Sexual activity in patients with cardiovascular disease

INTRODUCTION — 

Sexual activity is an important component of quality of life and a common concern for both patients with cardiovascular disease (CVD) and their clinicians. Individuals with CVD may fear that sexual activity will trigger angina, myocardial infarction (MI), or sudden cardiac death and may therefore have sex less frequently. They may also experience sexual dysfunction; some may seek treatment, while others may avoid discussing sexual concerns with their clinicians.

This topic discusses the cardiovascular effects of sexual activity, the rationale for and approach to discussing sexual activity with patients who have cardiac disease, the evaluation and risk stratification of patients for safety with sexual activity, modification of risk for sexual activity, association between sexual activity and MI, and the management of sexual dysfunction in patients with CVD.

Sexual dysfunction in the general adult population is discussed elsewhere. (See "Sexual dysfunction in older adults" and "Overview of sexual dysfunction in females: Epidemiology, risk factors, and evaluation" and "Overview of sexual dysfunction in females: Management" and "Evaluation of male sexual dysfunction" and "Treatment of male sexual dysfunction".)

CARDIOVASCULAR EFFECTS OF SEXUAL ACTIVITY — 

Sexual activity, including arousal, orgasm, refractory period, and resolution, depends in part upon changes in the autonomic nervous system. The main outflow to the cardiovascular system during sexual intercourse is sympathetic and is mediated by outputs from the brain carried by efferent pathways originating from the thoracic spinal cord [1].

Cardiovascular demands of sexual activity — Sexual activity causes a modest, brief increase in myocardial oxygen demand [2]. Sexual activity consumes two to three metabolic equivalents (METs) of oxygen during the preorgasmic phase and three to four METs during orgasm. This is equivalent to walking at two to four miles per hour on a level surface [3]. However, moderately intense sexual activity in younger individuals may be closer to five to six METs [4]. This is equivalent to walking uphill or bicycling with moderate effort.

●Studies performed in "real-life" settings (ie, not in a laboratory setting) suggest that heart rate and blood pressure changes that occur during sexual activity are within the range of those that occur with normal daily activities [5-8]. As an example, one study monitored couples during sexual intercourse in their own bedrooms [7,8]. The mean heart rate at the time of orgasm was 117 beats per minute, which was lower than the heart rate during normal daily activities (mean 120 beats per minute), and the mean estimated blood pressure was 162/89 mmHg. A second study compared maximal heart rate and blood pressure responses during maximal Bruce protocol treadmill exercise testing and sexual activity (using noninvasive home monitoring) in 32 individuals (19 males and 13 females). Their results suggested that the physical stress of sexual activity was comparable with stage II of a standard Bruce treadmill protocol for males and stage I for females [6].

●A subsequent study in 42 younger participants (mean age 22.6 years) found higher levels of exercise intensive with sexual activity (mean intensity of 6 METs for males and 5.6 METs for females) [4].

Unclear role of sexual position — It is unclear whether sexual position affects the degree of hemodynamic stresses of sexual activity. Few studies have examined this question, especially in females. In males, limited data suggest that the cardiovascular response to sexual intercourse is not less in the supine position.

As an example, one study monitored eight males (ages 24 to 40) during sexual intercourse and found no difference in heart rate (114 versus 117 beats per minute) or blood pressure (163/81 versus 161/77 mmHg) when the male was on top versus on the bottom [8]. A second study found a slightly lower minute oxygen consumption for males in the supine position, but this lasted for only a brief period during orgasm [3].

COUNSELING PATIENTS ABOUT SEXUAL ACTIVITY

Discussing patients' sexual concerns — Clinicians should discuss sexual activity, concerns, and function with their patients with CVD and, potentially, their partners [9,10]. Clinicians should proactively raise the topic of sexual activity and tailor the discussion to the individual's needs, cardiovascular conditions, symptoms, and risk (table 1). Clinicians may need to acquire additional education and training to provide sexual counseling and/or utilize a team approach [11]. They should also familiarize themselves with cardiovascular risk stratification and risk reduction for sexual activity and ask about any cardiac symptoms that occur with sexual activity, including specific practices that trigger symptoms. (See 'General safety recommendations' below.)

Unfortunately, many clinicians do not discuss sexual issues with patients with CVD or their spouses [12,13]. We recommend the following approach, which is consistent with a 2013 consensus document from the American Heart Association and the European Society of Cardiology Association of Cardiovascular Nursing and Allied Professions [11].

