Associations between birthweight and preterm birth and the ages at menarche and menopause.

BACKGROUND: Women who reach menarche and menopause at earlier ages have been shown to be at increased risk for numerous conditions including cardiovascular disease, cancer, depression, and obesity; however, risk factors for earlier ages of menarche and menopause are not fully understood. Therefore, we aimed to perform a retrospective investigation of the associations between a personal birthweight and/or being born preterm and the age of and menarche and menopause and related events in the Women's Health Initiative, a large, racially and ethnically diverse cohort of postmenopausal women. METHODS: At study entry, women reported their birthweight by category (< 6 lbs., 6-7 lbs. 15 oz, 8-9 lbs. 15 oz, or ≥ 10 lbs.) and preterm birth status (4 or more weeks premature). Ages at events related to menarche and menopause were also self-reported. Linear regression and logistic regression models were used to estimate unadjusted and adjusted effect estimates (ß) and odds ratios (OR), respectively (n ≤ 86,857). Individuals born preterm were excluded from all birthweight analyses. RESULTS: After adjustments, individuals born weighing < 6lbs. were more likely to reach natural menopause at an earlier age (adjusted ß=-0.361, SE = 0.09, P = < 0.001) and have a shorter reproductive window (adjusted ß = -0.287, SE = 0.10, p < 0.004) compared to individuals weighing 6-7 lbs. 15 oz. Individuals born preterm were also more likely to reach natural menopause at an earlier age (adjusted ß=-0.506, SE = 0.16, P = 0.001) and have a shorter reproductive window (adjusted ß = -0.418, SE = 0.17, p < 0.006). CONCLUSIONS: These findings raise concerns that, as more preterm and low birthweight individuals survive to adulthood, the prevalence of earlier-onset menarche and menopause may increase. Clinical counseling and interventions aimed at reducing the incidence of preterm and low birthweight births, as well as intensification of lifestyle modifications to reduce CVD risk among women with these early-life risk factors, should be prioritized.

Association between Changes in Menarcheal Age and Adolescent Idiopathic Scoliosis: An Analysis of 38,879 Patients over 20 Years.

Backgroud: Menarche has a significant impact on the progression of adolescent idiopathic scoliosis (AIS); however, studies in this area are insufficient. This study used large-scale school screening data to investigate the relationship between menarcheal age and AIS, especially the severity of scoliosis. Methods: Of 2,326,577 students who participated in school screening for scoliosis (SSS) in South Korea from 2001 to 2021, 38,879 girls with AIS, who experienced menarche, were included. Data including the patient's demographics, such as menarcheal age, Cobb angle, Risser stage, and the interval between menarche and the time of screening were retrieved from the SSS database. Pearson correlation coefficient was used to identify the changes in menarcheal age according to the birth year and to investigate the relationship between menarcheal age and each variable of interest. Results: Based on the birth year, the mean menarcheal ages in girls with AIS from 1988 to 2008 demonstrated a steadily decreasing trend over time (r = -0.857, p < 0.001). Girls with AIS and late menarche demonstrated a higher Cobb angle at the time of screening (r = 0.095, p < 0.001). Other variables did not significantly correlate with menarcheal age. Conclusions: Based on the SSS, a large-scale school screening dataset, menarcheal age in girls with AIS demonstrated an ongoing downward trend in the recent 20 years in South Korea. Notably, girls with AIS and late menarche had a higher Cobb angle at screening. Our findings indicate the need for earlier screening of AIS in girls who have not undergone menarche.

Relationship between early age at menarche, older age at menopause and subtypes of breast cancer: a scoping review.

Objective: To determine the relationship between early age at menarche, late age at menopause with specific subtypes of breast cancer (BC). Methods: A literature search was conducted in Embase, Lilacs, PubMed, Scopus, and Scielo databases, following the Joanna Briggs Institute scoping review protocol and answering the question "How early age at menarche or late age at menopause are related to different breast cancer subtypes?". Results: A number of 4,003 studies were identified, of which 17 were selected. Most of the included articles found a clear relationship between early menarche, late menopause and some subtypes of BC, mainly, PR+, ER+, luminal, and HER-2 tumors. However, some studies have found a contradictory relationship and one study didn't find any relationship between them. Conclusion: A relationship between early age at menarche and advanced age at menopause was observed with some subtypes of breast cancer, since other factors must be considered in its understanding.

