue reduces. The labia majora and clitoral hood may contract.
    • This predisposes sensitive, now exposed tissues, to chafing4.
  • Pelvic floor muscles become weaker and urination may become more frequent and difficult to control2.
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    Menopause Is Associated With Significant Differences In Levels Of Systemic Markers

    Circulating factors, stratified based on menopausal status, are presented in . Menopause was associated with a significant increase in the levels of IL-6 , glucose , leptin , and hsCRP . The homeostatic model assessment 2 insulin resistance score, which reflects insulin resistance, was also elevated in postmenopausal women .

    Table 2.

    What Causes Vaginal Atrophy

    Microbiome

    During menopause, your body makes less estrogen. Without estrogen, the lining of the vagina can become thinner and less stretchy. The vaginal canal can also narrow and shorten. Less estrogen lowers the amount of normal vaginal fluids. It also changes the acid balance of the vagina. Women who have just had a baby and are breastfeeding also have a drop in estrogen. These symptoms also occur in women who have had their ovaries removed or are taking certain medications .

    The first sign of vaginal atrophy is usually a decrease in vaginal lubrication.

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    Can Vaginal Atrophy Get Worse

    Be sure to address your symptoms quickly with your healthcare provider. The sooner you get treatment, the less likely it is that your vaginal atrophy will worsen. For example, the longer you go without estrogen, the dryer the vagina will become. Without treatment, yes, your vaginal atrophy may get worse. Occasionally, atrophy can become so severe that it can significantly narrow the vaginal opening. This may make it harder to treat the atrophy if treatment is initiated too late.

    Effect Of Menopause On Autoimmune Diseases

    Menopause natural or premature may affect autoimmune disease in several ways. Menopause may affect morbidity and mortality in autoimmune disease patients through effects on cardiovascular, skeletal and other systems that are already impacted by autoimmune disease-related changes. Menopause has also been suggested to affect onset or activity of certain autoimmune diseases, possibly though alterations in gonadal hormone levels or androgen/estrogen ratios. The effects of sex hormones on the

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    Menopausal Transition And Medical Comorbidities

    One in five women develop AD in the seventh decade of life. Late-onset AD is the most common form of dementia, and two thirds of late-onset AD patients are women. The higher longevity is one of the explanations for the late-onset AD in women however, increasing evidence suggests that longevity alone is not the only explanation, and there may be other underlying mechanisms. Recent multi-modality brain imaging studies have compared cognitively normal 40- to 60-year-old peri-menopausal and post-menopausal women versus age- and education-matched men. The studies indicate that as women go through menopause, multiple imaging findings indicative of AD endophenotype emerge, including reduced brain glucose metabolism in frontal cortex, increased amyloid- accumulation, and gray matter and white matter loss. The patterns of brain hypometabolism correlated with measured reduction in platelet mitochondrial cytochrome oxidase activity, which suggests the emergence of AD-like bioenergetic deficits in peri- and post-menopausal women . Further studies indicate that systemic inflammation and estrogen decline associated with peri-menopause can contribute to accumulation of A. Direct effects of E2 on neuronal A have been demonstrated, showing that E2 decreased the generation and secretion of A in primary neuronal culture and that administration of estrogen in estrogen-deprived mice reversed the elevated levels of brain A .

    Effect Of Autoimmunity And Autoimmune Disease On Menopause

    Hormonal Medication Options for Preventing Alzheimer’s – 273 | Menopause Taylor

    Autoimmunity appears to underlie a significant proportion of cases of premature ovarian failure. Despite the reported prevalence of ANA, RF, and other autoantibodies in these patients, however, there are few reports of POF in non-endocrine autoimmune diseases. Anti-ovarian antibodies have been demonstrated in patients with systemic lupus erythematosus and primary Sogren’s syndrome , , . In one small series of SLE patients, 16/19 were positive for anti-ovarian antibodies .