●Timing and setting – Broaching this topic is particularly important with patients after an acute cardiac event, such as myocardial infarction (MI). However, patients with chronic cardiovascular conditions may also have ongoing sexual concerns. Depending on patient preference and clinical resources, discussions can occur in inpatient or outpatient settings or as part of a comprehensive cardiac rehabilitation program.

●Rationale for discussing sexual activity – Many patients and their partners have concerns about whether, when, and how to return to sexual activity after acute cardiac events, such as MI, percutaneous coronary intervention, coronary artery bypass graft surgery (CABG), and heart failure, and most want information about these issues [11]. Patients who experience cardiac events (eg, MI) and interventions (eg, CABG) often report at least a transient decrease in the frequency and satisfaction of sexual activity. Patients' partners may also have concerns. As an example, in one study, partners of patients undergoing cardiac rehabilitation reported sexual concerns as one of the most common stressors [14].

•Fears about and changes in sexual activity after a cardiac event can have a negative impact on patients' intimate relationships, sexual function, quality of life, and psychologic well-being (see 'Sexual dysfunction in patients with cardiovascular disease' below). They may also lead to anxiety and depression [11].

•Anxiety can increase the risk of cardiac events, so explicitly addressing patient anxiety and concern regarding sexual activity is an important component of overall cardiovascular risk reduction [11].

No high-quality evidence supports the effectiveness of sexual counseling in patients with CVD or the optimal content of counseling in this context [15]. In a study of 2801 participants, patients who discussed sexual activity with a clinician in the month following their MI were more likely to resume having sexual activity [16]. Another trial randomized 92 male participants in a cardiac rehabilitation program after MI or CABG to sexual therapy or usual care. Sexual therapy recipients reported higher-quality and more enjoyable sexual function and were more likely to resume sexual activity within one month of their cardiac event [17].

Sexual rehabilitation that includes sexual counseling may also improve sexual function. As an example, in a trial of 152 participants with erectile dysfunction (ED) and ischemic heart disease or an implanted defibrillator, those randomized to 12 weeks of sexual rehabilitation (physical exercise training, pelvic floor exercise, and psychoeducation) experienced improved sexual function at four- and six-month follow-up, compared with usual care [18].

●Beginning the discussion – Clinicians should start to explore patients' sexual concerns through open-ended questions with a nonjudgmental, empathic attitude (see "Sexuality in palliative care", section on 'Taking a sexual history'). Specific questions to begin the conversation are summarized in a table (table 1) [19].

●Minimizing barriers to discussing sexual activity – Clinicians cite inexperience, lack of training, concerns about upsetting the patient, and time constraints as barriers to discussing sexual function with patients [11]. Both clinicians and patients report embarrassment as one of the main barriers to talking about sexual issues. Language discordance and cultural backgrounds of the patient and provider can also inhibit conversation. Practical suggestions for addressing these barriers include:

•Inexperience – The BETTER acronym provides a practical framework for sexual assessment and counseling [11,20]. In counseling patients with CVD, clinicians should:

-Bring up the topic of sexuality

-Explain your concerns that cardiac disease/events can negatively affect patients' quality of life

-Tell patients you can provide resources to help address their concerns

-Consider Timing (reassure patients who may not want to discuss sexual concerns at this juncture that their issues can be discussed in the future)

-Educate patients about the potential effects of their cardiac disease/event/treatments on their sexual functioning

-Record or document the assessment and interventions provided

•Lack of training – For selected patients, clinicians can use structured assessment instruments to augment their evaluation of patients' sexual function and target individual needs and concerns [11].

•Concerns about upsetting patients – Most patients want to discuss their sexual concerns with their health care clinicians. Clinicians should not assume that patients who are older, female, single, in same-sex relationships, gender diverse, or from certain cultural backgrounds do not want to discuss sexual concerns. Although little data exist about the optimal content of and approach to sexual counseling of diverse populations in the context of CVD, sexual issues are common in patients with CVD of all sexes and ages [11]. Patients are more likely to feel comfortable discussing sexual issues when clinicians proactively start the discussion and routinely include discussions of sexual health and function in their assessments of patients [21].

