Age at natural menopause in three Central and Eastern European urban populations: The HAPIEE study

Objectives

To investigate the age at menopause in three urban populations in Central and Eastern Europe and to assess whether the (suspected) differences can be explained by a range of socioeconomic, reproductive and behavioural factors.

Methods

The Health, Alcohol and Psychosocial factors in Eastern Europe (HAPIEE) Study examined random samples of populations aged 45–69 years in Novosibirsk (Russia), Krakow (Poland) and six Czech towns. Participants completed a questionnaire and attended an examination in clinic. A total of 12,676 of women were included in these analyses.

Results

The median age at menopause was 50 years in Novosibirsk, 51 years in Czech towns and 52 years in Krakow; the Cox regression hazard ratios of menopause, compared with Krakow, were 1.47 (95% CI 1.40–1.55) for Novosibirsk and 1.10 (1.04–1.16) for Czech women. In multivariate analyses, higher education, using vitamin and mineral supplements and ever use of oral contraceptives were associated with later menopause, while smoking, abstaining from alcohol and low physical activity were associated with earlier menopause. These factors, however, did not explain the differences between populations; the multivariate hazard ratios of menopause, compared with Krakow, were 1.48 (1.40–1.57) for Novosibirsk and 1.11 (1.05–1.17) for Czech women.

Conclusions

In this large population based study, differences in age at menopause between Central and Eastern Europe populations were substantial and unexplained by a range of risk factors. Associations of age at menopause with risk factors were largely consistent with studies in other populations.     

Body mass index trajectories and age at menopause in a British birth cohort

OBJECTIVE: This study investigates the influence of body mass index (BMI) at ages 15, 20, 26, 36, and 43, and of BMI trajectories from 20 to 36 years on the timing of menopause and hormone therapy (HT) use until age 57 years. METHODS: A nationally representative British cohort of 1583 women born in March 1946 with prospective data across the life course. RESULTS: By age 57, a total of 695 women had experienced natural menopause while 431 women had started HT prior to menopause. Cox regression models indicated no significant associations between BMI at any age, or BMI trajectory, and timing of natural menopause. At every age BMI was strongly (p< or =0.01) and linearly associated with age at HT use and BMI from 26 years onwards was associated with age at first event (menopause or HT use). Decreasing BMI was associated with earlier HT use at all ages. These associations were not accounted for by parity, cigarette smoking or childhood and adult social class. CONCLUSION: BMI across the reproductive lifespan did not influence age at menopause to an extent that would be clinically relevant for postmenopausal health. Lower BMI at all ages and underweight trajectory were related to an earlier start of HT. Further studies are required to understand whether such relationships are due to underweight women experiencing menopause earlier (and because of menopausal symptoms starting HT earlier) than heavier women, or having behavioural characteristics related to earlier HT use, independent of menopause.     

The frequency distribution of age at natural menopause among Saudi Arabian women

Objective: Hormonal changes at the menopause are associated with the onset of a number of medical conditions. The distribution of age-at-menopause (AAM) within a given population can, therefore, indicate how the disease prevalence changes with age. The objective of this study was to estimate the distribution of AAM among Saudi Arabian women, in order to predict local trends in the prevalence of osteoporosis. Methods: Patient age, AAM, medical history and associated information for 858 Saudi Arabian women were extracted from a Dual Energy Absorptiometry database at King Faisal Specialist Hospital and Research Centre, resulting in an AAM distribution for 391 postmenopausal women with natural menopause. This was preprocessed using a Fast Fourier Transform 0.15 cycles/year low-pass filter, eliminating last-digit-preference errors and high frequency noise, and facilitating quantitative comparison with other published results. Results: Mean AAM was 48.94 years (S.E. 0.290 years) with a median of 50 years (25th/75th percentiles: 45 and 53 years, respectively). The AAM distribution was described by a quadruple-Gaussian curve with a major peak at almost 51 years and minor peaks at approximately 36, 44 and 59 years. Although both the central peaks were similar to that observed in other populations (UK, USA and Finland), the early menopause peak at 36 years was larger. The peak over 55 years may be unique to the Kingdom of Saudi Arabia. It may reflect local cultural and childbearing practices. Conclusions: Although the median menopause age and general shape of the AAM distribution in Saudi Arabia appear similar to that observed in the West, the parameters governing the distribution are different, and there is evidence that it may have a unique fourth peak.     

