3071 Men’s Health CHAPTER 399

TABLE 399-2 The Main Findings of the Testosterone Trials (TTrials)

TRIAL PRIMARY OUTCOME(S) MAIN FINDINGS

Sexual Function

Trial

Sexual activity Testosterone treatment improved

sexual activity, sexual desire, and

erectile function.

Physical

Function Trial

Distance walked over

6 min and self-reported

physical function

Testosterone treatment

consistently improved selfreported walking ability and

modestly improved 6-min walk

test distance across all TTtrials

participants but did not affect

falls.

Vitality Trial Energy measured

using the Functional

Assessment of Chronic

Illness Therapy (FACIT-F)

Testosterone did not improve

energy but modestly improved

mood and depressive symptoms.

Anemia Trial The proportion of men

with unexplained anemia

who increased their

hemoglobin ≥1.0 g/dL and

experienced correction

of anemia

Testosterone treatment, compared

to placebo, was associated with

a greater proportion of men with

unexplained anemia increasing

their hemoglobin by ≥1.0 g/dL and

correcting their anemia.

Cognitive

Function Trial

Delayed paragraph recall

(Wechsler-Memory

scale, a measure of

memory)

Testosterone treatment did not

improve delayed paragraph recall,

visual memory, spatial ability,

subjective memory complaints, or

global cognitive function.

Bone Trial Volumetric bone mineral

density (vBMD) assessed

using quantitative

computed tomography

Testosterone treatment increased

vBMD of the trabecular as well as

peripheral bone in the spine and

hip and increased estimated bone

strength in the spine and hip more

than placebo.

Cardiovascular

Trial

Noncalcified coronary

artery plaque volume

determined by computed

tomographic angiography

Testosterone treatment was

associated with greater increase

in the volume of noncalcified

plaque in the coronary arteries

than placebo.

Note: The TTrials were a set of seven coordinated placebo-controlled trials whose

primary goal was to determine whether testosterone treatment for 1 year of men

aged 65 years or older with an average of two morning, fasting total testosterone

levels <275 ng/dL plus one or more of three conditions (low sexual desire, mobility

limitation, and/or low vitality) was more efficacious than placebo in improving

sexual function, mobility, and/ or vitality. The other four linked trials evaluated the

effects of testosterone treatment on volumetric bone mineral density, anemia,

cognitive function, and coronary artery plaque volume.

a lifestyle program for 2 years reduced the proportion of participants

with type 2 diabetes more than placebo plus lifestyle program. Testosterone therapy has not been shown to improve fracture risk, cognitive

function, or response to phosphodiesterase inhibitors in older men.

Neither the long-term risks nor the clinical benefits of testosterone

therapy in older men have been demonstrated in adequately powered

trials. Erythrocytosis is the most frequent adverse event associated with

testosterone treatment. While there is no evidence that testosterone

causes prostate cancer, there is concern that testosterone therapy might

cause subclinical prostate cancers to grow. Testosterone therapy is associated with increased risk of detection of prostate events. Testosterone

does not worsen LUTS in older men who do not have severe LUTS

prior to treatment.

There is no clear evidence that testosterone treatment increases

the risk of major adverse cardiovascular events (MACE). No randomized trial to date has been long enough or large enough to determine

whether testosterone increases the risk of MACE. In two placebocontrolled trials, the rates of atherosclerosis progression did not differ

significantly between the testosterone and placebo groups. In the Cardiovascular Trial of the TTrials, testosterone treatment was associated

with a greater increase in the volume of the noncalcified plaque, compared to placebo. A large randomized trial to determine the effects of

testosterone replacement therapy on MACE in middle-aged and older

hypogonadal men aged 45–85 years (TRAVERSE Trial, ClincalTrials.

gov identifier: NCT03518034) is in progress. The number of venous

thromboembolic events in randomized testosterone trials has been too

small to draw meaningful inferences. The risk for venous thromboembolic events may be increased in men with hypercoagulable states.

APPROACH TO THE PATIENT

Older Men with Age-Related Decline in Testosterone

Population screening of all older men for low testosterone levels is

not recommended; testing should be restricted to men who have

symptoms or physical features attributable to androgen deficiency.

Testosterone treatment of older men with symptomatic testosterone deficiency offers some clinical benefits (e.g., improvement of

sexual symptoms in men with low libido, correction of anemia),

but because of the lack of evidence of long-term safety and limited

evidence of long-term efficacy, an expert panel of the Endocrine

Society recommended against testosterone treatment of all older

men with low testosterone levels. Instead, the expert panel recommended that “testosterone therapy should be offered on an

Sexual function

0

Erectile function

Intercourse

Morning erections

Sexual satisfaction

Sexual thoughts

1 2 3

Body composition and muscle strength

Difference between change in testosterone and placebo (kg)

Bone health

A

B

C

Difference between testosterone and placebo

change in bone mineral density (%)

Standardized mean difference between

testosterone and placebo

Grip strength

Fat mass

Lean body mass

Lumbar spine

Femoral neck

–2 0

0 5 10

246

FIGURE 399-2 The effects of testosterone therapy on body composition, muscle

strength, bone mineral density (BMD), and sexual function in intervention trials.

The point estimates and the associated 95% confidence intervals are shown.

A. The effects of testosterone therapy on lean body mass, grip strength, and fat

mass in a meta-analysis of randomized trials. B. The effects of testosterone

therapy on lumbar and femoral BMD in a meta-analysis of randomized trials. C.

The effects of testosterone therapy on measures of sexual function in men with

baseline testosterone <10 nmol/L (290 ng/dL). (A. Data from S Bhasin et al: Drug

insight: Testosterone and selective androgen receptor modulators as anabolic

therapies for chronic illness and aging. Nat Clin Pract Endocrinol Metab 2:146,

2006; B. Data from MJ Tracz et al: Testosterone use in men and its effects on bone

health. A systematic review and meta-analysis of randomized placebo-controlled

trials. J Clin Endocrinol Metab 91:2011, 2006. C. Data from AM Isidori et al: Effects of

testosterone on sexual function in men: results of a meta-analysis. Clin Endocrinol

(Oxf) 63:381, 2005.)