General safety recommendations — Patients with CVD should undergo assessment for the safety of sexual activity, particularly after an acute event (eg, MI) or intervention (eg, revascularization) [10].

●Sexual counseling – General recommendations for sexual activity counseling for patients with CVD appear in a table (table 2) [11,12,22]. Clinicians should clearly convey the patient's individual risk for MI with sexual activity and discuss when it is safe for the patient to resume sexual activity after an acute cardiovascular event and/or to receive treatment for sexual dysfunction and what measures can reduce the risk of MI with sexual activity (see 'Risk stratification and modification' below and 'Measures to modify risk of sexual activity' below). It is also imperative to counsel patients about the benefits and risks of phosphodiesterase 5 inhibitors (sildenafil, tadalafil, vardenafil, avanafil) for ED and especially the avoidance of coadministration with either short- or long-acting nitrate therapy. (See 'Coadministration with nitrates contraindicated' below.)

Clinicians should advise patients to alert them if they develop new, acute cardiac symptoms as well as provide recommendations for how to modify a patient's risk for MI. For most patients, regular aerobic exercise is an important intervention to improve sexual and cardiac health [10,11].

●Risk stratification – Clinicians should stratify patients with CVD based on active cardiovascular symptoms, disease severity, recency of cardiovascular events, and functional capacity. The overall risk of an MI or other cardiac event (angina, arrhythmias, exacerbation of heart failure) associated with sexual activity is low (see 'Low risk of MI for most patients' below). However, selected patients, such as those with unknown disease burden, unstable or severe disease, recent MI, or uncertain exercise tolerance, may be at increased risk and require additional testing and/or treatment prior to engaging in sexual activity or being treated for sexual dysfunction. Risk stratification and recommendations for patients with specific cardiovascular conditions are discussed below.

Low risk of MI for most patients — Most individuals with CVD can safely engage in sexual activity [23,24]. Although sexual activity can contribute to the onset of myocardial infarction (MI), only a small proportion of MIs occur in the context of sexual activity (ie, approximately 1 percent). Studies suggest that the relative risk increase of MI following sexual activity ranges from 2.1 to 2.5, although the absolute risk increase is low [25,26]. The period of increased risk lasts approximately two hours.

As an example, the Determinants of Myocardial Infarction Onset Study (MIOS) interviewed 1774 patients within one week of an acute MI, 858 of whom were sexually active prior to the event [25,27]. The relative risk of MI within two hours after sexual activity was 2.5; there was no increased risk of MI beyond this time window. Moreover, the relative risk was similar in participants with a history of prior angina or MI and those with no prior cardiac disease. A second study yielded similar results [26].

●Low absolute risk of MI – The absolute risk of MI with sexual activity is very small since sexual activity is a transient trigger that increases risk for only a two-hour period. Most patients and clinicians care more about the absolute increase in risk (ie, the risk of MI from sexual activity minus the risk at all other times, or the "attributable risk"). (See "Glossary of common biostatistical and epidemiological terms".)

•Only 3 percent of MIOS patients engaged in sexual activity in the important two-hour time interval prior to their MI [25]. As a result, the absolute increase in risk was small, with sexual activity contributing to the onset of MI in only 0.9 percent of participants. Based upon these results, a 50-year-old person free of cardiac disease with an annual baseline risk of MI of 1 percent would increase the annual risk of MI to only 1.01 percent from weekly sexual activity [28]. Even a person with a high annual risk for an MI of 10 percent would increase the annual risk to only 10.1 percent from weekly sexual activity.

•A 2011 meta-analysis of four studies estimated that one additional hour of sexual activity per week conferred an absolute risk increase of MI of two to three per 10,000 person-years [29]. This risk was attenuated in individuals who exercised regularly.

●Risk of sexual activity compared with other triggers for MI – Many other triggers of a myocardial infarction (MI), such as psychologic stress, anger, or physical activity, may cause a greater increase in absolute risk because they occur more frequently [27]. As an example, another analysis from the MIOS reported that 4.4 percent of patients with an acute MI reported heavy physical exertion within one hour prior to the MI. Compared with less strenuous or no physical exercise, the relative risk of MI after heavy physical exertion was 5.9 percent, which is over twice that reported with sexual activity [30].

RISK STRATIFICATION AND MODIFICATION — 

Risk stratification and risk-based management for individuals with specific conditions are discussed below. Most recommendations regarding specific risk classifications are based on limited observational data and expert consensus [9,10,31].

