The authors have declared that no competing interest exists.
Postmenopausal women are at an increased risk of Cardiovascular Disease. We aimed to investigate whether this risk differed between individuals with a naturally occurring and other reasons for menopause within a large population-based Iranian sample.
A total number of 1763 postmenopausal women (defined by amenorrhea for more than a year, or FSH > 30-40 mIU/ml), 900 of them with a natural menopause and 863 of them with other reasons for menopause caused by (hysterectomy without oophorectomy or one side oophorectomy, hysterectomy with oophorectomy or two side oophorectomy without hysterectomy) were recruited as part of the Mashhad Stroke and Heart Atherosclerotic Disorders (MASHAD) cohort study. Biochemical and hematological risk factors were measured in all the subjects and the data were analyzed by SPSS software version 20
There was a significant difference in the presence of cardiovascular disease in the natural menopause group compared with other reasons for menopause group (p<0.05). There was also a meaningful difference between the prevalence of depression and anxiety in the natural menopause individuals compared with other reasons for menopause group (p<0.05).
High prevalence of CVD, depression and anxiety in other reasons in menopause women were observed among Mashhad urban females. It should be considered as a noticeable message. Furthermore, studies are necessary to determine different parameters between evaluating CVD, depression and anxiety among menopauses women.
Menopause means the permanent cessation of menstruation due to loss of ovarian follicular function, which occurs at a mean age of 51 years normally. It is expected that a woman will spends almost a third of her life beyond the menopause. After the menopause, a marker of the end of a woman’s reproductive life, the amount of circulating estrogen falls significantly so the symptoms and disorders related to estrogen deficiency will appear
Menopause can occur before the median age of natural menopause (age 51 years) that called early menopause. It is may be occur due to medical or surgical interventions such as chemotherapy or surgical procedures such as oophorectomy
Menopause can increase the risk of cardiovascular diseases (CVD)
The importance of CVD among women has been highlighted over past decade, leading researchers to investigate the impact of gender differences in CVD risk factors. In some of these studies mentioned higher CVD risk in postmenopausal women but it is not certainly clear whether menopause is an issue of aging, estrogen deficiency or both6. Metabolic syndrome (MetS) is used to define the risk of cardiovascular diseases including obesity, dyslipidemia, hypertension and insulin resistance
In this study we want to explore the associations between normal and other reasons of menopause with CVD and lipid profile as a risk factor of CVD in a large population-based Iranian samples.
In current cross-sectional study, 1556 postmenopausal women (with amenorrhea for more than a year by questioner or FSH > 30-40 mIU/ml )
Anthropometric parameters, including height, body weight, body mass index (BMI) and hip circumference (WC and HC) were measured in all the subjected as previously described
Hematological factors, including white blood cell (WBC), red blood cell (RBC), hemoglobin (HGB), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red cell distribution width (RDW), platelet count (PLT), platelet distribution width (PDW) were measured in all the subjects, as described previously
Depression Inventory (BDI) and Beck Anxiety Inventory (BAI)
Data were analyzed using SPSS-18 software (SPSS Inc., IL, and USA). The normality of distribution was evaluated using Kolmogorov–Smirnov test. Descriptive statistics including mean ± standard deviation was considered for normally distributed variables or median ± interquartile range for variables that were not normally distributed. For normally distributed variables, Student’s t-test was applied to compare clinical and baseline demographics characteristics between groups. The Mann-Whitney U test was used for continuous variables and non-normally distributed variables. For categorical parameters, Chi-square or Fisher exact tests were used. All the analyses were two-sided and
Clinical and demographic characteristics of participants are presented in
Our results demonstrated that the mean of BMI was significantly higher in other reasons of menopause than natural menopause status (p< 0.05). But WC was significantly lower in other reasons of menopause than natural menopause (p< 0.05). Also, there were not significant differences between two groups in HC, mid upper circumference, systolic and diastolic blood pressure (p>0.05).
