Testing predictions of the programmed and stochastic theories of aging: Comparison of variation in age at death,menopause, and sexual maturation

One of the arguments against aging being programmed is the assumption that variation in the timing of aging-related outcomes is much higher compared to variation in timing of the events programmed by ontogenesis. The main objective of this study was to test the validity of this argument. To this aim, we compared absolute variability (standard deviation) and relative variability (coefficient of variation) for parameters that are known to be determined by the developmental program (age at sexual maturity) with variability of characteristics related to aging (ages at menopause and death). We used information on the ages at sexual maturation (menarche) and menopause from the nationally representative survey of the adult population of the United States (MIDUS) as well as published data for 14 countries. We found that coefficients of variation are in the range of 8–13% for age at menarche, 7–11% for age at menopause, and 16–21% for age at death. Thus, the relative variability for the age at death is only twice higher than for the age at menarche, while the relative variability for the age at menopause is almost the same as for the age at menarche.     

Menopause in Blackfeet women--a life span perspective

A lifespan perspective, combining quantitative and qualitative approaches, is used to examine factors related to the timing of menopause in Blackfeet women of northern Montana (USA). Cross-sectional survey data demonstrate a median age at menopause using a status quo method of 51.6 years, and a mean age of 47.0 +/- 5.0 years among those women who had already experienced menopause. Age at menopause is inversely associated with age at menarche and having been breastfed, and positively associated with use of contraceptives, household income, and current or recent employment. Household income and age at menarche influence menopause age jointly in multivariate models. These and other patterns are examined in the lives of two women with very divergent ages at menopause. Although these data support an effect of early life influences on shaping reproductive trajectories that culminate in menopause, environmental factors and human agency during adult life may play a modifying role.     

Menarcheal age of Turkish girls in Bremen

Several studies have shown that there is a Northwest-Southeast gradient in menarcheal age of European girls, with menarche occurring on the average about one year earlier in girls living in the Southern parts of Europe as compared with those from the Northern and Northwestern European countries. Eveleth & Tanner (1976) as well as Danker-Hopfe (1986a) suggested that this gradient is due primarily to genetic differences rather than climatic or nutritional variation. To substantiate this hypothesis menarcheal age of Turkish girls who lived in Bremen for several years has been investigated. The mean age at menarche estimated by probit analysis based on status quo data from n = 494 girls aged from 9.0 to 16.5 years was 12.90 +/- 1.21 years. These results correspond very well to those reported by Neyzi et al. (1975) for girls from Istanbul. On the other hand mean menarcheal age of Turkish girls living in Bremen is distinctly lower than mean age at menarche of urban German girls, living in the same district. In summary the results of the present study support the hypothesis of a predominantly genetic cause for the observed Northwest-Southeast gradient in age at menarche in Europe.     

The effects of high altitude on age at menarche and menopause

The age at menarche and menopause of three groups of Bhotia females living at high altitude, Himalayan region — Uttar Pradesh, North India, were studied. The Johari Bhotia women had earliest menarche (¯X=15.1±1.1 years) as compared to Rang Bhotias, settled (¯X=15.6±0.9 years) and Rang Bhotias, migratory (¯X=16.0±1.0 years). The differences between all these three groups for age at menarche were significant. A trend towards increase in age at menarche with an increase in altitude has been observed, but the total fertility period in the three groups remained similar as early menarche has been found to be associated with early onset of menopause and late menarche with late menopause.     

Reproductive life of some Gujar women of Punjab

Data was collected on current age, age at menarche, marriage age, maternal age at 1st birth, age at the birth of last child, age at menopause, total number of conceptions, live births, stillbirths, abortions, dead children and living children for a sample of 150 Gunjar women of Punjab, India, during September and October 1977 to study their reproductive life. The women ranged in age from 45-55 years. The mean age at menarche was 14.90 years for the sample. The median age at menopause was 46.20 years. The mean age at marriage of the present sample was 12.56+-2.50 years; the mean age of the mother at the birth of her 1st child was 16.85 years; and the mean age at the birth of the last child was 38.68 years. The average number of conceptions was 7.2; the average number of live births of these 150 women was 6.90. The fertility of this population was natural as they were not using any family planning method.     