Reproductive characteristics and risk of kidney cancer: Iowa Women's Health Study

Objectives

Kidney (renal cell) cancer accounts for approximately 3–4% of all new cases of primary cancer diagnosed in the United States. A relationship between kidney cancer and female reproductive factors has been hypothesized but supporting evidence is inconsistent. Our objectives were to explore the relationship between female reproductive factors and kidney cancer and identify independent risk factors related to female reproductive history and its effects on development of kidney cancer.

Methods

We measured risk factors for kidney cancer and reproductive characteristics in a group of 37,440 postmenopausal women in Iowa. From 1986 to 2003, 165 cases of incident kidney cancer were identified through a statewide cancer registry.

Results

After adjustment for age and other risk factors, past use of estrogen showed an increased risk of renal cancer (RR 1.56; 95% CI 1.13–2.17) when compared to no use. Women with no live birth (RR 1.91, p = 0.02) and women with three to four live births (RR 1.62, p = 0.02) also had an increased risk of kidney cancer when compared with women who had one to two live births. There was also a lower risk of kidney cancer with greater lifetime duration of ovulation.

Conclusion

Although most reproductive variables were not significantly associated with kidney cancer, our study indicates that a greater exposure to estrogens may increase risk for kidney cancer.     

The impact of hormonal therapy for infertility on the age at menopause

Objectives: To look for possible association between past history of ovulation induction and age at menopause. Design: Women attending our postmenopausal outpatient clinic were asked to fill questionnaires with demographic data, obstetrical history (including treatment for infertility), and medical details related to menopause. Patients: The study group (n=31) consisted of women with a history of ovulation induction, and a control group (n=200) included women who did not experience such intervention. Results: The age at the final menstrual bleeding was 46.4±5 in the study group, and 50±4 for the control group (P<0.001). This difference was most prominent for women who had induction of ovulation prior to age 35 years: they entered menopause at age 43.8±5 years. Smoking had a weak effect on the age at menopause (48.5±4 for current, vs. 49.9±4 for non- or past-smokers; P<0.03). Conclusions: This retrospective and preliminary study raises the question whether hormonal manipulations and ovarian over-stimulation during fertility treatments could be a risk factor for premature menopause.     

Cigarette smoking and age of menopause: a large prospective study

Objectives

One of the possible consequences of tobacco consumption is that it contributes to an earlier age of menopause, though the causal relationship is yet to be confirmed. This study aimed to examine the prospective association between smoking and earlier age of menopause in a cohort of middle age Australian women after adjustment for a number of potential confounders.

Study design

21-Year follow-up of a cohort prospective study, Brisbane, Australia.

Main outcome measures

Age of menopause measured at the 21-year follow-up. Smoking and menopausal status were assessed by self-report. Other covariates were measured prospectively in the previous follow-ups.

Results

This study is based on 3545 women who provided data on their menopausal status at the 21-year follow-up of the study, and prospective as well as concurrent data on smoking. In univariate analysis tobacco smoking during the reproductive life course, socio-economic status and gravidity were significantly associated with earlier age of menopause. In multivariate analyses women who smoked cigarettes were more likely to experience earlier menopause than non-smokers. Compared to current smokers, risk of early menopause was significantly lower in those women who quit smoking in the past.

Conclusions

The data suggest that the impact of smoking is independent of other covariates associated with both smoking and age of menopause. The findings raise the possibility that effective quit smoking interventions may lead to a later age of menopause, and reduce the risk of adverse health consequences of early menopause.     

Preprocessing histograms of age at menopause using the fast Fourier transform

Objective: In epidemiological and biological studies, the interpretation of frequency distributions (histograms) of the age at menopause (AAM) is hampered by the presence of background noise such as the last-digit-preference (LDP) of each woman. The objective of this study was to develop a standard method of preprocessing the AAM histogram such that noise can be effectively eliminated, thereby enabling a more thorough investigation of the underlying properties of the distribution. Methods: The Fast Fourier transform (FFT) is a technique which eliminates individual sources of noise based on their characteristic frequencies. Its effectiveness in eliminating noise from AAM data was explored using both simulated and published data, especially in regard to the elimination of cyclical LDP errors. Results: By preprocessing the histogram ‘signal’ using a low-pass filter of 0.15 cycles per year (cpy), common LDP noise is eliminated. Furthermore, this preprocessing also eliminates other forms of high-frequency noise, revealing a true AAM ‘signal’ which comprises three separate low-frequency components. The two major peaks correspond in the time domain to Gaussian functions with means at 51 and 43 years and peak-widths of 6 years; a smaller peak also exists at 35 years. Conclusions: The FFT is an effective tool in preprocessing AAM frequency distributions to reveal their underlying shape, which appears similar across several previously published studies and is characterized by three distinct peaks. These currently have no definitive interpretation, but call into question the analysis of epidemiological risk factors for AAM using statistical techniques which assume a single distribution.     

