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Testosterone therapy is a form of hormone therapy in which testosterone is administered to supplement existing low level of the hormone

Routes of administration Edit

File:Depo-testosterone 200 mg ml crop.jpg

There are many routes of administration for testosterone. Forms of testosterone for human administration currently available include injectable (such as testosterone cypionate or testosterone enanthate in oil), oral,[1] buccal,[2] transdermal skin patches, and transdermal creams or gels.[3]

In the pipeline are "roll on" methods and nasal sprays.

Indications Edit

The original and primary use of testosterone is for the treatment of males who have too little or no natural endogenous testosterone production—males with hypogonadism. Appropriate use for this purpose is legitimate hormone replacement therapy (testosterone replacement therapy [TRT]), which maintains serum testosterone levels in the normal range.

However, over the years, as with every hormone, testosterone or other anabolic steroids has also been given for many other conditions and purposes besides replacement, with variable success but higher rates of side effects or problems. Examples include infertility, lack of libido or erectile dysfunction, osteoporosis, penile enlargement, height growth, bone marrow stimulation and reversal of anemia, and even appetite stimulation. By the late 1940s testosterone was being touted as an anti-aging wonder drug (e.g., see Paul de Kruif's The Male Hormone).[4] Decline of testosterone production with age has led to interest in androgen replacement therapy.[5]

To take advantage of its virilizing effects, testosterone is often administered to transsexual men as part of the hormone replacement therapy, with a "target level" of the normal male testosterone level. Like-wise, transsexual men are sometimes prescribed anti-androgens to decrease the level of testosterone in the body and allow for the effects of estrogen to develop.

Testosterone patches are effective at treating low libido in post-menopausal women.[6] Low libido may also occur as a symptom or outcome of hormonal contraceptive use. Women may also use testosterone therapies to treat or prevent loss of bone density, muscle mass and to treat certain kinds of depression and low energy state. Women on testosterone therapies may experience an increase in weight without an increase in body fat due to changes in bone and muscle density. Most undesired effects of testosterone therapy in women may be controlled by hair-reduction strategies, acne prevention, etc. There is a theoretical risk that testosterone therapy may increase the risk of breast or gynaecological cancers, and further research is needed to define any such risks more clearly.[6]

Hormone replacement therapy Edit

Main article: Androgen replacement therapy

Testosterone levels decline gradually with age in human beings. The clinical significance of this decrease is debated (see andropause). There is disagreement about when to treat aging men with testosterone replacement therapy. The American Society of Andrology's position is that:[7]

"... testosterone replacement therapy in aging men is indicated when both clinical symptoms and signs suggestive of androgen deficiency and decreased testosterone levels are present."


The American Association of Clinical Endocrinologists says:[8]

"Hypogonadism is defined as a free testosterone level that is below the lower limit of normal for young adult control subjects. Previously, age-related decreases in free testosterone were once accepted as normal. Currently, they are not considered normal. Patients with low-normal to subnormal range testosterone levels warrant a clinical trial of testosterone."


There is not total agreement on the threshold of testosterone value below which a man would be considered hypogonadal. (Currently there are no standards as to when to treat women.) Testosterone can be measured as "free" (that is, bioavailable and unbound) or more commonly, "total" (including the percentage which is chemically bound and unavailable). In the United States, male total testosterone levels below 300 ng/dL from a morning serum sample are generally considered low.[9] However these numbers are typically not age-adjusted, but based on an average of a test group which includes elderly males with low testosterone levels.[citation needed] Therefore a value of 300 ng/dL might be normal for a 65-year-old male, but not normal for a 30-year-old.[citation needed] Identification of inadequate testosterone in an aging male by symptoms alone can be difficult. The signs and symptoms are non-specific, and might be confused with normal aging characteristics, such as loss of muscle mass and bone density, decreased physical endurance, decreased memory ability[citation needed], and loss of libido.

Replacement therapy can take the form of injectable depots, transdermal patches and gels, subcutaneous pellets, and oral therapy. Adverse effects of testosterone supplementation include minor side effects such as acne and oily skin, and more significant complications such as increased hematocrit which can require venipuncture in order to treat, exacerbation of sleep apnea and acceleration of pre-existing prostate cancer growth in individuals who have undergone androgen deprivation. Exogenous testosterone also causes suppression of spermatogenesis and can lead to infertility.[10] It is recommended that physicians screen for prostate cancer with a digital rectal exam and PSA (prostate specific antigen) level before starting therapy, and monitor hematocrit and PSA levels closely during therapy.

