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.     

Reproductive and dietary determinants of the age at menopause in EPIC-Heidelberg

OBJECTIVES: The aim of the study was to explore the influence of reproductive and dietary factors on the age at menopause. METHODS: During follow-up of the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort in Heidelberg (median duration 5.8 years), 1009 women experienced natural menopause. They were compared to 3798 women who did not experience menopause. Baseline dietary intake was obtained by means of validated food frequency questionnaires. Data on reproductive history and medication was collected by means of questionnaires. Cox' proportional hazard models were applied in order to identify determinants of the age at natural menopause. RESULTS: Increasing age at first full term pregnancy and a longer time interval until occurrences of regular menses are associated with later onset of natural menopause. Compared to never smokers, current smokers have the risk of younger age at menopause. High carbohydrate consumption and high intake of vegetable, fibre and cereal products are inversely related to the age at natural menopause. Women with higher intake of total fat, protein and meat experienced a delayed onset of natural menopause. CONCLUSION: Age at natural menopause is influenced by lifestyle and dietary factors. Further studies including biological markers are needed to clarify these associations.     

The role of genetic factors in age at natural menopause

BACKGROUND: Environmental factors explain only a small part of the age variance at which menopause commences. The variation in natural menopause is a trait predominantly determined by interaction of multiple genes, whose identity and causative genetic variation remains to be determined. Menopause is a retrospective marker for the reproductive capacity of preceding years, since subfertility and infertility precede menopause at distinct time-intervals. In the present study we have investigated the contribution of genetic factors to menopausal age. METHODS: Data were collected from a random population sample of singleton and twin sisters participating in a prospective breast cancer screening project, who had subsequently experienced natural menopause. Heritability of menopausal age was estimated with analysis of variance, Mx modelling and Gibbs sampling. RESULTS: All produced almost identical heritability estimates of 0.85-0.87 for singleton sisters, suggesting a strong genetic contribution to menopausal age. Twin data were used to distinguish additive genetic from common environmental effects; a heritability of 0.71-0.72 was determined, which does not deviate significantly from the estimate for singleton sisters. CONCLUSIONS: According to our findings, a woman with a family history of early menopause risks early menopause and consequently early reproductive failure herself.     

A comparison of health-related quality of life (HRQOL) after natural and surgical menopause

Objective

To compare the health-related quality of life (HRQOL) of women at surgical menopause with that of women at natural menopause, utilizing the Menopause Rating Scale (MRS-II).

Study design

An institution-based cross-sectional study design was used, with 32 participants in each of two groups: women who had undergone surgical menopause of 9–12 months previously; and women who were more than 40 years of age and had had oligomenorrhoea for at least 1 year. The MRS-II was used to assess HRQOL. None of the women had received any hormonal therapy before assessment.

Main outcome measures

Total MRS-II scores along with the scores on the somato-vegetative, psychological and urogenital sub-scales were compared between the two groups.

Results

HRQOL was rated as worse by the surgical menopause group than by the natural menopause group: the total MRS-II scores were much higher for the surgical menopause group (mean = 29.4, SD = 6.7) than for natural menopause group (mean = 20.7, SD = 6.5), and this difference was significant (p < 0.0001). Similar results were obtained on the three sub-scales—somato-vegetative (p = 0.030), psychological (p < 0.0001) and urogenital (p < 0.0001).

Conclusion

HRQOL is worse after surgical than in natural menopause. Routine surgical castration at hysterectomy should be avoided because of adverse short-term effects and, potentially, long-term consequences.     

The male menopause: lifestyle and sexuality

The existence of a variety of disturbing symptoms, sometimes loosely described as 'the male menopause', has received wide confirmation in both professional and lay literature over the last few years. Whilst there is no conclusive empirical evidence that the majority of men undergo a hormonal 'change of life' equivalent to that found in women, it has become clear that a significant number do experience psychological and social difficulties at some point in middle age. It has also become clear that in certain respects, these negative experiences resemble those typically associated with a traumatic menopause in middle-aged women. Amongst the various symptoms reported, one is of particular interest: the recurring expression of male sexual anxiety and/or dissatisfaction with sex-life. This paper draws upon a comparative analysis of professional and lay publications concerning the male menopause and menopause, which appeared in the U.K. and U.S.A. between approx. 1930-1983, to locate this expression of sexual anxiety in the context of a changing conception of middle age in the western world. The main focus is on the influence of contemporary models of sexualised lifestyle on sexual expectations and relations between the sexes during mid-life. Attention is also paid to the possible future implications of changing images of middle age for the diagnosis and treatment of the male menopause/climacteric or mid-life crisis.     

