Associations of the age of menarche and menopause with hypertension in menopausal women in Rasht, Iran in 2020-2021

doi:10.21203/rs.3.rs-2079659/v1

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Associations of the age of menarche and menopause with hypertension in menopausal women in Rasht, Iran in 2020-2021

https://doi.org/10.21203/rs.3.rs-2079659/v1

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Background

A woman's age of menarche as well as her age of menopause are two important points in her reproductive life. Furthermore, hypertension (HTN) is one of the important causes of cardiovascular diseases (CVD) as well as death, and has been considered as a public health issue all around the world. The current study aims at investigating the association of the age of menarche and menopause with HTN in menopausal women.

Methods

The participants who took part in this cross-sectional study included 1500 postmenopausal women. Baecke Habitual Physical Activity Questionnaire (BHPAQ), blood sample and blood pressure (BP) data were analyzed. The researchers examined the association using logistic regression. Data analysis was conducted using SPSS v.21 software. The significance level was considered P<0.05 for all the tests.

Results

Results was seen between the age of menarche and systolic BP (Pearson's Correlation Coefficient, r=0.086, p=0.001). No significant relationship was observed between the age of menarche and menopause with the chance of high BP in postmenopausal women. A significant relationship was reported between the age of menarche and systolic BP in postmenopausal women. The level of cholesterol (P<o/oo1) and LDL (P<o/oo1) had a positive effect on increasing systolic BP. However, FBS had a negative effect on increasing BP.

Conclusions

These results suggested that the associations of age at menarche with hypertension could be reduced by factors related to place of residence in Iran and knowledge of the association between age at menarche and living in urban areas, number of children, cholesterol levels, LDL, and FBS in women help prevent the development of hypertension.

Menarche

Menopause

Hypertension

Blood pressure

The age of menarche and the age of menopause are two important stages in women's reproductive life (1). Menarche is defined as a girl's first menstrual period and can be seen as a marker of puberty, after which the ovaries and other endocrine functions related to reproduction begin (2). The prevalence of early menarche (≤ 11 years) has increased worldwide (3–5). In a number of primary studies conducted in western countries an early age of menarche are believed to be associated with a higher risk of cardiovascular diseases (CVD) and its risk factors in women (6, 7) including hypertension or high blood pressure (BP) (8). Also it is shown that age at menarche can be associated with the risk of cardiovascular diseases (9).

The next clinically significant stage of women's life, which has been defined by the World Health Organization, is menopause, which is characterized by amenorrhea for at least 12 consecutive cycles. The average age of women at menopause is 51, although 4% of women experience menopause naturally before the age of 40 (10). Previous studies have shown that both the age of menarche and menopause are associated with BP and/or hypertension (HTN). In children and adolescents, early menarche is associated with higher blood pressure and risk of HTN (11, 12). HTN is a major cause of cardiovascular disease and death and has been recognized as a public health problem all around the world (13, 14). Menopause has also been linked to increased salt sensitivity of BP (15). Another study conducted in Shanghai stated that there was no association between age at menarche and total CVD (16).

Although the above-mentioned studies have been conducted investigating the relationship between the age of menarche and HTN, the heterogeneity of the studies motivated us to bridge the gap. Thus, in this study, we aimed to examine the relationship between age at menarche and menopause and HTN in menopausal women.

Study population

We utilized a cross-sectional study in Rasht, Guilan, Iran. The present research is conducted among a population of postmenopausal women who referred to Dr. Heshmat Hospital during 2020–2021. Eligible people will be selected to enter the study by available sampling method.

The inclusion criteria in the study included menopause only if it the participants have reached this stage of life naturally in the last year, no cancer, no HTN before menopause, no menopause following uterine and ovarian disease and surgery. On the other hand, the exclusion criteria were inability to remember the age of menarche and menopause, history of HTN during pregnancy, thyroid problems, calcium, phosphorus, serum creatinine disorders, kidney problems and kidney dysfunction, and secondary HTN.

Overall, 1553 women with HTN participated in this study. Later on, 53 women were excluded from the study since they did not meet the inclusion criteria. In the end, a sample size of 1500 women were included in the analysis.

Data collection

The collected information in the present study includes demographic variables (age, place of residence, and education level) and the physical activity measurement tool Baecke Habitual Physical Activity Questionnaire (BHPAQ), which is an international standard questionnaire for assessing the level of physical activity. Both the validity and reliability of this questionnaire have been repeatedly checked and confirmed in different countries as well as Iran and with different groups (17, 18). This tool evaluated the activity level of people according to their job type and had 16 five-choice items. Each item was rated on a five-point Likert scale (never = 1, always = 5, “except question number 2, which was scored the other way around”).

