by Ed Barillas, Staff Writer
Testosterone, by itself, cannot be given orally because the liver breaks it down (hepatic metabolism) substantially and thus causing very slight androgenic effects. However, alkylated forms of oral testosterone, which are much more resistant to hepatic metabolism, can exert a positive clinical effect when ingested, even though alkylated forms of testosterone are weaker than testosterone by itself.
The clinical efficacy of oral testosterone is further complicated by irregular absorption and varying degrees of hepatic breakdown on the first pass through the liver. In such, varying results can be seen when giving these agents. Its important to note that liver toxicity may be substantial with oral androgens and such toxicity may range from an elevation of liver enzymes to development of hemorrhagic liver cysts. Liver neoplasms have also been reported in men undergoing oral androgen therapy. Therefore, oral androgen therapy has very little place in the treatment of hypogonadism.
As far as injectable agents go, testosterone esters allow for some definite advantages. Esters are actually resistant to hepatic breakdown and are released slowly from oil-based carriers and are hydrolyzed to yield testosterone itself so delivery in a long-acting injection is possible and the biological effects of the injected form of testosterone is indistinguishable from the native hormone. The usual dosage is approximately 100mg of drug per week and the interval can be varied to smooth out these wide swings. So in other words, 100mg every week, 200mg every two weeks, 300mg every three weeks, so on and so forth. An acting injection is possible, and the biological effects of the injected form of T are indistinguishable from the native hormone.
After a testosterone injection, the serum T level rises to the high, normal or supernormal range for the first few days, which is followed by a progressive drop until the next injection is administered. The T level may drop below the normal range during this time and these wide swings may cause varying efficacy from the treatment.
As far as testosterone patch therapy, there are currently two available, Testoderm and Androderm. Testoderm is a patch that must be worn on the scrotum. In this location, skin absorption is increased due to the thin nature of the skin. Because of the thinness of the scrotal skin, permeation enhancers do not need to be placed into the formulation to achieve adequate drug absorption. Disadvantages include the necessity to shave the scrotal hair, irritation and difficulty with adherence of the patch, which has been partially circumvented with the addition of adhesive strips. Another potential disadvantage of Testoderm is the high level of 5-reductase activity in the scrotal skin with the potential of elevation of DHT levels. Herein, there is no evidence that an elevation of peripheral DHT levels will have any adverse effects on the prostatic tissue. Testosderm is applied to the scrotum each morning, and comes in 4 and 6 mg dosages.
Androderm is a patch that may be worn throughout the body and because of the increased thickness of the skin and a relative resistance to absorption of the testosterone; it is necessary to place permeation enhancers within the drug vehicle. Since permeation enhancers are present, this patch should never be worn on the scrotal skin where extreme absorption might occur. Two patches of only one dose are worn on flat areas of the skin and not overlying any joints or high movement areas. The pharmacokinetics dictate Androderm patches function best whey they are placed in the evening. Patch sites are rotated on a weekly basis so a patch is not placed in the same site anytime during the same week. Some of the advantages of Androderm include non-scrotal application and good adhesion and disadvantages include a non-discrete location and potential for skin reactions.
Both Androderm and Testoderm when placed properly at the correct time of day can cause a rise to the mid to upper normal range of serum T in the morning and a decrease to the low normal range in the evening. Therefore, patch therapy mimics the diurnal variation of normal testosterone secretion and appears to be more physiological. Wide swings seen with injection therapy are not seen and whether or not this more physiological pattern of delivery is more beneficial has not been proven.