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.     

International variability of ages at menarche and menopause: patterns and main determinants.

The purpose of this study was to review published studies on the variability of age at menarche and age at menopause throughout the world, and to identify the main causes for age variation in the timing of these events. We first present a summary table including mean (or median) values of the age at menarche in 67 countries, and of the age at menopause in 26 countries. General linear models showed that mean age at menarche was strongly linked to the mean female life expectancy, suggesting that one or several variables responsible for inequalities in longevity similarly influenced the onset of menarche. A closer examination of the data revealed that among several variables reflecting living conditions, the factors best explaining the variation in age at menarche were adult illiteracy rate and vegetable calorie consumption. Because adult illiteracy rate has some correlation with the age at which children are involved in physical activities that can be detrimental in terms of energy expenditure, our results suggest that age at menarche reflects more a trend in energy balance than merely nutritional status. In addition, we found the main determinant of age at menopause to be the mean fertility. This study thus suggests that, on a large scale, age at menarche is mainly determined by extrinsic factors such as living conditions, while age at menopause seems to be mainly influenced by intrinsic factors such as the reproductive history of individuals. Finally, these findings suggest that human patterns cannot be addressed solely by traditional, small-scale investigations on single populations. Rather, complementary research on a larger scale, such as this study, may be more appropriate in defining some interesting applications to the practical problems of human ecology.     

Age at menarche,socio‐sexual behavior,and fertility

Abstract

This paper examines the relationship between age at menarche and fertility from two perspectives. Age at menarche is regarded as a crude indicator of the timing of fecundity that may affect the timing of conception among those sexually active; and age at menarche is regarded as a crude indicator of the timing of sexual maturation that may influence the timing of socio‐sexual behavior, namely dating and sexual intercourse. The data are drawn from a survey of New York City women who recently had their first child. The findings suggest that age at menarche as an indicator of fecundity is not a good predictor of the timing of the first birth, when controlling for age at first sexual intercourse. Looking only at initial noncontraceptors, however, we find the relationship is stronger. Age at menarche, viewed as an indicator of the timing of sexual maturation, does seem to have some influence on the timing of dating, but only for Blacks. For both races, age at first date is related to age at first sexual intercourse.     

Reproductive development and behavior of captive female chimpanzees

The reproductive histories and behavior of six chimpanzees were analyzed in order to evaluate the female reproductive pattern. This analysis indicated that captive females undergo an earlier menarche and an acceleration of subsequent reproductive phases as compared to wild chimpanzees. Menarche occurred between 7.7–9.3 years of age and first conceptions occurred between 8.2–10.7 years of age. Changes in the females' sex skins across menarche, pregnancy, and the menstrual cycle were also evaluated. The fluctuation in sex skin size was shown to have a marked effect on the occurrence of sexual behavior. In addition, the social context and relative familiarity of the chimpanzees affected the choice of sexual partners.     

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.     

A large-scale candidate gene association study of age at menarche and age at natural menopause

Recent genome-wide association (GWA) studies have identified several novel genetic loci associated with age at menarche and age at natural menopause. However, the stringent significance threshold used in GWA studies potentially led to false negatives and true associations may have been overlooked. Incorporating biologically relevant information, we examined whether common genetic polymorphisms in candidate genes of nine groups of biologically plausible pathways and related phenotypes are associated with age at menarche and age at natural menopause. A total of 18,862 genotyped and imputed single nucleotide polymorphisms (SNPs) in 278 genes were assessed for their associations with these two traits among a total of 24,341 women from the Nurses’ Health Study (NHS, N = 2,287) and the Women’s Genome Health Study (WGHS, N = 22,054). Linear regression was used to assess the marginal association of each SNP with each phenotype. We adjusted for multiple testing within each gene to identify statistically significant SNP associations at the gene level. To evaluate the overall evidence for an excess of statistically significant gene associations over the proportion expected by chance, we applied a one-sample test of proportion to each group of candidate genes. The steroid-hormone metabolism and biosynthesis pathway was found significantly associated with both age at menarche and age at natural menopause (P = 0.040 and 0.011, respectively). In addition, the group of genes associated with precocious or delayed puberty was found significantly associated with age at menarche (P = 0.013), and the group of genes involved in premature ovarian failure with age at menopause (P = 0.025).     

