Androgen suppression

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Rim Halaby, M.D. [2]

Synonyms and keywords: Androgen ablation, androgen deprivation, androgen deprivation therapy, ADT

Overview

Androgen suppression is a medical treatment to suppress or block the production or action of male sex hormones, typically in order to attempt to treat certain types of cancer that rely upon male hormones for their growth. Androgen suppression therapy, which includes GnRH agonist, antiandrogens and bilateral orchiectomy, is used for the treatment of prostate cancer. Androgen suppression therapy use has been associated with increased incidence of cardiovascular risk factors such as obesity, decreased insulin sensitivity and dyslipidemia. The association between androgen suppression therapy and increased cardiovascular mortality is controversial.[1]

Types of Androgen Suppression Therapy

Cardiovascular Effects of Androgen Suppression Therapy in Prostate Cancer

Androgen suppression therapy, which includes GnRH agonist, antiandrogens and bilateral orchiectomy, is used for the treatment of prostate cancer. Androgen suppression therapy use has been associated with increased incidence of cardiovascular risk factors. In fact, androgen suppression therapy contributes to an increase in obesity, modification of the body composition, a decrease in insulin sensitivity and dyslipidemia.[1] The science advisory from the American Heart Association, American Cancer Society, and American Urological Association recommends regular follow up for the evaluation of cardiovascular risk factors among patients with prostate cancer on androgen suppression therapy. Among patients with pre-existing cardiovascular disease, secondary prevention should be optimized.[1]

In addition, androgen suppression therapy use is associated with increased risk of myocardial infarction (MI), stroke[2] and shorter time to MI.[3] A cohort of 73,196 patients with prostate cancer, among which one third received GnRH agonist revealed an association between GnRH agonist use and increased incidence of diabetes (HR=1.44; P < 0.001), coronary heart disease (HR=1.16; P < 0.001) and MI (HR=1.11; P = 0.03).[4]

The association between androgen suppression therapy use and increased cardiovascular mortality is controversial. While this association has been reported in some studies,[5][6] others suggest that this association is only valid when the subject has co-existing comorbidities or other cardiac risk factors.[7] A metanalysis of 8 randomized clinical trials of 4141 patients demonstrates that androgen suppression therapy use in prostate cancer is not significantly associated with increased cardiovascular mortality (RR=0.93; 95% CI, 0.79-1.10; P = 0.41).[8] However, a metanalysis of 11 randomized clinical trials of 4805 patients reports that androgen suppression therapy use is associated with decreased prostate cancer related mortality (RR=0.69; 95% CI, 0.56-0.84; P < 0.001) and decreased overall mortality (RR=0.86; 95% CI, 0.80-0.93; P <0.001).[8]

References

  1. ↑ 1.0 1.1 1.2 Levine GN, D'Amico AV, Berger P, Clark PE, Eckel RH, Keating NL; et al. (2010). "Androgen-deprivation therapy in prostate cancer and cardiovascular risk: a science advisory from the American Heart Association, American Cancer Society, and American Urological Association: endorsed by the American Society for Radiation Oncology". Circulation. 121 (6): 833–40. doi:10.1161/CIRCULATIONAHA.109.192695. PMC 3023973. PMID 20124128.
  2. ↑ Jespersen CG, Nørgaard M, Borre M (2014). "Androgen-deprivation Therapy in Treatment of Prostate Cancer and Risk of Myocardial Infarction and Stroke: A Nationwide Danish Population-based Cohort Study". Eur Urol. 65 (4): 704–9. doi:10.1016/j.eururo.2013.02.002. PMID 23433805.
  3. ↑ D'Amico AV, Denham JW, Crook J, Chen MH, Goldhaber SZ, Lamb DS; et al. (2007). "Influence of androgen suppression therapy for prostate cancer on the frequency and timing of fatal myocardial infarctions". J Clin Oncol. 25 (17): 2420–5. doi:10.1200/JCO.2006.09.3369. PMID 17557956.
  4. ↑ Keating NL, O'Malley AJ, Smith MR (2006). "Diabetes and cardiovascular disease during androgen deprivation therapy for prostate cancer". J Clin Oncol. 24 (27): 4448–56. doi:10.1200/JCO.2006.06.2497. PMID 16983113.
  5. ↑ Tsai HK, D'Amico AV, Sadetsky N, Chen MH, Carroll PR (2007). "Androgen deprivation therapy for localized prostate cancer and the risk of cardiovascular mortality". J Natl Cancer Inst. 99 (20): 1516–24. doi:10.1093/jnci/djm168. PMID 17925537.
  6. ↑ Van Hemelrijck M, Garmo H, Holmberg L, Ingelsson E, Bratt O, Bill-Axelson A; et al. (2010). "Absolute and relative risk of cardiovascular disease in men with prostate cancer: results from the Population-Based PCBaSe Sweden". J Clin Oncol. 28 (21): 3448–56. doi:10.1200/JCO.2010.29.1567. PMID 20567006.
  7. ↑ Nanda A, Chen MH, Braccioforte MH, Moran BJ, D'Amico AV (2009). "Hormonal therapy use for prostate cancer and mortality in men with coronary artery disease-induced congestive heart failure or myocardial infarction". JAMA. 302 (8): 866–73. doi:10.1001/jama.2009.1137. PMID 19706860.
  8. ↑ 8.0 8.1 Nguyen PL, Je Y, Schutz FA, Hoffman KE, Hu JC, Parekh A; et al. (2011). "Association of androgen deprivation therapy with cardiovascular death in patients with prostate cancer: a meta-analysis of randomized trials". JAMA. 306 (21): 2359–66. doi:10.1001/jama.2011.1745. PMID 22147380. Review in: Ann Intern Med. 2012 Apr 17;156(8):JC4-04, JC4-05

See also

 This article incorporates public domain material from the U.S. National Cancer Institute document "Dictionary of Cancer Terms".

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