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Testosterone Therapy in Adult Men with Androgen Deficiency Syndromes: An Endocrine Society Clinical Practice Guideline

Boston University School of Medicine (S.B.), Boston, Massachusetts 02118; Baylor College of Medicine/Veterans Affairs Medical Center (G.R.C.), Houston, Texas 77030; Massachusetts General Hospital/Harvard Medical School (F.J.H.), Boston, Massachusetts 02114; University of Washington/Veterans Affairs Puget Sound Health Care System (A.M.M.), Seattle, Washington 98108; University of Pennsylvania School of Medicine (P.J.S.), Philadelphia, Pennsylvania 19104; Harbor University of California, Los Angeles Medical Center (R.S.S.), Torrance, California 90502; and Mayo Clinic (V.M.M.), Rochester, Minnesota 55905

Address all questions to: The Endocrine Society, 8401 Connecticut Avenue, Suite 900, Chevy Chase, MD 20815. E-mail: govt-prof{at}endo-society.org. Telephone: 301-941-0200. Address all reprint requests for orders 101 and more to: Heather Edwards, Reprint Sales Specialist, Cadmus Professional Communications, Telephone: 410-691-6214, Fax: 410-684-2789 or by E-mail: endoreprints{at}cadmus.com. Address all reprint requests for orders 100 or less to Society Services, Telephone: 301-941-0210 or by E-mail: societyservices{at}endo-society.org.

	Abstract

Top Abstract Summary of Evidence-Based... METHOD OF DEVELOPMENT OF... GUIDELINES 1.2 Screening for Androgen... 2.0 Treatment of Androgen... 2.2. Testosterone Therapy in... 2.3 Older Men with... 2.4 Patients with Chronic... 2.4.2 Glucocorticoid-Treated Men References

 
Objective: The objective was to provide guidelines for the evaluation and treatment of androgen deficiency syndromes in adult men.

Participants: The Task Force was composed of a chair, selected by the Clinical Guidelines Subcommittee of The Endocrine Society, five additional experts, a methodologist, and a professional writer. The Task Force received no corporate funding or remuneration.

Evidence: The Task Force used systematic reviews of available evidence to inform its key recommendations. The Task Force used consistent language and graphical descriptions of both the strength of recommendation and the quality of evidence, using the recommendations of the Grading of Recommendations, Assessment, Development, and Evaluation group.

Consensus Process: Consensus was guided by systematic reviews of evidence and discussions during three group meetings, several conference calls, and e-mail communications. The drafts prepared by the panelists with the help of a professional writer were reviewed successively by The Endocrine Society’s Clinical Guidelines Subcommittee, Clinical Affairs Committee, and Council. The version approved by the Council was placed on The Endocrine Society’s web site for comments by members. At each stage of review, the Task Force received written comments and incorporated needed changes.

Conclusions: We recommend making a diagnosis of androgen deficiency only in men with consistent symptoms and signs and unequivocally low serum testosterone levels. We suggest the measurement of morning total testosterone level by a reliable assay as the initial diagnostic test. We recommend 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 accurate assays. We recommend testosterone therapy for symptomatic men with androgen deficiency, 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. We recommend against starting testosterone therapy in patients with breast or prostate cancer, a palpable prostate nodule or induration or prostate-specific antigen greater than 3 ng/ml without further urological evaluation, erythrocytosis (hematocrit > 50%), hyperviscosity, untreated obstructive sleep apnea, severe lower urinary tract symptoms with International Prostate Symptom Score (IPSS) greater than 19, or class III or IV heart failure. When testosterone therapy is instituted, we suggest aiming at achieving testosterone levels during treatment in the mid-normal range with any of the approved formulations, chosen on the basis of the patient’s preference, consideration of pharmacokinetics, treatment burden, and cost. Men receiving testosterone therapy should be monitored using a standardized plan.

	Summary of Evidence-Based Guidelines for Use of Testosterone Therapy in Adult Men with Androgen Deficiency Syndromes

Top Abstract Summary of Evidence-Based... METHOD OF DEVELOPMENT OF... GUIDELINES 1.2 Screening for Androgen... 2.0 Treatment of Androgen... 2.2. Testosterone Therapy in... 2.3 Older Men with... 2.4 Patients with Chronic... 2.4.2 Glucocorticoid-Treated Men References

 
THE TASK FORCE used systematic reviews of available evidence to inform its key recommendations. The number 1 indicates a strong recommendation and is associated with the phrase "we recommend"; 2 denotes a weak recommendation and is associated with the phrase "we suggest." Evidence grading: denotes very low quality evidence; , low quality; , moderate quality; and , high quality. Numbers to the left of individual recommendations correspond to numbers in the text. Hence, there may be duplicate numbers below, and the order may not be strictly numerical.

1. Diagnosis

1.1 We recommend making a diagnosis of androgen deficiency only in men with consistent symptoms and signs and unequivocally low serum testosterone levels. (1|)

1.1 We suggest the measurement of morning total testosterone level by a reliable assay as the initial test for the diagnosis of androgen deficiency in men. (2|)

1.1 We recommend 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|)

1.2.1 We recommend against screening for androgen deficiency in the general population. (1|)

1.2.2 We suggest that clinicians not use the available case-finding instruments for detection of androgen deficiency in men receiving health care for unrelated reasons. (2|)

1.2.2 We suggest that clinicians consider case detection by measurement of total testosterone levels in men with certain clinical disorders, listed in Table 3, in which the prevalence of low testosterone levels is high or for whom testosterone therapy is suggested/recommended in Section 2.0. (2|)

2.1 We recommend 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|)

2.2 We suggest that clinicians offer testosterone therapy to men with low testosterone levels and low libido to improve libido (2|) 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|)

2.3 We recommend against a general clinical policy of offering testosterone therapy to all older men with low testosterone levels. (1|)

2.3 We suggest 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|)

2.4.1 We suggest that clinicians consider short-term testosterone therapy as an adjunctive therapy in 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|)

2.4.2 We suggest 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|)

2.1 We recommend against starting testosterone therapy in patients with breast (1|) or prostate cancer. (1|)

2.1 We recommend 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|)

2.1 We recommend against starting testosterone therapy in patients with erythrocytosis (hematocrit >50%), hyperviscosity, untreated obstructive sleep apnea, severe untreated benign prostatic hypertrophy with IPSS symptom score >19, or uncontrolled severe heart failure. (1|)

2.1.D Administration

When testosterone therapy is recommended, we suggest 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|)

75–100 mg of testosterone enanthate or cypionate administered im weekly, or 150–200 mg administered every 2 wk.

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 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 h.

Oral testosterone undecanoate, injectable testosterone undecanoate, and testosterone pellets where available.

2.1.D Monitoring strategies and schedule

We recommend 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|)

We suggest monitoring testosterone levels 3 months after initiation of testosterone therapy. (2|)

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/liter) or less than 350 ng/dl (12.3 nmol/liter), adjust dose or frequency.

Transdermal patch: assess testosterone levels 3 to 12 h 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 wk.

We recommend 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|)

We suggest 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|)

We recommend 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|)

We recommend that clinicians obtain urological consultation if there is: (1|)

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·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 yr.

Detection of a prostatic abnormality on digital rectal examination.

An American Urological Association (AUA) prostate symptom score of more than 19.

We recommend evaluation for symptoms and signs of formulation-specific adverse events at each visit: (1|)

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.

	METHOD OF DEVELOPMENT OF EVIDENCE-BASED GUIDELINES

Top Abstract Summary of Evidence-Based... METHOD OF DEVELOPMENT OF... GUIDELINES 1.2 Screening for Androgen... 2.0 Treatment of Androgen... 2.2. Testosterone Therapy in... 2.3 Older Men with... 2.4 Patients with Chronic... 2.4.2 Glucocorticoid-Treated Men References

 
The Clinical Guidelines Subcommittee of The Endocrine Society deemed testosterone therapy in androgen-deficient men a priority area in need of practice guidelines and appointed a six-member Task Force to formulate evidence-based recommendations. The Task Force elected to use the approach recommended by the Grading of Recommendations, Assessment, Development, and Evaluation group, an international group with expertise in development and implementation of evidence-based guidelines (1).

The Task Force used systematic reviews of available evidence to inform its key recommendations and consistent language and graphical descriptions of both the strength of a recommendation and the quality of evidence. The strength of a recommendation is indicated by the number 1 (strong recommendation, associated with the phrase "we recommend") or 2 (weak recommendation, associated with the phrase "we suggest"). The quality of the evidence is indicated by cross-filled circles, such that denotes very low quality evidence; , low quality; , moderate quality; and , high quality.

Each recommendation is followed by a description of the evidence, values that panelists considered in making the recommendation, and in some instances remarks, a section in which panelists offer technical suggestions for dosing and monitoring. These technical comments reflect the best available evidence applied to a typical patient. Often, this evidence comes from the unsystematic observations of the panelists and their values and preferences; therefore, these remarks should be considered suggestions.

	GUIDELINES

Top Abstract Summary of Evidence-Based... METHOD OF DEVELOPMENT OF... GUIDELINES 1.2 Screening for Androgen... 2.0 Treatment of Androgen... 2.2. Testosterone Therapy in... 2.3 Older Men with... 2.4 Patients with Chronic... 2.4.2 Glucocorticoid-Treated Men References

 
1.0 Diagnosis of Hypogonadism

1.0.1 Definition of hypogonadism. Hypogonadism in men is a clinical syndrome that results from failure of the testis to produce physiological levels of testosterone (androgen deficiency) and the normal number of spermatozoa due to disruption of one or more levels of the hypothalamic-pituitary-gonadal (HPG) axis.

1.0.2 Classification of hypogonadism. Abnormalities of the HPG axis at the testicular level cause primary testicular failure, whereas central defects of the hypothalamus or pituitary cause secondary testicular failure.

Primary testicular failure results in low testosterone levels, impairment of spermatogenesis, and elevated gonadotropin levels.

Secondary testicular failure is associated with low or low-normal gonadotropin levels and low testosterone levels.

This classification has therapeutic implications because fertility can be restored with appropriate hormonal stimulation in patients with secondary hypogonadism, but not primary hypogonadism. Fertility options for men with primary testicular failure are limited to the use of donor sperm, adoption, or, in some patients, intracytoplasmic sperm injection. Also, further evaluation of secondary hypogonadism may uncover a pituitary tumor or systemic illness.