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.     

Temporal scaling of age-dependent mortality: Dynamics of aging in <Emphasis Type="Italic">Caenorhabditis elegans</Emphasis> is easy to speed up or slow down,but its overall trajectory is stable

The dynamics of aging is often described by survival curves that show the proportion of individuals surviving to a given age. The shape of the survival curve reflects the dependence of mortality on age, and it varies greatly for different organisms. In a recently published paper, Stroustrup and coauthors ((2016) Nature, {vn530}, 103–107) showed that many factors affecting the lifespan of Caenorhabditis elegans do not change the shape of the survival curve, but only stretch or compress it in time. Apparently, this means that aging is a programmed process whose trajectory is difficult to change, although it is possible to speed it up or slow it down. More research is needed to clarify whether the “rule of temporal scaling” is applicable to other organisms. A good indicator of temporal scaling is the coefficient of lifespan variation: similar values of this coefficient for two samples indicate similar shape of the survival curves. Preliminary results of experiments on adaptation of Drosophila melanogaster to unfavorable food show that temporal scalability of survival curves is sometimes present in more complex organisms, although this is not a universal rule. Both evolutionary and environmental changes sometimes affect only the average lifespan without changing the coefficient of variation (in this case, temporal scaling is present), but often both parameters (i.e. both scale and shape of the survival curve) change simultaneously. In addition to the relative stability of the coefficient of variation, another possible argument in favor of genetic determination of the aging process is relatively low variability of the time of death, which is sometimes of the same order of magnitude as the variability of timing of other ontogenetic events, such as the onset of sexual maturation.     

Environmental risk factors differ between rheumatoid arthritis with and without auto-antibodies against cyclic citrullinated peptides

The aim of this study was to evaluate new and previously hypothesised non-genetic risk factors for serologic subtypes of rheumatoid arthritis (RA) defined by the presence or absence of auto-antibodies to cyclic citrullinated peptides (CCP). In a national case-control study, we included 515 patients recently diagnosed with RA according to the American College of Rheumatology 1987 classification criteria and 769 gender- and age-matched population controls. Telephone interviews provided information about non-genetic exposures, and serum samples for patients were tested for anti-CCP-antibodies. Associations between exposure variables and risk of anti-CCP-positive and anti-CCP-negative RA were evaluated using logistic regression. A series of RA subtype-specific risk factors were identified. Tobacco smoking (odds ratio [OR] = 1.65; 95% confidence interval: 1.03–2.64, for >20 versus 0 pack-years) was selectively associated with risk of anti-CCP-positive RA, whereas alcohol consumption exhibited an inverse dose-response association with this RA subtype (OR = 1.98, 1.22–3.19, for 0 versus >0–5 drinks per week). Furthermore, coffee consumption (OR = 2.18; 1.07–4.42, for >10 versus 0 cups per day), ever use of oral contraceptives (OR = 1.65; 1.06–2.57) and having a first-degree relative with schizophrenia (OR = 4.18; 1.54–11.3) appeared more strongly associated with risk of anti-CCP-positive RA. Obesity was selectively associated with risk of anti-CCP-negative RA, with obese individuals being at more than 3-fold increased risk of this subtype compared with normal-weight individuals (OR = 3.45; 1.73–6.87). Age at menarche was the only examined factor that was significantly associated with both serologic subtypes of RA (p-trends = 0.01); women with menarche at age ≥ 15 years had about twice the risk of either RA subtype compared with women with menarche at age ≤ 12 years. Major differences in risk factor profiles suggest distinct etiologies for anti-CCP-positive and anti-CCP-negative RA.     

Age at menarche, schooling, and sexual debut in northern Malawi

Background

Age at sexual debut is a key behavioural indicator used in HIV behavioural surveillance. Early age at menarche may precipitate early sex through perceived readiness for sex, or through school drop-out, but this is rarely studied. We investigated trends and circumstances of sexual debut in relation to schooling and age at menarche.

