gms | German Medical Science

Introduction: Recent demographic changes toward older parental age at first childbirth have raised concerns about the potential health outcomes for offspring. Research indicates that older fathers tend to have children with longer telomeres, which are critical biomarkers of biological aging. Additionally, evidence suggests that women with longer telomeres generally experience menopause at a later age. Consequently, we hypothesize that a higher paternal age at birth may lead to a delayed onset of menopause in daughters, potentially influencing the age at which these daughters might have children. The relationship between paternal age at childbirth and the age at menopause of daughters remains underexplored. Our research aims to fill this gap by investigating how paternal age at childbirth affects the timing of menopause in daughters.

Methods: Our research utilizes the UK Biobank dataset, focusing specifically on a cohort of approximately 131,000 women who experienced natural menopause. To investigate the influence of paternal age at the time of a daughter’s birth on her age at menopause, we conduct multiple linear regression. This analysis includes controls for several variables: maternal age at the time of birth, sex of the offspring, birth year, and factors of the family structure which include birth order and the number of siblings. Indicators of socioeconomic status such as education and income, as well as lifestyle factors including alcohol intake and smoking habits, are also accounted for. For an accurate assessment of genetic and family-related influences, kinship coefficients and IBS0 measures are applied to establish the relatedness among study participants. This approach enables us to identify the study participants within their extended familial configurations and sibling relationships. By implementing family and sister fixed effects, we are able to control for shared familial and genetic backgrounds, using the variation in paternal ages at birth to determine its effect on menopausal age in daughters, both within family groups and among sisters.

Results: Our findings demonstrate that the father’s age at the time of birth significantly impacts the age at which his daughter reaches menopause (0.055, 95% CI: 0.023, 0.087, p-value: 0.001). Specifically, for every additional 9 years in paternal age at birth, the daughter’s age at menopause increases by approximately 6 months. In contrast, maternal age does not significantly affect the daughter’s menopausal timing (0.003, 95% CI: -0.031, 0.036, p-value: 0.880). When accounting for family and sister fixed effects, the results indicate an even more pronounced relationship: the daughter’s age at menopause increases by 6 months for every 5-7 year increase in the father’s age at birth.

Conclusion: This study reveals that daughters experience menopause at a later stage when their fathers were older at the time of birth. This finding thus provides evidence of a potential epigenetic mechanism that may prepare women for extended reproductive years when born to older fathers. These results imply a shift in reproductive timelines for future generations, indicating that, if this current trend of older parental ages continues, daughters may enter menopause increasingly later in life.

The authors declare that they have no competing interests.

The authors declare that an ethics committee vote is not required.