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. 1992 Mar;42(356):120–125.

Hormone replacement therapy and breast cancer, endometrial cancer and cardiovascular disease: risks and benefits.

M K Goddard 1
PMCID: PMC1371997  PMID: 1493029

Abstract

The relatively restricted use of hormone replacement therapy in the United Kingdom has frequently been noted. It is possible that low prescribing rates may, in part, be due to the difficulty in interpreting the wealth of research evidence relating to the risks and benefits of hormone replacement therapy. Conflicting conclusions from research can cause considerable uncertainty and confusion. This paper reviews the evidence relating to hormone replacement therapy and the risks of breast cancer, endometrial cancer and cardiovascular disease and discusses the issues which require critical assessment. This should add to the information base available to general practitioners and thus assist in decision-making in the context of uncertainty.

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Selected References

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  1. Adam S., Williams V., Vessey M. P. Cardiovascular disease and hormone replacement treatment: a pilot case-control study. Br Med J (Clin Res Ed) 1981 Apr 18;282(6272):1277–1278. doi: 10.1136/bmj.282.6272.1277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Antunes C. M., Strolley P. D., Rosenshein N. B., Davies J. L., Tonascia J. A., Brown C., Burnett L., Rutledge A., Pokempner M., Garcia R. Endometrial cancer and estrogen use. Report of a large case-control study. N Engl J Med. 1979 Jan 4;300(1):9–13. doi: 10.1056/NEJM197901043000103. [DOI] [PubMed] [Google Scholar]
  3. Bain C., Willett W., Hennekens C. H., Rosner B., Belanger C., Speizer F. E. Use of postmenopausal hormones and risk of myocardial infarction. Circulation. 1981 Jul;64(1):42–46. doi: 10.1161/01.cir.64.1.42. [DOI] [PubMed] [Google Scholar]
  4. Barrett-Connor E. Postmenopausal estrogen replacement and breast cancer. N Engl J Med. 1989 Aug 3;321(5):319–320. doi: 10.1056/NEJM198908033210510. [DOI] [PubMed] [Google Scholar]
  5. Belchetz P. Hormone replacement treatment. BMJ. 1989 Jun 3;298(6686):1467–1468. doi: 10.1136/bmj.298.6686.1467. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bergkvist L., Adami H. O., Persson I., Hoover R., Schairer C. The risk of breast cancer after estrogen and estrogen-progestin replacement. N Engl J Med. 1989 Aug 3;321(5):293–297. doi: 10.1056/NEJM198908033210505. [DOI] [PubMed] [Google Scholar]
  7. Bergkvist L., Persson I., Adami H. O., Schairer C. Risk factors for breast and endometrial cancer in a cohort of women treated with menopausal oestrogens. Int J Epidemiol. 1988 Dec;17(4):732–737. doi: 10.1093/ije/17.4.732. [DOI] [PubMed] [Google Scholar]
  8. Brinton L. A., Hoover R., Fraumeni J. F., Jr Menopausal oestrogens and breast cancer risk: an expanded case-control study. Br J Cancer. 1986 Nov;54(5):825–832. doi: 10.1038/bjc.1986.246. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Bryce F. C., Lilford R. J. General practitioners use of hormone-replacement therapy in Yorkshire. Eur J Obstet Gynecol Reprod Biol. 1990 Oct;37(1):55–61. doi: 10.1016/0028-2243(90)90095-i. [DOI] [PubMed] [Google Scholar]