3072 PART 12 Endocrinology and Metabolism

3. Conditions that might

 increase risk of harm

 from TRT

1. Severity of testosterone

deficiency

4. Weigh burden of symptoms and patient’s values against potential risks/benefits

Potential risks:

Adverse events for which there is strong evidence

Erythrocytosis

Acne

Detection of subclinical prostate cancer

Growth of metastatic prostate cancer

Reduced sperm production and fertility

Adverse events for which there is weak evidence

Gynecomastia

Male pattern balding (familial)

Growth of breast cancer

Induction of worsening of obstructive sleep apnea

Adverse events with insufficient data to assess risk

Major cardiovascular events

Prostate cancer

Do not

treat

Treat

Potential benefits:

Strong evidence of efficacy

Improves sexual activity, sexual desire, and erections

in men with low libido

Corrects unexplained anemia in the elderly

Suggestive evidence of efficacy

Improves depressive symptoms in late-life patients

Modestly improves mobility in older adults with mobility limitation

Insufficient data or inconclusive evidence of efficacy

Improves fatigue

Reduces bone fracture risk

Evidence of lack of efficacy

Improves cognitive function in older men without cognitive deficit

Improves major depressive disorder

2. Burden of symptoms and

likelihood they will

respond to TRT

+

+

–

–

–

+

Lean toward treatment Lean against treatment

FIGURE 399-3 An individualized, patient-centric approach to shared treatment decision-making in older men with testosterone deficiency. Testosterone treatment is not

indicated in all older men with low testosterone levels. The decision to treat should be individualized based on considerations of the severity of testosterone deficiency, the

burden of symptoms and conditions associated with testosterone deficiency, the presence of conditions that might increase the patient’s risk of harm from testosterone

treatment, and the patient’s values and willingness to accept the uncertainty of the long-term benefits and risks and the burden of treatment and monitoring. TRT, testosterone

replacement therapy. (Reproduced with permission from S Bhasin. Testosterone replacement in aging men: an evidence-based patient-centric perspective. J Clin Invest

131:e146607, 2021.)

individualized basis . . . in men >65 years who have symptoms or

conditions suggestive of testosterone deficiency (e.g., low libido or

unexplained anemia) and consistently low testosterone.” The decision to offer testosterone treatment to older men with low testosterone levels should be a shared decision, guided by an individualized

assessment of potential benefits and risks, and careful weighing

of the burden of symptoms/conditions against the potential benefits and risks (Fig. 399-3). Evaluate whether the patient has clear

evidence of testosterone deficiency. The diagnosis of testosterone

deficiency should be made on the basis of two or more early morning, fasting testosterone levels below the lower limit of normal for

healthy young men plus the presence of symptoms. Weigh the

burden of symptoms/conditions against the known benefits and the

uncertainty of long-term harm. Ascertain whether the patient has

any conditions that might increase the risk of harm, such as prostate

cancer, severe LUTS, erythrocytosis, or deep-venous thrombosis. Older men considering testosterone supplementation should

undergo baseline evaluation of risk factors for prostate cancer. The

initiation of prostate screening and monitoring should be a shared

decision because prostate cancer screening has some risks. A shared

decision to treat should be accompanied by a standardized monitoring plan to optimize the benefit-to-risk ratio.

AGE-RELATED CHANGES IN FECUNDITY

Although testicular morphology, semen production, and fertility are

maintained up to a very old age in men, advanced paternal age is a

risk factor for reduced fertility. Compared to men aged 21–25 years,

men >50 years old have lower sperm motility and sperm morphology,

a higher frequency of sperm tail defects, and lower fecundity. The

fecundity is reduced when both parents are >40 years old. Increased

workforce participation and changing career expectations of women, a

higher age at reproductive union, and the availability of contraceptives

that enable couples to separate their sexual and procreative lives have

underpinned powerful secular trends toward postponement of childbearing to an older age. The median age at first childbirth has been

increasing steadily across the world; postponement of childbirth to an

older age increases the risk of involuntary childlessness because of the

adverse effects of advanced maternal and paternal age on fecundity,

increased risk of comorbidities that may indirectly affect fecundity, and

the age-related changes in reproductive behaviors. Increased paternal

age is associated with increased risk of germline mutations in the

FGFR2, FGFR3, and RET genes and the associated autosomal dominant diseases, such as achondroplasia, Pfeiffer’s syndrome, Crouzon’s

syndrome, Apert’s syndrome, multiple endocrine neoplasia (MEN) 2A,

and MEN 2B. Advanced paternal age also increases the risk of Klinefelter’s syndrome, trisomy 13 and 18, neurodevelopmental disorders such

as schizophrenia, autism, bipolar disorders, and cardiac malformations

such as ventricular septal defects, atrial septal defects, and patent ductus arteriosus.

Sexual Dysfunction Various forms of sexual dysfunction are a

major motivating factor for men seeking care at men’s health clinics.

The landmark descriptions of the human sexual response cycle by

Masters and Johnson demonstrating that men and women display

predictable physiologic responses after sexual stimulation provided the

basis for rational classification of human sexual disorders. Accordingly,

sexual disorders have been classified into four categories depending on

phase of sexual response cycle in which the abnormality exists:

1. Hypoactive sexual desire disorder

2. Erectile dysfunction

3. Ejaculatory and orgasmic disorders

4. Disorders of pain

Classification of the patient’s disorder into these categories is important as the etiologic factors, diagnostic tests, and therapeutic strategies

vary for each class of sexual disorder. Historically, the classification and

nomenclature for sexual disorders were based on the Diagnostic and

Statistical Manual of Mental Disorders (DSM), based on the erroneous

belief that sexual disorders in men are largely psychogenic in origin.

However, the recognition of erectile dysfunction as a manifestation of

systemic disease and the availability of easy-to-use oral selective phosphodiesterase-5 (PDE5) inhibitors have placed sexual disorders in men

3073 Men’s Health CHAPTER 399

within the purview of the primary care provider. These disorders have

been discussed in Chap. 397 (Sexual Dysfunction).

■ MUSCLE DYSMORPHIA SYNDROME IN MEN—A

FORM OF BODY IMAGE DISORDER

Muscle dysmorphia is a form of body image disorder characterized by

a pathologic preoccupation with muscularity and leanness. The men

with muscle dysmorphia express a strong desire to be more muscular

and lean. These men describe shame and embarrassment about their

body size and shape and often report aversive symptoms such as dissatisfaction with appearance, preoccupation with bodybuilding and muscularity, and functional impairment. Patients with muscle dysmorphia

also report higher rates of mood and anxiety disorders and obsessive

and compulsive behaviors than individuals with no history of muscle

dysmorphia. These men often experience impairment of social and

occupational functioning.

Patients with muscle dysmorphia syndrome—nearly all men—are

almost always engaged in weightlifting and body building and are

more likely to use performance-enhancing drugs, especially AASs,

than men in the general population or even weightlifters without

body dysmorphia. Muscle dysmorphia disorder exposes men to an

increased risk of disease due to the combined interactive effects of the

intensity of physical exercise, the use of performance-enhancing drugs,

and other lifestyle factors associated with weightlifting and the use of

performance-enhancing drugs. These patients are also at increased

risk of functioning poorly in their occupation and social life than men

without this disorder. No randomized trials of any treatment modalities have been conducted; anecdotally, behavioral and cognitive therapies have been tried with varying degrees of success.