Benefits Edit

Appropriate testosterone therapy can prevent or reduce the likelihood of osteoporosis, type 2 diabetes,[11] cardio-vascular disease (CVD), obesity, depression and anxiety and the statistical risk of early mortality. Low testosterone also brings with it an increased risk for the development of Alzheimer’s Disease.[12][13]

A small trial in 2005 showed mixed results.[14]

Large scale trials to assess the efficiency and long-term safety of testosterone are still lacking.[15]

Adverse effects Edit

Exogenous testosterone supplementation comes with a number of health risks. Fluoxymesterone and methyltestosterone are synthetic derivatives of testosterone. In 2006 it was reported that women taking Estratest, a combination pill including estrogen and methyltestosterone, were at considerably heightened risk of breast cancer.[citation needed] That said, methyltestosterone and Fluoxymesterone are no longer prescribed by physicians given their poor safety record, and testosterone replacement in men does have a very good safety record as evidenced by over sixty years of medical use in hypogonadal men.

One adverse effect that many men complain of is that of the development of gynecomastia (breasts), [citation needed] but this is something that can be prevented by appropriate choice and dosing of medication, and, in required cases, the use of ancillary medications that help lower SHBG or estradiol. Another side-effect is having difficulty urinating. [citation needed]

Athletic use Edit

Testosterone may be administered to an athlete in order to improve performance, and is considered to be a form of doping in most sports. There are several application methods for testosterone, including intramuscular injections, transdermal gels and patches, and implantable pellets.

Anabolic steroids (including testosterone) have also been taken to enhance muscle development, strength, or endurance. They do so directly by increasing the muscles' protein synthesis. As a result, muscle fibers become larger and repair faster than the average person's. After a series of scandals and publicity in the 1980s (such as Ben Johnson's improved performance at the 1988 Summer Olympics), prohibitions of anabolic steroid use were renewed or strengthened by many sports organizations. Testosterone and other anabolic steroids were designated a "controlled substance" by the United States Congress in 1990, with the Anabolic Steroid Control Act.[16] The levels of testosterone abused in sport greatly exceed the quantities of the steroid that are prescribed for medical use in hypogonadism.[citation needed] It is the supraphysiological doses and ultra high levels of testosterone that bring with it many undesirable effects and potential long term adverse health effects.[citation needed] Coupled with the nature of cheating in sport, this is seen as being a seriously problematic issue in modern sport, particularly given the lengths to which athletes and professional laboratories go to in trying to conceal such abuse from sports regulators. Steroid abuse once again came into the spotlight recently as a result of the Chris Benoit double murder-suicide in 2007, and the media frenzy surrounding it - however, there has been no evidence indicating steroid use as a contributing factor.

ReferencesEdit

  1. Andriol. Food and Drug Administration.
  2. Striant. Food and Drug Administration.
  3. Androgel. (PDF) Food and Drug Administration. and Testim. Food and Drug Administration.
  4. Cite error: Invalid <ref> tag; no text was provided for refs named de_Kruif_1945
  5. Myers JB, Meacham RB (2003). Androgen replacement therapy in the aging male. Rev Urol 5 (4): 216–26.
  6. 6.0 6.1 Davis SR, Moreau M, Kroll R, Bouchard C, Panay N, Gass M, Braunstein GD, Hirschberg AL, Rodenberg C, Pack S, Koch H, Moufarege A, Studd J (November 2008). Testosterone for low libido in postmenopausal women not taking estrogen. N. Engl. J. Med. 359 (19): 2005–17.
  7. (2006) Testosterone replacement therapy for male aging: ASA position statement. J. Androl. 27 (2): 133–4.
  8. Guay AT, Spark RF, Bansal S, Cunningham GR, Goodman NF, Nankin HR, Petak SM, Perez JB (2003). American Association of Clinical Endocrinologists medical guidelines for clinical practice for the evaluation and treatment of male sexual dysfunction: a couple's problem--2003 update. Endocr Pract 9 (1): 77–95.
  9. Holt EH, Zieve D. Testosterone. MedlinePlus Medical Encyclopedia. U.S. National Library of Medicine. URL accessed on 2009-07-17.
  10. (October 1990) Contraceptive efficacy of testosterone-induced azoospermia in normal men. World Health Organization Task Force on methods for the regulation of male fertility. Lancet 336 (8721): 955–9.
  11. Traish AM, Saad F, Guay A (2009). The dark side of testosterone deficiency: II. Type 2 diabetes and insulin resistance. J. Androl. 30 (1): 23–32.
  12. Cite error: Invalid <ref> tag; no text was provided for refs named pmid16785599
  13. Cite error: Invalid <ref> tag; no text was provided for refs named pmid15383512
  14. Emmelot-Vonk MH, Verhaar HJ, Nakhai Pour HR, Aleman A, Lock TM, Bosch JL, Grobbee DE, van der Schouw YT (January 2008). Effect of testosterone supplementation on functional mobility, cognition, and other parameters in older men: a randomized controlled trial. JAMA 299 (1): 39–52.
  15. Cunningham GR. Testosterone treatment in aging men. EndocrineToday.com. URL accessed on 2009-07-17.
  16. (1990). Anabolic Steroid Control Act. United States Sentencing Commission.

