Endocrine characteristics of adolescent menstrual cycles: impact of early menarche

An initial group of 200 girls, 7-17 years old, was investigated longitudinally 4 times at 1.5-, 1.5- and 5-year intervals. The present study gives information of the impact of early menarche, a risk factor for breast cancer, on some physical and endocrine characteristics in these subjects. The frequency of ovulation depended significantly on both the time since menarche and the age at menarche. Early menarche was associated with early onset of ovulatory cycles. Even in early puberty, before menarche, the subjects who displayed early menarche during follow-up had higher serum FSH and estradiol concentrations than the girls whose menarche took place after the age of 13.0 years. Adrenal androgen secretion (dehydroepiandrosterone) was not influenced by age at menarche but it increased, as expected, on the basis of chronological age. The group with early menarche was characterized by high circulating estradiol concentrations also after menarche, even in the oldest subjects so far studied, 17-25 years of chronological age. At these ages, the differences in the frequencies of ovulatory cycles were disappearing between the groups formed on the basis of age at menarche. The present findings in pre- and postmenarcheal subjects suggest that the increased risk of breast cancer associated with early menarche is created over several years of exposure to high-level estrogen stimulus.     

Menarche age,fatness, and fat distribution in Hawaiian adolescents

Menarche age was assessed in 93 adolescent females in a sample of public schools in East Hawaii. Native Hawaiian girls had significantly lower reported age at menarche than non-Hawaiian classmates. Age at menarche was significantly correlated with total fatness as measured by the sum of six skinfolds in girls who had reached menarche at least 2 years previous to measurement. When fatness was controlled in comparisons, the ethnic differences were not significant. Fat distribution, independent of fatness, was also significantly related to age at menarche. Socioeconomic, cultural, and admixture variables were not significantly related to age at menarche. Adiposity appears to be both a cause and a consequence of early age at menarche, with the relationship dependent on the elapsed time between menarche and measurement. This suggests that studies relating body composition to age at menarche must carefully control for the time interval between measurement and the date of menarche. © 1996 Wiley-Liss, Inc.     

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.     

Heritability of age at menarche in girls from the Fels Longitudinal Study

Menarche is the hallmark maturational event of female childhood. Many studies indicated a significant genetic contribution to the timing of the onset of menstruation, but most of these studies were limited by the use of retrospective data and by the use of data from only certain types of relatives (i.e., mothers and daughters, sisters, or twin sisters). The primary goal of this study was to use a modern maximum likelihood quantitative genetic method to estimate the heritability (h(2)) of age at menarche, using familial data collected over the course of the 74-year-old Fels Longitudinal Study. The secondary goal was to review earlier studies of the heritability of age at menarche. The study of the heritability of age at menarche presented here is unique for two reasons. First, because of the Fels Longitudinal Study's serial design, age-at-menarche data were collected prospectively from most participants. Second, because the Fels Longitudinal Study is a family study that has been conducted for decades, age-at-menarche data are available from many types of female relatives spanning multiple households and generations. The best-fitting and most parsimonious quantitative genetic model included provision for a secular decrease in age at menarche, and estimated the h(2) of age at menarche to be 0.49+/- 0.13 (95% confidence interval of h(2),=0.24-0.73). The results of this study are in general agreement with the findings of most previous studies of genetic influences on age at menarche, and suggest that it is reasonable to consider it well-established that approximately half the phenotypic variation among girls from developed nations in the timing of menarche is due to genetic factors.     

