Intramuscular injections of testosterone enanthate have, for many years, been the standard form of testosterone therapy in male hypogonadism. Testosterone enanthate is administered every two to three weeks. Testosterone enanthate is characterized by a wide margin of safety. However, 24 to 48 hours after injection there are unphysiologically high serum tstosterone concentrations, followed by an exponential drop to subnormal values before the next injection. In some patients these fluctuations lead to impairment in well-being and mood swings.
The long-acting injectable testosterone ester - testosterone undecanoate - overcomes the shortcomings of conventional testosterone injections. 1000mg testosterone undecanoate are dissolved in an oily solution. Only four injections are required per year for long-term testosterone therapy. Testosterone levels remain constantly in the eugonadal range, avoiding unphysiological peaks and troughs. Patients value the consistent, reliable efficacy and the long duration of effect, which mean they are not dependent on taking frequent medication. Consequently, testosterone undecanoate is believed to become the standard preparation for long-term treatment..
Transdermal
Testosterone Gel
The gel contains native testosterone. It is clear and colorless and 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.
Testosterone Patches
The first transdermal preparation was the testosterone patch. The patches contain native testosterone. Reservoir patches are applied to the skin of the abdomen, back, shoulders, upper arms or thighs. Theycontain native testosterone and have to be replaced daily. As testosterone is lipid-soluble and cannot be easily transported through the skin from a limited area, the formulation has to contain absorption-enhancing carrier substances. These lead to poor skin tolerance in many patients often resulting in irritation and inflammation.
Oral
Testosterone undecanoate is available as capsule for oral administration. The testosterone is esterified with a medium-chain fatty acid so that, after absorption, it enters the bloodstream via the lymphatics, thus partially circumventing the first-pass effect of the liver. The duration of action is nevertheless short, so that distribution of the total dose over several administrations per day is recommended. Also, the absorption is not very reliable. It is improved by simultaneous ingestion of a high-fat meal.
Mesterolone, a derivative of dihydrotestosterone, is a special case. It cannot be converted either to estrogens or to testosterone and therefore does not have the full spectrum of action of testosterone.
Methyltestosterone and fluoxymesterone are now only available in a few countries as it has emerged that these 17-alpha-methylated androgens are potentially hepatotoxic on prolonged use.
Subcutaneous Administration
Testosterone implants contain native testosterone in the form of pellets. These pellets are implanted under the skin of the abdomen under local anesthesia. Three to six pellets ensure gradually declining testosterone levels within the normal range for a duration of four to six months. Then new pellets have to be implanted. Infections and rejection reactions occasionally occur.
These pellets are currently only available in the United Kingdom and Australia.
Buccal System
The buccal system for testosterone delivery has been developed with a tablet-like product that adheres to the gum surface of the mouth. Testosterone is absorbed into the blood stream through the gum and delivered directly into the vena cava superior, bypassing the gastrointestinal system and the liver. Twice daily dosing is necessary to achieve mean average serum levels of testosterone within the normal range. Patients frequently report problems with the buccal system not sticking to the gum.