Skip to main content

Advertisement

SpringerLink
Log in

Estrogen in Patients with Prostatic Cancer

An Assessment of the Risks and Benefits

  • Review Article
  • Risk-Benefit Assessment
  • Published:
Drug Safety Aims and scope Submit manuscript

Summary

Estrogen therapy of patients with prostatic carcinoma appears to be at least as effective in antitumour activity as surgical castration; the recent therapeutic alternative of gonadorelin (gonadotrophin-releasing hormone) analogues has not to date been shown to improve patient outcome.

Oral estrogen therapy in these patients increases the incidence of arterial ischaemic events, thromboembolic events and congestive heart failure. A plausible mechanism behind the enhanced cardiovascular morbidity is an increase in the formation of proteins synthesised by the liver, including coagulation factors. Oral estrogens induce a ‘hypercoagulable state’ which can be expected to have an adverse influence on the cardiovascular system. The effect of estrogen on cholesterol metabolism is likely to be beneficial for the cardiovascular system, with decreased levels of the atherogenic low density lipoprotein (LDL) cholesterol and increased levels of the putatively beneficial high density lipoprotein (HDL) cholesterol.

The effects of estrogen on platelets and cardiovascular prostanoids are difficult to evaluate at present. A possible approach to reduce its impact on the liver, and thereby possibly to minimise the risk of cardiovascular side effects, is parenteral administration. The promising results obtained in a pilot study of parenteral estrogen therapy in patients with prostatic carcinoma await confirmation in a randomised study, but where treatment with estrogen is considered for these patients, it may be that parenteral administration would be preferable.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Agardh CD, Nilsson-Ehle P, Lundgren R, Gustafsson A. The influence of treatment with estrogens and estramustine phosphate on platelet aggregation and plasma lipoproteins in non-disseminated prostatic carcinoma. Journal of Urology 132: 1021–1024, 1984

    PubMed  CAS  Google Scholar 

  • Bailer III JC, Byar DP, Veterans Administration Cooperative Urological Research Group. Estrogen treatment for cancer of the prostate: early results with 3 doses of diethylstilbestrol and placebo. Cancer 26: 257–261, 1970

    Article  Google Scholar 

  • Bayard S, Greenberg R, Showalter D, Byar D. Comparison of treatment for prostatic cancer using an exponential type life model relating survival to concomitant information. Cancer Chemotherapy Reports 58: 845–859, 1974

    CAS  Google Scholar 

  • Blackard CE, Byar DP, Jordan Jr WP. Orchiectomy for advanced prostatic carcinoma: a reevaluation. Urology 1: 553–560, 1973

    Article  PubMed  CAS  Google Scholar 

  • Blackard CE, Doe RP, Mellinger GT, Byar DP. Incidence of cardiovascular disease and death in patients receiving diethylstilbestrol for carcinoma of the prostate. Cancer 26: 249–256, 1970

    Article  PubMed  CAS  Google Scholar 

  • Blombäck M, Hall K, Ritzén EM. Estrogen treatment of tall girls: risk of thrombosis? Pediatrics 72: 416–419, 1983

    PubMed  Google Scholar 

  • Bradley DD, Wingerd J, Petitti DB, Krauss RM, Ramcharan S. Serum high-density-lipoprotein cholesterol in women using oral contraceptives, estrogen and progestins. New England Journal of Medicine 299: 17–20, 1978

    Article  PubMed  CAS  Google Scholar 

  • Büller HR, Boon TA, Henny CP, Dabhoiwala NF, ten Cate JW. Estrogen-induced deficiency and decrease in antithrombin II activity in patients with prostatic cancer. Journal of Urology 128: 72–74, 1982

    PubMed  Google Scholar 

  • Byar DP. The Veterans Administration Cooperative Urological Research Group’s studies of cancer of the prostate. Cancer 32: 1126–1130, 1973

    Article  PubMed  CAS  Google Scholar 

  • Byar DP. VACURG studies of conservative treatment. Scandinavian Journal of Urology and Nephrology (Suppl. 55): 99–102, 1980