According to our findings the levels of LDL, BUN, creatinine, AST were significantly higher in the natural menopause group, whereas uric acid and hs-CRP were meaningfully lower in natural menopause group compared with the group of other reasons for the menopause (p< 0.05). But no statistically differences were found in HC, MC, SBP, DBP, glucose, triglyceride, HDL, total and direct bilirubin, and ALT between natural menopause groups and other reasons for menopause groups (
Natural menopause | Other reasons for menopause | p-value | |
N | 900 | 863 | |
Age (years) | 54.32±3.88 | 48.12±7.06 | < 0.001 |
BMI (Kg/m2) | 28.0±4.8 | 29.4±4.9 | 0.007 |
Waist circumference (cm) | 101.4±12.6 | 95.7±12.8 | < 0.001 |
Hip circumference (cm) | 104.87±9.89 | 106.04±10.63 | 0.2 |
Mid upper circumference (cm) | 30.50±3.71 | 31.25±5.51 | 0.094 |
Systolic blood pressure (mmHg) | 128.7±22.3 | 122.8±19.6 | 0.76 |
Diastolic blood pressure (mmHg) | 81.7±11.5 | 79.6±11.7 | 0.63 |
FBG (mg/dl) | 98.91±48.28 | 96.13±36.39 | 0.27 |
Uric acid (mg/dl) | 4.41±1.31 | 4.49±1.25 | 0.007 |
Cholesterol (mg/dl) | 206.99±41.38 | 198.05±40.02 | 0.9 |
Triglyceride (mg/dl) | 127(92-179) | 125(91-173) | 0.9 |
HDL (mg/dl) | 46.6±9.9 | 47.2±10.5 | 0.13 |
LDL (mg/dl) | 127.9±37.8 | 112.2±39.5 | <0.001 |
hs-CRP (mg/l) | 1.98(1.18-4.19) | 2.41(1.25-5.76) | 0.02 |
BUN (mg/dl) | 13.65±4.55 | 11.95±4.09 | <0.001 |
Creatinine (mg/dl) | 0.83±0.27 | 0.79±0.20 | 0.014 |
Total Bilirubin (mg/dl) | 0.43±0.24 | 0.41±0.18 | 0.26 |
Direct Bilirubin (mg/dl) | 0.29±0.14 | 0.26±0.12 | 0.076 |
AST (mg/dl) | 25.18±16.08 | 22.39±10.93 | 0.003 |
ALT (mg/dl) | 16.61±13.37 | 16.59±10.53 | 0.9 |
Depression score | 14.43 | 15.53 | 0.029 |
Anxiety score | 12.46 | 13.92 | 0.006 |
Data are presented as mean (SD) or inter quartile range. Using ANCOVA analyses with age included as model covariates
BMI: body mass index, FBG: fasting blood glucose, HDL: high density lipoprotein, LDL: low density lipoprotein, hs-CRP: high sensitive C reactive protein, BUN: blood urea nitrogen, AST: aspartate transaminase, ALT: alanine transaminase
We also compared the level of different hematological parameters of the participants between natural menopause group and other reasons of menopause group. Results presented in
Natural menopause | Natural menopause | p-value | |
WBC | 5.86±1.44 | 5.91±1.43 | 0.34 |
RBC | 4.72±0.4 | 4.72±0.41 | 0.97 |
HGB | 13.39±1.08 | 13.13±1.31 | 0.07 |
HCT | 40.28±3.45 | 39.95±3.12 | 0.08 |
MCV | 84.37±5.36 | 84.79±5.73 | 0.6 |
MCH | 28.32±2.11 | 27.92±2.46 | 0.42 |
MCHC | 33.15±1.25 | 32.87±1.4 | 0.001 |
PLT | 239.78±61.26 | 235.30±59.16 | 0.004 |
RDW | 41.57±2.98 | 41.36±2.88 | 0.094 |
PDW | 12.87±2.03 | 12.94±1.93 | 0.46 |
MPV | 10.09±1.07 | 10.14±0.92 | 0.27 |
Data are presented as mean (SD). Using ANCOVA analyses with age included as model covariates. CBC: cell blood count, WBC: Wight blood cell, RBC: red blood cell, HGB: hemoglobin, HCT: hematocrit, MCV: Mean Corpuscular Volume, MCH: Mean Corpuscular Hemoglobin, MCHC: Mean Corpuscular Hemoglobin Concentration, PLT: platelets, RDW: Red Cell Distribution Width, PDW: Platelets Distribution Width, MPW: Mean platelet volume.
