Effects of flaxseed and Hypericum perforatum on hot flash, vaginal atrophy and estrogen-dependent cancers in menopausal women: a systematic review and meta-analysis

Document Type: Review Article


1 Student Research Committee, Department of Midwifery and Reproductive Health, Nursing and Midwifery School, Mashhad University of Medical Science, Mashhad, Iran

2 Nuclear Medicine Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

3 Evidence-Based Care Research Centre, Department of Midwifery, School of Nursing and Midwifery, Mashhad University of Medical Sciences, Mashhad, Iran

4 Department of Midwifery, School of Nursing and Midwifery, Mashhad University of Medical Sciences, Mashhad, Iran Mashhad, Iran

5 Department of Microbiology, Islamic Azad University of Varamin-pishva,Tehran, Iran

6 Obstetrics and Gynecology, Women's Health Research Center, Department of Obstetrics and Gynecology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

7 Esfarayen faculty of Medical Sciences, Esfarayen, Iran


Objective: In this study, we aimed at evaluation of the efficacy of Hypericum perforatum and flaxseed on hot flash, vaginal atrophy and estrogen-dependent cancers in menopausal women

Materials and Methods: We searched MEDLINE, Scopus, and the Cochrane Central Register of Controlled Trials (RCT) to explore trials that assessed the effectiveness of H. perforatum and flaxseed on hot flash, vaginal atrophy and estrogen-dependent cancers. In this regard, the following terms were used “menopause AND H. perforatum OR flaxseed OR Linum usitatissimum. Only randomized controlled trials were included in the study.

Results: Nine RCTs were included in this systematic review. Based on the literature, flaxseed showed beneficial effect on hot flash frequency and intensity, which was not statistically significant. According to two trials, flaxseed showed estrogenic effects; however, no conclusion regarding cancer promoting or protecting effects can be made. The evidence of the efficacy of the flaxseed on alleviating vaginal atrophy was also limited due to inconsistent findings in this regard. One trial declared that Vitex agnus-castus and H. perforatum showed comparable decrease in the frequency of hot flashes.

Conclusion: The results of our systematic review suggest beneficial effect on vasomotor symptom with both of flaxseed and H. perforatum. Consistent conclusion regarding estrogen-dependent cancers and maturation value is limited due to small number of trials related to flaxseed. Further trials are still needed to confirm the results of our systematic review.


Main Subjects

Avis NE, Stellato R, Crawford S, Johannes C, Longcope C. 2000. Is there an association between menopause status and sexual functioning?.Menopause, 7: 297-309.

Baber RJ, Templeman C, Morton T, Kelly GE, West L.1999. Randomized placebo-controlled trial of an isoflavone supplement and menopausal symptoms in women. Climacteric, 2: 85-92.

Briese V, Stammwitz U, Friede M, Henneicke-von Zepelin HH. 2007. Black cohosh with or without St. John's wort for symptom-specific climacteric treatment—Results of a large-scale, controlled, observational study. Maturitas, 57: 405-414.

Buck K, Zaineddin AK, Vrieling A, Linseisen J, Chang-Claude J. 2010. Meta-analyses of lignans and enterolignans in relation to breast cancer risk. Am J Clin Nutr, 92: 141-153.

Chung DJ, Kim HY, Park KH, Jeong KA, Lee SK, Lee YI, Hur SE, Cho MS, Lee BS, Bai SW, Kim CM, Cho SH, Hwang JY, Park JH. 2007. Black Cohosh and St. John's wort (GYNO-Plus®) for climacteric symptoms. Yonsei Med , 48: 289-294.

Colli MC, Bracht A, Soares AA, de Oliveira AL, Bôer CG, de Souza CG, Peralta RM. 2012. Evaluation of the Efficacy of Flaxseed Meal and Flaxseed Extract in Reducing Menopausal Symptoms. J Med Food, 15: 840-845.

Cramer H, Lauche R, Langhorst J, Dobos G. 2012. Effectiveness of yoga for menopausal symptoms: a systematic review and meta-analysis of randomized controlled trials. Evid Based Complement Alternat Med, Article ID 863905.

Dalais FS, Rice GE, Wahlqvist ML, Grehan M, Murkies AL, Medley G, Ayton R, Strauss BJ. 1998. Effects of dietary phytoestrogens in postmenopausal women. Climacteric, 1: 124-129.

Dew TP, Williamson G. 2013. Controlled flax interventions for the improvement of menopausal symptoms and postmenopausal bone health: a systematic review. Menopause, 20:1207-1215.

