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The Journal of Adolescent Health :... Nov 2019Earlier ages at menarche are associated with elevations in internalizing and externalizing that persist into adulthood. The present study examines whether early pubertal...
PURPOSE
Earlier ages at menarche are associated with elevations in internalizing and externalizing that persist into adulthood. The present study examines whether early pubertal timing precipitates experiences during adolescence that account for long-term elevations in depressive symptoms and antisocial behavior among early maturing girls.
METHODS
Using data from the National Longitudinal Study of Adolescent and Adult Health (Add Health), the study examines significant postmenarcheal life events that might mediate associations of age at menarche with depressive symptoms and antisocial behavior in adulthood: teenage criminal arrest, teenage pregnancy and childbearing, high school dropout, and different forms of postpubertal physical and sexual traumatic assault.
RESULTS
Results indicate that earlier menarche was associated with greater likelihood of postmenarcheal discontinued education, physical and sexual assault, and teenage pregnancy and childbearing. Discontinued education, physical assault, and sexual assault mediated associations of pubertal timing with adult depressive symptoms; sexual assault mediated associations of pubertal timing with adult antisocial behavior.
CONCLUSIONS
Earlier menarche seems to precipitate postpubertal stressful events that, in turn, account for higher rates of psychological problems in adulthood. These results suggest that the adolescent experiences of early maturing girls channel them into life paths where stress, adversity, and other risks to psychological well-being are more likely to be a continuing facet of daily life.
Topics: Adolescent; Adult; Age Factors; Depression; Female; Health Surveys; Humans; Internal-External Control; Longitudinal Studies; Menarche; Risk-Taking; Sexual Maturation; Stress, Psychological; Young Adult
PubMed: 31500947
DOI: 10.1016/j.jadohealth.2019.06.004 -
Molecular Human Reproduction Jan 2014Genetic factors contribute to risk of many common diseases affecting reproduction and fertility. In recent years, methods for genome-wide association studies (GWAS) have... (Review)
Review
Genetic factors contribute to risk of many common diseases affecting reproduction and fertility. In recent years, methods for genome-wide association studies (GWAS) have revolutionized gene discovery for common traits and diseases. Results of GWAS are documented in the Catalog of Published Genome-Wide Association Studies at the National Human Genome Research Institute and report over 70 publications for 32 traits and diseases associated with reproduction. These include endometriosis, uterine fibroids, age at menarche and age at menopause. Results that pass appropriate stringent levels of significance are generally well replicated in independent studies. Examples of genetic variation affecting twinning rate, infertility, endometriosis and age at menarche demonstrate that the spectrum of disease-related variants for reproductive traits is similar to most other common diseases. GWAS 'hits' provide novel insights into biological pathways and the translational value of these studies lies in discovery of novel gene targets for biomarkers, drug development and greater understanding of environmental factors contributing to disease risk. Results also show that genetic data can help define sub-types of disease and co-morbidity with other traits and diseases. To date, many studies on reproductive traits have used relatively small samples. Future genetic marker studies in large samples with detailed phenotypic and clinical information will yield new insights into disease risk, disease classification and co-morbidity for many diseases associated with reproduction and infertility.
Topics: Endometriosis; Female; Fertility; Genetic Predisposition to Disease; Genetic Variation; Genome-Wide Association Study; Humans; Leiomyoma; Menarche; Menopause; Polymorphism, Single Nucleotide; Reproduction
PubMed: 23982303
DOI: 10.1093/molehr/gat058 -
Reproductive Biology and Endocrinology... Sep 2010Menarche is a milestone in a woman's life as it denotes the start of reproductive capacity. Aim of this report is to review the recent developments and the current... (Review)
Review
Menarche is a milestone in a woman's life as it denotes the start of reproductive capacity. Aim of this report is to review the recent developments and the current knowledge in the neuroendocrinology of pubertal onset and the factors, genetic and environmental, that influence menarcheal age. We also review the implications of early or late menarcheal age on a young woman's life.