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    Ht Forms And Regimens

    HT comes in several forms:

    • Oral tablets or pills
    • Vaginal ring
    • Topical gel or spray

    HT pills and skin patches are considered “systemic” therapy because the medication delivered affects the entire body. The risk for blood clots, heart attacks, and certain types of cancers is higher with hormone pills than with skin patches or other transdermal forms.

    Vaginal forms of HT are called “local” therapy. Doctors generally prescribe vaginal applications of low-dose estrogen therapy to specifically treat menopausal symptoms such as vaginal dryness and pain during sex. This type of ET is available in a cream, tablet, or ring that is inserted into the vagina.

    “Bioidentical” Hormones

    “Bioidentical” hormone therapy is promoted as a supposedly more natural and safer alternative to commercial prescription hormones. Bioidentical hormones are typically compounded in a pharmacy. Some compounding pharmacies claim that they can customize these formulations based on saliva tests that show a woman’s individual hormone levels.

    The FDA and many professional medical associations warn patients that “bioidentical” is a marketing term that has no scientific validity. Formulations sold in these pharmacies have not undergone FDA regulatory scrutiny. Some of these compounds contain estriol, a weak form of estrogen, which has not been approved by the FDA for use in any drug. In addition, saliva tests do not give accurate or realistic results, as a woman’s hormone levels fluctuate throughout the day.

    When Should I See My Healthcare Provider For Vaginal Atrophy

    Even if youre not menopausal, be sure to report any symptoms of dryness, pain, burning/itching, urinary problems, UTIs, unusual spotting or bleeding or discharge to your healthcare provider. If weeks go by and the over-the-counter medications youre using for dryness dont work, you should see your healthcare provider then. If you see unusual discharge or bleeding, thats also a reason to see your healthcare provider. Also, always see your healthcare provider for any symptoms that negatively impact your daily life.

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    Calcium And Vitamin D

    A combination of calcium and vitamin D can reduce the risk of osteoporosis, the bone loss associated with menopause. The best sources are from calcium-rich and vitamin D-fortified foods.

    Doctors are currently reconsidering the use of calcium and vitamin D supplements. The U.S. Preventive Services Task Force advises that healthy postmenopausal women don’t need to take these supplements. According to the USPSTF, taking daily low-dose amounts of vitamin D supplements , with or without calcium supplements , does not prevent fractures. For higher doses, the USPSTF says there is not enough evidence to make a recommendation. In addition to possible lack of benefit, these supplements are associated with certain risks, like kidney stones.

    However, calcium and vitamin D are important nutrients. Supplements may be appropriate for certain people including those who do not get enough vitamin D through sunlight exposure and those who do not consume enough calcium in their diet. They are also helpful for people who have been diagnosed with osteoporosis. Talk with your doctor about whether or not you should take supplements.

    The National Osteoporosis Foundation recommends:

    Calcium

    Vitamin D

    Vitamin D is necessary for the absorption of calcium in the stomach and gastrointestinal tract and is the essential companion to calcium in maintaining strong bones.

    Age At Natural Menopause

    Estrogen, Menopause, and the Aging Brain: How Basic ...

    summarizes the results of the estimations of age at natural menopause. The mean recalled age at menopause was 46.4 years . The median age at menopause computed by logit analysis was 50.7 years, quite similar to the age of 50.5 years that resulted from the analysis restricted to women 40 years of age . The median age calculated by the KaplanMeier survival analysis was 50.8 years this figure was consistent with that obtained by logit analysis. In survival analyses, 101 patients with amenorrhoea who did not fulfil the criteria of natural menopause were censored: 39 by age at hysterectomy, 61 by age at first exposure to CYC and 1 by age at diagnosis of SCKD. Premenopausal patients were censored by age at interview. When competing risks were considered in the KaplanMeier analysis, the median age at natural menopause was 2.45 years later: 53.3 years . At age 50 years the adjusted cumulative incidence was 0.32, therefore the cumulative survival proportion by each age year was higher across the analysis.

    Distribution of age at natural menopause among women with SLE

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