Influence of Childhood Adversity and Infection on Timing of Menarche in a Multiethnic Sample of Women

Childhood adversities (CAs) and infections may affect the timing of reproductive development. We examined the associations of indicators of CAs and exposure to tonsillitis and infectious mononucleosis (mono) with age at menarche. A multiethnic cohort of 400 women (ages 40–64 years) reported exposure to parental maltreatment and maladjustment during childhood and any diagnosis of tonsillitis and/or mono; infections primarily acquired in early life and adolescence, respectively. We used linear and relative risk regression models to examine the associations of indicators of CAs individually and cumulatively, and history of tonsillitis/mono with an average age at menarche and early onset of menarche (<12 years of age). In multivariable models, histories of mental illness in the household (RR = 1.44, 95% CI: 1.01–2.06), and tonsillitis diagnosis (RR = 1.67, 95% CI: 1.20–2.33) were associated with early menarche (<12 years), and with an earlier average age at menarche by 7.1 months (95% CI: −1.15, −0.02) and 8.8 months (95% CI: −1.26, −0.20), respectively. Other adversities indicators, cumulative adversities, and mono were not statistically associated with menarcheal timing. These findings provided some support for the growing evidence that early life experiences may influence the reproductive development in girls.

Causal relationship between the timing of menarche and young adult body mass index with consideration to a trend of consistently decreasing age at menarche

Younger age at menarche (AAM) is associated with higher body mass index (BMI) for young women. Considering that continuous trends in decreasing AAM and increasing BMI are found in many countries, we attempted to assess whether the observed negative association between AAM and young adult BMI is causal. We included 4,093 women from the Korean Genome and Epidemiology Study (KoGES) and Healthy twin Study (HTS) with relevant epidemiologic data and genome-wide marker information. To mitigate the remarkable differences in AAM across generations, we converted the AAM to a generation-standardized AAM (gsAAM). To test causality, we applied the Mendelian randomization (MR) approach, using a genetic risk score (GRS) based on 14 AAM-associated single nucleotide polymorphisms (SNPs). We constructed MR models adjusting for education level and validated the results using the inverse-variance weighted (IVW), weighted median (WM), MR-pleiotropy residual sum and outliers test (MR-PRESSO), and MR-Egger regression methods. We found a null association using observed AAM and BMI level (conventional regression; -0.05 [95% CIs -0.10–0.00] per 1-year higher AAM). This null association was replicated when gsAAM was applied instead of AAM. Using the two-stage least squares (2SLS) approach employing a univariate GRS, the association was also negated for both AAM and gsAAM, regardless of model specifications. All the MR diagnostics suggested statistically insignificant associations, but weakly negative trends, without evidence of confounding from pleiotropy. We did not observe a causal association between AAM and young adult BMI whether we considered the birth cohort effect or not. Our study alone does not exclude the possibility of existing a weak negative association, considering the modest power of our study design.

Pubertal development and risk of premenstrual disorders in young adulthood

STUDY QUESTION Is pubertal timing associated with risk of premenstrual disorders (PMDs) in young adulthood? SUMMARY ANSWER Late pubertal development is associated with decreased premenstrual symptom burden and risk of PMDs in young adulthood. WHAT IS KNOWN ALREADY PMDs, including premenstrual syndrome and premenstrual dysphoric disorder, may begin during the teenage years. Few risk factors in early life have been identified for PMD development. STUDY DESIGN, SIZE, DURATION A prospective cohort study of 6495 female participants during 1996–2013. PARTICIPANTS/MATERIALS, SETTING, METHODS We included participants from the Growing Up Today Study (GUTS). Pubertal development was indicated by the timing of menarche, breast and pubic hair growth. Self-reported age at menarche was longitudinally assessed at enrollment (in 1996/2004 for GUTS I/II) and onwards, and classified as early (age ≤ mean − SD, 11.64 years), normative and late menarche (age ≥ mean + SD, 13.95 years). Timing of pubic hair and breast growth were assessed multiple times during follow-up via Tanner scales, and classified into early, normative and late development according to mean ± SD. Using a validated questionnaire based on the Calendar of Premenstrual Experiences, we assessed premenstrual symptoms and identified probable cases of PMDs in 2013. We examined the associations of timing of pubertal development with premenstrual symptom score and disorders using multivariable linear and logistic regressions, respectively. MAIN RESULTS AND THE ROLE OF CHANCE In 2013 (mean age = 26), 1001 (15.4%) individuals met criteria for a PMD. An inverse association was found between age at menarche and premenstrual symptom z-score (β −0.05 per year, 95% CI −0.07 to −0.03) and risk of PMDs (odds ratio (OR) 0.93 per year, 95% CI 0.88 to 0.99). Compared to individuals with normative menarche, individuals with late menarche had a lower risk of PMDs (OR 0.73, 95% CI 0.59 to 0.91), while individuals with early menarche had comparable odds (OR 0.98, 95% CI 0.81 to 1.18). Moreover, early growth of pubic hair was associated with increased premenstrual symptoms (z-score β 0.09 per year, 95% CI 0.02 to 0.17) and PMD risk (OR 1.28, 95% CI 1.04 to 1.56), independent of age at menarche. No associations were noted for breast development. LIMITATIONS, REASONS FOR CAUTION One major limitation is some misclassification of menarche due to recall. We, however, showed robust association among participants who were premenarcheal at baseline. WIDER IMPLICATIONS OF THE FINDINGS Our findings suggest that pubertal timing, particularly timing of menarche, is inversely associated with the risk of developing premenstrual symptoms in young adulthood, and that women with later menarche have significantly lower risk of PMDs. Information on PMDs should be provided to teenage girls and their parents. If these findings are confirmed in independent populations, prevention strategies and early detection programs may be considered for women with early pubertal development. STUDY FUNDING/COMPETING INTEREST(S) The work is supported by the National Institutes of Health and Swedish Research Council. TRIAL REGISTRATION NUMBER N/A