Less commonly, hypogonadism can reflect dual defects in the HPG axis in men with DAX-1 mutations, hemochromatosis, sickle cell disease, thalassemia, glucocorticoid treatment, and alcoholism, and in older men (2).

The age-related decline in testosterone levels, confirmed in several cross-sectional and longitudinal studies (3, 4), results from defects in both testicular and hypothalamic-pituitary function. Because the average decline in serum testosterone levels with aging in men is 1–2% per year (3, 4), only a subset of aging men has levels clearly below the lower limit of the normal range for healthy, young men (5).

1.1 Diagnosis and Evaluation of Patients with Suspected Androgen Deficiency

1.1.A RECOMMENDATIONS

We recommend making a diagnosis of androgen deficiency only in men with consistent symptoms and signs and unequivocally low serum testosterone levels. (1|)

We suggest that clinicians measure serum testosterone level in patients with clinical manifestations shown in Table 1A. We suggest that clinicians also consider measuring serum testosterone level when the less specific symptoms and signs listed in Table 1B occur in conjunction with those listed in Table 1A. (2|)

We recommend confirmation of the diagnosis by repeating measurement of total testosterone and in some patients by measurement of free or bioavailable testosterone level, using an appropriate assay. (1|)

We suggest that a diagnosis of androgen deficiency should not be made during an acute or subacute illness. (2|)

1.1.B EVIDENCE

The clinical presentation of male hypogonadism depends on the age of onset of androgen deficiency. Onset in adulthood leads to a clinical syndrome substantially different from that resulting from onset in the fetal or prepubertal period.

Diagnosis of androgen deficiency in men poses challenges. Symptoms and signs are nonspecific and modified by age, comorbid illness, severity and duration of androgen deficiency, variation in androgen sensitivity, and previous testosterone therapy. The signs and symptoms listed in Table 1 are based on the panelists’ experience in clinic-based populations of androgen-deficient men who are likely to have more severe androgen deficiency; population-based surveys in men with classical androgen deficiency have not been conducted. In one cross-sectional survey of middle-aged and older men, the presence of diabetes mellitus and coronary artery disease was a good predictor of low testosterone levels (6).

Serum testosterone levels vary significantly as a result of circadian and circannual rhythms, episodic secretion, and measurement variations. Testosterone concentrations may be affected by illness and certain medications (e.g. opiates and glucocorticoids). Testosterone measurements are also influenced by alterations in SHBG concentrations.

The threshold testosterone level below which symptoms of androgen deficiency and adverse health outcomes occur is not known and may be age-dependent. Furthermore, the testosterone concentration below which testosterone administration improves outcomes is unknown and may vary among individuals and among target organs (7, 8, 9). Therefore, the available evidence does not support use of an arbitrary threshold for testosterone level below which clinical androgen deficiency occurs and that confirms the diagnosis of hypogonadism in all patients.

It is important to confirm low testosterone concentrations in men with an initial testosterone level in the mildly hypogonadal range, because 30% of such patients may have a normal testosterone level on repeat measurement (10). Also, 15% of healthy young men may have a testosterone level below the normal range in a 24-h period (11).

Serum total testosterone concentrations, representing the sum of unbound and protein-bound testosterone in circulation, are measured by RIA, immunometric assays, or liquid chromatography tandem mass spectrometry. Most of the circulating testosterone is bound to SHBG and to albumin (2); only 0.5–3% of circulating testosterone is unbound or "free." The free fraction can be measured by equilibrium dialysis. The term "bioavailable testosterone" refers to unbound testosterone plus testosterone bound loosely to albumin; this term reflects the view that in addition to the unbound testosterone, albumin-bound testosterone is readily dissociable and thus bioavailable. Bioavailable testosterone levels can be measured by the ammonium sulfate precipitation method. Free and bioavailable testosterone concentrations can also be calculated from total testosterone and SHBG concentrations using published algorithms (2).

Automated assays for total testosterone are available in most hospital laboratories and usually are sufficiently accurate to distinguish eugonadal from hypogonadal men (12). Total testosterone levels are affected by alterations in SHBG that occur in obese men; older men; men with comorbid illness, hyper- and hypothyroidism, and acromegaly; and men taking certain medications (Table 2).

The normative ranges for total and free testosterone levels in healthy young men vary among laboratories and assays. In some laboratories, the lower limit of the normal range for total testosterone level in healthy young men is 300 ng/dl (10.4 nmol/liter). Similarly, in some reference laboratories, the lower limit of the normal range for serum free testosterone level, measured by the equilibrium dialysis method, is 50 pg/ml (0.17 nmol/liter). The clinicians should use the lower limit of normal range for healthy young men established in their reference laboratory.

The assessment of men for androgen deficiency should include a general health evaluation to exclude systemic illness, use of certain medications (e.g. opiates or high-dose glucocorticoid therapy) and recreational drugs that affect testosterone production or metabolism, eating disorders, and excessive exercise (2) because these conditions can lower testosterone levels transiently. The diagnosis of androgen deficiency should not be made during an acute illness.

1.1.C VALUES

Our proposed diagnostic strategy places higher value on avoiding the labeling of men with low testosterone levels due to SHBG abnormalities, natural variations in testosterone levels, or transient disorders, and lower value on treatment of men without unequivocally low testosterone levels and symptoms in whom the benefits and risks of testosterone therapy are unclear.

1.1.1 Further evaluation of men deemed androgen deficient (Fig. 1)

View larger version (27K): [in this window] [in a new window]   FIG. 1. An approach for the diagnostic evaluation of adult men suspected of having androgen deficiency. T, Testosterone; bio T, bioavailable T; SFA, seminal fluid analysis; 1°, primary testicular failure; 2°, secondary hypogonadism. #, In some laboratories, the lower limit of the normal testosterone range in healthy young men is approximately 300 ng/dl (10.4 nmol/liter); however, this range may vary in different laboratories. Use the lower limit of the range established in your reference laboratory. , Refer to Table 2 for a list of conditions that alter SHBG concentrations. @, In some reference laboratories, the lower limit of the normal free testosterone range in healthy young men is approximately 5 ng/dl (0.17 nmol/liter) (approximate lower limit of normal in three major commercial laboratories) using equilibrium dialysis or calculated from total testosterone and SHBG; however, this range may vary in different laboratories [approximate lower limits of normal ranging from 4 to 9 ng/dl (0.14 to 0.31 nmol/liter) in major commercial laboratories) using equilibrium dialysis or calculated from total testosterone and SHBG and the reference population used. Use the lower limit of the range established in your reference laboratory. *, Perform pituitary imaging (MRI) to exclude pituitary and/or hypothalamic tumor or infiltrative disease, if severe secondary hypogonadism (serum T < 150 ng/dl), panhypopituitarism, persistent hyperprolactinemia, or symptoms or signs of tumor mass effect, such as headache, visual impairment, or visual field defect, are present.

We recommend measurement of serum LH and FSH levels to distinguish between primary (testicular) and secondary (pituitary-hypothalamic) hypogonadism. (1|)

In men with secondary hypogonadism, we suggest further evaluation on an individualized basis 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 (MRI) scanning. (2|)

In men with primary testicular failure of unknown etiology, we suggest obtaining a karyotype to exclude Klinefelter’s syndrome. (2|)

In men being evaluated for infertility, we recommend obtaining seminal fluid analysis. (1|)

We suggest measurement of bone mineral density by using DXA scanning in men with severe androgen deficiency or low trauma fracture. (2|)

1.1.1.B EVIDENCE

In men deemed to have secondary hypogonadism, additional diagnostic evaluation may be needed to exclude pituitary neoplasia, hyperprolactinemia, hemochromatosis and other infiltrative diseases, obstructive sleep apnea, and genetic disorders associated with gonadotropin deficiency. The measurement of serum prolactin and iron saturation can help determine the presence of hyperprolactinemia and hemochromatosis, respectively. Assessment of anterior pituitary function, if clinically indicated or in the presence of severe secondary hypogonadism (testosterone level < 150 ng/dl), can uncover other pituitary hormone deficiencies. A diagnosis of idiopathic hypogonadotropic hypogonadism is made after excluding other causes of hypogonadotropic hypogonadism. Patients with idiopathic hypogonadotropic hypogonadism should be examined for dysmorphic features—such as extreme obesity, polydactyly, anosmia, short stature, or kidney abnormalities—to facilitate recognition of specific syndromes by pattern recognition.

The cost-effectiveness of pituitary imaging (MRI) to exclude pituitary and/or hypothalamic tumor is unknown. One survey of men with sexual dysfunction revealed a low prevalence of hypothalamic-pituitary abnormalities (14). The diagnostic yield of pituitary imaging to exclude pituitary and/or hypothalamic tumor can be improved by performing this procedure in men with serum testosterone below 150 ng/dl, panhypopituitarism, persistent hyperprolactinemia, or symptoms of tumor mass effect (headache, visual impairment, or visual field defect) (15).

Klinefelter’s syndrome, a common identifiable cause of primary testicular failure, can be diagnosed by obtaining a karyotype. These patients can benefit from genetic counseling.

Testosterone stimulates bone formation and inhibits bone resorption through multiple mechanisms that involve both androgen and estrogen receptor-mediated processes (16). However, the cost-effectiveness of measuring bone mineral density and the frequency at which it should be performed are still being debated.

The cost-effectiveness of these diagnostic strategies has not been evaluated in clinical trials.

1.1.1.C VALUES

Recommendations in favor of performing additional tests to diagnose primary etiologic disorders place a higher value on detecting the presence of pituitary neoplasia or other treatable pituitary disorders and on ascertaining the need for additional treatment or counseling and a lower value on avoiding the burden and cost of tests with unknown yield.