People who were physically more active got higher scores, and the minimum total score was 5 and the maximum score was 15. This scale has three sub-scales activities including 1- occupational activity, 2- sports activities, and 3- leisure time activities.

Fertility factors (number of births, number of live children, use of OCP (oral contraceptive pill) or HRT), and body mass index BMI were measured. The blood sample was collected by the nurse to measure HbA1C-FBS-TG-Cholesterol-HDL-LDL. Also, the BP was measured with a calibrated digital device (Tech model MA100). At first, the participants rest for 10 minutes before the BP check, did not use cigarettes or liquids for half an hour before the BP measurement, and their bladders were empty. The patient sited on a chair and BP was measured from the right arm. High systolic blood pressure (SBP) considered higher than 140 and high diastolic blood pressure (DBP) considered higher than 90 (19).

Statistical analysis

Mean (± standard deviation) used to describe age, BMI, reproductive factors, laboratory factors data. Drug history data described as frequency (percentage). Simple and multiple logistic regression analysis were used to investigate the relationship between age, BMI, reproductive factors, laboratory factors data, and drug history with HTN. The normal distribution of quantitative study variables was measured using kurtosis and skewness values, Q-Q plot and Wilk-Shapiro test. Wherever needed, T-test (or Mann-Whitney) was used to compare the average of quantitative variables in two groups, and chi-square test was also used to compare ratios in two groups. Data analysis was done by using SPSS v.21 software. The level of significance of the tests was considered P < 0.05.

The characteristics of the study participants are presented in Table 1. The participants were on average 50.38 ± 3.76 years old. Most women (80.7%) were married and living with their spouses. A significant proportion (14.7%) of women were illiterate and only 10.9% had secondary or higher education. The participants were weighed normally with an average BMI of 26.88 ± 2.35 kg/m2. The mean ages at menarche and menopause were 11.15 ± 1.2 and 49.38 ± 3.76 years, respectively. About a fifth (20.9%) of the women were taking antihypertensive medication.

The frequency of high SBP and DBP in postmenopausal women referred to Dr. Heshmat Hospital in Rasht was reported as 70.2% and 3.1%, respectively. No statistical difference was observed between age at menarche and age at menopause in postmenopausal women with high systolic and diastolic blood pressure and normal blood pressure.

The results of the correlation between the age of menarche and menopause with SBP presented in Table.2 showed that a very weak negative (reverse) correlation was observed between the age of menarche and SBP (Pearson's Correlation Coefficient, r = 0.086, p = 0.001). Additionally, the correlation between the age of menarche and menopause with DBP was negative (inverse), very weak and non-significant.

In order to investigate the simultaneous effect of variables and eliminate possible confounding variables in the group with and without high SBP, using univariate logistic regression, the relationship between each variable with high SBP and DBP was measured, and then the menarche age and menopause age variables and the variables with a lower p value of 0.25 were entered in the multiple model of logistic regression analysis using the Enter method. Based on the results of the multiple logistic regression model, no significant relationship was observed between the age of menarche and menopause with the chance of high BP in postmenopausal women.

Based on the results of the multiple linear regression model, a significant relationship was reported between the age of menarche and SBP in postmenopausal women, so that under the same conditions regarding other variables included in the model, for each year of increase in the menarche age, the average SBP of a person decreases by 0.857 (BP increases for each year of premature menarche). Among other factors affecting SBP; municipal, the number of children, the level of cholesterol 001/0 > and LDL 001/0 > had a positive effect on increasing SBP. Also, FBS had a negative effect on increasing BP Also, based on the results of this model, no significant relationship was reported between age of menarche and menopause with DBP in postmenopausal women(Table.3).

The present study illustrates that premature menarche, living in urban areas, the number of children, the level of cholesterol, LDL and FBS were destructive against increasing SBP. Also, based on the results obtained by this model, no significant relationship was reported between the age of menarche and menopause with DBP in postmenopausal women.

The results of our study agree with those of Bubach S et al. in 2018 which illustrated that early menarche is associated with HTN among adult women. The higher mean SBP and DBP among women who experienced early menarche may have occurred by chance (20). Additionally, Liu’s study results showed that the late menarche is related to a higher risk of HTN among adult women in China, and the same association could be seen among different subgroups.