Causal effects of female reproductive features on nonalcoholic fatty liver disease: A mendelian randomization study.

BACKGROUND AND AIMS: Epidemiological evidence on the associations between female reproductive features and nonalcoholic fatty liver disease (NAFLD) is conflicting. To explore their causalities, we conducted a Mendelian randomization (MR) study. METHODS: Summary-level data were obtained, and univariable MR was performed to explore the causalities between female reproductive features and NAFLD. And we performed multivariable MR and MR mediation analysis to explore the mediation effects of educational attainment (EA) and body mass index (BMI) for these associations. Sensitivity analyses were performed to evaluate pleiotropy and heterogeneity. RESULTS: There were causal effects of age at menarche (AAMA) (odds ratio [OR]: 0.817, 95% confidence interval [CI]: 0.736-0.907, per year-increase), age at first birth (AFB) (OR: 0.851, 95%CI: 0.791-0.926, per year-increase) and age at first sexual intercourse (AFS) (OR: 0.676, 95%CI: 0.511-0.896, per standard deviation-increase) on NAFLD risk. Besides, the causal effects were also observed on NAFLD phenotypes including liver fat content (LFC) and alanine aminotransferase (ALT). Further mediation analysis showed that BMI mediated partial proportion of effects of AAMA and AFS on NAFLD/ALT, AFB on NAFLD/LFC/ALT, while EA mediated partial proportion of effects of AFB on NAFLD/LFC/ALT, and AFS on NAFLD/ALT. CONCLUSIONS: This study provided convincing evidence that early AAMA, AFB, and AFS were risk factors for NAFLD. Reproductive health education, obesity management, and education spread might be the beneficial strategies for NAFLD prevention.

Health condition and socioeconomic status mediate the causal effect of reproductive traits on nonalcoholic fatty liver disease: evidence from Mendelian randomization study.

Background: Observational data posits a correlation between reproductive traits and nonalcoholic fatty liver disease (NAFLD), but their causal inference is still unclear. This investigation seeks to elucidate the causal influence of reproductive traits on NAFLD and determine the intervening role of health condition and socioeconomic status in these connections. Methods: Utilizing a Mendelian Randomization (MR) approach, this research leveraged a comprehensive dataset from the Genome-wide Association Study (GWAS) database. The study incorporated body mass index, major depression, educational level, household income and Townsend deprivation index as intermediary variables. Initially, a bidirectional two-sample MR study was conducted to explore the genetic associations between reproductive traits and NAFLD. Then, two-step MR analyses were implemented to quantify the extent of mediation by these indicators. The weighted inverse variance method was the primary analytical approach, complemented by several sensitivity analyses to affirm the robustness of the MR assumptions. Finally, these findings were validated in the FinnGen research. Results: The bidirectional MR analysis indicated that earlier reproductive traits (age at menarche, age at first sexual intercourse, and age at first birth) were associated with an elevated risk of NAFLD, absent any evidence of the reverse relationship. Body mass index accounted for 35.64% of the association between premature menarche and NAFLD. Additionally, body mass index, major depression, educational level and household income mediated 41.65%, 14.35%, 37.88%, and 18.59% of the connection between early sexual intercourse and NAFLD, respectively. Similarly, these same variables elucidated 36.36%, 15.58%, 41.56%, and 22.73% of the correlation between younger age at first birth and NAFLD. Conclusion: Our study elucidated the causal relationships between reproductive traits and NAFLD. Potential underlying mechanisms may involve factors such as body mass index, major depression, educational attainment and household income.

Small for gestational age and age at menarche in a contemporary population-based U.S. sample.

Children born small for gestational age (SGA) may be at risk for earlier puberty and adverse long-term health sequelae. This study investigates associations between SGA and age at menarche using secondary data on 1,027 female children in a population-based U.S. birth cohort that over-sampled non-marital births, which in the U.S. is a policy-relevant population. SGA was defined as <10th percentile of weight for gestational age compared to the national U.S. distribution. We estimated unadjusted and adjusted Ordinary Least Squares (OLS) models of associations between SGA and age at menarche in years, as well as unadjusted and adjusted logistic regression models of associations between SGA and early menarche (before age 11). SGA was not significantly associated with earlier age at menarche, even when adjusting for maternal sociodemographic characteristics, prenatal smoking, and maternal pre-pregnancy overweight and obesity. Similarly, SGA was not significantly associated with the odds of menarche occurring before age 11. However, maternal non-Hispanic Black race-ethnicity, Hispanic ethnicity, and pre-pregnancy obesity all had independent associations with average earlier age at menarche and menarche before age 11. Thus, maternal risk factors appear to play more influential roles in determining pubertal development.

