Treatment Options

What Treatments Are Available?

Currently marketed treatment options for testosterone replacement therapy for male hypogonadism are summarized in Table 4.

Table 4. Currently Available Testosterone Replacement Therapy
Table 4
(Click to view Table 4)

Table 4. Currently Available Testosterone Replacement Therapy (Hide table)
PreparationsWay usedAdvantagesDisadvantages
Commonly used testosterone replacement preparations
Depot Injection Therapy (testosterone enanthate or cyprionate) Injected deep intramuscularly (IM) every 1 to 4 weeks (usually in the buttocks)
  • Testosterone absorbed directly into bloodstream[1-5]
  • Requires regular IM injections[1-5]
  • Fluctuating levels of testosterone with high initial levels[
  • Mood swings as testosterone levels rise and fall (“roller coaster” effect)[
  • Local pain on injection[
  • Abscess formation (rare)
Long-acting Injection Therapy (testosterone undecanoate) Injected IM every 3 months following an initial loading dose to stabilize testosterone levels
  • Testosterone absorbed directly into blood stream[1-7]
  • Consistent, reliable efficacy and infrequent dosing relating to long duration of effect valued by patients[
  • Provides a steady level of testosterone in the normal range[
  • Avoids unphysiological peaks and troughs[
  • Fewer adverse events such as mood swings or blood changes[
  • Local pain on injection[1,3]
  • Abscess formation (rare)
  • Requires injection of a 4 mL volume[
Gels (native testosterone) A clear testosterone gel rubbed onto the shoulders, chest or back once a day – dries within a few minutes
  • Convenient sites of application
  • Quickly normalizes testosterone levels [1,2,4,5,6]
  • Stable blood levels of testosterone throughout the 24-hour dosing period[
  • Less skin irritation than patches[
  • No operation needed
  • Skin irritation may be a rare side effect[1,3,4,5]
  • Potential for transfer to partner or child[
Oral Testosterone Undecanoate Taken in pill or capsule form 2 or 3 times daily
  • Orally active and convenient to take (but see short duration of action)[1-5]
  • Enters the bloodstream via the lymphatic system, thus partially circumventing the first-pass effect of the liver[
  • Absorption improved by ingestion of a high-fat meal[
  • Short duration of action requiring several administrations per day[1,2,3,5]
  • Absorption may be unreliable[
  • Variable clinical response[
Preparations with limited current utilization
Patches (native testosterone) Applied to various areas of the skin daily or every other day (generally applied on a non-hairy part of the upper body or to a shaved area of the scrotum)
  • Efficient – steady absorption of testosterone mimics the normal diurnal rhythm of testosterone secretion[1,2]
  • May require application of 2 patches daily in some men to achieve adequate levels of testosterone[1,2,3,5]
  • Require formulation with absorption-enhancing carrier substances[
  • High chance of skin irritation[
  • May be inconvenient to apply and can be dislodged[
Implant Therapy (native testosterone) Small pellets are placed subcutaneously (usually in the stomach or buttocks) under local anesthetic
  • Infrequent dosing - usually required twice a year[1,3,5]
  • Testosterone levels peak after 1 month then remain stable for 4 to 6 months as the pellets are slowly absorbed[
  • May be pain and/or local infection at the site where pellets are inserted[1,3,5,6]
  • Special equipment and minor surgical procedure required[
  • Occasionally a pellet is expelled spontaneously by the body[
  • Scars after pellet removal[
Buccal System Controlled-release, bioadhesive testosterone tablets. Used twice daily
  • Absorbed from buccal mucosa and delivered directly to the vena cava superior, bypassing the gastrointestinal system and the liver[2,3]
  • Failure to adhere to gum[1,3]
  • Gum-related adverse events
Other forms of Oral Therapy (17-α-methyl testosterone, fluoxymesterone) Other androgen formulations taken orally as pills or capsules – not recommended for long-term replacement of testosterone
  • Orally active[1-5]
  • Considerable variation in absorption of dose[1-4]
  • Testosterone has to be in an altered form so that it is not broken down by the liver
  • Another form (methyl testosterone) produces harmful side effects including liver toxicity and elevated cholesterol levels and should not be used[
1. Bhasin S, et al. J Clin Endocrinol Metab 2006; 91(6): 1995-2010;
2. Qoubaitary A, et al. Expert Opin Pharmacother 2005; 6(9): 1493-506;
3. Seftel A. Int J Impot Res 2007; 19(1): 2-24;
4. Sharma V, Perros P. Postgrad Med 2009; 121(1): 113-21;
5. Tung DS, Cunningham GR. The Endocrinologist 2007; 17(2): 101-115;
6. Zitzmann M, Nieschlag E. J Reproduktionsmed Endokrinol 2006; 3(2): 109-116;
7. Bayer Schering Pharma AG. Global Nebido Satisfaction Study 2009.