Topics: Adipose Tissue; Age Factors; Female; Humans; Menarche; Models, Biological; Motor Activity; Neurosecretory Systems; Nutritional Physiological Phenomena; Women's Health
PubMed: 20920296
DOI: 10.1186/1477-7827-8-115 -
Philosophical Transactions of the Royal... Apr 2016Developmental environments are crucial for shaping our life course. Elements of the early social and biological environments have been consistently associated with... (Review)
Review
Developmental environments are crucial for shaping our life course. Elements of the early social and biological environments have been consistently associated with reproduction in humans. To date, a strong focus has been on the relationship between early stress, earlier menarche and first child birth in women. These associations, found predominately in high-income countries, have been usefully interpreted within life-history theory frameworks. Fertility, on the other hand--a missing link between an individual's early environment, reproductive strategy and fitness--has received little attention. Here, we synthesize this literature by examining the associations between early adversity, age at menarche and fertility and fecundity in women. We examine the evidence that potential mechanisms such as birth weight, childhood body composition, risky health behaviours and developmental influences on attractiveness link the early environment and fecundity and fertility. The evidence that menarche is associated with fertility and fecundity is good. Currently, owing to the small number of correlational studies and mixed methodologies, the evidence that early adversity predicts fecundity and fertility is not conclusive. This area of research is in its infancy; studies examining early adversity and adult fertility decisions that can also examine likely biological, social and psychological pathways present opportunities for future fertility research.
Topics: Biological Evolution; Decision Making; Environment; Fertility; Health Behavior; Human Development; Humans; Life History Traits; Menarche
PubMed: 27022073
DOI: 10.1098/rstb.2015.0146 -
Communications Biology Jan 2024Age at menarche (AAM) and age at natural menopause (ANM) are highly heritable traits and have been linked to various health outcomes. We aimed to identify circulating...
Age at menarche (AAM) and age at natural menopause (ANM) are highly heritable traits and have been linked to various health outcomes. We aimed to identify circulating proteins associated with altered ANM and AAM using an unbiased two-sample Mendelian randomization (MR) and colocalization approach. By testing causal effects of 1,271 proteins on AAM, we identified 22 proteins causally associated with AAM in MR, among which 13 proteins (GCKR, FOXO3, SEMA3G, PATE4, AZGP1, NEGR1, LHB, DLK1, ANXA2, YWHAB, DNAJB12, RMDN1 and HPGDS) colocalized. Among 1,349 proteins tested for causal association with ANM using MR, we identified 19 causal proteins among which 7 proteins (CPNE1, TYMP, DNER, ADAMTS13, LCT, ARL and PLXNA1) colocalized. Follow-up pathway and gene enrichment analyses demonstrated links between AAM-related proteins and obesity and diabetes, and between AAM and ANM-related proteins and various types of cancer. In conclusion, we identified proteomic signatures of reproductive ageing in women, highlighting biological processes at both ends of the reproductive lifespan.
Topics: Humans; Female; Menarche; Mendelian Randomization Analysis; Proteomics; Biomarkers; Menopause; HSP40 Heat-Shock Proteins
PubMed: 38184718
DOI: 10.1038/s42003-023-05737-7 -
BMC Medicine Apr 2024The timing of puberty may have an important impact on adolescent mental health. In particular, earlier age at menarche has been associated with elevated rates of...
BACKGROUND
The timing of puberty may have an important impact on adolescent mental health. In particular, earlier age at menarche has been associated with elevated rates of depression in adolescents. Previous research suggests that this relationship may be causal, but replication and an investigation of whether this effect extends to other mental health domains is warranted.
METHODS
In this Registered Report, we triangulated evidence from different causal inference methods using a new wave of data (N = 13,398) from the Norwegian Mother, Father, and Child Cohort Study. We combined multiple regression, one- and two-sample Mendelian randomisation (MR), and negative control analyses (using pre-pubertal symptoms as outcomes) to assess the causal links between age at menarche and different domains of adolescent mental health.
RESULTS
Our results supported the hypothesis that earlier age at menarche is associated with elevated depressive symptoms in early adolescence based on multiple regression (β = - 0.11, 95% CI [- 0.12, - 0.09], p < 0.01). One-sample MR analyses suggested that this relationship may be causal (β = - 0.07, 95% CI [- 0.13, 0.00], p = 0.03), but the effect was small, corresponding to just a 0.06 standard deviation increase in depressive symptoms with each earlier year of menarche. There was also some evidence of a causal relationship with depression diagnoses during adolescence based on one-sample MR (OR = 0.74, 95% CI [0.54, 1.01], p = 0.03), corresponding to a 29% increase in the odds of receiving a depression diagnosis with each earlier year of menarche. Negative control and two-sample MR sensitivity analyses were broadly consistent with this pattern of results. Multivariable MR analyses accounting for the genetic overlap between age at menarche and childhood body size provided some evidence of confounding. Meanwhile, we found little consistent evidence of effects on other domains of mental health after accounting for co-occurring depression and other confounding.
CONCLUSIONS
We found evidence that age at menarche affected diagnoses of adolescent depression, but not other domains of mental health. Our findings suggest that earlier age at menarche is linked to problems in specific domains rather than adolescent mental health in general.
