# Genetic Insights Into the Relationship Between Menstrual Factors and Site‐/Age‐Specific Bone Mineral Density

## TL;DR

This study finds that menstrual factors like last menstrual period and cycle length have causal effects on bone mineral density, with differences across body sites and age groups.

## Contribution

The study provides novel causal evidence linking specific menstrual factors to bone health using genetic data and Mendelian randomization.

## Key findings

- LMP is causally associated with increased BMD in the heel and lumbar spine.
- LMC is inversely associated with total body BMD in both discovery and replication cohorts.
- LMP effects on BMD vary by age group, being negative in 15–30 years and positive in 45–60 years.

## Abstract

Observational studies have suggested possible links between reproductive factors and bone mineral density (BMD) and osteoporosis (OP), but the causal impact of menstrual factors on BMD remains obscure.

This study is aimed at inferring causal associations between key menstrual factors and site‐/age‐specific BMD.

Genetic variants associated with age at menarche (AAM), last menstrual period (LMP), and length of menstrual cycle (LMC) were obtained from genome‐wide association studies (GWASs). The site‐/age‐specific BMD genetic data were derived from the Genetic Factors for OP Consortium (GEFOS). Causal associations were evaluated using a two‐sample Mendelian randomization (MR) approach and a multivariable MR (MVMR) model.

LMP was causally associated with increased estimated heel BMD (eBMD) (beta = 0.055; 95% CI: 0.020, 0.089; P
FDR = 0.001) and lumbar spine BMD (LS‐BMD) (beta = 0.103; 95% CI: 0.031, 0.175; P
FDR = 0.039). LMC was inversely associated with TB‐BMD in both discovery (beta = −0.207; 95% CI: −0.323, −0.091; P
FDR = 0.001) and replication cohorts (beta = −0.211; 95% CI: −0.335, −0.087; P
FDR = 0.002). LMP was negatively associated with TB‐BMD among individuals aged 15–30 but was positively associated in those aged 45–60. Additional MVMR analysis supported direct causal relationships of LMP and LMC with site‐specific BMD (eBMD and TB‐BMD) and age‐specific BMD (age 45–60).

Our study observes the causal effects of LMP and LMC on BMD, with variations across anatomical sites and age groups. These findings enhance our understanding of the relationship between menstrual factors and bone health, providing evidence to inform targeted prevention strategies for OP.