The frequency of erectile dysfunction (ED) increases with age, with a prevalence of less than 10 % in men younger than 40-year-olds and up to 75 % in 75-year-old or older men [22]. The cost of treatment with sildenafil, tadalafil, and vardenafil to treat ED exceeds $1 billion dollars worldwide per year [23]. Erectile dysfunction has also shown to inversely impact the quality of life of men [24]. The diagnosis of ED is based on a patient’s self-report of difficulties forming or maintaining an erection. A careful history might help determine the major causes of ED such as hormonal, neurologic, vascular, or psychogenic. Diseases such as diabetes mellitus and renal disease may cause ED through all of the above mechanisms [25]. A careful medication and substance history should be obtained, as many medications including opioids and alcohol are implicated in erectile dysfunction [26].

A history of penile and spinal cord trauma and urologic procedures such as radical prostatectomy history should be determined. Multiple other medical problems have been shown to be risk factors for ED including chronic kidney disease, with an estimate of 80 % of patients having ED [25]. A limited physical exam is recommended including evaluation for neurologic deficits, prostate disease, penile deformities, cardiovascular disease, and signs of hypogonadism [27]. Laboratory evaluation may include screening for diabetes, hyperlipidemia, and low testosterone [27] (Fig. 9.3).

One expert guideline includes an algorithm with routine screening of thyroid-stimulating hormone and a behavioral therapy referral if there isn’t a definable medical etiology [28]. Imaging studies for difficult-to-treat ED can be ordered usually by a urologist in a few unique situations. This testing includes (1) dynamic penile Doppler to evaluate blood flow in high-risk vascular patients who would benefit from curative vascular surgery and (2) RigiScan or nocturnal penile tumescence to evaluate neurologic function in patients with complex psychologic disease [28, 29]. However, recent expert opinion recommends avoiding the term psychogenic ED, since all ED likely has some psychological component [30].

Since detecting ED at an early age has helped patients find out about silent CAD, diagnosing ED has been described as lifesaving [31]. Microvascular damage causing endothelial dysfunction is the etiology of both coronary disease and vascular ED. However, it appears that this damage leads to ED symptoms often before cardiac symptoms. It is recommended that men with ED be risk stratified with the Framingham risk calculator, with low-risk (<5 %, 10 year CVD) factors be addressed, medium risk (5–20 %) be evaluated with a stress test, and high risk (>20 %) be referred to a cardiologist [32]. Men in between the ages of 40 and 50 with erectile dysfunction are at a 50-fold higher risk for CAD [33] (Fig. 9.4). The third Princeton Consensus guidelines on ED recommend obtaining a resting EKG on patients with ED who also have risks such as diabetes and hypertension, and the guidelines base further testing depending on exercise tolerance [34].

Depression and anxiety are also associated with erectile dysfunction. Both can be a result or a cause of ED. Newly diagnosed men with ED had a twofold greater risk of developing depression in next 5 years [35]. While surgical abdominal aneurysm repair has been shown to cause ED, a preoperative screening found 82 % had ED prior to surgery [36]. Men with hypertension have been found to have a twofold increase in ED, and hypertension medications may also contribute to ED [37]. Therefore, a careful sexual history and counseling in hypertensive patients may help with management.

Many men with ED are not treated [38]. The rates of treatment tend to be based on patient income level, with the wealthy far more likely to receive treatment, due to the current high cost and limited access to care [39]. Current guidelines recommend lifestyle change as a first-line treatment for men with ED [27]. While smoking doubles the risk of ED, smoking cessation rapidly decreases that risk back to baseline [40]. Diet and exercise have also shown to be helpful with improving ED [41]. Treatment options and approach should involve shared decision making. A recent study demonstrated that Hispanic men prefer to discuss lifestyle changes versus becoming “viagraed” [42]. In a randomized control trial, about one-third of obese patients had improved ED based on IIEF scores over a 2-year diet and exercise program [43]. Diets high in soy may have beneficial cardiovascular effects, and they may negatively affect testosterone levels leading to ED [44].

After discussing lifestyle modifications, treatment of other possible etiologies should be the next step in treating patient with ED. Common medications implicated with ED will be discussed below and include antidepressants, antihypertensive medications, and opioids. In depression treatment, bupropion may be a better option for depressed patients with ED than SSRIs [45]. In the hypertension class, experts advise avoiding beta blockers and diuretics and recommend the use of ARBs in hypertensive patients with ED [37]. Opioid dose and duration have also been found to be associated with ED [46]. Discussing with patients other pain control options might be useful. Testosterone replacement in men with hypogonadism has shown to improve ED; however, this is not an additive effect to phosphodiesterase type-5 inhibitors (PDE5is) [47]. It is also not useful to treat ED with testosterone in men with baseline normal testosterone levels [48]. A Cochrane review has shown that psychotherapy is effective for treatment of ED and adds to the effectiveness of pharmacologic therapy [49].

