Are the effects of risk factors for timing of menopause modified by age? Results from a British birth cohort study

OBJECTIVES: This study investigated the influence of mother's age at menopause, early life and adult behavioral factors on the timing of menopause until age 57 years, and whether these effects vary according to the women's age at menopause. DESIGN: A nationally representative cohort of 1,583 British women born in March 1946 with prospective data across the life course. For factors that vary with age at menopause, analyses were stratified by age at menopause younger than 50 years or 50 years or older. RESULTS: Cox regression models indicated that for women with earlier menopause, those who were heaviest at 2 years had a 59% lower hazard ratio for menopause than those who were the lightest (hazard ratio [HR]=0.41, 95% CI: 0.16-1.01), whereas this figure was 35% lower (HR=0.65; 95% CI: 0.42-1.00) for the later menopause group. For women in the earlier group with parental divorce during childhood, the HR was 6.5 (95% CI: 2.021.3) times higher than that of other women. This rate decreased to 2.5 (95% CI: 1.5-4.2) for those with later menopause. In both groups, increasing mother's age at menopause was associated with decreasing HR (P<0.0001). For all women, being breast-fed (P=0.05), increasing cognitive ability (P=0.009), and increasing parity (P=0.001) delayed menopause. CONCLUSIONS: This study found that the impact of weight at 2 years, parental divorce during childhood, and mother's age at menopause varied according to the women's age at menopause. There was further evidence that being breast-fed, higher childhood cognitive ability, and increasing parity delayed menopause. These results suggest the interaction of genetic and environmental factors in determining age at menopause.     

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.     

Age at natural menopause and factors associated with menopause state among Puerto Rican women aged 40-59 years, living in Puerto Rico

OBJECTIVE: The timing of menopause is associated with multiple health outcomes in female populations including all-cause mortality, heart disease, breast cancer, and osteoporosis. Although research suggests that age at menopause varies in different ethnic groups, data on age at menopause among Hispanic women are limited. DESIGN: The present cross-sectional study estimates age at natural menopause among a sample of 1,272 Puerto Rican women aged 40 to 59 years who participated in health fairs held in 22 municipalities of Puerto Rico between May 2000 and November 2001. Cox proportional hazard regression analysis was used to characterize age at natural menopause and its association with relevant covariates. RESULTS: The overall adjusted median age at natural menopause was 51.3 years. Current employment (hazard ratio = 0.75, 95% CI: 0.59-0.95) and parity of two or three children as compared with having no children or one child (hazard ratio = 0.73, 95% CI: 0.54-0.98) were associated with a later menopause. CONCLUSIONS: This study provides a robust estimate of age at menopause for Puerto Rican women, which is similar to overall estimates previously reported for US populations, but higher than estimates for other Hispanic populations. Our results confirm attributes associated with age at menopause and provide information relevant to understanding the potential chronic disease burden of Puerto Rican women as they age.     

Factor V Leiden mutation accelerates the onset of natural menopause

OBJECTIVE: Smoking is consistently associated with a younger age for menopause. Although this may be because of the direct toxic effects of tobacco smoke on follicles, we hypothesize that there may also be a relationship between smoking and a vascular origin of early menopausal onset. Several lifestyle factors have been investigated, but never factors of the clotting cascade. The objective of this study, then, was to determine the effect of factor V Leiden mutation and smoking with respect to age at menopause. DESIGN: Data were used from a subset of 373 postmenopausal participants of a Dutch population-based cohort, born between 1911 and 1925. All women had experienced natural menopause, without use of hormone replacement therapy. RESULTS: Female carriers of the factor V Leiden mutation (n = 14) reported the onset of menopause at an earlier age than noncarriers (n = 359; difference, 3.1 years; 95% CI: 0.3, 5.9). Smoker carriers (n = 5) were 4.3 years younger at menopause than smoker noncarriers (n = 92; 95% CI: 0.9,7.6). In nonsmokers, this relationship was less strong. CONCLUSIONS: We found that the factor V Leiden mutation was related, but not statistically significant, to an earlier age at menopause; smoking possibly enhances this effect. The mutation can be one of the genetic determinants of menopausal age operating through a vascular mechanism.     

