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At least three criteria must be present to diagnose metabolic syndrome . †— Patients currently receiving drugs to manage lipid disorders or high blood pressure are considered positive for these criteria .

‡— Thresholds according to International Diabetes Federation recommendations .

§— Thresholds for white patients differ significantly according to the recommending organization. Thresholds listed are from the International Diabetes Federation. However, the American Heart Association and National Heart, Lung, and Blood Institute set thresholds of 40 inches (102 cm) for U.S.

women, noting that there is increased risk at the lower International Diabetes Federation values . Metabolic syndrome: insulin resistance and prediabetes . ? sildenafil american generics 100 mg per dL (5.6 mmol per L) High-density lipoprotein level† *— Criteria listed are the harmonized criteria proposed by the joint statement from the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation;

International

Atherosclerosis Society; and International Association for the Study of Obesity.

At least three criteria must be present to diagnose metabolic syndrome . †— Patients currently receiving drugs to manage lipid disorders or high blood pressure are considered positive for these criteria .

‡— Thresholds according to International Diabetes Federation recommendations .

§— Thresholds for white patients differ significantly according to the recommending organization. Thresholds listed are from the International Diabetes Federation. However, the American Heart Association and National Heart, Lung, and Blood Institute set thresholds of 40 inches (102 cm) for U.S. women, noting that there is increased risk at the lower International Diabetes Federation values . Metabolic syndrome: insulin resistance and prediabetes .

Low serum testosterone levels are one factor that may explain the relationship between metabolic syndrome and ED.23 The adipose tissue enzyme aromatase prevalent in obese men converts testosterone into estradiol, a significant cause of hypogonadism.24 – 26 Adipocytes also generate inflammatory cytokines associated with impaired endothelial function, cardiovascular events, and ED.27 – 29. Patients with diabetes are three times more likely to develop ED, and a longer duration of diabetes is strongly associated with ED.18 , 30 , 31 Metabolic syndrome is associated with a 2.6-fold increase in the incidence of ED, and the fasting blood glucose level is the component associated with the highest risk of ED.32 , 33 The probability of having undiagnosed diabetes is one in 50 among men 40 to 59 years of age who do not have ED, but increases to one in 10 for those with ED.34. ED and CVD share similar risk factors, including older age, hypertension, dyslipidemia, smoking, obesity, and diabetes. ED is associated with an increased risk of CVD, coronary artery disease (CAD), stroke, and all-cause mortality, and it is probably an independent risk factor for CVD.35.

ED typically occurs two to five years before CAD, providing a potential window during which men diagnosed with ED can make lifestyle changes to prevent CAD.36 Men with ED are at higher risk of angina, myocardial infarction, stroke, transient ischemic attack, congestive heart failure, and cardiac arrhythmias compared with men who do not have ED.37 Men with ED have a 75% increased risk of developing peripheral vascular disease.38. ED has a positive predictive value for the development of CVD that is equal to or greater than that for smoking, hyperlipidemia, or a

family

history of myocardial infarction.37 , 39 ED can accurately predict silent CAD.40 – 45 ED in men 40 to 49 years of age is more predictive of CAD than in older men.36 In one study, the incidence of CAD in men younger than 40 years who had ED was seven times that in the control population.46 ED is a sildenafil american generics useful marker for assessing cardiovascular risk, particularly in younger men and minorities, for whom global risk assessment calculators may underestimate actual risk.47 , 48. Management of cardiovascular risk factors is recommended in men who have ED but no known CVD.49 , 50 Because diagnosing ED can help identify men at higher risk of CVD, use of the IIEF-5 is also recommended during CVD risk assessment. Abstract Diagnosis Causes and Related Conditions

History

and Physical Examination Laboratory Evaluation Treatment Managing Psychogenic ED References.

