Isoflavone supplementation reduced serum sex hormone-binding globulin concentration in postmenopausal women

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ML. Edy Parwanto
Yanti Indrawati
Herman Setiawan


The bone loss that occurs with ageng in postmenopausal women is related to a decrease in serum levels of bioavailable estrogen and testosterone, which are mainly bound to sex hormone-binding globulin (SHBG) and albumin. Phytoestrogens are thought to exert hormonal effects in the body due to their structural resemblance to 17â-estradiol. The objective of this study was to evaluate the effect of isoflavone supplementation on levels of SHBG in postmenopausal women aged 47- 60 years.

A study of pre and post test design with controls was conducted in 70 women aged 47- 60 years. Subjects were randomly divided into 2 groups, the isoflavone group received 100 mg isoflavones/day + calcium 500 mg/day and the control group calcium 500 mg/day for 6 months. Measurement of bone mineral density was performed prior to supplementation, and serum SHBG levels before and after supplementation.

Supplementation of isoflavones for 6 months reduced the SHBG levels by 31.1% in the isoflavone group (p=0.000), whereas supplementation of calcium for 6 months did not affect the levels of SHBG in the control group (p=0.359). Supplementation of isoflavones for 6 months reduced SHBG levels of postmenopausal women in the isoflavone group with either osteopenia (p=0.028) or osteoporosis (p=0.008).

Supplementation of isoflavones for 6 months decreased the SHBG levels of postmenopausal women in the isoflavone group with osteopenia and osteoporosis. Our findings suggest that phytoestrogens may significantly decreased SHBG levels in postmenopausal women.

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How to Cite
Parwanto, M. E., Indrawati, Y., & Setiawan, H. (2012). Isoflavone supplementation reduced serum sex hormone-binding globulin concentration in postmenopausal women. Universa Medicina, 31(1), 52–62.
Review Article


Venkat K, Desai M, Arora MM, Singh P. Age – related changes in sex steroid levels influence bone mineral density in healthy Indian men. Osteoporos Int 2009;20:955–62.

Häussler B, Gothe H, Göl D, Glaeske G, Pietnka L, Felsenberg D. Epidemiology, treatment and cost of osteoporosis in Germany – the Bone Eva Study. Osteoporosis Int 2006;18:77–84.

World Health Organization. Assessment of fracture risk and its application to screening for post menopausal osteoporosis. Geneva: World Health Organization;1994.

Lukanova A, Lundin E, Micheli A, Aeslan A, Ferrari P, Rinaldi S, et al. Circulating levels of sex steroid hormones and risk of endometrial cancer in postmenopausal women. Int J Cancer 2004;108:425–32.

Lindsay R, Gallagher JC, Kleerekoper M, Pickar JH. Effect of lower doses of conjugated equine estrogens with and without medroxyprogesterone acetate on bone in early postmenopausal women. JAMA 2002;287: 2668-76.

Abaza MM, Ragab WS, Magour GM, Aref TY, Zaki MA, Sharkawi RM. Evaluation of serum estradiol, intact parathyroid hormone, and interleukin – 6 levels in relation to bone mineral density in postmenopausal women. J Med Res 2005;26:363–8.

Ayala M, Pizarro F, Mëndez MA, Arredondo M, Araya M. Copper and liver function indicators vary depending on the female hormonal cycle and serum hormone binding globulin (SHBG) concentration in healthy women. Biol Trace Elem Res 2008;121:9–15.

Mozzanega B, Babbo GL, Salmaso L, de Toni R, Schiavo A, Mioni R, et al. Oral 17 [beta]-estradiol and sequential progesterone in menopause: effects on insulin-like growth factors and their binding proteins. Gynecol Endocrinol 2007;23:50–7.

Pilekofe L, Rieansky L, Jagla F. The physiological actions of isoflavone phytoestrogens. Physiol Res 2010;59:651–64.

