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Doing well on the gel: Declining testosterone levels on treatment pose challenge
A 68-year-old man presented in follow-up for hypogonadism. He was last seen by me half a year earlier. Since that visit, the patient reported generally feeling energetic, with good libido and good erectile function until he started feeling “a bit drab” approximately 1 month before this visit.
The patient had been treated for hepatitis C virus 3 years earlier and in the aftermath had been diagnosed with secondary hypogonadism that did not resolve after recovery from treatment. The patient was subsequently started on transdermal testosterone supplementation and always tolerated the medication well.
Ronald Tamler
He shaved once a day, denied changes in body hair or weight and denied a history of fractures. He applied the transdermal testosterone daily on his shoulders after showering, the way he always had. He denied rashes or pruritus.
Medications and nutritional supplements were unchanged from the previous visit:
- Testosterone (AndroGel 1%; AbbVie), 50 mg/5 g gel in packet; one packet applied to skin daily.
- Arginine (L-Arginine, Ajinomoto), 3 g daily by mouth.
- Coenzyme Q10, 10-mg oral capsule daily by mouth.
- Omega-3 fatty acids (fish oil oral), 1,000 mg daily by mouth.
- Calcium carbonate-vitamin D3-mineral, 600 mg calcium, 400-unit tablet by mouth twice daily.
- Zinc 50 mg, oral capsule once daily.
Medical history:
- Viral hepatitis
- Glaucoma
- Chronic hepatitis C
- Nephrolithiasis
- Cholelithiasis
- Hypogonadism
Surgical history:
- Hx glaucoma surgery
The patient had no known allergies, was single and worked as a functionary in a nonprofit organization.
He had never smoked and denied alcohol or drug use.
On physical exam, the patient’s weight was stable, at 174 lb. Blood pressure 113 mm Hg/58 mm Hg; pulse 67; height 6’3”; Estimated BMI was 21.75 kg/m2.
The patient was in no acute distress, well developed/well nourished. Physical exam was generally unremarkable, with no gynecomastia, no rashes and no leg edema.
Labs:
- CBC, chemistry and PSA within normal limits.
- Labs from his previous visit, 6 months prior:
- Testosterone, 524.48 ng/dL (at goal).
- Estradiol, <20 pg/ml
This visit:
- Testosterone, 167.8 ng/dL (Low)
What is the next best step in this patient’s management?
A) No change. Return to practice in 6 months for follow-up.
B) Stop testosterone supplementation and start anastrozole 1 mg daily.
C) Ask the patient to apply the testosterone gel on the upper part of his abdomen and measure testosterone level approximately 10 days later.
D) Change the patient’s regimen to testosterone cypionate 200 mg intramuscularly every 4 weeks.
E) Stop all testosterone supplementation.
Answer: C
Every once in a while, a patient previously successfully treated with transdermal testosterone will present with unusually low testosterone levels.
If the patient has symptoms to match these levels over an extended period of time, chances are that the gel is not absorbing properly at the location of application (a batch of the product with production or storage issues would have run out at some point).
Simply asking the patient to return for follow-up half a year later ignores the patient’s interests and well-being (A). Stopping all testosterone supplementation altogether — currently a matter of debate in older men given recent reports of cardiovascular concerns in that group — also does not solve this patient’s dilemma of low serum testosterone levels while on treatment (E). Anastrozole, an aromatase inhibitor, is not approved by the FDA for treatment of male hypogonadism, but it will increase testosterone by inhibiting conversion of testosterone to estradiol. That said, in a patient with an estradiol level of <20 pg/ml, it is dubious whether this poorly documented treatment would add much (B). It is perfectly reasonable to recommend an alternate method of testosterone supplementation when poor absorption of transdermal testosterone is documented however, monthly dosing with intramuscular testosterone cypionate will predispose the patient to wild swings of testosterone levels, with subsequent changes in mood and other parameters (D).
More realistically, a different topical formulation can be tried. In this case, I opted to have the patient apply his prescription to a different area of the body for a few days (C). Test results 10 days later showed that levels were at goal, and the patient was starting to feel better: testosterone, 541.76 ng/dL.
For more information:
- Ronald Tamler, MD, PhD, MBA, is clinical director of the Mount Sinai Diabetes Center in New York. He also is an Endocrine Today Editorial Board member. He reports no relevant financial disclosures.