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Erschienen in: Osteoporosis International 1/2010

01.01.2010 | Original Article

Baseline serum estradiol and fracture reduction during treatment with hormone therapy: The Women's Health Initiative randomized trial

verfasst von: J. A. Cauley, A. Z. LaCroix, J. A. Robbins, J. Larson, R. Wallace, J. Wactawski-Wende, Z. Chen, D. C. Bauer, S. R. Cummings, R. Jackson

Erschienen in: Osteoporosis International | Ausgabe 1/2010

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Abstract

Introduction

The purpose of the study was to test the hypothesis that the reduction in fractures with hormone therapy (HT) is greater in women with lower estradiol levels.

Methods

We conducted a nested case–control study within the Women's Health Initiative HT Trials. The sample included 231 hip fracture case–control pairs and a random sample of 519 all fracture case–control pairs. Cases and controls were matched for age, ethnicity, randomization date, fracture history, and hysterectomy status. Hormones were measured prior to randomization. Incident cases of fracture were identified over an average follow-up of 6.53 years.

Results

There was no evidence that the effect of HT on fracture differed by baseline estradiol (E2) or sex hormone binding globulin (SHBG). Across all quartiles of E2 and SHBG, women randomized to HT had about a 50% lower risk of fracture, including hip fracture, compared to placebo.