	1.2 Screening for Androgen Deficiency

Top Abstract Summary of Evidence-Based... METHOD OF DEVELOPMENT OF... GUIDELINES 1.2 Screening for Androgen... 2.0 Treatment of Androgen... 2.2. Testosterone Therapy in... 2.3 Older Men with... 2.4 Patients with Chronic... 2.4.2 Glucocorticoid-Treated Men References

 
1.2.1 Screening in the general population

1.2.1.A RECOMMENDATION

We recommend against screening for androgen deficiency in the general population. (1|)

1.2.1.B EVIDENCE

Because of the lack of consensus on a case definition and the extent to which androgen deficiency is an important health problem, as well as the lack of data on the performance characteristics of candidate screening tools, the usefulness of population screening cannot be evaluated at present. The long-term health consequences of low testosterone levels are unknown in the two largest subsets of men with low testosterone levels—older men and men with chronic illness. The impact of untreated androgen deficiency on mortality is unclear (17). The benefits and adverse consequences of long-term testosterone therapy on patient-important outcomes in asymptomatic men with presumed hypogonadism remain unclear (5, 18). Therefore, screening for androgen deficiency does not fulfill any of the necessary criteria to justify it. No clinical trials have assessed the effectiveness of screening strategies. (Quality of evidence: )

1.2.1.C VALUES

The recommendation not to screen men in the general population places a high value on avoiding labeling and medicalization of otherwise healthy men for whom testing, treatment, and monitoring would represent a burden with unclear benefit. This recommendation also places a high value on avoiding interventions with unclear outcomes. It places a low value on the potential benefits of early detection and treatment of androgen deficiency in men who have not sought medical attention.

1.2.2 Case finding of androgen deficiency

1.2.2.A RECOMMENDATIONS

We suggest that clinicians not use the available case-finding instruments for detection of androgen deficiency in men receiving health care for unrelated reasons. (2|)

We suggest that clinicians consider case detection by measurement of total testosterone levels in men with certain clinical disorders, listed in Table 3, in which the prevalence of low testosterone levels is high or for whom testosterone therapy is suggested/recommended in Section 2.0. (2|)

1.2.2.B EVIDENCE

Ideally, case detection should identify from the clinic population patients who present with medical problems apparently unrelated to androgen deficiency, but who are likely to benefit from testosterone therapy. Candidate groups in whom there is high prevalence of low testosterone levels and in whom we suggest measurement of serum testosterone level are listed in Table 3; these include men with chronic illness, such as those with HIV-associated weight loss, end-stage renal disease on dialysis, chronic obstructive pulmonary disease, osteoporosis or fracture after low trauma at a young age, type 2 diabetes mellitus, and men receiving chronic glucocorticoid and opioids (2, 22, 23, 24, 25). Most surveys of men with chronic illness included relatively small, convenience samples. The information about the benefits and risks of testosterone therapy in these conditions is either limited or not available.

There is limited information about the performance properties of case-detection instruments that rely on self-report, namely, Androgen Deficiency in Aging Males (ADAM) (19), the Aging Males’ Symptoms (AMS) Rating Scale (20), and the Massachusetts Male Aging Study Questionnaire (21). There are no trials of case-detection strategies in these patient populations, and the cost-effectiveness of the use of case-finding instruments over measurement of serum testosterone levels is unknown. (Quality of evidence: )

1.2.2.C VALUES

Our recommendation in favor of case detection by measurement of testosterone levels places a relatively high value on the potential benefits and a relatively low value on the burden of testosterone therapy and uncertainty about its long-term safety.

	2.0 Treatment of Androgen Deficiency with Testosterone

Top Abstract Summary of Evidence-Based... METHOD OF DEVELOPMENT OF... GUIDELINES 1.2 Screening for Androgen... 2.0 Treatment of Androgen... 2.2. Testosterone Therapy in... 2.3 Older Men with... 2.4 Patients with Chronic... 2.4.2 Glucocorticoid-Treated Men References

 
2.1 Testosterone Therapy in Adult Men with Classical Androgen Deficiency

2.1.A RECOMMENDATIONS

We recommend 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|)

We recommend against testosterone therapy in patients with breast (1|) or prostate cancer. (1|)

We recommend against testosterone therapy in patients with palpable prostate nodule or induration or PSA below 3 ng/ml without further urological evaluation. (1|)

We recommend against testosterone therapy in patients with erythrocytosis, hyperviscosity, untreated obstructive sleep apnea, severe benign prostatic hyperplasia symptoms (AUA prostate symptom score > 19), or uncontrolled severe heart failure. (1|)

We suggest that when clinicians prescribe testosterone therapy, the therapeutic target should be to raise serum testosterone levels into a range that is mid-normal for healthy, young men. (2|)

2.1.B EVIDENCE

2.1.1 Non-placebo-controlled studies. Lowering of testosterone concentrations in adult men by surgical orchiectomy or by GnRH agonist or antagonist administration is associated with rapid and marked loss of bone mineral density (16), increase in fat mass (26), and a loss of muscle mass and strength (26). Lowering of testosterone concentrations also results in hot flushes and a decrease in overall sexual activity, thoughts, and fantasies.

Testosterone therapy of young, hypogonadal men is associated with improvements in overall sexual activity scores, frequency of sexual thoughts and fantasies, an increase in attentiveness to erotic stimuli, and an increase in the frequency and duration of nighttime erections (27, 28, 29). Testosterone therapy increases hair growth in several androgen-sensitive areas. Testosterone therapy of healthy, hypogonadal men also increases fat-free mass (29, 30, 31, 32, 33, 34, 35, 36, 37, 38) and muscle strength (30) and decreases fat mass (29, 33, 35, 37). Testosterone administration in hypogonadal men is associated with a dose-dependent increase in hemoglobin levels (39); the increase in hemoglobin is greater in older men than in young hypogonadal men (40).

Although testosterone therapy of healthy, hypogonadal men increases bone mineral density, the effects of testosterone on fracture risk are unknown (33, 41).

Testosterone therapy improves the positive and reduces the negative aspects of mood (29). Uncontrolled studies report improvements in energy and sense of well-being after testosterone therapy (42). The effects of testosterone on cognitive function are poorly understood; some studies report small effects on visuospatial cognition and verbal memory and fluency (43, 44).

Previous studies have reported conflicting effects of testosterone therapy on insulin sensitivity (45, 46).

Testosterone therapy may be associated with increased risk of serious adverse effects in men with some types of disorders (Table 4). Metastatic prostate cancer and breast cancer are hormone-dependent cancers that may be stimulated to grow during testosterone treatment (47); testosterone should not be administered to men with these cancers. Although some have suggested that patients with low testosterone levels who have been disease-free 2 or more years after radical prostatectomy and who have undetectable PSA levels may be considered for testosterone replacement on an individualized basis (48, 49), the lack of randomized trials data precluded a general recommendation.

Open-label studies in young, hypogonadal men have found a low frequency of adverse events with replacement doses of testosterone (50). Common drug-related adverse events include increase in hematocrit, acne, oiliness of skin, and breast tenderness (Table 5). The frequency of breast enlargement, sleep apnea, and prostate events is low in trials of young, hypogonadal men.

Most studies of testosterone therapy in young, hypogonadal men have been open-label and did not include a placebo group. The observations in these open-label studies are consistent with the sparse data from randomized trials and with the experience of the panelists. (Quality of evidence: )

2.1.C VALUES

The recommendation to offer testosterone therapy to healthy, hypogonadal men with classical androgen deficiency syndromes places a relatively higher value on alleviating hypogonadal symptoms and other benefits of testosterone therapy and a relatively lower value on avoiding the potential burden of long-term treatment, monitoring, cost, and its unclear long-term safety.

2.1.D REMARKS

Table 6 summarizes the clinical pharmacology of the available testosterone formulations. When clinicians recommend testosterone therapy, we suggest aiming at achieving testosterone levels in a range that is mid-normal for healthy, young men. Testosterone therapy can be initiated with any of the suggested regimens, in accord with considerations of the patient’s preference, pharmacokinetics of testosterone formulation, treatment burden, and cost (Table 7).

	2.2. Testosterone Therapy in Men with Sexual Dysfunction

Top Abstract Summary of Evidence-Based... METHOD OF DEVELOPMENT OF... GUIDELINES 1.2 Screening for Androgen... 2.0 Treatment of Androgen... 2.2. Testosterone Therapy in... 2.3 Older Men with... 2.4 Patients with Chronic... 2.4.2 Glucocorticoid-Treated Men References

 
2.2.A RECOMMENDATION

We suggest that clinicians offer testosterone therapy to men with low testosterone levels and low libido to improve libido (2|) and to men with ED who have unequivocally low testosterone levels after evaluation of underlying causes of ED and consideration of established therapies for ED. (2|)

2.2.B EVIDENCE

Spontaneous and experimentally induced androgen deficiency is associated with a decreased frequency of sexual thoughts and fantasies, nighttime erections, and overall sexual activity and decreased attentiveness to erotic stimuli (9, 28, 29, 52, 60, 61). Androgen deficiency is an important cause of hypoactive sexual desire disorder. However, androgen deficiency and ED are two independently distributed clinical disorders with distinct pathophysiology; the two disorders may coexist in middle-aged and older men (62).

Libido. Among randomized trials that enrolled patients with total testosterone levels below 300 ng/dl (10.4 nmol/liter), we found two parallel trials (36, 63) and three crossover trials (51, 53, 64) reporting effects on libido; the longest trial followed participants for 6 months. The results of these trials were inconsistent but revealed a large improvement in libido (1.2 SD units; 95% CI, 0.3, 2.2). (Quality of evidence: )

Among trials that enrolled men with total testosterone levels above 300 ng/dl (10.4 nmol/liter), we found four trials in men with ED or low libido that reported effects on libido (54, 65, 66). The pooled effect of testosterone on libido was not significant (0.4 SD units; 95% CI, –0.1, 0.9). Lack of precision around this estimate weakens this inference. (Quality of evidence: )

Erectile dysfunction. A meta-analysis by Jain et al. (67) evaluated the effects of testosterone therapy in men with ED. Among 16 published studies (67), 57% of subjects experienced an improvement in erectile function. In our systematic review of randomized placebo-controlled trials that enrolled patients with total testosterone less than 300 ng/dl (10.4 nmol/liter), two parallel trials (36, 63) and two crossover trials (54, 55) reported effects on erectile function. The results were inconsistent across trials, and the pooled estimate was not significant (0.8 SD units; 95% CI, –0.05, 1.6). (Quality of evidence: )

In the trial of older men with low free testosterone levels and borderline low total testosterone levels (63), oral testosterone yielded a moderate treatment effect on sexual function (0.5 SD units; 95% CI, 0.05, 0.9). In two trials of young, hypogonadal men with low total testosterone levels (55, 68), oral testosterone administration was associated with a larger treatment effect (1.8 SD units; 95% CI, 1.0, 2.7). The largest trial (36) that examined the effects of transdermal testosterone on erectile function reported a nonsignificant effect (–0.2 SD units, 95% CI, –0.6, 0.1). The inconsistency across trials and the imprecision of the pooled estimates weaken the inference. (Quality of evidence: )

Among trials that enrolled men with total testosterone greater than 300 ng/dl (10.4 nmol/liter), we found two parallel trials in men with ED in whom sildenafil had failed (65, 69) and three crossover trials in men with either low libido or ED (66, 70). These trials reported inconsistent and nonsignificant effects on erectile function (0.4 SD units; 95% CI, –0.1, 0.8). The inconsistency across trials and the imprecision of the pooled estimate weaken our inferences. (Quality of evidence: )

Other sexual outcomes. Several trials reported on the impact of testosterone therapy on other sexual outcomes, namely, orgasmic and ejaculatory function, intercourse, and overall satisfaction. Generally, the effect of testosterone was positive, but the data came from a few trials with inconsistent findings and incomplete reporting yielding imprecise estimates. (Quality of evidence: )

2.2.C VALUES

Our recommendation to offer testosterone therapy to men with hypoactive sexual desire or ED who have unequivocally low testosterone levels places a relatively higher value on improving these complaints and a relatively lower value on avoiding the burden of testosterone therapy and its unclear long-term safety. Older patients with a greater potential for adverse effects may opt to avoid testosterone therapy.

