Comparative Effectiveness of Hormonal Replacement Therapy Versus Integrative Non-Pharmacological Interventions in the Management of Menopausal Syndrome: A 24-Month Longitudinal Analysis

Background: Menopausal syndrome substantially diminishes health-related quality of life in midlife women globally. Hormone replacement therapy (HRT) has long been the standard of care for symptom management; however, long-term safety concerns—including elevated risks of breast malignancy, cardiovascular events, and venous thromboembolism—have prompted growing interest in holistic, non-pharmacological alternatives. Direct longitudinal comparative data across Southeast Asian populations remain scarce.Objective: To evaluate and contrast the efficacy of HRT versus a structured integrative intervention programme on symptom severity and quality of life over a 24-month follow-up period.Methods: This prospective, comparative longitudinal study enrolled 500 women aged 45–60 years presenting with moderate-to-severe menopausal syndrome across six Type B hospitals in Indonesia between January 2023 and December 2025. Participants were allocated to either HRT (conjugated equine oestrogen plus progestin; n = 250) or integrative care (individualised lifestyle modification, cognitive behavioural therapy, mindfulness-based stress reduction, and standardised phytoestrogen supplementation; n = 250). Primary outcomes were change in Menopause Rating Scale (MRS) total score and WHO Quality of Life–BREF (WHOQOL-BREF) domain scores at baseline, 6, 12, and 24 months. Mixed-effects regression models were used to estimate group differences over time.Results: Both groups demonstrated statistically significant reductions in MRS scores over the study period (p < 0.001 for each). HRT produced more rapid symptomatic improvement at 6 months (adjusted mean difference −6.4; 95% confidence interval −7.8 to −5.0; p < 0.001). By 24 months, the between-group difference was no longer statistically significant (−0.4; −1.1 to 0.3; p = 0.08). Integrative-care participants recorded significantly higher WHOQOL-BREF domain scores at 24 months, particularly in the psychological (difference 8.2; p < 0.001) and social (difference 8.3; p < 0.001) domains.Conclusion: HRT confers rapid, short-term relief of menopausal symptoms, whereas integrative non-pharmacological interventions yield equivalent long-term symptomatic control and superior sustained quality-of-life outcomes. A stratified, shared-decision approach—aligning treatment selection with patient priorities, risk profiles, and cultural context—is recommended.