On the other hand, the results of our study are inconsistent with a study administered in Fujian with 3304 postmenopausal women as participants, showing that late menarche was significantly associated with lower CVD risk (21). Another study by Lulu Zhang et al. in 2019 found that there is a significant association between late menarche and a lower risk of HTN (22). Also, a study among 7119 Chinese women represented that women with late menarche (women older than 18 years old) had a 39% higher risk of developing hypertension (23). However, an even larger study among 13,242 women reported that instead of late menarche, early menarche was associated with a higher risk of self-reported hypertension(24). The difference between our study and other studies, can be due to differences in populations, differences in definitions of early and late menarche, and differences in lifestyles. The women who took part in our study were postmenopausal urban women, among whom the mean age at recruitment and age of menarche were higher than participants in other studies. Relatively backward economic conditions may delay bodily development. Furthermore, although the age of recruitment was significantly different between the categories of age of menarche, the higher the age at menarche, the higher the age at recruitment. This phenomenon could be explained by the trend reported in a study, which showed a significant decrease in age of menarche over three generations (from mothers to daughters and grandmothers to granddaughters).

Our study illistrated that age of menarche was negatively associated with FBS. After adjustment for multiple confounders, FBS had a negative effect on increasing blood pressure.

Shen et al. findings showed that age at menarche was negatively associated with both SBP and DBP after controlling for age, education, marital status, smoking, drinking, and antihypertensive medication use. For women with a 1-year early onset of menarche, SBP and DBP were 0.82 and 0.41mm Hg higher, respectively. Additionally, a 1-year early onset of menarche was associated with 6% higher odds of hypertension when adjusting for age, education, marital status, smoking, and drinking. By further controlling for number of biological children, fasting glucose, HbA1c, LDL-C, HDL-C, and triglycerides, the associations were attenuated but still significant for SBP and DBP and marginally significant for hypertension. The associations of age at menarche with BP and hypertension were similar among postmenopausal women. When the results were broken down by area of residence, the associations of menarche age with blood pressure and hypertension were only significant among women living in rural areas. There were significant interactions between menarche age and area of residence for SBP and DBP and a marginally significant interaction for hypertension (25). Furthermore, Yang et al. findings showed that the number of live births and having two children were found to be protective factors for the incidence of hypertension compared with having less than two children among the postmenopausal women. Moreover, the postmenopausal women with three children showed a negative association with the prevalence of prehypertension compared with having five or more children(1). Chen et al. findings showed that Women who were older at the age of menarche were more likely to reside in rural areas, have more children, have later menopause, and have higher mean blood pressure. The positive association between age at menarche and hypertension was evident among age at recruitment groups. This association was stronger in urban women and postmenopausal women (26).

In summary, women with early menarche are likely to have a higher risk of hypertension especially SBP. Knowing the association between age at menarche and urban areas of residence, the number of children, the level of cholesterol, LDL and FBS may help women prevent the development of hypertension. These results suggest that the increased level of cholesterol, LDL and FBS prevention strategies may be helpful to reduce the risk of hypertension in women who experience menarche at an age under 18 years old. Further studies are needed to validate and expand these findings.

This study has several potential limitations that should be considered. Firstly, the menarche age was self-reported by participants, which may have recall bias. Secondly, this cross sectional study could not deduce a causal relationship, for which prospective studies will be needed. Finally, we did not collect information on salt intake by the participants, which appears to be a residual confounder of hypertension.

HTN: Hypertension; CVD: Cardio Vascular Diseases; BHPAQ: BaeckeHabitual Physical Activity; Questionnaire; BP: Blood Pressure; SBP: systolic blood pressure; DBP: diastolic blood pressure; BMI: body mass index; LDL: low-density lipoprotein; HDL: high-density lipoprotein; TG: Triglycerides; FBS: Fasting Blood Sugar; HRT: Hormone replacement therapy; OCP: Oral contraceptive pills ;HbA1C: Hemoglobin A1C.

Author contributions

ZA, AF,SK and AS: Concept and design, data acquisition, interpretation, drafting, final approval, and agree to be accountable for all aspects of the work. ZA, ER, YB, and MM: Data acquisition, interpretation, drafting, final approval and agree to be accountable for all aspects of the work.

Funding

Not Applicable.

Acknowledgements

The authors thank the Vice-Chancellor of Research and Technology, head of the department, the managers and nurses at Dr. Heshmat Rasht Medical Education Center, and all those who helped us with this research.

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Ethics approval and consent to participate

All participants gave their informed consent prior to their inclusion in the study. Moreover, the study protocol was approved by scientific vice chancellor for research and the ethics committee of Guilan University of Medical Sciences (IR.GUMS.REC.1399.195.) and conformed to the ethical guidelines of the 1975 Declaration of Helsinki.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

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Tables 1 to 3 are available in the Supplementary Files section.

No competing interests reported.

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Associations of the age of menarche and menopause with hypertension in menopausal women in Rasht, Iran in 2020-2021

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Abstract

Background

Methods

Study population

Data collection

Statistical analysis

Results

Discussion

Conclusions

Study Limitations

Abbreviations

Declarations

References

Tables

Additional Declarations

Supplementary Files

Status:

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