    Google Scholar 

  • Byar DP, Corle DK. Selecting optimal treatment in clinical trials using covariate information. Journal of Chronic Diseases 30: 445–459, 1977

    Article  PubMed  CAS  Google Scholar 

  • Coronary Drug Project Research Group. The Coronary Drug Project: initial findings leading to modifications of its research protocol. Journal of the American Medical Association 214: 1303–1313, 1970

    Article  Google Scholar 

  • Coronary Drug Project Research Group. The Coronary Drug Project: findings leading to discontinuation of the 2.5-mg/day estrogen group. Journal of the American Medical Association 226: 652–657, 1973

    Article  Google Scholar 

  • Daehlin L, Damber JE, von Schoultz B, Bergman B. The oestrogenic effects of ethinyl oestradiol/polyestradiol phosphate and estramustine phosphate in patients with prostatic carcinoma. British Journal of Urology 58: 412–416, 1986

    Article  PubMed  CAS  Google Scholar 

  • Damber MG, Sandström B, von Schoultz B, Stigbrand T. A new and sensitive method for quantifying and comparing the biological potency of various estrogens in man. Acta Obstetrica et Gynecologica Scandinavica 58: 527–530, 1979

    Article  CAS  Google Scholar 

  • Egeberg O. Inherited antithrombin deficiency causing thrombophilia. Thrombosis et Diathesis Haemorrhagica 13: 516–530, 1965

    PubMed  CAS  Google Scholar 

  • El Makhzangy MN, Wynn V, Lawrence DM. Sex hormone binding globulin capacity as an index of estrogenicity and androgenicity in women on oral contraceptive steroids. Clinical Endocrinology 10: 39–45, 1979

    Article  PubMed  Google Scholar 

  • Eriksson M, Berglund L, Rudling M, Henriksson P, Angelin B. Effects of estrogen on low density lipoprotein metabolism in males. Short-term and long-term studies during hormonal treatment of prostatic carcinoma. Journal of Clinical Investigation 84: 802–810, 1989

    Article  PubMed  CAS  Google Scholar 

  • Fogelberg M, Vesterqvist O, Diczfalusy U, Henriksson P. Experimental atherosclerosis: effects of oestrogen and atherosclerosis on thromboxane and prostacyclin formation. European Journal of Clinical Investigation 20: 105–110, 1990

    Article  PubMed  CAS  Google Scholar 

  • Geola FL, Frumar AM, Tataryn IV, Lu KH, Jershman JM, et al. Biological effects of various doses of conjugated equine estrogens in postmenopausal women. Journal of Clinical Endocrinology and Metabolism 51: 620–625, 1980

    Article  PubMed  CAS  Google Scholar 

  • Goebelsmann MD, Mashchak CA, Mishell DR. Comparison of hepatic impact of oral and vaginal administration of ethinyl estradiol. American Journal of Obstetrics and Gynecology 151: 868–877, 1985

    PubMed  CAS  Google Scholar 

  • Hedlund PO, Gustafson H, Sjögren S. Cardiovascular complications to treatment of prostate cancer with estramustine phosphate (Estracyt) or conventional estrogen: a follow-up of 212 randomized patients. Scandinavian Journal of Urology and Nephrology (Suppl. 55): 103–105, 1980

    Google Scholar 

  • Heiss G, Tamir I, Davis CE, Tyroler HA, Rifkind BM, et al. Lipoprotein cholesterol distributions in selected North American populations: the Lipid Research Clinics Program Prevalence Study. Circulation 61: 302–315, 1980

    Article  PubMed  CAS  Google Scholar 

  • Helgason S. Estrogen replacement after the menopause: estrogenicity and metabolic effects. Acta Obstetrica et Gynecologica Scandinavica (Suppl. 107): 7–29, 1982

  • Henderson BE, Paganini-Hill A, Ross RK. Estrogen replacement therapy and protection from acute myocardial infarction. American Journal of Obstetrics and Gynecology 159: 312–317, 1988

    PubMed  CAS  Google Scholar 

  • Henny CP, ten Cate H, Dabhoiwala NF, Büller HR, ten Date JW. Effect of hormonal manipulation on antithrombin III activity in patients with prostatic carcinoma. European Urology 10: 202–206, 1984

