1Student Research Committee, Department of Midwifery and Reproductive Health, Nursing and Midwifery School, Mashhad University of Medical Science, Mashhad, Iran
2Nuclear Medicine Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
3Evidence-Based Care Research Centre, Department of Midwifery, School of Nursing and Midwifery, Mashhad University of Medical Sciences, Mashhad, Iran.
4Department of Midwifery, School of Nursing and Midwifery, Mashhad University of Medical Sciences, Mashhad, Iran
5Department of community of Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
6Department of Midwifery, Islamic Azad University, Firuzabad, Fars, Iran,
7Department of Midwifery, School of Nursing and Midwifery, Mashhad University of Medical Sciences, Mashhad, Iran Mashhad, Iran
Objectives: To critically evaluate the effect of red clover on hot flash, endometrial thickness, and hormones status in postmenopausal and peri- and post-menopausal women. Materials and Methods: MEDLINE (1966 to July 2014), Scopus (1990 to July 2014), and the Cochrane Central Register of Controlled Trials (The Cochrane Library issue 1, 2014) were searched for published randomized controlled Trials (RCTs). Results: Of 183 relevant publication trials, 11 RCTs met the inclusion criteria. The mean hot flashes frequency in red clover was lower than the control groups (MD -1.99; p=0.067). There was larger decrease in FSH (SMD -0.812; CI: -1.93 to 0.312; p=0.157) and SHBG (SMD -0.128; CI-0.425 to 0.170; P=0.4) in red clover group, compared with placebo, which was not however statistically significant. LH (SMD 0.144; CI-0.097 to 0.384, p=0.242), estradiol (SMD 0.240; CI-0.001 to 0.482, p=0.051), testosterone (MD 0.083; CI: -0.560 to 0.726; p=0.901), and endometrial thickness (SDM 0.022; CI: -0.380 to 0.424, p=0.915) showed greater increase in red clover, compared with placebo, although the effect of estradiol was only significant. Conclusion: Red clover had a positive effect of alleviating hot flash in menopausal women. Our data, however, suggested very slight changes in FSH, LH, testosterone, and SHBG and significant effect in estrogen status by red clover consumption. However, the interpretation of results of the current study is limited due to methodological flaws of the included studies, menopause status, and large heterogeneity among them. Further trials are still needed to confirm the current finding.
Atkinson C, Warren RM, Sala E, Dowsett M, Dunning AM, Healey CS, Runswick S, Day NE, Bingham SA.2004. Red-clover-derived isoflavones and mammographic breast density:a double –bilnd, randomaized , placebo- controlled trial. Breast Cancer Res, 6:R170-9.
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.
Hidalgo LA, Chedraui PA, Morocho N, Ross S, San Miguel G. 2005. The effect of red clover isflavones 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, 4:423-40.
Imhof M, Gocan A, Reithmayr F, Lipovac M, Schimitzek C, Chedraui P, Huber J. 2006. Effects of a red clover extract (MF11RCE) on endometrium and sex hormones in postmenopausal women. Maturitas, 55: 76-81.
Jeri AR.2002. The use of an isoflavone supplement to relieve hot flashes. Female patient;27:35-37.
Knight DC, Howes JB, Eden JA. 1999. The effect of Promensil™, an isoflavone extract, on menopausal symptoms. Climacteric, 2:79-84.
Kotsopoulos D, Dalais FS, Liang YL, McGrath BP, Teede HJ. 2000. "The effects of soy
Krebs EE, Ensrud KE, MacDonald R, Wilt TJ. 2004. Phytoestrogens for treatment of menopausal symptoms: a systematic review. Obstet Gynecol,104: 824-836.
Lethaby AE, Brown J, Marjoribanks J, Kronenberg F, Roberts H, Eden J. 2007. Phytoestrogens for vasomotor menopausal symptoms. Cochrane Database Syst Rev:4.
Lipovac M, Chedraui P, Gruenhut C, Gocan A, Kurz C, Neuber B, Imhof M. 2012. The effect of red clover isoflavone supplementation over vasomotore 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.
Maclennan AH, Broadbent JL, Lester S, Moore V. 2004. Oral oestrogen and combined oestrogen/Progestrog therapy versus placebo for hot flushes. Cochrane Database Syst Rev, 4.
Maki PM, Rubin LH, Fornelli D, Drogos L, Banuvar S, Shulman LP, Geller SE. 2009. Effects of botanicals and combined hormone therapy on cognition in postmenopausal women. Menopause, 16: 1167.
Meherishi S, Khandelwal S, Swarankar ML, Kaur P. 2010. Attitudes and practices of gynecologists in Jaipur toward management of menopause. J Midlife Health, 1: 74-8.
Menati L, Khaleghinezhad K, Tadayon M, Siahpoosh A. 2014. Evaluation of contexual and demographic factors on licorice effects on reducing hot flashes in postmenopause women. Health Care Women Int, 35: 87-99.
Nelson HD, Vesco KK, Haney E, Fu R, Nedrow A, Miller J, Nicolaidis C, Walker M, Humphrey L. 2006. Nonhormonal therapies for menopausal hot flashes: systematic review and meta-analysis. Jama, 295: 2057-2071.
Salehi K, Ehsanpour S., Zolfaghari B, Salehi Z. Honagoo M. 2013. Effect of red clover isoflavone extract on menopausal symptoms. J Gorgan Univ Med Sci, 15: 21-27.
Sites DS, Johnson NT, Miller JA, Torbush PH, Hardin JS, Knowles SS, Nance J, Fox TH, Tart RC. 2014. Controlled breathing with or without peppermint aromatherapy for postoperative nausea and/or vomiting symptom relief: a randomized controlled trial. J Perianesth Nurs, 29: 12-19.
Taavoni S, Shakeri F, Haghani H. Gooshegir S. 2012. Effect of red clover on vasomotor symptoms and heart discomfort of menopausal women . CMJA 3: 32-40.
Tice JA, Ettinger B, Ensrud K, Wallace R, Blackwell T, Cummings SR. 2003. Phytoestrogen supplements for the treatment of hot flashes: the Isoflavone Clover Extract (ICE) Study: a randomized controlled trial. Jama, 290: 207-214.
van de Weijer PH1, Barentsen R. 2002. Isoflavones from red clover (Promensil®) significantly reduce menopausal hot flush symptoms compared with placebo. Maturitas, 42:187-193.
Yavari Kia P, Safajou F, Shahnazi M, Nazemiyeh H. 2014. The effect of lemon inhalation aromatherapy on nausea and vomiting of pregnancy: a double-blinded, randomized, controlled clinical trial. Iran Red Crescent Med J, 16:e14360
Zheng W, Dai Q, Custer LJ, Shu XO, Wen WQ, Jin F, Franke AA.1999. Urinary excretion of isoflavonoids and the risk of breast cancer. Cancer Epidemiol Biomarkers Prev, 8: 35-40.