Genetic links between ovarian ageing, cancer risk and de novo mutation rates.

Human genetic studies of common variants have provided substantial insight into the biological mechanisms that govern ovarian ageing1. Here we report analyses of rare protein-coding variants in 106,973 women from the UK Biobank study, implicating genes with effects around five times larger than previously found for common variants (ETAA1, ZNF518A, PNPLA8, PALB2 and SAMHD1). The SAMHD1 association reinforces the link between ovarian ageing and cancer susceptibility1, with damaging germline variants being associated with extended reproductive lifespan and increased all-cause cancer risk in both men and women. Protein-truncating variants in ZNF518A are associated with shorter reproductive lifespan-that is, earlier age at menopause (by 5.61 years) and later age at menarche (by 0.56 years). Finally, using 8,089 sequenced trios from the 100,000 Genomes Project (100kGP), we observe that common genetic variants associated with earlier ovarian ageing associate with an increased rate of maternally derived de novo mutations. Although we were unable to replicate the finding in independent samples from the deCODE study, it is consistent with the expected role of DNA damage response genes in maintaining the genetic integrity of germ cells. This study provides evidence of genetic links between age of menopause and cancer risk.

Causal association of menstrual reproductive factors on the risk of osteoarthritis: A univariate and multivariate Mendelian randomization study.

OBJECTIVE: Several observational studies have revealed a potential relationship between menstrual reproductive factors (MRF) and osteoarthritis (OA). However, the precise causal relationship remains elusive. This study performed Mendelian randomization (MR) to provide deeper insights into this relationship. METHODS: Utilizing summary statistics of genome-wide association studies (GWAS), we conducted univariate MR to estimate 2 menstrual factors (Age at menarche, AAM; Age at menopause, AMP) and 5 reproductive factors (Age at first live birth, AFB; Age at last live birth, ALB; Number of live births, NLB; Age first had sexual intercourse, AFSI; Age started oral contraceptive pill, ASOC) on OA (overall OA, OOA; knee OA, KOA and hip OA, HOA). The sample size of MRF ranged from 123846 to 406457, and the OA sample size range from 393873 to 484598. Inverse variance weighted (IVW) method was used as the primary MR analysis methods, and MR Egger, weighted median was performed as supplements. Sensitivity analysis was employed to test for heterogeneity and horizontal pleiotropy. Finally, multivariable MR was utilized to adjust for the influence of BMI on OA. RESULTS: After conducting multiple tests (P<0.0023) and adjusting for BMI, MR analysis indicated that a lower AFB will increase the risk of OOA (odds ratio [OR] = 0.97, 95% confidence interval [CI]: 0.95-0.99, P = 3.39×10-4) and KOA (OR = 0.60, 95% CI: 0.47-0.78, P = 1.07×10-4). ALB (OR = 0.61, 95% CI: 0.45-0.84, P = 2.06×10-3) and Age AFSI (OR = 0.66, 95% CI: 0.53-0.82, P = 2.42×10-4) were negatively associated with KOA. In addition, our results showed that earlier AMP adversely affected HOA (OR = 1.12, 95% CI: 1.01-1.23, P = 0.033), and earlier ASOC promote the development of OOA (OR = 0.97, 95% CI: 0.95-1.00, P = 0.032) and KOA (OR = 0.58, 95% CI: 0.40-0.84, P = 4.49×10-3). ALB (OR = 0.98, 95% CI: 0.96-1.00, P = 0.030) and AFSI (OR = 0.98, 95% CI: 0.97-0.99, P = 2.66×10-3) also showed a negative association with OOA but they all did not pass multiple tests. The effects of AAM and NLB on OA were insignificant after BMI correction. CONCLUSION: This research Certificates that Early AFB promotes the development of OOA, meanwhile early AFB, ALB, and AFSI are also risk factors of KOA. Reproductive factors, especially those related to birth, may have the greatest impact on KOA. It provides guidance for promoting women's appropriate age fertility and strengthening perinatal care.

