Testosterone Therapy in Men
Testosterone replacement is indicated in men only if they are truly hypogonadal. This could be due to
primary gonadal disease or to pituitary gland insufficiency. Also could be due to chronic disease or opioid
use. It is not common for healthy men at any age to be hypogonadal. This diagnosis must be carefully
established, since (1) therapy has risks and (2) once started it is difficult to stop due to suppression of the
pituitary-gonadal axis.
In order to establish a diagnosis of hypogonadism in a person without known pituitary or gonadal disease,
the following steps are required.
1) Total testosterone that is generally <300 ng/dl when measured in the morning generally before
10AM. It should not be measured when the patient is sick, even with a virus.
2) If the testosterone appeared low it should be repeated in a few weeks to confirm (levels vary with
the patient’s state of well being.) This repeat test should include a free testosterone or a sex
hormone binding globulin. If the free testosterone is normal, then the patient is normal. If the sex
hormone binding globulin (SHBG) is at the low end or below the normal range, then a “low” total
testosterone is expected and normal. A mid-normal or higher SHBG and a low total testosterone
would indicate true hypogonadism.
3) If testosterone is truly low, then you must ask why. FSH and LH assay are indicated.
a. If FSH and LH are high (especially over 20 IU/ml) then the patient has gonadal failure.
Testosterone therapy is indicated.
b. If the FSH and LH are low (especially under 3 IU/ml) then there is pituitary insufficiency
that requires more extensive evaluation. The patient may have a pituitary tumor.
4) If the patient has serious chronic disease or chronic high dose opioid use, modest testosterone
therapy can be carefully given when FSH, LH and total testosterone are all somewhat low.
Caveats:
1) Testosterone is atherogenic. Excessive replacement must be avoided. Testosterone is known to
advance atherosclerotic coronary artery disease and to promote stroke. Elevation of hematocrit
increases risk.
a. Testosterone cypionate injections should generally not exceed 100 mg per injection or
300 mg total in divided doses per month.
b. Levels should be checked mid-way between injections and should be in mid-normal
range. A trough level can be done also to ensure dose is not excessive. Trough level
should be <300 ng/dl.
c. If taking testosterone gel, levels should be monitored mid-day and should be in the midnormal range.
d. Hemogram must be monitored for excessive erythropoiesis caused by testosterone.
2) Testosterone can advance prostate cancer. Prostate should be evaluated prior to therapy. PSA
should be monitored yearly.
3) Testosterone renders a male infertile. This is reversible, but may take a year. Patients should be
asked if they might have a future desire to father children.
4) The only somewhat reliable symptom of low testosterone is loss of libido. Fatigue is NOT a
reliable symptom. Testosterone therapy usually does not improve fatigue. Truly hypogonadal men
do have a decrease in strength and endurance and decreased growth of secondary sexual hair.
5) Uncertain cases and pituitary cases should be referred for endocrine evaluation BEFORE starting
testosterone therapy.
Integris Health Partners Pharmacy Task Force
John S. Muchmore MD, PhD