2.2.D REMARKS

Diagnostic and treatment recommendations are the same as for patients with classical androgen deficiency (Sections 1.1 and 2.1). Men with sexual dysfunction should be evaluated for the underlying causes, including low testosterone levels.

	2.3 Older Men with Low Serum Testosterone Concentration

Top Abstract Summary of Evidence-Based... METHOD OF DEVELOPMENT OF... GUIDELINES 1.2 Screening for Androgen... 2.0 Treatment of Androgen... 2.2. Testosterone Therapy in... 2.3 Older Men with... 2.4 Patients with Chronic... 2.4.2 Glucocorticoid-Treated Men References

 
2.3.A RECOMMENDATION

We recommend against a general clinical policy of offering testosterone therapy to all older men with low testosterone levels. (1|)

We suggest that clinicians consider offering testosterone therapy on an individualized basis to older men with consistently 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|)

The panelists disagreed on serum testosterone levels below which testosterone therapy should be offered to older men with symptoms. Depending on the severity of clinical manifestations, some panelists favored treating symptomatic older men with a testosterone level below 300 ng/dl (10.4 nmol/liter); others favored a level below 200 ng/dl (6.9 nmol/liter).

2.3.B EVIDENCE

Several cross-sectional and longitudinal studies (3, 4) demonstrate that serum total and free testosterone concentrations in men fall with increasing age. Although the fall is gradual, by the eighth decade, according to one study (4), 30% of men had total testosterone values in the hypogonadal range, and 50% had low free testosterone values. The rate of age-related decline in serum testosterone levels varies in different individuals and is affected by chronic disease and medications (4, 6).

Testosterone Trials in Older Men

In randomized, placebo-controlled trials of 1- to 3-yr duration in older men with low-normal to low testosterone concentrations (71, 72, 73), testosterone administration was associated with sustained increase in testosterone levels. Overall, testosterone trials in older men were characterized by small sample size, inclusion of healthy older men with low or low-normal testosterone levels who were asymptomatic, and the use of surrogate outcomes; these studies did not have sufficient power to detect either meaningful gains in patient-important outcomes or changes in prostate and cardiovascular event rates (72, 73, 74, 75, 76, 77, 78, 79).

Bone mineral density. We did not find any trials reporting the effect of testosterone on bone fractures. A systematic review of randomized, placebo-controlled trials of 1- to 3-yr duration that evaluated effects on bone mineral density yielded inconsistent and imprecise results: the trial following patients for 1 yr yielded an insignificant effect (72) (–0.01 SD units; 95% CI, –0.6, 0.6); two longer trials (71, 80) showed a moderate treatment effect on lumbar bone mineral density (0.4 SD units; 95% CI, 0.1, 0.7), equivalent to an increase in lumbar bone density of 2% (95% CI, 0.5, 3.3). These trials ruled out a moderate-to-large testosterone effect on femoral neck bone density (0.0 SD units; 95% CI, –0.3, 0.3).

Body composition. In our systematic review (72, 73, 74, 77, 79, 81, 82), testosterone therapy was associated with a significantly greater increase in LBM (2.7 kg; 95% CI, 1.6, 3.7) and a greater reduction in fat mass (–2.0 kg; 95% CI, –3.1, –0.8) than placebo. The body weight change did not differ significantly between groups (–0.6 kg; 95% CI, –2.0, 0.8).

Muscle strength and physical function. Testosterone therapy was associated with a greater improvement in grip strength than placebo (3.3 kg; 95% CI, 0.7, 5.8) (76, 77, 78, 82). Changes in lower-extremity muscle strength and measures of physical function were reported in only a few studies and were inconsistent. One study reported no changes in physical function (73), whereas another reported improvement in a composite measure of physical function (77).

Sexual function. Two placebo-controlled trials (63, 73) reported on the effect of testosterone on overall sexual satisfaction, yielding imprecise results (0.2 SD units; 95% CI, –0.02, 0.57).

Quality of life. Four placebo-controlled randomized trials (75, 83, 84, 85) reported on testosterone’s effect on quality of life. The results were inconsistent across trials and imprecise. There was significant improvement only for the physical function domain (0.5 SD units; 95% CI, 0.03, 0.9).

Depression. Systematic review of three randomized trials (63, 75, 86) found no significant effects of testosterone therapy for 3 months or longer on depression in older men with low or low-normal testosterone levels (–0.5 SD units; 95% CI, –1.0, 0.1). The inconsistent and imprecise results limit the inferential strength.

Cognition. Three placebo-controlled randomized trials (75, 87, 88), one of which studied patients with Alzheimer’s dementia and low testosterone levels (88), reported imprecise effects on several dimensions of cognition, none of which was significant after pooling.

Adverse Outcomes Associated with Testosterone Therapy

In a systematic review of 19 randomized trials to determine the risks of adverse events associated with testosterone therapy in older men (50), the combined rate of all prostate events was significantly greater in testosterone-treated men than in placebo-treated men (odds ratio, 1.78; 95% CI, 1.07, 2.95). Rates of prostate cancer, PSA greater than 4 ng/ml, and prostate biopsies were numerically higher in the testosterone group than in the placebo group, although differences between groups were not individually statistically significant. Testosterone-treated men were nearly four times more likely than placebo-treated men to experience hematocrit greater than 50% (odds ratio, 3.69; 95% CI, 1.82, 7.51). The frequency of cardiovascular events, sleep apnea, or death did not differ significantly between groups. Thus, testosterone therapy of older men was associated with a higher risk of detecting prostate events and hematocrit above 50% than placebo (50).

In a systematic review of placebo-controlled trials, studies (77, 89, 90, 91) that enrolled older men with low or low-normal testosterone levels reported insignificant changes in major lipid fractions [total cholesterol, –8 mg/dl (0.2 mmol/liter); 95% CI, –20, 1.2; LDL cholesterol, –4 mg/dl (0.1 mmol/liter); 95% CI, –15, 4; high-density lipoprotein cholesterol, –0.6 mg/dl (0.02 mmol/liter); 95% CI, –4.8, 3.2; and triglycerides, –9 mg/dl (0.1 mmol/liter); 95% CI, –36, 9].

2.3.C VALUES

The recommendation not to treat asymptomatic older men with age-related decline in testosterone level places a lower value on the unproven, potential benefits of testosterone therapy and a higher value on avoiding the burdens of testosterone administration, monitoring, and cost, as well as on unknown long-term risks.

2.3.D REMARKS

Diagnostic and treatment recommendations are the same as for patients with classical androgen deficiency. However, for older men, we suggest that clinicians aim at achieving total testosterone levels in the lower part of the normal range of young men [400–500 ng/dl (14.0–17.5 nmol/liter)]. Physicians should recognize considerable disagreement among experts on this issue (92).

	2.4 Patients with Chronic Illness and Low Testosterone Levels

Top Abstract Summary of Evidence-Based... METHOD OF DEVELOPMENT OF... GUIDELINES 1.2 Screening for Androgen... 2.0 Treatment of Androgen... 2.2. Testosterone Therapy in... 2.3 Older Men with... 2.4 Patients with Chronic... 2.4.2 Glucocorticoid-Treated Men References

 
2.4.1 HIV-infected men with weight loss

2.4.1.A RECOMMENDATION

We suggest that clinicians consider short-term testosterone therapy as an adjunctive therapy in HIV-infected men with low testosterone levels and weight loss to promote weight maintenance and gains in LBM and muscle strength. (2|)

2.4.1.B EVIDENCE

There is a high prevalence of low testosterone levels in HIV-infected men (22, 24): 20 to 25% of HIV-infected men on highly active antiretroviral therapy have low testosterone levels (93). Low testosterone levels are associated with weight loss, progression to AIDS (94), wasting (24), depression, and loss of muscle mass and exercise capacity (95).

Body weight and LBM. In a systematic review (96) of randomized, placebo-controlled trials of testosterone therapy in HIV-infected patients with weight loss that reported body composition (97, 98, 99, 100, 101, 102), 3 to 6 months of testosterone therapy was associated with greater gains in body weight (+1.54 kg; 95% CI, 0.03, 3.10) and LBM (+1.22 kg; 95% CI, 0.2, 2.2) than placebo. Difference in LBM between placebo and testosterone groups was greater in trials that used testosterone esters (+3.34 kg) (96).

Muscle strength. In two of three trials that measured muscle strength (98, 99, 102), testosterone administration was associated with significantly greater improvements in maximal voluntary strength than was placebo.

Other outcomes. In a systematic review of placebo-controlled trials, we found four reporting on depression in patients with HIV infection (103, 104, 105, 106). A large loss to follow-up in one trial, inconsistency across trials, incomplete data reporting, and imprecision limit the strength of inferences. Overall, testosterone therapy had a moderate effect on depression (–0.6 SD units; 95% CI, –1.0, –0.2). There were no significant testosterone effects on quality of life.

Adverse outcomes. The adverse event rates did not differ significantly between placebo and testosterone groups (98, 99, 100, 101). Changes in CD4+ T lymphocyte counts, HIV viral load, PSA, and plasma high-density lipoprotein cholesterol were not significantly different between groups.