Methods and Findings

A cross-sectional sexual behaviour survey was conducted on all individuals age 15–59 within a demographic surveillance site in Karonga District, Malawi. Time trends were assessed using birth cohorts. Survival analysis was used to estimate the median age at menarche, sexual debut and first marriage. The 25^th centile was used to define “early” sex, and analyses of risk factors for early sex were restricted to those who had reached that age, and were done using logistic regression. Of the 8232 women and 7338 men resident in the area, 88% and 78%, respectively, were seen, and, 94% and 92% of these were interviewed. The median reported age at first sex was 17.5 for women and 18.8 for men. For women, ages at menarche, sexual debut and first marriage did not differ by birth cohort. For men, age at sexual debut and first marriage decreased slightly in later birth cohorts. For both men and women increased schooling was associated with later sexual debut and a longer delay between sexual debut and first marriage, but the associations were stronger for women. Earlier age at menarche was strongly associated with earlier sexual debut and marriage and lower schooling levels. In women early sexual debut (<16 years) was less likely in those with menarche at age 14–15 (odds ratio (OR) 0.31, 95%CI 0.26–0.36), and ≥16 (OR 0.04, 95%CI 0.02–0.05) compared to those with menarche at <14. The proportion of women who completed primary school was 46% in those with menarche at <14, 60% in those with menarche at 14–15 and 70% in those with menarche at ≥16. The association between age at menarche and schooling was partly explained by age at sexual debut. The association between age at menarche and early sex was not altered by adjusting for schooling.

Conclusions

Women with early menarche start sex and marry early, leading to school drop-out. It is important to find ways to support those who reach menarche early to access the same opportunities as other young women.     

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.     

The lower salivary testosterone levels among unmarried and married sexually active men

We examined the influences of regular sexual activity and marital status on salivary testosterone levels in healthy adult Japanese men. Forty-four men (20–66 years) collected their saliva thrice a day (0900–1000, 1300–1400, and 1700–1800). The testosterone levels at each collection time negatively correlated with the ages of the participants; therefore, residual testosterone levels were used for analyses after correcting for age by linear regression. The testosterone-lowering effect of marriage was marginal and the regular sexual activity more strongly associated with lower testosterone levels in morning saliva. The possible neurofeedback systems underlying the phenomenon are discussed.     

Age at Menarche and Natural Menopause and Number of Reproductive Years in Association with Mortality: Results from a Median Follow-Up of 11.2 Years among 31,955 Naturally Menopausal Chinese Women

Background

Studies conducted in Western countries suggest that early age at menarche and early age at menopause are both associated with increased total mortality, but limited data are available for Asian populations. We examined associations of age at menarche and natural menopause and duration of the reproductive span with mortality in a population-based cohort study of Chinese women.

Methods

We evaluated the effects of age at menarche, age at natural menopause, and number of reproductive years on total and cause-specific mortality among 31,955 naturally menopausal Chinese women who participated in the Shanghai Women''s Health Study, a population-based, prospective cohort study.

Results

A total of 3,158 deaths occurred during a median follow-up of 11.2 years. Results from Cox proportional hazards models showed that younger age at menopause (<46.64 years) was associated with higher risk of total mortality (P_trend  = 0.02). Younger age at menarche (<14 years) was associated with higher risk of mortality from stroke (P_trend  = 0.03) and diabetes (P_trend = 0.02) but lower risk of mortality from respiratory system cancer (P_trend  = 0.01). Women with a shorter reproductive span had lower risk of mortality from gynecological cancers (P_trend = 0.03).

Conclusions

Our study found that menstrual characteristics are important predictors of mortality, suggesting an important role of sex hormones in biological aging.     

Age at menarche, at first intercourse, and at first pregnancy

Data from an urban sample of American women of reproductive ages demonstrate that age at menarche is correlated with age at first intercourse, that age at first intercourse is correlated with age at first pregnancy, and that menarche is therefore correlated with age at first pregnancy. This applied to both blacks and whites when examined for the early years of the reproductive cycle. Girls with early menarche, compared to those with late menarche, are more than twice as likely to have had intercourse by age 16, and almost twice as likely to have given birth or had a pregnancy terminated by age 18. It is therefore useful to think of the timing of menarche as an indicator of the probability of early intercourse and early childbearing.     

