Risks of testosterone replacement therapy in ageing men

Expert Opinion on Drug Safety

Volumn 3, Issue 6, 2004, Pages 599-606

  Tan, Robert S ^a   Salazar, J A ^a  

^a UNIVERSITY OF TEXAS   (United States)

Author keywords

Andropause; Hypogonadism; Prostate; Safety; Testosterone

Indexed keywords

ANDROGEN; ANDROSTANOLONE; ESTRADIOL; HIGH DENSITY LIPOPROTEIN; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; LOW DENSITY LIPOPROTEIN; PLACEBO; PRASTERONE; PROSTATE ANTIGEN; PROTEIN C; PROTEIN S; TESTOSTERONE; TESTOSTERONE ENANTATE; TESTOSTERONE UNDECANOATE;

ACNE; AGED; ALOPECIA; ANDROPAUSE RELATED DISORDER; BREAST CARCINOMA; CARDIOVASCULAR DISEASE; CARDIOVASCULAR RISK; CLINICAL TRIAL; DEMENTIA; DEPRESSION; DISEASE EXACERBATION; DRUG BLOOD LEVEL; DRUG DELIVERY SYSTEM; DRUG FORMULATION; DRUG MARKETING; DRUG PROTEIN BINDING; DRUG SAFETY; EPIDEMIOLOGICAL DATA; ERYTHROCYTOSIS; FRACTURE; GYNECOMASTIA; HEART DISEASE; HUMAN; HYPOGONADISM; ISCHEMIC HEART DISEASE; KIDNEY DISEASE; LEG SWELLING; LIVER CELL CARCINOMA; LIVER DYSFUNCTION; LIVER TOXICITY; MALE; MEDICOLEGAL ASPECT; MORBIDITY; MORTALITY; OSTEOPOROSIS; PATIENT MONITORING; POLYCYTHEMIA; PRESCRIPTION; PREVALENCE; PROSTATE CANCER; PROSTATE CARCINOMA; PROSTATE HYPERTROPHY; QUALITY OF LIFE; REVIEW; RISK ASSESSMENT; SKIN ALLERGY; SLEEP APNEA SYNDROME; STABLE ANGINA PECTORIS; SUBSTITUTION THERAPY; SYMPTOMATOLOGY; THROMBOEMBOLISM; TRANSDERMAL PATCH; VASODILATATION;

ADENOCARCINOMA; AGED; CARDIOVASCULAR DISEASES; DOUBLE-BLIND METHOD; HEPATITIS, TOXIC; HORMONE REPLACEMENT THERAPY; HUMANS; HYPERLIPIDEMIAS; HYPOGONADISM; MALE; MIDDLE AGED; NEOPLASMS, HORMONE-DEPENDENT; POLYCYTHEMIA; PROSTATIC HYPERPLASIA; PROSTATIC NEOPLASMS; RANDOMIZED CONTROLLED TRIALS; SLEEP APNEA, OBSTRUCTIVE; TESTOSTERONE;

EID: 8844263744     PISSN: 14740338     EISSN: None     Source Type: Journal    
DOI: 10.1517/14740338.3.6.599     Document Type: Review

References (64)

