Testosterone therapy in hypogonadal men

There are several FDA-approved testosterone preparations for men with documented hypogonadism: intramuscular injection of testosterone cypionate or testosterone enanthate; transdermal preparations available as individual packets, as a pump bottle or in a tube preparation; and a buccal preparation. Once a decision to prescribe therapy has been made I present each of these preparations to the patient and not surprisingly they want to know which one I prefer. I do have a preference for injectable testosterone initially, because I have found that the clinical response occurs more quickly than with the other preparations, and I explain that I plan to switch to a noninjectable preparation after one to two months. That is clearly not the patient’s preferred choice and most elect to use a transdermal preparation.

As with most medications, the dose depends almost entirely on the patient’s response to the initial therapy, but this can at times be difficult to determine. There are patients who happily report improvement in overall health and well-being after just two weeks of therapy, but for many the response is slower and at times frustrating. If the initial therapy has been intramuscular injection and the patient does not experience any benefit, I quickly recommend a change to something else. In contrast if the initial therapy is transdermal, I probe a little deeper into what specifically they were expecting as a response and recommend patience through at least two months of therapy before recommending a dose increase. I try to avoid an increase in the dose until I have obtained my first set of follow-up labs.

Once the etiologic diagnosis of hypogonadism is determined and a decision to appropriately start testosterone (it is not appropriate, for example, in patients with a prolactinoma) I check the fasting lipid profile, hematocrit and prostate-specific antigen levels at baseline. I usually monitor these every three months on therapy but rely on them to temporarily interrupt therapy and not in determining whether the dose should be increased. For that I rely on the patient’s clinical response. I reserve serial measurement of testosterone for patients who report an unsatisfactory clinical response.

Small increments in PSA are expected, but the many clinical trials that led to FDA approval of each of the available therapies indicate that the increase is very infrequently of clinical significance. I have found that the most common reason to interrupt therapy is a worrying increase in hematocrit that usually resolves after four weeks without therapy, at which time I restart with a lower dose, again relying heavily on the patient’s clinical response to assess the adequacy.

I have most trouble with monitoring the changes in the lipid profile, particularly the HDL. The anticipated decrease is usually small and less so with enanthate than cypionate, but there are patients, such as the man I saw recently, in whom the HDL was very low at 16 mg/dL (reference >40). I have reservations about giving therapy that will lower this even further, albeit by a small amount. To complete his picture, his LDL was 70 mg/dL, but his fasting triglycerides were elevated at 220 mg/dL (reference <150). There are no data that testosterone will harm this patient with respect to risk of cardiovascular disease, but it is certainly something I will be monitoring closely. I could add therapy to try and improve his lipid profile, but I will start with advising him about his diet and wait to see what happens to the profile on testosterone.