Conclusion

The effect of HT on fracture reduction is independent of estradiol and SHBG levels.
Literatur
1.
Zurück zum Zitat Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, Jackson RD, Beresford SA, Howard BV, Johnson KC, Kotchen JM, Ockene J (2002) Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA 288:321–333CrossRefPubMed Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, Jackson RD, Beresford SA, Howard BV, Johnson KC, Kotchen JM, Ockene J (2002) Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA 288:321–333CrossRefPubMed
2.
Zurück zum Zitat Anderson GL, Limacher M, Assaf AR, Bassford T, Beresford SA, Black H, Bonds D, Brunner R, Brzyski R, Caan B, Chlebowski R, Curb D, Gass M, Hays J, Heiss G, Hendrix S, Howard BV, Hsia J, Hubbell A, Jackson R, Johnson KC, Judd H, Kotchen JM, Kuller L, LaCroix AZ, Lane D, Langer RD, Lasser N, Lewis CE, Manson J, Margolis K, Ockene J, O'Sullivan MJ, Phillips L, Prentice RL, Ritenbaugh C, Robbins J, Rossouw JE, Sarto G, Stefanick ML, Van Horn L, Wactawski-Wende J, Wallace R, Wassertheil-Smoller S (2004) Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial. JAMA 291:1701–1712CrossRefPubMed Anderson GL, Limacher M, Assaf AR, Bassford T, Beresford SA, Black H, Bonds D, Brunner R, Brzyski R, Caan B, Chlebowski R, Curb D, Gass M, Hays J, Heiss G, Hendrix S, Howard BV, Hsia J, Hubbell A, Jackson R, Johnson KC, Judd H, Kotchen JM, Kuller L, LaCroix AZ, Lane D, Langer RD, Lasser N, Lewis CE, Manson J, Margolis K, Ockene J, O'Sullivan MJ, Phillips L, Prentice RL, Ritenbaugh C, Robbins J, Rossouw JE, Sarto G, Stefanick ML, Van Horn L, Wactawski-Wende J, Wallace R, Wassertheil-Smoller S (2004) Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial. JAMA 291:1701–1712CrossRefPubMed
3.
Zurück zum Zitat Cauley JA, Robbins J, Chen Z, Cummings SR, Jackson RD, LaCroix AZ, LeBoff M, Lewis CE, McGowan J, Neuner J, Pettinger M, Stefanick ML, Wactawski-Wende J, Watts NB (2003) Effects of estrogen plus progestin on risk of fracture and bone mineral density: the Women's Health Initiative randomized trial. Jama 290:1729–1738CrossRefPubMed Cauley JA, Robbins J, Chen Z, Cummings SR, Jackson RD, LaCroix AZ, LeBoff M, Lewis CE, McGowan J, Neuner J, Pettinger M, Stefanick ML, Wactawski-Wende J, Watts NB (2003) Effects of estrogen plus progestin on risk of fracture and bone mineral density: the Women's Health Initiative randomized trial. Jama 290:1729–1738CrossRefPubMed
4.
Zurück zum Zitat Jackson RD, Wactawski-Wende J, LaCroix AZ, Pettinger M, Yood RA, Watts NB, Robbins JA, Lewis CE, Beresford SA, Ko MG, Naughton MJ, Satterfield S, Bassford T (2006) Effects of conjugated equine estrogen on risk of fractures and BMD in postmenopausal women with hysterectomy: results from the women's health initiative randomized trial. J Bone Miner Res 21:817–828CrossRefPubMed Jackson RD, Wactawski-Wende J, LaCroix AZ, Pettinger M, Yood RA, Watts NB, Robbins JA, Lewis CE, Beresford SA, Ko MG, Naughton MJ, Satterfield S, Bassford T (2006) Effects of conjugated equine estrogen on risk of fractures and BMD in postmenopausal women with hysterectomy: results from the women's health initiative randomized trial. J Bone Miner Res 21:817–828CrossRefPubMed
5.
Zurück zum Zitat The North American Menopause Society (2008) Estrogen and progestogen use in postmenopausal women: July 2008 position statement of The North American Menopause Society. Menopause: The Journal of The North American Menopause Society 15:584 The North American Menopause Society (2008) Estrogen and progestogen use in postmenopausal women: July 2008 position statement of The North American Menopause Society. Menopause: The Journal of The North American Menopause Society 15:584
6.
Zurück zum Zitat Rapuri PB, Gallagher JC, Haynatzki G (2004) 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 89:4954–4962CrossRefPubMed Rapuri PB, Gallagher JC, Haynatzki G (2004) 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 89:4954–4962CrossRefPubMed
7.
Zurück zum Zitat Huang AJ, Ettinger B, Vittinghoff E, Ensrud KE, Johnson KC, Cummings SR (2007) Endogenous estrogen levels and the effects of ultra-low-dose transdermal estradiol therapy on bone turnover and BMD in postmenopausal women. J Bone Miner Res 22:1791–1797CrossRefPubMed Huang AJ, Ettinger B, Vittinghoff E, Ensrud KE, Johnson KC, Cummings SR (2007) Endogenous estrogen levels and the effects of ultra-low-dose transdermal estradiol therapy on bone turnover and BMD in postmenopausal women. J Bone Miner Res 22:1791–1797CrossRefPubMed
