Soy Isoflavones for Hot Flashes

Soy-derived isoflavones are popular non-hormonal supplements used to alleviate menopausal symptoms, particularly hot flushes. Researchers have explored their effects across various populations—including breast cancer survivors, women with higher BMI, and those experiencing frequent hot flashes—to determine optimal dosing, efficacy, and administration strategies.

Protocols Studied in Research

Effect of Soy‑Derived Isoflavones on Hot Flushes and Vascular Parameters [1]

• Protocol: In this double‑blind, randomized, placebo‑controlled trial, 62 postmenopausal women aged 45–60 received 72 mg/day of soy‑derived isoflavones or placebo. Participants recorded the daily number of hot flushes, while endometrial thickness was measured via transvaginal ultrasound and arterial pulsatility indices (PI) of uterine and cerebral arteries were assessed using Doppler ultrasound.
• Outcome: Both groups experienced a 40% reduction in hot flush frequency, with no significant differences between treatments. Isoflavones had no measurable effect on endometrial thickness or the PI of the uterine and cerebral arteries, indicating that 72 mg/day isoflavones were no more effective than placebo for reducing hot flushes in this population.

Effect of Soy Phytoestrogens on Hot Flashes in Postmenopausal Breast Cancer Survivors [2]

• Protocol: In a randomized, double‑blind, placebo‑controlled trial, 123 postmenopausal breast cancer survivors with moderate hot flashes were stratified by tamoxifen use and randomized to receive a soy beverage containing 90 mg of isoflavones or a placebo rice beverage. Participants recorded hot flash frequency and severity in daily diaries over 12 weeks.
• Outcome: Both the soy and placebo groups experienced significant reductions in hot flashes, with no significant differences between groups. Mild gastrointestinal side effects were more frequent in the soy group, suggesting that the observed benefits may be attributable to a strong placebo effect rather than a true pharmacologic effect.

Effect of Soy‑Derived Isoflavones on Hot Flushes, Menopausal Symptoms, and Mood in Women with Increased BMI [3]

• Protocol: In this single‑arm study, 50 symptomatic climacteric women aged 40–59 with BMI ≥25 received 100 mg/day of soy‑derived isoflavones (Climasoy) for 3 months. Hot flush frequency and intensity were recorded, while menopausal symptoms were assessed using the Menopause Rating Scale (MRS) and mood using the Hamilton Depressive Rating Scale (HDRS) at baseline and after 90 days.
• Outcome: After 3 months, participants experienced significant reductions in the percentage, number, and severity of hot flushes (e.g., a drop from 100% to 31.1% reporting hot flushes), along with marked improvements in overall menopausal symptoms and mood (HDRS scores decreased from 16.3 to 6.9; depressed mood dropped from 93.3% to 28.9%, p < 0.001). No changes were noted in blood pressure or BMI.

Comparative Efficacy of S‑Equol and Soy Isoflavones on Hot Flash Frequency [4]

• Protocol: In an 8‑week randomized, double‑blind, active comparator trial involving 102 postmenopausal women experiencing ≥5 hot flashes/day, participants were assigned to receive either 10, 20, or 40 mg/day of S‑equol or a soy isoflavone supplement. Hot flash frequency and menopausal symptom severity were recorded throughout the study.
• Outcome: All groups exhibited reductions in hot flash frequency; however, cumulative analyses indicated that 40 mg/day S‑equol produced a significantly greater reduction compared to soy isoflavones (p = 0.021). Subgroup analysis of women with >8 hot flashes/day further demonstrated that both 20 and 40 mg/day S‑equol were superior (p = 0.045 and p = 0.001, respectively). Additionally, lower doses of S‑equol (10 and 20 mg/day) significantly improved muscle and joint pain scores compared with isoflavones.