  10. Burch J. C., Byrd B. F., Jr, Vaughn W. K. The effects of long-term estrogen on hysterectomized women. Am J Obstet Gynecol. 1974 Mar 15;118(6):778–782. doi: 10.1016/0002-9378(74)90487-6. [DOI] [PubMed] [Google Scholar]
  11. Buring J. E., Bain C. J., Ehrmann R. L. Conjugated estrogen use and risk of endometrial cancer. Am J Epidemiol. 1986 Sep;124(3):434–441. doi: 10.1093/oxfordjournals.aje.a114414. [DOI] [PubMed] [Google Scholar]
  12. Buring J. E., Hennekens C. H., Lipnick R. J., Willett W., Stampfer M. J., Rosner B., Peto R., Speizer F. E. A prospective cohort study of postmenopausal hormone use and risk of breast cancer in US women. Am J Epidemiol. 1987 Jun;125(6):939–947. doi: 10.1093/oxfordjournals.aje.a114632. [DOI] [PubMed] [Google Scholar]
  13. Bush T. L., Barrett-Connor E., Cowan L. D., Criqui M. H., Wallace R. B., Suchindran C. M., Tyroler H. A., Rifkind B. M. Cardiovascular mortality and noncontraceptive use of estrogen in women: results from the Lipid Research Clinics Program Follow-up Study. Circulation. 1987 Jun;75(6):1102–1109. doi: 10.1161/01.cir.75.6.1102. [DOI] [PubMed] [Google Scholar]
  14. Colditz G. A., Stampfer M. J., Willett W. C., Hennekens C. H., Rosner B., Speizer F. E. Prospective study of estrogen replacement therapy and risk of breast cancer in postmenopausal women. JAMA. 1990 Nov 28;264(20):2648–2653. [PubMed] [Google Scholar]
  15. Colditz G. A., Willett W. C., Stampfer M. J., Rosner B., Speizer F. E., Hennekens C. H. Menopause and the risk of coronary heart disease in women. N Engl J Med. 1987 Apr 30;316(18):1105–1110. doi: 10.1056/NEJM198704303161801. [DOI] [PubMed] [Google Scholar]
  16. Coope J., Roberts D. A clinic for the prevention of osteoporosis in general practice. Br J Gen Pract. 1990 Jul;40(336):295–299. [PMC free article] [PubMed] [Google Scholar]
  17. Gambrell R. D., Jr, Maier R. C., Sanders B. I. Decreased incidence of breast cancer in postmenopausal estrogen-progestogen users. Obstet Gynecol. 1983 Oct;62(4):435–443. [PubMed] [Google Scholar]
  18. Garnett T., Mitchell A., Studd J. Patterns of referral to a menopause clinic. J R Soc Med. 1991 Mar;84(3):128–130. doi: 10.1177/014107689108400304. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Gordon T., Kannel W. B., Hjortland M. C., McNamara P. M. Menopause and coronary heart disease. The Framingham Study. Ann Intern Med. 1978 Aug;89(2):157–161. doi: 10.7326/0003-4819-89-2-157. [DOI] [PubMed] [Google Scholar]
  20. Gray L. A., Sr, Christopherson W. M., Hoover R. N. Estrogens and endometrial carcinoma. Obstet Gynecol. 1977 Apr;49(4):385–389. [PubMed] [Google Scholar]
  21. Hammond C. B., Jelovsek F. R., Lee K. L., Creasman W. T., Parker R. T. Effects of long-term estrogen replacement therapy. I. Metabolic effects. Am J Obstet Gynecol. 1979 Mar 1;133(5):525–536. doi: 10.1016/0002-9378(79)90288-6. [DOI] [PubMed] [Google Scholar]
  22. Henderson B. E., Casagrande J. T., Pike M. C., Mack T., Rosario I., Duke A. The epidemiology of endometrial cancer in young women. Br J Cancer. 1983 Jun;47(6):749–756. doi: 10.1038/bjc.1983.127. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Henderson B. E., Paganini-Hill A., Ross R. K. Estrogen replacement therapy and protection from acute myocardial infarction. Am J Obstet Gynecol. 1988 Aug;159(2):312–317. doi: 10.1016/s0002-9378(88)80074-7. [DOI] [PubMed] [Google Scholar]
