Innovative Drug Delivery Systems for Management of Menopausal Symptoms: A Systematic Review

Zahra Bostani Khalesi,1 Mahmood Abedinzade,2 Mostafa Golshekan2,3 1Department of Midwifery, Biomedicine Research Center, Trauma Institute, Guilan University of Medical Sciences, Rasht, Iran; 2Department of Physiology, biomedicine research center, trauma institute, Guilan university of medical sciences, Rasht, Iran; 3Department of Medicinal Chemistry, Biomedicine Research Center, Trauma Institute, Guilan University of Medical Sciences, Rasht, IranCorrespondence: Mahmood Abedinzade, Department of Physiology, Biomedicine Research Center, Trauma Institute, Guilan University of Medical Sciences, Rasht, Iran, Fax +981333360669, Email [email protected]: Menopause characterized by estrogen deficiency and has various symptoms, including vasomotor, genitourinary, and psychological manifestations. Innovative drug delivery systems (IDDSs) offer targeted approaches that increase therapeutic efficacy, reduce side effects, and improve patient adherence. To update our knowledge about Drug Delivery Systems (DDS) for decrease menopausal symptoms and its benefits compare with conventional systems. This review systematically examines the application and clinical potential of IDDS for managing menopause-related symptoms, with a particular emphasis on improvements in efficacy, safety, and patient adherence. A comprehensive literature search across multiple databases (PubMed, Em-base, Cochran, Scopus; 2001– 2024) yielded 23 studies, including RCTs and observational studies on trans dermal, intravaginal, and Nano-based DDS s (patches, vaginal rings, nano particles) and Neurokinin-3 (NK3) antagonists. Transdermal systems, such as estrogen patches, maintained stable hormone levels and reduced thromboembolism risk by 30% compared to oral hormone replacement therapy (HRT), by bypassing first-pass metabolism. Intravaginal DDS s, like estradiol rings, relieved genitourinary symptoms with less than 1% systemic absorption, thereby minimizing endometrial risks. Non-hormonal Neurokini3 antagonists like fezolinetant, decreased VMS by 60% and benefited high-risk patients. Emerging technologies, like hydro gels, showed preclinical potential but lack long-term safety data. Adherence to treatment was better with sustained-release formulations, such as pellet implants, compared to daily dosing regimens. DDSs offer personalized menopause management, balancing safety and efficacy. Future research should focus on pharmacogenomics, equity, and long-term safety of advanced DDSs, especially those using nanotechnology.Keywords: Drug Delivery Systems, Menopause, Hormone Replacement Therapy, Nanoparticles