European Journal of Nutrition

, Volume 43, Issue 4, pp 246–257

Soymilk or progesterone for prevention of bone loss

A 2 year randomized, placebo–controlled trial
  • E. Lydeking–Olsen
  • J.-E. Beck-Jensen
  • K. D. R. Setchell
  • T. Holm–Jensen
ORIGINAL CONTRIBUTION

Summary

Background

Given concerns over the use of hormone replacement therapy (HRT), women are seeking natural alternatives to cope with the symptoms and effects of menopause. The bone sparing effects of soy protein and its isoflavones is well established in animal studies, while 5 previous human studies on soy and bone have yielded variable outcomes due in part to their short duration of study. Progesterone has been suggested as a bone–trophic hormone, but the effect of long–term, low dose transdermal progesterone is unknown.

Aim

The aim of the study was to compare for the first time the long–term effects of soymilk, with or without isoflavones with natural transdermal progesterone, or the combination, on bone mineral density in the lumbar spine and hip.

Methods

Postmenopausal, Caucasian women with established osteoporosis or at least 3 risk–factors for osteoporosis, were randomly assigned, double–blind to one of four treatment–groups: soymilk containing isoflavones (soy+, n = 23), transdermal progesterone (TPD+, n = 22), or the combination of soy+ and TDP+,(n = 22) or placebo (isoflavone–poor soymilk, soy÷ and progesterone–free–cream TDP÷, n = 22). All subjects received comparable intakes of calcium, minerals and vitamins. Bone mineral content (BMC) and density (BMD) were measured in lumbar spine and hip by using dual–energy X-ray absorptiometry (DEXA) at baseline and after 2 years.

Findings

The percentage change in lumbar spine BMD and BMC respectively, did not differ from zero in the soy+ group (+1.1%, +2.0%) and TDP+ group (÷1.1%, +0.4 %) but significant bone loss occurred in the control group (÷4.2%,÷4.3 %) and the combined treatment group (÷2.8%, ÷2.4 %). No significant changes occurred for femoral neck BMD or BMC.

Interpretation

Daily intake of two glasses of soymilk containing 76 mg isoflavones prevents lumbar spine bone loss in postmenopausal women. Transdermal progesterone had bone–sparing effects but when combined with soy milk a negative interaction between the two treatments occurs resulting in bone–loss to a greater extent than either treatment alone.

Key words

soy isoflavones genistein daidzein equol transdermal progesterone bone density bone conservation postmenopausal women 