Does early growth influence timing of the menopause? Evidence from a British birth cohort

BACKGROUND: Few adult environmental or behavioural factors have been consistently associated with age at menopause. The peak number of follicles attained in utero or lost before ovulation begins may be more important. This study investigates whether birthweight, childhood body size, having been breastfed and early socioeconomic circumstances are associated with age at menopause. METHODS: Menopausal status and risk factor information have been collected prospectively from 1572 British women followed up since their birth in 1946, so far until 53 years. Cox's regression models were used to investigate the relationships between early life factors and rate of menopause. RESULTS: Age at menopause varied by duration of breastfeeding, weight at age 2 years, childhood socioeconomic status, but not birthweight. In a multiple regression model, women of low weight at 2 years had an earlier menopause [hazard ratio (HR) = 0.75 for highest versus lowest quarter: 95% confidence interval (CI) 0.54-1.02] and those who had been breastfed had a later menopause (HR = 0.69 for vertical line 7 months versus never breastfed: 95% CI 0.51-0.92) than others. The influence of socioeconomic status was attenuated. CONCLUSIONS: Early life influences may influence ovarian ageing, highlighting the importance of investigating factors from across the life course.     

Correlates of the age at natural menopause in Morocco

Primary objective : To determine the median age of natural menopause and factors associated with the timing of menopause in Morocco. Research design : A population-based sample of 299 women from Rabat, Morocco were interviewed using a semi-structured questionnaire. Methods and procedures : Logit analysis and logistic regression were used to estimate the median age and identify factors associated with the age at menopause. Main outcomes and results : The median age of natural menopause in Morocco is estimated to be 48.4 years (95% CI: 36.9, 70.3). Women who reported the onset of menstruation at age 11 or younger (OR = 2.84, 95% CI: 1.00, 8.10) had an earlier age at menopause than women who started menstruating at age 12 or older. Women who had ever used oral contraceptives were more likely to have a later age at menopause (OR = 0.55, 95% CI: 0.30, 1.00). The length of time a woman used oral contraceptives influenced the timing of the menopause in unadjusted models but after adjusting for the age at menarche the effect was no longer statistically significant. Marital status, parity, education level, and social class were not statistically associated with the age at menopause. Conclusions : The estimated age at natural menopause in Morocco is 1-3 years earlier than the median ages reported in industrialized countries and some developing countries. Factors that alter the frequency of ovulation or rate of follicular atresia appear to be important in determining the age at menopause.     

Correlates of the age at natural menopause in Morocco

PRIMARY OBJECTIVE: To determine the median age of natural menopause and factors associated with the timing of menopause in Morocco. RESEARCH DESIGN: A population-based sample of 299 women from Rabat, Morocco were interviewed using a semi-structured questionnaire. METHODS AND PROCEDURES: Logit analysis and logistic regression were used to estimate the median age and identify factors associated with the age at menopause. MAIN OUTCOMES AND RESULTS: The median age of natural menopause in Morocco is estimated to be 48.4 years (95% CI: 36.9, 70.3). Women who reported the onset of menstruation at age 11 or younger (OR = 2.84, 95% CI: 1.00, 8.10) had an earlier age at menopause than women who started menstruating at age 12 or older. Women who had ever used oral contraceptives were more likely to have a later age at menopause (OR = 0.55, 95% CI: 0.30, 1.00). The length of time a woman used oral contraceptives influenced the timing of the menopause in unadjusted models but after adjusting for the age at menarche the effect was no longer statistically significant. Marital status, parity, education level, and social class were not statistically associated with the age at menopause. CONCLUSIONS: The estimated age at natural menopause in Morocco is 1-3 years earlier than the median ages reported in industrialized countries and some developing countries. Factors that alter the frequency of ovulation or rate of follicular atresia appear to be important in determining the age at menopause.     