Fatness, menarche, and female fertility

It is hypothesized that a particular ratio of fat to lean mass is required for menarche and the maintenance of regular menstrual cycles. Females who lose 10-15% of normal weight for height, equivalent to a loss of 1/3 of body fat, become amenorrheic, presumably due to hypothalamic dysfunction. Adipose tissue may provide signals to the central nervous system and gonadotropin regulatory areas either directly, by estrogen production, or indirectly, by the effects of relative fatness on temperature control and metabolic rate, or by both means. Women with hypothalamic dysfunction experience changes in the secretion of gonadotropins, luteinizing hormone, follicle-stimulating hormone, and estrogen. Weight gain restores postmenarcheal secretion patterns. This approach suggests that the secular trend toward earlier age at menarche reflects earlier attainment of critical weight as a result of improved nutrition and child care. In many societies, subnutrition may explain the observed submaximum fertility. This suggests a need to integrate family planning programs with nutrition programs in many developing countries. It is important to note that the prediction of the minimum weight for height for onset and maintenance of ovulatory cycles is from total water as percentage of body weight. Although the percentage of fat in the body is inversely related to the percent of body water, only the latter is predictive. Successful prediction of the minimum weights for height is related to a lean mass/fat ratio represented by about 17% fat of body weight at menarche and 22% of body weight at the completion of growth at age 18 years.     

Factors regulating the timing of puberty onset in female rhesus monkeys (Macaca mulatta): role of prenatal androgens, social rank, and adolescent body weight

This study investigated whether prenatal androgen exposure, social rank, and body weight are factors regulating pubertal development in outdoor-housed female rhesus monkeys. Subjects' mothers received injections of testosterone enanthate (20 mg/ wk), flutamide (an androgen receptor blocker, 30 mg/kg twice daily), or vehicle during Gestational Days 35/40-70 (early) or Days 105/110-140 (late). Monitoring of pubertal development began around 28 mo of age during the fall breeding season, with frequent assessment of menstruation, circulating steroids, and weight. Menarche occurred 1.5 mo later in females treated late in gestation than in females treated early in gestation. This short menarche delay occurred in females treated with androgen, flutamide, or vehicle. No effect of prenatal manipulations on first ovulation were found. Social rank was related to first ovulation but not menarche, with low-ranked females less likely than high- or middle-ranked females to ovulate at 2.5 yr than at 3.5 yr of age. Females ovulating early, around 2.5 yr, had higher pubertal body weights and body mass indexes (BMI) than did females ovulating later, suggesting that better nutritional reserves or positive energy balance affect pubertal development. Thus, social rank and likely nutritional status influenced pubertal development in this study. Hormonal manipulations had no detectable effect; instead, handling late in gestation, which may have increased maternal adrenal activity, delayed menarche. This finding contrasts with earlier studies that showed that prenatal androgens delay menarche by 4-6 mo on average. This study supports late gestation as a period of increased sensitivity to environmental insult and demonstrates that multiple factors, including prenatal programming, modulate the specific timing of pubertal events.     

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.     

Trends and differentials in menarcheal age in China

This study examines trends in menarcheal age of women born in China between 1950 and 1973, and explores the impact of relevant social background characteristics on the timing of first menarche. Data on recalled ages of menarche collected in the 1988 Chinese Two-per-Thousand Fertility Survey are used in a linear regression model where the covariates are transformed with the help of an Alternating Conditional Expectation (ACE) algorithm. The results indicate that a trend towards early menarche has evolved in China during recent decades. The pattern of early menarche is especially pronounced among women residing in urban areas, and those who are better educated.     

Early sexual maturity among Pumé foragers of Venezuela: fitness implications of teen motherhood

Because humans have slow life histories, discussions of the optimal age at first birth have stressed the benefits of delayed reproduction. However, given the diversity of ecological, fertility, and mortality environments in which humans live, reproductive maturity is expected to be highly variable. This article uses reproductive histories to examine a pattern of early menarche and first birth among the Pume, a group of South American foragers. Age at menarche and first birth are constructed using both retrospective and cross‐sectional data for females over the age of 10 (n = 83). The objectives are first to define these patterns and then discuss their reproductive consequences. On average, Pume girls reach menarche at age 12.9, and give birth to their first child at age 15.3–15.5 (retrospective and cross‐sectional data, respectively). This populational average falls several years prior to what often is considered the human norm. Two questions are then considered. What are the infant mortality costs across a mother's reproductive career? How does surviving fertility vary with age at first birth? Results indicate that the youngest of first‐time mothers (<14) are four times more likely to loose their firstborns than older first‐time mothers (≥17). Given parity‐specific mortality rates, the optimal strategy to minimize infant mortality and maximize reproductive span is to initiate childbearing in the midteens. Women gain no additional advantage in surviving fertility by delaying childbearing until their late teens. Am J Phys Anthropol, 2008. © 2008 Wiley‐Liss, Inc.     

