Maternal Periconceptional OCP Use and Epigenetic Programming of Endometriosis Risk in Female Offspring — A Generational Hypothesis

This project pre-registers a novel research hypothesis proposing that maternal periconceptional combined oral contraceptive pill (COCP) use — particularly high-dose formulations prevalent in the 1960s–1980s — may contribute to endometriosis susceptibility in female offspring through epigenetic reprogramming of uterine developmental genes including HOXA10, ESR1, and PGR during critical fetal developmental windows. The hypothesis draws on the DES multigenerational literature, transgenerational epigenetic inheritance models, and epidemiological data showing a 32% rise in endometriosis diagnosis since 2017 disproportionately affecting Gen X, Millennial, and Gen Z women. A retrospective matched case-control study design with a nested DNA methylation sub-study is proposed. Pre-registration date establishes intellectual priority prior to formal academic supervision or institutional ethics application.