AAS Abuse by Athletes and Recreational Bodybuilders The

illicit use of AASs to enhance athletic performance first surfaced in the

1950s among powerlifters and spread rapidly to other sports, professional as well as high school athletes, and recreational bodybuilders. In

the early 1980s, the use of AAS spread beyond the athletic community

into the general population. As many as 3 million Americans—most

of them men—have likely used these compounds. Most AAS users are

not athletes, but rather recreational weightlifters who use these drugs

to look lean and more muscular.

The most commonly used AASs include testosterone esters, nandrolone, stanozolol, methandienone, and methenolol. AAS users

generally use increasing doses of multiple steroids in a practice known

as stacking.

The adverse effects of long-term AAS abuse remain poorly understood. Most of the information about the adverse effects of AAS has

emerged from case reports, uncontrolled studies, or clinical trials that

used replacement doses of testosterone (Table 399-3). The adverse

event data from clinical trials using physiologic replacement doses of

testosterone have been extrapolated unjustifiably to AAS users who

may administer 10–100 times the replacement doses of testosterone

over many years and to support the claim that AAS use is safe. A substantial fraction of AAS users also use other drugs that are perceived

to be muscle-building or performance-enhancing, such as growth

hormone; erythropoiesis-stimulating agents; insulin; stimulants such

as amphetamine, clenbuterol, cocaine, ephedrine, and thyroxine; and

drugs perceived to reduce adverse effects such as human chorionic

gonadotropin (hCG), aromatase inhibitors, or estrogen antagonists.

Men who abuse AAS are more likely to engage in other high-risk

behaviors than nonusers. The adverse events associated with AAS use

may be due to AAS themselves, concomitant use of other drugs, highrisk behaviors, and host characteristics that may render these individuals more susceptible to AAS use or to other high-risk behaviors.

The high rates of mortality and morbidities observed in AAS users

are alarming. One Finnish study reported 4.6 times the risk of death

among elite power lifters than in age-matched men from the general

population. The causes of death among power lifters included suicides,

myocardial infarction, hepatic coma, and non-Hodgkin’s lymphoma.

A retrospective review of patient records in Sweden also reported

higher standardized mortality ratios for AAS users than for nonusers.

TABLE 399-3 Potential Adverse Effects Associated with the Use of

Anabolic-Androgenic Steroids

ORGAN SYSTEM EFFECT

Cardiovascular Dyslipidemia

Atherosclerotic disease

Sudden death

Myocardial fibrosis, cardiomyopathy

Cardiac conduction abnormalities

Hypertension

Neuroendocrine HPT suppression; hypogonadism on AAS withdrawal

Gynecomastia

Females Virilizing effects

Neuropsychiatric Major mood disorders (mania, hypomania, depression)

Aggression, violence

AAS dependence

Neuronal apoptosis; cognitive deficits

Hematologic Polycythemia

Hypercoagulability and thrombosis

Hepatic Inflammatory and cholestatic effects

Peliosis hepatis (rare)

Neoplasms (rare)

Musculoskeletal Premature epiphyseal closure (in adolescents)

Tendon rupture

Kidney Renal failure secondary to rhabdomyolysis

Focal segmental glomerulosclerosis

Dermatologic Acne

Striae

Abbreviations: AAS, anabolic-androgenic steroids; HPT axis, hypothalamicpituitary-testicular axis.

Source: Data from HG Pope Jr et al: Adverse health consequences of performanceenhancing drugs: an Endocrine Society scientific statement. Endocr Rev 35:341,

2014.

Studies indicate that 32% of deaths among AAS users were suicidal,

26% homicidal, and 35% accidental. The median age of death among

AAS users—24 years—is even lower than that for heroin or amphetamine users.

Numerous reports of cardiac death among young AAS users raise

concerns about the adverse cardiovascular effects of AAS. High doses

of AAS may induce proatherogenic dyslipidemia, increase thrombosis

risk via effects on clotting factors and platelets, induce vasospasm

through their effects on vascular nitric oxide, and induce myocardial

hypertrophy and fibrosis.

Replacement doses of testosterone, when administered parenterally,

are associated with only a small decrease in high-density lipoprotein

(HDL) cholesterol and little or no effect on total cholesterol, lowdensity lipoprotein (LDL) cholesterol, and triglyceride levels. In contrast, supraphysiologic doses of testosterone and orally administered,

17-α-alkylated, nonaromatizable AAS are associated with marked

reductions in HDL cholesterol and increases in LDL cholesterol.

Recent studies of AAS users using tissue Doppler and strain imaging and magnetic resonance imaging (MRI) have reported diastolic

and systolic dysfunction, including significantly lower early and late

diastolic tissue velocities, reduced E/A ratio, and reduced peak systolic

strain in AAS users than in nonusers. Power athletes using AAS often

have short QT intervals but increased QT dispersion, which may predispose them to ventricular arrhythmias. Long-term AAS use may be

associated with myocardial hypertrophy and fibrosis. Myocardial tissue

of power lifters using AAS has been shown to be infiltrated with fibrous

tissue and fat droplets. AAS users demonstrate higher coronary artery

plaque volume than nonusers, and lifetime AAS dose is associated with

coronary atherosclerotic burden.

Long-term AAS use suppresses LH and follicle-stimulating hormone

(FSH) secretion and inhibits endogenous testosterone production and

spermatogenesis. Men who have used AAS for more than a few months

experience marked suppression of the HPT axis after stopping AAS

3074 PART 12 Endocrinology and Metabolism

that may be associated with sexual dysfunction, fatigue, infertility, and

depressive symptoms. In some AAS users, HPT suppression may last

more than a year, and in a few individuals, complete recovery may not

occur. The symptoms of androgen deficiency during AAS withdrawal

may cause some men to revert back to using AAS, leading to continued use and AAS dependence. As many as 30% of AAS users develop

a syndrome of AAS dependence, characterized by long-term AAS use

despite adverse medical and psychiatric effects. In some men’s health

clinics, as many as 25% of young men receiving testosterone replacement therapy have anabolic steroid withdrawal hypogonadism.

Supraphysiologic doses of testosterone may also impair insulin

sensitivity. Orally administered androgens have been associated with

insulin resistance and diabetes.

Unsafe injection practices, high-risk behaviors, and increased rates

of incarceration render AAS users at increased risk of HIV and hepatitis B and C. In one survey, nearly 1 in 10 gay men had injected AAS or

other substances, and AAS users were more likely to report high-risk

unprotected anal sex than other men.