Age at menopause and determinants of hysterectomy and menopause in a multi-ethnic community: The Hilo Women's Health Study

Objectives

A lifespan approach was used to evaluate age at menopause, and determinants of surgical and natural menopause, in the multi-ethnic community of Hilo, Hawaii.

Study design

Participants aged 40–60 years (n = 898) were drawn from a larger, randomly generated sample recruited by postal questionnaires. Median age at natural menopause was computed by probit analysis. Logistic regression analysis was applied to examine determinants of hysterectomy, and Cox regression analysis was used to examine risk factors for an earlier age at menopause.

Main outcome measures

History of hysterectomy, age at menopause.

Results

Frequency of hysterectomy was 19.2% at a mean age of 40.5 years. The likelihood of hysterectomy increased with older ages, lower education, mixed ancestry, having been overweight at age 30, and married 20 years prior to survey. Median age at natural menopause was 53.0 years. Smoking and not being married 10 years before survey were associated with an earlier age at menopause.

Conclusions

Median age at menopause was later than the national average. Ethnicity and education were determinants of hysterectomy, but not associated with age at natural menopause. Events later in the lifespan (e.g., smoking and not being married 10 years prior to the survey) were more important than earlier events (e.g., childhood residence) in relation to age at menopause. The timing of weight gain and marital status appear to be important in relation to surgical menopause, and the timing of marital status appears to be important in relation to the timing of natural menopause.     

The age and symptomatology of natural menopause among United Arab Emirates women

Objectives: To determine the median age of natural menopause in United Arab Emirates women, the factors affecting that age and the prevalence of climacteric symptoms amongst those women. Methods: A population-based survey was conducted on a community sample of United Arab Emirates women who had had natural menopause defined as cessation of menstruation for at least 6 months at the end of reproductive years. A total of 742 women aged 40 years and above were recruited from both urban and rural areas of the country using the multi-stage stratified cluster sampling technique. Data were collected using a structured questionnaire and face to face interviews and included a number of familial, reproductive and life-style variables. Results: The median age of the menopause in the United Arab Emirates is 48 years (mean=47.3±3.29, range 40–59). This is significantly lower than the median age reported from the West (50.3 years). The subject median age of the menopause was significantly related to that of the mother (P<0.001), older sister (P<0.001), parity (P<0.0001) and the previous use of oral contraceptive pills for more than 1 year (P<0.001). Hot flushes were the commonest feature of the menopause occurring in 45% of women. Conclusion: The age of natural menopause in United Arab Emirates women, as in other developing countries, is less than in Western women and may be influenced by genetic factors, parity and previous use of oral contraceptives. Climacteric symptomatology, however, is similar in the different patient groups.     

Premenopausal factors influencing premature ovarian failure and early menopause

OBJECTIVES: We conducted this study to examine premenopausal risk factors associated with premature ovarian failure (POF) and early menopause (EM) among Korean women. METHODS: A 73% of total women aged 30-69 at four districts in the KMCC (Korean Multi-center Cancer Cohort) was participated in this study during 2002-2003. We selected 137 POF and 281 EM cases who had menopause before age 40 and at age 40-44, respectively, and 1318 normal menopause (NM) controls that experienced menopause at age 45-60, and among them, selected idiopathic POF (n=84) and EM (n=261) after excluding surgical/medical menopause. We collected the information of premenopausal lifestyle and reproductive risk factors. Multivariate and polytomous logistic regression were used to estimate POF and EM risk and to differentiate POF and EM risk using ordinal and nominal scale. RESULTS: Cigarette smoking was associated with an increased risk of idiopathic POF (OR=1.82 [1.03-3.23]), whereas oral contraceptive use was associated with a reduced risk of natural EM (OR=0.62 [0.43-0.90]). Idiopathic POF risk by both factors differed from idiopathic EM risk (p-nominal<0.05). Factors related to ovulation, such as later menarche, irregular menstruation and longer breast feeding cumulatively reduced the risk of natural EM and POF (p-ordinal<0.05). In analysis including medical and surgical menopause, lung tuberculosis, hysterectomy, past cancers, and lower number of deliveries before menopause were associated with POF. CONCLUSIONS: Our findings indicate that etiology in POF development may partly differ from that in EM.     

Factors associated with the age of natural menopause and menopausal symptoms in Chinese women

Objective

To investigate the factors associated with the age of natural menopause and menopausal symptoms in a large population of Chinese middle-aged women.

