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 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 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 and intrapopulational variation in age at menopause in Spanish women

Menopause is associated with the general ageing process and marks the end of follicular depletion, a process that begins in the intrauterine stage and lasts throughout the lifetime of women until their reproductive senescence. Controversy persists about whether the age at menopause is sensitive to the ecological determinants prevailing during the lifecycle or whether it has a predominantly genetic component that would allow groups of women to be characterized with respect to particular menstrual characteristics manifested throughout their fertile life. By contrast, there is a definite secular trend in age at menarche in populations that have registered improvements in their environment: sexual maturation is closely associated with the general processes of growth and development. These aspects were analysed in a sample of Spanish women, mothers and daughters, born between 1883 and 1941. The results show (a) indications--although not conclusive--of a secular trend in the age at menopause, (b) a possible association between the age at menopause of mothers and their daughters, and (c) an association at the individual level between age at menarche, particular characteristics of ovarian function (fetal loss) and age at menopause. The reproductive ageing process therefore seems to result from the expression of the influence of ecological conditions in which the lifecycle of the women develops and of a degree of heritability that affects not only the age at menopause but also a range of characteristics of ovarian function.     

Reproductive and external hormonal factors and the risk of renal cell cancer in the Netherlands Cohort Study

BackgroundSeveral reproductive and hormonal factors, like age at menarche, parity, age at menopause, use of oral contraceptives and postmenopausal treatment, have been associated with the risk of renal cell cancer (RCC) in women, but results have not always been consistent. We therefore investigated the association between these factors and the risk of RCC in postmenopausal women participating in the Netherlands Cohort Study on Diet and Cancer.MethodsInformation on reproductive history, exogenous hormone use and gynecological surgery was obtained through a self-administered questionnaire at baseline in 1986. After 20.3 years of follow-up, 204 cases and 2280 subcohort members were available for case-cohort analysis. Multivariable hazard ratios (HR) were calculated using Cox Proportional Hazard analysis.ResultsWomen who reported a hysterectomy had an increased RCC risk compared to women who did not (HR, 1.42, 95%CI, 1.01–2.00). Women with a natural age at menopause between 45 and 49 years compared to 50–54 years had an increased RCC risk (HR, 1.61; 95%CI, 1.10–2.35). RCC risk was slightly and not statistically significant increased among parous women with three or more children and age at first birth before 25 years compared to nulliparous women (HR, 1.36; 95% confidence interval (CI), 0.84–2.20). No associations were observed with RCC risk for age at menarche, use of oral contraceptives and use of hormonal replacement therapy.ConclusionHysterectomy and age at natural menopause were associated with an increased RCC risk. Other hormonal and reproductive factors and RCC risk were not increased. Further studies are required to establish the mechanism(s) that explain the observed association.     

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.     

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.     

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.     

Predictors of age at menarche in the newcastle thousand families study

Several studies have found relationships between early life factors (birth weight, length of gestation, height, weight, duration of breast-feeding, maternal age, social class, periods of infection, presence of adverse life events, and quality of housing conditions in childhood) and age at menarche but none has considered all of these factors in the same study. The follow-up study of the Newcastle Thousand Families birth cohort, established in 1947, provided age at menarche data collected retrospectively at age 50 from 276 women who returned self-completion questionnaires in 1997. Three main independent associations were observed: girls who experienced a shorter gestation, girls whose mothers were younger when they were born, and girls who were heavier at age 9 had earlier menarche. Birth weight, standardized for gestational age, was found to have different relationships with age at menarche depending upon how heavy or light a girl was at age 9. The results of this study support the hypotheses that conditions in fetal and early life are associated with the timing of menarche and that greater childhood growth is associated with earlier menarche. It is suggested that future work should focus on illuminating the mechanisms underlying these statistical relationships.     

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 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.     

Biological and behavioral determinants of fertility in Tierra del Fuego

The reproductive history of 182 women in postreproductive life or near menopause from the Chilean part of Tierra del Fuego was traced back by means of familial interviews. These postmenopausal women represent the population since almost the beginning of the settlement, and their reproductive years were spent on the island. Path analysis was applied to analyze fertility determinants of these women and to propose a complex model of interconnections among factors. The reproductive history of these women is characterized by a long fertile span, a short childbearing period, and low fertility. Age at menarche is relatively late, and the age of the women at first birth is mainly determined by their late age at marriage. The use of contraception is related to both spacing and stopping behaviors. The late age of women at marriage, the rhythm of conception, and practices of contraception are proposed as the main determinants of fertility in Tierra del Fuego.     

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.     

Age at menarche, the leg length to sitting height ratio, and risk of diabetes in middle-aged and elderly Chinese men and women

Aims

To evaluate the associations of age at menarche and the leg length-to-sitting-height ratio, markers of adolescent growth, with risk of diabetes in later life.

Materials and Methods

Information from 69,385 women and 55,311 men, aged 40–74 years from the Shanghai Women''s Health Study and Shanghai Men''s Health Study, were included in the current analyses. Diabetes status was ascertained through biennial in person follow-up. Cox models, with age as the time scale, were used.