  24. Henderson B. E., Ross R. K., Paganini-Hill A., Mack T. M. Estrogen use and cardiovascular disease. Am J Obstet Gynecol. 1986 Jun;154(6):1181–1186. doi: 10.1016/0002-9378(86)90696-4. [DOI] [PubMed] [Google Scholar]
  25. Hernandez Avila M., Walker A. M., Jick H. Use of replacement estrogens and the risk of myocardial infarction. Epidemiology. 1990 Mar;1(2):128–133. doi: 10.1097/00001648-199003000-00008. [DOI] [PubMed] [Google Scholar]
  26. Hiatt R. A., Bawol R., Friedman G. D., Hoover R. Exogenous estrogen and breast cancer after bilateral oophorectomy. Cancer. 1984 Jul 1;54(1):139–144. doi: 10.1002/1097-0142(19840701)54:1<139::aid-cncr2820540128>3.0.co;2-x. [DOI] [PubMed] [Google Scholar]
  27. Holzman G. B., Ravitch M. M., Metheny W., Rothert M. L., Holmes M., Hoppe R. B. Physicians' judgments about estrogen replacement therapy for menopausal women. Obstet Gynecol. 1984 Mar;63(3):303–311. [PubMed] [Google Scholar]
  28. Hoover R., Glass A., Finkle W. D., Azevedo D., Milne K. Conjugated estrogens and breast cancer risk in women. J Natl Cancer Inst. 1981 Oct;67(4):815–820. [PubMed] [Google Scholar]
  29. Horwitz R. I., Feinstein A. R. Alternative analytic methods for case-control studies of estrogens and endometrial cancer. N Engl J Med. 1978 Nov 16;299(20):1089–1094. doi: 10.1056/NEJM197811162992001. [DOI] [PubMed] [Google Scholar]
  30. Hulka B. S., Chambless L. E., Deubner D. C., Wilkinson W. E. Breast cancer and estrogen replacement therapy. Am J Obstet Gynecol. 1982 Jul 15;143(6):638–644. doi: 10.1016/0002-9378(82)90108-9. [DOI] [PubMed] [Google Scholar]
  31. Hulka B. S., Fowler W. C., Jr, Kaufman D. G., Grimson R. C., Greenberg B. G., Hogue C. J., Berger G. S., Pulliam C. C. Estrogen and endometrial cancer: cases and two control groups from North Carolina. Am J Obstet Gynecol. 1980 May 1;137(1):92–101. doi: 10.1016/0002-9378(80)90391-9. [DOI] [PubMed] [Google Scholar]
  32. Hunt K. Perceived value of treatment among a group of long-term users of hormone replacement therapy. J R Coll Gen Pract. 1988 Sep;38(314):398–401. [PMC free article] [PubMed] [Google Scholar]
  33. Hunt K., Vessey M., McPherson K., Coleman M. Long-term surveillance of mortality and cancer incidence in women receiving hormone replacement therapy. Br J Obstet Gynaecol. 1987 Jul;94(7):620–635. doi: 10.1111/j.1471-0528.1987.tb03166.x. [DOI] [PubMed] [Google Scholar]
  34. Hutchison G. B., Rothman K. J. Correcting a bias? N Engl J Med. 1978 Nov 16;299(20):1129–1130. doi: 10.1056/NEJM197811162992010. [DOI] [PubMed] [Google Scholar]
  35. Jelovsek F. R., Hammond C. B., Woodard B. H., Draffin R., Lee K. L., Creasman W. T., Parker R. T. Risk of exogenous estrogen therapy and endometrial cancer. Am J Obstet Gynecol. 1980 May 1;137(1):85–91. doi: 10.1016/0002-9378(80)90390-7. [DOI] [PubMed] [Google Scholar]
  36. Jick H., Dinan B., Rothman K. J. Noncontraceptive estrogens and nonfatal myocardial infarction. JAMA. 1978 Apr 3;239(14):1407–1409. [PubMed] [Google Scholar]
  37. Jick H., Watkins R. N., Hunter J. R., Dinan B. J., Madsen S., Rothman K. J., Walker A. M. Replacement estrogens and endometrial cancer. N Engl J Med. 1979 Feb 1;300(5):218–222. doi: 10.1056/NEJM197902013000502. [DOI] [PubMed] [Google Scholar]
