The Role of Sexual Hormones and Their Receptors in Cancer: Mechanisms, Epidemiology, and Clinical Translation

Abstract

Background: The relationship between hormones and cancer development constitutes one of the most clinically consequential intersections in modern oncology. Sex hormones, mainly oestrogen, progesterone, and androgens, play a significant role in the onset, development, and advancement of various prevalent cancers, such as breast, endometrial, prostate, and ovarian cancers. Aims: This mini-review provides a comprehensive and mechanistically organized synthesis of the dual, and context-dependent roles of steroid hormones in cancer biology. Understanding these mechanisms is essential for advancing precision oncology, improving targeted therapeutic interventions, and guiding future translational research. By integrating molecular insights with clinical and epidemiological evidence, this work positions itself as a valuable resource for researchers and clinicians seeking to better understand hormone-driven carcinogenesis. Study Design: Narrative mini-review of published peer-reviewed literature. Methods: A review of existing literature was performed utilizing the PubMed/MEDLINE, Scopus, and Web of Science databases. Key search terms included: hormones, cancer, carcinogenesis, oestrogen receptor, androgen receptor, hormone replacement therapy, molecular mechanisms, chemoprevention, and precision oncology. Priority was given to meta-analyses, large prospective cohort studies, landmark randomised controlled trials, and high-impact mechanistic studies published between 1941 and 2024. Results: Hormones drive carcinogenesis through genomic receptor activation, direct genotoxic effects via oestrogen-quinone DNA adducts, and epigenetic reprogramming. Epidemiological evidence consistently supports cumulative lifetime oestrogen exposure as the main determinant of breast and endometrial cancer risk. In prostate cancer, androgen receptor signalling is indispensable for disease initiation and progression. Emerging evidence implicates the gut microbiome, circadian rhythm disruption, and metabolic dysfunction as modulators of hormonal carcinogenesis. Clinical translation has produced a suite of highly effective interventions, aromatase inhibitors, selective oestrogen receptor modulators and degraders, CDK4/6 inhibitors, and next-generation androgen receptor antagonists that have substantially improved outcomes in hormone-sensitive cancers. Conclusion: The hormone-cancer axis remains a productive frontier for both basic science and clinical oncology. Advances in liquid biopsy, single-cell genomics, and artificial intelligence are poised to refine our mechanistic understanding and therapeutic precision further, ultimately enabling individualised risk stratification and treatment optimisation in hormone-sensitive malignancies.