1. VERMEULEN A, VERDONCK L, KAUFMAN JM: A critical evaluation of simple methods for the estimation of free testosterone in serum. J. Clin. Endocrinol. Metab. (1999) 84:3666-3672.
2. ZMUDA JM, CAULEY JA, KRISKA et al.: Longitudinal relation between endogenous testosterone and cardiovascular disease risk factors in middle-aged men. A 13-year follow-up of former Multiple Risk Factor Intervention Trial participants. Am. J. Epidemiol. (1997) 8:609-617.
3. KABACKI G, YILDIRIR A, CAN I et al.: Relationship between endogenous sex hormone levels, lipoproteins and coronary atherosclerosis in men undergoing coronary angiography. Cardiology (1999) 4:221-225.
4. ENGLISH KM, STEEDS RP, JONES TH et al.: Low-dose transdermal testosterone therapy improves angina threshold in men with chronic stable angina: a randomized, double-blind, placebo-controlled study. Circulation (2000) 16:1906-1911.
5. WEBB CM, MCNEILL JG, HAYWARD CS et al.: Effects of testosterone on coronary vasomotor regulation in men with coronary heart disease. Circulation (1999) 16:1690-1696.
6. ANDERSON RA, LUDLAM CA, WU FC: Haemostatic effects of supraphysiological levels of testosterone in normal men. Thromb. Haemost (1995) 2:693-697.
7. HAJJAR RR, KAISER FE, MORLEY JE: Outcomes of long-term testosterone replacement in older hypogonadal males: a retrospective analysis. J. Clin. Endocrinol. Metab. (1997) 11:3793-3796.
8. ALEXANDERSEN P, HAARBO J, CHRISTIANSEN C: The relationship of natural androgens to coronary heart disease in males: a review. Atherosclerosis (1996) 125:1-13.
9. SINGH AB, HSIA S, ALAUPOVIC P et al.: The effects of varying doses of T on insulin sensitivity, plasma lipids, apolipoproteins, and C-reactive protein in healthy young men. J. Clin. Endocrinol. Metab. (2002) 1:136-143.
10. KOURI EM, POPE HG, OLIVIA PS: Changes in lipoprotein-lipid levels in normal men following administration of increasing doses of testosterone cypionate. Clin. J. Sport Med. (1996) 3:152-157.
11. KUNELIUS P, LUKKARINENO, HANNUKESELA ML et al.: The effects of transdermal dihydrotestosterone in the aging male: a prospective, randomized, double blind study. J. Clin. Endocrinol. Metab. (2002) 4:1467-1472.
12. VON ECKARDSTEIN S, NIESCHLAG E: Treatment of male hypogonadism with testosterone undecanoate injected at extended intervals of 12 weeks: a Phase II study. J. Androl. (2002) 3:419-425.
13. WHITSEL EA, BOYKO EJ, MATSUMOTO AM et al.: Intramuscular testosterone esters and plasma lipids in hypogonadal men: a meta-analysis. Am. J. Med. (2001) 4:261-269.
14. DOBS AS, MIEKLE AW, ARVER S et al.: Pharmacokinetics, efficacy, and safety of a permeation-enhanced testosterone transdermal system in comparison with bi-weekly injections of testosterone enanthate for the treatment of hypogonadal men. J. Clin. Endocrinol. Metab. (1999) 84:3469-3478.
15. RHODEN EL, MORGENTALER A: Risks of testosterone-replacement therapy and recommendations for monitoring. N. Engl. J. Med. (2004) 5:482-489.
16. VAN STEENBRUGGE GJ, SCHRODER FH: Androgen-dependent human prostate cancer in nude mice: the PC-82 tumor model. Am. J. Clin. Oncol. (1988) 2(Suppl.):S8-S12.
17. BASARIA S, DOBS AS: Risk versus benefits of testosterone therapy in elderly men. Drugs Aging (1999) 15:131-142.
18. TYMCHUK CN, BARNARD JR, NGO TH et al.: Role of testosterone, estradiol, and insuline in diet and exercise-induced reductions in serum-stimulated prostate cancer cell growth in vitro. Nutr. Cancer. (2002) 42:112-116.
19. HUGGINS C, STEVENS RE, HODGES CV: Studies on prostatic cancer. II. The effects of castration on advanced carcinoma of the prostate. Arch. Surg. (1941) 43:209-223.
20. WENDEL EF, BRANNEN GE, PUTONG PB et al.: The effect of orchiectomy and estrogens on benign prostatic hyperplasia. J. Urol. (1972) 108:116.
