Exploring Plant-derived Estrogenic Compounds as Female Anti-fertilityAgents

Introduction: This review evaluates plant-derived estrogenic compounds (PDECs) as antifertility agents and assesses their underlying mechanisms, translational prospects, and associated challenges. Materials and Methods: A narrative synthesis of estrogen biology was combined with a systematic search of Google Scholar, Web of Science, and PubMed using compound-centric and fertility- regulation keywords. The search was limited to English full-text in-vivo studies up to November 2025 on PDECs reporting female anti-fertility outcomes. Results: Pre-clinical findings indicate that multiple flavones, isoflavones, flavanones, phytosterols, and related polyphenols disrupt early pregnancy via anti-implantation, post-coital interceptory, anti-ovulatory, and abortifacient effects. These compounds exhibit weak estrogenic (e.g., apigenin, luteolin, and butin) and anti-estrogenic (e.g., curcumin) activities. Mechanistic specificity has been reported for puerarin as a selective estrogen receptor modulator (SERM), altering uterine ERα: ERβ balance and implantation factors. Nanoparticle-based delivery improves bioavailability and reduces the effective dose while maintaining reversibility. Despite its promising efficacy, translation is constrained by rodent–human endocrine differences, high and poorly justified minimum effective doses, limited bioavailability, non-monotonic dose responses, insufficient long-term safety, toxicity, and independent verifiable reversibility data, which complicate risk– benefit interpretation relative to chronic low-dose dietary phytoestrogen exposure under varied regulatory frameworks. Discussion: PDECs exhibit diverse and complex mechanisms, including weak estrogenic, partial agonistic, antagonistic, and SERM-like activities at specific experimental doses. However, their clinical translation is limited due to insufficient data on fertility reversibility and long-term safety. Conclusion: PDECs represent a potential pipeline for novel contraceptives. However, advancement requires mechanism-resolved pharmacology, standardized formulations, rigorous toxicological evaluation, and well-designed clinical studies.