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 and Evaluation of Patients with Suspected Androgen Deficiency
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 that clinicians measure serum testosterone level in patients with clinical manifestations shown in Table 1A in the original guideline document. The Task Force suggests that clinicians also consider measuring serum testosterone level when patients report the less specific symptoms and signs listed in Table 1B in the original guideline document. (2 | +OOO)
The Task Force suggests the measurement of morning total testosterone level by a reliable assay as the initial diagnostic test. (2 | +OOO)
The Task Force recommends confirmation of the diagnosis by repeating measurement of total testosterone. (1 | ++OO)
The Task Force suggests measurement of free or bioavailable testosterone level, using an accurate and reliable assay, in some men in whom total testosterone concentrations are near the lower limit of the normal range and in whom alterations of sex hormone binding globulin (SHBG) are suspected. (2 | ++OO)
The Task Force suggests that an evaluation of androgen deficiency should not be made during an acute or subacute illness. (2 | ++OO)
Further Evaluation of Men Deemed Androgen Deficient
The Task Force recommends measurement of serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels to distinguish between primary (testicular) and secondary (pituitary-hypothalamic) hypogonadism. (1 | ++OO)
In men with secondary hypogonadism, the Task Force suggests further evaluation to identify the etiology of hypothalamic and/or pituitary dysfunction. This evaluation may include measurements of serum prolactin and iron saturation, pituitary function testing, and magnetic resonance imaging of the sella turcica. (2 | +OOO)
In men with primary testicular failure of unknown etiology, the Task Force suggests obtaining a karyotype to exclude Klinefelter syndrome, especially in those with testicular volume less than 6 ml. (2 | +OOO)
The Task Force suggests measurement of bone mineral density by using dual-energy x-ray absorptiometry (DXA) scanning in men with severe androgen deficiency or low trauma fracture. (2 | +OOO)
Screening for Androgen Deficiency (General Population)
The Task Force recommends against screening for androgen deficiency in the general population. (1 | +OOO)
Case Finding of Androgen Deficiency
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 in Table 3 in the original guideline document, in which the prevalence of low testosterone levels is high or for whom testosterone therapy is suggested/recommended below. (2 | +OOO)
Treatment of Androgen Deficiency with Testosterone
The Task Force recommends testosterone therapy for symptomatic men with classical androgen deficiency syndromes aimed at inducing and maintaining secondary sex characteristics and at improving their sexual function, sense of well-being, and bone mineral density. (1 | ++OO)
The Task Force recommends against testosterone therapy in patients with breast (1 | +OOO) or prostate cancer. (1 | ++OO)
The Task Force recommends against testosterone therapy without further urological evaluation in patients with palpable prostate nodule or induration or prostate-specific antigen (PSA) 4 ng/ml or PSA 3 ng/ml in men at high risk of prostate cancer, such as African Americans or men with first-degree relatives with prostate cancer. (1 | +OOO)
The Task Force recommends against testosterone therapy in patients with hematocrit above 50%, untreated severe obstructive sleep apnea, severe lower urinary tract symptoms [American Urological Association (AUA)/International Prostate Symptom Score (IPSS) 19], or uncontrolled or poorly controlled heart failure, or in those desiring fertility. (1 | +OOO)
The Task Force suggests initiating testosterone therapy with any of the following regimens, chosen on the basis of the patient's preference, consideration of pharmacokinetics, treatment burden, and cost. (2 | ++OO)
- 75–100 mg of testosterone enanthate or cypionate administered intramuscularly (IM) weekly, or 150–200 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.
- 5–10 g of a 1% 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.
- Testosterone pellets implanted subcutaneously at intervals of 3 to 6 months; the dose and regimen vary with the formulation used.
- Oral testosterone undecanoate, injectable testosterone undecanoate, testosterone-in-adhesive matrix patch, and testosterone pellets where available.
Monitoring Strategies and Schedule
The Task Force recommends evaluating the patient 3 to 6 months after treatment initiation and then annually to assess whether symptoms have responded to treatment and whether the patient is suffering any adverse effects, and to check compliance. (1 | +OOO)
The Task Force suggests monitoring testosterone levels 3 to 6 months after initiation of testosterone therapy. The Task Force suggests aiming at achieving serum testosterone levels during treatment in the mid-normal range. In men receiving testosterone enanthate or cypionate, the Task Force suggests aiming for testosterone levels between 400 and 700 ng/dl one week after the injection. (2 | ++OO)
The Task Force recommends determining hematocrit at baseline, at 3 to 6 months, and then annually. If hematocrit is >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 years of testosterone therapy in hypogonadal men with osteoporosis or low trauma fracture. (2 | +OOO)
In men 40 years of age or older who have a baseline PSA >0.6 ng/ml, the Task Force recommends digital examination of the prostate and PSA measurement before initiating treatment, at 3 to 6 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)
- 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·yr 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.
- American Urological Association/International Prostate Symptom Score >19.
The Task Force recommends evaluation for symptoms and signs of formulation-specific adverse events at each visit: (1 | +OOO)
- Injectable testosterone esters: Inquire about fluctuations in mood or libido, and cough after injection, 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.
- Buccal testosterone tablets: Inquire about alterations in taste and examine gums and oral mucosa for irritation.
Testosterone Therapy in Men with Sexual Dysfunction
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 low testosterone levels after evaluation of underlying causes of ED and consideration of established therapies for ED. (2 | +OOO)
Older Men with Low Serum Testosterone Concentration
The Task Force recommends against a general 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 low testosterone levels on more than one occasion and clinically significant symptoms of androgen deficiency, after explicit discussion of the uncertainty about the risks and benefits of testosterone therapy. (2 | +OOO)
Patients with Chronic Illness and Low Testosterone Levels
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 testosterone therapy to men receiving high doses of glucocorticoids who have low testosterone levels to promote preservation of lean body mass and bone mineral density. (2 | ++OO)
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."
+OOO Denotes very low quality evidence
++OO Denotes low quality evidence
+++O Denotes moderate quality evidence
++++ Denotes high quality evidence