A polymorphism in the AMH type II receptor gene is associated with age at menopause in interaction with parity

BACKGROUND: Anti-Müllerian hormone (AMH) inhibits primordial follicle recruitment in the mouse ovary. We hypothesize that in women AMH signaling also regulates the usage of the primordial follicle pool and hence influences the onset of menopause. Since age at menopause has a strong genetic component, we investigated the role of AMH signaling using a candidate gene approach. METHODS: In two large population-based cohorts of Dutch post-menopausal women (n = 2381 and n = 248), we examined the association between two polymorphisms, one in the AMH gene and one in the AMH type II receptor (AMHR2) gene, and natural age at menopause. RESULTS: The AMH Ile(49)Ser polymorphism (rs10407022) was not associated with age at menopause in either cohort. In the Rotterdam cohort, the AMHR2 -482 A > G polymorphism (rs2002555) was associated with age at menopause in interaction with the number of offspring (P = 0.001). Nulliparous women homozygous for the G-allele entered menopause 2.6 years earlier compared with nulliparous women homozygous for the A-allele (P = 0.005). In the LASA cohort, women with the G/G genotype tended to enter menopause 2.8 years earlier compared with the A/A genotype (P = 0.063). CONCLUSIONS: The observed association of the AMHR2 -482 A > G polymorphism with natural age at menopause suggests a role for AMH signaling in the usage of the primordial follicle pool in 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.     

High-dose testosterone is associated with atherosclerosis in postmenopausal women

OBJECTIVES: To study the long-term effects of androgen treatment on atherosclerosis in postmenopausal women. METHODS: In a population-based study in 513 naturally postmenopausal women aged 54-67 years, we studied the association between self-reported intramuscularly administered high-dose estrogen-testosterone therapy (estradiol- and testosterone esters) and aortic atherosclerosis. Aortic atherosclerosis was diagnosed by radiographic detection of calcified deposits in the abdominal aorta, which have been shown to reflect intima atherosclerosis. Hormone therapy users were compared with never users. RESULTS: Intramuscular hormone therapy use for 1 year or longer was reported by 25 women. In almost half of these women severe atherosclerosis of the aorta was present (n=11), while in women without hormone use severe atherosclerosis of the aorta was present in less than 20% (OR 3.1; 95% CI, 1.1-8.5, adjusted for age, years since menopause, smoking, and body mass index). The association remained after additional adjustment for diabetes, cholesterol level, systolic blood pressure, or alcohol use. No association was found for hormone use less than 1 year. CONCLUSION: Our results suggest that high-dose testosterone therapy may adversely affect atherosclerosis in postmenopausal women and indicate that androgen replacement in these women may not be harmless.     

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.     

An overview of age of onset of menopause in northern India

OBJECTIVES: This study was conducted to establish the age at onset of natural menopause (ANM) in northern Indian women and also to determine any socio-demographic, reproductive or physical factors that may affect it. MATERIALS AND METHODS: Three hundred and fifty women who were accompanying other patients to the outpatient clinic of obstetrics and gynaecology. They came from different parts of northern India since AIIMS is a tertiary health referral centre. All women who had permanent cessation of menstruation for more than 1 year naturally were interviewed (n=201). A semi-structured questionnaire was designed to study the ANM and various demographic, reproductive, and socio-economic factors which affect it. Data were analyzed using logistic regression analysis to see if there was any association between age at natural menopause and various socio-demographic factors. RESULTS: The median ANM of the study sample was 48 years with the mean age of 46.7 years. There was no association between the various socio-demographic and reproductive factors and age at onset of menopause. CONCLUSION: The age at onset of menopause in northern India is 48 years which is about 3 years earlier than the west. Socio-demographic and reproductive factors did not affect the age at onset of menopause in our study.     

Childhood cognitive ability and age at menopause: evidence from two cohort studies

OBJECTIVE: To investigate whether poorer cognitive ability in childhood is associated with an earlier menopause. DESIGN: Two cohorts were included: a nationally representative British birth cohort study of 1,350 women born in March 1946 and followed up to age 54 years, and an Aberdeen cohort study of 3,465 women born in Aberdeen from 1950 to 1956 and followed up to age 44 to 50 years. Both cohorts had prospective information on childhood cognitive ability at age 7 or 8 years. RESULTS: In both cohorts, women with lower cognitive scores in childhood reached menopause earlier than women with higher scores. With follow-up of menopause to 49 years, the hazard ratio (HR) for one standard deviation of the cognitive score was 0.80 (95% CI, 0.72-0.90) in the Aberdeen cohort and 0.84 (95% CI, 0.73-0.97) in the older 1946 birth cohort. The effect was still evident in the 1946 birth cohort with follow-up of menopause to 53 years (HR = 0.87; 95% CI, 0.79-0.95). These ratios were weakly attenuated by adjustment for potential confounding effects of lifetime socioeconomic circumstances, parity, and smoking. CONCLUSIONS: The association between early cognitive ability and timing of menopause only partially reflects common risk factors, although residual confounding remains a possibility. Alternatively, early environmental or genetic programming may explain this association, perhaps through setting lifelong patterns of hormone release or causing transient hormonal changes at sensitive periods of development. These findings have implications for the interpretation of studies investigating an association between age at menopause and adult cognitive function.     