The mainstay of pharmacologic treatment for ED is the PDE5i class of medications which include sildenafil, tadalafil, and vardenafil. In 2012, a fourth medication, avanafil, was approved by the US Food and Drug Administration (FDA). Studies have shown similar efficacy and side effects between all four medications, with improved erections in 50–80 % of men and a number needed to treat of two patients [27]. Treatment also has been shown to improve the sexual satisfaction of the man’s sexual partner [50]. Time of onset (30–60 min) is similar with these medications, except oral disintegrating vardenafil, and avanafil’s onset is 15 min.

Each of these drugs has some potential benefits: sildenafil has been studied the longest, tadalafil has longest duration of action, and vardenafil has shown promise in difficult-to-treat patients. Cost is the most common cause for discontinuation of PDE5is [39]. Several online resources cite the typical patient’s cost ranging from $10 to $40 per pill (goodrx.com). The starting doses are as follows: sildenafil (50 mg), tadalafil (10 mg), avanafil (100 mg), and vardenafil (10 mg). These doses then can be adjusted based on tolerance and/or efficacy. Daily tadalafil (5 mg) is an option for patients that prefer spontaneity in their sexual life and has been shown to have positive effects on lower urinary tract symptoms in patients with benign prostatic hyperplasia (BPH). Many insurance programs currently do not cover PDE5i therapy.

Side effects and risks of these medications should be discussed prior to prescribing them. Phosphodiesterase receptors are present in several other areas of the body, and this leads to a variety of adverse effects. Headache and flushing are the most common side effects noted in the PDE5is with a low rate of 6 % in avanafil and high rate of 14 % in sildenafil [51]. There are PDE6 receptors in the eye, and therefore visual changes can occur like blue vision (self-limited) or, more seriously, optic neuropathy [52]. While PDE5is have been associated with sudden hearing loss, sudden hearing loss has also been shown to be a risk factor for ED [53]. A 2014 study showed sildenafil use increased the risk of melanoma (HR: 2.2), and while the mechanism isn’t clear, it is felt to be a class effect [54]. Other unique individual side effects include tadalafil’s association with back pain and vardenafil’s potential to increase the QT interval [55].

PDE5is and alpha-blockers have efficacy in treating both BPH and ED. However, this combination should be used with caution as it can lead to severe hypotension. Likewise, nitrates and PDE5is also can cause severe hypotension and syncope due to a synergistic effect, and this combination is an absolute contraindication. Apomorphine is a sublingual dopamine agonist and is not as effective as PDE5is but is safe to take with nitrates when indicated for treatment of ED. Other drug interactions to be aware of with PDE5is include rifampin and human immunodeficiency (HIV) protease inhibitors [52].

Alprostadil has been available in the past only in an injectable formulation, but now recently a topical intraurethral version is available. Intraurethral alprostadil may be an option if oral treatments are not warranted, and efficacy has been reported over 80 % [56]. Injectable alprostadil is also effective, but side effects including urethral pain, UTI, priapism, fibrosis, and permanent erectile dysfunction have been noted, so intensive patient education is recommended [27]. Unlike PDE5i, alprostadil avoids the nitrous oxide pathway and therefore doesn’t require erectogenic stimulus to form an erection. This may be an advantage to patients with difficulties in the initiation phase of erectile dysfunction.

Proper patient education mainly about PDE5i timing is recommended to increase the effectiveness of PDE5is. PDE5is are not erotogenic and so patients should be advised they require sexual arousal to work properly. One study determined that in a primary care office, when patients who did not respond to PDE5is were reeducated, improvement in ED was seen in 40 % of cases [57].

When patients fail to respond to PDE5i treatment, and other lifestyle changes and underlying disease management have failed, alternative options exist. These include vacuum constriction devices (Fig. 9.5), alprostadil intracavernous injections, or penile prostheses. Advantages of the vacuum device include rapid action (30 s to 7 min), few contraindications (which are anticoagulation, bleeding diatheses, and sickle cell), and one-time cost [58]. Disadvantages include bluish erection, pain, and petechia (25–39 % of cases) [58]. Penile implants for refractory ED have shown to be effective with low risks of infection [59]. Penile prosthesis is a good option for patients who have failed other treatments or want a permanent treatment. Their success rate and patient satisfaction rates are 70–80 % [60].

