Early Menopause Group Research Articles

Impact of early age at menopause on disease outcomes in postmenopausal women with rheumatoid arthritis: a large observational cohort study of Korean patients with rheumatoid arthritis

ObjectivesTo assess the differences in clinical outcomes between patients with rheumatoid arthritis (RA) with early menopause (EM) (<45 years) and usual menopause (UM) (≥45 years) and to identify the impact...

Echocardiographic Evaluation of Diastolic Dysfunction among Menopausal Women: A Cross-sectional Study

Introduction: Heart Failure with Normal Ejection Fraction (HFNEF), also known as Diastolic Heart Failure (DHF), has been well-studied since the past two decades. The signs of HFNEF are signs of heart failure and abnormal ventricular filling pressure with normal systolic function. A Metabolic Syndrome (MS) is a clustering of metabolic risk factors. Cardiovascular disease caused by metabolic syndrome includes vascular and myocardial abnormalities such as diastolic dysfunction and relaxation abnormalities. Aim: To study the assosciation between the timing of menopause and Left Ventricular Diastolic Dysfunction (LVDD) in those with and without MS. Materials And Methods: This cross-sectional study was conducted in the period between December 2021 to June 2022 at the Department of Cardiology in A.C.S Medical College and Hospital, Chennai, Tamil Nadu, India. All female patients that underwent a medical examination were selected for the study. Postmenopausal women without overt heart diseases (such as a history of heart valve disease or myocardial infarction, or a prior LV ejection fraction &gt; 50%) were included. This study included 80 patients grouped into two: those with and without MS. The MS group included 30 subjects divided into two subgroups: those who experienced menopause at or before 50 years of age (early menopause group) and those who experienced menopause at or after 50 years of age (late menopause group). Out of 80, 50 participants were divided into early menopause and late menopause groups among women without MS. This study analyse the evolution of left ventricular diastolic dysfunction (LVDD), assessed by transthoracic echocardiography (TTE), in 80 postmenopausal women with and without MS. Independent t-tests was applied to assess the association between the timing of menopause and LVDD. Results: The mean age was 60±7.3 years in women with MS and 62±8.8 years in women without MS. There were no significant differences in the duration since menopause between the postmenopausal women with and without MS. No significant difference was found between the two groups (early vs. late menopause group) with respect to any diastolic parameter, including Early (E) and Late (A), E/A ratio, and E/e in women with MS. In postmenopausal women without MS, there was a significant difference in diastolic parameters including the A, early diastolic annular velocity (e’), ratio of early diastolic transmitral flow velocity to annular flow velocity was calculated (E/e’) between the two groups (early vs. late menopause group). In comparison to patients with MS, patients without the condition had significantly lower early peak mitral inflow velocity (E, p-value=0.019), early diastolic mitral annulus motion velocity (e’-septal, p-value=0.05), late peak mitral inflow velocity ratio (E/A, p-value=0.07), and LV filling pressure values (E/e, p-value=0.02). Conclusion: Early menopause impacts diastolic function in postmenopausal women and LVDD progression in women without MS. LVDD progression in women with MS was unaffected by early menopause.

Does Arterial Stiffness Increase in Patients with Surgical Early Menopause?

Background Surgical early menopause is early menopause due to medical reasons rather than the natural aging process. Pulse wave velocity (PWV) and augmentation index (AIx) are simple and non-invasive parameters for assessment of arterial stiffness. The aim of this study investigated the arterial stiffness in the surgical early menopause patients. Material and Method We included 40 patients with surgical early menopause and 40 healthy controls for the study. The patients’ arterial stiffness and hemodynamic parameters were measured with Mobil-O-Graph NG (IEM GmbH, Stolberg, Germany) 24-hour ambulatory blood pressure monitor arteriography. Result There was no difference between the groups in baseline demographic, laboratory, and echocardiographic parameters. In patients with surgical early menopause (n=40), the etiology was malignancy in 27 (67.5%), myoma in 11 (27.5%) and bleeding in 2 (5%) patients. PWV was significantly higher in the early menopause group (6.5 m/s, (4.7-8.2) versus 5.6 m/s, (4.5-9.0 m/s); P&amp;lt;0.001), but there was no statistically significant difference in Alx (28.3±10.9% versus 27.4±9.0%; P=0.69). Also, there was no statistically significant difference in terms of cardiac hemodynamic parameters and central aortic pressures. Conclusion Arterial stiffness is significantly increased in surgical early menopause patients compared with healthy subjects independent of other risk factors.