Timing of menarche, childbearing and hysterectomy risk

Objectives

To examine the associations of age at menarche, timing of first birth and parity with hysterectomy rates; to investigate whether these associations were independent of each other and other potential confounders and varied by reason for hysterectomy.

Methods

Women from the Medical Research Council National Survey of Health and Development, a cohort followed prospectively since birth in March 1946 across England, Scotland and Wales, were studied. Survival analyses were used to assess the relationships between reproductive characteristics and hysterectomy.

Results

Age at menarche was inversely associated with hysterectomy rates (adjusted Hazard Ratio for hysterectomy associated with a 1 year increase in menarche = 0.85 (95% CI: 0.77–0.95)). Parity was also associated with hysterectomy; women with ≥3 children experienced higher rates of hysterectomy than women with 1–2 children, who themselves experienced higher rates than nulliparous women. The associations of parity and age at menarche with hysterectomy were independent of each other and potential confounders. The association between age at menarche and hysterectomy was stronger for hysterectomies performed for fibroids than for other reasons.

Conclusions

Our findings suggest that age at menarche is most likely acting to influence hysterectomy risk through its association with lifetime oestrogen exposure whereas parity is most likely acting through an effect on decision-making processes. This highlights the importance of considering both biological and social pathways to hysterectomy and confirms that medical need is not the only factor which needs to be considered when making treatment decisions for gynaecological problems.     

A new way of looking at environmental variables that may affect the age at menopause

Environmental variables that might affect the age at menopause were analysed by means of the segmentation method AID. Marital status, occupation, smoking habits, age at last pregnancy and height were shown to be significant discriminating variables. The material and design of the study and the method of analysis are given and its results are discussed. A proposal is made concerning the nature of a ‘secular trend’.     

A polymorphism of apolipoprotein E (APOE) gene is associated with age at natural menopause in Caucasian females

Objective

The present study aimed to investigate possible association of the apolipoprotein E (APOE) gene polymorphisms with age at natural menopause (ANM) in Caucasian females.

Design

Four SNPs (including two replacements, SNP3 Cys112Arg and SNP4 Arg158Cys) were genotyped in 253 randomly selected unrelated Caucasian women having experienced natural menopause. The comprehensive statistical analyses focusing on the association of the APOE gene and some environmental factors with ANM were conducted.

Results

Alcohol consumption was a significantly predictor of earlier natural menopause (P < 0.05). One SNP (rs769450) was significantly associated with ANM according to both population based and the transmission disequilibrium test (TDT) analyses (P = 0.007 and 0.046, respectively). However, no association was observed between APOE ?2, ?3, ?4 and ANM.

Conclusions

Genetic variation in the APOE gene may influence the variation in ANM in Caucasian women.     

Climacteric and menopause in seven south-east Asian countries

The menopause is universal, but what about the climacteric? In an attempt to answer this question, a study was conducted in seven south-east Asian countries, namely, Hong Kong, Indonesia, Korea, Malaysia, the Philippines, Singapore and Taiwan. Samples of approximately 400 women in each country were questioned about a number of climacteric complaints, incontinence and dyspareunia, consultation of a physician, menopausal status and several background characteristics. Special care was taken to overcome linguistic and cultural problems, and the data collected were kept as objective as possible. From the results obtained we were able to show that the climacteric was indeed experienced in south-east Asian countries, although in a mild form. The prevalence of hot flushes and of sweating was lower than in western countries, but was nevertheless not negligible. The percentages of women who reported the more psychological types of complaint were similar to those in western countries. The occurrence of climacteric complaints affected perceived health status. A physician was consulted for climacteric complaints by 20% of the respondents, although this was most frequently associated with the occurrence of psychological complaints and less so with that of hot flushes and sweating. The median age at menopause (51.09) appeared to be within the ranges observed in western countries. Ethnic background and age at menarche were found to have a significant influence on age at menopause. The study clearly demonstrated that climacteric complaints occur in south-east Asia. The findings suggest, however, that vasomotor-complaint-related distress might be ‘translated’ into psychological complaints, which are more frequently considered to warrant consulting a physician.     