Weight, height, thorax and of menarche in Spanish schoolgirls.

In this paper, the authors study the correlation which exists between somatic development, represented by weight, height and thorax, and the age of onset of menarche. The results indicate that girls showing early menarche have a somatic development greater than the mean. It has also been possible to show that the greatest increase in height occurs before the menarche, while the greatest increase in weight coincides with the appearance of the menarche, or occurs shortly afterwards.     

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.     

Analysis of specific bacteria from environmental samples using a quantitative polymerase chain reaction

This article describes the use of quantitative PCR for measuring bacterial abundance in environmental samples. The two approaches discussed are: 1) The use of an internal PCR standard constructed to be the same size and have the same sequence as the primary amplification target, but differing from the primary target by 2-3 bases, corresponding to a unique restriction site. This allows the amount of target amplicon to be compared with the internal standard and circumvents the problem of differential amplification efficiencies when using dissimilar targets and standard amplicons. 2) The use of Taqman technology (Applied Biosystems, Foster City, California) with a dual labeled oligonucleotide probe which binds internal to the PCR primers. The detection of Bacteroides is used as an example for both approaches.     

Early stress predicts age at menarche and first birth,adult attachment,and expected lifespan

Life history theory suggests that in risky and uncertain environments the optimal reproductive strategy is to reproduce early in order to maximize the probability of leaving any descendants at all. The fact that early menarche facilitates early reproduction provides an adaptationist rationale for our first two hypotheses: that women who experience more risky and uncertain environments early in life would have (1) earlier menarche and (2) earlier first births than women who experience less stress at an early age. Attachment theory and research provide the rationale for our second two hypotheses: that the subjective early experience of risky and uncertain environments (insecurity) is (3) part of an evolved mechanism for entraining alternative reproductive strategies contingent on environmental risk and uncertainty and (4) reflected in expected lifespan. Evidence from our pilot study of 100 women attending antenatal clinics at a large metropolitan hospital is consistent with all four hypotheses: Women reporting more troubled family relations early in life had earlier menarche, earlier first birth, were more likely to identify with insecure adult attachment styles, and expected shorter lifespans. Multivariate analyses show that early stress directly affected age at menarche and first birth, affected adult attachment in interaction with expected lifespan, but had no effect on expected lifespan, where its original effect was taken over by interactions between age at menarche and adult attachment as well as age at first birth and adult attachment. We discuss our results in terms of the need to combine evolutionary and developmental perspectives and the relation between early stress in general and father absence in particular. This work was supported by The University of Melbourne Department of Obstetrics and Gynaecology. James S. Chisholm is Professor in the School of Anatomy and Human Biology at the University of Western Australia. He is an anthropologist whose interests lie in the fields of human behavioral biology, evolutionary ecology, life history theory, and parental investment theory, where he focuses on infant social-emotional development, the development of reproductive strategies, and the integration of evolutionary, developmental, and cultural psychology and public health. Julie A. Quinlivan is Associate Professor in Obstetrics and Gynaecology at the University of Melbourne and Head of the Maternity Care Program at the Royal Women’s Hospital, Melbourne. Her interests are teenage pregnancy, domestic violence, child abuse prevention, and high-risk pregnancy. Rodney W. Petersen is Senior Lecturer in Obstetrics and Gynaecology at the University of Melbourne and Senior Consultant in Obstetrics and Gynaecology at the Royal Women’s Hospital and Sunshine Hospital in Melbourne. His interests are in psychosocial aspects of women’s health and cancer. David A. Coall is a Ph.D. student in the School of Anatomy and Human Biology at the University of Western Australia. His main interest lies in the application of evolutionary theory within an epidemiological framework. He is currently working on the synthesis of life history theory, parental investment theory, and parent-offspring conflict theory in exploring factors that influence variation in human birth weight and placental weight.     