Study design

In this cross-sectional study, a total of 20,275 women (40–65 years) attending health screening in Jiangsu Province of China were enrolled. A structured questionnaire was used to collect data of demographics, menopausal status, chronic diseases, reproductive history, etc. Also we evaluated the severity of menopausal symptoms by Kupperman menopause index (KMI).

Main outcome measure

Menopausal age and scorings of Kupperman menopause index.

Results

The overall median age at natural menopause was 50 years. Lower educational level, poor economic status, lower body mass index (BMI), age at menarche less than 14 years, nulliparity and smoking were associated with earlier onset of natural menopause (P < 0.05). The most frequently symptoms in postmenopausal women were sexual problems (57.05%), muscle/joint pain (53.29%) and insomnia (51.02%), while fatigue, insomnia and muscle/joint pain were predominant symptoms in pre- and peri-menopausal women. After adjusting for confounding factors, logistic regression analysis revealed that women with poor educational background, low income, divorce, higher BMI, higher parity, smoking and chronic diseases presented higher KMI scores (P < 0.05).

Conclusion

The study provided an estimate of median age at natural menopause in Chinese women. The main factors contributing to earlier onset of menopause and severity of menopausal symptoms were lower educational level, poor economic status, and smoking. Thus, this study provides important insights for physicians to prevent and treat menopause related symptoms.     

Early menarche and premature natural menopause in Indonesia

Background: An association has been suggested between early menarche and premature natural menopause. However, existing studies in developed countries show mixed findings.

Aim: This study examined whether early menarche (first menstrual period ≤11 years old) is a factor for premature natural menopause (final menstrual period <40 years old) in the context of a developing country.

Subjects and methods: Data came from the Indonesia Family Life Survey (IFLS) 2014, which consists of 1608 post-menopausal women.

Results: Results of hierarchical logistic regression show that women who experienced early menarche (first menstrual period ≤11 years old) were found to be at higher risk of premature natural menopause (β?=?0.94, p?<?0.01, CI?=?0.24–1.63). The results are robust against potential confounding factors including individual reproductive history, lifestyle and sociodemographic characteristics, as well as unobserved factors at the household and community levels.

Conclusion: The findings support early monitoring of women with early menarche, especially those who have no children, for preventive health interventions aimed at mitigating the risk of adverse health outcomes associated with premature natural menopause.     

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.     

Risk factors of early menopause in two generations of gainfully employed French women

Objectives: Numerous studies have been focused on the detection of factors which can act on the age of menopause. Little is known about the factors related to the occurrence of an early menopause. Some factors such as occupational work factors and generational effects have not been taken into account as yet. Methods: We examined the risk factors of early natural menopause (before age 45) in a large random sample of gainfully employed French women born in the years 1938 (n = 1743) and 1943 (n = 1959). The subjects were selected from files of an occupational physician. A woman was considered to be post-menopausal when at least 12 consecutive months had passed without menstruation at the time of the survey. Subjects were questioned and examined during their annual visit by the occupational physician. Occupational history, working conditions, living conditions, smoking habits and reproductive history were explored. Results: The prevalence of early natural menopause, before age 45, was higher in the generation of 1938 (5.3%) than in that of 1943 (3.3%) with P < 0.01. After multivariate regressions, significant relationships existed statistically between the occurrence of early natural menopause and marital status, educational level, age at first childbirth and breast-feeding of children. Conclusions: Our results show important generation effects. There was no evidence of a significant relationship between early natural menopause at 45 years of age and factors relative to heavy physical work conditions.     

Oral contraceptives, menopause hormone replacement therapy, and risk of stroke

Objectives: To review available evidence from observational and intervention studies on oral contraceptives (OC), menopause hormone replacement therapy (HRT) and stroke. Methods: Qualitative literature review. Results: High dose OC were associated to elevated risk of stroke. However, the use of low oestrogen OC preparations by non-hypertensive women not at high baseline risk is not related to an appreciable risk of stroke. With reference to HRT, randomised clinical trials showed an excess risk of stroke among users of combined therapy. Conclusions: In non-hypertensive women below age 35 stroke is not materially related to the use of low dose OC. HRT is associated to a moderate excess risk in randomised studies, and should therefore not be used for the prevention of stroke.     

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.     

Factors associated with premature ovarian failure, early menopause and earlier onset of menopause in Japanese women

Objective

The purpose of this study is to clarify the median age at natural menopause and the proportions of women with premature ovarian failure (POF) and early menopause (EM) by using Kaplan–Meier cumulative estimates and differences in reproductive and lifestyle factors associated with POF, EM and median age at menopause in a large population of Japanese women.