There was considerable heterogeneity across trials (varying degrees of weight loss, disease severity, testosterone regimens, treatment duration, and methods to assess body composition). There are no data on testosterone’s effects on physical function, risk of disability, or long-term safety. Overall, short-term (3- to 6-month) testosterone use in HIV-infected men with low testosterone levels and weight loss can lead to small gains in body weight and LBM with minimal change in quality of life and mood. This inference is weakened by inconsistent results across trials.

2.4.1.C VALUES

The recommendation to offer short-term testosterone therapy to HIV-infected men with low testosterone levels and weight loss places a relatively higher value on gaining LBM and muscle strength and a relatively lower value on avoiding the potential for testosterone-related adverse effects, cost, and unclear long-term safety. Patients with a different value structure may decide to avoid testosterone therapy.

2.4.1.D REMARKS

Diagnostic and treatment recommendations are the same as for patients with classical androgen deficiency (Sections 1.1 and 2.1). Additionally, appropriate counseling for safe sex practices should be provided.

	2.4.2 Glucocorticoid-Treated Men

Top Abstract Summary of Evidence-Based... METHOD OF DEVELOPMENT OF... GUIDELINES 1.2 Screening for Androgen... 2.0 Treatment of Androgen... 2.2. Testosterone Therapy in... 2.3 Older Men with... 2.4 Patients with Chronic... 2.4.2 Glucocorticoid-Treated Men References

 
2.4.2.A RECOMMENDATION

We suggest 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|)

2.4.2.B EVIDENCE

Testosterone levels are lower in glucocorticoid-treated men than in age-matched controls (25). There is a high prevalence of low testosterone levels in glucocorticoid-treated men due to glucocorticoid-induced suppression of all components of the HPG axis. Typically, administration of more than 5–7.5 mg/d of prednisone or its equivalent increases the risk of gonadotropin and testosterone suppression and alterations in muscle and bone mass (107, 108).

In two placebo-controlled trials (107, 109), testosterone therapy of men receiving glucocorticoid treatment for bronchial asthma or chronic obstructive pulmonary disease was associated with a greater gain in LBM (2.3 kg; 95% CI, 2.0, 3.6) and a greater decrease in fat mass (–3.1 kg; 95% CI, –3.5, –2.8) than placebo. These two trials reported significant increase in lumbar bone mineral density in association with testosterone therapy (4%; 95% CI, 2%, 7%); the effect on femoral bone mineral density was inconsistent and not significant. There are no bone fracture data in this population.

Testosterone administration was associated with a low frequency of adverse events (107, 109). However, these inferences are weakened by the small size of these studies and their inconsistent results.

2.4.2.C VALUES

Our recommendation to offer testosterone therapy to glucocorticoid-treated men with low testosterone levels places a relatively higher value on the potential benefit of maintaining muscle mass and bone mineral density and a relatively lower value on avoiding the potential for adverse effects, on avoiding the burdens of testosterone administration, monitoring, and cost, and on the unclear long-term safety of the therapy.

2.4.2.D REMARKS

Diagnostic and treatment recommendations are the same as for patients with classical androgen deficiency.

	Acknowledgments

 
The members of the task force thank Dr. Robert Vigersky, the members of the Clinical Guidelines Subcommittee, the Clinical Affairs Committee, and The Endocrine Society Council for their careful review of earlier versions of this manuscript and their helpful suggestions. We thank Patricia A. Stephens, Ph.D., medical writer on this guideline, who meticulously checked the references and formatted the guideline into its current form. In addition, we thank the many members of The Endocrine Society who reviewed the draft version of this manuscript when it was posted on the Society web site and who sent a great number of additional comments, most of which were incorporated into the final version of the manuscript. To view responses to comments from members, go to http://www.endo-society.org/quickcontent/clinicalpractice/clinical-guidelines/

Finally, we thank the staff at The Endocrine Society office for their helpful support during the development of this Guideline.

Financial Disclosure of Writing Task Force

Shalender Bhasin, MD—Consultation or Advisement: GTx, Pfizer, TAP; Grant or Other Research Support: Solvay, GSK; Honoraria: Solvay, Auxilium. Glenn R. Cunningham, MD—Consultation or Advisement: Solvay Pharma, Columbia Lab, GSK; Grant or Other Research Support: Solvay Pharma; Columbia Lab, GSK; Speakers List: Solvay Pharma, Columbia Lab. Frances J. Hayes, MB, FRCPI—Consultation or Advisement: Auxilium Pharma, GSK, New England Research Institute; Speakers Bureau for Solvay. Alvin M. Matsumoto, MD—Consultation or Advisement: Solvay, GSK, Johnson & Johnson (J&J), Auxilium, GTx, TAP Pharmaceutical Products, Inc. (TAP), Threshold; Grant or Other Research Support: GSK, Columbia Labs, Solvay, Ascend. Peter J. Snyder, MD—Consultation or Advisement: None Declared; Grant or Other Research Support: Solvay Pharma. Ronald S. Swerdloff, MD—Consultation or Advisement: None Declared; Grant or Other Research Support: Actelion Pharma, ARYx Theraputics, Inc., Auxilium, Bayer Corp., Besins/Ascend, BNS, Clarus, Columbia, Corcept, GSK, Eli Lilly & Co., MacroChem Corp., Organon, Schering AG, Solvay Pharma, Inc. Co. Victor M. Montori, MD—Consultation or Advisement: Lilly/Takeda, Pfizer, Merck, Merck/Schering Plough, AstraZeneca, Abbott; Grant or Other Research Support: Novo/Nordisk, Pfizer, Merck, KOS, AstraZeneca, Sankyo; Speakers List: Lilly/Takeda, Pfizer, Merck, Merck/Schering Plough, KOS, AstraZeneca, Abbott.

	Footnotes

 
DISCLAIMER: Clinical Practice Guidelines are developed to be of assistance to endocrinologists by providing guidance and recommendations for particular areas of practice. The Guidelines should not be considered inclusive of all proper approaches or methods, or exclusive of others. The Guidelines cannot guarantee any specific outcome, nor do they establish a standard of care. The Guidelines are not intended to dictate the treatment of a particular patient. Treatment decisions must be made based on the independent judgment of healthcare providers and each patient’s individual circumstances.

The Endocrine Society makes no warranty, express or implied, regarding the Guidelines and specifically excludes any warranties of merchantability and fitness for a particular use or purpose. The Society shall not be liable for direct, indirect, special, incidental, or consequential damages related to the use of the information contained herein.

First Published Online May 23, 2006

Abbreviations: CI, Confidence interval; ED, erectile dysfunction; HPG, hypothalamic-pituitary-gonadal; LBM, lean body mass; MRI, magnetic resonance imaging.

Received December 30, 2005.

Accepted March 20, 2006.

	References

Top Abstract Summary of Evidence-Based... METHOD OF DEVELOPMENT OF... GUIDELINES 1.2 Screening for Androgen... 2.0 Treatment of Androgen... 2.2. Testosterone Therapy in... 2.3 Older Men with... 2.4 Patients with Chronic... 2.4.2 Glucocorticoid-Treated Men References

 