Grados F, Brazier M, Kamel S, Mathieu M, Hurtebize N, Maamer M, et al. Prediction of bone mass density variation by bone remodeling markers in postmenopausal women with vitamin D insufficiency treated with calcium and vitamin D supplementation. J Clin Endocrin Metab 2003;88:5175–9.

Hooper L, Ryder JJ, Kurzer MS, Lampe JW, Messina MJ, Phipps WR, et al. 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 2009;1: 1–18.

Tedee AJ, Dalais FS, Mc Grath BP. Dietary soy containing phytoestrogens does not have detectable estrogenis effects on hepatic protein synthesis in postmenopausal women. Am J Clin Nutr 2004;79:396–401.

Aubertin – Leheudre M, Lord C, Khalil A, Dionne IJ. Effect of 6 months of exercise and isoflavone supplementation on clinical cardiovascular risk factors in obese postmenopausal women: a randomized, double – blind study. Menopause 2007;14:1–6.

Erdman JW, Badger TM, Lampe JW, Setchell KDR, Messina M. Not all soy products are created equal: caution needed in interpretation of research results. J Nutr 2004;134 Suppl 5: 1229S–33S.

Arjmandi BH, Lucas EA, Khalil DA, Devareddy L, Smith BJ, McDonald J, et al. One year soy protein supplementation has positive effects on bone formation markers but not bone density in postmenopausal women. J Nutr 2005;4:1–9.

Vrieling A, Rookus MA, Kampman E, Bonfre JMG, Bosma A, Cats A, et al. No effect of red clover–derived isoflavone intervention on the insulin-like growth factor system in women at increased risk of colorectal cancer. Cancer Epidemiol Biomark Prev 2008;17:2585-93. doi:10.1158/1055-9965.EPI-08-0329.

Labrie F, Luu–The V, Bélanger A, Lin SX, Simard J, Pelletier G, et al. Is dehydroepiandro- sterone a hormone? J Endocrinol 2005;187:169-96.

Luu – The V, Labrie F. The intracrine sex steroid biosynthesis pathways. Prog Brain Res 2010; 181:177–92.

Hoppe E, Bouvardd B, Royer M, Audran M, Legrand E. Sex hormone-binding globulin in osteoporosis. Joint Bone Spine 2010;77:306-12.

Lee JS, LaCroix AZ, Wu LL, Cauley JA, Jackson RD, Kooperberg C, et al. Associations of serum sex hormone-binding globulin and sex hormone concentrations with hip fracture risk in postmenopausal women. J Clin Endocrinol Metab 2008;93:1796–803.

Low YL, Dunning AM, Dowsett M, Luben RN, Khaw KT, Wareham NJ, et al. Implications of gene – environment interaction in studies of gene variants in breast cancer: an example of dietary isoflavones and the D356N polymorphism in the sex hormone binding globulin gene. Cancer Res 2006;66:8980–3.

Hryb DJ, Nakhla AM, Khan MS, St. George J, Levy NC, Romas NA, et al. Sex hormone-binding globulin in the human prostate is locally synthesized and may act as an autocrine/paracrine effector. J Biol Chem 2002;277: 26618–22.

Lee C, Cheong M, Hsiao W, Liu H, Tsai C, Wang M, et al. Use of iQPR-H2O for bone regeneration and its potential in the improvement of osteoporosis. BMC Musculoskel Disord 2011;12: 227–36.

Enríquez J, Lemus AE, Chimal–Monroy J, Arzate H, Garcý´a GA, Herrero B, et al. The effects of synthetic 19 – norprogestins on osteoblastic cell function are mediated by their non-phenolic reduced metabolites. J Endocrinol 2007;193:493–504.

Yamaguchi M. Isoflavone and bone metabolism: its cellular mechanism and preventive role in bone loss. J Health Sci 2002;48:209–22.