Milk intake and total dairy consumption: associations with early menarche in NHANES 1999-2004

Background

Several components of dairy products have been linked to earlier menarche.

Methods/Findings

This study assessed whether positive associations exist between childhood milk consumption and age at menarche or the likelihood of early menarche (<12 yrs) in a U.S sample. Data derive from the National Health and Nutrition Examination Survey (NHANES) 1999–2004. Two samples were utilized: 2657 women age 20–49 yrs and 1008 girls age 9–12 yrs. In regression analysis, a weak negative relationship was found between frequency of milk consumption at 5–12 yrs and age at menarche (daily milk intake β = −0.32, P<0.10; “sometimes/variable milk intake” β = −0.38, P<0.06, each compared to intake rarely/never). Cox regression yielded no greater risk of early menarche among those who drank milk “sometimes/varied” or daily vs. never/rarely (HR: 1.20, P<0.42, HR: 1.25, P<0.23, respectively). Among the 9–12 yr olds, Cox regression indicated that neither total dairy kcal, calcium and protein, nor daily milk intake in the past 30 days contributed to early menarche. Girls in the middle tertile of milk intake had a marginally lower risk of early menarche than those in the highest tertile (HR: 0.6, P<0.06). Those in the lowest tertiles of dairy fat intake had a greater risk of early menarche than those in the highest (HR: 1.5, P<0.05, HR: 1.6, P<0.07, lowest and middle tertile, respectively), while those with the lowest calcium intake had a lower risk of early menarche (HR: 0.6, P<0.05) than those in the highest tertile. These relationships remained after adjusting for overweight or overweight and height percentile; both increased the risk of earlier menarche. Blacks were more likely than Whites to reach menarche early (HR: 1.7, P<0.03), but not after controlling for overweight.

Conclusions

There is some evidence that greater milk intake is associated with an increased risk of early menarche, or a lower age at menarche.     

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.     

Age at Menarche,Level of Education,Parity and the Risk of Hysterectomy: A Systematic Review and Meta-Analyses of Population-Based Observational Studies

Background

Although rates have declined, hysterectomy is still a frequent gynaecological procedure. To date, there has been no systematic quantification of the relationships between early/mid-life exposures and hysterectomy. We performed a systematic review and meta-analyses to quantify the associations between age at menarche, education level, parity and hysterectomy.

Methods

Eligible studies were identified by searches in PubMed and Embase through March 2015. Study-specific estimates were summarised using random effects meta-analysis. Heterogeneity was explored using sub-group analysis and meta-regression.

Results

Thirty-two study populations were identified for inclusion in at least one meta-analysis. Each year older at menarche was associated with lower risk of hysterectomy—summary hazard ratio 0.86 (95% confidence interval: 0.78, 0.95; I² = 0%); summary odds ratio 0.88 (95% confidence interval: 0.82, 0.94; I² = 61%). Low education levels conferred a higher risk of hysterectomy in the lowest versus highest level meta-analysis (summary hazard ratio 1.87 (95% confidence interval: 1.25, 2.80; I² = 86%), summary odds ratio 1.51 (95% confidence interval: 1.35, 1.69; I² = 90%)) and dose-response meta-analysis (summary odds ratio 1.17 (95% confidence interval: 1.12, 1.23; I² = 85%) per each level lower of education). Sub-group analysis showed that the birth cohort category of study participants, the reference category used for level of education, the year the included article was published, quality of the study (as assessed by the authors) and control for the key variables accounted for the high heterogeneity between studies in the education level meta-analyses. In the meta-analyses of studies of parity and hysterectomy the results were not statistically significant.