1. Atkins D, Best D, Briss PA, Eccles M, Falck-Ytter Y, Flottorp S, Guyatt GH, Harbour RT, Haugh MC, Henry D, Hill S, Jaeschke R, Leng G, Liberati A, Magrini N, Mason J, Middleton P, Mrukowicz J, O’Connell D, Oxman AD, Phillips B, Schunemann HJ, Edejer TT, Varonen H, Vist GE, Williams Jr JW, Zaza S 2004 Grading quality of evidence and strength of recommendations. BMJ 328:1490
2. Matsumoto AM 2001 The testis. In: Felig P, Frohman LA, eds. Endocrinology and metabolism, 4th ed. New York: McGraw-Hill; 635–705
3. Feldman HA, Longcope C, Derby CA, Johannes CB, Araujo AB, Coviello AD, Bremner WJ, McKinlay JB 2002 Age trends in the level of serum testosterone and other hormones in middle-aged men: longitudinal results from the Massachusetts Male Aging Study. J Clin Endocrinol Metab 87:589–598[Abstract/Free Full Text]
4. Harman SM, Metter EJ, Tobin JD, Pearson J, Blackman MR 2001 Longitudinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore Longitudinal Study of Aging. J Clin Endocrinol Metab 86:724–731[Abstract/Free Full Text]
5. Bhasin S, Buckwalter JG 2001 Testosterone supplementation in older men: a rational idea whose time has not yet come. J Androl 22:718–731[Medline]
6. Gray A, Feldman HA, McKinlay JB, Longcope C 1991 Age, disease, and changing sex hormone levels in middle-aged men: results of the Massachusetts Male Aging Study. J Clin Endocrinol Metab 73:1016–1025[Abstract/Free Full Text]
7. Buena F, Swerdloff RS, Steiner BS, Lutchmansingh P, Peterson MA, Pandian MR, Galmarini M, Bhasin S 1993 Sexual function does not change when serum testosterone levels are pharmacologically varied within the normal male range. Fertil Steril 59:1118–1123[Medline]
8. Kelleher S, Conway AJ, Handelsman DJ 2004 Blood testosterone threshold for androgen deficiency symptoms. J Clin Endocrinol Metab 89:3813–3817[Abstract/Free Full Text]
9. Seftel AD, Mack RJ, Secrest AR, Smith TM 2004 Restorative increases in serum testosterone levels are significantly correlated to improvements in sexual functioning. J Androl 25:963–972[Abstract/Free Full Text]
10. Swerdloff RS, Wang C, Cunningham G, Dobs A, Iranmanesh A, Matsumoto AM, Snyder PJ, Weber T, Longstreth J, Berman N 2000 Long-term pharmacokinetics of transdermal testosterone gel in hypogonadal men. J Clin Endocrinol Metab 85:4500–4510[Abstract/Free Full Text]
11. Spratt DI, O’Dea LS, Schoenfeld D, Butler J, Rao PN, Crowley Jr WF 1988 Neuroendocrine-gonadal axis in men: frequent sampling of LH, FSH, and testosterone. Am J Physiol 254:E658–E666
12. Wang C, Catlin DH, Demers LM, Starcevic B, Swerdloff RS 2004 Measurement of total serum testosterone in adult men: comparison of current laboratory methods versus liquid chromatography-tandem mass spectrometry. J Clin Endocrinol Metab 89:534–543[Abstract/Free Full Text]
13. Vermeulen A, Verdonck L, Kaufman JM 1999 A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab 84:3666–3672[Abstract/Free Full Text]
14. Buvat J, Lemaire A 1997 Endocrine screening in 1,022 men with erectile dysfunction: clinical significance and cost-effective strategy. J Urol 158:1764–1767[CrossRef][Medline]
15. Citron JT, Ettinger B, Rubinoff H, Ettinger VM, Minkoff J, Hom F, Kan P, Alloo R 1996 Prevalence of hypothalamic-pituitary imaging abnormalities in impotent men with secondary hypogonadism. J Urol 155:529–533[CrossRef][Medline]
16. Riggs BL, Khosla S, Melton 3rd LJ 2002 Sex steroids and the construction and conservation of the adult skeleton. Endocr Rev 23:279–302[Abstract/Free Full Text]
17. Nieschlag E, Nieschlag S, Behre HM 1993 Lifespan and testosterone. Nature 366:215
18. Liverman CT, Blazer DG 2004 Testosterone and aging, clinical research directions. Washington, DC: National Academies Press
19. Morley JE, Charlton E, Patrick P, Kaiser FE, Cadeau P, McCready D, Perry 3rd HM 2000 Validation of a screening questionnaire for androgen deficiency in aging males. Metabolism 49:1239–1242[CrossRef][Medline]
20. Moore C, Huebler D, Zimmermann T, Heinemann LA, Saad F, Thai do M 2004 The aging males’ symptoms scale (AMS) as outcome measure for treatment of androgen deficiency. Eur Urol 46:80–87[CrossRef][Medline]
21. Smith KW, Feldman HA, McKinlay JB 2000 Construction and field validation of a self-administered screener for testosterone deficiency (hypogonadism) in ageing men. Clin Endocrinol (Oxf) 53:703–711[CrossRef][Medline]
22. Arver S, Sinha-Hikim I, Beall G, Guerrero M, Shen R, Bhasin S 1999 Serum dihydrotestosterone and testosterone concentrations in human immunodeficiency virus-infected men with and without weight loss. J Androl 20:611–618[Abstract/Free Full Text]
23. Bliesener N, Albrecht S, Schwager A, Weckbecker K, Lichtermann D, Klingmuller D 2005 Plasma testosterone and sexual function in men receiving buprenorphine maintenance for opioid dependence. J Clin Endocrinol Metab 90:203–206[Abstract/Free Full Text]
24. Dobs AS, Few 3rd WL, Blackman MR, Harman SM, Hoover DR, Graham NM 1996 Serum hormones in men with human immunodeficiency virus-associated wasting. J Clin Endocrinol Metab 81:4108–4112[Abstract/Free Full Text]
25. Reid IR, Ibbertson HK, France JT, Pybus J 1985 Plasma testosterone concentrations in asthmatic men treated with glucocorticoids. Br Med J (Clin Res Ed) 291:574
26. Mauras N, Hayes V, Welch S, Rini A, Helgeson K, Dokler M, Veldhuis JD, Urban RJ 1998 Testosterone deficiency in young men: marked alterations in whole body protein kinetics, strength, and adiposity. J Clin Endocrinol Metab 83:1886–1892[Abstract/Free Full Text]
27. Alexander GM, Swerdloff RS, Wang C, Davidson T, McDonald V, Steiner B, Hines M 1997 Androgen-behavior correlations in hypogonadal men and eugonadal men. I. Mood and response to auditory sexual stimuli. Horm Behav 31:110–119[CrossRef][Medline]
28. Kwan M, Greenleaf WJ, Mann J, Crapo L, Davidson JM 1983 The nature of androgen action on male sexuality: a combined laboratory-self-report study on hypogonadal men. J Clin Endocrinol Metab 57:557–562[Abstract/Free Full Text]
29. Wang C, Swedloff RS, Iranmanesh A, Dobs A, Snyder PJ, Cunningham G, Matsumoto AM, Weber T, Berman N 2000 Transdermal testosterone gel improves sexual function, mood, muscle strength, and body composition parameters in hypogonadal men. Testosterone Gel Study Group. J Clin Endocrinol Metab 85:2839–2853[Abstract/Free Full Text]
30. Bhasin S, Storer TW, Berman N, Yarasheski KE, Clevenger B, Phillips J, Lee WP, Bunnell TJ, Casaburi R 1997 Testosterone replacement increases fat-free mass and muscle size in hypogonadal men. J Clin Endocrinol Metab 82:407–413[Abstract/Free Full Text]
31. Brodsky IG, Balagopal P, Nair KS 1996 Effects of testosterone replacement on muscle mass and muscle protein synthesis in hypogonadal men—a clinical research center study. J Clin Endocrinol Metab 81:3469–3475[Abstract]
32. Dobs AS, Meikle AW, Arver S, Sanders SW, Caramelli KE, Mazer NA 1999 Pharmacokinetics, efficacy, and safety of a permeation-enhanced testosterone transdermal system in comparison with bi-weekly injections of testosterone enanthate for the treatment of hypogonadal men. J Clin Endocrinol Metab 84:3469–3478[Abstract/Free Full Text]
33. Katznelson L, Finkelstein JS, Schoenfeld DA, Rosenthal DI, Anderson EJ, Klibanski A 1996 Increase in bone density and lean body mass during testosterone administration in men with acquired hypogonadism. J Clin Endocrinol Metab 81:4358–4365[Abstract]
34. McNicholas TA, Dean JD, Mulder H, Carnegie C, Jones NA 2003 A novel testosterone gel formulation normalizes androgen levels in hypogonadal men, with improvements in body composition and sexual function. BJU Int 91:69–74[CrossRef][Medline]
35. Snyder PJ, Peachey H, Berlin JA, Hannoush P, Haddad G, Dlewati A, Santanna J, Loh L, Lenrow DA, Holmes JH, Kapoor SC, Atkinson LE, Strom BL 2000 Effects of testosterone replacement in hypogonadal men. J Clin Endocrinol Metab 85:2670–2677[Abstract/Free Full Text]
36. Steidle C, Schwartz S, Jacoby K, Sebree T, Smith T, Bachand R 2003 AA2500 testosterone gel normalizes androgen levels in aging males with improvements in body composition and sexual function. J Clin Endocrinol Metab 88:2673–2681[Abstract/Free Full Text]
37. Wang C, Cunningham G, Dobs A, Iranmanesh A, Matsumoto AM, Snyder PJ, Weber T, Berman N, Hull L, Swerdloff RS 2004 Long-term testosterone gel (AndroGel) treatment maintains beneficial effects on sexual function and mood, lean and fat mass, and bone mineral density in hypogonadal men. J Clin Endocrinol Metab 89:2085–2098[Abstract/Free Full Text]
38. Wang C, Iranmanesh A, Berman N, McDonald V, Steiner B, Ziel F, Faulkner SM, Dudley RE, Veldhuis JD, Swerdloff RS 1998 Comparative pharmacokinetics of three doses of percutaneous dihydrotestosterone gel in healthy elderly men—a clinical research center study. J Clin Endocrinol Metab 83:2749–2757[Abstract/Free Full Text]
39. Bhasin S, Woodhouse L, Casaburi R, Singh AB, Bhasin D, Berman N, Chen X, Yarasheski KE, Magliano L, Dzekov C, Dzekov J, Bross R, Phillips J, Sinha-Hikim I, Shen R, Storer TW 2001 Testosterone dose-response relationships in healthy young men. Am J Physiol Endocrinol Metab 281:E1172—E1181
40. Bhasin S, Woodhouse L, Casaburi R, Singh AB, Mac RP, Lee M, Yarasheski KE, Sinha-Hikim I, Dzekov C, Dzekov J, Magliano L, Storer TW 2005 Older men are as responsive as young men to the anabolic effects of graded doses of testosterone on the skeletal muscle. J Clin Endocrinol Metab 90:678–688[Abstract/Free Full Text]
41. Behre HM, Kliesch S, Leifke E, Link TM, Nieschlag E 1997 Long-term effect of testosterone therapy on bone mineral density in hypogonadal men. J Clin Endocrinol Metab 82:2386–2390[Abstract/Free Full Text]
42. Rabkin JG, Rabkin R, Wagner G 1995 Testosterone replacement therapy in HIV illness. Gen Hosp Psychiatry 17:37–42[CrossRef][Medline]
43. Cherrier MM, Asthana S, Plymate S, Baker L, Matsumoto AM, Peskind E, Raskind MA, Brodkin K, Bremner W, Petrova A, LaTendresse S, Craft S 2001 Testosterone supplementation improves spatial and verbal memory in healthy older men. Neurology 57:80–88[Abstract/Free Full Text]
44. Janowsky JS, Oviatt SK, Orwoll ES 1994 Testosterone influences spatial cognition in older men. Behav Neurosci 108:325–332[CrossRef][Medline]
45. Marin P, Krotkiewski M, Bjorntorp P 1992 Androgen treatment of middle-aged, obese men: effects on metabolism, muscle and adipose tissues. Eur J Med 1:329–336[Medline]
46. Singh AB, Hsia S, Alaupovic P, Sinha-Hikim I, Woodhouse L, Buchanan TA, Shen R, Bross R, Berman N, Bhasin S 2002 The effects of varying doses of T on insulin sensitivity, plasma lipids, apolipoproteins, and C-reactive protein in healthy young men. J Clin Endocrinol Metab 87:136–143[Abstract/Free Full Text]
47. Fowler Jr JE, Whitmore Jr WF 1981 The response of metastatic adenocarcinoma of the prostate to exogenous testosterone. J Urol 126:372–375[Medline]
48. Agarwal PK, Oefelein MG 2005 Testosterone replacement therapy after primary treatment for prostate cancer. J Urol 173:533–536[CrossRef][Medline]
49. Kaufman JM, Graydon RJ 2004 Androgen replacement after curative radical prostatectomy for prostate cancer in hypogonadal men. J Urol 172:920–922[CrossRef][Medline]
50. Calof OM, Singh AB, Lee ML, Kenny AM, Urban RJ, Tenover JL, Bhasin S 2005 Adverse events associated with testosterone replacement in middle-aged and older men: a meta-analysis of randomized, placebo-controlled trials. J Gerontol A Biol Sci Med Sci 60:1451–1457[Abstract/Free Full Text]
51. Bancroft J, Wu FC 1983 Changes in erectile responsiveness during androgen replacement therapy. Arch Sex Behav 12:59–66[CrossRef][Medline]
52. Carani C, Scuteri A, Marrama P, Bancroft J 1990 The effects of testosterone administration and visual erotic stimuli on nocturnal penile tumescence in normal men. Horm Behav 24:435–441[CrossRef][Medline]
53. Clopper RR, Voorhess ML, MacGillivray MH, Lee PA, Mills B 1993 Psychosexual behavior in hypopituitary men: a controlled comparison of gonadotropin and testosterone replacement. Psychoneuroendocrinology 18:149–161[CrossRef][Medline]
54. Carani C, Bancroft J, Granata A, Del Rio G, Marrama P 1992 Testosterone and erectile function, nocturnal penile tumescence and rigidity, and erectile response to visual erotic stimuli in hypogonadal and eugonadal men. Psychoneuroendocrinology 17:647–654[CrossRef][Medline]
55. Skakkebaek NE, Bancroft J, Davidson DW, Warner P 1981 Androgen replacement with oral testosterone undecanoate in hypogonadal men: a double blind controlled study. Clin Endocrinol (Oxf) 14:49–61[Medline]