Some AAS users develop hypomanic and manic symptoms during

AAS exposure (irritability, aggressiveness, reckless behavior, and occasional psychotic symptoms, sometimes associated with violence) and

major depression (sometimes associated with suicidality) during AAS

withdrawal. Users may also develop other forms of illicit drug use,

which may be potentiated or exacerbated by AAS.

AAS use has been associated with difficulties with spatial as well

as working memory, problem solving, and attention, and structural

and functional changes in many brain regions involved in inhibitory

control and emotional regulation. A structural MRI study of users of

high doses of AAS reported smaller cortical, gray matter, putamen,

and corpus callosum volumes. Both low and high androgen levels have

been associated with increased Aβ and tau-P levels and Aβ toxicity.

These data have raised concern that long-term AAS use may increase

the risk of Alzheimer’s disease and related dementias.

Elevated liver enzymes, cholestatic jaundice, hepatic neoplasms, and

peliosis hepatis have been reported with oral, 17-α-alkylated AAS. AAS

use may cause muscle hypertrophy without compensatory adaptations

in tendons, ligaments, and joints, thus increasing the risk of tendon and

joint injuries. AAS use is associated with acne, baldness, and increased

body hair.

APPROACH TO THE PATIENT

Detection of AAS Use

AAS users generally mistrust physicians and seek medical help

infrequently; when they do seek medical help, it is often for the

treatment of AAS withdrawal syndrome, infertility, gynecomastia,

or other medical or psychiatric complications of AAS use. The

suspicion of AAS use should be raised by the increased hemoglobin

and hematocrit levels; suppressed LH, FSH, and testosterone levels;

low HDL cholesterol; and low testicular volume and sperm density

in a person who looks highly muscular (Table 399-4). A combination of these findings along with self-report of their use by the

patient—which usually can be elicited by a tactful interview—are

often sufficient to establish a diagnosis in clinical practice.

Accredited laboratories use gas chromatography and mass spectrometry or liquid chromatography and mass spectrometry to detect

AAS abuse. In recent years, the availability of high-resolution mass

spectrometry and tandem mass spectrometry has further improved

the sensitivity of detecting AAS abuse. Illicit testosterone use is

detected generally by the application of the measurement of the urinary testosterone-to-epitestosterone ratio and further confirmed by

the use of the 13C:12C ratio in testosterone by the use of isotope ratio

combustion mass spectrometry. Exogenous testosterone administration increases urinary testosterone glucuronide excretion and

consequently the testosterone-to-epitestosterone ratio. Ratios >4

suggest exogenous testosterone use but can also reflect genetic

variation. Genetic variations in the uridine diphospho-glucuronyl

transferase 2B17 (UGT2B17), the major enzyme for testosterone

glucuronidation, affect the testosterone-to-epitestosterone ratio.

Synthetic testosterone has a lower 13C:12C ratio than endogenously

produced testosterone, and these differences in the 13C:12C ratio can

be detected by isotope ratio combustion mass spectrometry and

used to confirm exogenous testosterone use in individuals with a

high testosterone-to-epitestosterone ratio.

TREATMENT

Integrated Management of Patients with AAS Use

The nonathlete weightlifters who abuse AAS frequently do not seek

medical treatment and often mistrust physicians. They also do not

view these drugs and the associated lifestyle as deleterious to their

health. In turn, many internists erroneously view AAS abuse as

largely a problem of cheating in competitive sports, while, in fact,

most AAS users are not athletes at all. Also, physicians often have

a poor understanding of the factors motivating the use of these

performance-enhancing drugs, the long-term health effects of AAS,

and the associated psychopathologies that may affect treatment

choices.

In addition to treating the underlying body dysmorphia disorder that motivates the use of these drugs, the treatment should be

directed at the symptoms or the condition for which the patient

seeks therapy, such as infertility, sexual dysfunction, gynecomastia,

or depressive symptoms. Accordingly, therapy may include some

combination of cognitive and behavioral therapy for muscle dysmorphia syndrome, antidepressant therapy for depression, selective

PDE5 inhibitors for erectile dysfunction, and/or use of selective

estrogen receptor modulators or aromatase inhibitors to reactivate

HPT axis or hCG to restore testosterone levels.

As discussed above, AASs suppress the male hypothalamicpituitary-gonadal axis, and men with long-term AAS use may experience symptoms of profound androgen deficiency such as sexual

dysfunction, fatigue, and depressive symptoms during AAS withdrawal. Some of these patients may resume AAS use or start using

other drugs to combat the distressing withdrawal symptoms. There

are no randomized trials of any therapies for AAS withdrawal. Case

reports and clinical experience suggest that administration of selective estrogen receptor modulators, CYP19 aromatase inhibitors,

or hCG may restore circulating testosterone levels. Clomiphene

citrate, a partial estrogen receptor agonist, administered in a dose

TABLE 399-4 Detection of the Use of Anabolic-Androgenic Steroids

Clinical indicators that should raise suspicion of anabolic-androgenic steroid use

1. Very muscular phenotype

2. Reduced testicular volume (<15 mL)

Laboratory indicators

1. Suppressed LH and FSH levels

2. Increased hematocrit

Detection of anabolic-androgenic steroids

1. LC-MS/MS analysis of urine

Detection of exogenous testosterone use

1. Urinary testosterone-to-epitestosterone ratio

2. Isotope ratio mass spectrometry analysis to detect differences in 13C:12C ratio

in exogenous and endogenous testosterone

Note: In clinical settings, the use of anabolic-androgenic steroids can often be

ascertained simply by direct questioning. Reduced testicular volume, suppressed

LH and FSH, and increased hematocrit in an unusually muscular man should raise

suspicion of anabolic-androgenic steroid use. Although rarely needed in clinical

practice, recent use of anabolic-androgenic steroids can be confirmed by LC-MS/

MS analysis of urine. Exogenous testosterone use can be detected using the

urinary testosterone-to-epitestosterone ratio and isotope ratio mass spectrometry

analysis to detect differences in 13C:12C ratio in exogenous and endogenous

testosterone.

Abbreviations: FSH, follicle-stimulating hormone; LC-MS/MS, liquid

chromatography–tandem mass spectrometry; LH, luteinizing hormone.

3075 Men’s Health CHAPTER 399

of 25–50 mg on alternate days, can increase LH and FSH levels

and restore testosterone levels in a vast majority of men with AAS

withdrawal syndrome. However, the recovery of sexual function

during clomiphene administration is variable despite improvements

in testosterone levels. Anecdotally, other aromatase inhibitors such

as anastrozole have also been used. hCG, administered by intramuscular injections of 750–1500 IU three times each week, can

raise testosterone levels into the normal range. Some patients may

not respond to either clomiphene or hCG therapy, raising the possibility of irreversible long-term toxic effects of AAS on Leydig cell

function.

