Age at menarche in Iceland

The purpose of this study was to elucidate the mean age at menarche in Icelandic girls and compare it with results from other Scandinavian populations as well as in other ethnic groups. The study was performed during the school year 1972-1973 on a cross-sectional sample of 682 girls (aged 8.5 to over 17 years), constituting 9.5% of the girls from the third to eleventh forms in all the primary and secondary schools of Reykjavik. The mean age at menarche in Iceland, elicited by the status quo method, proved to be 13.06 +/- 0.10 years (S.D. 1.17 years). According to the information given by the girls (recall method), the earliest time of menstruation was 9.83 years and the latest 15.17 years, at which age all but one of the girls were menstruating.     

Age of the menarche of girls in Thessaloniki, Greece

In 1982-1983 a total of 977 girls from Thessaloniki has been investigated for their menarcheal ages, using the retrospective and the status quo methods. 565 of these girls aged between 11 and 18.5 years (age classes 1964-1972) were found to menstruate. The mean menarcheal age amounts to 12.0 years. The results are compared with corresponding data from literature. They confirm a clear secular trend for the menarcheal age in Greek population.     

Gonadotropin pulsatile secretion in girls with premature menarche

Five prepubertal girls (2.3-8.1 years old) were studied for isolated or recurrent vaginal bleeding in the absence of other signs of precocious puberty (premature menarche). Four of these girls with recurrent vaginal bleeding were studied for pulsatile gonadotropin secretory patterns. During sleep 3 girls showed luteinizing hormone (LH) pulses with low amplitude and a pubertal pattern of frequency whereas follicle-stimulating hormone (FSH) increased without demonstrable episodic secretion. Luteinizing hormone-releasing hormone (LHRH) tests demonstrated that FSH responses are greater than the LH responses, as in prepuberty. In 3 cases estradiol levels had augmented above normal prepubertal range. The menses spontaneously stopped during the follow-up. A reevaluation of the gonadotropin pattern, having the menses stopped for 6 months, in one of the girls with pulsatile LH secretion showed an apulsatile prepubertal LH pattern. Also estradiol levels returned to prepubertal range. A follow-up of 10-66 months of these patients did not show any growth and bone acceleration or signs of precocious puberty. Our data suggest that in premature menarche a partial and transient activation of hypothalamo-pituitary axis could be present. Premature menarche seems to be a benign and self-limiting condition and one of the girls had a normal onset of puberty during follow-up.     

Age at menarche: the influence of environmental conditions

Age at menarche was studied by the recollection method in two groups of Causasian Jewish high school girls, inhabitants of two towns in Israel, Safad and Elat. The two towns differ mainly in climatic conditions. The age at menarche was found to be significantly lower (P<0.02) in the hot town of Elat than in the temperate town of Safad: 13.30±1.21 and 13.58±0.9 years, respectively (mean ±SD). A significant association was found between the age at menarche and the town in which the girls lived. Accordingly, in the hot town of Elat, the percentage of girls who had their first menstrual cycle by the age of 12 years and earlier, was more than double that of the girls in Safad (17.9% and 7.1%, respectively). It is concluded that the environmental temperature, with or without any possible interaction of humidity, is probably responsible for the tendency for an earlier onset of menarche in girls living in the hot town of Elat.     

Age at menarche and its association with the metabolic syndrome and its components: results from the KORA F4 study

Objective

The metabolic syndrome is a major public health challenge and identifies persons at risk for diabetes and cardiovascular disease. The aim of this study was to examine the association between age at menarche and the metabolic syndrome (IDF and NCEP ATP III classification) and its components.

Design

1536 women aged 32 to 81 years of the German population based KORA F4 study were investigated. Data was collected by standardized interviews, physical examinations, and whole blood and serum measurements.

