Testosterone is a hormone produced primarily in the testes in males, and in smaller amounts, by the ovaries and adrenal glands in females. It plays a role in developing male reproductive tissues, maintaining muscle mass, bone density, and influencing sex drive. Standard testosterone cannot be taken orally due to how the body processes it. However, specific modified oral formulations have been developed to address this challenge.
Challenges with Standard Oral Testosterone
When standard testosterone is swallowed, it faces first-pass metabolism. This process occurs as the substance is absorbed from the gastrointestinal tract and travels directly to the liver. The liver rapidly metabolizes and breaks down the testosterone before it can reach the bloodstream in sufficient amounts. This rapid breakdown renders unmodified oral testosterone largely ineffective as a therapeutic agent.
Historically, attempts to modify testosterone for oral use, such as 17-alpha-alkylated derivatives like methyltestosterone, led to liver toxicity concerns. These older formulations could cause liver damage, indicated by elevated liver enzymes, and in rare cases, jaundice or liver tumors.
Specific Oral Testosterone Formulations
To overcome first-pass metabolism, specific oral testosterone formulations have been developed. Testosterone undecanoate (TU) is an example designed to bypass the liver’s metabolic processes. This lipophilic molecule is absorbed into the intestinal lymphatic system after oral administration. From there, it enters the bloodstream, largely avoiding direct passage through the liver.
Once in the bloodstream, testosterone undecanoate is cleaved by enzymes to release active testosterone. This unique absorption pathway minimizes the liver’s exposure to high drug concentrations.
Newer oral TU products include brand names like Jatenzo, Kyzatrex, and Tlando. Another approach uses modified buccal tablets, such as Striant, placed against the gum for direct absorption into the bloodstream, also bypassing the liver.
Safety and Efficacy of Oral Testosterone
The safety profile of newer oral testosterone undecanoate formulations differs from older, liver-toxic oral steroids. Studies on these forms indicate that increased liver enzyme levels are not commonly associated with their use, and significant liver toxicities have not been noted in clinical trials. Unlike older formulations such as methyltestosterone, newer testosterone undecanoate forms avoid liver damage due to their unique absorption mechanism.
Oral testosterone, like other testosterone therapies, can affect cardiovascular health. Increases in blood pressure have been observed, with some studies showing an average rise of 4.9/2.5 mm Hg after several months of treatment. Monitoring blood pressure during therapy is important.
Testosterone therapy can also influence lipid profiles, sometimes lowering “good” cholesterol (HDL). Side effects reported with oral testosterone undecanoate include headache, nausea, diarrhea, and an increase in red blood cell count. While these increases are also seen with other forms of testosterone therapy, monitoring of hematocrit (red blood cell levels) is recommended.
Oral testosterone undecanoate has been shown to restore testosterone levels to the normal range in a significant percentage of men with hypogonadism. However, some oral formulations may require twice-daily dosing to maintain consistent levels.
Other Testosterone Delivery Methods
Beyond oral options, several alternative methods exist for testosterone administration.
Intramuscular injections involve administering testosterone directly into a muscle, providing a longer-lasting effect, typically requiring injections every one to four weeks. This method can lead to fluctuations in hormone levels, with peaks shortly after injection and troughs before the next dose.
Topical gels or creams are applied daily to the skin, allowing for continuous absorption. These offer convenience and consistent hormone levels, but there is a risk of transferring the hormone to others through skin-to-skin contact.
Transdermal patches are another daily option, providing a steady release of testosterone through the skin. Some individuals may experience skin irritation at the application site.
Subcutaneous pellets involve the surgical implantation of small testosterone pellets under the skin, usually in the hip or buttocks. These pellets release testosterone gradually over several months, offering sustained and consistent hormone levels without daily administration. While convenient, this method requires a minor procedure for implantation and removal.