Subjects and methods

This study is a cross-sectional analysis of the Japan Nurses’ Health Study (JNHS). We analyzed data for 24,152 pre- and postmenopausal women who were 40 years or older at the JNHS baseline survey.

Results

The overall estimated median age at natural menopause was 52.1 years, and the proportions of women with POF and EM were 0.28% and 1.67%, respectively. Older generation, cigarette smoking, low body mass index, regular menstruation cycles at 18–22 years of age, nulliparity and unilateral oophorectomy were associated with earlier onset of natural menopause.Only unilateral oophorectomy was associated with increased risk of POF, and nulliparity and unilateral oophorectomy were associated with increased risk of EM.

Conclusion

Unilateral oophorectomy is a common factor associated with earlier onset of menopause, EM and POF, although other reproductive and lifestyle factors are not associated with POF or EM.     

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.     

Risk factors for onset of menopausal symptoms: results from a large cohort study

OBJECTIVES: Menopause, the permanent cessation of ovarian activity, is part of normal aging, resulting in climacteric symptoms for most women, particularly in Western countries. The objective of the present study was to analyse risk factors for onset of menopausal symptoms. METHODS: Analyses were based on the 28,118 women participating in the French E3N cohort study who reached menopause between 1990 and 2000. Questionnaires were sent every 2 years, and specifically enquired about use of hormonal treatments, reproductive factors, smoking status, anthropometric measurements, dietary habits and personal medical history, including onset of menopausal symptoms. Hazard ratios were computed from multivariable Cox proportional hazard models with age as the time-scale. RESULTS: The risk of onset of menopausal symptoms was negatively associated with education level and with some hormonal and reproductive factors (usual duration of menstrual cycles, parity and current use of oral contraceptives). A decrease in risk was found in those with underweight, overweight and obesity, but only in post-menopause. The risk was positively associated with smoking and alcohol consumption; it was also positively related to certain frequent medical conditions (depression, migraine, benign thyroid disease, atopy), possibly due to underlying common mechanisms such as the influence of vaso-active substances. Among dietary factors, rapidly absorbed sugars and snacking were positively associated with the risk of onset of menopausal symptoms. CONCLUSIONS: Onset of menopausal symptoms seems to be affected by various reproductive, hormonal and environmental factors. Some of them are modifiable, which may allow suggesting recommendations.     

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.     

Sun exposure and age at natural menopause: a cross-sectional study in Turkish women

OBJECTIVES: In a cross-sectional study of 157 Turkish women attending outpatient clinics of a university hospital during April-May 2003, association between various subject characteristics and menopause timing was investigated. METHODS: Characteristics were self-reported by women aged 45-60. Of the lifestyle factors, sun exposure, physical activity, food intake and dressing with headscarf were obtained as recalled average lifelong practices up to time of menopause. Cox proportional hazard modeling was used, censoring for hysterectomy, oopherectomy and HRT use. RESULTS: Median age at natural menopause was 52 years. In multivariate analysis, earlier natural menopause was associated with low level of lifelong sun exposure (HR=6.381, 95% CI: 2.996-13.588, p< or =0.0001), heavy physical activity (HR=2.335, 95% CI: 1.305-4.177, p=0.0043), current calcium supplement use (HR=3.191, 95% CI: 1.361-7.485, p=0.0076), diagnosis of hypertension (HR=2.002, 95% CI: 1.186-3.378, p=0.0093), not owning a house (HR=3.002, 95% CI: 1.148-7.852, p=0.0250) and longer years on oral contraceptives (HR=1.085, 95% CI: 1.000-1.176, p=0.0487). Engagement in farming (HR=2.043, 95% CI: 1.056-3.952, p=0.0339), height (cm) (HR=0.953, 95% CI: 0.907-0.994, p=0.0279) and fish consumption (servings/week) (HR=0.600, 95% CI: 0.375-0.960, p=0.0331) were associated with age at menopause in univariate analysis only. For n=109 women who recalled whether maternal menopausal age was <50 or > or =50, sun exposure (HR=7.221, 95% CI: 2.971-17.547, p<0.0001) was a stronger predictor of age at natural menopause than maternal menopausal age (HR=2.882, 95% CI: 1.477-5.621, p=0.0019). CONCLUSIONS: We identify some previously unrecognized correlates of age at natural menopause, namely self-reported lifelong sun exposure, lifelong physical activity, house-ownership, current use of calcium supplements, and lifelong fish consumption. These findings should be confirmed in larger studies.