Use of time to event analysis to estimate the normal duration of human pregnancy.

BACKGROUND: Current estimates of the average duration of human pregnancy are flawed by inaccurate estimation of the time of conception and by failure to account adequately for the effect of routine elective delivery post-term. METHODS: In this study, 1514 healthy pregnant women were studied in whom the discrepancy between the menstrual history and first trimester crown-rump length estimated gestational age was within -1 to +1 day difference. The duration of gestation was estimated using time to event analysis: non-elective delivery was taken to be the event, and elective delivery was taken to be censoring. RESULTS: The median time to non-elective delivery using the Kaplan-Meier product limit estimate was 283 days after last menstrual period (LMP) and there was no difference comparing male and female fetuses. The median was significantly greater for nulliparous women compared with multiparous women (284 versus 282 days, P < 0.0001). Multivariate analysis using Cox's proportional hazards model confirmed the independent effect of nulliparity on duration of pregnancy [hazard ratio, 0.75; 95% confidence interval (CI) 0.67-0.85] and demonstrated no effect of maternal age, previous abortions, fetal sex, high parity, or bleeding before 24 completed weeks of gestation. Bleeding in the third trimester of pregnancy was, however, associated with an earlier onset of spontaneous labour (hazard ratio, 1.38; 95% CI 1.03-1.84). CONCLUSION: This study provides a basis for predicting the probability of labour at a given gestational age at term.     

Anti-mullerian hormone (AMH) is associated with natural menopause in a population-based sample: The CARDIA Women's Study

ObjectiveAMH is associated with menopausal timing in several studies. In contrast to prior studies that were restricted to women with regular cycles, our objective was to examine this association in women with either regular or irregular menstrual cycles.MethodsCARDIA is a longitudinal, population-based study that recruited adults ages 18–30 when it began in 1985–1986. AMH was measured in serum stored in 2002–2003. Natural menopause was assessed by survey in 2005–2006 and 2010–2011.ResultsAmong 716 premenopausal women, median [25th, 75th] AMH was 0.77 [0.22–2.02] ng/dL at a median age of 42 [39–45] years. Twenty-nine percent of the women (n = 207) reported natural menopause during 9 years of follow up. In fully adjusted discrete-time hazard models, a 0.5 ng/dL AMH decrement was associated with higher risk of menopause (p < 0.001). Hazard ratios varied with time since AMH measurement. The HR (95% CI) for menopause was 8.1 (2.5–26.1) within 0–3 years and 2.3 (1.7–3.3) and 1.6 (1.3–2.1) for 3–6 and 6–9 years, respectively. When restricted to women with regular menses, results were similar (e.g., HR = 6.1; 95% CI: 1.9–20.0 for 0–3 years).ConclusionAMH is independently associated with natural menopause. AMH appears most useful in identifying women at risk of menopause in the near future (within 3 years of AMH measurement).     

Age at natural menopause in Beirut,Lebanon: the role of reproductive and lifestyle factors

Summary. Primary objective: To determine the median age of natural menopause and factors associated with the timing of menopause in Beirut, Lebanon. Research design: A population-based sample of 298 women were interviewed using a semistructured questionnaire. Methods and procedures: Logit analysis and logistic regression were used to estimate the median age and identify correlates of menopausal status. Main outcomes and results: The median age of natural menopause in Beirut, Lebanon is estimated to be 49.3 years. Not being currently married (odds ratio (OR)=4.19, 95% CI: 1.53, 11.51) and smoking (OR=1.02 for each year of smoking, 95% CI: 1.00, 1.05) are significantly associated with an earlier age at menopause. Women with menstrual bleeding longer than 5 days have later ages at menopause (OR=0.50, 95% CI: 0.26, 0.97). Age at menarche, parity, education and socio-economic status are not statistically associated with the age at menopause. Conclusions: The age at natural menopause in Lebanon is comparable to median ages reported for women in industrialized countries (49.3-51.4). Our results emphasize the role of smoking in determining an earlier age at menopause and indicate that reproductive characteristics affect the timing of menopause.     