Topics: Child; Female; Adolescent; Humans; Mental Health; Menarche; Cohort Studies; Causality; Mendelian Randomization Analysis
PubMed: 38609914
DOI: 10.1186/s12916-024-03361-8 -
Arquivos de Gastroenterologia 2020Celiac disease (CD) is a chronic enteropathy in response to ingestion of gluten. CD was associated with gynecological disorders.
BACKGROUND
Celiac disease (CD) is a chronic enteropathy in response to ingestion of gluten. CD was associated with gynecological disorders.
OBJECTIVE
In this retrospective study, we aimed to investigate the age of menarche, age of menopause, number of pregnancies and abortions in Brazilian celiac patients.
METHODS
We studied 214 women diagnosed with CD and as control group 286 women were investigated.
RESULTS
Regarding the mean age of menarche, a significant difference was found (12.6±1.40 in CD and 12.8±1.22 years in healthy group; P=0.04). Regarding abortions, in CD women 38/214 (17.8%) and 28/286 (9.8%) in the control group reported abortion (P=0.0092, OR:1.98; CI95%=1.1- 3.3). There was no significant difference in the mean age of menopause nor number of pregnancies per woman.
CONCLUSION
In this study, we found that celiac women had a higher mean age of menarche and higher risk of spontaneous abortions.
Topics: Abortion, Spontaneous; Adolescent; Adult; Aged; Case-Control Studies; Celiac Disease; Female; Humans; Menarche; Menopause; Middle Aged; Parity; Retrospective Studies; Young Adult
PubMed: 32294744
DOI: 10.1590/S0004-2803.202000000-18 -
Human Reproduction (Oxford, England) Mar 2017Are parity and the timing of menarche associated with premature and early natural menopause?
STUDY QUESTION
Are parity and the timing of menarche associated with premature and early natural menopause?
SUMMARY ANSWER
Early menarche (≤11 years) is a risk factor for both premature menopause (final menstrual period, FMP <40 years) and early menopause (FMP 40-44 years), a risk that is amplified for nulliparous women.
WHAT IS KNOWN ALREADY
Women with either premature or early menopause face an increased risk of chronic conditions in later life and of early death. Findings from some studies suggest that early menarche and nulliparity are associated with early menopause, however overall the evidence is mixed. Much of the evidence for a direct relationship is hampered by a lack of comparability across studies, failure to adjust for confounding factors and inadequate statistical power.
STUDY DESIGN, SIZE, DURATION
This pooled study comprises 51 450 postmenopausal women from nine observational studies in the UK, Scandinavia, Australia and Japan that contribute to the International collaboration for a Life course Approach to reproductive health and Chronic disease Events (InterLACE).
PARTICIPANTS/MATERIALS, SETTING, METHODS
Age at menarche (categorized as ≤11, 12, 13, 14 and 15 or more years) and parity (categorized as no children, one child and two or more children) were exposures of interest. Age at FMP was confirmed by at least 12 months of cessation of menses where this was not the result of an intervention (such as surgical menopause due to bilateral oophorectomy or hysterectomy) and categorized as premature menopause (FMP before age 40), early menopause (FMP 40-44 years), 45-49 years, 50-51 years, 52-53 years and 54 or more years. We used multivariate multinomial logistic regression models to estimate relative risk ratio (RRR) and 95% CI for associations between menarche, parity and age at FMP adjusting for within-study correlation.
MAIN RESULTS AND THE ROLE OF CHANCE
The median age at FMP was 50 years (interquartile range 48-53 years), with 2% of the women experiencing premature menopause and 7.6% early menopause. Women with early menarche (≤11 years, compared with 12-13 years) were at higher risk of premature menopause (RRR 1.80, 95% CI 1.53-2.12) and early menopause (1.31, 1.19-1.44). Nulliparity was associated with increased risk of premature menopause (2.26, 1.84-2.77) and early menopause (1.32, 1.09-1.59). Women having early menarche and nulliparity were at over 5-fold increased risk of premature menopause (5.64, 4.04-7.87) and 2-fold increased risk of early menopause (2.16, 1.48-3.15) compared with women who had menarche at ≥12 years and two or more children.
LIMITATIONS, REASONS FOR CAUTION
Most of the studies (except the birth cohorts) relied on retrospectively reported age at menarche, which may have led to some degree of recall bias.
WIDER IMPLICATIONS OF THE FINDINGS
Our findings support early monitoring of women with early menarche, especially those who have no children, for preventive health interventions aimed at mitigating the risk of adverse health outcomes associated with early menopause.
