How do you monitor and adjust testosterone replacement therapy dose?

A primary care colleague asked me this question recently. The answer depends on the form of testosterone therapy that has been prescribed. After confirming a patient has hypogonadism and treatable causes are ruled out, testosterone replacement therapy is initiated. Subsequent monitoring is done to confirm the dose is optimal.

Patients who are on intramuscular testosterone often have a nonphysiologic “saw tooth” pattern of testosterone levels which are higher than optimal soon after injection and decrease to lower than optimal before the next injection. This is why I tend to prefer transdermal preparations in most patients, except those who have financial limitations or who cannot apply the transdermal testosterone themselves.

After a patient has been on testosterone injections, I measure a trough testosterone on day of injection (before it is given) and a peak testosterone level about 24 to 48 hours after the injection. The goal is to keep the peak from being too high and the trough from being too low. This can be difficult in many patients. If a patient seems to be having too much variation in levels but cannot be switched to transdermal testosterone, I sometimes decrease the dose while increasing the frequency of injections. For example instead of 400 mg IM every month I might prescribe 100 to 150 mg IM every 7 to 10 days.

Transdermal testosterone patches are placed nightly. Patches keep testosterone levels stable and with less variation than injections. I usually test an early morning testosterone in patients on transdermal testosterone patches. The goal for the majority of patients is a total testosterone in at least the mid to normal range of 400 to 600 ng/dL. I aim for higher levels in younger patients and accept lower levels in older patients.

Transdermal testosterone patches do have a higher rate of dermatologic reactions compared with testosterone gel. These skin reactions can often be managed with corticosteroid creams. However, because of this adverse effect, my preference for transdermal testosterone replacement therapy is topical gel.

Patients on testosterone gel usually apply first thing in the morning after a shower. Testosterone levels may appear too low if obtained immediately before gel is applied and too high if it is measured within the hour or two afterwards. Therefore, I usually measure a total testosterone after levels have plateaued, about 6 to 8 hours after application. The goal is a total testosterone in at least the mid to normal range or higher.

If levels are too low in a patient on testosterone gel, often the explanation is poor application technique. I instruct patients on how to apply, and to apply over as large a surface area as possible to maximize absorption. As I wrote in a previous post, there is risk of exposing others. Patients on testosterone gel must take special precautions to avoid this.

Once the dose is optimized, I do not repeat levels very often, perhaps once a year, unless the patient is having symptoms or the dose is changed. Patients will also need a baseline CBC before treatment, at 3 months, 6 months and then annually thereafter. The risk for erythrocytosis seems to be greatest with testosterone injection therapy, but could occur with any form of testosterone if the dose is too high. Prostate-specific antigen and rectal exams are also advised in those aged older than 40 years.

(Disclosure: I have never had any relationship with any manufacturer of transdermal testosterone gel. My preference is based purely on my own clinical experience.)