Further readingEdit

  • Andrew, R. J., & Jones, R. (1992). Increased distractibility in capons: An adult parallel to androgen-induced effects in the domestic chick. Behavioural Processes, 26(2-3), 201-209.
  • Bain, J., Brock, G., & Kuzmarov, I. (2007). Canadian Society for the Study of the Aging Male: Response to health Canada's position paper on testosterone treatment. Journal of Sexual Medicine, 4(3), 558-566.
  • Basson, R. (2007). Hormones and sexuality: Current complexities and future directions. Maturitas, 57(1), 66-70.
  • Burris, A. S., Gracely, R. H., Carter, C., Sherins, R. J., & et al. (1991). Testosterone therapy is associated with reduced tactile sensitivity in males. Hormones and Behavior, 25(2), 195-205.
  • Buvat, J. (2006). It is time for a large trial of testosterone therapy for older men. Journal of Men's Health & Gender, 3(2), 169-171.
  • Carlson, N., Brenner, L., Wierman, M., Harrison-Felix, C., Morey, C., Gallagher, S., et al. (2009). Hypogonadism on admission to acute rehabilitation is correlated with lower functional status at admission and discharge. Brain Injury, 23(4), 336-344.
  • Chaudhry, M. (2003). A 60-year-old man with progressive malaise, fatigue and decreased libido. Canadian Medical Association Journal, 169(5), 445.
  • Cherry, J. A., & Lepri, J. J. (1986). Sexual dimorphism and gonadal control of ultrasonic vocalizations in adult pine voles, Microtus pinetorum. Hormones and Behavior, 20(1), 34-48.
  • Crenshaw, T. L. (1985). Transsexual problem. Medical Aspects of Human Sexuality, 19(12), 53-56.
  • Daly, R. C., Schmidt, P. J., Roca, C. A., & Rubinow, D. R. (2001). Testosterone's effects not limited to mood. Archives of General Psychiatry, 58(4), 403.
  • Davis, S. (2000). Testosterone and sexual desire in women. Journal of Sex Education & Therapy, 25(1), 25-32.
  • Davis, S. R., Wolfe, R., Farrugia, H., Ferdinand, A., & Bell, R. J. (2009). The incidence of invasive breast cancer among women prescribed testosterone for low libido. Journal of Sexual Medicine, 6(7), 1850-1856.
  • Davis, S. R., Wolfe, R., Farrugia, H., Ferdinand, A., & Bell, R. J. (2010). "Testosterone and breast cancer": Author response. Journal of Sexual Medicine, 7(2, Pt 2), 1036-1037.
  • Emmelot-Vonk, M. H., Verhaar, H. J., & van der Schouw, Y. T. (2008). Effects of testosterone therapy in older men: Reply. JAMA: Journal of the American Medical Association, 299(16), 1900-1901.
  • Freeman, M. P., & Freeman, S. A. (2003). Treatment of leuprolide-induced depression with intramuscular testosterone: A case report. Journal of Clinical Psychiatry, 64(3), 341-343.
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  • Guay, A. T., Smith, T. M., & Offutt, L. A. (2009). Absorption of testosterone gel 1% (Testim) from three different application sites. Journal of Sexual Medicine, 6(9), 2601-2610.
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  • Morelli, A., Fibbi, B., Marini, M., Silvestrini, E., De Vita, G., Chavalmane, A. K., et al. (2009). Dihydrotestosterone and leptin regulate gonadotropin-releasing hormone (GnRH) expression and secretion in human GnRH-secreting neuroblasts. Journal of Sexual Medicine, 6(2), 397-407.
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  • Pennebaker, J. W., Groom, C. J., Loew, D., & Dabbs, J. M. (2004). Testosterone as a Social Inhibitor: Two Case Studies of the Effect of Testosterone Treatment on Language. Journal of Abnormal Psychology, 113(1), 172-175.
  • Perry, P. J., Yates, W. R., Williams, R. D., Andersen, A. E., MacIndoe, J. H., Lund, B. C., et al. (2002). Testosterone therapy in late-life major depression in males. Journal of Clinical Psychiatry, 63(12), 1096-1101.
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  • Rabkin, J. G., Wagner, G. J., & Rabkin, R. (2000). A double-blind, placebo-controlled trial of testosterone therapy for HIV-positive men with hypogonadal symptoms. Archives of General Psychiatry, 57(2), 141-147.
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