Coefficient of variation of lifespan across the tree of life: Is it a signature of programmed aging?

Measurements of variation are of great importance for studying the stability of pathological phenomena and processes. For the biology of aging, it is very important not only to determine average mortality, but also to study its stability in time and the size of fluctuations that are indicated by the variation coefficient of lifespan (CV_LS). It is believed that a relatively small (～20%) value of CV_LS in humans, comparable to the coefficients of variation of other events programmed in ontogenesis (for example, menarche and menopause), indicates a relatively rigid determinism (N. S. Gavrilova et al. (2012) Biochemistry (Moscow), 77, 754-760). To assess the prevalence of this phenomenon, we studied the magnitude of CV_LS, as well as the coefficients of skewness and kurtosis in diverse representatives of the animal kingdom using data provided by the Institute for Demographic Research (O. R. Jones et al. (2014) Nature, 505, 169-173). We found that, unlike humans and laboratory animals, in most examined species the values of CV_LS are rather high, indicating heterogeneity of the lifespan in the cohorts studied. This is probably due to the large influence of background mortality, as well as the non-monotonicity of total mortality in the wild, especially at the earliest ages. One way to account for this influence is to “truncate” the data (removing the earliest and latest ages from consideration). To reveal the effect of this procedure, we proposed a new indicator, the stability coefficient of mortality dynamics, which indicates how quickly CV_LS is reduced to values that characterize a relatively homogeneous population (33%) when the data are “truncated”. Such indicators facilitate the use of the parameters of survival curves for analysis of the effects of geroprotectors, lifestyle, and other factors on lifespan, and for the quantification of relative contributions of genetic and environmental factors to the dynamics of aging in human and animal populations, including those living in the wild.     

Reproductive aging in captive and wild common chimpanzees: factors influencing the rate of follicular depletion

We examine and discuss evidence of contrasting differences in fertility patterns between captive and wild female chimpanzees, Pan troglodytes, as they age; in the wild females reproduce in their 40s, but captive studies suggest that menopause occurs around that time. Thus, despite the increased longevity generally observed in captive populations reproductive life span is shortened. We outline a hypothesis to explain the apparent differential pace of reproductive decline observed between wild and captive populations. The breeding schedules of captive primates may contribute to accelerated reproductive senescence because continuous cycling in captive animals results in early depletion of the ovarian stock and premature senescence. Available evidence supports the hypothesis that women with patterns of high oocyte loss experience earlier menopause. Chimpanzees in captivity live longer, and thus, similar to humans, they may experience follicular depletion that precedes death by many years. In captivity, chimpanzees typically have an early age at menarche and first birth, shorter interbirth intervals associated with short lactational periods as young mature faster, and nursery rearing, which allows mothers to begin cycling earlier. Variables typical of wild chimpanzee populations, including late age at menarche and first birth, long interbirth intervals associated with prolonged lactational periods, and a long period of female infertility after immigration, spare ovulations and may be responsible for the later age at reproductive termination. Finally, we describe and discuss the timing of specific reproductive landmarks that occur as female chimpanzees age, distinguishing between functional menopause (age at last birth) and operational menopause (end of cycling). Am. J. Primatol. 71:271–282, 2009. © 2008 Wiley‐Liss, Inc.     

Association study of the oestrogen signalling pathway genes in relation to age at natural menopause

Genetic factors play a significant role in influencing the variation of age at natural menopause (AANM). Estrogen receptor β (ESR2), is an important factor in the mechanism of action of estrogen, while the aromatase gene (CYP19) and the 17-alphahydroxylase gene (CYP17) are involved in the biosynthesis of estrogen. We tested whether polymorphisms of ESR2, CYP19 and CYP17 genes are associated with AANM in Caucasian females. A total of 52 SNPs (17 for ESR2, 28 for CYP19, and 7 for CYP17) were successfully genotyped for 229 Caucasian women having experienced natural menopause. Comprehensive statistical analyses focusing on the association of these genes with AANM were conducted. The effects of age, height and age at menarche on AANM were adjusted when conducting association analyses. We found that six SNPs (2, 6–7, 9, 13 and 16) within ESR2 were not significantly associated with AANM after Bonferroni correction. However, two blocks of ESR2 were associated with AANM. For CYP19, two SNPs (24 and 27) were nominally associated with AANM. No significant association was observed between CYP17 and AANM. Our results suggest that genetic variation in the ESR2 and CYP19 genes may influence the variation in AANM in Caucasian women.     