Adjunctive cognitive and behavioral therapy or antidepressants

to treat depression inadequately responsive to endocrine therapies

alone may be needed. Emerging human and animal evidence suggests AAS and opioids likely promote dependence via common

mechanisms. The opioid antagonist naltrexone blocks AAS dependence in animals. Therefore, treatments for human opioid dependence might also benefit AAS dependence. Many patients who

abuse AAS suffer from body-image disorder and require psychiatric

treatment for this underlying disorder.

■ LUTS IN MEN

LUTS in men include storage symptoms (urgency, daytime as well

as nighttime frequency, and urgency incontinence), voiding disturbances (slow or intermittent stream, difficulty in initiating micturition,

straining to void, pain or discomfort during the passage of urine, and

terminal dribbling), or postmicturition symptoms (a sense of incomplete voiding after passing urine and postmicturition dribble). The

overactive bladder syndrome refers to urgency with or without urgency

incontinence, usually with urinary frequency and nocturia, and is often

due to detrusor muscle overactivity. A presumptive diagnosis of benign

prostatic hyperplasia should be made only in men with LUTS, who

have demonstrable evidence of prostate enlargement and obstruction

based on the size of the prostate. LUTS have historically been attributed

to benign prostatic hyperplasia, although it has become apparent that

the pathophysiologic mechanisms of LUTS are complex and multifactorial and may include structural or functional abnormalities of the

bladder, bladder neck, prostate, distal sphincter mechanism, and urethra, as well as abnormalities in the neural control of the lower urinary

tract. Diuretics, antihistamines, antidepressants, and other medications

that have anticholinergic properties can cause or exacerbate LUTS in

older men. The intensity of LUTS tends to fluctuate over time.

LUTS is highly prevalent in older men, affecting nearly 50% of men

>65 and 70% of men >80 years old. The LUTS adversely affects quality

of life because of its impact on sleep, ability to perform activities of

daily living, and depressive symptoms. LUTS is often associated with

erectile dysfunction.

APPROACH TO THE PATIENT

Lower Urinary Tract Symptoms

Medical evaluation should include assessment of potential causes

of symptoms; medications including herbal and over-the-counter

products that might contribute to symptoms; the symptom severity

and bother using an International Prostate Symptom Score; and

in some patients, a frequency-volume chart. The impact of LUTS

on sleep, activities of daily living, and quality of life should be

evaluated. Evaluation should also include digital prostate examination, neurologic examination focused on perineum and lower

extremities, urinalysis, fasting blood glucose, electrolytes, creatinine, and prostate-specific antigen (PSA). Urodynamic studies are

not required in most patients but are recommended when invasive

surgical therapies are being considered. A urologic referral may be

appropriate if the patient has hydronephrosis, renal insufficiency,

recurrent urinary tract infections, hematuria, or history of acute

urinary retention.

TREATMENT

Patients with LUTS

Considerations of the severity of symptoms; the impact of symptoms

on sleep, activities of daily living, and quality of life; the natural history of the disease; and potential adverse effects of the intervention

should guide the decision to intervene. In men with mild to moderately severe LUTS, the symptoms typically progress slowly over

many years and may remain stable or even improve in some men.

The men who have mild symptoms can usually be reassured and

followed. Several simple steps such as reducing caffeine and alcohol

intake, especially late in the day, taking the diuretic medication early

in the day, avoiding excessive water intake close to bedtime, bladder

training, pelvic floor exercises including biofeedback to promote pelvic floor relaxation, and timed voiding regimens or double voiding to

ensure complete emptying of the bladder may be helpful in reducing

the severity of symptoms. Men with mild to moderate bothersome

LUTS can be treated effectively using α-adrenergic antagonists,

steroid 5α-reductase inhibitors, PDE5 inhibitors, or anticholinergic

agents alone or in combination. Selective α-adrenergic antagonists

are typically the first line of therapy; their side effects include

hypotension, dizziness, nasal congestion, retrograde or delayed ejaculation, and rarely floppy iris syndrome. In men with probable

benign prostate obstruction with gland enlargement and LUTS, therapy with steroid 5α-reductase inhibitors, finasteride, or dutasteride

for 1 or more years improves urinary symptoms and flow rate and

reduces prostatic volume. Long-term treatment with 5α-reductase

inhibitors can reduce the risk of acute urinary retention and need for

prostate surgery. Combined administration of a steroid 5α-reductase

inhibitor and an α1

-adrenergic blocker can rapidly improve urinary

symptoms and reduce the relative risk of acute urinary retention and

surgery. PDE5 inhibitors, when administered chronically alone or in

combination with α-adrenergic blockers, are effective in improving

LUTS and erectile dysfunction through their effects on nitric oxide–

cyclic guanosine monophosphate (cGMP) in the bladder, urethra,

and prostate. PDE5 inhibitors do not improve uroflow parameters,

and their hypotensive effect may be potentiated by α1

-adrenergic

blockers. Anticholinergic drugs are used for the treatment of overactive bladder in men with prominent irritative symptoms, such as

frequency, urgency, and incontinence, and no evidence of elevated

postvoid residual urine. Containment products, such as pads, can

help improve social life in men who have severe storage symptoms,

including incontinence. Surgery is indicated when medical therapy

fails, symptoms progress in spite of medical therapy, or the patient

develops acute urinary retention, hydronephrosis, renal insufficiency, or recurrent urinary tract infections, or if the patient has

postvoid residual urine volume >25% of the urinary bladder volume.

■ MEDICAL COMPLICATIONS OF

PROSTATE CANCER THERAPY

Prostate cancer is the most common malignancy in American men,

accounting for 19% of all diagnosed cancers and ~8% of all cancer

deaths; its incidence is on the rise, partly due to increased screening with PSA. The American Cancer Society estimates that, in

2021, 248,530 new cases of prostate cancer will be diagnosed in the

United States and 34,130 men will die from this disease. The majority

of these men have low-grade, organ-confined prostate cancer and

excellent prospects of long-term survival. Substantial improvement

in survival in men with prostate cancer has focused attention on the

high prevalence of sexual dysfunction, physical dysfunction, and low

vitality in the men, which are important contributors to poor quality

of life among patients treated for prostate cancer. The pathophysiology

of these symptoms after radical prostatectomy is multifactorial, but

denervation and androgen deficiency are important contributors to

these symptoms.

