Effect of Soy Isoflavone Supplementation on Menopausal Symptoms and Lipid Profile in Perimenopausal and Postmenopausal Women: A Randomized Controlled Trial

Abstract

Background: Hormone replacement therapy for menopausal symptoms carries established risks of breast cancer, thromboembolic events, and cardiovascular disease, creating a critical need for safe and effective non-hormonal alternatives. Soy isoflavones, as phytoestrogens with selective estrogen receptor beta affinity, represent a biologically plausible and clinically promising alternative.Objective: To evaluate the efficacy and safety of standardised soy isoflavone supplementation on menopausal symptoms assessed by the Menopause Rating Scale and on lipid profile in perimenopausal and postmenopausal women attending a tertiary care hospital in South India. Methods: This was a prospective, open-label, randomized controlled trial conducted from May 2024 to June 2025 at SRM Medical College Hospital and Research Centre, Potheri, Tamil Nadu. One hundred sixty women aged 45 to 60 years with a Menopause Rating Scale score of at least 5 were randomly allocated to an intervention group (soy isoflavone capsules 100 mg twice daily for 12 weeks) or a control group (no treatment), with 80 participants in each arm. Primary outcome was change in Menopause Rating Scale total score from baseline to 12 weeks. Secondary outcomes included lipid profile, fasting blood glucose, glycated haemoglobin, and body mass index. Analyses included independent t-tests, paired t-tests, Cohen's d effect size, and number needed to treat calculations. Results: All 170 participants completed the 12-week study, with a retention rate of 94%, the intervention group showed a mean reduction of 5.2 points in Menopause Rating Scale total score versus 1.0 point in controls, a between-group difference of 4.2 points (p < 0.001; Cohen's d = 0.89, large effect size). Clinically significant improvement was achieved by 72.5% of intervention participants versus 22.5% of controls, yielding a number needed to treat of 2.0. Domain-specific effect sizes were largest for somatic symptoms (d = 1.02), followed by psychological (d = 0.79) and urogenital symptoms (d = 0.58). Postmenopausal women showed greater benefit (d = 1.08) than perimenopausal women (d = 0.74). Lipid profile showed favourable but non-significant trends. Adverse events occurred in 13.8% of intervention participants versus 10.0% of controls, with no serious adverse events or treatment discontinuations. Conclusion: Soy isoflavone supplementation at 200 mg daily for 12 weeks produces large, clinically significant improvements in menopausal symptoms across all domains. These findings support soy isoflavones as an effective, safe, non-hormonal alternative for menopausal symptom management, particularly in postmenopausal women.