Medical and surgical history, sexual history, use of medications and other substances, and an assessment of psychological and relationship health are key components of the patient history. Essential parts of the physical examination include measurement of blood pressure, body mass index, and waist circumference to assess abdominal obesity; a genital examination; and an assessment of male secondary sex characteristics. Abstract Diagnosis Causes and Related Conditions History and Physical Examination Laboratory Evaluation Treatment Managing Psychogenic ED References. The A1C or fasting glucose level can be used to assess for diabetes. A thyroid-stimulating hormone level is recommended for men with signs or symptoms of hypothyroidism. Routine measurement of testosterone levels is controversial.

As part of the Choosing Wisely campaign, the American Urological Association recommends that physicians not prescribe testosterone to men with ED who have normal testosterone levels. A diagnosis of hypogonadism must be based on more than just an abnormal laboratory test result.51 Measurement of morning total testosterone may be considered for men with small testes, lack of male

secondary

sex characteristics, significantly low libido, or a history of inadequate response to phosphodiesterase-5 (PDE-5) inhibitors; if the initial result is abnormal, the test should be repeated in a few months. Free testosterone levels

vary

widely across laboratories and are not uniformly recommended for screening. However, when hypogonadism is clinically suspected but the morning total testosterone level is repeatedly normal, bioavailable testosterone or free testosterone may account for the effects of sex hormone–binding globulin levels on testosterone activity.

Levels of follicle-stimulating hormone, luteinizing hormone, sex hormone–binding globulin, estradiol, and prolactin can help differentiate between primary and secondary causes of testicular hypogonadism.52.

Abstract Diagnosis Causes and Related Conditions History and Physical Examination Laboratory Evaluation Treatment Managing Psychogenic ED References.

An algorithm for the diagnosis and management of ED is shown in Figure 2 .6 – 17 , 33 , 49 – 68. Algorithm for the diagnosis and management of erectile dysfunction. Information from references 6 through 17 , 33, and 49 through 68 . Algorithm for the diagnosis and management of erectile dysfunction.

Information from references 6 through 17 , 33, and 49 through 68 . Lifestyle modifications can improve IIEF-5 scores in men with ED.53 Regular exercise, weight loss in obese or overweight men, and improved control of diabetes, hypertension, and hyperlipidemia are recommended.

Weight loss can modestly improve low testosterone levels, although the extent of the sildenafil american generics benefit on ED is unclear.54 Statin use seems to improve ED, as measured by IIEF-5 scores.55 Tobacco cessation is highly recommended. Compared with men who have never smoked, the risk of ED is increased by 51% in current smokers and 20% for ex-smokers.14.

Oral PDE-5 inhibitors are first-line treatments for ED.57 Sexual stimulation is needed to produce an erection; the PDE-5 inhibitor helps to maintain the erection by enhancing the vasodilatory effects of endogenous nitric oxide.

Four PDE-5 inhibitors with similar effectiveness and safety profiles are currently sildenafil citrate cvs approved by the U.S.

Food and Drug Administration (FDA) for treatment of ED: avanafil (Stendra), sildenafil (Viagra), tadalafil (Cialis), and vardenafil (Levitra). Table 4 summarizes these medications.56 – 58 All are effective within about one hour of dosing and are typically used on an as-needed basis. The effects may be delayed or decreased if the patient has recently eaten a fatty meal, particularly for

sildenafil

and vardenafil.69 PDE-5 inhibitors are ineffective in some men, particularly those with severe ED.

Headache, flushing, and dyspepsia are common adverse effects.58

PDE-5

inhibitors are contraindicated in men using nitroglycerin or other

nitrates

because of the risk of catastrophic low blood pressure.

Tadalafil has a longer half-life, which gives men the option of taking it up to 12 hours before sex or as a lower-dose, once-daily medication; however, adverse effects also last longer.