Conclusions

The present meta-analyses suggest that the early life factors of age at menarche and lower education level are associated with hysterectomy, although this evidence should be interpreted with some caution due to variance across the included studies.     

Effects of menstrual cycle and oral contraceptive use on calf venous compliance

Numerous studies have shown that the female sex hormones estrogen and progesterone have multiple effects on the vasculature. Thus our goal was to investigate the effects of estrogen and progesterone on calf venous compliance by looking for cyclic changes during the early follicular, ovulatory, and midluteal phases of the menstrual cycle and during high and low hormone phases of oral contraceptive use. Additionally, we wanted to compare the venous compliance of normally menstruating women, oral contraceptive users, and men. We studied eight normally menstruating women (23 +/- 1 yr of age) during the early follicular, ovulatory, and midluteal phases of the menstrual cycle. Nine triphasic oral contraceptive users (21 +/- 1 yr of age) were studied during weeks of high and low hormone concentrations. Eight men (23 +/- 1 yr of age) were studied twice within 2-4 wk. With the use of venous occlusion plethysmography with mercury in-Silastic strain gauges, lower limb venous compliance was measured by inflating a venous collection cuff that was placed on the thigh to 60 mmHg for 8 min and then reducing the pressure to 0 mmHg at a rate of 1 mmHg/s. Venous compliance was calculated as the derivative of the pressure-volume curves. There were no differences between early follicular, ovulatory, and midluteal phases of the menstrual cycle or between high and low hormone phases of oral contraceptive use (P > 0.05). Male venous compliance was significantly greater than in normally menstruating women (P < 0.001) and oral contraceptive users (P < 0.002). These data support a sex difference but also suggest that venous compliance does not change with menstrual cycle phase or during the course of oral contraceptive use.     

Changes and Tracking of Fat Mass in Pubertal Girls

Puberty is a critical period in body composition development. The influence of puberty on the development of fat mass asks for further investigation. We investigated the development of fat mass during puberty in a longitudinal prospective study in 152 healthy nonobese white girls, initial ages between 9 to 12 years. The influence of menarcheal age and the existing of tracking of fat mass have been analyzed. In 10 years time, participants were measured on eight time points. Various anthropometric data were collected, breast development was staged according to Tanner and body composition was determined with the dual‐energy X‐ray absorptiometry (DXA) scan. Calculations were made with the use of a linear mixed model. Fat mass increases from 7.9 kg (23.6%) at B1 to 18.5 kg (29.3%) at B5. Fat mass is higher in girls with an early menarche than in girls with a late menarche from B2. Girls in the quartile with initially the lowest fat mass have a chance of being in the same quartile after 10 years of 77% (P < 0.001). Girls in the quartile with initially the highest fat mass, have a risk of staying in the highest quartile of 55% (P < 0.001). Menarcheal age is of great influence on the development of fat mass. Girls with an early menarche, will have a bigger fat mass, especially at the end of puberty. Tracking of fat mass exists: a high amount of fat mass in early puberty will continue to exist at young adulthood.     

Association between maternal age at menarche and newborn size

The impact of maternal age at menarche on newborn size was tested using data from 4,996 single births taking place at Vienna, Austria, between 1985 and 1995--so-called teenager pregnancies were excluded from the present analyses. All women experienced pregnancies between the ages of 19 to 42 years. Maturational time was related significantly to infant weight and length independent of maternal age and behavioral variables such as smoking. Early maturation, i.e., age at menarche before the 12th birthday, was significantly associated with decreased newborn weight and size. The incidence of low-weight newborns was significantly higher in early-maturing mothers. The more favorable nutritional status of women whose menarche occurred relatively early was not able to compensate for the negative effects of early maturation on intrauterine growth. Higher circulating estrogen levels in early maturers preserved into adulthood are discussed as possible reasons for intrauterine growth retardation of the offspring of early-maturing mothers.