Low-dose estrogen therapy for prevention of osteoporosis: Working our way back to monotherapy

Menopause

Volumn 13, Issue 1, 2006, Pages 148-155

  Richman, Susan ^a   Edusa, Valentine ^a   Fadiel, Ahmed ^a   Naftolin, Frederick ^a  

^a YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Bone; Estrogen; Fracture prevention; Menopause; Monotherapy

Indexed keywords

BISPHOSPHONIC ACID DERIVATIVE; CONJUGATED ESTROGEN; ESTROGEN; MEDROXYPROGESTERONE ACETATE; RALOXIFENE; SELECTIVE ESTROGEN RECEPTOR MODULATOR; GESTAGEN;

BONE DENSITY; CANCER RISK; CLINICAL TRIAL; COLORECTAL CANCER; ENDOMETRIUM HYPERPLASIA; ESTROGEN THERAPY; FIRST PASS EFFECT; FRACTURE; HUMAN; LOW DRUG DOSE; MONOTHERAPY; OSTEOLYSIS; POSTMENOPAUSE OSTEOPOROSIS; REVIEW; RISK REDUCTION; VASOMOTOR DISORDER; ARTICLE; COMPARATIVE STUDY; CONTROLLED CLINICAL TRIAL; DRUG EFFECT; FEMALE; INTRADERMAL DRUG ADMINISTRATION; MIDDLE AGED; RANDOMIZED CONTROLLED TRIAL; WOMEN'S HEALTH;

ADMINISTRATION, CUTANEOUS; BONE DENSITY; DIPHOSPHONATES; ESTROGEN REPLACEMENT THERAPY; ESTROGENS; FEMALE; HUMANS; MIDDLE AGED; OSTEOPOROSIS, POSTMENOPAUSAL; PROGESTINS; RALOXIFENE; RANDOMIZED CONTROLLED TRIALS; WOMEN'S HEALTH;

EID: 33646012340     PISSN: 10723714     EISSN: None     Source Type: Journal    
DOI: 10.1097/01.gme.0000191205.20738.01     Document Type: Review

References (73)