56. Riehmann M, Rhodes PR, Cook TD, Grose GS, Bruskewitz RC 1993 Analysis of variation in prostate-specific antigen values. Urology 42:390–397[CrossRef][Medline]
57. Gormley GJ, Stoner E, Bruskewitz RC, Imperato-McGinley J, Walsh PC, McConnell JD, Andriole GL, Geller J, Bracken BR, Tenover JS, Vaughan ED, Pappas F, Taylor A, Binkowitz B, Ng J 1992 The effect of finasteride in men with benign prostatic hyperplasia. The Finasteride Study Group. N Engl J Med 327:1185–1191[Abstract]
58. Bhasin S, Singh AB, Mac RP, Carter B, Lee MI, Cunningham GR 2003 Managing the risks of prostate disease during testosterone replacement therapy in older men: recommendations for a standardized monitoring plan. J Androl 24:299–311[Free Full Text]
59. Carter HB 1997 PSA variability versus velocity. Urology 49:305
60. Bancroft J 1981 Hormones and human sexual behaviour. Br Med Bull 37:153–158[Free Full Text]
61. Cunningham GR, Hirshkowitz M, Korenman SG, Karacan I 1990 Testosterone replacement therapy and sleep-related erections in hypogonadal men. J Clin Endocrinol Metab 70:792–797[Abstract/Free Full Text]
62. Korenman SG, Morley JE, Mooradian AD, Davis SS, Kaiser FE, Silver AJ, Viosca SP, Garza D 1990 Secondary hypogonadism in older men: its relation to impotence. J Clin Endocrinol Metab 71:963–969[Abstract/Free Full Text]
63. Cavallini G, Caracciolo S, Vitali G, Modenini F, Biagiotti G 2004 Carnitine versus androgen administration in the treatment of sexual dysfunction, depressed mood, and fatigue associated with male aging. Urology 63:641–646[CrossRef][Medline]
64. Carani C, Granata AR, Bancroft J, Marrama P 1995 The effects of testosterone replacement on nocturnal penile tumescence and rigidity and erectile response to visual erotic stimuli in hypogonadal men. Psychoneuroendocrinology 20:743–753[CrossRef][Medline]
65. Aversa A, Isidori AM, Spera G, Lenzi A, Fabbri A 2003 Androgens improve cavernous vasodilation and response to sildenafil in patients with erectile dysfunction. Clin Endocrinol (Oxf) 58:632–638[CrossRef][Medline]
66. O’Carroll R, Bancroft J 1984 Testosterone therapy for low sexual interest and erectile dysfunction in men: a controlled study. Br J Psychiatry 145:146–151[Abstract/Free Full Text]
67. Jain P, Rademaker AW, McVary KT 2000 Testosterone supplementation for erectile dysfunction: results of a meta-analysis. J Urol 164:371–375[CrossRef][Medline]
68. Carani C, Zini D, Baldini A, Della Casa L, Ghizzani A, Marrama P 1990 Effects of androgen treatment in impotent men with normal and low levels of free testosterone. Arch Sex Behav 19:223–234[CrossRef][Medline]
69. Shabsigh R, Kaufman J, Aurora CO, Steidle C, Padma-Natha H 2003 Testosterone replacement therapy with testosterone gel 1% converts sildenafil non-responders in men with hypogonadism and erectile dysfunction who failed prior sildenafil therapy. J Urol 169:247 (854A)
70. Schiavi RC, White D, Mandeli J, Levine AC 1997 Effect of testosterone administration on sexual behavior and mood in men with erectile dysfunction. Arch Sex Behav 26:231–241[CrossRef][Medline]
71. Amory JK, Watts NB, Easley KA, Sutton PR, Anawalt BD, Matsumoto AM, Bremner WJ, Tenover JL 2004 Exogenous testosterone or testosterone with finasteride increases bone mineral density in older men with low serum testosterone. J Clin Endocrinol Metab 89:503–510[Abstract/Free Full Text]
72. Kenny AM, Prestwood KM, Gruman CA, Marcello KM, Raisz LG 2001 Effects of transdermal testosterone on bone and muscle in older men with low bioavailable testosterone levels. J Gerontol A Biol Sci Med Sci 56:M266–M272
73. Snyder PJ, Peachey H, Hannoush P, Berlin JA, Loh L, Lenrow DA, Holmes JH, Dlewati A, Santanna J, Rosen CJ, Strom BL 1999 Effect of testosterone treatment on body composition and muscle strength in men over 65 years of age. J Clin Endocrinol Metab 84:2647–2653[Abstract/Free Full Text]
74. Ferrando AA, Sheffield-Moore M, Paddon-Jones D, Wolfe RR, Urban RJ 2003 Differential anabolic effects of testosterone and amino acid feeding in older men. J Clin Endocrinol Metab 88:358–362[Abstract/Free Full Text]
75. Kenny AM, Bellantonio S, Gruman CA, Acosta RD, Prestwood KM 2002 Effects of transdermal testosterone on cognitive function and health perception in older men with low bioavailable testosterone levels. J Gerontol A Biol Sci Med Sci 57:M321—M325
76. Morley JE, Perry 3rd HM, Kaiser FE, Kraenzle D, Jensen J, Houston K, Mattammal M, Perry Jr HM 1993 Effects of testosterone replacement therapy in old hypogonadal males: a preliminary study. J Am Geriatr Soc 41:149–152[Medline]
77. Page ST, Amory JK, Bowman FD, Anawalt BD, Matsumoto AM, Bremner WJ, Tenover JL 2005 Exogenous testosterone (T) alone or with finasteride increases physical performance, grip strength, and lean body mass in older men with low serum T. J Clin Endocrinol Metab 90:1502–1510[Abstract/Free Full Text]
78. Sih R, Morley JE, Kaiser FE, Perry 3rd HM, Patrick P, Ross C 1997 Testosterone replacement in older hypogonadal men: a 12-month randomized controlled trial. J Clin Endocrinol Metab 82:1661–1667[Abstract/Free Full Text]
79. Tenover JS 1992 Effects of testosterone supplementation in the aging male. J Clin Endocrinol Metab 75:1092–1098[Abstract]
80. Snyder PJ, Peachey H, Hannoush P, Berlin JA, Loh L, Holmes JH, Dlewati A, Staley J, Santanna J, Kapoor SC, Attie MF, Haddad Jr JG, Strom BL 1999 Effect of testosterone treatment on bone mineral density in men over 65 years of age. J Clin Endocrinol Metab 84:1966–1972[Abstract/Free Full Text]
81. Harman SM, Blackman MR 2003 The effects of growth hormone and sex steroid on lean body mass, fat mass, muscle strength, cardiovascular endurance and adverse events in healthy elderly women and men. Horm Res 60:121–124[Medline]
82. Wittert GA, Chapman IM, Haren MT, Mackintosh S, Coates P, Morley JE 2003 Oral testosterone supplementation increases muscle and decreases fat mass in healthy elderly males with low-normal gonadal status. J Gerontol A Biol Sci Med Sci 58:618–625
83. English KM, Steeds RP, Jones TH, Diver MJ, Channer KS 2000 Low-dose transdermal testosterone therapy improves angina threshold in men with chronic stable angina: a randomized, double-blind, placebo-controlled study. Circulation 102:1906–1911[Abstract/Free Full Text]
84. Liu PY, Yee B, Wishart SM, Jimenez M, Jung DG, Grunstein RR, Handelsman DJ 2003 The short-term effects of high-dose testosterone on sleep, breathing, and function in older men. J Clin Endocrinol Metab 88:3605–3613[Abstract/Free Full Text]
85. Reddy P, White CM, Dunn AB, Moyna NM, Thompson PD 2000 The effect of testosterone on health-related quality of life in elderly males: a pilot study. J Clin Pharm Ther 25:421–426[CrossRef][Medline]
86. Orengo CA, Fullerton L, Kunik ME 2005 Safety and efficacy of testosterone gel 1% augmentation in depressed men with partial response to antidepressant therapy. J Geriatr Psychiatry Neurol 18:20–24[Abstract]
87. Kenny AM, Fabregas G, Song C, Biskup B, Bellantonio S 2004 Effects of testosterone on behavior, depression, and cognitive function in older men with mild cognitive loss. J Gerontol A Biol Sci Med Sci 59:75–78
88. Tan RS, Culberson JW 2003 An integrative review on current evidence of testosterone replacement therapy for the andropause. Maturitas 45:15–27[CrossRef][Medline]
89. Ferrando AA, Sheffield-Moore M, Yeckel CW, Gilkison C, Jiang J, Achacosa A, Lieberman SA, Tipton K, Wolfe RR, Urban RJ 2002 Testosterone administration to older men improves muscle function: molecular and physiological mechanisms. Am J Physiol Endocrinol Metab 282:E601–E607
90. Kenny AM, Prestwood KM, Gruman CA, Fabregas G, Biskup B, Mansoor G 2002 Effects of transdermal testosterone on lipids and vascular reactivity in older men with low bioavailable testosterone levels. J Gerontol A Biol Sci Med Sci 57:M460–M465
91. Snyder PJ, Peachey H, Berlin JA, Rader D, Usher D, Loh L, Hannoush P, Dlewati A, Holmes JH, Santanna J, Strom BL 2001 Effect of transdermal testosterone treatment on serum lipid and apolipoprotein levels in men more than 65 years of age. Am J Med 111:255–260[CrossRef][Medline]
92. Nieschlag E, Swerdloff R, Behre HM, Gooren LJ, Kaufman JM, Legros JJ, Lunenfeld B, Morley JE, Schulman C, Wang C, Weidner W, Wu FC 2005 Investigation, treatment and monitoring of late-onset hypogonadism in males. ISA, ISSAM, and EAU recommendations. Eur Urol 48:1–4[CrossRef][Medline]
93. Rietschel P, Corcoran C, Stanley T, Basgoz N, Klibanski A, Grinspoon S 2000 Prevalence of hypogonadism among men with weight loss related to human immunodeficiency virus infection who were receiving highly active antiretroviral therapy. Clin Infect Dis 31:1240–1244[CrossRef][Medline]
94. Salehian B, Jacobson D, Swerdloff RS, Grafe MR, Sinha-Hikim I, McCutchan JA 1999 Testicular pathologic changes and the pituitary-testicular axis during human immunodeficiency virus infection. Endocr Pract 5:1–9[Medline]
95. Grinspoon S, Corcoran C, Lee K, Burrows B, Hubbard J, Katznelson L, Walsh M, Guccione A, Cannan J, Heller H, Basgoz N, Klibanski A 1996 Loss of lean body and muscle mass correlates with androgen levels in hypogonadal men with acquired immunodeficiency syndrome and wasting. J Clin Endocrinol Metab 81:4051–4058[Abstract/Free Full Text]
96. Kong A, Edmonds P 2002 Testosterone therapy in HIV wasting syndrome: systematic review and meta-analysis. Lancet Infect Dis 2:692–699[CrossRef][Medline]
97. Berger JR, Pall L, Hall CD, Simpson DM, Berry PS, Dudley R 1996 Oxandrolone in AIDS-wasting myopathy. Aids 10:1657–1662[Medline]
98. Bhasin S, Storer TW, Asbel-Sethi N, Kilbourne A, Hays R, Sinha-Hikim I, Shen R, Arver S, Beall G 1998 Effects of testosterone replacement with a nongenital, transdermal system, Androderm, in human immunodeficiency virus-infected men with low testosterone levels. J Clin Endocrinol Metab 83:3155–3162[Abstract/Free Full Text]
99. Bhasin S, Storer TW, Javanbakht M, Berman N, Yarasheski KE, Phillips J, Dike M, Sinha-Hikim I, Shen R, Hays RD, Beall G 2000 Testosterone replacement and resistance exercise in HIV-infected men with weight loss and low testosterone levels. JAMA 283:763–770[Abstract/Free Full Text]
100. Dobs AS, Cofrancesco J, Nolten WE, Danoff A, Anderson R, Hamilton CD, Feinberg J, Seekins D, Yangco B, Rhame F 1999 The use of a transscrotal testosterone delivery system in the treatment of patients with weight loss related to human immunodeficiency virus infection. Am J Med 107:126–132[CrossRef][Medline]
101. Grinspoon S, Corcoran C, Askari H, Schoenfeld D, Wolf L, Burrows B, Walsh M, Hayden D, Parlman K, Anderson E, Basgoz N, Klibanski A 1998 Effects of androgen administration in men with the AIDS wasting syndrome. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 129:18–26[Abstract/Free Full Text]
102. Grinspoon S, Corcoran C, Parlman K, Costello M, Rosenthal D, Anderson E, Stanley T, Schoenfeld D, Burrows B, Hayden D, Basgoz N, Klibanski A 2000 Effects of testosterone and progressive resistance training in eugonadal men with AIDS wasting. A randomized, controlled trial. Ann Intern Med 133:348–355[Abstract/Free Full Text]
103. Grinspoon S, Corcoran C, Stanley T, Baaj A, Basgoz N, Klibanski A 2000 Effects of hypogonadism and testosterone administration on depression indices in HIV-infected men. J Clin Endocrinol Metab 85:60–65[Abstract/Free Full Text]
104. Rabkin JG, Ferrando SJ, Wagner GJ, Rabkin R 2000 DHEA treatment for HIV+ patients: effects on mood, androgenic and anabolic parameters. Psychoneuroendocrinology 25:53–68[CrossRef][Medline]
105. Rabkin JG, Wagner GJ, McElhiney MC, Rabkin R, Lin SH 2004 Testosterone versus fluoxetine for depression and fatigue in HIV/AIDS: a placebo-controlled trial. J Clin Psychopharmacol 24:379–385[CrossRef][Medline]
106. Rabkin JG, Wagner GJ, Rabkin R 1999 Testosterone therapy for human immunodeficiency virus-positive men with and without hypogonadism. J Clin Psychopharmacol 19:19–27[CrossRef][Medline]
107. Crawford BA, Liu PY, Kean MT, Bleasel JF, Handelsman DJ 2003 Randomized placebo-controlled trial of androgen effects on muscle and bone in men requiring long-term systemic glucocorticoid treatment. J Clin Endocrinol Metab 88:3167–3176[Abstract/Free Full Text]
108. van Staa TP, Leufkens HG, Cooper C 2002 The epidemiology of corticosteroid-induced osteoporosis: a meta-analysis. Osteoporos Int 13:777–787[CrossRef][Medline]
109. Reid IR, Wattie DJ, Evans MC, Stapleton JP 1996 Testosterone therapy in glucocorticoid-treated men. Arch Intern Med 156:1173–1177[Abstract/Free Full Text]