Age at Menopause and Suicidal Ideation in Menopausal Women: A Study of Korea National Health and Nutrition Examination Survey Data

BackgroundAlthough menopause is considered a risk factor for depression, no association has been established between the risk of suicidal ideation and age at menopause. This study aimed to evaluate the association between age at menopause and suicidal ideation in middle-aged menopausal Korean women.MethodsThis cross-sectional study used data from the Korea National Health and Nutrition Examination Survey (2013–2018). Women aged 40–65 years were divided into the following three categories: primary ovarian insufficiency (POI), early menopause, and menopause, according to age at natural menopause (< 40, 40–45, and > 45 years, respectively). Depressive symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9).ResultsAmong 2,232 menopausal women, 25 (1.1%) experienced POI and 114 (5.1%) experienced early menopause. The PHQ-9 items that pertained to low self-esteem and suicidal ideation scored higher in women with POI than in those who experienced menopause after 45 years of age. The prevalence of suicidal ideation differed significantly according to age at menopause (POI, 30.0%; early menopause, 12.7%; menopause, 8.0%; P = 0.016). Logistic regression analysis revealed that POI was significantly associated with suicidal ideation after the adjustment for age, body mass index, and education, household income, and walking levels (odds ratio, 4.2; 95% confidence interval, 1.0–17.7).ConclusionKorean middle-aged women with POI were more likely to have suicidal ideation than those who experienced menopause at 45 years or above, despite not being diagnosed with major depressive disorder.     

Complementary/alternative and conventional medicine use amongst menopausal women: Results from the Australian Longitudinal Study on Women's Health

Large population-based studies of complementary and alternative medicine (CAM) and conventional medicine use amongst menopausal women are lacking. This study helps address this gap by analysing data from a nationally representative sample of 10 011 Australian women aged 59–64 years. Overall, 39% of menopausal women consulted CAM practitioners, 75% used self-prescribed CAM, 95% consulted general practitioners (GP) and 50% consulted specialists during the previous year, and 12% were current hormone replacement therapy (HRT) users. Our findings suggest that CAM is a significant healthcare option utilized by women to treat menopausal symptoms, and so requires attention from GPs and specialists.     

The clinical features of the menopause and its relation to the length of pregnancies and lactation

The clinical features of the menopause and the influence of the length of pregnancies and lactation on the age of menopause and on the incidence of hot flushes were studied in 154 women aged 50–85 yr. The mean age at menopause was 46.6 ± 4.7 SD yr. The cessation of menses occurred abruptly in 43.5% of the cases or after a period of menstrual irregularities (56.4% of the cases). The prevalent abnormalities were oligomenorrhea (45.4%) or functional bleeding (10.4%), both of short duration in the majority of the cases. Hot flushes were experienced more frequently (68.9%) in women with menstrual irregularities before the onset of menopause and especially those who presented an oligo-menorrhea (71.4%) than in women with abrupt cessation of menses (41.7%). The length of pregnancies did not seem to influence the age at menopause. The mean age at menopause in 17 nulligravida women was 46.5 yr and did not differ significantly from the mean age at menopause of women with 1–19, 20–39, 40–59 and 60–110 mth of pregnancies. The duration of pregnancies, however, seemed to influence the incidence of hot flushes. Women with more than 20 mth of pregnancy had a significantly smaller incidence of hot flushes than nulligravida or women with 1–19 mth of pregnancy.

The length of lactation was also not correlated with the age at menopause. Finally, the age of last pregnancy was not found to be related with the menopause or the incidence of hot flushes.     

