# Cumulative gonadal hormone exposure is nonlinearly associated with risk of canine cranial cruciate ligament disease: a generalised additive model analysis of 20,590 dogs (1988‐2023)

## TL;DR

This study found that the risk of a knee ligament disease in dogs is not linearly related to the timing of gonadectomy, with the highest risk seen in dogs with the least hormone exposure.

## Contribution

The study introduces a nonlinear relationship between cumulative gonadal hormone exposure and canine cranial cruciate ligament disease risk using generalized additive models.

## Key findings

- The risk of CrCLD was greatest in dogs with the least gonadal hormone exposure.
- The risk sharply decreased to minima at 1054 days for females and 805 days for males.
- Early gonadectomy may be defined as before 2.9 years in females and 2.2 years in males.

## Abstract

To investigate the association between cumulative gonadal hormone exposure and the risk of cranial cruciate ligament disease (CrCLD) in dogs.

Secondary analysis of retrospective cohort data of 20,590 dogs (9845 female, 10,745 male) investigating the association between age at gonadectomy and various health outcomes in dogs was conducted. Cumulative gonadal hormone exposure was defined as the continuous independent variable. The occurrence of CrCLD was binarily defined as the outcome measure. Generalised additive models were used to assess the relationship between hormone exposure and risk of CrCLD, adjusted for potential confounders.

The prevalence of CrCLD was 245 of 9845 (2.49%) in females and 203 of 10,745 (1.89%) in males. The risk of CrCLD was nonlinearly associated with cumulative gonadal hormone exposure in both sexes. The risk of CrCLD was greatest in dogs with the least gonadal hormone exposure, sharply decreasing to minima at 1054 days for females and 805 days for males.

Risk of CrCLD is nonlinearly associated with age at gonadectomy in dogs. Early gonadectomy may be preliminarily defined as that before 2.9 and 2.2 years in female and male dogs, respectively, in the context of CrCLD risk.