Initial evaluation

History and physical examination

●History – Clinicians should take a thorough history that details the complete cardiovascular history (ie, history of coronary disease, valvular heart disease, arrhythmia, and heart failure). The history should also elicit any symptoms of ischemia, arrhythmia, or heart failure and, for symptomatic patients, classify their severity. This should include an assessment of patients' exercise tolerance. Clinicians can ask about common physical or household activities to estimate patients' functional status in terms of the number of metabolic equivalents (METs) (table 3). Clinicians should also assess for other atherosclerotic CVD conditions, such as peripheral artery disease, stroke, or transient ischemic attack.

History taking should include a sexual history, particularly in individuals who have experienced a recent cardiovascular event (see 'Discussing patients' sexual concerns' above). Specifically, clinicians should ask if sexual activity precipitates symptoms that could be anginal equivalents or arrhythmia and ask about sexual function. (See 'Sexual dysfunction in patients with cardiovascular disease' below.)

●Physical examination – Examination should focus on measuring blood pressure and identifying signs of arrhythmia, valvular heart disease, and decompensated heart failure.

Assessment of exercise tolerance — Clinicians should assess patients' functional capacity via history or exercise stress testing. When the clinical history does not clearly indicate the patient's functional capacity, exercise testing can provide formal risk stratification (algorithm 1).

●Given that the cardiovascular stresses with sexual activity are similar to those with other forms of exercise, exercise testing can be used to assess both exercise tolerance and tolerance for sex [32].

●Individuals who can achieve at least four to six METs (table 3) without ischemia on exercise testing are at very low risk of a cardiovascular event during sexual activity [10].

●We use higher thresholds for adequate exercise tolerance (>5 to 6 METs) in younger patients (age <55) than older patients (>4 METs) [23].

Recommendations for patients with coronary artery disease

Asymptomatic coronary artery disease — Individuals with asymptomatic coronary artery disease (CAD) are generally considered low risk if they have average to good exercise tolerance for their age (see 'General safety recommendations' above). Asymptomatic CAD includes individuals with known CAD and advanced subclinical coronary atherosclerosis (ie, coronary artery calcium >1000) [33,34].

We classify individuals with uncertain exercise tolerance as having indeterminate risk and recommend risk stratification by exercise testing as part of optimal management (algorithm 1) [9]. Patients with low exercise tolerance for their age are considered high risk and require risk management, cardiologist evaluation, and cardiac rehabilitation, if eligible.

Stable angina

●Mild to moderate symptoms and adequate exercise tolerance – Patients with stable angina of mild severity (Canadian Classification System [CCS] class I or II) (table 4) are at low risk. These individuals can safely engage in sexual activity if they can exercise four to six METs without symptoms or ischemia. (See 'Assessment of exercise tolerance' above.)

●Mild to moderate symptoms and unknown exercise tolerance – Those with mild to moderate anginal symptoms and unknown exercise tolerance may benefit from additional risk stratification with exercise stress testing.

●Severe symptoms or symptoms with sexual activity – Patients with stable, but severe or refractory, angina are at high risk (CCS class III or IV) and must optimize management prior to having sex. Similarly, patients for whom sexual activity triggers angina or anginal equivalent symptoms are considered high risk and should defer sexual activity until further workup and management [10].

●Managing anginal symptoms that occur with sexual activity – We recommend antianginal medications (ie, beta blockers and nitrates) for individuals who experience mild to moderate anginal symptoms with sexual activity. Medical therapy can improve or resolve anginal symptoms that occur with sexual activity.

•Although sexual activity can trigger angina [7,35], it accounts for only 5 percent of all angina attacks [36]. The increase in heart rate and blood pressure that occurs with sex is similar to other forms of exercise. One study monitored 35 patients with stable angina (30 males and 5 females) during intercourse in their homes; 65 percent experienced angina on at least some occasions [35].

•In one study, pharmacotherapy with beta blockers and, in some cases, prophylactic sublingual nitrates rendered previously symptomatic individuals free of angina during sexual activity [35].