Weather Variability, Sunspots, and the Blooms of Cyanobacteria

The roles of weather variability and sunspots in the occurrence of cyanobacteria blooms, were investigated using cyanobacteria cell data collected from the Fred Haigh Dam, Queensland, Australia. Time series generalized linear model and classification and regression tree (CART) model were used in the analysis. Data on notified cell numbers of cyanobacteria and weather variables over the periods 2001 and 2005 were provided by the Australian Department of Natural Resources and Water, and Australian Bureau of Meteorology, respectively. The results indicate that monthly minimum temperature (relative risk [RR]: 1.13, 95% confidence interval [CI]: 1.02–1.25) and rainfall (RR: 1.11; 95% CI: 1.03–1.20) had a positive association, but relative humidity (RR: 0.94; 95% CI: 0.91–0.98) and wind speed (RR: 0.90; 95% CI: 0.82–0.98) were negatively associated with the cyanobacterial numbers, after adjustment for seasonality and auto-correlation. The CART model showed that the cyanobacteria numbers were best described by an interaction between minimum temperature, relative humidity, and sunspot numbers. When minimum temperature exceeded 18°C and relative humidity was under 66%, the number of cyanobacterial cells rose by 2.15-fold. We conclude that weather variability and sunspot activity may affect cyanobacteria blooms in dams.     

Sexual and Hormonal Cycles in Geriatric Gorilla gorilla gorilla

As our closest living relatives, great apes likely experience behavioral and physiological patterns associated with reproductive aging and menopause that are similar to human patterns. We present results from a nationwide zoo-based study on behavioral and hormonal changes in female western gorillas. We evaluated progestogen concentrations via daily fecal sampling in 30 gorillas, 22 of which were geriatric (≥30). We collected concurrent behavioral data 1–3 times weekly on 16 of the females. While control females cycled regularly, ca. 23% of geriatric females are acyclic (menopausal), and another 32% show variable hormonal patterns suggesting perimenopause. Patterns included increased variability in cycle length and peak progestogen values, and frequent insufficient increases in progestogen levels during the luteal phase. Acyclic females have significantly lower overall progestogen concentrations than the self cycling females, though differences are not significant when cycle phase is incorporated. We detected behavioral estrus in 9 of 10 cycling females for which data were available. In all but 1 case, proceptive behavior occurred during the follicular phase, preceding ovulation on average by 6.6 d. Females spent more time in proximity to the silverback male while in behavioral estrus than during other periods. To date, maximum longevity in captive female gorillas is 52 yr, with poor reproductive prognosis beginning from the age of 37. We demonstrate that both perimenopause and menopause characterize aged female gorillas, which may experience a postreproductive lifespan of >25% of their lives. Continued study of aging apes is warranted, and apes may serve as models for age-related reproductive changes in humans.     

Scaling of Size and Dimorphism in Primates I: Microevolution

I used a new quantitative genetics model to predict relationships between sex-specific body size and sex-specific relative variability when populations experience differences in relative intensity of sex-specific selection pressures—stronger selection on males or females—and direction of selection: increase or decrease in size. I combined Lande's (Evolution 34: 292–305) model for the response of sex-specific means to selection with a newly derived generalization of Bulmer's (Am. Nat. 105: 201–211) model for the response of relative variability to selection. I used this combined response model to predict correlations of sex-specific size and relative variability under various starting conditions, which one can compare to correlations between closely related primate populations. One can then compare predicted patterns of sex-specific selection pressures to social and ecological variables pertaining to those populations to identify likely forces producing microevolutionary change in sexual size dimorphism (SSD). I provide examples of this approach for populations representing three taxa: Papio anubis, Saguinus mystax, and Cercopithecus aethiops pygerythrus. Model results suggest that microevolutionary changes in SSD can result from greater selection acting on males or females, and that natural selection or natural and sexual selection combined, rather than sexual selection alone, may sometimes explain sex-specific selection differentials.