Особливості психологічної адаптації жінок з ранньою менопаузою

Psychoemotional disorders belong to the early symptoms of climacteric syndrome, especially expressed on the background of history of depression. The objective: to investigate the features of the level of situational and personal anxiety, as well as the level of depression in women with early onset menopause. Materials and methods. 214 women were examined, 74 of them had complaints of termination of menstruation in the age group under 40 years old (Group I), 70 menopausal women at the age of 45 years (Group II) and 70 women in age 38–42 years with unbreakable menstrual function (III group). All women were offered a scale of reactive and personal anxiety, the results for each type of anxiety were evaluated in gradations: up to 30 points – low; 31–45 – average; 46 or more – high anxiety. In addition, all participants were asked to complete the Tsong scale, the result was evaluated in the range of the sum of points in gradations: 25–49 – normal, 50–59 – light depression, 60–69 – moderate depression, 70 and more – severe depression. The statistical probability of differences between groups is estimated by the Kolmogorov-Smirnov method. Results. Regardless of the age of menopause, no more than 28% of patients had a low level of situational anxiety, while this result is characteristic of more than half of women of the same age group with preserved reproductive function. A high level of personal anxiety was found among patients in Group I – 27%, which is significantly higher than in women with menopause after 45 years or with preserved reproductive function. In the group of early completion of reproductive function, 87.8% of women in the survey indicated a degree of severity of depression, in the menopause group after 45 years – only half. The absolute majority of patients in both groups had a mild depressive mood, but the frequency of severe depression was almost 6 times higher in the early menopause group. Conclusion. The findings suggest that early menopause is accompanied not only by more severe physical manifestations, such as cardiovascular damage, but also by more pronounced psychological disorders, a high level of not only situational but also personality anxiety, as well as greater prevalence of depression and severe her shape. Such data is an additional argument in favor of the need for correction of menopausal disorders in such women. Key words: early menopause, depression, situational and personality anxiety.

Relationship between Early Menopause and Periodontal Disease in Korean Postmenopausal Women

The purpose of this study was to evaluate the relationship between early menopause and periodontal disease in postmenopausal women using data from the 6th Korean National Health and Nutrition Examination Survey (2013∼2015). A study was conducted with 2,048 postmenopausal women aged 45 to 74 years. Participants were divided into the early menopause group (menopause occurring at age 45 years or before) and normal menopause group (menopause occurring after age 45 years). A community periodontal index greater than or equal to code 3 was used to define periodontal treatment needs. A chi-square test was used to confirm the bivariate relationship between the variables. Multinomial logistic regression analysis was used to adjust for covariates (age, education, family income, body mass index, alcohol drinking, smoking, visiting dentist in the last year, use of oral care products, frequency of tooth brushing per day). The risk of periodontal disease was higher in the early menopause group after adjusting for potential confounders (odds ratio, 1.59). In particular, the relationship between early menopause and periodontal disease was more evident in women with low education and those who did not use oral care products. The findings of this study suggest that early menopause is a significant factor of periodontal disease in Korean women.

