What The Endocrine Society Guidelines on Testosterone Therapy Mean for Endocrinologists
The evidence-based guidelines on the evaluation and treatment of androgen deficiency syndromes in adult men updated in 2010 by The Endocrine Society are the most current recommendations available to guide practitioners. The following are highlights of the recommendations.
Diagnosis: Diagnosis should only be made in men with consistent signs and symptoms of androgen deficiency as well as low testosterone level documented by repeated laboratory tests. Use of morning total testosterone measurement is preferred; however, in men with borderline total testosterone levels or with suspected abnormal sex hormone binding globulin level, measurement of free or bioavailable testosterone level may be used. Evaluation should not occur during acute illness.
Treatment: Testosterone therapy is recommended for symptomatic men, to induce/maintain secondary sex characteristics and to increase sexual function, sense of well-being, muscle mass and strength, and bone mineral density. It is not recommended for patients with breast or prostate cancer, palpable prostate nodule or induration, or a prostate specific antigen (PSA) >4 ng/mL or PSA >3 ng/mL in men at high risk of prostate cancer, hematocrit >50%, severe lower urinary tract symptoms associated with benign prostatic hypertrophy (ie, AUA/IPSS score >19), uncontrolled or poorly controlled congestive heart failure, or uncontrolled severe obstructive sleep apnea.
The choice of testosterone formulation should be made based on patient preference, pharmacokinetics, cost, and treatment burden. The goal of treatment should be to achieve testosterone levels in the mid-normal range, according to the guidelines.
Treatment options include:
- 75 to 100 mg of testosterone enanthate or cypionate intramuscularly weekly, or 150–200 mg intramuscularly every 2 weeks
- One or two 5-mg testosterone patches nightly
- 5 to 10 g of 1% testosterone gel daily
- 30 mg of a bioadhesive buccal testosterone tablet every 12 hours
- Testosterone pellets implanted subcutaneously every 3 to 6 months (the dose and regimen vary by formulation)
- [Other formulations are available outside the United States]
Monitoring: Patients should be monitored every 3 to 6 months and then annually thereafter.
Key to the guidelines for use of testosterone treatment are: 1) confirmed low testosterone measurements, 2) signs or symptoms of low testosterone, and 3) absence of contraindications. As testosterone levels fluctuate throughout the day and night, to determine whether someone has hypogonadism, testosterone levels should be measured in the morning, when they are usually the highest. (This is assuming a normal sleep-wake cycle; it may be blunted in older individuals.) If free testosterone levels are used, they should be calculated (from total testosterone, albumin, and sex hormone-binding globulin) or measured by equilibrium dialysis; analog methods may well be inaccurate. The reference range should be age- and assay-specific. Signs and symptoms of low testosterone are necessary to determine the risk-benefit ratio of testosterone therapy, and those signs/symptoms should be monitored along with testosterone levels if treatment is initiated. Contraindications are based on known effects of testosterone, such as on red blood cell count.
Following establishment of low testosterone level, further testing should be conducted prior to initiation of treatment, to determine the etiology of the deficiency. In some situations, testosterone itself may not be the appropriate treatment, such as in men with secondary hypogonadism who desire fertility. Certain adjunct evaluations should be undertaken as well, to establish whether there are contraindications to testosterone therapy (PSA level and prostate exam, hematocrit, et al).
At present, there is no evidence to support screening of the general population. Evaluation should be sparked by signs or symptoms consistent with hypogonadism, or a history of certain illnesses.
The decision to start testosterone therapy is tailored to each patient. Broadly speaking, the use of testosterone treatment in adult men (that is, beyond puberty) can be separated into two categories: 1) use in adults with testosterone deficiency such as caused by disturbances in the hypothalamic-pituitary-testicular axis, and 2) use in adults with symptomatic hypogonadism of unknown cause. [Other uses may include induction of delayed puberty, use in transgendered individuals, and use in certain chronic disease states.] When the testosterone deficiency is due to known disease, the situation is more clear-cut for most physicians. It is less clear in older men with levels that begin to fall, as the normal range has not been established for all ages; identification of symptoms and signs (such as using bone densitometry) is important. The Endocrine Society recommends against general use of testosterone therapy in older men with low testosterone levels. In cases in which clinically significant symptoms accompany repeat low testosterone levels, opinions of the committee varied as to the testosterone level below which testosterone treatment is warranted (<200 ng/dL or <300 ng/dL). In each situation, it is important to weigh a patient’s symptoms against potential risks before initiating treatment, and to monitor testosterone levels and clinical signs and symptoms.
In February of this year, The Endocrine Society came out with a statement calling for larger and longer trials on the use of testosterone therapy, and a recommendation that doctors speak with their patients regarding the risks—particularly regarding heart disease—and benefits of testosterone use.