Acute coronary syndromes — Individuals with the unstable angina or acute myocardial infarction (MI) within the past week are considered high risk and should be stabilized and receive optimal management prior to engaging in sexual activity [9,10]. Patients who are at least one week out from an uncomplicated MI and are asymptomatic with mild to moderate physical activity (four to six METs) are at low risk; these patients can safely resume sexual activity [10]. Patients whose exercise tolerance or ability to participate in cardiac rehabilitation is unknown after an acute MI generally benefit from additional risk stratification, particularly if they have not undergone revascularization [9]. (See 'After coronary revascularization' below.)

After coronary revascularization — Individuals who have undergone complete revascularization with percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG) and are asymptomatic are at low risk of MI and ischemic symptoms following sexual activity. Those who have undergone incomplete revascularization are at indeterminate risk and benefit from exercise testing to determine functional capacity and extent of ischemia [10]. Alternatively, a thorough clinical history to assess functional capacity may suffice for such individuals.

Patients should delay sexual activity in the immediate period after coronary revascularization or cardiac surgery [10]. Patients can resume sexual activity within:

●Two to three days of uncomplicated PCI without vascular access site complications

●Six to eight weeks of uncomplicated CABG if sternotomy site is well healed

●Six to eight weeks of uncomplicated noncoronary cardiac surgery if sternotomy site is well healed

Other disease-specific recommendations

Heart failure — Most patients with stable heart failure can safely engage in sexual activity [10]. Risk stratification for individuals with heart failure depends on functional status because functional status likely correlates with safety of sexual activity (algorithm 1) [10].

●New York Heart Association class I or II – Patients with mild chronic heart failure (New York Heart Association [NYHA] class I or II) are at low risk (table 4) and can safely participate in sexual activity.

●New York Heart Association class III or IV – High-risk patients include those with severe heart failure (NYHA class III or IV chronic heart failure) or acutely decompensated heart failure. Individuals with severe symptoms from obstructive hypertrophic cardiomyopathy are also at high risk. High risk patients should have their management optimized prior to engaging in sexual activity [10].

Valvular heart disease

●Aortic stenosis – Patients with mild aortic stenosis are generally at low risk and should undergo risk stratification based on functional capacity (algorithm 1). Patients with moderate to severe aortic stenosis who are symptomatic are at high risk and should discuss the safety of sexual activity with their cardiologist. Patients with moderate to severe aortic stenosis who are asymptomatic should undergo further risk stratification with exercise stress testing.

●Other valvular heart disease – Patients with the following conditions are at low risk and can safely engage in sexual activity if they are able to exercise at least four to six METs (algorithm 1).

•Mild to moderate valvular heart disease and no to mild symptoms (NYHA class I or II)

•Asymptomatic mitral valve prolapse

•Normally functioning prosthetic or repaired valves

•Successful transcatheter valve intervention

Patients with severe valvular disease who are asymptomatic should undergo risk stratification with exercise testing. Patients in this subgroup who are symptomatic are at high risk and should discuss the safety of sexual activity with their cardiologist.

Arrhythmias, pacemakers, and implantable cardioverter defibrillators — Low-risk patients include asymptomatic individuals with pacemakers or implantable cardioverter defibrillators that were implanted for primary prevention and who have no recent history of multiple shocks. Patients with paroxysmal atrial fibrillation or flutter, or those with atrial fibrillation or flutter with well-controlled ventricular rates, are also at low risk. Patients with atrial fibrillation or flutter and uncontrolled ventricular rates should defer sexual activity until rate control has been achieved. The risks of sexual activity in patients with or at risk for ventricular arrhythmias is markedly elevated. One study of 43 patients with implantable cardioverter defibrillators found that the risk of tachyarrhythmias with sexual activity was comparable to that with mental stress or exercise [10,37].

Measures to modify risk of sexual activity

●Regular exercise – Engaging in regular exercise is associated with a lower risk of MI following sexual activity. Patients should undergo cardiac rehabilitation after MI in part because exercise training may reduce the risk of recurrent MI during sexual activity. Cardiac rehabilitation is discussed separately. (See "Cardiac rehabilitation: Indications, efficacy, and safety in patients with coronary artery disease".)

•Exercise may reduce hemodynamic stress – Exercise training may attenuate the hemodynamic stress associated with sexual activity. Exercise training increases the aerobic capacity and decreases the peak heart rate in post-MI subjects engaging in sexual intercourse [38]. In one report, 16 patients with a prior MI had a 5.5 percent reduction in mean peak heart rate during orgasm and an 11.5 percent increase in aerobic capacity after undergoing a 16-week exercise training program [38].