Association between factors related to the pregnancy, neonatal period, and later complications (especially asthma) and menarcheal age in a sample of Lebanese girls

Background Studies about the majority of the factors that may potentially influence the pubertal timing and menarche were controversial. The objective was to evaluate the association between factors related to the pregnancy, neonatal period, and the complications that may happen later in life and the menarcheal age in a sample of Lebanese girls admitted or not to the NICU at birth. Our secondary objective was to try to find, for the first time in literature, a correlation between respiratory distress at birth and the need of oxygen therapy with the age of the first menses in these girls. Methods It is a cross-sectional retrospective study, conducted between January and March 2019. Our sample included all the 2474 girls born in Notre-Dame-de-Secours hospital, between 2000 and 2005; the sample consisted of 297 girls (97 girls admitted to the NICU and 200 randomly chosen to participate in our study with a ratio of 1:2 (1 girl admitted to the NICU vs 2 girls born in the nursery). Results Asthma later in life was significantly associated with lower age at menarche in girls, whereas a higher mother’s age at menarche and a higher gestational age were significantly associated with higher age at menarche in girls. When taking each cause of NICU admission as an independent variable, showed that a higher mother’s age at menarche was significantly associated with higher age at menarche in girls, whereas a higher number of days of phototherapy, a preeclampsia in the mother during pregnancy and asthma later in life in the girl were significantly associated with a lower age at menarche in girls. Conclusion The timing of menarche seems to be associated with many factors in Lebanese girls that should not be disregarded by physicians.

Heritability of pubertal timing: detailed evaluation of specific milestones in healthy boys and girls

Objective Pubertal timing is highly heritable. Observational studies were inconclusive concerning a potential sex-specific difference in the parental contribution, while genome-wide association studies highlighted a heterogeneity in the genetic architecture of pubertal timing between sexes. Our objectives were to evaluate the association of timing of pubertal milestones in offspring with parental pubertal timing and to identify the genetic basis of the heterogeneity. Design (1.) Population-based mixed cross-sectional/longitudinal cohort (2006–2014, COPENHAGEN Puberty Study) comprising 1381 healthy Danish children including their parents. (2.) UK Biobank-based summary statistics of genetic data on timing of menarche (n = 188 644), voice-break (n = 154 459) and facial hair (n = 161 470). Methods (1.) Participants underwent clinical examination(s) including blood sampling. Parental pubertal timing was obtained by questionnaire. Timing of milestones were analyzed using SAS-lifereg. (2.) Genetic correlations between pubertal outcomes were estimated using LD Score regression. Genetic heterogeneity was analyzed using METAL. Results We observed significant associations of relative parental pubertal timing with timing of pubertal milestones in offspring of concordant sex, that is, fathers/sons (e.g. testicular enlargement: P = 0.004, β = 0.34 years per relative category) and mothers/daughters (e.g. thelarche: P < 0.001, β = 0.45 years per relative category). Fewer milestones were associated with relative parental pubertal timing in offspring of discordant sex compared to concordant sex. Large-scale genetic data highlight both moderate to strong genetic correlations between timing of menarche, voice-break and facial hair. Out of 434 lead single-nucleotide polymorphisms significantly associated with at least one outcome, 39 exhibited a significant genetic heterogeneity between sexes (P < 1.15 × 10−4). Conclusion Our results highlight a distinct genetic heterogeneity of pubertal timing between sexes.