Study of the impact of multiple sclerosis on the reproductive life of Spanish women: An online survey.

BACKGROUND: Women have a higher risk of developing multiple sclerosis (MS) than men. The natural reproductive period from menarche to menopause corresponds to the period of active inflammatory disease in MS. Mothers and pregnant women with MS need information about how their disease may affect pregnancy and breastfeeding. AIM: The aim was to explore the reproductive factors in an MS-diagnosed population and to identify ways to support patients and their decision-making process. METHODS: We conducted a cross-sectional, Web-based survey of women living with MS in Asturias (Spain) using a community-based participatory approach. FINDINGS: Early menarche may predict the onset of MS. Pregnancy improves the general health of patients and reduces the number of relapses. Breastfeeding is often not practised and may cause concern in women. MS does not affect the age of menopause, but it can worsen symptoms. However, menopause does not increase the number of MS relapses. CONCLUSIONS: MS is increasingly diagnosed at an earlier age, which increases the number of women who become pregnant after being diagnosed with MS. The decrease in MS relapses during pregnancy and the increase during the postpartum period are consistent with previous reports. Women who choose to breastfeed are in the minority due to treatment incompatibility, although some currently used treatments are compatible with breastfeeding. However, there is a lack of information on this which should be investigated.

Associations of urinary heavy metals with age at menarche, age at menopause, and reproductive lifespan: A cross-sectional study in U.S. women.

Female reproductive timing and lifespan, with a close relation to long-term health outcomes, have been altered in U.S. women over the past decades. However, epidemiologic evidence of the potential causes was lacking. On the basis of 1981 naturally postmenopausal women from the National Health and Nutrition Examination Survey 1999-2020, this study aimed to investigate the associations of urinary heavy metals with age at menarche, age at menopause, and reproductive lifespan. Multivariate generalized linear regression and addictive models were used for single metal exposure analysis, and weighted quantile sum (WQS) and Bayesian kernel machine regression (BKMR) models were employed for mixed exposures. In the fully adjusted model, higher urinary antimony concentration was associated with earlier age at menarche of 0.137 years, while higher concentrations of cadmium, cesium, lead, antimony, and thallium were associated with delayed age at menopause of 0.396-0.687 years. Additionally, urinary barium, cesium, lead, antimony, and thallium levels were associated with longer reproductive lifespan ranging between 0.277 and 0.713 years. Both WQS and BKMR models showed significantly positive associations of metal mixtures with age at menopause (ß: 0.667, 95 % CI: 0.120-1.213) and reproductive lifespan (ß: 0.686, 95 % CI: 0.092-1.280), with cadmium and lead identified as principal contributors. In conclusion, heavy metal exposures were associated with reproductive timing and lifespan of U.S. women, highlighting the need for further prevention and intervention strategies.

Coming of age in war: Early life adversity, age at menarche, and mental health.

Armed conflict and forced migration (ACFM) represent a set of extreme environments that are increasingly common for children and adolescents to experience. Adolescence may constitute a sensitive period (puberty and psychoneurological maturation) through which ACFM adversity leaves a lasting mark. Adolescence has become a focal point for analysis and intervention as it relates to the effects of early life adversity on puberty, linear growth, and mental health. Research in public health and psychological science suggests early life adversity (ELA) may accelerate puberty, heightening risks for mental health disorders. However, it is not well substantiated whether ACFM-derived adversities accelerate or delay relative pubertal timing. Secondly, ACFM provides salient context through which to probe the relationships between nutritional, psychosocial, and demographic changes and their respective impact on puberty and mental health. We conducted a narrative review which 1) examined constructions of early life adversity and their proposed influence on puberty 2) reviewed empirical findings (n = 29 studies, n = 36 samples) concerning effects of ACFM ELA on age at menarche and 3) discussed proposed relationships between early life adversity, puberty, and mental ill-health. Contrary to prior research, we found war-derived early life adversity was more consistently associated with pubertal delay than acceleration and may exert counterintuitive effects on mental health. We show that ELA cannot be operationalized in the same way across contexts and populations, especially in the presence of extreme forms of human stress and resilience. We further discuss the ethics of puberty research among conflict-affected youth.