Early menopause does not influence left ventricular diastolic dysfunction: A clinical observational study in healthy subjects

BackgroundThe prevalence of left ventricular diastolic dysfunction (LVDD) sharply increases in women after their 50s and may contribute to the high prevalence of diastolic heart failure in elderly women. A decrease in estrogen levels after menopause is postulated to be one of the mechanisms responsible for this phenomenon. However, there is a paucity of data on the relationship between the timing of menopause and the progression of LVDD in the clinical setting; thus, we investigated this relationship in healthy postmenopausal women. MethodsWe enrolled 115 women and divided them into two groups according to median menopause age: 61 who experienced menopause at ≤50 years (early menopause group), and 54 who experienced menopause at >50 years (late menopause group). We compared the echocardiographic and clinical characteristics between the two groups. ResultsThere were no significant differences in LV diastolic parameters (mitral E/A, p=0.561; e’, p=0.052; E/e’, p=0.081; DCT, p=0.082; prevalence of LVDD class, p=0.801), as well as other echocardiographic parameters and clinical characteristics between the two groups. Multivariate linear regression analysis showed that the independent determinants of LVDD were age and body mass index, but not the timing of menopause. ConclusionsEarly menopause did not influence the progression of LVDD in postmenopausal women. The sharp progression of LVDD in elderly women is complex and probably influenced by multiple factors.

Differential effects of estradiol on carotid artery inflammation when administered early versus late after surgical menopause

The aim of this study was to determine the effects of estrogen therapy (ET) on carotid artery inflammation when initiated early and late relative to surgical menopause. Female cynomolgus macaques consuming atherogenic diets were ovariectomized and randomized to control or oral estradiol (E2; human equivalent dose of 1 mg/d micronized E2) initiated at 1 month (early menopause, n = 24) or 54 months (late menopause, n = 40) after ovariectomy. The treatment period was 8 months. Carotid artery expression of the markers of monocyte/macrophages (CD68 and CD163), dendritic cells (CD83), natural killer cells (neural cell adhesion molecule-1), and interferon-γ was significantly lower in E2-treated animals in the early menopause group but not in the late menopause group (P < 0.05). In contrast, carotid artery transcripts for T-cell markers (CD3, CD4, CD8, and CD25), interleukin-10, type I collagen, monocyte chemoattractant protein-1, matrix metalloproteinase-9, and tumor necrosis factor-α were lower in E2-treated monkeys regardless of menopausal stage (P < 0.05). ET initiated soon after menopause inhibits macrophage accumulation in the carotid artery, an effect that is not observed when E2 is administered after several years of estrogen deficiency. No evidence for pro-inflammatory effects of late ET is observed. The results provide support for the timing hypothesis of postmenopausal ET with implications for the interpretation of outcomes in the Women's Health Initiative.

Aerobic physical training has little effect on cardiovascular autonomic control in aging rats subjected to early menopause

We investigated and compared the effects of physiological menopause (PM) and early menopause (EM) and the adaptations promoted by physical training on the cardiovascular autonomic control of aged rats. Female Wistar rats (N=72) were assigned to 3 groups: control (22weeks old rats, undergoing sham surgery in the 10th week of life), PM (82weeks old rats, undergoing sham surgery in the 10th week of life) and EM (82weeks old rats, undergoing ovariectomy in the 10th week of life). In each group, half of the rats were subjected to swimming training over a period of 10weeks. Sedentary PM and EM groups had higher basal mean arterial pressure (MAP) and heart rate (HR) and lower intrinsic HR compared to the sedentary control group. Physical training reduced MAP in PM group. All trained groups had lower basal HR; however, only control and PM-trained groups showed decreased intrinsic HR. The assessment of cardiac autonomic balance showed that PM and EM sedentary groups exhibited sympathetic predominance compared to control group. After physical training, only EM group presented sympathetic predominance. HR variability (pulse interval) was similar among all sedentary groups. However, control and PM-trained groups showed lower power in low frequency band (LF; 0.2–0.75Hz) and higher power in high frequency band (HF; 0.75–3.0Hz). The analysis of systolic arterial pressure variability revealed that PM and EM sedentary groups had higher LF power. However, PM group showed lower LF power following physical training. Finally, PM and EM groups had a reduction in spontaneous baroreflex sensitivity, that was attenuated by physical training. The overall results suggest that PM or EM promotes similar negative effects on MAP, HR and cardiovascular autonomic control. However, unlike the PM group, physical training was not able to mitigate all negative effects of EM on cardiovascular autonomic control.

