Definitions for the levels of evidence (+OOO, ++OO, +++O, and ++++); the strength of the recommendation (1 or 2); and for the difference between a "recommendation" and a "suggestion" are provided at the end of the "Major Recommendations" field.
Diagnosis
The Task Force recommends making a diagnosis of androgen deficiency only in men with consistent symptoms and signs and unequivocally low serum testosterone levels. (1 | +OOO )
The Task Force suggests the measurement of morning total testosterone level by a reliable assay as the initial test for the diagnosis of androgen deficiency in men. (2 | ++OO )
The Task Force recommends confirmation of the diagnosis by repeating the measurement of morning total testosterone and in some patients by measurement of free or bioavailable testosterone level, using an appropriate assay system. (1 | +OOO )
The Task Force recommends against screening for androgen deficiency in the general population. (1 |+ OOO )
The Task Force suggests that clinicians not use the available case-finding instruments for detection of androgen deficiency in men receiving health care for unrelated reasons. (2 | +OOO )
The Task Force suggests that clinicians consider case detection by measurement of total testosterone levels in men with certain clinical disorders, listed below, in which the prevalence of low testosterone levels is high or for whom testosterone therapy is suggested/recommended in the "Treatment" section.(2 | +OOO )
- Sellar mass, radiation to the sellar region, or other diseases of the sellar region
- Treatment with medications that affect testosterone production or metabolism, such as glucocorticoids, ketoconazole, and opioids
- Human immunodeficiency virus (HIV)-associated weight loss
- End-stage renal disease and maintenance hemodialysis
- Moderate to severe chronic obstructive lung disease
- Infertility
- Osteoporosis or low trauma fracture, especially in a young man
- Type 2 diabetes mellitus
Treatment
The Task Force recommends testosterone therapy for symptomatic men with the classical androgen deficiency syndromes who have low testosterone levels to induce and maintain secondary sex characteristics and to improve their sexual function, sense of well-being, muscle mass and strength, and bone mineral density. (1 | ++OO )
The Task Force suggests that clinicians offer testosterone therapy to men with low testosterone levels and low libido to improve libido (2 | ++OO ) and to men with erectile dysfunction (ED) who have unequivocally low testosterone levels, after evaluation of underlying causes of ED and consideration of established therapies for ED. (2 | +OOO )
The Task Force recommends against a general clinical policy of offering testosterone therapy to all older men with low testosterone levels. (1 | +OOO )
The Task Force suggests that clinicians consider offering testosterone therapy on an individualized basis to older men with consistently low testosterone levels on more than one occasion and significant symptoms of androgen deficiency, after appropriate discussion of the uncertainties of the risks and benefits of testosterone therapy in older men. (2 | +OOO )
The Task Force suggests that clinicians consider short-term testosterone therapy as an adjunctive therapy in human immunodeficiency virus (HIV)-infected men with low testosterone levels and weight loss to promote weight maintenance and gains in lean body mass (LBM) and muscle strength. (2 | ++OO )
The Task Force suggests that clinicians offer short-term testosterone therapy to men receiving high doses of glucocorticoids who have low testosterone levels to promote preservation of LBM and bone mineral density. (2 | ++OO )
The Task Force recommends against starting testosterone therapy in patients with breast (1 | +OOO ) or prostate cancer. (1 | +OOO )
The Task Force recommends against starting testosterone therapy in patients with a palpable prostate nodule or induration, or prostate-specific antigen (PSA) greater than 3 ng/mL without further urological evaluation. (1 | +OOO )
The Task Force recommends against starting testosterone therapy in patients with erythrocytosis (hematocrit 50%), hyperviscosity, untreated obstructive sleep apnea, severe untreated benign prostatic hypertrophy with International Prostate Symptom Score (IPSS) symptom score 19, or uncontrolled severe heart failure. (1 | +OOO )
Administration
When testosterone therapy is recommended, The Task Force suggests aiming at achieving serum testosterone levels during treatment in the mid-normal range with any of the following regimens, chosen on the basis of the patient's preference, consideration of pharmacokinetics, treatment burden, and cost: (2 | ++OO )
- 75 to 100 mg of testosterone enanthate or cypionate administered intramuscularly (im) weekly, or 150 to 200 mg administered every 2 weeks.