Exploring the impact of women-specific reproductive factors on phenotypic aging and the role of life's essential 8.

BACKGROUND: Aging is an inevitable biological process. Accelerated aging renders adults more susceptible to chronic diseases and increases their mortality rates. Previous studies have reported the relationship between lifestyle factors and phenotypic aging. However, the relationship between intrinsic factors, such as reproductive factors, and phenotypic aging remains unclear. METHODS: This study utilized data from the National Health and Nutrition Examination Survey (NHANES), spanning from 1999 to 2010 and 2015-2018, with 14,736 adult women. Random forest imputation was used to handle missing covariate values in the final cohort. Weighted linear regression was utilized to analyze the relationship between women-specific reproductive factors and PhenoAgeAccel. Considering the potential impact of menopausal status on the results, additional analyses were conducted on premenopausal and postmenopausal participants. Additionally, the Life's Essential 8 (LE8) was used to investigate the impact of healthy lifestyle and other factors on the relationship between women-specific reproductive factors and PhenoAgeAccel. Stratified analyses were conducted based on significant interaction p-values. RESULTS: In the fully adjusted models, delayed menarche and gynecological surgery were associated with increased PhenoAgeAccel, whereas pregnancy history were associated with a decrease. Additionally, early or late ages of menopause, first live birth, and last live birth can all negatively impact PhenoAgeAccel. The relationship between women-specific reproductive factors and PhenoAgeAccel differs between premenopausal and postmenopausal women. High LE8 scores positively impacted the relationship between certain reproductive factors (age at menarche, age at menopause, age at first live birth, and age at last live birth) and phenotypic age acceleration. Stratified analysis showed significant interactions for the following variables: BMI with age at menarche, pregnancy history, and age at menopause; ethnicity with age at menopause, age at first live birth, and parity; smoking status with use of contraceptive pills and gynecologic surgery; hypertension with use of contraceptive pills, pregnancy history, and age at menopause. CONCLUSION: Delayed menarche, gynecological surgery, and early or late ages of menopause, first live birth, and last live birth are associated with accelerated phenotypic aging. High LE8 score may alleviate the adverse effects of reproductive factors on phenotypic aging.

A study of association between early menarche and anxiety in undergraduate students.

Background: Anxiety has been reported to be one of the most common epidemics in recent years. The present study focused on understanding the association between early menarche and the prevalence of anxiety and anxiety symptoms among adult undergraduate students. Methods: This was an observational, case-control study. The sample included 146 young female adults aged more than or equal to 18 years pursuing the Bachelor of Medicine and Bachelor of Surgery (MBBS) and Bachelor of Dental Sciences (BDS). Using an online questionnaire, participants were asked to recall and enter the age at which they attained menarche. We used the Generalized Anxiety Disorder 7- Item Questionnaire (GAD-7) to measure the severity of their present anxiety symptoms. Results: The results showed a significant increase in anxiety symptoms in participants who had early menarche compared to those who did not have early menarche. The mean score on the GAD-7 Questionnaire for the cases was 9.93 and the control group was 6.89. The GAD-7 scores among the cases group were significantly higher in the GAD-7 scores than in the control group. Conclusions: This study concluded that early menarche is associated with higher anxiety levels in young adults.

Trends in breast density and other risk factors for breast cancer and associations with trends in the incidence of breast cancer in Korean women.

INTRODUCTION: This study investigated the trends in breast density in Korean women and their association with the incidence of breast cancer, incorporating the trends in the known risk factors for breast cancer from an ecological perspective. METHODS: The prevalence of risk factors for breast cancer from the National Health and Nutrition Survey, breast density from Korea's national breast cancer screening program, and breast cancer incidence from the Korea Central Cancer Registry during 2010-2018 were applied after age-standardization to the population at the middle of the year 2000. The association between the prevalence of risk factors for breast cancer, the prevalence of dense breast, and the incidence rate of breast cancer was estimated using linear regression. RESULTS: The proportion of age-standardized dense breasts steadily increased from 45.8 % in 2010 to 51.5 % in 2018. The increased prevalence of dense breasts in women was positively related to the prevalence of smoking, drinking, lack of exercise, early menarche age (<15 years old), premenopausal status, nulliparity, and no history of breastfeeding, and negatively related to the prevalence of obesity. The increased prevalence of the dense breast was associated with an increase in the incidence of breast cancer, and 96 % of the variation in breast cancer incidence could be explained by the variation in the prevalence of dense breast. The factors associated with dense breast and breast cancer incidence overlapped. CONCLUSIONS: Trends in breast cancer risk factors were associated with an increased prevalence of dense breast, which, in turn, was associated with an increased incidence of breast cancer in Korea.