Duration of ovarian hormone exposure and gynecological cancer risk in Korean women: the Korean Heart Study

BackgroundAlthough reproductive and hormonal factors – such as early menarche and late menopause – have been reported as independent risk factors for cancer, few studies have examined these factors in East Asian populations.MethodsWe performed a large prospective cohort study of 66,466 women. Ovarian hormone exposure was defined as length of time between menarche and menopause. Incidence rates for breast, ovarian, endometrial and cervical cancers were examined separately in relation to reproductive lifespan defined as age at menopause minus age at menarche. Multivariable adjusted hazard ratios (HRs) with 95% confidence intervals (95% CIs) were calculated using the Cox proportional hazards model.ResultsWomen with early menarche were at increased risk for developing breast cancer (HR, 1.57, 95% CI, 1.17–2.10) for age at menarche ≤12 years compared to women with age at menarche ≥17 years. Women with late age at menopause (≥52 years) had increased risks for cancers of the breast (HR, 1.59, 95%CI, 1.11–2.28) and ovary (HR, 3.22, 95% CI, 1.09–9.55) compared to women with early menopause (≤45 years of age). Women with longer duration of ovarian hormone exposure (≥40 years) were at increased risk for developing breast cancer (HR, 2.23, 95% CI, 1.35–3.68) as well as endometrial cancer (p for trend, 0.0209).ConclusionsWe showed that longer reproductive spans are associated with an increased risk of breast and endometrial cancer in Korean women.     

Hormonal aspects in the causation of human breast cancer: epidemiological hypotheses reviewed, with special reference to nutritional status and first pregnancy

Epidemiology of breast cancer has identified early age at menarche, late first pregnancy, low parity and late menopause as risk factors, but in addition genetic factors, height, weight and living in western countries play a significant role. The international variation in incidence is almost exclusively due to non-genetic factors. Hypotheses in prevention-oriented research are reviewed: 1. obesity-related oestrogen production as a stimulus of the tumour in postmenopausal women; 2. nutritional status and energy expenditure during puberty and adolescence, developed for fertility and fecundity and extended later to breast cancer; 3. reproductive life during early adulthood, age at first pregnancy and its specific effects on breast tissues. The message of preventability of breast cancer is that mammary epithelial differentiation should come early. Our insight concerning events in puberty and early adulthood can be consolidated in one concept on the risk of extended proliferation of breast epithelium during early adulthood in the absence of full differentiation induced by pregnancy. The combined effects of Western-type nutrition, lack of exercise and Western-type women's emancipation sets the stage for breast cancer already at a young age. Since it is unlikely that emancipated women in affluent societies will return to the original life-style of getting pregnant as soon as it is biologically possible, a novel daring way of protection has to be considered. Could a "Breast Differentiation Pill" be developed to offer protection?     

Secular Trends of Reproductive Indices in Chuvashian Women

In the present cross-sectional study of the Chuvashian rural population, we examined the secular trends of age at menarche, the age at menopause, the reproductive period, and the age of the first marriage of Chuvashian women. The cohort included 745 women aged 18–90 years; age at menarche (N = 653) ranging from 10 to 24 years (mean 15.42 ± 2.11). Data regarding menopausal age was obtained from 316 women born between 1920 and 1950 (mean 48.5 ± 4.6). Statistical analyses included the maximum likelihood estimation and a Whiskers plot. Women born during the second through the fourth decade of the 20th century showed increasing mean values of age at menarche from 15.4 (second decade) up to 16.5 (fourth decade) and after that a decrease of the mean values to 14.0 (ninth decade). The mean values of menopausal age increased from 47.0 (women born from 1920 to 1925) to 49.3 (born from 1945 to 1950). Age at first marriage showed a trend of decreasing age. Our study demonstrated secular trends of age at menarche in Chuvashian women who had matured after World War II and also confirmed secular trends of increased age at menopause and the duration of the reproductive period. Women, whose maturation was during or immediately after World War II, showed a higher age at menarche and a higher dispersion of age at menopause.     