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References

  1. 1.
    Scharbo-Dehaan M (1996) Hormone replacement therapy. Nurse Pract 21:1–13PubMedGoogle Scholar
  2. 2.
    Groeneveld FP, Bareman FP, Barentsen R, Doktor HJ, Drogendijk AC, Hoes AW (1994) Determinants of first prescription of hormone replacement therapy. A follow-up study among 1689 women aged 45–60 years. Maturitas 20:81–89PubMedGoogle Scholar
  3. 3.
    de Lignieres B (1996) Hormone replacement therapy: Clinical benefits and side-effects. Maturitas 23(suppl):S31–S36CrossRefPubMedGoogle Scholar
  4. 4.
    Writing group for the Women’s Health Initiative Investigators (2002) Risk and benefits of estrogen plus progestin in healthy postmenopausal women. JAMA 288:321–333PubMedGoogle Scholar
  5. 5.
    Grady D, Harrington D, Bittner V, Blumenthal R,Davidson M, Hlatky M, et al. (2002) Cardiovascular disease outcomes during 6.8 years of hormone therapy. JAMA 288:49–57CrossRefPubMedGoogle Scholar
  6. 6.
    Kuiper GG, Enmark E, Pelto-Huikko M, Nilsson S,Gustafsson JA (1996) Cloning of a novel receptor expressed in rat prostate and ovary. Proc Natl Acad Sci 93:5925–5930CrossRefPubMedGoogle Scholar
  7. 7.
    Kuiper GG, Carlsson B, Grandien K, Enmark E, Haggblad J, Nilsson S, Gustafsson JA (1997) Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta. Endocrinology 138:863–870CrossRefPubMedGoogle Scholar
  8. 8.
    Williams JP, Jordan SE, Barnes S, Blair HC (1998) Tyrosine kinase inhibitor effects on avian osteoclastic acid transport. Am J Clin Nutr 68:1369S–1374SPubMedGoogle Scholar
  9. 9.
    Rassi CM, Lieberherr M, Chaumaz G, Pointillart A, Cournot G (2001) Daidzein inhibits osteoclast differentiation and activity in vitro. Ann Nutr Metab 45:230 (Abstract)Google Scholar
  10. 10.
    Cho Y, Chung S, Cho K, et al. (2002) Black bean (Rhynchosia molubilis,Yak-Kong) exerts a prominent estrogenic effect on the proliferation of human MG- 63 osteoblastic cells. J Nutr 132:614SGoogle Scholar
  11. 11.
    Chen X, Anderson JJB (2002) Effects of isoflavones on osteoblast proliferation and differentiation. J Nutr 132(3):616S (Abstract)Google Scholar
  12. 12.
    Setchell KDR, Lydeking-Olsen E (2003) Dietary phytoestrogens and their impact on bone-evidence from in vitro and in vivo, human observational and dietary intervention studies. Am J Clin Nutr 78(suppl):593S–609SPubMedGoogle Scholar
  13. 13.
    Scheiber MD, Liu JH, Subbiah MT,Rebar RW, Setchell KD (2001) Dietary inclusion of whole soy foods results in significant reductions in clinical risk factors for osteoporosis and cardiovascular disease in normal postmenopausal women. Menopause 8(5):384–392CrossRefPubMedGoogle Scholar
  14. 14.
    Potter SM, Baum JA, Teng H, Stillman RJ, Shay NF, Erdman JW Jr (1998) Soy protein and isoflavones: Their effect on blood lipids and bone density in postmenopausal women. Am J Clin Nutr 68(suppl):1375S–1379SPubMedGoogle Scholar
  15. 15.
    Alekel DL, St Germain A, Peterson CT, Hanson KB, Stewart JW, Toshiya T (2000) Isoflavone rich soy protein isolate attenuates bone loss in the lumbar spine of perimenopausal women. Am J Clin Nutr 72:844–852PubMedGoogle Scholar
  16. 16.
    Clifton-Bligh PB, Baber RJ, Fulcher GR, Nery ML, Moreton T (2001) The effect of isoflavones extracted from red clover (Rimostil) on lipid and bone metabolism. Menopause 8:S259–S265Google Scholar
  17. 17.