Age at Menarche and Its Association With Adult-Onset Metabolic Syndrome and Related Disorders in Women: A Cross-Sectional Study of a Nationally Representative Sample Over 10 Years.

The prevalence of metabolic syndrome (MetS) as well as related social costs and efforts is increasing. The purpose of this study was to investigate the association between age at menarche and the risk of MetS, obesity, diabetes, and cardiovascular disease (CVD) in women over 30 years, using data from the Korean National Health and Nutrition Examination Survey (2010-2020). The analysis of 30 916 participants showed that early menarche (before 11 years) significantly increased the risk of obesity, diabetes, and MetS compared with the median age of 14 years. Late menarche (after 17 years) was also linked to MetS and related disorders. The relationship between age at menarche (at <10 years and >19 years) and the risk of MetS and related disorders exhibited a reversed J-shaped (し) pattern characterized by a pronounced increased risk among those who experience early menarche, whereas the increased risk associated with late menarche was less consistent. These results will help to decrease the risk of MetS and related disorders by enabling early intervention in early and late menarche age groups.

Female Reproductive Factors and Risk of Mild Cognitive Impairment and Dementia: The HUNT Study.

BACKGROUND: More women are living with dementia than men worldwide and there is a need to investigate causes for this female preponderance. While reproductive factors have been investigated as risk factors, the results are conflicting. We aim to clarify this using a large cohort with a long observation time, adjusting for multiple health and lifestyle variables and encompassing a wider range of cognitive impairment. OBJECTIVE: To study the association between menopause age, menarche age and risk of and risk of mild cognitive impairment (MCI) and dementia. SETTING: The Trøndelag Health study (HUNT), a longitudinal population health study in Norway (1984-2019). PARTICIPANTS: Women who were ≥70 years in 2017-2019 were assessed for cognitive impairment. MEASUREMENTS: Data on menopause age and menarche age were obtained from questionnaires. Diagnosis of MCI or dementia was set using a standardised procedure by a diagnostic group of nine physicians. Multinomial logistic regression was used to study the association between menopause age, menarche age and risk of MCI and dementia with adjustment for birth year, education, smoking, ApoE4, number of children, diabetes, body mass index, alcohol use and physical inactivity. RESULTS: We evaluated 5314 women where 900 (16.9%) had dementia, and 1747 (32.8%) had MCI. Multiple adjusted relative risk ratio (RRR) and 95% confidence intervals (CI) for dementia were: 0.96(95%CI 0.95-0.98) (p<0.001) for menopause age, 0.97(95%CI 0.94-0.99) (p=0.007) for natural menopause age (excluding hysterectomy and/or oophorectomyp<55 years) and 0.97(95%CI 0.95-0.99) (pp<0.001) for reproductive span (menopause age minus menarche age). Menopause age p<45years was associated with a 56% higher risk compared to mean menopause age 50 years. We found no significant associations between menarche age and dementia and no associations with MCI. CONCLUSIONS: Older menopause age and longer reproductive span corresponding to longer oestrogen exposure were associated with a lower dementia risk. Future studies should explore therapeutical options to offset this risk in women.

Association of birth weight, childhood obesity, and age at menarche with the risk of ovarian dysfunction: A mendelian randomization study.