8.
Zurück zum Zitat (1998) Design of the Women's Health Initiative clinical trial and observational study. The Women's Health Initiative Study Group. Control Clin Trials 19:61–109. (1998) Design of the Women's Health Initiative clinical trial and observational study. The Women's Health Initiative Study Group. Control Clin Trials 19:61–109.
9.
Zurück zum Zitat Hays J, Hunt JR, Hubbell FA, Anderson GL, Limacher M, Allen C, Rossouw JE (2003) The Women's Health Initiative recruitment methods and results. Ann Epidemiol 13:S18–S77CrossRefPubMed Hays J, Hunt JR, Hubbell FA, Anderson GL, Limacher M, Allen C, Rossouw JE (2003) The Women's Health Initiative recruitment methods and results. Ann Epidemiol 13:S18–S77CrossRefPubMed
10.
Zurück zum Zitat Anderson GL, Manson J, Wallace R, Lund B, Hall D, Davis S, Shumaker S, Wang CY, Stein E, Prentice RL (2003) Implementation of the Women's Health Initiative study design. Ann Epidemiol 13:S5–S17CrossRefPubMed Anderson GL, Manson J, Wallace R, Lund B, Hall D, Davis S, Shumaker S, Wang CY, Stein E, Prentice RL (2003) Implementation of the Women's Health Initiative study design. Ann Epidemiol 13:S5–S17CrossRefPubMed
11.
Zurück zum Zitat Probst-Hensch NM, Ingles SA, Diep AT, Haile RW, Stanczyk FZ, Kolonel LN, Henderson BE (1999) Aromatase and breast cancer susceptibility. Endocr Relat Cancer 6:165–173CrossRefPubMed Probst-Hensch NM, Ingles SA, Diep AT, Haile RW, Stanczyk FZ, Kolonel LN, Henderson BE (1999) Aromatase and breast cancer susceptibility. Endocr Relat Cancer 6:165–173CrossRefPubMed
12.
Zurück zum Zitat Goebelsmann U, Stanczyk FZ, Brenner PF, Goebelsmann AE, Gentzschein EK, Mishell DR Jr (1979) Serum norethindrone (NET) concentrations following intramuscular NET enanthate injection. Effect upon serum LH, FSH, estradiol and progesterone. Contraception 19:283–313CrossRefPubMed Goebelsmann U, Stanczyk FZ, Brenner PF, Goebelsmann AE, Gentzschein EK, Mishell DR Jr (1979) Serum norethindrone (NET) concentrations following intramuscular NET enanthate injection. Effect upon serum LH, FSH, estradiol and progesterone. Contraception 19:283–313CrossRefPubMed
13.
Zurück zum Zitat Sodergard R, Backstrom T, Shanbhag V, Carstensen H (1982) Calculation of free and bound fractions of testosterone and estradiol-17 beta to human plasma proteins at body temperature. J Steroid Biochem 16:801–810CrossRefPubMed Sodergard R, Backstrom T, Shanbhag V, Carstensen H (1982) Calculation of free and bound fractions of testosterone and estradiol-17 beta to human plasma proteins at body temperature. J Steroid Biochem 16:801–810CrossRefPubMed
14.
Zurück zum Zitat Vermeulen A, Verdonck L, Kaufman JM (1999) A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab 84:3666–3672CrossRefPubMed Vermeulen A, Verdonck L, Kaufman JM (1999) A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab 84:3666–3672CrossRefPubMed
15.
Zurück zum Zitat Sipila S, Heikkinen E, Cheng S, Suominen H, Saari P, Kovanen V, Alen M, Rantanen T (2006) Endogenous hormones, muscle strength, and risk of fall-related fractures in older women. J Gerontol A Biol Sci Med Sci 61:92–96PubMed Sipila S, Heikkinen E, Cheng S, Suominen H, Saari P, Kovanen V, Alen M, Rantanen T (2006) Endogenous hormones, muscle strength, and risk of fall-related fractures in older women. J Gerontol A Biol Sci Med Sci 61:92–96PubMed
16.
Zurück zum Zitat Rinaldi S, Dechaud H, Toniolo P, Kaaks R (2002) Reliability and validity of direct radioimmunoassays for measurement of postmenopausal serum androgens and estrogens. IARC Sci Publ 156:323–325PubMed Rinaldi S, Dechaud H, Toniolo P, Kaaks R (2002) Reliability and validity of direct radioimmunoassays for measurement of postmenopausal serum androgens and estrogens. IARC Sci Publ 156:323–325PubMed
17.