•Association of regular exercise with reduced risk of MI with sexual activity – Regular exercise is associated with a reduced risk of myocardial infarction (MI) following sexual activity [25,26]. As an example, in one study, the estimated relative risk of an MI in the hour after sexual intercourse was 4.4 in those with a sedentary lifestyle, compared with 0.7 in those who were physically active [26]. Similarly, in a study of adults with recent MI, regular physical exercise at levels of ≥6 METs was associated with a lower risk of MI from sexual activity [27].

•Association of regular exercise with reduced risk of MI with heavy physical exertion – Regular exercise is also associated with a lower relative risk of MI with any heavy physical exertion [30,39]. In a study of individuals with recent MI, participants who exercised less than once weekly had an estimated relative risk of MI with heavy physical exertion of 107. In contrast, the relative risk for those who exercised five or more times per week was only 2.4 [30].

●Medications – For individuals with heart failure, CAD, and valvular heart disease, we recommend evidence-based pharmacotherapies with established efficacy for reducing risks of mortality and cardiovascular death [24].

Pharmacotherapy for these patients is discussed separately. (See "Chronic coronary syndrome: Overview of care" and "Primary pharmacologic therapy for heart failure with reduced ejection fraction" and "Treatment and prognosis of heart failure with preserved ejection fraction" and "Chronic primary mitral regurgitation: General management".)

SEXUAL DYSFUNCTION IN PATIENTS WITH CARDIOVASCULAR DISEASE — 

The epidemiology, causes, and evaluation of sexual dysfunction in the general adult population are discussed in depth elsewhere. (See "Epidemiology and etiologies of male sexual dysfunction" and "Overview of sexual dysfunction in females: Epidemiology, risk factors, and evaluation".)

Epidemiology and pathogenesis of sexual dysfunction

●Shared etiology with atherosclerotic cardiovascular disease – Sexual dysfunction and atherosclerotic CVD share many common risk factors, including cigarette smoking, obesity, metabolic syndrome, hypertension, and diabetes. Males with erectile dysfunction (ED) are more likely to have subclinical coronary atherosclerosis, and incident ED is associated with increased rates of future cardiovascular events [40]. Some experts include ED as a risk-enhancing factor for myocardial infarction (MI) [23]. Cardiovascular evaluation and risk stratification of males with ED who do not have established CVD is discussed separately. (See "Evaluation of male sexual dysfunction", section on 'Evaluation for cardiovascular disease'.)

●Frequency in patients with established CVD – Sexual dysfunction occurs frequently in patients with CVD [16] and is more prevalent in these individuals than in the general population. As an example, in one study, approximately 25 percent of patients with heart failure reported stopping sexual activity completely while 60 to 87 percent reported some level of sexual dysfunction, including a loss of interest in sexual activity [10]. (See "Epidemiology and etiologies of male sexual dysfunction", section on 'Cardiovascular disease'.)

●Frequency of sexual dysfunction after acute cardiovascular events – Sexual dysfunction after an MI occurs in up to three-quarters of patients [16,41,42]. All adults have less sexual activity and less satisfaction with sexual activity after an MI [12,42,43]. However, decrease in or loss of sexual activity after MI may occur more commonly in females [16]. In one study, 71 percent of females noted a decrease in or no sexual activity after experiencing an MI [12]. Common sexual problems in the year following MI include lack of interest, difficulty with vaginal lubrication in females, and ED in males [16]. Sexual dysfunction is also seen after coronary artery bypass graft surgery [44].

●Reasons for sexual dysfunction – Both physical and psychologic factors contribute to sexual dysfunction in patients with CVD. Psychologic factors include depression, anxiety, and concerns about the safety of sexual activity. Patients and their partners are often afraid that sexual activity will trigger an MI or sudden death. Depression and anxiety also occur commonly in patients who have experienced an MI and can trigger or exacerbate a lack of interest and sexual dysfunction [12,45-48]. Physical causes of sexual dysfunction include medication side effects (eg, diuretics, beta blockers) as well as presence of cardiovascular risk factors that affect sexual function (eg, hypertension, smoking, diabetes, postmenopause) [12,43,45,49-53].