Androgen deficiency is common in men with prostate cancer. Testosterone levels decline with age, and men with prostate cancer are

at risk of having low testosterone levels simply by virtue of their age.

3076 PART 12 Endocrinology and Metabolism

However, total and free testosterone levels are even lower in men with

prostate cancer who have undergone prostatectomy, when compared to

noncancer age-matched controls. This age-related androgen deficiency

in men with prostate cancer is associated with fatigue, sexual dysfunction, mobility limitation, and decreased physical function. Even

with bilateral nerve-sparing procedure, >50% of men develop sexual

dysfunction after surgery. Although there is some recovery of sexual

function with passage of time, 40–50% of men undergoing radical

prostatectomy find their sexual performance to be a moderate to large

problem 18 months after surgery. Sexual problems are a source of psychosocial distress in men with localized prostate cancer. The men with

locally advanced or metastatic prostate cancer who undergo androgen

deprivation therapy (ADT) encounter even more distressing symptoms

because of the profound androgen deficiency. In addition to fatigue,

sexual dysfunction, and hot flushes, these men are at increased risk

for diabetes, metabolic syndrome, coronary heart disease, and frailty.

Testosterone Therapy in Men with a History of Prostate

Cancer A history of prostate cancer has historically been considered

a contraindication for testosterone therapy. This guidance is based

on observations that testosterone promotes the growth of metastatic

prostate cancer. Metastatic prostate cancer generally regresses after

orchidectomy and ADT. Androgen receptor signaling plays a central

role in maintaining growth of normal prostate and prostate cancer. PSA

levels are lower in hypogonadal men and increase after testosterone

therapy. Prostate volume is lower in hypogonadal men and increases

after testosterone therapy to levels seen in age-matched controls.

However, the role of testosterone in prostate cancer is complex.

Epidemiologic studies and their meta-analyses have not revealed a

consistent relationship between serum testosterone and prostate cancer. Others have reported that low testosterone levels are associated

with high-grade cancers. In a landmark randomized trial, testosterone

therapy of older men with low testosterone did not affect intraprostatic

androgen levels or the expression of androgen-dependent prostatic

genes. The suppression of circulating testosterone levels by a GnRH

antagonist also does not affect intraprostatic androgen concentrations.

Open-label trials and retrospective analyses of testosterone therapy in

men with prostate cancer, who have undergone radical prostatectomy

and have undetectable PSA levels after radical prostatectomy, have

found very low rates of PSA recurrence. Even in men with high-grade

prostatic intraepithelial neoplasia (HGPIN)—a group at high risk of

developing prostate cancer—testosterone therapy for 1 year did not

increase PSA or rates of prostate cancer.

A majority of men diagnosed with prostate cancer today have

localized disease that can be potentially cured by radical prostatectomy. The men with organ-confined prostate cancer (pT2, N0, M0)

and Gleason score <6 are at a very low risk of disease recurrence after

radical prostatectomy with 0.5% biochemical recurrence rate and 0.2%

local recurrence rate at >10–15 years. Similarly, preoperative PSA

<10 ng/mL is associated with lower risk of disease recurrence than PSA

>10 ng/mL. After radical prostatectomy, in the absence of residual

cancer, PSA becomes undetectable within a month. An undetectable

PSA after radical prostatectomy is a good indicator of biochemical

recurrence-free survival at 5 years. Therefore, men with organ-confined prostate cancer (pT2), Gleason score <6, and a preoperative PSA

of <10 ng/mL, who have had undetectable PSA levels (<0.1 ng/mL)

for >2 years after radical prostatectomy, have very low risk of disease

recurrence (<0.5% at 10 years) and may be considered for testosterone

therapy on an individualized basis. If testosterone therapy is instituted,

it should be associated with careful monitoring of PSA levels and close

consultation with a urologist.

■ MEDICAL COMPLICATIONS OF ADT

In patients with prostate cancer and distant metastases, ADT improves

survival. In patients with locally advanced disease, ADT in combination with external beam radiation or as an adjuvant therapy (postprostatectomy and pelvic lymphadenectomy) also has been shown to

improve survival. However, ADT is being increasingly used as primary

therapy in men with localized disease and in men encountering biochemical recurrence without clear evidence of survival advantage. The

overall use of ADT in men with prostate cancer has increased in the

past two decades, and its use in men with localized disease and biochemical recurrence accounts for a substantial fraction of this increase.

Since most men with prostate cancer die of conditions other than their

primary malignancy, recognition and management of these adverse

effects is paramount.

Profound hypogonadism resulting from ADT is associated with

sexual dysfunction, vasomotor symptoms, gynecomastia, decreased

muscle mass and strength, frailty, increased fat mass, anemia, fatigue,

bone loss, loss of body hair, depressive symptoms, and reduced quality

of life. Diabetes and cardiovascular disease have recently been added

to the list of these complications (Fig. 399-4). Treatment with GnRH

agonists in men with prostate cancer is associated with rapid induction

of insulin resistance, hyperinsulinemia, and a significant increase in

the risk of incident diabetes. Metabolic syndrome is prevalent in >50%

of men undergoing long-term ADT when compared to age-matched

men with prostate cancer not undergoing ADT (22%) and their agematched eugonadal counterparts (20%). Some but not all studies have

reported an increased risk of cardiovascular events, death due to cardiovascular events, and peripheral vascular disease in men undergoing

ADT. Some reports suggest that men receiving ADT are at an increased

risk of thromboembolic events and cognitive dysfunction. The rates of

acute kidney injury are higher in men currently receiving ADT than in

men not receiving ADT; the increased risk appears to be particularly

associated with the use of combined regimens of a GnRH agonist plus

an antiandrogen. ADT also is associated with substantially increased

risk of osteoporosis and bone fractures.