Figure 6. Available Fromulations of Testosterone Replacement Therapy
Available Fromulations of Testosterone Replacement Therapy

Not all preparations are available in all markets. An ideal preparation of testosterone will raise testosterone levels back into the mid-normal range to reverse the symptoms of hypogonadism. It will also be safe, and offer a convenient dosing schedule and means of administration at a reasonable cost. Several months of treatment may be required before changes are apparent.1,6 See Monitoring During Testosterone Replacement Treatment

Intramuscular injections of testosterone enanthate, which have been the standard form of testosterone therapy in male hypogonadism, are increasingly being replaced by more recent therapies using transdermal formulations of testosterone and long-acting injectables such as testosterone undecanoate. Such preparations are easier to administer and provide more stable physiological levels of testosterone. Two such preparations are injectable long-acting testosterone undecanoate (Nebido®) and testosterone gel (Testogel®).

The long-acting injectable formulation of testosterone undecanoate was developed to overcome the shortcomings of conventional testosterone injections, usually requiring only four injections per year to maintain testosterone levels constantly in the eugonadal range, without the nonphysiological peaks and troughs associated with conventional testosterone injections.2,5 Patients value the consistent, reliable efficacy and the long duration of effect, which means they are not dependent on taking frequent medication.7 Consequently, testosterone undecanoate is likely to become the standard preparation for long-term testosterone replacement therapy. Read more on Nebido®  

The transdermal gel contains native testosterone in a clear and colorless formulation which is absorbed by the skin within a few minutes after the morning application to the upper arms, shoulders and abdomen, without leaving any residue. The serum testosterone concentration remains very reliably within the normal range for 24 hours after application.2,4,5. Read more on Testogel® 

The advantages and disadvantages of other testosterone formulations are listed in Table 4 In summary, testosterone patches are transdermal formulations of native testosterone applied to the skin of the abdomen, back, shoulders, upper arms or thighs (or scrotum, in the case of scrotal patches). Although a steady absorption of testosterone is provided over a 24-hour period, some men may require two patches daily to achieve serum testosterone levels in the middle of the normal physiological range recommended as a goal for testosterone replacement therapy.1

Oral testosterone undecanoate has the convenience of oral administration without the same potential for liver toxicity as another oral testosterone formulation, 17-α-testosterone.1-4 However, a short duration of action requires 2-3 times daily dosing, and clinical responses are less consistent than with the long-acting injectable formulation of testosterone undecanoate or the testosterone gel.1-2 

References:
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. Qoubaitary A, Swerdloff RS, Wang C. Advances in male hormone substitution therapy. Expert Opin Pharmacother 2005; 6(9): 1493-506.
3. Seftel A. Testosterone replacement therapy for male hypogonadism: part III. Pharmacologic and clinical profiles, monitoring, safety issues, and potential future agents. Int J Impot Res 2007; 19(1): 2-24
4. Sharma V, Perros P. The management of hypogonadism in aging male patients. Postgrad Med 2009; 121(1): 113-21
5. Zitzmann M, Nieschlag E. Testosterone substitution: current modalities and perspectives. J Reproduktionsmed Endokrinol 2006; 3(2): 109-116
6. Wang, C., E. Nieschlag, R. Swerdloff, et al. Investigation, treatment and monitoring of late-onset hypogonadism in males: ISA, ISSAM, EAU, EAA and ASA recommendations. Eur J Endocrinol 2008, 159(5): 507-514
7. Bayer Schering Pharma AG. Global Nebido Satisfaction Study 2009

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