    PubMed  CAS  Google Scholar 

  • Henriksson P, Blombäck M, Bratt G, Edhag O, Eriksson A. Activators and inhibitors of coagulation and fibrinolysis in patients with prostatic cancer treated with estrogen or orchidectomy. Thrombosis Research 44: 783–791, 1986

    Article  PubMed  CAS  Google Scholar 

  • Henriksson P, Blombäck M, Bratt G, Edhag O, Eriksson A, et al. Effects of oestrogen therapy and orchidectomy on coagulation and prostanoid synthesis in patients with prostatic cancer. Medical Oncology and Tumour Pharmacotherapy 6: 219–225, 1989a

    CAS  Google Scholar 

  • Henriksson P, Blombäck M, Eriksson A, Stege R, Carlström K. Effects of parenteral estrogen on the coagulation system in patients with prostatic carcinoma. British Journal of Urology 65: 282–285, 1990

    Article  PubMed  CAS  Google Scholar 

  • Henriksson P, Edhag O. Orchidectomy versus oestrogen for prostatic cancer: cardiovascular effects. British Medical Journal 293: 413–415, 1986

    Article  PubMed  CAS  Google Scholar 

  • Henriksson P, Edhag O, Eriksson A, Johansson S-E. Patients at high risk of cardiovascular complications in oestrogen treatment of prostatic cancer. British Journal of Urology 63: 186–190, 1989b

    Article  PubMed  CAS  Google Scholar 

  • Henriksson P, Einarsson K, Eriksson A, Kelter U, Angelin B. Estrogen-induced gallstone formation in males: relation to changes in serum and biliary lipids during hormonal treatment of prostatic carcinoma. Journal of Clinical Investigation 84: 811–816, 1989c

    Article  PubMed  CAS  Google Scholar 

  • Henriksson P, Eriksson A, Stege R, Collste L, Pousette Å, et al. Cardiovascular follow-up of patients with prostatic cancer treated with single-drug polyestradiol phosphate. Prostate 13: 257–261, 1988

    Article  PubMed  CAS  Google Scholar 

  • Henriksson P, Johansson SE. Prediction of cardiovascular complications in patients with prostatic cancer treated with estrogen. American Journal of Epidemiology 125: 970–978, 1987

    PubMed  CAS  Google Scholar 

  • Henriksson P, Stamberger M, Eriksson M, Rudling M, Diczfalusy U, et al. Estrogen induced changes in lipoprotein metabolism: role in prevention of atherosclerosis in the cholesterol-fed rabbit. European Journal of Clinical Investigation 19: 395–403, 1989d

    Article  PubMed  CAS  Google Scholar 

  • Hough JL, Zilversmit DB. Effect of 17 \-estradiol on aortic cholesterol content and metabolism in cholesterol-fed rabbits. Arteriosclerosis 6: 57–63, 1986

    Article  PubMed  CAS  Google Scholar 

  • Huggins C, Hodges CV. Studies on prostatic cancer: I. The effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. Cancer Research 1: 293–297, 1941

    CAS  Google Scholar 

  • Huggins C, Scott WW, Hodges CV. Studies on prostatic cancer: III. The effects of fever, of desoxycorticosterone and of estrogen on clinical patients with metastatic carcinoma of the prostate. Journal of Urology 46: 997–1006, 1941a

    CAS  Google Scholar 

  • Huggins C, Stevens RE, Hodges CV. Studies on prostatic cancer: II. The effects of castration on advanced carcinoma of the prostate gland. Archives of Surgery 43: 209–223, 1941b

    Article  CAS  Google Scholar 

  • Hunter J. Observations on certain parts of the animal oeconomy, 1st ed., p. 39, London, 1786. Jönsson G, Olsson AM, Luttrop W, Cekan Z, Purvis K, et al. Treatment of prostatic carcinoma with various types of estrogen derivatives. Vitamins and Hormones 33: 351–376, 1975