- One or two 5-mg nongenital, testosterone patches applied nightly over the skin of the back, thigh, or upper arm, away from pressure areas.
- 5 to 10 g of a testosterone gel applied daily over a covered area of nongenital skin (patients should wash hands after application).
- 30 mg of a bioadhesive buccal testosterone tablet applied to buccal mucosa every 12 hours.
- Oral testosterone undecanoate, injectable testosterone undecanoate, and testosterone pellets where available.
Monitoring Strategies and Schedule
The Task Force recommends evaluating the patient 3 months after treatment initiation and then annually to assess whether symptoms have responded to treatment and whether the patient is suffering any adverse effects. (1 | +OOO )
The Task Force suggests monitoring testosterone levels 3 months after initiation of testosterone therapy. (2 | ++OO )
- Therapy should restore serum testosterone levels to the mid-normal range.
- Testosterone cypionate or enanthate: measure serum testosterone levels midway between injections. If serum testosterone level is greater than 700 ng/dL (24.5 nmol/L) or less than 350 ng/dL (12.3 nmol/L), adjust dose or frequency.
- Transdermal patch: assess testosterone levels 3 to 12 hours after application of the patch.
- Buccal tablet: assess levels immediately before application of fresh system.
- Transdermal gel: assess testosterone level after patient has been on treatment for 1 to 2 weeks
The Task Force recommends determining hematocrit at baseline, at 3 months, and then annually. If hematocrit is greater than 54%, stop therapy until hematocrit decreases to a safe level, evaluate the patient for hypoxia and sleep apnea, and reinitiate therapy at a reduced dose. (1 | +OOO )
The Task Force suggests repeating bone mineral density of the lumbar spine, femoral neck, and hip after 1 to 2 yr of testosterone therapy in hypogonadal men with osteoporosis or low trauma fracture. (2 | +OOO )
The Task Force recommends digital examination of the prostate and PSA measurement before initiating treatment, at 3 months, and then in accordance with evidence-based guidelines for prostate cancer screening, depending on the age and race of the patient. (1 | +OOO )
The Task Force recommends that clinicians obtain urological consultation if there is: (1 | +OOO )
- Verified serum or plasma PSA concentration greater than 4.0 ng/mL.
- An increase in serum or plasma PSA concentration greater than 1.4 ng/mL within any 12-month period of testosterone treatment.
- A PSA velocity of more than 0.4 ng/mL per year using the PSA level after 6 months of testosterone administration as the reference. PSA velocity should be used only if there are longitudinal PSA data for more than 2 years.
- Detection of a prostatic abnormality on digital rectal examination.
- An American Urological Association (AUA) prostate symptom score of more than 19.
The Task Force recommends evaluation for symptoms and signs of formulation-specific adverse events at each visit: (1 | +OOO )
- Buccal testosterone tablets: inquire about alterations in taste and examine gums and oral mucosa for irritation.
- Injectable testosterone esters: inquire about fluctuations in mood or libido and evaluate hematocrit to detect excessive erythrocytosis, especially in older patients.
- Testosterone patch: look for signs of skin reaction at the application site.
- Testosterone gels: advise patients to cover the application site with clothing and wash the skin before having skin-to-skin contact, because gels leave a residue of testosterone on the skin that can be transferred to a woman or child who comes in close contact.
Definitions:
Strength of Recommendations
1 - Indicates a strong recommendation and is associated with the phrase "The Task Force recommends."
2 - Denotes a weak recommendation and is associated with the phrase "The Task Force suggests."
Evidence Grading
+OOO Denotes very low quality evidence
++OO Denotes low quality evidence
+++O Denotes moderate quality evidence
++++ Denotes high quality evidence