Initial management for all patients

●Risk stratification – One risk of treating sexual dysfunction in patients with CVD derives from the small risk of ischemic events associated with sexual activity itself, especially in patients who are physically inactive [54]. Consequently, the management of sexual dysfunction in patients with CVD should start with risk stratification and risk-based management as detailed above (algorithm 1) (see 'General safety recommendations' above and 'Recommendations for patients with coronary artery disease' above). Patients in low-risk categories can safely be treated for sexual dysfunction, whereas those in high-risk groups require stabilization and optimization of management prior to treatment for sexual dysfunction [9,31]. Those with indeterminable risk should undergo exercise stress testing.

●Addressing psychologic factors – Evaluation of patients who report a loss of interest in sexual activity should include an assessment for depression or anxiety since these conditions can cause or contribute to sexual dysfunction. Clinicians should also elicit and address patients' concerns about sexual activity, including issues with sexual dysfunction, and reassure patients at low risk that sexual activity is safe. Specific questions about sexual dysfunction appear in a table (table 1). (See 'Discussing patients' sexual concerns' above.)

Treatment of psychiatric conditions and reassurance of the low attributable risk of MI have been associated with improved sexual function [45,55]. (See 'General safety recommendations' above.)

●Assessing for medication-related sexual dysfunction – Because the risk of sexual dysfunction from common cardiovascular medications is generally low, clinicians should carefully assess the onset of sexual dysfunction in relation to the timing of medication initiation and dose changes before attributing sexual dysfunction to drug therapy. Thiazide diuretics and beta blockers can increase the risk of ED, although the risk associated with beta blockers is low. In patients with sexual dysfunction, we typically discontinue beta blocker therapy in those with normal left ventricular ejection fraction, no MI in the past year, and no other indication for beta blockers [24].

Clinicians should reassure patients that statin therapy and other classes of antihypertensive agents (eg, angiotensin receptor blockers, angiotensin-converting enzyme [ACE] inhibitors, calcium channel blockers, and alpha blockers) confer little to no increased risk of ED [56-58]. The role of specific medications in causing ED is discussed elsewhere. (See "Epidemiology and etiologies of male sexual dysfunction", section on 'Drugs'.)

●Cardiovascular risk factor modification – Modification of some cardiovascular risk factors (eg, smoking cessation, weight loss, increased physical activity) may also improve sexual function. This is discussed elsewhere. (See "Treatment of male sexual dysfunction", section on 'Lifestyle changes'.)

ED is a common symptom of sexual dysfunction in males with CVD. This section highlights key features of pharmacotherapy for ED in males with CVD. General approaches to the management of sexual dysfunction are discussed separately. (See "Overview of sexual dysfunction in females: Management" and "Sexual dysfunction in older adults" and "Treatment of male sexual dysfunction".)

Use of PDE-5 inhibitors in males with CVD — Phosphodiesterase 5 (PDE-5) inhibitors are widely used in the treatment of ED in males. Although most data regarding the efficacy and safety of PDE-5 inhibitors in individuals with CVD come from studies of sildenafil, results appear to be generalizable to other PDE-5 inhibitors (vardenafil, tadalafil, avanafil). Two decades of experience with PDE-5 inhibitors in males with ED support their safety.

Efficacy, safety, and choice of agent

●Choice of PDE-5 – We recommend sildenafil for the treatment of ED in patients with CVD because its efficacy and safety in this population have been more extensively studied.

●Efficacy – PDE-5 inhibitors can improve ED in males with ischemic heart disease. In a study comparing sildenafil with placebo for the treatment of ED in 357 males with ischemic heart disease, sildenafil improved erection in 70 percent of participants, compared with 20 percent with placebo [59]. Sildenafil reduces rates of ED in males with vascular (eg, hypertension, diabetes mellitus), nonvascular, and psychogenic causes [60]. (See "Treatment of male sexual dysfunction", section on 'Sildenafil'.)

The effectiveness of vardenafil and tadalafil appears equivalent to that of sildenafil. Tadalafil has a longer duration of action, which affords more spontaneity in sexual activity but may increase the likelihood of drug-drug interactions (ie, with nitrates) and cardiovascular side effects.

The clinical use, adverse effects, and drug-drug interactions of PDE-5 inhibitors appear in a table (table 5). (See "Treatment of male sexual dysfunction", section on 'Choice of drug'.)