Results

Young age at menarche was significantly associated with elevated body mass index (BMI), greater waist circumference, higher fasting glucose levels, and 2 hour glucose (oral glucose tolerance test), even after adjusting for the difference between current BMI and BMI at age 25. The significant effect on elevated triglycerides and systolic blood pressure was attenuated after adjustment for the BMI change. Age at menarche was inversely associated with the metabolic syndrome adjusting for age (p-values: <0.001 IDF, 0.003 NCEP classification) and additional potential confounders including lifestyle and reproductive history factors (p-values: 0.001, 0.005). Associations remain significant when additionally controlling for recollected BMI at age 25 (p-values: 0.008, 0.033) or the BMI change since age 25 (p-values: 0.005, 0.022).

Conclusion

Young age at menarche might play a role in the development of the metabolic syndrome. This association is only partially mediated by weight gain and increased BMI. A history of early menarche may help to identify women at risk for the metabolic syndrome.     

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.     

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.     

Breast cancer susceptibility loci in association with age at menarche,age at natural menopause and the reproductive lifespan

Background: Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) associated with breast cancer risk. Some of these loci have unknown functional significance and may mediate the effects of hormonal exposures on breast cancer risk. We examined relationships between breast cancer susceptibility variants and menstrual/reproductive factors using data from two population-based studies. Methods: The first analysis was based on a sample of 1328 women age 20–74 who participated as controls in a case–control study of breast cancer conducted in three U.S. states. We evaluated the associations between age at menarche, age at natural menopause and the reproductive lifespan with 13 previously identified breast cancer variants. Associations were also examined with a genetic score created as the sum of at-risk alleles across the 13 variants. For validation, significant results were evaluated in a second dataset comprised 1353 women age 43–86 recruited as part of a cohort study in Wisconsin. Results: Neither the genetic score nor any of the 13 variants considered individually were associated with age at menarche or reproductive lifespan. Two SNPs were associated with age at natural menopause; every increase in the minor allele (A) of rs17468277 (CASP8) was associated with a 1.12 year decrease in menopause age (p = 0.02). The minor allele (G) of rs10941679 (5p12) was associated with a 1.01 year increase in age at natural menopause (p = 0.01). The results were not replicated in the validation cohort (B = −0.61, p = 0.14 and B = −0.01, p = .0.98, respectively). Conclusions: The evaluated variants and reproductive experiences may work through separate pathways to influence breast cancer risk.     

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).     

Replication of genomewide association studies on age at menarche in the Korean population

Early menarche is associated with adverse health outcomes, including breast cancer, endometrial cancer, obesity, type 2 diabetes, and cardiovascular disease. Recently, a genomewide association study (GWAS) of age at menarche (AAM) in 104,533 individuals of European ancestry was reported by the ReproGen consortium. They identified 42 loci known and novel loci that were linked to age at menarche. Because age at menarche varies between ethnic groups, we decided to investigate if these results would be replicated in the Korean population. To this end, we examined the association of the SNPs reported in the ReproGen GWAS with AAM in 3,194 individuals from the Korean Genome and Epidemiology Study (KoGES) cohort. Genotype data for total 17 SNPs (6 genotyped SNPs and 11 imputed SNPs) were available for the association analysis using linear regression analysis for age at menarche with controlling current age, waist-to-hip ratio, and body mass index as the covariates. We found replication of the ReproGen study in two SNPs; one SNP (rs466639) in the retinoic acid receptor gamma gene (RXRG), showing a significant association with early menarche (beta = ?0.224 ± 0.065, p value = 5.2 × 10^?4, Bonferroni-corrected p value = 0.009), and the other (rs10899489), in GRB2 (growth factor receptor bound protein 2)-associated binding protein 2 (GAB2), linked to late menarche (beta = 0.140 ± 0.047, p value = 2.8 × 10^?3, Bonferroni-corrected p value = 0.049). This result possibly suggests that genetic factors governing AAM in the Korean population would be distinct from those in the Europeans, implying roles of modulating or interacting factors in determining AAM, including environmental factors such as nutritional status.