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				C. Hammond, J. R. Abrams, and K. L. Syrjala Fertility and Risk Factors for Elevated Infertility Concern in 10-Year Hematopoietic Cell Transplant Survivors and Case-Matched Controls J. Clin. Oncol., August 10, 2007; 25(23): 3511 - 3517. [Abstract] [Full Text] [PDF]

				S. A. Hall, S. T. Page, T. G. Travison, R. B. Montgomery, C. L. Link, and J. B. McKinlay Do Statins Affect Androgen Levels in Men? Results from the Boston Area Community Health Survey Cancer Epidemiol. Biomarkers Prev., August 1, 2007; 16(8): 1587 - 1594. [Abstract] [Full Text] [PDF]

				T. L. Nielsen, C. Hagen, K. Wraae, K. Brixen, P. H. Petersen, E. Haug, R. Larsen, and M. Andersen Visceral and Subcutaneous Adipose Tissue Assessed by Magnetic Resonance Imaging in Relation to Circulating Androgens, Sex Hormone-Binding Globulin, and Luteinizing Hormone in Young Men J. Clin. Endocrinol. Metab., July 1, 2007; 92(7): 2696 - 2705. [Abstract] [Full Text] [PDF]

				B. B Yeap, O. P Almeida, Z. Hyde, P. E Norman, S A P. Chubb, K. Jamrozik, and L. Flicker In men older than 70 years, total testosterone remains stable while free testosterone declines with age. The Health in Men Study Eur. J. Endocrinol., May 1, 2007; 156(5): 585 - 594. [Abstract] [Full Text] [PDF]

				D. Kapoor, H. Aldred, S. Clark, K. S. Channer, and T. H. Jones Clinical and Biochemical Assessment of Hypogonadism in Men With Type 2 Diabetes: Correlations with bioavailable testosterone and visceral adiposity Diabetes Care, April 1, 2007; 30(4): 911 - 917. [Abstract] [Full Text] [PDF]

				S. Bhasin, R. A. Parker, F. Sattler, R. Haubrich, B. Alston, T. Umbleja, C. M. Shikuma, and for the AIDS Clinical Trials Group Protocol A5079 Effects of Testosterone Supplementation on Whole Body and Regional Fat Mass and Distribution in Human Immunodeficiency Virus-Infected Men with Abdominal Obesity J. Clin. Endocrinol. Metab., March 1, 2007; 92(3): 1049 - 1057. [Abstract] [Full Text] [PDF]

				S. T. Page, A. M. Matsumoto, W. J. Bremner, M. Yasuda, S. Horie, T. T. Perls, N. Gleicher, D. Barad, K. S. Nair, and G. Smith DHEA and Testosterone in the Elderly N. Engl. J. Med., February 8, 2007; 356(6): 635 - 637. [Full Text] [PDF]

				D. Shames, A. Gassman, and H. Handelsman Guideline for Male Testosterone Therapy: A Regulatory Perspective J. Clin. Endocrinol. Metab., February 1, 2007; 92(2): 414 - 415. [Full Text] [PDF]

				A. Morgentaler Guideline for Male Testosterone Therapy: A Clinician's Perspective J. Clin. Endocrinol. Metab., February 1, 2007; 92(2): 416 - 417. [Full Text] [PDF]

				F. C. W. Wu Guideline for Male Testosterone Therapy: A European Perspective J. Clin. Endocrinol. Metab., February 1, 2007; 92(2): 418 - 419. [Full Text] [PDF]

				E. R. Bolona, M. V. Uraga, R. M. Haddad, M. J. Tracz, K. Sideras, C. C. Kennedy, S. M. Caples, P. J. Erwin, and V. M. Montori Testosterone Use in Men With Sexual Dysfunction: A Systematic Review and Meta-analysis of Randomized Placebo-Controlled Trials Mayo Clin. Proc., January 1, 2007; 82(1): 20 - 28. [Abstract] [Full Text] [PDF]

				R. M. Haddad, C. C. Kennedy, S. M. Caples, M. J. Tracz, E. R. Bolona, K. Sideras, M. V. Uraga, P. J. Erwin, and V. M. Montori Testosterone and Cardiovascular Risk in Men: A Systematic Review and Meta-analysis of Randomized Placebo-Controlled Trials Mayo Clin. Proc., January 1, 2007; 82(1): 29 - 39. [Abstract] [Full Text] [PDF]

				B. H. Lewis, M. Legato, and H. Fisch Medical Implications of the Male Biological Clock. JAMA, November 15, 2006; 296(19): 2369 - 2371. [Full Text] [PDF]

				Practice Guideline: Androgen Deficiency in Adult Men Journal Watch (General), July 13, 2006; 2006(713): 5 - 5. [Full Text]

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