Roughly 20% to 30% of adult men currently have at least one manifest sexual dysfunction (occurring "somewhat often," "often," "nearly always," or "always") [13]. A survey of 1,709 men 40 to 70 years of age found a 52% prevalence of past-year ED, with 17.2% minimal, 25.2% moderate, and 9.6% complete ED. ED severity, prevalence, and incidence increase with age, and higher ED rates are found in those with low education level, heart disease, hypertension, and diabetes. A Canadian survey of 3,921 male primary care patients 40 to 88 years of age found a roughly 50% prevalence of ED [14,15,16].

A survey of adults 18 to 59 years of age reported past-year rates of premature ejaculation (PE) in 28.5%, lack of sexual interest in 15.8%, sexual performance anxiety in 17%, inability to achieve or maintain an erection in 10.4%, and lack of sexual pleasure in 8.1% [2]. The National Health and Social Life Survey (NHSLS) indicates a fairly steady 30% prevalence of PE through all adult age categories (in contrast to ED, which rises in prevalence with increasing age) [19]. PE is the most common sexual disorder in men younger than 40 years of age, and 30% to 70% of men experience some degree of PE at some time point [19,20]. The prevalence of diagnosable PE varies from 8% to 30% for all age groups, with most studies reporting prevalence rates ranging from 12% to 19% [13]. Acquired PE is more prevalent than lifelong PE.

In patients showing an otherwise positive therapeutic response, switching medications to an antidepressant with fewer sexual side effects is highly undesirable and should be avoided, if possible. Another strategy is antidepressant dose reduction, on the basis of a dose-response relationship in sexual side effects. The incidence of male sexual dysfunction (particularly ejaculatory delay) is much higher with SSRIs and serotonin-norepinephrine reuptake inhibitors, and much lower in antidepressants with primary adrenergic or dopaminergic mechanism. However, this can be a desired instead of adverse effect in men with PE, and the SSRI dapoxetine has been approved as first-line therapy for PE in more than 50 countries, but not in the United States [9,22,23,24]. To date, no drug has been specifically approved by the U.S. Food and Drug Administration (FDA) for the treatment of PE [19]. However, the SSRIs sertraline, paroxetine, fluoxetine, and citalopram are used off-label for PE [24].

As noted, emotional and psychological factors can contribute to most types of male sexual dysfunction. For example, ED almost doubles in men with depression compared with those without depression. Also, male veterans with post-traumatic stress disorder (PTSD) have higher rates of sexual dysfunction than veterans without PTSD [64,65].

The vascular endothelium is essential for regulating normal circulatory function, and the association between ED and vascular disease resides in vascular endothelial dysfunction [56,77]. Endothelial and vascular smooth muscle dysfunction are highly prevalent in patients with ED and represent shared etiologic pathways for other vascular disease states such as cerebral vascular accidents, myocardial infarction, heart disease, hypertension, hyperlipidemia, low high-density lipoprotein (HDL), arteriosclerosis, and peripheral vascular disease [13]. Most risk factors of ED promote endothelial dysfunction, including hypertension, dyslipidemia, diabetes, depression, obesity, cigarette smoking, and metabolic syndrome [52,77,78,79].

Transurethral resection of the prostate for benign prostatic hyperplasia is associated with a 10% to 20% rate of ED from cauterization-induced nerve damage, but newer procedures using microwave, laser, or radiofrequency ablation have reduced ED rates to nearly 0%. Radical prostatectomy treatment of prostate cancer poses a significant risk of ED, but erectile function may be preserved if both nerves that run through the lateral edges of the prostate are saved. Potency preservation is related to surgeon experience and patient age, with baseline erectile function maintained in 75% to 80% of men younger than 60 years of age, and 10% to 15% of men older than 70 years of age. At two-year follow-up of early-stage prostate cancer treatment, patient ability to achieve erection suitable for intercourse was 35% with radical prostatectomy, 37% with external beam radiotherapy, and 43% with brachytherapy [91].