STUDY FUNDING/COMPETING INTEREST(S)
InterLACE project is funded by the Australian National Health and Medical Research Council project grant (APP1027196). G.D.M. is supported by Australian Research Council Future Fellowship (FT120100812). There are no competing interests.
Topics: Adolescent; Adult; Age Factors; Child; Female; Humans; Menarche; Menopause; Menopause, Premature; Middle Aged; Parity; Pregnancy; Risk Factors
PubMed: 28119483
DOI: 10.1093/humrep/dew350 -
International Journal of Environmental... Nov 2021Adolescent pregnancy (occurring < age 20) is considered a public health problem that creates and perpetuates inequities, affecting not only women, but societies as a... (Review)
Review
Adolescent pregnancy (occurring < age 20) is considered a public health problem that creates and perpetuates inequities, affecting not only women, but societies as a whole globally. The efficacy of current approaches to reduce its prevalence is limited. Most existing interventions focus on outcomes without identifying or addressing upstream social and biological causes. Current rhetoric revolves around the need to change girls' individual behaviours during adolescence and puberty. Yet, emerging evidence suggests risk for adolescent pregnancy may be influenced by exposures taking place much earlier during development, starting as early as gametogenesis. Furthermore, pregnancy risks are determined by complex interactions between socio-structural and ecological factors including housing and food security, family structure, and gender-based power dynamics. To explore these interactions, we merge three complimentary theoretical frameworks: "Eco-Social", "Life History" and "Developmental Origins of Health and Disease". We use our new lens to discuss social and biological determinants of two key developmental milestones associated with age at first birth: age at girls' first menstrual bleed (menarche) and age at first sexual intercourse (coitarche). Our review of the literature suggests that promoting stable and safe environments starting at conception (including improving economic and social equity, in addition to gender-based power dynamics) is paramount to effectively curbing adolescent pregnancy rates. Adolescent pregnancy exacerbates and perpetuates social inequities within and across generations. As such, reducing it should be considered a key priority for public health and social change agenda.
Topics: Adolescent; Adult; Female; Humans; Menarche; Pregnancy; Pregnancy in Adolescence; Puberty; Young Adult
PubMed: 34831907
DOI: 10.3390/ijerph182212152 -
Arthritis Research & Therapy Apr 2021Hormonal reproductive factors have been suggested to play an important role in the etiology of rheumatoid arthritis (RA), an autoimmune inflammatory disorder affecting...
BACKGROUND
Hormonal reproductive factors have been suggested to play an important role in the etiology of rheumatoid arthritis (RA), an autoimmune inflammatory disorder affecting primarily women. We conducted a two-sample Mendelian randomization (MR) study examining three relevant exposures, age at menarche (AAM), age at natural menopause (ANM), and age at first birth (AFB) with the risk of RA.
METHODS
We collected summary statistics from the hitherto largest GWAS conducted in AAM (N = 329,345), ANM (N = 69,360), AFB (N = 251,151), and RA (N = 14,361, N = 43,923), all of European ancestry. We constructed strong instruments using hundreds of exposure-associated genetic variants and estimated causal relationship through different MR approaches including an inverse-variance weighted method, an MR-Egger regression and a weighted median method. We conducted a multivariable MR to control for pleiotropic effect acting in particular through obesity and socioeconomic status. We also performed important sensitivity analyses to verify model assumptions.
RESULTS
We did not find any evidence in support for a causal association between genetically predicted reproductive factors and risk of RA (OR = 1.06 [0.98-1.15]; OR = 1.05 [0.98-1.11], OR = 0.85 [0.65-1.10]). Results remained consistent after removing palindromic SNPs (OR = 1.06 [0.97-1.15], OR = 1.05 [0.98-1.13], OR = 0.81 [0.61-1.07]) or excluding SNPs associated with potential confounding traits (OR = 1.03 [0.94-1.12], OR = 1.04 [0.95-1.14]). No outlying instrument was identified through the leave-one-out analysis.
CONCLUSIONS
Our MR study does not convincingly support a casual effect of reproductive factors, as reflected by age at menarche, age at menopause, and age at first birth, on the development of RA. Despite the largely augmented set of instruments we used, these instruments only explained a modest proportion of phenotypic variance of exposures. Our knowledge regarding this topic is still insufficient and future studies with larger sample size should be designed to replicate or dispute our findings.
Topics: Arthritis, Rheumatoid; Female; Genome-Wide Association Study; Humans; Menarche; Mendelian Randomization Analysis; Menopause; Polymorphism, Single Nucleotide
PubMed: 33836822
DOI: 10.1186/s13075-021-02495-x