Test your medicine knowledge with the MKSAP challenge, in partnership with the American College of Physicians.

A 37-year-old man is evaluated for a 2-year history of low libido, loss of morning erections, fatigue, and decreasing muscle mass. His medical history is otherwise unremarkable. He takes no medications.

On physical examination, vital signs are normal. BMI is 35. The remainder of the examination, including genital examination, is normal.

Laboratory studies:

Luteinizing hormone	10 mU/mL (10 U/L)
Prolactin	Normal
Morning testosterone (total)	148 ng/dL (5.1 nmol/L)
Confirmatory morning testosterone (total)	137 ng/dL (4.7 nmol/L))
Thyroid-stimulating hormone	Normal

A pituitary MRI is normal.

Before initiating therapy for this patient, which of the following should be determined?

A. Bone mineral density
B. Desire for fertility
C. Fasting plasma glucose level
D. Scrotal ultrasound

MKSAP Answer and Critique

The correct answer is B. Desire for fertility.

Before initiating therapy for this patient with hypogonadism, his desire for fertility should be explored. Testosterone replacement therapy can be associated with decreased spermatogenesis and infertility. Exogenous testosterone suppresses both hypothalamic gonadotropin-releasing hormone and pituitary follicle-stimulating hormone and luteinizing hormone (LH) production, resulting in depletion of intratesticular testosterone. The effect is suppression of spermatogenesis so pronounced that testosterone replacement therapy has been studied as a male hormonal contraceptive. Based on Endocrine Society guidelines, men with hypogonadism should be treated with exogenous testosterone when they have consistent signs and symptoms of hypogonadism and low serum testosterone levels. Symptomatic men may report reduced libido, erectile dysfunction, mood changes, irritability, fatigue, or memory loss. Although this patient’s symptoms would likely be improved with exogenous administration of androgen, replacement therapy may also result in infertility due to oligospermia. Patients with hypogonadism who desire fertility may require treatment with human chorionic gonadotropin (HCG). HCG has LH-like activity and stimulates the production of intratesticular testosterone, resulting in the high concentrations required for induction and maintenance of spermatogenesis.

Asymptomatic men with low serum testosterone levels may experience decreased bone mineral density and osteoporosis. Hormone replacement therapy will decrease the risk of osteoporosis. A bone mineral density measurement prior to the initiation of hormone replacement therapy is not needed.

Male hypogonadism is associated with increased visceral fat and insulin resistance, and hormone replacement therapy improves these metabolic parameters. There is no recommendation that hypogonadal patients initiating hormone replacement therapy be screened for diabetes mellitus with fasting plasma glucose measurement or other testing.

A 2010 systematic review of hypogonadal men receiving testosterone therapy found no evidence of increased risk of prostate cancer when compared with the placebo/nonintervention group. The Endocrine Society guideline on testosterone replacement therapy recommends a digital rectal examination and prostate-specific antigen (PSA) level determination at 3 and 6 months following the initiation of replacement therapy. Continued regular screening is recommended for men older than 40 years of age with a baseline PSA level greater than 0.6 ng/mL (0.6 µg/L). Scrotal ultrasound is unnecessary prior to initiation of testosterone therapy; a clinical testicular examination to rule out abnormalities or a testicular mass is sufficient.

Key Point

• Prior to initiation of testosterone therapy for hypogonadism, the desire for fertility should be ascertained because exogenous testosterone replacement therapy may result in oligospermia and infertility.

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