BACKGROUND: Observational studies have revealed associations between birth weight, childhood obesity, age at menarche, and ovarian dysfunction. However, these studies are susceptible to unavoidable confounding factors, leading to ongoing debates regarding their conclusions and making causal relationships challenging to infer. In light of these challenges, Mendelian randomization was employed in this study to investigate the causal relationships between birth weight, childhood obesity, age at menarche, and ovarian dysfunction. METHODS: This study employed a two-sample Mendelian randomization approach using genetic variation as instrumental variables to investigate causal relationships. Genetic variation data were sourced from summary data of genome-wide association studies in European populations. Instrumental variables were selected based on the principles of Mendel's three assumptions. The study utilized the inverse variance weighted method to assess the relationships between birth weight, childhood obesity, age at menarche, and ovarian dysfunction. Supplementary analyses were conducted using MR-Egger regression, the weighted median method, and the weighted median mode to complement the IVW results. Furthermore, the study conducted heterogeneity, horizontal pleiotropy, and sensitivity analyses to evaluate the robustness of the results. RESULTS: Based on the inverse variance weighted method, it was found that there exists a causal relationship between childhood obesity (OR = 1.378, 95% CI: 1.113∼1.705, p = 0.003), age at menarche (OR = 0.639, 95% CI: 0.468∼0.871, p = 0.005), and ovarian dysfunction, while no causal relationship was observed between birth weight and ovarian dysfunction. Heterogeneity tests, multiplicity tests, and leave-one-out sensitivity analyses did not detect any heterogeneity or multiplicity effects in the estimated impact of these three exposure factors on the risk of ovarian dysfunction. CONCLUSIONS: This study represents the first evidence suggesting a potential causal relationship between childhood obesity, age at menarche, and ovarian dysfunction. Childhood obesity was found to increase the risk of ovarian dysfunction, while a later age at menarche was associated with a reduced risk of ovarian dysfunction.

Reproductive history is associated with functional disabilities and symptoms in women with knee osteoarthritis: a case-control study.

OBJECTIVES: Studies that have examined the correlation between reproductive history and knee osteoarthritis (KOA) have had heterogeneous findings. We aimed to investigate the reproductive history and its relationship with pain and physical dysfunction in women with KOA. This case-control study, comprising 204 women aged 50 and older with and without KOA recruited through random cluster sampling, was executed from February 2018 to October 2018 in the health centers of Tabriz City. The reproductive history questionnaire was completed for the subjects in two groups. Pain intensity and functional dysfunction caused by KOA were evaluated using the Visual analogue scale and the Western Ontario and McMaster index, respectively. RESULTS: The women's age of menarche in the case group was significantly lower (p = 0.031), and the number of pregnancies (p = 0.017) and the average duration of breastfeeding (p = 0.039) were substantially higher than those of the control group. Older age at the first menstruation (OR = 0.851) was a protective factor, and higher parity (OR = 8.726) was a risk factor for KOA. In the women with KOA, the younger age of the mother at the birth of the first alive baby and the longer duration of breastfeeding were associated with higher pain intensity and functional disorders.

Puberty in girls with Prader-Willi syndrome: cohort evaluation and clinical recommendations in a Latin American tertiary center.

Introduction: Prader-Willi syndrome (PWS) is a genetic disorder characterized by hypothalamic-pituitary deficiencies including hypogonadism. In girls with PWS, hypogonadism can present early in childhood, leading to genital hypoplasia, delayed puberty, incomplete pubertal development, and infertility. In contrast, girls can present with premature activation of the adrenal axis leading to early pubarche and advanced bone age. We aim to evaluate the progression of puberty and adrenarche signals in girls with PWS. Methodology: A longitudinal retrospective cohort study included girls with PWS followed at a Pediatric Endocrinology Outpatient Clinic in a Tertiary University Hospital in Sao Paulo, Brazil from 2002 to 2022. Data collected via chart review included clinical information on birth history, breast and pubic hair Tanner stages, presence of genital hypoplasia, age at menarche, regularity of menstrual cycles, body mass index (BMI) z-score, final height, age of initiation of estrogen replacement and growth hormone replacement, as well as results for PWS genetic subtype; biochemical investigation (LH, FSH, estradiol, DHEA-S); radiographic bone age and pelvic ultrasound. Results: A total of 69 girls were included in the study and the mean age of puberty onset was 10.2 years in those who started puberty after the age of 8 years. Breast Tanner stage IV was reached by 29.1% girls at a mean age of 14.9 years. Spontaneous menarche was present in 13.8% and only one patient had regular menstrual cycles. Early adrenarche was seen in 40.4% of cases. Conclusion: Our study demonstrated in a large sample that girls with PWS often present with delayed onset of puberty despite frequent premature adrenarche. Based on our results, we suggest an estrogen replacement protocol for girls with PWS to be started at the chronological age or bone age of 12-13 years, taking into consideration the uterus size. Further prospective studies are needed.