Normal intravaginal ejaculatory latency time has been found to be between half a minute and 5 min. The definition of premature ejaculation (PE) has changed over the last 20 years to be more specific. In order to treat and study men who suffer from this condition, the International Society on Sexual Medicine formed a committee who published a paper defining premature ejaculation as [61]:

The panel acknowledged this definition does not include the same gender sexual intercourse, or oral or anal penetration, citing lack of evidence to define problematic early ejaculation in these situations [61]. The Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5), uses a similar definition for PE with the addition of a fourth criteria that the condition is not related to another nonsexual mental disorder or a severe relationship or other significant stressor or medication use. Given the prior history of vague definitions and men’s reluctance to discuss this condition, the exact number of men suffering from PE is not well known. A recent survey over 2000 men in China found that 25 % of men had some PE symptoms, and of those with symptoms, 18 % fit the criteria for acquired PE and 12 % fit the criteria for lifelong PE [62].

Premature ejaculation, like ED, can be caused by both physiological and psychological factors. There have not been as many medical comorbidities associated with PE as there is with ED. The exact etiology is often unknown. There is association with PE and other sexual disorders such as ED and infertility [63]. Many studies use a stopwatch to measure intravaginal ejaculatory latency time (IELT), but the use in clinical practice has been discouraged as it can disrupt spontaneity and pleasure. Studies have found that self-report is often as accurate as a stopwatch in defining measurable time. A physical exam for lifelong PE is usually not as helpful as for acquired PE, when the thyroid and prostate function and glands should be examined. PE can be very disruptive to a relationship causing significant emotional distress for the patient and their partner [64].

Both pharmacologic and behavioral therapies have been found to be effective for PE. Combining behavioral and pharmacologic treatment increases effectiveness. Despite studies showing the effectiveness of SSRIs, currently no FDA-approved medications are available for PE. Treatments can be divided into either daily dosing or on-demand treatment. Daily dosing medications that have shown to be effective include paroxetine, citalopram, fluoxetine, and clomipramine. On-demand medications include paroxetine, clomipramine, dapoxetine (not available in the USA), and topical lidocaine or prilocaine.

Topical EMLA (eutectic mixture of local anesthetics) cream has been shown to be effective when applied 15 min before sexual activity [65]. The authors encourage a trial of condom use for patients with PE. Although studies with condom use alone were not found to demonstrate effectiveness, most studies evaluating topical anesthetic used condoms to avoid diffusion into the vaginal wall and numbing of the partner. The most effective daily dosing SSRI appears to be paroxetine with over an eightfold delay in ejaculation [66]. The on-demand medications usually take 3–6 h to be effective and are not as effective as daily dosing. However, men often are reluctant to take any medications for PE, and despite effectiveness of treatment, one study found that 90 % of men stopped after a year [67]. Other potential treatments for PE which have limited evidence include acupuncture and caffeine 100 mg orally, 2 h prior to sexual intercourse [68].

Hematospermia, or hemospermia, is a rare condition where blood is found in the ejaculate. While it is often distressing for men, it is rarely a sign of a more significant disease. A single episode in men less than 40 without other systemic or urinary symptoms like hematuria does not require an extensive evaluation [68]. For men greater than 40, or those whom have recurrent symptoms, an evaluation for urologic disorders such as genitourinary infections or cancers or systemic diseases like uncontrolled hypertension or bleeding disorders is recommended [69]. This evaluation depends upon the history and physical examination but may include a serum prostate-specific antigen (PSA) assay, prostate ultrasound, testicular ultrasound, prostate biopsy, or serologic evaluation for coagulation disorders. Treatment is directed based on any etiology discovered.

Painful ejaculation has been described to be prevalent in about 1 % of the male population over 50 years of age [70]. Painful ejaculation is a known complication of a radical prostatectomy and has been implicated in other prostate disorders such as benign prostate hypertrophy and chronic prostatitis [71]. While the frequency of painful ejaculation in patients with BPH is low (15 %), the frequency in men with interstitial cystitis is quite high (60 %) [71]. Other causes include hernia repair, intra-abdominal cancer or abscesses, or urethral stricture, but often the etiology is unknown. A review of the literature did not find a valid treatment for this condition, but a small randomized controlled clinical trial (RCT) showed no effect with tamsulosin versus placebo [72]. Treatment should be focused at the underlining condition, and referral to a urologist may be appropriate.