Birth weight and age at menopause in Australian female twin pairs: exploration of the fetal origin hypothesis

In a twin sample where duration of gestation can be controlled, a specific example of the fetal origins hypothesis concerning association between low birth weight and early age at menopause is explored. The hypothesis is based on the physiologically plausible path from intrauterine growth retardation and reduced numbers of primary follicles to an earlier menopause. The sample comprised 323 Australian female twin pairs where both co-twins had reached menopause naturally and reported on their weight at birth. Regression analysis showed no linear association between the two variables (P = 0.371, r(2) = 0.0009). Intra-pair differences in age at menopause were investigated in the context of relative birth weight of co-twins. In 265 pairs an intra-pair birth weight difference was reported. In monozygotic (MZ) pairs (n = 168) this allowed for control of genetic effects as well as gestation duration. No significant differences dependent on birth weight relative to co-twin were found for age at natural menopause in either MZ or dizygotic (DZ) twin pairs, even in pairs whose birth weights differed markedly. There was some indication that twins with premature ovarian failure were heavier at birth than twins with normal or later menopausal age. We conclude that the hypothesis that lower birth weight is associated with earlier menopause is not supported by our data.     

The timing of natural menopause in Poland and associated factors

OBJECTIVES: The outcome of interest was the assessment of age at natural menopause and the variables hypothesized as covariates of age at menopause were indicators of demographic and social status, characteristics of the reproductive history and lifestyle behaviour. METHODOLOGY: Seven thousand one hundred and eighty-three women from all social strata of non-clinical population, and aged between 35 and 65 years were investigated in cross-sectional survey across Poland in 2000-2004. The demographic, social, lifestyle behaviour and reproductive history aspects of the menopause-specific questionnaire were examined. The non-parametric Kaplan-Meier cumulative survivorship estimates were used to assess the timing of natural menopause. Univariate and multivariate Cox proportional hazards regression models were used to assess the association of age at natural menopause with factors of interest and to estimate relevant relative risk (the hazard ratio) for earlier age at menopause. RESULTS: The overall median age at natural menopause was 51.25 years; 25th percentile 49; 75th percentile 54 years. Temporal changes in age at menopause were not demonstrated in the sample (p=0.9 for differences among age cohorts). Univariate Cox models were first fitted to the age at natural menopause for all covariates singly. The findings revealed that marital status, living environment, employment, BMI, age at first live birth delivered by a woman, breastfeeding, physical activity, smoking amount, and consumption of alcohol were not associated with age at menopause (p>0.05). The multiple Cox model revealed that early menarche, short menstrual cycle length, smoking cigarettes, a low level of education, and a negative health perception were associated with younger age at menopause (p<0.01). Use of oral contraceptives and parity were associated with later menopause (p<0.01). CONCLUSION: The present study provides an estimate of median age at natural menopause in Poland that may be used as a measure of health for the growing number of Polish women whose survival is calculated at 30 years after menopause. This study has revealed that the pattern of relationship between age at menopause and the study factors reflects its population-specific character for its social and cultural backgrounds, socio-economic status, and social behaviours.     

The age of menopause and the menopause transition in a multiracial population: a nation-wide Singapore study

OBJECTIVE: To describe the prevalence of menopausal symptoms, define the mean age of menopause, and determine contributory factors, which influence the experience of symptoms among Singaporean women of different racial groups. DESIGN: Cross-sectional nation-wide study of a random sample of 1000 women drawn from the entire population of Singaporean female (Chinese, Malay, and Indian) citizens between 45 and 60 years of age. Face-to-face interviews using structured questionnaires were conducted. RESULTS: The response rate was 69.9%. The mean age of natural menopause was 49.0 years. This was not significantly different between the three ethnic groups. Increasing parity delayed the age of menopause (P=0.007). Muscle and joint ache was the most commonly reported symptom (52.6%). Although the prevalence of significant hot flushes in the general study population was low (3.9%), it was the most commonly reported complaint by peri-menopausal women (14.6%). Prevalence of significant hot flushes decreased with time from menopause (P=0.007) and completely disappeared beyond the fifth year of menopause. Recent unhappy events were associated with an increased risk of symptoms (P<0.001). Women of Chinese origin experienced a lower risk of menopausal symptoms when compared with other ethnic groups (P<0.05). CONCLUSION: The mean age of menopause was 49.0 years among Singaporean women. Ethnicity and recent unhappy events were two major factors, which influenced the risk of experiencing menopausal symptoms. Among the three ethnic groups studied, Chinese women were the least likely to experience disturbing menopausal symptoms. The overall prevalence of menopausal symptoms was low when compared to studies on women in western societies.