    Google Scholar 

  • Kovanen PT, Brown MS, Goldstein JL. Increased binding of low density lipoprotein to liver membranes from rats treated with 17 α-ethinyl estradiol. Journal of Biological Chemistry 254: 1367–1373, 1979

    Google Scholar 

  • Krakoff LR, Eisenfeld AJ. Hormonal control of plasma renin substrate (angiotensinogen). Circulation Research 41 (Suppl. II): 43–46, 1977

    Article  PubMed  CAS  Google Scholar 

  • Kushwaha RS, Hazzard WR. Exogenous estrogens attenuate dietary hypercholesterolemia and atherosclerosis in the rabbit. Metabolism 30: 359–366, 1981

    Article  PubMed  CAS  Google Scholar 

  • Laurell CB, Rannevik G. Comparison of plasma protein changes induced by danazol, pregnancy and estrogens. Journal of Clinical Endocrinology and Metabolism 49: 719–724, 1979

    Article  PubMed  CAS  Google Scholar 

  • Lundgren R, Sundin T, Colleen S, Lindstedt E, Wadström L, et al. Cardiovascular complications of estrogen therapy for non-disseminated prostatic carcinoma: a preliminary report from a randomized study. Scandinavian Journal of Urology and Nephrology 20: 101, 1986

    Article  PubMed  CAS  Google Scholar 

  • Ma PTS, Yamamoto T, Goldstein JL, Brown MS. Increased mRNA for low density lipoprotein receptor in livers of rabbits treated with 17 α-ethinyl estradiol. Proceedings of the National Academy of Sciences 83: 792–796, 1986

    Article  CAS  Google Scholar 

  • Meade TW, Chakrabarti R, Haines AP, North WRS, Stirling Y, et al. Haemostatic function and cardiovascular death: early results of a prospective study. Lancet 1: 1050–1054, 1980

    Article  PubMed  CAS  Google Scholar 

  • Paganini-Hill A, Ross RK, Henderson BE. Postmenopausal estrogen treatment and stroke: a prospective study. British Medical Journal 297: 519–522, 1988

    Article  PubMed  CAS  Google Scholar 

  • Pavone-Macaluso M, De Voogt HJ, Viggiano G, Barasolo E, Lardennois B, et al. Comparison of diethylstilbestrol, cyproterone acetate and medroxyprogesterone acetate in the treatment of advanced prostatic cancer: final analysis of a randomized phase III trial of the European Organization for Research on Treatment of Cancer Urological Group. Journal of Urology 136: 624–631, 1986

    PubMed  CAS  Google Scholar 

  • Poller L. Oral contraceptives, blood clotting and thrombosis. British Medical Bulletin 34: 151–156, 1978

    PubMed  CAS  Google Scholar 

  • Rössner S, Hedlund P-O, Jogestrand T, Säwe U. Treatment of prostatic cancer: effects on serum lipoproteins and the cardiovascular system. Journal of Urology 133: 53–57, 1985

    PubMed  Google Scholar 

  • Slone D, Shapiro S, Kaufman DW, Rosenberg L, Miettinen OS, et al. Risk of myocardial infarction in relation to current and discontinued use of oral contraceptives. New England Journal of Medicine 305: 420–424, 1981

    Article  PubMed  CAS  Google Scholar 

  • Smith PH, Suciu S, Robinson MRG, Richards B, Bastable JRG, et al. A comparison of the effect of diethylstilbestrol with low dose estramustine phosphate in the treatment of advanced prostatic cancer: final analysis of a phase III trial of the European Organization for Research on Treatment of Cancer. Journal of Urology 136: 619–623, 1986

    PubMed  CAS  Google Scholar 

  • Stadel BV. Oral contraceptives and cardiovascular disease. New England Journal of Medicine 305: 612–618, 672–677, 1981

    Article  PubMed  CAS  Google Scholar 

  • Stamler J. The Coronary Drug Project —findings with regard to estrogen, dextrothyroxine, clofibrate and niacin. Advances in Experimental Medicine and Biology 82: 52–75, 1977