    Morabitu N, Crisafulla A, Vergara C, GaudioA, Lasco MA, Frisina N, D’Anna R, Corrado F, Pizzoleo MA, Cincotta M Altavilla D, Ientile R, Squadrito F (2002) Effects of genistein and hormone-replacement therapy on bone loss in early postmenopausal women: A randomized double-blind placebo-controlled study. J Bone Miner Res 17(10):1904–1912PubMedGoogle Scholar
  18. 18.
    Somekawa Y, Chiguchi M, Ishibashi T, Aso T (2001) Soy Intake Related to Menopausal Symptoms, Serum Lipids, and Bone Mineral Density in Postmenopausal Japanese Women. Obstet Gynecol 97(1):109–115PubMedGoogle Scholar
  19. 19.
    Mei J, Yeung SS, Kung AW (2001) High dietary phytoestrogen intake is associated with higher bone mineral density in postmenopausal but not premenopausal women. J Clin Endocrinol Metab 86(11):5217–5221Google Scholar
  20. 20.
    Gallagher JC, Rafferty K, Haynatzka V, Wilson M (2000) The effect of soy protein on bone metabolism. J Nutr 130:667S (abstr)Google Scholar
  21. 21.
    Vitolins M, Anthony M, Lenschik L, Bland DR, Burke GL (2002) Does Soy Protein and Its Isoflavones Prevent Bone Loss in Peri- and Postmenopausal Women? Results of a Two-Year Randomized Clinical Trial. J Nutr 132:582SGoogle Scholar
  22. 22.
    Prior JC, Vigna YM, Schechter MT, Burgess AE (1990) Spinal bone loss and ovulatory disturbances. N Engl J Med 323(18):S1221–S1227Google Scholar
  23. 23.
    Prior JC (1990) Progesterone as a Bone- Trophic Hormone. Endocrine Rev 11(2):S386–S398Google Scholar
  24. 24.
    Prior JC, Vigna YM, Alojado N (1991) Progesterone and the prevention of osteoporosis. Can J Ob/Gyn & Women’s Health Care 3(4):S178–S184Google Scholar
  25. 25.
    Lee JR (1991) Is Natural Progesterone the Missing Link in Osteoporosis Prevention and Treatment? Medical Hypotheses 35:314–316CrossRefGoogle Scholar
  26. 26.
    Leonetti HB, Longo S, Anasti JN (1999) Transdermal Progesterone Cream for Vasomotor Symptoms and Postmenopausal Bone loss. Obstet Gynec 94(2):225–228CrossRefPubMedGoogle Scholar
  27. 27.
    Potosky AL, Block G, Hartman AM (1990) The apparent validity of diet questionnaires is influenced by number of diet-record days used for comparison. J Am Diet Assoc 90:810–813PubMedGoogle Scholar
  28. 28.
    Nordisk Ministerråd (1996) Nordiska näringsrekommendationer. Nord 28, CopenhagenGoogle Scholar
  29. 29.
    Setchell KD,Welsh MB, Lim CK (1987) High-performance liquid chromatographic analysis of phytoestrogens in soy protein preparations with ultraviolet, electrochemical and thermospray mass spectrometric detection. J Chromatogr 386:315–323CrossRefPubMedGoogle Scholar
  30. 30.
    Omi N, Aoi S, Murata K, Ezawa I (1994) Evaluation of the effect of soybean milk peptide on bone metabolism in the rat model with ovariectomized osteoporosis. J Nutr Sci Vitaminol (Tokyo) 40:201–211PubMedGoogle Scholar
  31. 31.
    Arjmandi BH, Birnbaum R, Goyal NV, et al. (1998) Bonesparing effect of soy protein in ovarian hormone-deficient rats is related to its isoflavone content. Am J Clin Nutr 68:364S–368SGoogle Scholar
  32. 32.
    Arjmandi BH, Alekel L,Hollis BW, et al. (1996) Dietary soybean protein prevents bone loss in an ovariectomized rat model of osteoporosis. J Nutr 126:161–167PubMedGoogle Scholar
  33. 33.
    Arjmandi BH, Getlinger MJ, Goyal NV, et al. (1998) Role of soy protein with normal or reduced isoflavone content in reversing bone loss induced by ovarian deficiency in rats. Am J Clin Nutr 68(suppl):1358S–1363SPubMedGoogle Scholar
  34. 34.