APPROACH TO THE PATIENT

Men Receiving ADT

The benefits of ADT in treating nonmetastatic prostate cancer

should be carefully weighed against the risks of ADT-induced

adverse events (Table 399-5). If ADT is medically indicated, consider whether intermittent ADT is a feasible option. Men being

considered for ADT should undergo assessment of cardiovascular, diabetes, and fracture risk; this assessment may include

measurement of blood glucose, plasma lipids, and bone mineral

density by dual energy x-ray absorptiometry. Institute measures

to prevent bone loss, including physical activity, adequate calcium

and vitamin D intake, and pharmacologic therapy in men with a

previous minimal trauma fracture and those with 10-year risk of

a major osteoporotic fracture >20%, unless contraindicated. Bisphosphonates and denosumab have been shown to reduce fracture

risk in men undergoing ADT, and zoledronic acid and denosumab

have been approved by the U.S. Food and Drug Administration

for the prevention of metastasis-related skeletal-related events in

this population. Men with prostate cancer who are receiving ADT

should be monitored for weight gain and diabetes. Encourage lifestyle interventions, including physical activity and exercise, and

attention to weight, blood pressure, lipid profile, blood glucose, and

smoking cessation to reduce the risk of cardiometabolic complications. In randomized trials, medroxyprogesterone, cyproterone

acetate, and the serotonin reuptake inhibitor venlafaxine have

been shown to be more efficacious than placebo in alleviating hot

flushes. The side effects of these medications—increased appetite

and weight gain with medroxyprogesterone, gynecomastia with

estrogenic compounds, and dry mouth with venlafaxine—should be

weighed against their relative efficacy. Acupuncture, soy products,

vitamin E, herbal medicines, and transdermal estradiol have been

used empirically for the treatment of vasomotor symptoms without

clear evidence of efficacy. Gynecomastia can be prevented by the

use of an antiestrogen, an aromatase inhibitor, or local radiation

therapy; these therapies are effective in alleviating pain and tenderness but are less effective in reducing established gynecomastia. For

long-standing gynecomastia that persists after cessation of ADT

and is bothersome, mammoplasty is an effective treatment option.

3077 Men’s Health CHAPTER 399

Thromboembolic

Any fracture (1.54)

Fracture requiring hospitalization (1.66)

Diabetes (1.44)

Cardiovascular Metabolic Skeletal

Myocardial infarction (1.11)

Keating et al 2006, JCO

Keating et al 2006, JCO

Shahinian et al 2005, NEJM

Hu et al 2012, Eur Urol

Peripheral vascular disease (1.16)

Sudden death (1.16)

0123

Coronary heart disease (1.16)

FIGURE 399-4 Adverse cardiometabolic and skeletal effects of androgen deprivation therapy (ADT) in men receiving ADT for prostate cancer. Administration of ADT has

been associated with increased risk of thromboembolic events, fractures, and diabetes. Some, but not all, studies have reported increased risk of cardiovascular events in

men receiving ADT. (Data from VB Shahinian et al: N Engl J Med 352:154, 2005; NL Keating et al: J Clin Oncol 24:4448, 2006; JC Hu et al: Eur Urol 61:1119, 2012.)

■ PREVENTION OF SEXUALLY

TRANSMITTED DISEASES

Adolescent boys and young men aged 15–24 years; men who have sex

with men, have multiple sex partners, have unprotected sex without

condom, or have sex with sex workers; men who use illicit drugs; men

who have a history of previous sexually transmitted infection (STI); and

transgender men are at increased risk for STIs. STIs increase the risk of

oropharyngeal and anogenital cancers, liver disease, pelvic pain, infertility, inadvertent transmission of infection to others, and emergency

department visits and are a preventable cause of excess morbidity and

mortality. HIV, hepatitis B and C infections, and syphilis can have additional disease-specific complications. The prevention and treatment of

STIs are discussed in Chap. 136. Additionally, the Centers for Disease

Control and Prevention (CDC) and U.S. Preventive Services Task Force

(USPSTF) have published guidelines on the prevention, treatment, and

pre- and postexposure prophylaxis of STIs. The approach to the prevention of STIs includes a structured risk assessment; counseling about

safe sex practices including condom use; immunization of individuals

at risk; diagnosis and treatment of infected individuals whether or

not they are symptomatic; detection and treatment of sexual partners;

and targeted sex education of adolescents and young men who are at

high risk for STIs. The USPSTF recommends screening for HIV in

all men aged 15–65 years, regardless of risk, and for hepatitis B virus

and syphilis in men at increased risk. Because more than half of STIs

occur in persons aged 15–24 years, the USPSTF also recommends

behavioral counseling for all sexually active adolescents and adult men

at increased risk of STIs to encourage condom use and other protective

behaviors, including consideration of abstinence, reducing the number

of sex partners, and avoidance of unsafe sex practices. Consistent and

correct condom use is the most important method of preventing STIs.

Effective immunizations are available against hepatitis B, human papillomavirus (HPV), and Neisseria meningitides. The CDC’s Advisory

Committee on Immunization Practices (ACIP) recommends universal

hepatitis B immunization for all unvaccinated adults presenting to an

STI clinic, all HIV-infected adults, and health workers. Although ACIP

recommends HPV vaccination in males aged 9–21 years and in men

aged 9–26 if they have sex with men or have an immunocompromising

condition, recent data suggest that the prevalence of HPV and its complications continue to increase until middle age, and some experts recommend extending the age limit for HPV vaccination. Meningococcal

vaccination is indicated for men who have sex with men from an area

of outbreak and for all HIV-infected men.

Because men seeking care in men’s health clinics often do so for

sexual and urogenital problems, these visits offer opportunities for

counseling, screening, and treatment of STIs and institution of immunization and other preventive measures for STIs.

■ SEX DIFFERENCES IN COVID-19

DISEASE OUTCOMES

The COVID-19 pandemic has highlighted sex differences in the susceptibility to respiratory viral infections. Men infected with SARS-CoV-2

TABLE 399-5 Checklist for Men Undergoing Androgen Deprivation

Therapy (ADT)

1. Weigh the risks and benefits of ADT and whether intermittent ADT is a

feasible and safe option.

2. Perform a baseline assessment including fasting glucose, plasma lipids,

blood pressure, bone mineral density, and FRAX score.

3. Optimize calcium and vitamin D intake, encourage structured physical activity

and exercise, and consider pharmacologic therapy in men with a previous

minimal trauma fracture and those with a 10-year risk of a major osteoporotic

fracture >20%, unless contraindicated.

4. Monitor body weight, fasting glucose, plasma lipids, blood pressure, and

bone mineral density, and encourage smoking cessation and physical

activity.

5. In men who are receiving ADT and who experience bothersome hot flushes,

as indicated by sleep disturbance or interference with work or activities

of daily living, consider initial therapy with venlafaxine. If ineffective, add

medroxyprogesterone acetate.

6. In men who experience painful breast enlargement, consider therapy with an

estrogen receptor antagonist, such as tamoxifen.