1. American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for the Prevention and Treatment of Postmenopausal Osteoporosis: 2001 edition, with selected updates for 2003. Endocr Pract 2003;9:544-564.
2. Cummings SR, Browner WS, Bauer D, et al. Endogenous hormones and the risk of hip and vertebral fractures among older women. N Engl J Med 1998;339:733-738.
3. Siris ES, Miller PD, Barrett-Connor E, et al. Identification and fracture outcomes of undiagnosed low bone mineral density in postmenopausal women. Results from the National Osteoporosis Risk Assessment. JAMA 2001;286:2815-2822.
4. National Osteoporosis Foundation. Osteoporosis: review of the evidence for prevention, diagnosis, and treatment and cost-effectiveness analysis. Osteoporos Int 1998;8:S1-S88.
5. Writing Group for the PEPI Trial. Effects of hormone therapy on bone mineral density: results from the Postmenopausal Estrogen/Progestin Interventions (PEPI) trial. JAMA 1996;276:1389-1396.
6. Torgerson DJ, Bell-Syer SE. Hormone replacement therapy and prevention of nonvertebral fractures: a meta-analysis of randomized trials. JAMA 2001;285:2891-2897.
7. Writing Group for the Women's Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women. JAMA 2002;288:321-333.
8. Anderson GL, Limacher M, Assaf AR, et al. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial. JAMA 2004;291:1701-1712.
9. Ettinger B, Grady D, Tosteson AN, Pressman A, Macer JL. Effect of the Women's Health Initiative on women's decisions to discontinue postmenopausal hormone therapy. Obstet Gynecol 2003;102:1225-1232.
10. Grady D, Ettinger B, Tosteson ANA, Pressman A, Macer JL. Predictors of difficulty when discontinuing postmenopausal hormone therapy. Obstet Gynecol 2003;102:1233-1239.
11. Gambrell RD Jr. Strategies to reduce the incidence of endometrial cancer in postmenopausal women. Am J Obstet Gynecol 1997;177:1196-1204.
12. Aitken JM, Hart DM, Lindsay R. Oestrogen replacement therapy for prevention of osteoporosis after oophorectomy. BMJ 1973;3:515-518.
13. Genant HK, Baylink DJ, Gallagher JC, Harris ST, Steiger P, Herber M. Effect of estrone sulfate on postmenopausal bone loss. Obstet Gynecol 1990;76:579-584.
14. Weiss NS, Ure CL, Ballard JH, Williams AR, Daling JR. Decreased risk of fractures of the hip and lower forearm with postmenopausal use of estrogen. N Engl J Med 1980;303:1195-1198.
15. Wells G, Tugwell P, Shea B, et al. Meta-analyses of therapies for postmenopausal osteoporosis, V: meta-analysis of the efficacy of hormone replacement therapy in treating and preventing osteoporosis in postmenopausal women. Endocr Rev 2002;23:529-539.
16. Naftolin F, Silver D. Is progestogen supplementation of ERT really necessary? Menopause 2002;9:1-2.
17. Harman SM, Brinton EA, Clarkson T, et al. Is the WHI relevant to HRT started in the perimenopause? Endocrine 2004;24:195-202.
18. Cauley JA, Robbins J, Chen Z, et al. Effects of estrogen plus progestin on risk of fracture and bone mineral density. The Women's Health Initiative Randomized Trial. JAMA 2003;290:1729-1738.
19. Writing Group of the IMS Executive Committee. Guidelines for the hormone treatment of women in the menopausal transition and beyond: position statement by the Executive Committee of the International Menopause Society. Climacteric 2004;7:8-11.
20. American College of Obstetricians and Gynecologists. Questions and answers on hormone therapy. In response to the Women's Health Initiative study results on estrogen and progestin hormone therapy. Available at: www.acog.com/from_home/publications/press_releases/nr08-30-02.cfm. Accessed January 22, 2004.
21. American College of Obstetricians and Gynecologists. Statement of the American College of Obstetricians and Gynecologists on hormone therapy for the prevention and treatment of postmenopausal osteoporosis. Available at: www.acog.com/from_home/publications/press_releases/nr10-07-03.cfm. Accessed January 22, 2004.
22. US Preventive Services Task Force. Agency for Healthcare Research and Quality. Chemoprevention. Hormone replacement therapy. Update, 2002 release. Available at: www.ahrq.gov/clinic/uspstf/uspspmho.htm. Accessed January 15, 2004.
23. NHLBI advisory for physicians on the WHI trial of conjugated equine estrogens versus placebo. Available at: http://www.nhlbi.nih.gov/whi/e- a_advisory.htm. Accessed April 9, 2004.
24. Naftolin F, Taylor HS, Karas R, et al. The Women's Health Initiative (WHI) could not have detected cardioprotective effects of starting hormone therapy during the menopausal transition. Fertil Steril 2004;81:1498-1501 .and/or estrogen-deprived/-replaced rats. J Bone Miner Res 1997;12:820-831.
25. Cranney A, Tugwell P, Adachi J, et al. Meta-analyses of therapies for postmenopausal osteoporosis, III: meta-analysis of risedronate for the treatment of postmenopausal osteoporosis. Endocr Rev 2002;23:517-523.
26. Cranney A, Wells G, Willan A, et al. II. Meta-analysis of alendronate for the treatment of postmenopausal women. Endocr Rev 2002;23:508-516.