  38. Kadri A. Z. Hormone replacement therapy--a survey of perimenopausal women in a community setting. Br J Gen Pract. 1991 Mar;41(344):109–112. [PMC free article] [PubMed] [Google Scholar]
  39. Kaufman D. W., Miller D. R., Rosenberg L., Helmrich S. P., Stolley P., Schottenfeld D., Shapiro S. Noncontraceptive estrogen use and the risk of breast cancer. JAMA. 1984 Jul 6;252(1):63–67. [PubMed] [Google Scholar]
  40. La Vecchia C., Franceschi S., Gallus G., Decarli A., Colombo E., Liberati A., Tognoni G. Prognostic features of endometrial cancer in estrogen users and obese women. Am J Obstet Gynecol. 1982 Oct 15;144(4):387–390. doi: 10.1016/0002-9378(82)90241-1. [DOI] [PubMed] [Google Scholar]
  41. Mack T. M., Pike M. C., Henderson B. E., Pfeffer R. I., Gerkins V. R., Arthur M., Brown S. E. Estrogens and endometrial cancer in a retirement community. N Engl J Med. 1976 Jun 3;294(23):1262–1267. doi: 10.1056/NEJM197606032942304. [DOI] [PubMed] [Google Scholar]
  42. McDonald T. W., Annegers J. F., O'Fallon W. M., Dockerty M. B., Malkasian G. D., Jr, Kurland L. T. Exogenous estrogen and endometrial carcinoma: case-control and incidence study. Am J Obstet Gynecol. 1977 Mar 15;127(6):572–580. doi: 10.1016/0002-9378(77)90351-9. [DOI] [PubMed] [Google Scholar]
  43. Nomura A. M., Kolonel L. N., Hirohata T., Lee J. The association of replacement estrogens with breast cancer. Int J Cancer. 1986 Jan 15;37(1):49–53. doi: 10.1002/ijc.2910370109. [DOI] [PubMed] [Google Scholar]
  44. Obrink A., Bunne G., Collén J., Tjernberg B. Estrogen regimen of women with endometrial carcinoma. A retrospective case-control study at Radiumhemmet. Acta Obstet Gynecol Scand. 1981;60(2):191–197. [PubMed] [Google Scholar]
  45. Paganini-Hill A., Ross R. K., Henderson B. E. Postmenopausal oestrogen treatment and stroke: a prospective study. BMJ. 1988 Aug 20;297(6647):519–522. doi: 10.1136/bmj.297.6647.519. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Paterson M. E., Wade-Evans T., Sturdee D. W., Thom M. H., Studd J. W. Endometrial disease after treatment with oestrogens and progestogens in the climacteric. Br Med J. 1980 Mar 22;280(6217):822–824. doi: 10.1136/bmj.280.6217.822. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Petitti D. B., Wingerd J., Pellegrin F., Ramcharan S. Risk of vascular disease in women. Smoking, oral contraceptives, noncontraceptive estrogens, and other factors. JAMA. 1979 Sep 14;242(11):1150–1154. [PubMed] [Google Scholar]
  48. Pfeffer R. I., Van Den Noort S. Estrogen use and stroke risk in postmenopausal women. Am J Epidemiol. 1976 May;103(5):445–456. doi: 10.1093/oxfordjournals.aje.a112246. [DOI] [PubMed] [Google Scholar]
  49. Pfeffer R. I., Whipple G. H., Kurosaki T. T., Chapman J. M. Coronary risk and estrogen use in postmenopausal women. Am J Epidemiol. 1978 Jun;107(6):479–497. doi: 10.1093/oxfordjournals.aje.a112567. [DOI] [PubMed] [Google Scholar]
  50. Ravnikar V. A. Compliance with hormone therapy. Am J Obstet Gynecol. 1987 May;156(5):1332–1334. doi: 10.1016/0002-9378(87)90173-6. [DOI] [PubMed] [Google Scholar]