3078 PART 12 Endocrinology and Metabolism

virus are more likely to have a more severe disease, require mechanical

ventilation, have disease complications, and die of the disease than

women. Somewhat similar sex differences in morbidity and mortality

have been reported for influenza infection. In the United States, the

incidence and rates of hospitalization for influenza are higher in men

than in women across all age groups. However, the sex-specific mortality rates associated with influenza vary substantially across countries

and age groups. The sex differences in susceptibility to SARS-CoV-2

infection and morbidity have been attributed to behavioral factors,

such as higher rates of smoking and alcohol use in men; biologic

factors, such as higher rates of comorbid conditions in men than in

women; sex differences in immune responses, including a poor T

lymphocyte response to SARS-CoV-2 infection; and lower expression

levels in men of X-linked genes that are involved in the innate detection

of RNA viruses and that escape X inactivation in women, resulting

in higher expression levels in women. Additionally, the expression of

angiotensin-converting enzyme 2 (ACE2) and the cell surface transmembrane protease serine 2 (TMPRSS2), the two host proteins that

facilitate the entry of SARS-CoV-2 into the alveolar cells, is regulated

by androgens in subsets of lung epithelial cells, and it is possible that

higher testosterone levels in men may contribute to increased susceptibility to the infection.

■ FURTHER READING

Abrams P et al: Evaluation and treatment of lower urinary tract symptoms in older men. J Urol 189:S93, 2013.

Baggish A et al: Cardiovascular toxicity of illicit anabolic-androgenic

steroid use. Circulation 135:1991, 2017.

Basaria S: Cardiovascular disease associated with androgen deprivation therapy: Time to give it due respect. J Clin Oncol 33:1232, 2015.

Bhasin S: Testosterone replacement in aging men: An evidence-based

patient-centric perspective. J Clin Invest 131:e146607, 2021.

Bhasin S et al: Testosterone therapy in men with hypogonadism: An

Endocrine Society clinical practice guideline. J Clin Endocrinol

Metab 103:1715, 2018.

Bhasin S et al: The implications of reproductive aging for the health,

vitality and economic welfare of human societies. J Clin Endocrinol

Metab 104:3821, 2019.

Case A, Deaton A: Mortality and morbidity in the 21st century.

Brookings Papers on Economic Activity, Spring 2017.

Centers for Disease Control and Prevention: Mortality tables.

http://www.cdc.gov/nchs/deaths.htm (HHS, CDC, NCHS).

Centers for Disease Control and Prevention: Sexually transmitted diseases treatment guidelines. MMWR Recomm Rep 64:51, 2015.

Choi PY et al: Muscle dysmorphia: A new syndrome in weightlifters.

Br J Sports Med 36:375, 2002.

Dos Santos MR, Bhasin S: Benefits and risks of testosterone treatment in men with age-related decline in testosterone. Annu Rev Med

72:75, 2021.

Jones C et al: Management of lower urinary tract symptoms in men:

Summary of NICE guidance. BMJ 340:c2354, 2010.

López AM et al: Fracture risk in patients with prostate cancer on

androgen deprivation therapy. Osteoporos Int 16:707, 2005.

Pope HG Jr et al: Adverse health consequences of performanceenhancing drugs: An endocrine society scientific statement. Endocr

Rev 35:341, 2014.

Ruth KS et al: Using human genetics to understand the disease

impacts of testosterone in men and women. Nat Med 26:252, 2020.

Smith MR et al: Denosumab in men receiving androgen deprivation

therapy for prostate cancer. N Engl J Med 361:745, 2009.

Snyder PJ et al: Effects of testosterone treatment in older men. N Engl

J Med 374:611, 2016.

U.S. Preventive Health Services Task Force. Final recommendation statement sexually transmitted infections: Behavioral counseling. https://www.uspreventiveservicestaskforce.org/Page/Document/

RecommendationStatementFinal/sexually-transmitted-infections-behavioral-counseling1. Accessed June 21, 2017.

Wittert G et al: Testosterone treatment to prevent or revert type

2 diabetes in men enrolled in a lifestyle programme (T4DM): A

randomised, double-blind, placebo-controlled, 2-year, phase 3b trial.

Lancet Diabetes Endocrinol 9:32, 2021.

Woolf SH, Schoomaker H: Life expectancy and mortality rates in

the United States, 1959–2017. JAMA 322:1996, 2019.

■ UNDERSTANDING LGBT HEALTH DISPARITIES

The acceptance of the lesbian, gay, bisexual, and transgender (LGBT)

community has greatly increased over the past decade in certain communities and parts of the world. However, numerous studies highlight

health disparities involving the care of LGBT people. Lesbian and

bisexual women are less likely to receive recommended preventive

screenings such as breast, cervical, and colorectal cancer screenings.

Among men who have sex with men, rates of human papillomavirus–

associated anal cancers are 17 times higher than those of heterosexual

men. In addition, gay and bisexual men accounted for 70% of all new

HIV diagnoses in the United States in 2018, and they disproportionately contract sexually transmitted infections. In 2018, men who have

sex with men accounted for 64% of primary and secondary syphilis

infections in the United States where the sex of the sexual partner

was known. Transgender individuals have a higher prevalence of HIV

infection and suicide compared with other groups.

Research has found that LGBT individuals are more likely to experience depression, anxiety, and alcohol and drug use than their counterparts. Most concerning are the rates of suicide attempts and ideation

among the LGBT community, particularly youth. Lesbian, gay, and

bisexual (LGB) youth are four times more likely to attempt suicide than

their heterosexual peers, and 61% of gender variant youth reported

suicidal ideation at some point in their life. Additionally, the recent U.S.

Transgender Survey found that 40% of transgender young adults and

adults reported attempting suicide at some point in their lives.

In addition, U.S. studies indicate that substance abuse is twice as common in LGBT youth compared with their counterparts. These findings

are mirrored among LGBT adults: the prevalence of substance abuse

disorders is 20–30% compared with ~9% in the general population.

These health issues are compounded by structural barriers to health

care, including decreased access to medical care, lack of awareness

to the unique health needs of LGBT individuals, and stigma and

discrimination toward the LGBT community. Many LGB individuals

perceive the health care setting and providers as threatening, which

may lead to avoiding needed medical care or withholding important

medical information. A large U.S. survey identified that 8% of LGB

and 27% of transgender individuals were refused needed health care,

and almost 11% of LGB and 21% of transgender people reported being

subjected to harsh or abusive language by health care professionals.

Apart from health care settings, more than two-thirds of LGB people

report discrimination in their personal lives, and 90% of transgender

individuals report harassment, mistreatment, or discrimination at

work. Chronic exposure to high levels of stress from real or anticipated

discrimination, referred to as “minority stress,” may be an important

factor contributing to the poor health outcomes experienced by LGBT

populations.

While some research on LGBT health has been conducted, there

remains a great opportunity to better understand the needs and

experiences of LGBT individuals. Moreover, many LGBT individuals

experience health disparities across their life cycle (e.g., LGBT youth

400 Lesbian, Gay, Bisexual,

and Transgender

(LGBT) Health

Baligh R. Yehia, Zachary B. R. McClain