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The pain with testosterone
Watch out for hypogonadism in patients taking opioids.
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A 40-year-old man was referred to me by his urologist for an evaluation of hypogonadism. The patient had been started on anastrozole five years ago, when a fertility evaluation revealed total testosterone levels in the low 200s.
The patient and his wife successfully conceived a child, and he was maintained on this treatment for five years until he moved and saw a new urologist. The patient related a history of chronic back pain that started after an accident eight years ago and was being treated with a cocktail of medications, with ever-increasing dosages over the past two years.
He also complained of depression, fatigue, impaired memory, suppressed libido and erectile dysfunction. Frequency of relations with his wife was decreased to once per month. He had gained 20 lb over the past two years and was rarely able to exercise due to fatigue and chronic back pain. He denied a history of fractures.
 Ronald Tamler |
Other medical history consists of migraine headaches and hypertension. Medications: anastrozole 1 mg daily, oxycodone hydrochloride (Oxycontin, Purdue Pharmaceuticals) 160 mg three times a day, methadone 5 mg daily, oxycodone 90 mg four time a day as required, pregabalin (Lyrica, Pfizer) 100 mg twice a day, clonazepam as required, pantoprazole sodium (Protonix; Wyeth) 20 daily, cetirizine (Zyrtec, McNeil Consumer) 10 daily and multiple vitamin injection.
The patient did not smoke and consumed one alcoholic beverage per week. He denied the use of recreational drugs.
On physical exam, this was a 40-year-old white man with depressed affect. He was mildly overweight with a BMI of 26, heart rate 80, BP 130/80, waist circumference 40 in. Urogenital examination showed that testicular size was normal at approximately 18 cc, normal consistency. Normal sized phallus. Normal amount and male distribution of pubic hair. Normal amount of axillary hair. The patient had a depressed affect throughout the interview and appeared a bit loopy. Exam was otherwise unremarkable.
Labs showed a total testosterone of 435 (normal), estradiol 12 (normal), sex hormone-binding globulin, prolactin, thyroid-stimulating hormone and free T normal, chem 12 normal, with the exception of aspartate transaminase and alanine transaminase elevations to twice the upper limit of normal.
The patient was wondering why the urologist had sent him to me, since his testosterone levels were fine. He was not planning on having more children in the next year.
What is the most appropriate plan of action for this patient?
- Continue his treatment with anastrozole, as it appears to be working fine.
- Change his treatment to clomiphene 50 mg daily.
- Discontinue anastrozole and start testolactone.
- Discontinue anastrozole, and see what happens.
- Discontinue anastrozole, order a bone mineral density test, start treatment with testosterone gel and contact the patient’s pain specialist to discuss whether his opiate regimen can be adjusted.
CASE DISCUSSION
The patient was being treated with anastrozole, an aromatase inhibitor, for hypogonadism. This class of drugs blocks the conversion of testosterone to estradiol by the enzyme aromatase. This has two effects: first of all, more testosterone is available, because there is no conversion. Secondly, it is estradiol that is being held responsible for the negative feedback loop at the pituitary level. Lower estradiol levels mean more stimulation of the testicle by luteinizing hormone to produce testosterone.
Unfortunately for this patient, however, decreased estradiol levels are also associated with a decline in BMD, which is one important reason why treatment with anastrozole in men (which is not approved by the FDA) should have a limited time horizon of a few months. In addition, there are very little data on effect and adverse events in men receiving more than six months of this treatment. A is therefore not the right answer.
In this case, the patient had osteopenia, with a T score at the spine of -1.7, and at the hip of -1.2. For the same reason, testolactone, another aromatase inhibitor, should not be used in this patient at this time (C).
Clomiphene (B) is a selective estrogen receptor modulator, which centrally stimulates testosterone production. While this treatment can indeed increase testosterone levels, there are little data on treatment and adverse events beyond six months in men.
While it is tempting to opt for option D, discontinuation of anastrozole would most likely lead to decreased testosterone levels with overt symptoms of hypogonadism in an already depressed patient. A taper should be attempted in patients who have received the treatment for reasons that are unclear. However, opiates suppress LH and follicle-stimulating hormone production, which is most likely the case in this patient. He is probably also affected by other centrally acting medications.
Therefore, the best choice is to contact the treating physician or physicians who are managing the patient’s pain and to discuss how the pain-relieving regimen can be consolidated or even tapered. This is particularly important in a patient who appears to be overmedicated during the interview. In this case, the patient was started on testosterone gel and underwent a tapering regimen for his pain medication. Nine months later, the patient was tapered off testosterone and off opiates and had a total testosterone level of 513. He was feeling much more energetic. A repeat BMD test has not yet been obtained.
Ronald Tamler, MD, PhD, is an Assistant Professor in the Division of Endocrinology at Mount Sinai School of Medicine.