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Age at menopause and cause-specific mortality in South Korean women: Kangwha Cohort Study

Objective The purpose of this study was to examine the relation between age at natural menopause and all-cause and cause-specific mortality among women. Methods This study used the data of the Kangwha Cohort that was followed up from 1985 to 2001, in particular, for the group of 55 years or older women ( n = 2658). We calculated the hazard ratio of mortality by the group of age at menopause using the Cox proportional hazards model with adjustment for age, alcohol consumption, education, age at first birth, self-cognitive health level, chronic disease, marital partner, parity, age at menarche, oral contraceptive use and hypertension. Results The mean (standard deviation) age at menopause was 46.9 (4.9) years, and the median age was 48 years. After adjusting for the relevant variables, the risk of total death in the early menopause group (<40 years at menopause) was 1.32 times higher than that of the reference group (45–49 years at menopause) (95% confidence interval [CI], 1.05–1.66, p = 0.02). For the early menopause group, relative to the reference group, the adjusted hazard ratios of death due to cardiovascular disease and cancer were 1.53 (95% CI, 1.00–2.39, p = 0.04) and 2.01 (95% CI, 1.06–3.82, p = 0.03), respectively. Conclusion Through this study, the age at menopause was found to be different between Asian and Caucasian women and the association of age at menopause with death, particularly caused by cardiovascular disease and cancer, was validated. Our study is one of rare studies regarding the age at menopause of Asian women and their risk of mortality, which could be considered to be meaningful.

Prospective investigation of annual bone loss rate in females in Changsha city, Hunan province

To investigate prospectively the annual bone loss rate at spine, proximal femur and distal radius in females and its relationship to relevant factors. The bone mineral density (BMD) at anteroposterior lumber, proximal femur and distal radius in 220 women of Mawangdui Township, aged 36 - 60, was measured twice, March to April 2000 and March to April 2004, using a Hologic QDR 4500A fan beam X-ray bone densitometer. The annual bone loss rate was the highest during the period of 1 to 5 years since menopause, showing an annual bone loss of 1.70% at the anteroposterior spine, and 2.21%, 1.92%, and 1.56% at the femoral neck, greater trochanter, and distal radius respectively. Even before menopause bone loss was found at the femoral neck and distal radius. BMD loss at the anteroposterior spine and greater trochanter was found in the peri-menopause group. The bone loss rate was the highest in the early menopause group (1.56%/year, P < 0.01), and became lower, however, not significantly in the late menopause group (0.38%/year, P > 0.05). Age was positively correlated with the annual bone loss rates at the anteroposterior spine, greater trochanter, and distal radius (gamma = 0.223 - 0.547, P < 0.05 - 0.01), and the number of year since menopause was also positively correlated with the annual bone loss rate at anteroposterior spine and greater trochanter (gamma = 0.432 - 0.569 P < 0.05 - 0.01). However, body weight and body mass index were negatively correlated with the annual bone loss rates at the anteroposterior spine, femoral neck, and greater trochanter (gamma = 0.239 - 0.466, P < 0.05 - 0.01). Annual bone loss varies at different skeletal region. Age, years since menopause, and body weight influence the bone loss at different skeletal regions in females.

Early menopause: increased fracture risk at older age.

The aim of this study was primarily to determine the relationship between early menopause and the presence of fractures later in life, and secondly, to check for the significance of confounding factors (such as smoking habits, body mass index (BMI), weight and use of hormones). In this cross-sectional population based study, the subjects were 4725 postmenopausal women, 50-80 years of age, registered with 23 general practitioners (GPs). For the purpose of the present study, the total population was analyzed as well as the subgroup of 2757 women (the study population) with a natural menopause. Medical history questionnaire, weight, height and bone mineral density measurements were taken. Bivariate and multivariate analyses were carried out with documented fractures in three categories: during lifetime; after menopause and after age 50 years) as dependent variable and age, BMI, bone mineral density, weight, smoking habits, use of hormones and early menopause as independent variables. The total study population as well as the subgroups "early" and "normal menopause", stratified in three 10-year and in six 5-year categories, were analyzed. Results are expressed as odds ratio and 95% confidence intervals (CI). Multivariate logistic regression analysis revealed that over 70 years of age, BMD< or =0.800 ( t-score<2.5) and early menopause were the only systemic independent predictors of all three fracture categories. Comparing the subgroups normal menopause and early menopause, the early menopause group showed a statistically significant higher overall fracture rate (OR=1.5; CI 1.2-1.8). Over age 70, the difference in the prevalence of fractures reached statistical significance in each age category (OR: 1.8 and 2.1, respectively). Smoking was found to be associated with early menopause (OR=1.5; CI 1.2-1.8) but not with the presence of fractures. Height above 165 cm was found to be associated with a higher prevalence of fractures during lifetime. The present study shows that early menopause is statistically significant associated with the presence of fractures during lifetime, after age 50 years and after menopause. Especially at older age, early menopause is an important predictor of fractures.