21. BOSCH RJ, GRIFFITH DJ, BLOM JH et al.: Treatment of benign prostate hyperplasia by androgen deprivation: effects on the prostate size and urodynamic parameters. J. Urol. (1989) 141 68-72.
22. FRICK J, JUNGWIRTH A, ROVAN E: Androgens and the prostate. Testosterone (1998) 1:259-291.
23. SHANEYFELT T, HUSEIN R, BUBLEY G, MANTZOROS CS: Hormonal predictors of prostate cancer: a meta-analysis. J. Clin. Oncol. (2000) 18:847-853.
24. HOFFMAN MA, DEWOLF WC, MORGENTALER A: Is low serum free testosterone a market for high-grade prostate cancer? J. Urol. (2000) 163:824-827.
25. RHODEN EL, MORGENTALER A: Testosterone replacement therapy in hypogonadal men at high risk for prostate cancer: results of 1 year of treatment in men with prostatic intraepithelial neoplasia. J. Urology (2003) 170:2348-2351.
26. LEFKOWITZ GK, TANEJA S, BROWN J et al.: Follow-up interval prostate biopsy 3 years after diagnosis of high grade prostatic intraepithelial neoplasia is associated with high likelihood of prostate cancer, independent of change in prostate specific antigen levels. J. Urol. (2002) 168:1415-1418.
27. LY LP, JIMENNEZ M, ZHUANG TN et al.: A double-blind, placebo-controlled, randomized clinical trial of transdermal dihydrotestosterone gel on muscular strength, mobility, and quality of life in older men with partial androgen deficiency. J. Clin. Endocrinol. Metab. (2001) 86:4078-4088.
28. PERCHERSKY AV, MAZUROV VI, SEMIGLAZOV VF: Androgen administration in middle-aged and ageing men: effect of oral testosterone undecanoate on dihydrotestosterone, oestradiol and prostate volume. Int. J. Androl. (2002) 25:119-125.
29. BEHRE HM, BOHMEYER J, NIESCHLAG E: Prostate volume in testosterone-treated and untreated hypogonadal men in comparison to age-matched normal controls. Clin. Endocrinol. (1994) 40 341-349.
30. JIN B, CONWAY AJ, HANDELSMAN DJ: Effects of androgen deficiency and replacement on prostate volumes. Clin. Endocrinol. (2001) 54:437-445.
31. ROEHRBORN CG, MCCONNELL JD, LIEBER M et al.: Serum prostate-specific antigen concentration is a powerful predictor of acute urinary retention and need for surgery in men with clinical benign prostatic hyperplasia. PLESS Study Group. Urology (1999) 53 473-480.
32. ZGLICZYNSKI S, OSSOWSKI M, SLOWINSKA-SRZEDNICKA J: Effect of testosterone replacement therapy on lipids and lipoproteins in hypogonadal and elderly men. Atherosclerosis (1996) 121 35-43.
33. SIH R, MORLEY JE, KAISER FE et al.: Testosterone replacement in older hypogonadal men: a 12-month randomized controlled trial. Clin. Endocrinol. Metab. (1997) 82:1661-1667.
34. LI JY, ZHU JC, DOU JT et al.: Effects of androgen supplementation therapy on partial androgen deficiency in the aging male: a preliminary study. Aging Male 5:47-51.
35. STEIDLE C, SCHWARTZ S, JACOBY K et al.: AA2500 testosterone gel normalizes androgen levels in aging males with improvements in body composition and sexual function. J. Clin. Endocrinol. Metab. (2003) 88:2673-2681.
36. RABIJEWSKI M, ADAMKIEWICZ M, ZGLICZYFSKI S: The influence of testosterone replacement therapy on well-being, bone mineral density and lipids in elderly men. Pol. Arch. Med Wewn. (2001) 100 212-221.
37. LIU P YEE B, WISHART et al.: The short-term effects of high-dose testosterone on sleep, breathing, and function in older men. J. Clin. Endocrinol. Metab. (2003) 88:3605-3613.
38. GOOREN L: A ten-year safety study of the oral androgen testosterone undecanoate. J. Androl. (1994) 15:212-215.
39. CRAWFORD B, LIU P. KEAN M et al.: Randomized placebo-controlled trial of androgen effects on muscle and bone in men requiring long-term systemic glucocorticoid treatment. J. Clin. Endocrinol. Metab (2003) 88:3167-3176.
40. MARCELLI M, CUNNINGHAM GR: Hormonal signaling in prostatic hyperplasia and neoplasia. J. Clin. Endocrinol. Metab. (1999) 84 3463-3468.