Age at natural menopause in Beirut, Lebanon: the role of reproductive and lifestyle factors

PRIMARY OBJECTIVE: To determine the median age of natural menopause and factors associated with the timing of menopause in Beirut, Lebanon. RESEARCH DESGIN: A population-based sample of 298 women were interviewed using a semi-structured questionnaire. METHODS AND PROCEDURES: Logit analysis and logistic regression were used to estimate the median age and identify correlates of menopausal status. MAIN OUTCOMES AND RESULTS: The median age of natural menopause in Beirut, Lebanon is estimated to be 49.3 years. Not being currently married (odds ratio (OR)=4.19, 95% CI: 1.53, 11.51) and smoking (OR = 1.02 for each year of smoking, 95% CI: 1.00, 1.05) are significantly associated with an earlier age at menopause. Women with menstrual bleeding longer than 5 days have later ages at menopause (OR = 0.50, 95% CI: 0.26, 0.97). Age at menarche, parity, education and socio-economic status are not statistically associated with the age at menopause. CONCLUSIONS: The age at natural menopause in Lebanon is comparable to median ages reported for women in industrialized countries (49.3-51.4). Our results emphasize the role of smoking in determining an earlier age at menopause and indicate that reproductive characteristics affect the timing of menopause.     

Age at natural menopause in Iran

Objectives: Estimation of mean and median age at menopause among Iranian women using a cumulative distribution by region. Methods: The number of 8194 women aged between 30 and 65+ who enrolled in National Health Survey in the year 2000 in Iran through cluster sampling were studied and according to their age and the onset of their menopause (12 month consecutive menstrual cessation), the pattern of age at natural menopause has been described using a cumulative distribution. Results: The median age of menopause has been calculated to be 49.9, 49.2, and 49.6 years in urban, rural, and total population, respectively. While the mean age at menopause in total population was 50.4 years (S.D.=4.3). As it has been shown, the median age of menopause in rural areas (49.2) is earlier than urban areas (49.9). This difference is statistically significant (95% CI: 1.00066, 1.03363). Conclusion: There are different factors influencing age at natural menopause but there are not certain and homogenous results about those factors in different studies. Therefore, it is obvious that exploring these factors in different regions in Iran merit to be done.     

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

ObjectiveTo investigate the factors associated with the age of natural menopause and menopausal symptoms in a large population of Chinese middle-aged women.Study designIn 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 measureMenopausal age and scorings of Kupperman menopause index.ResultsThe 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).ConclusionThe 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.     

Poor response to ovulation induction is a stronger predictor of early menopause than elevated basal FSH: a life table analysis

BACKGROUND: During the course of assisted reproduction treatment, a number of women exhibit a "poor response" to ovulation induction, or demonstrate an elevated basal FSH level (> or =10 IU/l) at a young age. We sought to determine whether these women are at increased risk of early menopause and poor reproductive performance. METHODS: A retrospective cohort study included 118 "poor responders" with normal basal FSH level (<10 IU/l), 164 women with raised basal FSH (> or =10 IU/l), and 265 controls, who underwent assisted reproduction treatment between 1987 and 1998. All women were < 40 years of age at the time of treatment and had normal menstrual cycles. Participants were sent a postal questionnaire in 2000-2001, seeking information on ovarian function and reproductive performance following cessation of treatment. RESULTS: After adjusting for age and smoking habits, women with poor response and raised basal FSH levels were more likely to experience symptoms of the peri-menopause [hazard ratios 2.4, 95% confidence interval (CI) 1.52-3.78, and 2.76, 95% CI 1.78-4.29 respectively, P = 0.0001]. Poor responders were six times and 23 times more likely to experience the menopause within 10 years of treatment than those with raised basal FSH levels and controls respectively (hazard ratio 5.97 and 23.9, P = 0.015 and 0.002 respectively). Poor responders and those with raised basal FSH levels have half the chance of spontaneous conception after discontinuation of treatment compared with controls (P < 0.007). CONCLUSIONS: Both poor response to ovarian stimulation and raised basal FSH are markers of reduced ovarian reserve and predict an increased risk of early menopause.