Premature ovarian failure

Secondary amenorrhoea with elevated gonadotrophins occurring under the age of 40 (premature ovarian failure (POF)), and at the age between 41 and 44 years (early menopause (EM)), respectively, affects 1–2% and 5% of women in the general population. Objective of this study was to evaluate the prevalence of familial cases of POF and EM and to assess the clinical and genetic characteristics of these patients. One hundred and sixty women with idiopathic secondary amenorrhoea before the age of 45 and serum follicle-stimulating hormone (FSH) levels greater than or equal to 40 IU/l were included in the study. Tests performed on patients included complete medical history, pedigree’s analysis, clinical pelvic examination, gonadotrophins and thyroid assessment, chromosomal analysis. The 160 patients included in the study showed idiopathic POF ( n=130) or EM ( n=30). Following pedigree assessment, we were able to identify an incidence of familial cases of 28.5% in the POF group ( n=37) and of 50% in the EM group ( n=15). POF and EM condition were often present in the same family. There were no differences between POF and EM patients and between familial and sporadic cases regarding age at menarche, personal history, gynaecological history, weight, height and diet habits. There was a statistically significant difference between sporadic and familial cases in age at POF onset: 32.0±7.3 years (12–40) compared to 35.0±5.8 (18–40), respectively ( P<0.05). The POF and EM families identified showed two or more affected females and transmission through either maternal or paternal relatives; in four families both maternal and paternal transmission was observed. This study suggests that idiopathic POF and EM conditions, differing only in age of menopause onset, may represent a variable expression of the same genetic disease. The different age of menopause onset in these patients may be explained by genetic heterogeneity and/or by different environmental factors. Our results indicate a high rate of familial transmission of the condition. Pedigree’s analysis suggests an autosomal or an X-linked dominant sex-limited pattern of inheritance for POF and EM.

Decreased bone mineral density associated with early menopause progresses for at least ten years: Cross-sectional comparisons between early and normal menopausal women

To establish whether early onset of menopause carries an increased risk of osteoporosis, we compared the bone mineral density (BMD) of the second to fourth lumbar vertebrae (L2-4) between 18 women who had menopause before 43 years of age (early menopause group) and 19 women who had menopause after reaching 43 years of age (normal menopause group). Serum levels of calcium, phosphorus, calcitonin, intact parathyroid hormone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), and alkaline phosphatase activity were measured, and urine samples were analyzed to derive calcium/creatinine, hydroxyproline/creatinine, pyridinoline/creatinine, and deoxypyridinoline/creatinine (D-Pyr/Cr) ratios. Mean BMD was significantly lower in the early menopause group than in the normal menopause group, and individual BMD values in about half of the subjects in the former group were below the fracture threshold for Japanese women. Serum concentrations of LH, FSH, and E2 were slightly, but not significantly, lower in the early menopause group than in the normal menopause group. The D-Pyr/Cr ratio was significantly higher in the early menopause group than in the normal menopause group. There was no correlation between L2-4 BMD and age or the number of years after menopause in the normal menopause group, but both age and the number of years after menopause were negatively correlated with L2-4 BMD in the early menopause group. These results indicate that BMD in women who have early menopause continues to decline for up to 10 years, and that menopause and aging increase the risk of osteoporosis.