41. SLATER S, OLIVER RT: Testosterone: its role in the development of prostate cancer and potential risk from use as hormone replacement therapy. Drugs Aging (2000) 17:431-439.
42. KRIEG M, NASS R, TUNN S: Effect of aging on endogenous level of 5 α-dihydrotestosterone, testosterone, estradiol, and estrone in epithelium and stroma of normal and hyperplastic human prostate. J. Clin. Endocrinol. Metab. (1993) 77:375-381.
43. SNYDER PJ, PEACHEY H, BERLIN J et al.: Effect of testostcrone replacement in hypogonadal men. J. Clin. Endocrinol. Metab. (2000) 85:2670-2677.
44. BLOCK AJ, BOYSEN PG, WYNNE JW et al.: Sleep apnoea, hypopnea and oxygen desaturation in normal subjects. N. Engl J. Med. (1979) 300:513-517.
45. DEXTER DD, DOVRE EJ: Obstructive sleep apnoea due to endogenous testosterone production in a woman. Mayo Clin. Proc. (1998) 73:246-248.
46. FOGEL RB, MALHOTRA A, PILLAR G, PITTMAN SD, DUNAIF A, WHITE DP: Increased prevalence of obstructive sleep apnoea in obese women with polycystic ovary syndrome. J. Clin. Endocrinol. Metab. (2001) 86 1175-1180.
47. CISTULLI PA, GRUNSTEIN RR, SULLIVAN CE: Effects of testosterone administration on upper airway collapsibility during sleep. Am. J. Respir. Crit. Care Med. (1994) 148:530-532.
48. STRUMPF IJ, REYNOLDS SF, VASH P et al.: A possible relationship between testosterone central control of ventilation and Pickwickian syndrome. Am. Rev. Respir. Dis. (1978) 117:183.
49. MATSUMOTO AM, SANDBLOM RE, SCHOENE RB et al.: Testosterone replacement in hypogonadal men: effects on obstructive sleep apnoea, respiratory drives, and sleep. Clin. Endocrinol. (1985) 22:713-721.
50. WHITTLE AT, MARSHALL I, MORTIMORE IL et al.: Neck soft tissue and fat distribution: comparison between normal men and women by magnetic resonance imaging. Thorax (1999) 54:323-328.
51. STEWART DA, GRUNSTEIN RR, BERTHON-JONES M: Androgen blockade does not affect sleep-disordered breathing or chemosensitivity in men with obstructive sleep apnoea. Am. Rev. Respir. Dis. (1992) 146 1389-1393.
52. SAARESRANTA T, POLO O: Hormones and breathing. Chest (2002) 122:2165-2182.
53. SHAHIDI NT: Androgens and erythropoiesis. N. Engl. J. Med. (1971) 289:72-80.
54. CLAUSTRES M, SULTAN C: Androgen and erythropoiesis evidence for an androgen receptor in erthyroblasts from human bone marrow cultures. Hormone Res. (1988) 29:17-22.
55. KRABBE S, CHRISTENSEN T, WORM J et al.: Relationship between haemoglobin and serum testosterone in normal children and adolescents and in boys with delayed puberty. Acta Paediatr. Scand. (1978) 67:655-658.
56. WIALLIAMSON CS: Influence of age and sex on haemoglobin aspectrophotometric analysis of nine hundred and nineteen cases. Arch. Intern. Med. (1916) 18:505-515.
57. WANG C, SWERDLOFF RS, IRANMANESH A et al.: Transdermal testosterone gel improves sexual function, mood, muscle strength, and body composition parameters in hypogonadal men. J. Clin. Endocrinol. Metab. (2000) 85:2839-2853.
58. TENOVER JL: Experience with testosterone replacement in the elderly. Mayo Clin. Proc. (2000) 75(Suppl.):S77-S82.
59. TAN RS, CULBERSON JW: An integrative review on current evidence of testosterone replacement therapy for the andropause. Maturitas (2003) 45:15-27.
60. BAGATELL CJ, BREMMER WJ: Androgens in men-uses and abuses. N. Engl. J. Med. (1996) 334:707-714.
61. HAMEED A, BROTHWOOD T, BOULOUX P et al.: Delivery of testosterone replacement therapy. Curr. Opin. Investig. Drugs (2003) 4:1213-1219.
62. YU MW, CHEN CJ: Elevated serum testosterone levels and risk of hepatocellular carcinoma. Cancer Res. (1993) 53:790-794.
63. ENDOCRINE SOCIETY. Andropause Consensus Statement (2001).
64. BHASIN S, SINGH AB, MAC RP et al.: Managing the risks of prostate disease during testosterone replacement therapy in older men: recommendations for a standardized monitoring plan. J. Androl. (2003) 24:299-311.