Dodin S, Lemay A, Jacques H, Légaré F, Forest JC, Mâsse B. 2005. The effects of flaxseed dietary supplement on lipid profile, bone mineral density, and symptoms in menopausal women: a randomized, double-blind, wheat germ placebo-controlled clinical trial. J Clin Endocrinol Metab, 90: 1390-1397.

Geller SE, Shulman LP, van Breemen RB, Banuvar S, Zhou Y, Epstein G, Hedayat S, Nikolic D, Krause EC, Piersen CE, Bolton JL, Pauli GF, Farnsworth NR. 2009. Safety and efficacy of black cohosh and red clover for the management of vasomotor symptoms: a randomized controlled trial. Menopause, 16: 1156-66.

Ghaderi E, Ghazanfarpour M, Kaviani M. 2010. Evaluation of menopausal women’s attitudes towards menopause in Shiraz. Pak J Med Sci, 26: 698-703.

Ghazanfarpour M, Ghaderi E, Kaviani M, Haddaian K. 2013. Comparison the efficacy of Hypericum perforatum and vitex agnus-castus in hot flashes: A double-blinded randomized controlled trial. Chron Dis J, 1: 67-73.

Anderson G, Cummings S, Freedman LS, et al. 1998. Design of the women’s health initiative clinical trial and observational study. Control Clin Trials, 19:61–109.

Hidalgo LA, Chedraui PA, Morocho N, Ross S, San Miguel G. 2005. The effect of red clover isoflavones on menopausal symptoms, lipids and vaginal cytology in menopausal women: a randomized, double-blind, placebo-controlled study. Gynecol Endocrinol, 21: 257-64.

Hooper L, Ryder JJ, Kurzer MS, Lampe JW, Messina MJ, Phipps WR, Cassidy A. 2009. Effects of soy protein and isoflavones on circulating hormone concentrations in pre-and post-menopausal women: a systematic review and meta-analysis. Hum Reprod Update, 15: 423-440.

Lewis JE, Nickell LA, Thompson LU, Szalai JP, Kiss A, Hilditch JR. 2006. A randomized controlled trial of the effect of dietary soy and flaxseed muffins on quality of life and hot flashes during menopause. Menopause, 13: 631-42.

Lipovac M, Chedraui P, Gruenhut C, Gocan A, Kurz C, Neuber B, Imhof M. 2012. The effect of red clover isoflavone supplementation over vasomotor and menopausal symptoms in postmenopausal women. Gynecol Endocrinol, 28: 203-7.

Loprinzi CL, Kugler JW, Sloan JA, Mailliard JA, LaVasseur BI, Barton DL, Novotny PJ, Dakhil SR, Rodger K, Rummans TA, Christensen BJ. 2000. Venlafaxine in management of hot flashes in survivors of breast cancer: a randomised controlled trial. Lancet, 356: 2059-2063.

Lowcock EC, Cotterchio M, Boucher BA. 2013. Consumption of flaxseed, a rich source of lignans, is associated with reduced breast cancer risk. Cancer Causes Control, 24:813-6.

Maclennan AH, Broadbent JL, Lester S, Moore V. 2004. Oral oestrogen and combined oestrogen/progestogen therapy versus placebo for hot flashes. Cochrane Database Syst Rev, 4.

Pruthi S, Qin R, Terstreip SA, Liu H, Loprinzi CL, Shah TR, Tucker KF, Dakhil SR, Bury MJ, Carolla RL, Steen PD, Vuky J, Barton DL. 2012. A phase III, randomized, placebo-controlled, double-blind trial of flaxseed for the treatment of hot flashes: North Central Cancer Treatment Group N08C7. Menopause, 19: 48-53.

Simbalista RL, Sauerbronn AV, Aldrighi JM, Arêas JA. 2010. Consumption of a flaxseed-rich food is not more effective than a placebo in alleviating the climacteric symptoms of postmenopausal women. J Nutr, 140: 293-7.

Uebelhack R, Blohmer JU, Graubaum HJ, Busch R, Gruenwald J, Wernecke KD. 2006. Black cohosh and St. John's wort for climacteric complaints: a randomized trial. Obstet Gynecol, 107: 247-255.

van Die MD, Burger HG, Bone KM, Cohen MM, Teede HJ. 2009. Hypericum perforatum with Vitex agnus-castus in menopausal symptoms: a randomized, controlled trial. Menopause, 16:156-163.