27. Sickles JM, Nip CS. Risedronate for the prevention of fractures in postmenopausal osteoporosis. Ann Pharmacother 2002;36:664-670.
28. Cranney A, Tugwell P, Zytaruk N, et al. Meta-analyses of therapies for postmenopausal osteoporosis, IV: meta-analysis of raloxifene for the prevention and treatment of postmenopausal osteoporosis. Endocr Rev 2002;23:524-528.
29. Jolly EE, Bjarnason NH, Neven P, et al. Prevention of osteoporosis and uterine effects in postmenopausal women taking raloxifene for 5 years. Menopause 2003;10:337-344.
30. Ettinger B, Black DM, Mitlak BH, et al. Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators. JAMA 1999;282:637-645.
31. Delmas PD, Ensrud KE, Adachi JD, et al. Efficacy of raloxifene on vertebral fracture risk reduction in postmenopausal women with osteoporosis: four-year results from a randomized clinical trial. J Clin Endocrinol Metab 2002;87:3609-3617.
32. Ettinger B, Pressman A, Skalrin P, Bauer DC, Cauley JA, Cummings SR. Associations between low levels of serum estradiol, bone density, and fractures among elderly women: the study of osteoporotic fractures. J Clin Endocrinol Metab 1998;83:2239-2243.
33. Delmas PD, Pornel B, Felsenberg D, et al. Three-year follow-up of the use of transdermal 17β-estradiol matrix patches for the prevention of bone loss in early postmenopausal women. Am J Obstet Gynecol 2001;184:32-40.
34. Ettinger B, Genant HK, Steiger P, Madvig P. Low-dosage micronized 17 beta-estradiol prevents bone loss in postmenopausal women. Am J Obstet Gynecol 1992;166:479-488.
35. Evans SF, Davie MW. Low and conventional dose transdermal oestradiol are equally effective at preventing bone loss in spine and femur at all post-menopausal ages. Clin Endocrinol (Oxf) 1996;44:79-84.
36. Genant HK, Lucas J, Weiss S, et al. Low-dose esterified estrogen therapy: effects on bone, plasma estradiol concentrations, endometrium, and lipid levels. Estratab/Osteoporosis Study Group. Arch Intern Med 1997;157:2609-2615.
37. Lindsay R, Gallagher JC, Kleerekoper M, Pieckar JH. Effect of lower dosages of conjugated equine estrogen with and without medroxyprogesterone acetate on bone in early postmenopausal women. JAMA 2002;287:2668-2676.
38. Notelovitz M, John VA, Good WR. Effectiveness of Alora estradiol matrix transdermal delivery system in improving lumbar bone mineral density in healthy, postmenopausal women. Menopause 2002;9:343-353.
39. Prestwood KM, Kenny AM, Kleppinger A, Kulldorff M. Ultralow-dose micronized 17β-estradiol and bone density and bone metabolism in older women. A randomized controlled trial. JAMA 2003;290:1042-1048.
40. Recker RR, Davies KM, Dowd RM, Heaney RP. The effect of low-dose continuous estrogen and progesterone therapy with calcium and vitamin D on bone in elderly women. A randomized, controlled trial. Ann Intern Med 1999;130:897-904.
41. Weiss SR, Ellman H, Dolker M, for the Transdermal Estradiol Investigator Group. A randomized controlled trial of four doses of transdermal estradiol for preventing postmenopausal bone loss. Obstet Gynecol 1999;94:330-336.
42. Parsey K, Ellman H, Rahman M. Randomised, controlled comparison of transdermal estradiol with oral conjugated estrogens for the relief of hot flushes. The Transdermal Estradiol Investigators. Clin Drug Invest 2000;20:207-214.
43. Speroff L, Whitcomb RW, Kempfert NJ, Boyd RA, Paulissen JB, Rowan JP. Efficacy and local tolerance of a low-dose, 7-day matrix estradiol transdermal system in the treatment of menopausal vasomotor symptoms. Obstet Gynecol 1996;88:587-592.
44. Utian WH, Burry KA, Archer DF, et al. Efficacy and safety of low, standard, and high dosages of an estradiol transdermal system (Esclim) compared with placebo on vasomotor symptoms in highly symptomatic menopausal patients. The Esclim Study Group. Am J Obstet Gynecol 1999;181:71-79.
45. Utian WH, Shoupe D, Bachmann G, Pinkerton JV, Pickar JH. Relief of vasomotor symptoms and vaginal atrophy with lower doses of conjugated equine estrogens and medroxyprogesterone acetate. Fertil Steril 2001;75:1065-1079.
46. Prestwood KM, Kenny AM, Unson C, Kulldorff M. The effect of low dose micronized 17β-estradiol on bone turnover, sex hormone levels, and side effects in older women: a randomized, double blind, placebo-controlled study. J Clin Endocrinol Metab 2000;85:4462-4469.
47. Sharp CA, Evans SF, Risteli L, Risteli J, Worsfold M, Davie MWJ. Effects of low- and conventional-dose transcutaneous HRT over 2 years on bone metabolism in younger and older postmenopausal women. Eur J Clin Invest 1996;26:763-771.
48. AACE medical guidelines for clinical practice for management of menopause. Endocrinol Pract 1999;5:355-366.
49. Crook D, Cust MP, Gangar KF, et al. Comparison of transdermal and oral estrogen-progestin replacement therapy: effects on serum lipids and lipoproteins. Am J Obstet Gynecol 1992;66:950-955.
