Testosterone Replacement Therapy: 10 Tips

Pharmacy Times, September 2016 Men's Health, Volume 82, Issue 9

The number of testosterone prescriptions has followed an upward trajectory since 1999.

Sometimes, all it takes for a prescription product to move from relative obscurity to remarkable utility is a little dosage-form engineering. That is testosterone’s story. The number of testosterone prescriptions has followed an upward trajectory since 1999, when prescribers wrote 648,000 of them. By 2002, that number had jumped to 1.75 million prescriptions; in 2012, 2.2 million.1,2

The primary indication for prescription testosterone is replacement therapy for a deficiency (ie, androgen deficiency syndrome or hypogonadism). Today, although a variety of testosterone formulations are available, public concern is substantial. Pharmacists need to be aware of 10 key points about testosterone replacement therapy (TRT) to allay concern and ensure patient safety.

1. Testosterone’s androgenic effects begin in the perinatal period, when sex organs develop. They continue at puberty, stimulating secondary sex characteristics such as voice deepening, beard growth, and development of axillary hair. Testosterone’s anabolic effects increase muscle mass, strength, bone density, and bone maturation throughout life.3,4

2. The FDA has approved TRT for classic androgen deficiency caused by pathologic conditions (eg, Klinefelter’s syndrome, orchiectomy, chemotherapy). Many prescribers also use testosterone for age-related testosterone decline, which is called late-onset hypogonadism. This is an off-label use.3

The 2010 Endocrine Society Clinical Practice Guidelines did not address some populations, but the results of later studies indicate that men with metabolic syndrome or frailty may benefit from TRT based on improvements in biometrics, insulin sensitivity, muscle strength, and bone health.4

3. The Endocrine Society’s guidelines indicate that to diagnose testosterone deficiency in a patient, the patient must present with the following:

  • Symptoms (eg, low energy, depressed mood, low sex drive, erectile dysfunction)
  • A serum testosterone concentration lower than 300 ng/dL5

Recent findings indicate that 25% of patients prescribed testosterone did not have their testosterone levels checked before starting treatment.

4. Serum testosterone concentrations are diurnal. In young men, the concentrations are highest in the morning. Older men tend to have similar, but blunted, patterns.6,7 Clinicians should draw serum testosterone levels between 8:00 am and 11:00 am.5 Patients’ serum testosterone levels vary over time, so providers should not rely on 1 test. For example, one-third of men who have low testosterone levels will have normal levels when they repeat the test.

5. Recent findings indicate that almost 20% of all new users received treatment for 30 days or less.6,7 TRT is designed to be long-term therapy, however. The high incidence of short-term use indicates that some TRT use may be injudicious.

6. The degree and duration of testosterone deficiency influence the signs and symptoms. Restoring serum testosterone concentrations to normal range can produce beneficial effects (Table 18-17).9,10

7. TRT has some risks and adverse effects (Table 23,18-23).

8. Testosterone is available as oral tablets that are well absorbed from the intestine, but quickly metabolized by liver enzymes. The gel, transdermal patch, buccal injection, and intramuscular injection avoid hepatic metabolism and improve delivery.24-26 The transbuccal route avoids first-pass hepatic metabolism and mimics endogenous testosterone’s diurnal pattern, while gels elevate serum testosterone for longer durations than the transdermal patch does.25 Another testosterone product available in solution form is applied to the underarms.27 The viscosity of oil-based esterified testosterone injection requires good administration technique using smaller-gauge needles to reduce tissue scarring.25 Subcutaneous testosterone pellet implants are also available and deliver normal serum levels of testosterone for 3 to 4 months.28

9. Monitoring is critical. Table 34 lists tests that clinicians should order at baseline and periodically during therapy.

Table 3. Laboratory Monitoring of Testosterone Therapy

  • Testosterone levels (at baseline; repeat at 3-6 months)
  • Digital rectal examinations and prostatic-specific antigen tests
  • Hematocrit to screen for polycythemia
  • Liver-function tests
  • Lipid panel

Adapted from reference 4.

10. Prescribers must consider pharmacokinetic properties, treatment burden, and therapy cost when they work with candidates for TRT.

CONCLUSION

When testosterone deficiency causes troublesome signs and symptoms, TRT can be beneficial. Pharmacists can use counseling and medication therapy management to help patients use TRT properly. Pharmacists must advise patients about skin irritation at the application or injection site and warn that direct skin-to-skin contact with women or children can transfer the product and cause adverse effects in the recipient.

Ms. Wick is a visiting professor at the University of Connecticut School of Pharmacy.

References

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