  51. Roberts P. J. The menopause and hormone replacement therapy: views of women in general practice receiving hormone replacement therapy. Br J Gen Pract. 1991 Oct;41(351):421–424. [PMC free article] [PubMed] [Google Scholar]
  52. Rosenberg L., Armstrong B., Jick H. Myocardial infarction and estrogen therapy in post-menopausal women. N Engl J Med. 1976 Jun 3;294(23):1256–1259. doi: 10.1056/NEJM197606032942302. [DOI] [PubMed] [Google Scholar]
  53. Rosenberg L., Slone D., Shapiro S., Kaufman D., Stolley P. D., Miettinen O. S. Noncontraceptive estrogens and myocardial infarction in young women. JAMA. 1980 Jul 25;244(4):339–342. [PubMed] [Google Scholar]
  54. Ross R. K., Paganini-Hill A., Gerkins V. R., Mack T. M., Pfeffer R., Arthur M., Henderson B. E. A case-control study of menopausal estrogen therapy and breast cancer. JAMA. 1980 Apr 25;243(16):1635–1639. [PubMed] [Google Scholar]
  55. Ross R. K., Paganini-Hill A., Mack T. M., Arthur M., Henderson B. E. Menopausal oestrogen therapy and protection from death from ischaemic heart disease. Lancet. 1981 Apr 18;1(8225):858–860. doi: 10.1016/s0140-6736(81)92138-3. [DOI] [PubMed] [Google Scholar]
  56. Ross R. K., Pike M. C., Henderson B. E., Mack T. M., Lobo R. A. Stroke prevention and oestrogen replacement therapy. Lancet. 1989 Mar 4;1(8636):505–505. doi: 10.1016/s0140-6736(89)91411-6. [DOI] [PubMed] [Google Scholar]
  57. Salmi T. Endometrial carcinoma risk factors, with special reference to the use of oestrogens. Acta Endocrinol Suppl (Copenh) 1980;233:37–43. [PubMed] [Google Scholar]
  58. Shapiro S., Kaufman D. W., Slone D., Rosenberg L., Miettinen O. S., Stolley P. D., Rosenshein N. B., Watring W. G., Leavitt T., Jr, Knapp R. C. Recent and past use of conjugated estrogens in relation to adenocarcinoma of the endometrium. N Engl J Med. 1980 Aug 28;303(9):485–489. doi: 10.1056/NEJM198008283030903. [DOI] [PubMed] [Google Scholar]
  59. Shapiro S., Kelly J. P., Rosenberg L., Kaufman D. W., Helmrich S. P., Rosenshein N. B., Lewis J. L., Jr, Knapp R. C., Stolley P. D., Schottenfeld D. Risk of localized and widespread endometrial cancer in relation to recent and discontinued use of conjugated estrogens. N Engl J Med. 1985 Oct 17;313(16):969–972. doi: 10.1056/NEJM198510173131601. [DOI] [PubMed] [Google Scholar]
  60. Spector T. D. Use of oestrogen replacement therapy in high risk groups in the United Kingdom. BMJ. 1989 Dec 9;299(6713):1434–1435. doi: 10.1136/bmj.299.6713.1434. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Spengler R. F., Clarke E. A., Woolever C. A., Newman A. M., Osborn R. W. Exogenous estrogens and endometrial cancer: a case-control study and assessment of potential biases. Am J Epidemiol. 1981 Oct;114(4):497–506. doi: 10.1093/oxfordjournals.aje.a113215. [DOI] [PubMed] [Google Scholar]
  62. Stampfer M. J., Sacks F. M. Patch up the menopause. Lancet. 1988 Jun 11;1(8598):1332–1332. doi: 10.1016/s0140-6736(88)92141-1. [DOI] [PubMed] [Google Scholar]
  63. Stampfer M. J., Willett W. C., Colditz G. A., Rosner B., Speizer F. E., Hennekens C. H. A prospective study of postmenopausal estrogen therapy and coronary heart disease. N Engl J Med. 1985 Oct 24;313(17):1044–1049. doi: 10.1056/NEJM198510243131703. [DOI] [PubMed] [Google Scholar]