Logistic regression analysis was performed to determine the odds ratio (OR) of the association between demographic, biochemical and hematological (
Odds Ratio (95% CI) | ||
Univariate | Multivariate |
|
BMI | 1.027(1.008-1.047) |
1.14(1.08-1.2) |
Waist circumference | 0.963(0.955-0.97) |
0.928(0.91-0.947) |
Uric acid | 1.047(0.974-1.124) | 1.268(1.096-1.467) |
LDL | 0.991(0.988-0.993) |
0.998(0.994-1.002) |
BUN | 0.888(0.861-0.916) |
0.94(0.897-0.985) |
Creatinine | 0.331(0.193-0.566) |
1.3(0.492-3.45) |
AST | 0.976(0.965-0.988) |
0.984(0.969-0.999) |
MCHC | 0.819(0.76-0.88) |
0.775(0.677-0.888) |
PLT | 0.999(0.997-1.0) | 0.997(0.994-1) |
CI, confidence interval
: In multivariate analysis age and all factors in table inter to model
: p< 0.001,
: p< 0.01
logistic regression has done; dependent variable was menopause status
In this study, we investigated metabolic syndrome in natural menopause individuals compared to other reasons of menopause groups (
In this study, we investigated diabetes in the natural menopause individuals compared with other reasons of menopause groups (
We have investigated the risk of cardiovascular disease in two groups (
Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI) were used for classification individuals to four groups, no (<13), mild (13-19), moderate (20-28) and severe (29-63) for depression and no (<9), mild (10-16), moderate (17-29) and severe (30-63) for anxiety. Our results showed that 21.9%, 19.7% and 10.1% of women with the other reasons of menopause had mild, moderate and severe depression, respectively (
Natural menopause | other reasons for menopause | p-value | ||
Metabolic syndrome | Yes | 520 (56.5%) | 400(43.5%) | < 0.001 |
no | 378 (44.9%) | 465(55.1%) | ||
Diabetes Mellitus | Yes | 212(60.2%) | 143 (39.8%) | < 0.001 |
No | 698 (49.5%) | 710 (50.5%) | ||
CVD | Yes | 79 (44.1%) | 100 (55.9%) | 0.031 |
No | 821 (51.8%) | 763 (48.2%) | ||
Depression | No | 461 (55.0%) | 410 (48.3%) | 0.043 |
Mild | 176 (19.2%) | 187 (21.9%) | ||
Moderate | 141 (16.5%) | 166 (19.7%) | ||
High | 110 (9.4%) | 112 (10.1%) | ||
Anxiety | No | 412 (47.3%) | 337 (39.9%) | 0.01 |
Mild | 231 (23.8%) | 222 (25.6%) | ||
Moderate | 173 (20.6) | 217 (26%) | ||
High | 87 (8.3%) | 99(8.5%) |
In logistic regression, we made two groups for anxiety (no <9 or yes >10) and depression (no <13 or yes >14). According to logistic regression our results suggested that there is a strong association of anxiety and depression with menopause in univariate and multivariate analysis that adjusted by age (
Odds Ratio (95% CI) | ||
Unadjusted | Multivariate adjusted |
|
Metabolic syndrome (reference: no) | 0.626(0.519-0.756) |
0.932(0.752-1.14) |
Diabetes (reference: no) | 0.648(0.5-0.83) |
0.945(0.727-1.23) |
CVD(reference: no) | 1.36(0.99-1.316) |
1.85(1.31-2.6) |
Depression (reference: no) | 1.53(1.272-1.86) |
1.52(1.23-1.87) |
Anxiety (reference: no) | 1.51(1.255-1.822) |
1.56(1.27-1.92) |
CI, confidence interval
: In multivariate model each disease adjusted for age.
: p< 0.001
: p< 0.01
Results interestingly shown prevalence of depression and anxiety in women with other reasons of menopause is higher than participants with a natural menopause. Many observational studies have shown that the transition to menopause is a period of increased risk of depression
Results of present study showed that the prevalence of cardiovascular disease was higher in participants with other reasons of menopause compared with natural menopause women. It may be explained by other reasons of menopause which it occurs earlier than normal menopause. It has been reported that cardiovascular disease, osteoporosis, urinary incontinence and depression are just a few of many common and major complaints among midlife women, which in result affects their quality of life
We also evaluated the anthropometric, biochemical and hematological indices. The BMI and uric acid were higher in the other reasons of menopause compared with natural menopause group.
The results of current study showed in spite of increased CVD in participants with the other reasons for menopause than normal menopause, they have a lower risk of diabetes and as a result, metabolic syndrome. Dørum et al. published conflict results and reported that women who had undergone bilateral oophorectomy had higher BMI and a trend towards higher blood pressure, lower HDL cholesterol, and elevated triglycerides, that all of them make the metabolic syndrome prevalence higher
It is worthy to mention that this research has some limitation. Our study was cross sectional and this was the most significant limitation of our study. However, it can help us to design a cohort study.
The prevalence of CVD, depression and anxiety was higher in women with other reasons of menopause than subjects with natural menopause in Iranian women. This study evaluated a wide range of disturbances and CVD risk factors in subjects with normal and other reasons for menopause for the first time. But further work is required to establish the accuracy of mentioned findings.
This study was support by grant from Mashhad University of Medical Science
We thank Prof. Gordon A. Ferns for his critical review of this manuscript.