Effects of a Standardized Soy Extract on Hot Flushes [5]

• Protocol: In this multicenter, randomized, double‑blind, placebo‑controlled trial, 75 menopausal women (with natural or surgical menopause and ≥7 hot flushes/day) were randomized to receive an oral soy isoflavone extract (providing a total of 70 mg genistin and daidzin per day) or placebo for 16 weeks.
• Outcome: Treatment with soy extract resulted in a 38% reduction in daily hot flushes by week 4, 51% by week 8, and 61% by week 16, compared to a 21% reduction in the placebo group. Responders (≥50% reduction in hot flushes) were significantly more frequent in the soy group (65.8% vs 34.2%, p < 0.005).

Optimizing the Timing of Soy Isoflavone Administration in Postmenopausal Women [6]

• Protocol: In a multicentric, observational, open, prospective study of 1,682 postmenopausal women with climacteric symptoms, participants were allocated to receive a compound containing 60 mg of dry soy seed extract (with 40% isoflavones), primrose oil, and α‑tocopherol either in the morning or in the evening. After 3 months, the administration time was switched, and evaluations were conducted at baseline, 3, and 6 months using the Blatt‑Kupperman and Greene scales.
• Outcome: Both morning and evening administration significantly improved climacteric symptoms over 3 and 6 months (p < 0.001), with no significant differences in efficacy between the two administration times, indicating that timing does not modify the therapeutic effect of soy isoflavones on menopausal symptoms.

Research Interpretation: Summary and Conclusion

In simple terms, while lower doses (around 72–90 mg/day) of soy isoflavones often yield results similar to placebo, higher doses (100 mg/day) and standardized extracts appear more effective in reducing hot flush frequency and improving overall menopausal symptoms and mood. Moreover, S equol, a related compound, may offer superior benefits for hot flash reduction and pain relief, and the timing of isoflavone administration does not seem to affect outcomes.

Publications

[1] Penotti M, Fabio E, Modena AB, Rinaldi M, Omodei U, Viganó P. Effect of soy-derived isoflavones on hot flushes, endometrial thickness, and the pulsatility index of the uterine and cerebral arteries. Fertil Steril. 2003 May;79(5):1112-7. doi: 10.1016/s0015-0282(03)00158-4. PMID: 12738504.

[2] Van Patten CL, Olivotto IA, Chambers GK, Gelmon KA, Hislop TG, Templeton E, Wattie A, Prior JC. Effect of soy phytoestrogens on hot flashes in postmenopausal women with breast cancer: a randomized, controlled clinical trial. J Clin Oncol. 2002 Mar 15;20(6):1449-55. doi: 10.1200/JCO.2002.20.6.1449. PMID: 11896091.

[3] Chedraui P, San Miguel G, Schwager G. The effect of soy-derived isoflavones over hot flushes, menopausal symptoms and mood in climacteric women with increased body mass index. Gynecol Endocrinol. 2011 May;27(5):307-13. doi: 10.3109/09513590.2010.490614. Epub 2010 Jun 8. PMID: 20528204.

[4] Jenks BH, Iwashita S, Nakagawa Y, Ragland K, Lee J, Carson WH, Ueno T, Uchiyama S. A pilot study on the effects of S-equol compared to soy isoflavones on menopausal hot flash frequency. J Womens Health (Larchmt). 2012 Jun;21(6):674-82. doi: 10.1089/jwh.2011.3153. Epub 2012 Mar 12. PMID: 22409590.

[5] Faure ED, Chantre P, Mares P. Effects of a standardized soy extract on hot flushes: a multicenter, double-blind, randomized, placebo-controlled study. Menopause. 2002 Sep-Oct;9(5):329-34. doi: 10.1097/00042192-200209000-00005. PMID: 12218721.

[6] Cancelo Hidalgo MJ, Castelo Branco C. Optimizing soy isoflavones effect in postmenopausal women: the impact of timing on climacteric symptoms. Gynecol Endocrinol. 2011 Sep;27(9):696-700. doi: 10.3109/09513590.2010.526665. Epub 2010 Oct 28. PMID: 20979541.