Age at menarche in urban Argentinian girls: association with biological and socioeconomic factors

Age at menarche is regarded as a sensitive indicator of physical, biological, and psychosocial environment. The aim of this study was to determine the age at menarche and its association with biological and socioeconomic factors in girls from Santa Rosa (La Pampa, Argentina). An observational cross-sectional study was carried out on 1,221 schoolgirls aged 9-15 years. Menarche data were obtained by the status-quo method. Height, sitting height, weight, arm circumference, tricipital and subscapular skinfolds were measured. We also calculated body mass index, measures of body composition and proportions, and fat distribution. To assess socioeconomic factors, parents completed a self-administered questionnaire about their occupation and education, family size, household, and other family characteristics. The median age at menarche - estimated by the logit method--was 12.84 years (95% CI: 12.71, 12.97). Compared with their premenarcheal age peers, postmenarcheal girls had greater anthropometric dimensions through age 12. After this age, only height was higher in the latter group. Data were processed by fitting two logistic regressions, both including age. The first model included anthropometric variables and birth weight, while the second model included the socioeconomic variables. The significant variables derived from each model were incorporated into a new regression: height, sitting height ratio (first model), and maternal education (second model). These three variables remained significantly associated with menarche. The results suggest a relationship between linear growth and menarche and agree with those found in other populations where the advancement of menarche is associated with improved living conditions. In relatively uniform urban contexts, maternal education may be a good proxy for the standard of living.     

The variation in age at menarche: an indicator of historic developmental tempo

Ample literature describes the history of the association between the advances in the health and wealth of people, and mortality rates, life expectancy and adult height. Twenty-nine German studies with n > 200 subjects published since 1848 on menarcheal age, were reanalyzed, and 101 studies from various other European and non-European countries. On average, mean age at menarche declined since the mid-19th century. Historic urban samples tended to decline earlier than rural groups, upper class women earlier than working class women. In Germany, minimum values for the age at menarche were seen already between the two World Wars (Leipzig 12.6 years in 1934, Halle 13.3 years in 1939). Values for mean age and SD for age at menarche were strongly associated. With improving historic circumstances, the two parameters declined in parallel. The standard deviation for menarcheal age dropped from over 2.5 years in mid-19" century France to little more or even less than 1 year in most modern countries. In the German studies the correlation between menarcheal age and SD was almost complete with r = 0.96 (y = 0.35x - 3.53). Similar associations between mean age at menarche and SD for age were found in other European countries. The obvious and immediate effects of historic events on menarcheal age, and particularly on the age distribution, indicate that menarche is a sensitive indicator of public health and wealth, and may be an appropriate estimator for the socio-economic background of historic populations.     

Correlates and predictors of the age of menarche

In a cross-sectional study of 452 girls between 10 and 16 years of age 36 indices of physical and 50 of mental development were tested for their correlation with age at menarche and chronological age, as well as for their predictive power for estimating menarche by multiple regression analysis. Indices of physical maturity and body weight when adjusted for chronological age showed the highest partial correlation coefficients with age at menarche. Among mental characters which show lower intercorrelations with menarche occurred the highest correlation coefficients for a handmotor factor "Spurennachzeichnen" and a factor "Gruppenabh?ngigkeit" (which indicates a type of social motivation). In general physical and mental factors correlate higher with chronological age than with age at menarche. By multiple regression analysis we determined 14 physical and 25 mental predictors explaining 21% and 17% respectively of the variance of age at menarche. The error of the estimate predicting menarche on body weight without knowledge of onset of menarche is +/- 1 year. Using chronological age in a sample of girls before menarche the error of the estimate only is +/- 6 months. To compare the predictive power of chronological age combined with body weight or with skeletal age the time interval is calculated within which 95% of girls attain menarche. The range of prediction extends from 4.3 to 1 year on chronological age (11-16 years); using mean body weight it can be improved by 1.8 to 6 months, while using mean skeletal age an improvement of 0.2 to 3.9 months is possible compared with body weight. The correlations between age at menarche and physical and mental variables are attributed to a common hormonal influence on rate of development.     

Natural selection and quantitative genetics of life-history traits in Western women: a twin study

Whether contemporary human populations are still evolving as a result of natural selection has been hotly debated. For natural selection to cause evolutionary change in a trait, variation in the trait must be correlated with fitness and be genetically heritable and there must be no genetic constraints to evolution. These conditions have rarely been tested in human populations. In this study, data from a large twin cohort were used to assess whether selection will cause a change among women in a contemporary Western population for three life-history traits: age at menarche, age at first reproduction, and age at menopause. We control for temporal variation in fecundity (the "baby boom" phenomenon) and differences between women in educational background and religious affiliation. University-educated women have 35% lower fitness than those with less than seven years education, and Roman Catholic women have about 20% higher fitness than those of other religions. Although these differences were significant, education and religion only accounted for 2% and 1% of variance in fitness, respectively. Using structural equation modeling, we reveal significant genetic influences for all three life-history traits, with heritability estimates of 0.50, 0.23, and 0.45, respectively. However, strong genetic covariation with reproductive fitness could only be demonstrated for age at first reproduction, with much weaker covariation for age at menopause and no significant covariation for age at menarche. Selection may, therefore, lead to the evolution of earlier age at first reproduction in this population. We also estimate substantial heritable variation in fitness itself, with approximately 39% of the variance attributable to additive genetic effects, the remainder consisting of unique environmental effects and small effects from education and religion. We discuss mechanisms that could be maintaining such a high heritability for fitness. Most likely is that selection is now acting on different traits from which it did in pre-industrial human populations.     

