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A number of testosterone formulations are available to treat male hypogonadism. How do long-acting testosterone formulations affect the treatment of this condition in male hypogonadal patients with differing needs and considerations?

Response by Richard Sadovsky, MD
Hypogonadism is associated with an array of signs and symptoms, many of them nonspecific, and several comorbid conditions, such as diabetes and osteoporosis.1 A common disorder in men, hypogonadism is becoming increasingly prevalent with the aging of the US population.2 The crude prevalence of symptomatic androgen deficiency was reported to be 6% at baseline in data from the Massachusetts Male Aging Study (MMAS).3 Of the 1691 men in that study for whom complete testosterone data were available at baseline, 561 were aged 40 to 49 years, 558 were aged 50 to 59, and 572 were aged 60 to 70. During the follow-up phase (n=1087; mean follow-up interval, 8.8 y; range, 7.0-10.4 y), the crude prevalence doubled to 12.3%. In data from the Boston Area Community Health (BACH) survey, the reported prevalence of symptomatic androgen deficiency was 5.6% (N=1475; mean age, 47.3 y).4

Successful treatment of hypogonadism requires that the patient adhere to a lifelong treatment regimen.5 Adherence is enhanced when the patient perceives the regimen as convenient to use and when it entails relatively little use of medical services. When the clinician expects adherence to be problematic or unlikely, the patient may benefit from “forgiving” medication regimens that are less affected by delayed or missed doses, such as long-acting depot (extended-release) medications or medications with longer half-lives.6

The clinician can optimize adherence by emphasizing to the patient the value of his treatment regimen, by keeping the regimen uncomplicated, and by customizing it to fit the patient’s lifestyle.6 Asking the patient in a nonjudgmental, nonconfrontational way about his medication-taking behavior is a simple way to disclose poor adherence. Patients who find adherence difficult may need more intensive strategies, more forgiving treatment regimens, or both.

Response by Abraham Morgentaler, MD
A number of short- and long-acting testosterone therapies are available for the treatment of hypogonadism.5 (For a detailed description of available testosterone formulations, click here.) Ultimately, the best outcome will result from collaboration between patient and clinician given the individual circumstances.6

In the United States, the most frequently used treatment options are topical gels and injectable agents.7 Using gels avoids the need for injections, however, gels require daily application. In addition, bathing or swimming is restricted within several hours after application. Inadvertent transfer of testosterone gel to the skin of a female partner or a child has the potential to cause adverse effects, such as inappropriate virilization, which prompted a recent change in labeling1,8,9: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm149580.htm.

Two formulations of testosterone injection therapy are available in the United States, testosterone cypionate and testosterone enanthate.1 These two agents offer similar pharmacokinetics, and intramuscular injections generally are performed every 1-3 weeks.1,10 Advantages of using these agents include excellent serum concentrations, and disadvantages include the frequency of injections.   
The only currently available long-acting testosterone formulation in the United States is testosterone pellets,1 which are implanted subcutaneously during an office procedure using local anesthetic.11 The treatment effects last up to 6 months. About one third of the testosterone pellet material is absorbed in the first month, one fourth in the second month, and one sixth in the third month.12 Rare risks include local infection and pellet extrusion.

Intramuscular testosterone undecanoate (TU) is available in more than 80 countries and is in development in the United States.7,10 In a 24-week US trial that enrolled 130 hypogonadal men, 94% of those who received intramuscular TU 750 mg at 0, 4, and 14 weeks had normal serum testosterone levels for 10 weeks after the third injection.7 This novel treatment option provides steady-state pharmacokinetics, is safe and well tolerated, and may be a good choice for symptomatic hypogonadal men for whom adherence to therapy is challenging.

Two key features of intramuscular TU are its ability to produce sustained, consistent testosterone values in the normal range for 10 weeks and its relatively simple dosing. These advantages translate into convenience for patients13 and enhance adherence. Whereas gels and patches require daily application, intramuscular TU would require only 5 injections per year.7

Successful testosterone therapy depends on matching the patient’s needs and lifestyle with an appropriate method of delivery.5,6 Important potential advantages of a long-acting TU injection are convenience and safety. For example, men who travel frequently may be reluctant to carry gels or needles for self-injection. Also, taking intramuscular TU would eliminate concerns about skin-to-skin transfer of gels in men with young children. Patients should have their prostate health monitored regularly regardless with which testosterone formulation they are treated.14


  1. Bhasin S, Cunningham GR, Hayes FJ, et al. Testosterone therapy in adult men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2006;91(6):1995-2010.
  2. Hall SA, Araujo AB, Esche GR, et al. Treatment of symptomatic androgen deficiency: results from the Boston Area Community Health Survey. Arch Intern Med. 2008;168(10):1070-1076.
  3. Araujo AB, O’Donnell AB, Brambilla DJ, et al. Prevalence and incidence of androgen deficiency in middle-aged and older men: estimates from the Massachusetts Male Aging Study. J Clin Endocrinol Metab. 2004;89(12):5920-5926.
  4. Araujo AB, Esche GR, Kupelian V, et al. Prevalence of symptomatic androgen deficiency in men. J Clin Endocrinol Metab. 2007;92(11):4241-4247.
  5. Gooren LJG, Bunck MCM. Androgen replacement therapy: present and future [review]. Drugs. 2004;64(17):1861-1891.
  6. Osterberg L, Blaschke T. Adherence to medication [review]. N Engl J Med. 2005;353(5):487-497.
  7. Morgentaler A, Dobs AS, Kaufman JM, et al. Long acting testosterone undecanoate therapy in men with hypogonadism: results of a pharmacokinetic clinical study. J Urol. 2008;180(6):2307-2313.
  8. Testosterone gel safety concerns prompt FDA to require label changes [news release]. Silver Spring, MD: US Food and Drug Administration; May 7, 2009. Accessed June 5, 2009.
  9. Voelker R. Children’s exposure to testosterone gel spurs FDA to order boxed label warning. JAMA. 2009;301(23):2428.
  10. AACE Hypogonadism Task Force. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hypogonadism in adult male patients—2002 update. Endocr Pract. 2002;8(6):439-456.
  11. Cavender RK. Subcutaneous testosterone pellet implantation procedure for treatment of testosterone deficiency syndrome. J Sex Med. 2009;6(1):21-24.
  12. Testopel [prescribing information]. Rye, NY: Bartor Pharmacal Co Inc; 2007.
  13. Harle L, Basaria S, Dobs AS. Nebido: a long-acting injectable testosterone for the treatment of male hypogonadism. Expert Opin Pharmacother. 2005;6(10):1751-1759.
  14. Rhoden EL, Morgentaler A. Risks of testosterone-replacement therapy and recommendations for monitoring [review]. N Engl J Med. 2004;350(5):482-492.

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