Psychological and interpersonal factors may cause or exacerbate acquired PE. Specific factors include the effects of early experience and sexual conditioning, sexual abuse, and attitudes toward sex internalized during childhood. Individual psychological factors may include poor body image, depression, performance anxiety, and alexithymia. Relationship factors include decreased intimacy or partner conflict. Anxiety is thought to activate the sympathetic nervous system and reduce ejaculatory threshold, leading to earlier ejaculation. Hypoactive sexual desire may lead to acquired PE from an unconscious desire to abbreviate the unwanted penetration or, conversely, may develop as a consequence of chronic and frustrating PE. Psychological factors and PE can be bi-directional, with either factor causing or exacerbating the other. An example is performance anxiety leading to PE, which further exacerbates the original performance anxiety [64,105,106,107,108].

Many factors may contribute to the etiology of MHSDD, including [4]:

Erectile function depends on peripheral nerve status, integrity of the vascular supply, and biochemical events within the corpus cavernosum. Erection and orgasm are mediated by the autonomic nervous system, and sustaining and maintaining erection is controlled by the parasympathetic nervous system. Vascular and neurogenic components in male sexual response are mediated by hormonal status and extrinsic factors. Disruption to any of these systems can induce sexual dysfunction [56].

In men with PE, all or almost all (75% to 100%) sexual activity is marked by a pattern of ejaculation occurring during partnered sexual activity within one minute after penetration and before the individual wishes it [4]. The severity of PE is specified as:

The sexual history should include information about previous and current sexual relationships; current emotional status; the onset, duration, and clinical course (stable or worsening) of the current problem and whether the problem is continuous, intermittent, or context-specific; and previous provider contact for sexual function concerns, including any treatments and treatment response. Partner sexual health status (when available) may be useful. A detailed description should be made of the rigidity and duration of both sexually stimulated and morning erections and problems with arousal, ejaculation, and orgasm. In patients with a sexual partner, clinicians should begin developing a sense of patient and partner distress surrounding the sexual dysfunction and whether the sexual dysfunction was antecedent to, or a consequence of, the current relationship. Sexual orientation and gender identity should be noted. Patients should also be asked whether they favor or oppose any specific treatment and the extent they wish to explore the cause of their sex concern [74,119].

Pure psychogenic ED is uncommon and is characterized objectively by the presence of good nocturnal and morning erections and negative findings on all other tests. However, a psychogenic component is usually present in men with organic ED. A history of highly variable erection function suggests a psychogenic cause.

A physical examination should be performed for all patients with sexual complaints, with focus on genitourinary, endocrine, vascular, and neurologic systems. A genital examination is recommended and is essential with a history of rapid onset of pain during sex, penile deviation during erection, symptoms of hypogonadism, and current or past history of other urologic symptoms [76]. The physical exam should involve the following minimal exploration [120,125]:

A shorter version of the IIEF, the IIEF-5, was developed as a sexual health inventory for men and is useful for screening patients for ED. The IIEF-5 asks the patient the five questions below, as applied to the previous six months. Answers to the five questions are scored on a 0–5 scale. A score of 25 is typical in healthy men; a score ≤11 indicates moderate-to-severe ED [133,134]:

The Self-Esteem and Relationship Questionnaire (SEAR) measures psychosocial outcomes in patients with ED by 14 items assessing two domains: sexual relationship and confidence. The confidence domain has two subscales: self-esteem and overall relationship [133,138].

Serum testosterone testing can be useful in patients with decreased sexual interest, delayed ejaculation, reduced ejaculate volume, PDE5I failure, or diabetes-related ED [119]. Testosterone level is measured to identify hypogonadism, defined by the American Urological Association (AUA) as biochemically low testosterone levels and the presence of a cluster of symptoms including male sexual dysfunction and impairments in mood, energy, and body composition [140]. The prevalence of biochemical hypogonadism in middle-aged men is 2.1% to 12.8%, and the prevalence of low testosterone and hypogonadism symptoms in men 40 to 79 years of age is 2.1% to 5.7%. Hypogonadism rates are higher in men who are older, who are obese, with medical comorbidities, and/or with poor health status [30].

LH levels vary according to physiologic requirements for testosterone. The hypothalamus regulates testosterone levels by releasing or inhibiting LH-releasing hormone, which activates pituitary production and release of LH. With a high LH level and a low testosterone level, primary testicular (Leydig cell) failure is suggested. Low levels of both LH and testosterone suggest a central defect [74].