Turhan NO, Bolkan F, Duvan CL, Ardicolu Y. The effect of isoflavones on bone mass and bone remodeling markers in postmenopausal women. Turk J Med Sci 2008;38:145–52.

Shakibaei M, Buhrmann C, Mobasheri A. Resveratrol-mediated SIRT – 1 interactions with p300 modulate receptor activator of NF – êB ligand (RANKL) activation of NF – êB signaling and inhibit osteoclastogenesis in bone – derived cells. J Biol Chem 2011;286:11492–505.

Morris C, Thorpe J, Ambrosio L, Santin M. The soybean isoflavone genistein induces differentiation of MG63 human osteosarcoma osteoblasts. J Nutr 2006;136:1166–70.

Lormeau C, Soudan B, d’Herbomez M, Pigny P, Duquesnoy B, Cortet B. Sex hormone-binding globulin, estradiol, and bone turnover markers in male osteoporosis. Bone 2004;34:933–9.

Ye L, Chan MY, Leung LK. The soy isoflavone genistein induces estrogen synthesis in an extragonadal pathway. Mol Cell Endocrinol 2009;302:73-80.

Riancho JA, Valero C, Zarrabeitia MT, García – Unzueta MT, Amado JA, Gonzalez – Marcías J. Genetic polymorphisms are associated with serum levels of sex hormone binding globulin in postmenopausal women. BMC Med Genet 2008;9:112–18.

Goderie-Plomp HW, van der KM, de Ronde W, Hofman A, de Jong FH, Pols HA. Endogenous sex hormones, sex hormone-binding globulin, and the risk of incident vertebral fractures in elderly men and women: the Rotterdam Study. J Clin Endocrinol Metab 2004;89:3261–9.

Rapuri PB, Gallagher JC, Haynatzki G. Endogenous levels of serum estradiol and sex hormone binding globulin determine bone mineral density, bone remodeling, the rate of bone loss, and response to treatment with estrogen in elderly women. J Clin Endocrinol Metab 2004;89:4954–62.

Abrahamson PE, Tworoger SS, Aiello EJ, Bernstein L, Ulrich CM, Gilliland FD, et al. Associations between the CYP17, CYPIB1, COMT and SHBG polymorphisms and serum sex hormones in post-menopausal breast cancer survivors. Breast Cancer Res Treat 2007;105: 45–54.

Cui Y, Shu XO, Cai Q, Jin F, Cheng JR, Cai H, et al. Association of breast cancer risk with a common functional polymorphism (Asp327Asn) in the sex hormone-binding globulin gene. Cancer Epidemiol Biomark Prev 2005;14:1096–101.

Harkness LS, Fiedler K, Sehgal AR, Oravec D, Lerner E. Decreased bone resorpstion with soy isoflavone supplementation in postmenopausal women. J Womens Health 2004;13:1000–7.

Prapan S, Udomrat S, Puntheeranurak T. Characterization of osteoblast and biomineral formation by atomic force microscopy study. J Microsc Soc Thailand 2009;23:7–11.

De Wilde A, Lieberherr M, Colin C, Pointillart A. A low dose of daidzein acts as an ER beta – selective agonist in trabecular osteoblasts of young female piglets. J Cell Physiol 2004;200: 253–62.

Kukuljan S, Nowson CA, Sanders KM, Nicholson GC, Seibel MJ, Salmon J, et al. Independent and combined effects of calcium-vitamin D3 and exercise on bone structure and strength in older men: an 18-month factorial design randomized controlled trial. J Clin Endocrinol Metab 2011;96:955–63.

Jackson RD, LaCroix AZ, Gass M, Wallace RB, Robbins J, Lewis CE, et al. Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med 2006;354:669–83.

Nakamura K, Saito T, Yoshihara A, Ishikawa M, Tsuchiya Y, Oshiki R, et al. Low calcium intake is associated with increased bone resorption in postmenopausal Japanese women: Yokogoshi Study. Public Health Nutr 2009;2: 2366–70.