Results

There were 2369 cases of diabetes (1831 women; 538 men) during an average of 7.3 and 3.6 years of follow-up of the women and men, respectively. In females, menarche age was inversely associated with diabetes risk after adjustment for birth cohort, education, and income (HR = 0.95, 0.92–0.98). In both genders, leg length-to-sitting-height ratio was inversely related to diabetes (HR = 0.88, 0.80–0.97 for men; HR = 0.91, 0.86–0.96 for women) after adjustment for birth cohort, education, and income. Further adjustment for adult BMI at study enrollment completely eliminated the associations of age at menarche (HR = 0.99, 0.96–1.02) and the leg length-to-sitting-height ratio (HR = 1.00, 0.91–1.10 for men; HR = 1.01, 0.96–1.07 for women) with diabetes risk.

Conclusions

Our study suggests that markers of an early age at peak height velocity, i.e. early menarche age and low leg-length-to-sitting height ratio, may be associated with diabetes risk later in life and this association is likely to be mediated through obesity.     

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).     

Female reproductive system and bone

The female reproductive system plays a major role in regulating the acquisition and loss of bone by the skeleton from menarche through senescence. Onset of gonadal sex steroid secretion at puberty is the major factor responsible for skeletal longitudinal and radial growth, as well as significant gain in bone density, until peak bone density is achieved in third decade of life. Gonadal sex steroids then help maintain peak bone density until menopause, including during the transient changes in skeletal mineral content associated with pregnancy and lactation. At menopause, decreased gonadal sex steroid production normally leads to rapid bone loss. The most rapid bone loss associated with decreased estrogen levels occurs in the first 8-10 years after menopause, with slower age-related bone loss occurring during later life. Age-related bone loss in women after the early menopausal phase of bone loss is caused by ongoing gonadal sex steroid deficiency, vitamin D deficiency, and secondary hyperparathyroidism. Other factors also contribute to age-related bone loss, including intrinsic defects in osteoblast function, impairment of the GH/IGF axis, reduced peak bone mass, age-associated sarcopenia, and various sporadic secondary causes. Further understanding of the relative contributions of the female reproductive system and each of the other factors to development and maintenance of the female skeleton, bone loss, and fracture risk will lead to improved approaches for prevention and treatment of osteoporosis.     

Relation of Body Fat Distribution to Reproductive Factors in Pre- and Postmenopausal Women

TROISI, REBECCA J, ANNE M WOLF, JOANN E MANSON, KELLY M. KLINGLER AND GRAHAM A. COLDITZ. Relation of body fat distribution to reproductive factors in pre- and postmenopausal women. Obes Res. 1995;3:143–151. The cross-sectional relations of several reproductive characteristics with self-reported waist-to-hip circumference ratio were evaluated in 44, 487 pre- and postmenopausal women 40 to 65 years of age who were free of cancer, cardiovascular disease, and diabetes. All results were adjusted for age, body mass index, cigarette smoking, physical activity, and alcohol intake. Current use of postmenopausal hormones was associated with a significantly lower waist-to-hip ratio than either past or never use independent of type of menopause (0.778 versus 0.784, p=0.0001 and 0.787, p=0.0001, respectively), although associations with type (unopposed estrogens versus combined estrogen and progesterone) and duration of hormone therapy were not noted. Waist-to-hip ratio did not differ between pre- and postmenopausal women, but demonstrated weak positive associations with age at menarche, parity, and age at first birth, and a weak inverse association with past duration of breast-feeding. These data confirm relations of several reproductive factors and use of hormone replacement therapy with body fat distribution. Epidemiologic studies relating body fat distribution to disease outcomes in women should consider these factors as potential confounders.     

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.     

Age at menopause in Puebla,Mexico

Comparisons of age at menopause are made difficult by the different methodologies applied across populations. This study extended an opportunity to apply different methodologies to the same data to draw some preliminary conclusions about age at menopause in Puebla, Mexico. Among 755 women aged 28 to 70 interviewed in the capital city of Puebla, Mexico, 447 (59.6%) were naturally or surgically postmenopausal. Mean recalled age at natural menopause in Puebla (46.7 years) appears to be similar to mean recalled age at menopause in Mexico City (46.5 years), suggesting that age at menopause is similar in urban Mexican populations. However, median age at menopause computed by probit analysis was later in the city of Puebla (49.6 years) compared to the median age computed by the same method in the capital city of León, Guanajuato, Mexico (48.2 years). Median age at menopause computed by Kaplan-Meier survival analysis suggests that age at menopause in Puebla (50.0 years) is older still, and close to that of the United States (51.1 years). The differences in median ages at menopause in Puebla are solely due to methodological choices and highlight the difficulty inherent in making inferences across studies of age at menopause between biological and/or cultural groups. Factors associated with age at menopause offer another avenue for comparing and understanding variation in this basic biological process. In Puebla, smoking, low levels of education, and nulliparity are associated with an earlier age at menopause.     

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.