Zurück zum Zitat Robbins J, Aragaki A, Kiiperberg C, Watts N, Wactawski-Wende J, Jackson R, Lewis C, Chen Z, Stefanick M, Cauley JA (2007) Factors associated five year risk of hip fracture in postmenopausal women: WHI. JAMA 298:2389–2398CrossRefPubMed Robbins J, Aragaki A, Kiiperberg C, Watts N, Wactawski-Wende J, Jackson R, Lewis C, Chen Z, Stefanick M, Cauley JA (2007) Factors associated five year risk of hip fracture in postmenopausal women: WHI. JAMA 298:2389–2398CrossRefPubMed
18.
Zurück zum Zitat Cummings SR (2002) How drugs decrease fracture risk: lessons from trials. J Musculoskelet Neuronal Interact 2:198–200PubMed Cummings SR (2002) How drugs decrease fracture risk: lessons from trials. J Musculoskelet Neuronal Interact 2:198–200PubMed
19.
Zurück zum Zitat Cummings SR, Karpf DB, Harris F, Genant HK, Ensrud K, LaCroix AZ, Black DM (2002) Improvement in spine bone density and reduction in risk of vertebral fractures during treatment with antiresorptive drugs. Am J Med 112:281–289CrossRefPubMed Cummings SR, Karpf DB, Harris F, Genant HK, Ensrud K, LaCroix AZ, Black DM (2002) Improvement in spine bone density and reduction in risk of vertebral fractures during treatment with antiresorptive drugs. Am J Med 112:281–289CrossRefPubMed
20.
Zurück zum Zitat Sarkar S, Mitlak BH, Wong M, Stock JL, Black DM, Harper KD (2002) Relationships between bone mineral density and incident vertebral fracture risk with raloxifene therapy. J Bone Miner Res 17:1–10CrossRefPubMed Sarkar S, Mitlak BH, Wong M, Stock JL, Black DM, Harper KD (2002) Relationships between bone mineral density and incident vertebral fracture risk with raloxifene therapy. J Bone Miner Res 17:1–10CrossRefPubMed
21.
Zurück zum Zitat Cummings SR, Melton LJ (2002) Epidemiology and outcomes of osteoporotic fractures. Lancet 359:1761–1767CrossRefPubMed Cummings SR, Melton LJ (2002) Epidemiology and outcomes of osteoporotic fractures. Lancet 359:1761–1767CrossRefPubMed
22.
Zurück zum Zitat Cummings SR, Duong T, Kenyon E, Cauley JA, Whitehead M, Krueger KA (2002) Serum estradiol level and risk of breast cancer during treatment with raloxifene. JAMA 287:216–220CrossRefPubMed Cummings SR, Duong T, Kenyon E, Cauley JA, Whitehead M, Krueger KA (2002) Serum estradiol level and risk of breast cancer during treatment with raloxifene. JAMA 287:216–220CrossRefPubMed
23.
Zurück zum Zitat Lee JS, LaCroix AZ, Wu L, Cauley JA, Jackson RD, Kooperberg C, Leboff MS, Robbins J, Lewis CE, Bauer DC, Cummings SR (2008) Associations of serum sex hormone-binding globulin and sex hormone concentrations with hip fracture risk in postmenopausal women. J Clin Endocrinol Metab 93:1796–1803CrossRefPubMed Lee JS, LaCroix AZ, Wu L, Cauley JA, Jackson RD, Kooperberg C, Leboff MS, Robbins J, Lewis CE, Bauer DC, Cummings SR (2008) Associations of serum sex hormone-binding globulin and sex hormone concentrations with hip fracture risk in postmenopausal women. J Clin Endocrinol Metab 93:1796–1803CrossRefPubMed
24.
Zurück zum Zitat Kahn SM, Hryb DJ, Nakhla AM, Romas NA, Rosner W (2002) Sex hormone-binding globulin is synthesized in target cells. J Endocrinol 175:113–120CrossRefPubMed Kahn SM, Hryb DJ, Nakhla AM, Romas NA, Rosner W (2002) Sex hormone-binding globulin is synthesized in target cells. J Endocrinol 175:113–120CrossRefPubMed
25.
Zurück zum Zitat Hammes A, Andreassen TK, Spoelgen R, Raila J, Hubner N, Schulz H, Metzger J, Schweigert FJ, Luppa PB, Nykjaer A, Willnow TE (2005) Role of endocytosis in cellular uptake of sex steroids. Cell 122:751–762CrossRefPubMed Hammes A, Andreassen TK, Spoelgen R, Raila J, Hubner N, Schulz H, Metzger J, Schweigert FJ, Luppa PB, Nykjaer A, Willnow TE (2005) Role of endocytosis in cellular uptake of sex steroids. Cell 122:751–762CrossRefPubMed
26.
Zurück zum Zitat Khosla S (2006) Editorial: sex hormone binding globulin: inhibitor or facilitator (or both) of sex steroid action? J Clin Endocrinol Metab 91:4764–4766CrossRefPubMed Khosla S (2006) Editorial: sex hormone binding globulin: inhibitor or facilitator (or both) of sex steroid action? J Clin Endocrinol Metab 91:4764–4766CrossRefPubMed
27.
Zurück zum Zitat Rosner W, Hryb DJ, Khan MS, Nakhla AM, Romas NA (1999) Sex hormone-binding globulin mediates steroid hormone signal transduction at the plasma membrane. J Steroid Biochem Mol Biol 69:481–485CrossRefPubMed Rosner W, Hryb DJ, Khan MS, Nakhla AM, Romas NA (1999) Sex hormone-binding globulin mediates steroid hormone signal transduction at the plasma membrane. J Steroid Biochem Mol Biol 69:481–485CrossRefPubMed
