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Tired of low testosterone: Record check reveals cause of weight gain and fatigue
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A 25-year-old man presented to my office for an initial evaluation of hypogonadism, fatigue and weight gain.
He reported a history of oral anabolic steroid prohormone use for 6 months at about age 22 years, after which he felt fatigued and listless. He saw a urologist approximately 1 year before seeing me and was diagnosed with secondary male hypogonadism. He started on clomiphene 25 mg daily at that time, initially taking half of a 50-mg tablet and then switched to 25-mg capsules, which he was taking initially every other day and now takes daily.
The patient has noticed a weight gain of 35 lb during the past 6 months, as well as fatigue, and he has recently embarked on a strict diet.
Ronald Tamler
The patient shaves once a day, entered puberty at about age 11 years, and reports no changes in body hair or gynecomastia and erectile dysfunction. Libido is fair, and he is not trying for children at the moment (although he wants to in the future). He has no history of fractures. He snores, but review of systems is otherwise negative.
Besides anabolic steroid use, medical history consists of acne and attention-deficit/hyperactivity disorder. The patient is adopted and cannot provide family history. He reports no use of nicotine, alcohol or recreational drugs. He works as a derivatives trader.
Medications consist of clomiphene 25 mg, Finacea (azelaic acid, Bayer) 15% topical and Adderall XR (amphetamine, dextroamphetamine mixed salts; Shire) 30 mg daily. He reports using no nutritional supplements.
Physical exam revealed blood pressure 134 mm Hg/88 mm Hg, pulse 98 bpm, temperature 36.7°C (98.1°F), height 5’10”, weight 102.9 kg and estimated BMI 32.5 kg/m2. The patient has centripetal obesity and fatty gynecomastia. Phallus is normal in shape and size. Hair shows normal male-pattern hair distribution (groomed). Testicular size is normal at approximately 20 mL bilaterally. The patient has acne. Broad violaceous striae are apparent on the lower left side of the patient’s back, but none under his arm pits or in the groin area.
There is no moon face or dorsocervical fat pad, and skin does not appear to be thin.
A morning testosterone measurement from his initial visit with the urologist 1 year before seeing me was remarkable for a low total morning testosterone of 98 ng/dL with a sex hormone-binding globulin level of 6 nmol/L and with luteinizing hormone and follicle-stimulating hormone in the low-normal range. Total testosterone was 457 ng/dL 3 months into the treatment, but 3 months before seeing me was down to 203 ng/dL. Prolactin is normal. Complete blood count and chemistry are within normal limits.
What is the next best step in the management of the patient?
A. Contact the patient’s pharmacy to ensure full medication reconciliation.
B. Order 24-hour urine cortisol.
C. Encourage lifestyle changes for more weight loss, which will improve testosterone profile.
D. Prescribe Belviq (lorcaserin, Eisai) for weight loss.
E. Prescribe testosterone supplementation.
Case discussion
Answer: A
Clomiphene is not FDA approved for treatment of male hypogonadism, but it has been used successfully for secondary hypogonadism in young men for decades. In a young man with a history of anabolic steroid use who eventually wants to father children, it is, therefore, not surprising that my colleague chose clomiphene as an initial treatment to rehabilitate the patient’s gonadotroph axis. A standard dose is 25 mg daily.
The patient’s history shows a remarkable arch of initial response to treatment and subsequent decrease in testosterone with weight gain and fatigue. What set off some suspicion for me was that the patient was describing taking 25-mg capsules of clomiphene, which typically comes in 50-mg tablets.
In this particular case, I did not need to call the pharmacy, since my electronic medical record was able to pull all medications dispensed to the patient during the past 6 months. Remarkably, it did not feature clomiphene. Instead, he had apparently been taking clomipramine, a tricyclic antidepressant that may cause … fatigue and weight gain! This episode truly highlighted the importance of medication reconciliation.
Testosterone supplementation may be an option after sperm banking, but clomiphene will preserve fertility while maintaining the hope that the patient may eventually phase out of that treatment (E). Lifestyle changes to support weight loss are always a good choice, but they may be more difficult to achieve in a fatigued hypogonadal patient (C). That said, lifestyle changes should generally be attempted before thinking of prescribing an agent for weight loss (D).
Finally, acne, striae and weight gain may be seen in the setting of Cushing’s disease, but we do have a good explanation for this patient’s weight gain, and he explained that he gained the striae in the setting of his rapid weight gain. Should treatment and lifestyle changes not bear fruit, a 24-hour urine cortisol or midnight salivary cortisol may be in order (B).
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.