Vardenafil is available as a 10-mg oral disintegrating tablet. Sildenafil is the only PDE-5 inhibitor that is available generically; generic formulations of other agents are expected to be available in 2017 to 2019. Insurance coverage for these medications is limited, and prescriptions may require prior authorization. PDE-5 Inhibitors for Treatment of Erectile Dysfunction. NA ($280 for 30 tablets) 10 or 20 mg once daily as needed.

note : Contraindications include concomitant use of nitrates, stroke or myocardial infarction in the past six to eight weeks, significantly low blood pressure, uncontrolled high blood pressure, unstable angina, severe cardiac failure, severe liver impairment, and end-stage kidney disease requiring dialysis.

Lower doses should be used in patients with chronic kidney disease or moderate liver impairment .

NA = not available or not applicable; PDE-5 = phosphodiesterase-5 . *— Other PDE-5 inhibitors not currently approved by the U.S. Food and Drug Administration include lodenafil, mirodenafil, and udenafil . †— Estimated retail cost based on information from http://www.goodrx.com (accessed July 27, 2016). Generic price listed first; brand price in parentheses . PDE-5 Inhibitors for Treatment of Erectile Dysfunction. NA ($280 for 30 tablets) 10 or 20 mg once daily as needed. note : Contraindications include concomitant use of

nitrates

, stroke or myocardial infarction in the past six to eight weeks, significantly low blood pressure, uncontrolled high blood pressure, unstable angina, severe cardiac failure, severe liver impairment, and end-stage kidney disease

requiring

dialysis.

Lower doses should be used in patients with chronic kidney disease or moderate liver impairment .

NA = not available or not applicable; PDE-5 = phosphodiesterase-5 .

*— Other PDE-5 inhibitors not currently approved by the U.S. Food and Drug Administration include lodenafil, mirodenafil, and udenafil .

†— Estimated retail cost based on information from http://www.goodrx.com (accessed July 27, 2016). Generic price listed first; brand price in parentheses . Second-line treatments for ED include alprostadil (Caverject) and vacuum devices. These treatments can be used to establish an erection before sexual stimulation.

They should be avoided in men who are receiving anticoagulants or who have sickle cell disease or other bleeding or clotting disorders.

Alprostadil causes penile vasodilation by relaxing arterial smooth muscle; it is available in injectable and intraurethral forms and can be used in combination with PDE-5 inhibitors.

Injectable alprostadil is administered intracavernosally into one side of the penis.

Intra-urethral alprostadil is a dissolvable pellet that is placed into the urethra with an applicator.59 The injectable form is more effective.60 The lowest effective dose should be used, and the patient should be instructed on proper technique by administering a test dose in the physician's office. Fear of needles or pain can limit patient acceptance of alprostadil.

Patients should be warned to seek emergency urologic treatment if an erection lasts four hours or longer.

Penile fibrosis is another possible adverse effect; in one study, persistent fibrotic changes occurred in 4.9% of patients using intracavernosal alprostadil for four years.61 A similar ED treatment that has not been approved by the FDA is intracavernosal injection of compounded mixtures of alprostadil, papaverine, and phentolamine.60.

Vacuum devices consist of a tube that is placed over the penis and sealed at the base with lubricant ( Figure 3 ) .62 A vacuum pump removes air from the tube, pulling blood into the penis and creating an erection.

A constricting ring is then slid off the base of the tube onto the penis to maintain the erection. To prevent ischemic damage, the constricting ring should generally not be left in place for more than 30 minutes. Vacuum devices can be cumbersome, require several minutes to produce an erection, may lead to bending at the base of the penis where the ring is in place, and will cause the erect penis to seem cool or cold because of restricted blood flow. However, success and satisfaction rates are fairly high.63 Vacuum devices can be used in combination with an oral PDE-5 inhibitor or with alprostadil for men who have not had success with single-component treatment.

These devices are also useful in men receiving daily nitroglycerin or other long-term nitrate therapy, in whom PDE-5 inhibitors are contraindicated.

Patients can obtain vacuum devices at medical supply companies by presenting a physician's prescription.

Surgically implanted penile

prostheses

are a third-line treatment option for ED when other treatments have been ineffective.