Hormonal and reproductive risk factors of papillary thyroid cancer: A population-based case-control study in France

The three times higher incidence of thyroid cancer in women compared to men points to a role of female sex hormones in its etiology. However the effects of these factors are poorly understood. We analyzed the association between thyroid cancer and hormonal and reproductive factors among women enrolled in CATHY, a population-based case-control study conducted in France. The study included 430 cases of papillary thyroid cancer and 505 controls frequency-matched on age and area of residence. The odds ratios for thyroid cancer increased with age at menarche (p trend 0.05). Postmenopausal women were at increased risk, as compared to premenopausal women, particularly if menopause followed an ovariectomy, and for women with age at menopause < 55 years. In addition, use of oral contraceptives and menopausal hormone therapy reduced the association with thyroid cancer by about one third, and breastfeeding by 27%. Overall, these findings provide evidence that the risk of thyroid cancer increases with later age at menarche and after menopause, and decreases with use of oral contraceptives and menopausal hormone therapy. These findings confirm an implication of hormonal factors in papillary thyroid cancer risk, whose mechanisms need to be elucidated.     

Formula feeding in infancy is associated with adolescent body fat and earlier menarche.

The tempo, level of growth and maturation during adolescence may have important implications to future adult health. The purpose of the study was to examine factors associated with menarche. Three hundred and forty girls, 9 to 14 years old, were selected from all age eligible girls at Kaiser Permanente Oahu (Honolulu). Girls' age, ethnicity, menstrual status and feeding pattern during infancy were obtained by questionnaire. The mean age of girls was 11.5 +/- 1.4 yr and the mean age at menarche among 112 (33%) girls who had reached menarche was 11.6 +/- 1.1 yr. In logistic regression, achievement of menarche was positively explained by age, Asian ethnicity and formula feeding during infancy. In simple linear regression, higher body mass index (BMI) and subcutaneous fat were also positively associated with formula feeding during infancy. The study suggests that girls who were formula fed deposit more body fat than girls who were breast-fed, resulting in early attainment of menarche.     

Season of birth and recalled age at menarche.

All 8th-form schoolgirls from the municipality of Odense in Denmark were asked at what age they reached menarche, and 886 girls (97.6%) gave this information. There is no evidence for seasonality in the time of birth but for far more girls than expected menarche occurred during winter or summer and fewer than expected during spring and autumn. This pattern appears primarily in girls living in the suburbs and was not seen in those living in central Odense. The seasonality appears to be brought about by differences in mean age at menarche according to time of the year at birth.     

Intergenerational context discontinuity affects the onset of puberty

The assumption that the onset of puberty is a context-sensitive marker of a reproductive strategy is tested by comparing parental and filial childhood context and somatic development in West and East Germany. Sixty-eight mother-daughter dyads and 35 father-son dyads were taken from two samples of families from Osnabrück in West Germany and Halle in East Germany. According to the observed context discontinuity between the generations in the male dyads, linear regression models show that no indicator of male sexual maturation was influenced significantly by the somatic development of the father. Instead of an inherited timing of maturation, antecedent distal factors like socioeconomic childhood context variables and critical life events lead to an acceleration of male sexual maturation. Finally we test the effect of two different conditions of childhood context continuity on daughter’s age at menarche with maternal age at menarche controlled. Linear regression models show that mother’s age at menarche predicts daughter’s age at menarche only under the condition of contextual continuity between generations, which was the case in the West German sample only. In East Germany, where mother’s age at menarche had no significant effect, the amount of variance explained by childhood context variables was almost the same. These results indicate the context sensitivity of somatic development which seems to follow an evolutionary rationale.     