50. Erenus M, Karakoç B, Gürler A. Comparison of effects of continuous combined transdermal with oral estrogen and oral progestogen replacement therapies on serum lipoproteins and compliance. Climacteric 2001;4:228-234.
51. Shulman LP, Yankov V, Uhl K. Safety and efficacy of a continuous once-a-week 17β-estradiol/levonorgestrel transdermal system and its effects on vasomotor symptoms and endometrial safety in postmenopausal women: the results of two multicenter, double-blind, randomized, controlled trials. Menopause 2002;9:195-207.
52. Walsh BW, Paul S, Wild RA, et al. The effects of hormone replacement therapy and raloxifene on C-reactive protein and homocysteine in healthy postmenopausal women: a randomized, controlled trial. J Clin Endocrinol Metab 2000;85:214-218.
53. West SG, Hinderliter AL, Wells EC, Birdler SS, Light KC. Transdermal estrogen reduces vascular resistance and serum cholesterol in postmenopausal women. Am J Obstet Gynecol 2001;14:926-933.
54. Alfie J, Lugones L, Belardo A, et al. Hemodynamic effects of transdermal estradiol alone and combined with norethisterone acetate. Maturitas 1997;27:163-169.
55. Cacciatore B, Paakkari B, Hasselblatt R, et al. Randomized comparison between orally and transdermally administered hormone replacement therapy regimens of long-term effects on 24-hour ambulatory blood pressure in postmenopausal women. Am J Obstet Gynecol 2001;184:904-909.
56. Hoibraaten E, Abdelnoor M, Sandset PM. Hormone replacement therapy with estradiol and risk of venous thromboembolism: a population-based case-control study. Thromb Haemost 1999;82:1218-1221.
57. Beral V, Banks E, Reeves G. Evidence from randomized trials on the long-term effects of hormone replacement therapy. Lancet 2000;360:942-944.
58. Scarabin P-Y, Oger E, Plu-Bureau G, on behalf of the Estrogen and ThromboEmbolism Risk (ESTHER) Study Group. Differential association of oral and transdermal oestrogen-replacement therapy with venous thromboembolism risk. Lancet 2000;362:429-432.
59. Grodstein F, Colditz GA, Stampfer MJ. Postmenopausal hormone use and cholecystectomy in a large prospective study. Obstet Gynecol 1994;83:5-11.
60. Simon JA, Hunninghake DB, Agarwal SK, et al. Effect of estrogen plus progestin on risk for biliary tract surgery in postmenopausal women with coronary artery disease. The Heart and Estrogen/Progestin Replacement Study. Ann Intern Med 2001;135:493-501.
61. Van Erpecum KJ, Van Berge Henegouwen GP, Vershoor L, Stoelwinder B, Willekens FLH. Different hepatobiliary effects of oral and transdermal estradiol in postmenopausal women. Gastroenterology 1991;100:482-488.
62. Cooper C, Stakkestad JA, Radowicki W, et al. Matrix delivery transdermal 17β-estradiol for the prevention of bone loss in postmenopausal women. Osteoporosis Int 1999;9:358-366.
63. Arrenbrecht S, Boermans WJM. Effects of transdermal estradiol delivered by a matrix patch on bone density in hysterectomized, postmenopausal women: a 2-year placebo-controlled trial. Osteoporos Int 2002;13:176-183.
64. Santen RJ. Risk of breast cancer with progestins: critical assessment of current data. Steroids 2003;68:953-964.
65. Pickar JH, Thorneycroft I, Whitehead M. Effects of hormone replacement therapy on the endometrium and lipid parameters: a review of randomized clinical trials, 1985 to 1995. Am J Obstet Gynecol 1998;178:1087-1099.
66. Writing Group for the PEPI Trial. Effects of hormone replacement therapy on endometrial histology in postmenopausal women: the Postmenopausal Estrogen/Progestin Interventions (PEPI) trial. JAMA 1996;275:370-375.
67. Woodruff JD, Pickar JH. Incidence of endometrial hyperplasia in postmenopausal women taking conjugated estrogens (Premarin) with medroxyprogesterone acetate or conjugated estrogens alone. The Menopause Study Group. Am J Obstet Gynecol 1994;170:1213-1223.
68. Pickar JH, Yeh I-T, Wheeler JE, Cunnane MF, Speroff L. Endometrial effects of lower doses of conjugated estrogens and medroxyprogesterone acetate. Fertil Steril 2001;76:25-31.
69. Ahotupa M, Rauramo I, Vasankari TJ, Skouby SO, Hakonen T. Estrogen replacement therapy in combination with continuous intrauterine progestin administration reduces the amount of circulating oxidized LDL in postmenopausal women: dependence on the dose of progestin. Ann Med 2004;36:278-284.
70. Naessen T, Rodriguez-Macias K. Endometrial thickness and uterine diameter not affected by ultralow doses of 17β-estradiol in elderly women. Am J Obstet Gynecol 2002;186:944-947.
71. Weiderpass E, Baron JA, Adami HO, et al. Low potency oestrogen and risk of endometrial cancer: a case control study. Lancet 1999;353:1824-1828.
72. Cushing AL, Weiss NS, Voigt LF, McKnight B, Beresford SAA. Risk of endometrial cancer in relation to use of low-dose, unopposed estrogens. Obstet Gynecol 1998;91:35-39.
73. Ieannidis JP, Ralston SH, Bennett S, et al. Differential genetic effects of ESRI gene polymorphisms on osteoporosis outcomes. JAMA 2004;292:2105-2114.