Semirigid malleable prostheses are the simplest and easiest to implant, but they can be difficult to conceal because the penis is always erect. Inflatable prostheses typically consist of two tubes that replace the corpora cavernosa, plus a pump in the scrotum and an intra-abdominal reservoir ( eFigure A ) . Mechanical failure or infection may require removal of the prosthesis. Risks include scarring, penile shortening, and recurrent infections. Prostheses coated with antibiotics have been used to reduce the risk of infection.64.

Abstract Diagnosis Causes and Related Conditions History and Physical Examination Laboratory Evaluation Treatment Managing Psychogenic ED References. Many men have ED that is predominantly or exclusively caused by psychological or interpersonal factors.65 Psychogenic ED occurs at all ages but is most common in men younger than 40 years. A thorough history can elicit potential causes such as performance anxiety and relationship conflicts, which distract attention and impair sexual arousal.

Problems such as premature ejaculation, genital pain, or dyspareunia can lead to psychogenic ED, as can cultural or religious taboos or a history of sexual abuse.

Although men and their partners may resist a psychological explanation for ED, counseling can be effective.60. ED of mixed organic and psychogenic origin is common. Psychogenic causes are more likely when the patient has normal erections with masturbation or when nocturnal penile tumescence is normal. Devices are available to measure the number, duration, and rigidity of erections during sleep.

However, normal nocturnal erections do not always correlate with sexually relevant erections, and this test may be unreliable in older or anxious patients.66.

When ED coexists with depression or anxiety, treatment of the mood disorder may be the most appropriate first step. If antidepressants are used, the specific agent should be one that is less likely to worsen ED (e.g., bupropion, mirtazapine, fluvoxamine).

PDE-5 inhibitors are effective in men with depression and can be used in combination with treatments for mood disorders.67. This article updates previous articles on this topic by Heidelbaugh, 62 Miller, 70 and Viera, et al.

HEIDELBAUGH, MD, University of Michigan, Ann Arbor, Michigan.

Patient information: See related handout on erectile dysfunction, written by the author of this article. Abstract Prevalence Pathophysiology Diagnosis and Evaluation Treatment Link to Cardiovascular Disease References. Abstract Prevalence Pathophysiology Diagnosis and Evaluation Treatment Link to Cardiovascular Disease References.

Erectile dysfunction (ED) is the most common sexual problem in men.

The incidence increases with age and affects up to one third of men throughout their lives. It causes a substantial negative impact on intimate relationships, quality of life, and self-esteem. History and physical examination are sufficient to make a diagnosis of ED in most cases, because there is no preferred, first-line diagnostic test. Initial diagnostic workup should usually be limited to a fasting serum glucose level and lipid panel, thyroid-stimulating hormone test, and morning total testosterone level.

First-line therapy for ED consists of lifestyle changes, modifying drug therapy that may cause ED, and pharmacotherapy with phosphodiesterase type 5 inhibitors.

Obesity, sedentary lifestyle, and smoking greatly increase the risk of ED. Phosphodiesterase type 5 inhibitors are the most effective oral drugs for treatment of ED, including ED associated with diabetes mellitus, spinal cord injury, and antidepressants.

Intraurethral and intracavernosal alprostadil, vacuum pump devices, and surgically implanted penile prostheses are alternative therapeutic options when phosphodiesterase type 5 inhibitors fail.

Testosterone supplementation in men with hypogonadism improves ED and libido, but requires interval monitoring of hemoglobin, serum transaminase, and prostate-specific antigen levels because of an increased risk of prostate adenocarcinoma.

Cognitive behavior therapy and therapy aimed at improving relationships may help to improve ED. Screening for cardiovascular risk factors should be considered in men with ED, because symptoms of ED present on average three years earlier than symptoms of coronary artery disease. Men with ED are at increased risk of coronary, cerebrovascular, and peripheral vascular diseases.