    PubMed  CAS  Google Scholar 

  • Stampfer MJ, Willett WC, Colditz GA, Rosner BR, Speizer FE, et al. A prospective study of postmenopausal estrogen therapy and coronary heart disease. New England Journal of Medicine 313: 1044–1049, 1985

    Article  PubMed  CAS  Google Scholar 

  • Stege R, Fröhlander N, Carlström K, Pousette A, von Schoultz B. Steroid-sensitive proteins, growth hormone and somatomedin C in prostatic cancer: effects of parenteral and oral estrogen therapy. Prostate 10: 333–338, 1987

    Article  PubMed  CAS  Google Scholar 

  • Sullivan JM, Zwaag RV, Lemp GF, Hughes JP, Maddock V, et al. Postmenopausal estrogen use and coronary atherosclerosis. Annals of Internal Medicine 108: 358–363, 1988

    PubMed  CAS  Google Scholar 

  • Varenhorst E, Wallentin L, Risberg B. The effects of orchidectomy, estrogen and cyproterone acetate on the antithrombin III concentrations in carcinoma of the prostate. Urological Research 9: 25–28, 1981

    Article  Google Scholar 

  • Vesterqvist O, Green K. Development of a GC-MS method for quantitation of 2,3-dinor-6-keto-PGF1α and determination of the urinary excretion rates in healthy humans under normal conditions and following drugs. Prostaglandins 28: 139–154, 1984

    Article  PubMed  CAS  Google Scholar 

  • Vesterqvist O, Green K, Lincoln FH, Sebek OK. Development of a GC-MS method for quantitation of 2,3-dinor-TxB2 and determinations of the daily urinary excretion rates in healthy humans. Thrombosis Research 33: 39–49, 1983

    Article  Google Scholar 

  • Veterans Administration Cooperative Urological Research Group. Carcinoma of the prostate: treatment comparisons. Journal of Urology 98: 516–522, 1967a

    Google Scholar 

  • Veterans Administration Cooperative Urological Research Group. Treatment and survival of patients with cancer of the prostate. Surgery, Gynecology and Obstetrics 124: 1011–1017, 1967b

    Google Scholar 

  • von Schoultz B. Potency of different oestrogen preparations. In Studd & Whitehead (Eds) The menopause, pp. 130–137, Black-well Scientific Publications, London, 1988

    Google Scholar 

  • von Schoultz B, Carlström K, Henriksson P, Stege R. Estrogen therapy and liver function —metabolic effects of oral and parenteral administration. Prostate 14: 389–395, 1989

    Article  Google Scholar 

  • Wallace RB, Hoover J, Barrett-Conner E, Rifkind BM, Hunninghake DB, et al. Altered plasma lipid and lipoprotein levels associated with oral contraceptive and estrogen use. Lancet 2: 111–115, 1979

    Article  CAS  Google Scholar 

  • Wallentin L, Varenhorst E. Changes of plasma lipid metabolism in males during estrogen treatment for prostatic carcinoma. Journal of Clinical Endocrinology and Metabolism 47: 596–599, 1978

    Article  PubMed  CAS  Google Scholar 

  • White JW. The results of double castration in hypertrophy of the prostate. Annals of Surgery 22: 1–80, 1895

    Article  PubMed  CAS  Google Scholar 

  • Wilson WF, Garrison RJ, Castelli WP. Postmenopausal estrogen use, cigarette smoking, and cardiovascular morbidity in women over 50. New England Journal of Medicine 313: 1038–1043, 1985

    Article  PubMed  CAS  Google Scholar 

  • Windler ET, Kovanen PT, Chao YS, Brown MS, Havel RJ, et al. The estradiol-stimulated lipoprotein receptor of rat liver. Journal of Biological Chemistry 255: 10464–10471, 1980

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine, Cardiac Division, Huddinge University Hospital, S-141 86, Huddinge, Sweden

    Peter Henriksson

Authors
  1. Peter Henriksson
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Henriksson, P. Estrogen in Patients with Prostatic Cancer. Drug-Safety 6, 47–53 (1991). https://doi.org/10.2165/00002018-199106010-00005

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00002018-199106010-00005

Keywords

Search

Navigation