# Effect of Oral Contraceptive Use in Relation to Fertile Years on the Risk of Endometriosis in Women with Primary Infertility: A Ten-Year Single-Centre Retrospective Analysis

## TL;DR

This study found that using oral contraceptives for less than 25% of fertile years may reduce the risk of certain endometriosis types in women with infertility.

## Contribution

The study introduces a novel analysis of OC use duration relative to fertile years in relation to endometriosis risk.

## Key findings

- OC use for less than 25% of fertile age was linked to reduced risk of rASRM stage III endometriosis.
- OC use for less than 25% of fertile age was associated with lower risk of superficial implants.
- Overall OC use was not associated with an increased risk of endometriosis diagnosis.

## Abstract

Background and Objectives: Oral contraceptives (OCs) are usually used to treat endometriosis; however, the evidence is inconsistent about whether OC use in the past, when given to asymptomatic women, is protective against the development of future disease. We aimed to assess the relationship between the use of OCs and the likelihood of discovering endometriosis, considering the length of time under OCs during their fertile age. Materials and Methods: This was a monocentric retrospective cohort study in a tertiary-care University Hospital (Department of Human Reproduction, Division of Gynaecology and Obstetrics, University Medical Centre Ljubljana, Slovenia) carried out from January 2012 to December 2022. Reproductive-aged women scheduled for laparoscopic surgery for primary infertility and subsequent histopathological diagnosis of endometriosis were compared to women without an endometriosis diagnosis. They were classified based on the ratio of years of OC use to fertile years in four subgroups: never, <25%, between 25 and 50%, and >50. Results: In total, 1923 women (390 with and 1533 without endometriosis) were included. Previous OC use was higher in those with endometriosis than controls (72.31% vs. 58.64%; p = 0.001). Overall, previous OC usage was not related to histopathological diagnosis of endometriosis (aOR 1.06 [95% CI 0.87–1.29]). Women who used OCs for less than 25% of their fertile age had reduced risk of rASRM stage III endometriosis (aOR 0.50 [95% CI 0.26–0.95]; p = 0.036) or superficial implants (aOR 0.88 [95% CI 0.58–0.95]; p = 0.040). No significant results were retrieved for other rASRM stages. Using OCs for <25%, between 25 and 50%, or >50% of fertile age did not increase the risk of developing superficial endometriosis, endometriomas, or DIE. Conclusions: When OCs are used at least once, histological diagnoses of endometriosis are not increased. A protective effect of OCs when used for less than 25% of fertile age on superficial implants may be present. Prospective research is needed to corroborate the findings due to constraints related to the study’s limitations.