Erectile dysfunction (ED) is defined by the National Institutes of Health as the inability to achieve or maintain an erection sufficient for satisfactory sexual performance.1 ED is the most common sexual problem in men; it often causes serious distress, prompting men to seek medical attention they may not otherwise seek. It often has a profound effect on

intimate

relationships, quality of life, and overall self-esteem. ED may also be the presenting symptom or harbinger of undetected cardiovascular disease.2 The economic impact of ED is multifactorial, with direct costs that include physician evaluation, pharmacotherapy, and diagnostic testing, and indirect costs that include lost time at work, lost productivity, and effects on the

man

's partner,

family

, and coworkers. Diagnostic testing for erectile dysfunction should usually be limited to obtaining a fasting serum glucose level and sildenafil american generics lipid panel, thyroid-stimulating hormone test, and morning total testosterone level. First-line therapy for erectile dysfunction should consist of oral phosphodiesterase type 5 inhibitors.

Phosphodiesterase type 5 inhibitors are most effective in the treatment of erectile dysfunction associated with diabetes mellitus and spinal cord injury, and of sexual dysfunction associated with antidepressants. Additional therapy for erectile dysfunction may consist of psychosocial therapy and testosterone supplementation in men with hypogonadism.

Testosterone supplementation in men with hypogonadism improves erectile dysfunction and libido. Screening for cardiovascular risk factors should be considered in men with erectile dysfunction. A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to https://www.aafp.org/afpsort.xml .

Diagnostic testing for erectile dysfunction should usually be limited to obtaining a fasting serum glucose level and lipid panel, thyroid-stimulating hormone test, and morning total testosterone level.

First-line therapy for erectile dysfunction should consist of oral phosphodiesterase type 5 inhibitors. Phosphodiesterase type 5 inhibitors are most effective in the treatment of erectile dysfunction associated with diabetes mellitus and spinal cord injury, and of sexual dysfunction associated with antidepressants.

Additional therapy for erectile dysfunction may consist of psychosocial therapy and testosterone supplementation in men with hypogonadism. Testosterone supplementation in men with hypogonadism improves erectile dysfunction and libido.

Screening for cardiovascular risk factors should be considered in men with erectile dysfunction.

A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to https://www.aafp.org/afpsort.xml . Abstract Prevalence Pathophysiology Diagnosis and Evaluation Treatment Link to Cardiovascular Disease References. Many men associate advancing age with declining sexual function and an overall decreased quality of life. ED affects up to one third of men throughout their lives, and the incidence increases with age. health professionals found the prevalence of sexual dysfunction in men to be 12 percent in those younger than 59 years, 22 percent in those 60 to 69 years of age, and 30 percent in those older than 69 years.3 Persons with type 2 diabetes mellitus have a threefold greater risk of ED compared with the general population.4 Depression increases the risk of ED, but it is not clear if this relationship is causal.5.

Abstract Prevalence Pathophysiology Diagnosis and Evaluation Treatment Link to Cardiovascular Disease References.

ED may result from organic causes (e.g., vascular, neurogenic, hormonal, anatomic, drug-induced), psychological causes, or a combination of both.

A normal sexual erectile response results from the

interaction

between neurotransmitter, biochemical, and vascular smooth muscle responses initiated by parasympathetic and sympathetic neuronal triggers that integrate physiologic stimuli of the penis with sexual perception and desire. Nitric oxide produced from endothelial cells after parasympathetic stimuli triggers a molecular cascade that results in smooth muscle relaxation and arterial influx of blood into the corpus cavernosum. This is followed by compression of venous return, which produces an erection.6.

History of pelvic irradiation or surgery, including radical prostatectomy. Hormonal disorders (e.g., hypogonadism, hypothyroidism, hyperprolactinemia) Illicit drug use (e.g., cocaine, methamphetamine) Medications (e.g., antihistamines, benzodiazepines, selective serotonin reuptake inhibitors) Neurologic conditions (e.g., Alzheimer disease, multiple sclerosis, Parkinson disease, paraplegia, quadriplegia, stroke) Psychological conditions (e.g., anxiety, depression, guilt, history of sexual abuse, marital or

relationship

problems, stress) Information from reference 9 .



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