Erections normally occur during rapid eye movement sleep. Nocturnal penile tumescence testing is used to measure and record nighttime erectile events to differentiate organic from psychogenic sexual dysfunction. Several bands are placed around the penis and connected to a device (e.g., a RigiScan monitor) and worn by the patient for two to three consecutive nights. With occurrence of an erection, the force and duration are measured. Inadequate or absent nocturnal erections suggest organic dysfunction, and a normal result strongly suggests psychogenic etiology [119].

Arteriography, the most invasive diagnostic test, is usually reserved for high-flow priapism or planned vascular bypass. Penile angiogram visualizes the penile circulation to guide embolization in penile injury [146].

Although most men with sexual dysfunction are successfully diagnosed and managed by their primary care physician, urologist referral remains an essential option in the following situations [51,119]:

A tiered approach for ED treatment based on level of invasiveness is recommended by the British Society for Sexual Medicine, the Canadian Urological Association, the American College of Physicians, the European Association of Urology, and the AUA [74,76,119,120,150]. First-line therapy with oral PDE5Is is universally recommended in patients without contraindications. Also, vacuum erection devices may be a viable first option. Second-line therapy consists of intracavernous injection or intraurethral alprostadil, and third-line therapy involves penile prostheses.

Guidelines recommend at least six maximum-dose PDE5I trials with sexual stimulation before classifying a patient as a non-responder [74]. The most common reasons for PDE5I nonresponse are incorrect drug use (e.g., failure to take an adequate dose, failure to engage in sexual stimulation) or lack of efficacy. Non-response management depends on identifying the underlying cause [74]. Inadequate counseling is a common cause of incorrect PDE5I use, and patient education may salvage apparent non-response by addressing dose, timing, and need for sexual stimulation. It is also important for patients to be aware of the window of efficacy after ingestion and initiation of sex. For sufficient effect, most patients need to wait 60 minutes after taking sildenafil and vardenafil and 120 minutes after tadalafil. Sildenafil absorption is delayed by a meal, and vardenafil absorption may be delayed by a fatty meal. The normal efficacy window is 6 to 8 hours for sildenafil and vardenafil and up to 36 hours for tadalafil [74].

Agents that increase serotonin neurotransmission are first-line therapy for PE. SSRIs and the TCA clomipramine are the preferred agents, though they are used off-label for PE treatment, as none are FDA-approved for this indication [24,215,216,217]. Topical local anesthetic agents may also be effective (Table 5).

For first-line therapy for premature ejaculation, the AUA recommends daily SSRIs, on-demand clomipramine or dapoxetine (where available), or topical penile anesthetics [265]. The second-line option is on-demand dosing of tramadol in men who have failed first-line therapy; the preferred third-line approach isα1-adrenoreceptor antagonists.

Men complaining of PE require careful assessment to rule out ED, subclinical ED, erectile compromise from systemic factors, and genital/lower urinary tract infection. When impaired erectile function is identified, ED (and not PE) should be addressed first by pharmacotherapy with or without cognitive-behavioral therapy. While concurrent treatment of PE and comorbid ED has been recommended, the approach of using two drugs to treat PE, which may resolve by treating the underlying cause of ED with a PDE5I, lacks merit. A better approach is to treat ED first; if PE remains symptomatic, dapoxetine should be prescribed [10].

Psychotherapy should be initiated before medication in patients with severe depression, with substance abuse disorders, or in abusive/chaotic relationships, as medication has little benefit in this context. Medical therapy alone is appropriate for cases in which the sexual dysfunction has a clear medical precipitant, couples in a high-quality relationship, or patients with few psychological concerns [10].

In PE, psychological interventions can help men develop sexual skills that promote ejaculatory delay, broaden the sexual script of the couple, increase sexual self-confidence, and reduce performance anxiety. Psychotherapy is also used in resolving psychological and interpersonal issues for the man, partner, or couple that were antecedent to or consequence of the PE [106,254]. Current approaches integrate psychodynamic, systems, behavioral, and cognitive approaches within a short-term psychotherapy model, delivered in an individual, couples, or group format [9]. The squeeze and stop-start techniques are the most common behavioral strategies for PE. Both are designed to help men recognize mid-level ranges of excitement. Men with variable PE should receive education and reassurance, while men with subjective PE may require psychotherapy referral [255].