    Picherit C, Coxam V, Bennetau-Peissero C, Kati-Coulibaly S, Davicco MJ, Lebecque P, Barlet JP (2000) Daidzein is more efficient than genistein in preventing ovariectomy-induced bone loss in rats. J Nutr 130(7):1675–1681PubMedGoogle Scholar
  35. 35.
    Viereck V, Grundker C, Blaschke S, Siggelkow H, Emons G, Hofbauer LC (2002) Phytoestrogen genistein stimulates the production of osteoprotegerin by human trabecular osteoblasts. J Cell Biol 84(4):725–735Google Scholar
  36. 36.
    Ishimi Y, Miyaura C, Ohmura M, Onoe Y, Sato T, Uchiyama Y, Ito M, Wang X, Suda T, Ikegami S (1999) Selective effects of genistein, a soybean isoflavone, on B-lymphopoiesis and bone loss caused by estrogen deficiency. Endocrinology 140(4):1893–1900CrossRefPubMedGoogle Scholar
  37. 37.
    Setchell KDR, Brown N, Lydeking-Olsen E (2002) Equol – the forgotten isoflavone may be the clue to the clinical effectiveness of soy and its isoflavones. J Nutr 132(12):3577–3584PubMedGoogle Scholar
  38. 38.
    Rowland IR, Wiseman H, Sanders TA, Adlercreutz H, Bowey EA (2000) Interindividual variation in metabolism of soy isoflavones and lignans: influence of habitual diet on equol production by the gut flora. J Nutr 36:27–32CrossRefGoogle Scholar
  39. 39.
    Lampe JW, Karr SC, Hutchins AM, Slavin JL (1998) Urinary equol excretion with a soy challenge: influence of habitual diet. Proc Soc Exp Biol Med 217:335–339PubMedGoogle Scholar
  40. 40.
    Marsh AG, Sanchez TV, Midkelsen O, Keiser J, Mayor G (1980) Cortical bone density of adult lacto-ovo-vegetarian and omnivorous women. J Am Diet Assoc 76(2):148–151PubMedGoogle Scholar
  41. 41.
    Marsh AG, Sanchez TV, Michelsen O, Chaffee FL, Fagal SM (1988) Vegetarian lifestyle and bone mineral density. Am J Clin Nutr 48(3 suppl):837–841PubMedGoogle Scholar
  42. 42.
    Tylavsky FA,Anderson JJ (1988) Dietary factors in bone health of elderly lactoovovegetarian and omnivorous women. Am J Clin Nutr 48(3S):842–849Google Scholar
  43. 43.
    Tesar R, Notelovitz M, Shim E, Kauwell G, Brown J (1992) Axial and peripheral bone density and nutrient intakes of postmenopausal vegetarian and omnivorous women. Am J Clin Nutr 56(4):699–704PubMedGoogle Scholar
  44. 44.
    Lloyd T, Schaeffer JM,Walker MA, Demers LM (1991) Urinary hormonal concentrations and spinal bone densities of premenopausal vegetarian and nonvegetarian women. Am J Clin Nutr 54(6):1005–1010PubMedGoogle Scholar
  45. 45.
    Spence LA, Lipscomb ER, Cadogan J, Martin BR, Peacock M, Weaver CM (2002) Effect of soy isoflavones on calcium metabolism in postmenopausal women. J Nutr 132:581S (abstr)Google Scholar
  46. 46.
    Lu L-JW,Anderson KE,Grady JE,Kohen F, Nagamani M (2000) Decreased Ovarian Hormones during a Soya Diet: Implication for Breast Cancer Prevention. Cancer Research 60(8):4112–4121PubMedGoogle Scholar
  47. 47.
    Persky VW, Turyk ME, Wang L, Freels S, Chatterton Jr R, Barnes S, Erdman Jr J, Sepkovic DW, Bradlow HL, Potter S (2002) Effect of soy protein on endogenous hormones in postmenopausal women. Am J Clin Nutr 75:145–153PubMedGoogle Scholar

Copyright information

© Steinkopff Verlag 2004

Authors and Affiliations

  • E. Lydeking–Olsen
    • 1
  • J.-E. Beck-Jensen
    • 2
  • K. D. R. Setchell
    • 3
  • T. Holm–Jensen
    • 1
  1. 1.Institute for Optimum NutritionCopenhagen KDenmark
  2. 2.The Osteoporosis and Metabolic Bone UnitDept. of Endocrinology Copenhagen University HospitalHvidovreDenmark
  3. 3.Clinical Mass SpectrometryChildren’s Hospital and Medical CenterCincinatti (OH)USA

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