In many societies throughout history, treatments to improve or enhance sexual function have been highly sought after. This has resulted in “quackery” where charismatic salesman flourishes, such as John Brinkley who, in the 1950s, promoted transplanting goat glands into humans to improve erections [73]. Currently, it has been found that the main ingredients in web-based sexual enhancement products are yohimbine, maca, gingko biloba, and horny goat weed [74]; please see Table 9.1 for further details on these. Also, many over-the-counter supplements have been found to have detectable PDE5i elements like sildenafil [75]. There is evidence from a small single-blinded study for supplementation with l-carnitine, l-arginine, and niacin combination to improve ED [76].

Infertility is defined as the inability for a couple to become pregnant after 12 months of unprotected intercourse [77]. Prior studies have looked at prevalence based upon referrals to infertility clinics, but a 2014 study looking at a wide male population found rates of infertility at 12 %, confirming data from older studies [78]. Factors associated with longer time to pregnancy in this study included male age (35–45 years vs. 17–24 years), biologic childlessness, and no health insurance [78]. Of the total infertility cases in one population study, men were found to be the cause 20 % of the time, women 33 % of the time, a combination of male and female factors 39 % of the time, and 8 % were unexplained [79]. The cost of diagnosing and treating infertility is often substantial, and many insurances do not cover this cost. Therefore, there is a socioeconomic disparity in the diagnosis and treatment of infertility [80].

The diagnosis of male infertility is based on having an abnormal semen analysis (SA). Azoospermia is defined as undetectable sperm in an SA; oligospermia is a diminished sperm count in an SA; asthenospermia is abnormal sperm motility; teratospermia is abnormal sperm morphology. The etiology of an abnormal SA is often unknown but could be due to pre-testicular, testicular, or post-testicular causes [81]. Environment, trauma, prior infections, and pharmaceuticals such as exogenous testosterone, spironolactone, carbamazepine, and calcium channel blockers may affect spermatogenesis [81].

Key points to determine in a man who is concerned about infertility include if he has had prior biologic children, his partner’s history of biologic children, testicular trauma, mumps, bicycling, hot tub use, smoking, dairy intake, sugar substitute intake, urologic procedures, medications (including over-the-counter), sexual activity, and illicit drug use. A 2014 cohort study of over 10,000 men found a significant decrease in semen volume and sperm concentration in men with obesity [82]. Physical examination should be conducted to evaluate for signs of hypogonadism or abnormalities in the genitourinary exam. Varicocele repair has been shown to improve sperm measurements and fertility, but the improvement may decrease over time [83]. Other physical findings that can affect male fertility are cryptorchidism, hernia or hernia repair, prostate disease, penile deformities (e.g., hypospadias), and the lack of a vas deferens.

The recommended initial laboratory testing for male infertility is the SA. Updated SA parameters by the World Health Organization (WHO) in 2010 include lower normal limits for sperm count (15 million/ml), total motility, and normal morphology [84]. This may result in a lower number of men diagnosed with male infertility. There is frequent day-to-day variability within a man’s SA, and any abnormal SA should be repeated to confirm a diagnosis of suspected male infertility [80]. Studies have obtained SA by masturbation at a clinic site after men had been asked to abstain from ejaculation for 48 h [85]. Home testing is available that reliably tests for sperm counts but not motility or morphology [86].

It is estimated that approximately 30 % of male infertility may be missed on SA, and so other special testing should include anti-sperm antibody tests and sperm penetration assays [84]. Routine endocrine testing (e.g., diabetes, thyroid disease) prior to obtaining SA has been found to be of low yield [87]. However, if there are significant abnormalities on the SA, then serum testosterone and follicle-stimulating hormone (FSH) levels are recommended to evaluate for hypogonadotropic hypogonadism. A testicular long axis less than 4.6 cm and an FSH level greater than 7.6 indicate nonobstructive azoopermia with high certainty, limiting the need for testicular biopsy [88].

Treatment for infertility depends on the etiology. Specific treatments based on etiology include alpha-adrenergic agonists for retrograde ejaculation, gonadotropin replacement for hypogonadotropic hypogonadism, and surgical varicocele repair. Treatments should also focus on lifestyle modification of factors mentioned above such as smoking cessation, weight loss, and dietary modifications to promote weight loss. Empiric treatment has been evaluated, and antioxidants, gonadotropins, and antiestrogens may be effective at improving sperm parameters and fertility rates [89]. Treatment for severe oligospermia or azoospermia often involves testicular sperm extraction (TESE) with intracytoplasmic injection (ICSI). There is a high rate of Y chromosome microdeletions in this population which would be passed on to offspring, so this testing is recommended prior to treatment [90].