28.
Zurück zum Zitat Shifren JL, Rifai N, Desindes S, McIlwain M, Doros G, Mazer NA (2008) A comparison of the short-term effects of oral conjugated equine estrogens versus transdermal estradiol on C-reactive protein, other serum markers of inflammation, and other hepatic proteins in naturally menopausal women. J Clin Endocrinol Metab 93:1702–1710CrossRefPubMed Shifren JL, Rifai N, Desindes S, McIlwain M, Doros G, Mazer NA (2008) A comparison of the short-term effects of oral conjugated equine estrogens versus transdermal estradiol on C-reactive protein, other serum markers of inflammation, and other hepatic proteins in naturally menopausal women. J Clin Endocrinol Metab 93:1702–1710CrossRefPubMed
29.
Zurück zum Zitat Bjornerem A, Ahmed LA, Joakimsen RM, Berntsen GK, Fonnebo V, Jorgensen L, Oian P, Seeman E, Straume B (2007) A prospective study of sex steroids, sex hormone-binding globulin, and non-vertebral fractures in women and men: the Tromso Study. Eur J Endocrinol 157:119–125CrossRefPubMed Bjornerem A, Ahmed LA, Joakimsen RM, Berntsen GK, Fonnebo V, Jorgensen L, Oian P, Seeman E, Straume B (2007) A prospective study of sex steroids, sex hormone-binding globulin, and non-vertebral fractures in women and men: the Tromso Study. Eur J Endocrinol 157:119–125CrossRefPubMed
30.
Zurück zum Zitat Garnero P, Sornay-Rendu E, Claustrat B, Delmas PD (2000) Biochemical markers of bone turnover, endogenous hormones and the risk of fractures in postmenopausal women: the OFELY study. J Bone Miner Res 15:1526–1536CrossRefPubMed Garnero P, Sornay-Rendu E, Claustrat B, Delmas PD (2000) Biochemical markers of bone turnover, endogenous hormones and the risk of fractures in postmenopausal women: the OFELY study. J Bone Miner Res 15:1526–1536CrossRefPubMed
31.
Zurück zum Zitat Chapurlat RD, Garnero P, Breart G, Meunier PJ, Delmas PD (2000) Serum estradiol and sex hormone-binding globulin and the risk of hip fracture in elderly women: the EPIDOS study. J Bone Miner Res 15:1835–1841CrossRefPubMed Chapurlat RD, Garnero P, Breart G, Meunier PJ, Delmas PD (2000) Serum estradiol and sex hormone-binding globulin and the risk of hip fracture in elderly women: the EPIDOS study. J Bone Miner Res 15:1835–1841CrossRefPubMed
32.
Zurück zum Zitat Kuchuk NO, van Schoor NM, Pluijm SM, Smit JH, de Ronde W, Lips P (2007) The association of sex hormone levels with quantitative ultrasound, bone mineral density, bone turnover and osteoporotic fractures in older men and women. Clin Endocrinol (Oxf) 67:295–303CrossRef Kuchuk NO, van Schoor NM, Pluijm SM, Smit JH, de Ronde W, Lips P (2007) The association of sex hormone levels with quantitative ultrasound, bone mineral density, bone turnover and osteoporotic fractures in older men and women. Clin Endocrinol (Oxf) 67:295–303CrossRef
33.
Zurück zum Zitat Goderie-Plomp HW, van der Klift M, de Ronde W, Hofman A, de Jong FH, Pols HA (2004) 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 89:3261–3269CrossRefPubMed Goderie-Plomp HW, van der Klift M, de Ronde W, Hofman A, de Jong FH, Pols HA (2004) 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 89:3261–3269CrossRefPubMed
34.
Zurück zum Zitat Cummings SR, Browner WS, Bauer D, Stone K, Ensrud K, Jamal S, Ettinger B (1998) Endogenous hormones and the risk of hip and vertebral fractures among older women. Study of Osteoporotic Fractures Research Group. N Engl J Med 339:733–738CrossRefPubMed Cummings SR, Browner WS, Bauer D, Stone K, Ensrud K, Jamal S, Ettinger B (1998) Endogenous hormones and the risk of hip and vertebral fractures among older women. Study of Osteoporotic Fractures Research Group. N Engl J Med 339:733–738CrossRefPubMed
Metadaten
Titel
Baseline serum estradiol and fracture reduction during treatment with hormone therapy: The Women's Health Initiative randomized trial
verfasst von
J. A. Cauley
A. Z. LaCroix
J. A. Robbins
J. Larson
R. Wallace
J. Wactawski-Wende
Z. Chen
D. C. Bauer
S. R. Cummings
R. Jackson
Publikationsdatum
01.01.2010
Verlag
Springer-Verlag
Erschienen in
Osteoporosis International / Ausgabe 1/2010
Print ISSN: 0937-941X
Elektronische ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-009-0953-7

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