Reproductive events and family history as risk factors for breast cancer in northern Alberta.

Reproductive events and family history as risk factors for breast cancer in northern Alberta were investigated with the use of data from a computerized population-based registry. Women aged 30 to 79 years attending diagnostic breast clinics at the Cross Cancer Institute from 1971 through 1975 constituted the two study groups; 1232 women had diagnosed breast cancer (malignant disease group) and 602 women were clinically free of all types of breast disease (control group). An increased relative risk of breast cancer was found in women with a family history of breast cancer, those who gave birth to their first term infant at age 30 years or older, those in whom more than 15 years elapsed between menarche and that birth, and those with a late natural menopause. There was a decreased risk, relative to nulliparity, in the postmenopausal women who first gave birth to a term infant 5 years or less after menarche. Artificial menopause (bilateral oophorectomy), parity and age at menarche had no apparent effect on the risk. The pattern of risk factors in northern Alberta differed from that reported for other geographic areas, including other provinces of Canada, thus emphasizing the need for local studies in the planning of screening programs.     

Secular trend in age at menarche in China: a case study of two rural counties in Anhui Province.

There is increasing evidence that age at menarche has decreased in Europe and the United States during the last century and in Japan over the last several decades. Data from a community-based survey conducted in two rural counties of Anhui Province in China indicate a similar, downward secular trend in age at menarche for Chinese women. The present study shows the mean age at menarche decreased by 2.8 years, from 16.5 to 13.7, over an approximate 40-year time interval. This rapid decrease in age at menarche may partly be due to better nutrition and living standards reflected by the improved socioeconomic standards experienced in China over the past few decades. To test this hypothesis, a number of determinants of age at menarche were assessed; year of birth, literacy status, county of residence, amount of physical labour, general health status, pesticide exposure before age at menarche, and drinking water source were all found to be associated with age at menarche.     

Malnutrition, menarche, and marriage in rural Bangladesh

In order to assess the impact of nutritional status on the onset of menarche and the association between age at menarche and age at marriage, a survey of 1155 girls, ages 10 through 20, was conducted in a rural area of Bangladesh in March 1976. In order to obtain an estimated mean of age of menarche, probit analysis was used. The mean age of menarche using this technique is estimated at 15.65 for Muslims and 15.91 for Hindus. It was learned that in recent years the age of menarche has increased in a rural area. This increase seems to be associated with malnutrition caused by the war, postwar inflation, floods and famines during the 1971-75 period. When age is controlled for, the prominent effect of weight on menstrual status is evident. 98% of the girls whose weights were 88 pounds or greater had reached menarche compared to only 1% of those weighing less than 66 pounds. Body weight appears to be 1 of the most important factors for the determination of onset of menarche. There exists a seasonality of onset of menarche with a peak in winter. Age of marriage among this rural population has increased and may be associated with the increasing age of menarche. Since both age of menarche and age of marriage have increased, fertility among females age 15-19 may be expected to decrease in the future if this pattern continues.     

Association between age at menarche and early-life nutritional status in rural Bangladesh

Age at menarche is associated with anthropometry in adolescence. Recently, there has been growing support for the hypothesis that timing of menarche may be set early in life but modified by changes in body size and composition in childhood. To evaluate this, a cohort of 255 girls aged <5 years recruited in 1988 were followed up in 2001 in Matlab, Bangladesh. The analysis was based on nutritional status as assessed by anthropometry and recalled age at menarche. Data were examined using lifetable techniques and the Cox regression model. The association between nutritional status indicators and age at menarche was examined in a multivariate model adjusting for potential confounding variables. Censored cases were accounted for. The median age at menarche was 15.1 years. After controlling for early-life predictors (birth size, childhood underweight, childhood stunting) it appeared that adolescent stunting stood out as the most important determinant of age at menarche. Adolescent stunting still resonates from the effect of stunting in early childhood (OR respectively 2.63 (p<0.01 CI: 1.32-5.24) and 8.47 (p<0.001 CI: 3.79-18.93) for moderately and severely stunted under-fives as compared with the reference category). Birth size was not a significant predictor of age at menarche. It is concluded that age at menarche is strongly influenced by nutritional status in adolescence, notably the level of stunting, which is in turn highly dependent on the level of stunting in early childhood. A 'late' menarche due to stunting may be detrimental for reproductive health in case of early childbearing because of the association between height and pelvic size.