  64. Stavraky K. M., Collins J. A., Donner A., Wells G. A. A comparison of estrogen use by women with endometrial cancer, gynecologic disorders, and other illnesses. Am J Obstet Gynecol. 1981 Nov 1;141(5):547–555. doi: 10.1016/s0002-9378(15)33276-2. [DOI] [PubMed] [Google Scholar]
  65. Sturdee D. W., Wade-Evans T., Paterson M. E., Thom M., Studd J. W. Relations between bleeding pattern, endometrial histology, and oestrogen treatment in menopausal women. Br Med J. 1978 Jun 17;1(6127):1575–1577. doi: 10.1136/bmj.1.6127.1575. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Szklo M., Tonascia J., Gordis L., Bloom I. Estrogen use and myocardial infarction risk: a case-control study. Prev Med. 1984 Sep;13(5):510–516. doi: 10.1016/0091-7435(84)90019-7. [DOI] [PubMed] [Google Scholar]
  67. Thompson S. G., Meade T. W., Greenberg G. The use of hormonal replacement therapy and the risk of stroke and myocardial infarction in women. J Epidemiol Community Health. 1989 Jun;43(2):173–178. doi: 10.1136/jech.43.2.173. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Vandenbroucke J. P. Postmenopausal oestrogen and cardioprotection. Lancet. 1991 Apr 6;337(8745):833–834. doi: 10.1016/0140-6736(91)92526-8. [DOI] [PubMed] [Google Scholar]
  69. Wallace W. A., Price V. H., Elliot C. A., MacPherson M. B., Scott B. W. Hormone replacement therapy acceptability to Nottingham post-menopausal women with a risk factor for osteoporosis. J R Soc Med. 1990 Nov;83(11):699–701. doi: 10.1177/014107689008301109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Weiss N. S., Szekely D. R., English D. R., Schweid A. I. Endometrial cancer in relation to patterns of menopausal estrogen use. JAMA. 1979 Jul 20;242(3):261–264. [PubMed] [Google Scholar]
  71. Whitehead M. I. Effects of hormone replacement therapy on cardiovascular disease: an interview. Am J Obstet Gynecol. 1988 Jun;158(6 Pt 2):1658–1659. doi: 10.1016/0002-9378(88)90205-0. [DOI] [PubMed] [Google Scholar]
  72. Whitehead M. I., Fraser D. Controversies concerning the safety of estrogen replacement therapy. Am J Obstet Gynecol. 1987 May;156(5):1313–1322. doi: 10.1016/0002-9378(87)90170-0. [DOI] [PubMed] [Google Scholar]
  73. Whitehead M., Lobo R. A. Consensus conference: Progestagen use in postmenopausal women. Lancet. 1988 Nov 26;2(8622):1243–1244. doi: 10.1016/s0140-6736(88)90824-0. [DOI] [PubMed] [Google Scholar]
  74. Wigle D. T., Grace M., Smith E. S. Estrogen use and cancer of the uterine corpus in Alberta. Can Med Assoc J. 1978 May 20;118(10):1276–1278. [PMC free article] [PubMed] [Google Scholar]
  75. Wilson P. W., Garrison R. J., Castelli W. P. Postmenopausal estrogen use, cigarette smoking, and cardiovascular morbidity in women over 50. The Framingham Study. N Engl J Med. 1985 Oct 24;313(17):1038–1043. doi: 10.1056/NEJM198510243131702. [DOI] [PubMed] [Google Scholar]
  76. Wingo P. A., Layde P. M., Lee N. C., Rubin G., Ory H. W. The risk of breast cancer in postmenopausal women who have used estrogen replacement therapy. JAMA. 1987 Jan 9;257(2):209–215. [PubMed] [Google Scholar]
  77. Ziel H. K., Finkle W. D. Increased risk of endometrial carcinoma among users of conjugated estrogens. N Engl J Med. 1975 Dec 4;293(23):1167–1170. doi: 10.1056/NEJM197512042932303. [DOI] [PubMed] [Google Scholar]

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