A stepwise, symptom-driven treatment model is recommended-beginning with non-hormonal options and advancing to local vaginal therapies or ospemifene when appropriate...Local estrogen is generally safer in tamoxifen users, but caution is warranted with aromatase inhibitors due to potential systemic absorption. In patients with estrogen receptor-negative disease, local hormone use may be considered but requires careful risk-benefit evaluation and shared decision making is essential. Until long-term safety data emerge, management should remain individualized, evidence-based, and multidisciplinary.

Vorinostat and raloxifene exhibited notable binding affinity for PEBP1. Furthermore, an independent prognostic model for LUAD was developed, enhancing our understanding of high-/low-risk cohorts' functional pathways. Drug prediction results provided valuable insights into potential therapeutic strategies for LUAD, warranting further investigation.

Among the most studied SERMs are Tamoxifen and Raloxifene. The pharmacological profile of SERMs therefore reflects a delicate equilibrium between receptor-mediated vascular protection and thrombotic liability. Indeed, their raison d'être increasingly extends beyond oncology into cardiovascular endocrine pharmacology, where they serve as prototypes for designing next-generation agents with optimized receptor selectivity and safer vascular outcomes.

P2, N=100, Completed, Sermonix Pharmaceuticals Inc. | Active, not recruiting --> Completed | Trial completion date: Dec 2024 --> May 2025 | Trial primary completion date: Dec 2024 --> May 2025

The existing treatments, such as hormonal drugs and selective estrogen receptor modulators like raloxifene, have side effects and recurrence, and thus indicate the need for less harmful non-hormonal therapies...Procyanidin is a phytochemical lead that shows promise for controlling ESR1 signaling in fibroids and endometriosis as a non-hormonal candidate. Procyanidin emerged as a promising in-silico lead for ESR1 modulation, showing high binding affinity and dynamic stability; nevertheless, further pharmacokinetic, ADMET, and experimental validation are required to substantiate its therapeutic potential.

P1, N=40, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed | Trial completion date: Jun 2026 --> Dec 2025

P2, N=242, Recruiting, Beth Israel Deaconess Medical Center | Not yet recruiting --> Recruiting

P1, N=62, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Oct 2025 --> Oct 2026

In this study, we rationally optimized the benzothiophene scaffold of the SERM raloxifene through strategic linker modifications, culminating in the discovery of B7, a potent ERα degrader validated by structure-activity relationship analysis. In the T47D xenograft mouse model, the combination of B7 and Palbociclib demonstrated potent antitumor activity, achieving a tumor growth inhibition rate of 89.2 %. Further structural modification based on B7 may lead to the development of a candidate.

P1/2, N=35, Not yet recruiting, Azure Biotech Inc. | Trial completion date: Dec 2024 --> Jun 2027 | Trial primary completion date: Sep 2024 --> Dec 2026

P2, N=156, Active, not recruiting, Northwestern University | Recruiting --> Active, not recruiting | Trial completion date: Jun 2024 --> Jun 2026 | Trial primary completion date: Jan 2024 --> Jan 2026

This framework invites translational trials using biomarker-enriched patient stratification. If validated, it could reshape the role of sex hormones in male psychiatry-not as contraindications, but as precision neuromodulators aligned with neurobiological pathology.