●Safety – Although PDE-5 inhibitors are generally safe for the treatment of ED in males with CVD [10,59], clinicians should exercise caution when using PDE-5 inhibitors in patients who are vulnerable to the systemic vasodilation or hypotension that they induce. Most importantly, concurrent use of PDE-5 inhibitors and nitrates is contraindicated. (See 'Coadministration with nitrates contraindicated' below.)

•Cardiovascular actions – PDE-5 inhibitors exert two important cardiovascular actions that can cause potentially dangerous side effects in patients with heart disease: They can lower blood pressure and cause vasodilation that reduces systemic vascular resistance.

Sildenafil, for example, lowers the systolic blood pressure by approximately 8 mmHg [54,61]. It can also produce a mild antianginal effect in patients with exercise-induced ischemia through dilation of epicardial coronary arteries. In patients with coronary heart disease, sildenafil also improves endothelial dysfunction and inhibits platelet activation [62].

Limited data exist on the cardiovascular effects of vardenafil or tadalafil in males with heart disease.

•Sildenafil and risk of cardiac events – The predominance of evidence suggests that sildenafil does not increase the risk of cardiovascular events in males who do not take nitrates [10]. Although case reports initially raised concerns that sildenafil could trigger cardiac events, especially in individuals with established CVD [63,64], subsequent observational and case-crossover studies did not find an association between sildenafil use and an increased risk of MI, serious cardiovascular events, or all-cause mortality [54,59,65-69]. As an example, a review of clinical trials involving 6527 participants found no increase in the incidence of all-cause mortality or MI [54].

In contrast, some large, retrospective cohorts suggest an association between PDE-5 inhibitor use and lower risks of cardiovascular outcomes. As an example, in a retrospective, claims-based study of over 70,000 males with ED, treatment with PDE-5 inhibitors was independently associated with lower rates of major adverse cardiovascular events (hazard ratio [HR] 0.87, 95% CI 0.79-0.95) at 15-year follow-up. This finding awaits confirmation in randomized trials.

•Sildenafil well-tolerated among males with stable CAD – Males with stable coronary artery disease (CAD) who use sildenafil do not experience significant worsening of ischemic symptoms or changes in cardiac hemodynamic parameters [61]. As an example, in males with stable coronary disease randomized to sildenafil or placebo one hour prior to exercise, sildenafil did not increase the incidence of exercise-induced symptoms or the development or severity of exercise-induced ischemia [70].

Coadministration with nitrates contraindicated — In patients with CVD and sexual dysfunction who have been prescribed nitrates, we assess for frequency and need for their use.

●Patients who need to take daily nitrates – We avoid the use of PDE-5 inhibitors in individuals who regularly take nitrates and continue to need them for symptom management or treatment of other conditions.

This includes any form of nitroglycerin (eg, sublingual, transdermal, and spray formulations), isosorbide mononitrate or isosorbide dinitrate, and pentaerythritol tetranitrate or erythrityl tetranitrate. Patients should also avoid the use of PDE-5 inhibitors with amyl nitrate (ie, "poppers").

Combining nitrates and PDE-5 inhibitors risks inducing severe hypotension and syncope [54,60,71].

•Nitrates directly potentiate the vasodilatory effects of PDE-5 inhibitors. Both PDE-5 inhibitors and nitrates cause nitric oxide-induced vasodilation via cyclic guanosine monophosphate. (See "Nitrates in the management of chronic coronary syndrome".)

•Patients who were treated with isosorbide mononitrate or sublingual nitroglycerin prior to a dose of sildenafil experienced a significantly greater reduction in blood pressure compared with treatment with the nitrate alone (mean maximum reduction with isosorbide mononitrate plus sildenafil 52/29 mmHg versus nitrate alone 25/15 mm Hg; mean maximum reduction with sublingual nitroglycerin plus sildenafil 36/21 mmHg versus nitrate alone 26/12 mmHg) [72].

●Patients who use nitrates intermittently – Individuals who take nitrates intermittently can use PDE-5 inhibitors but should avoid concurrent use [31,71]. Patients should avoid using nitrates within 24 hours of taking shorter-acting PDE-5 inhibitors (sildenafil, vardenafil, avanafil) and 48 hours of taking long-acting PDE-5 inhibitors (tadalafil).

Coprescription of nitrates and PDE-5 inhibitors can be safe in this group of patients as long as they understand the importance of not using these medications concurrently [23,71]. As an example, a cohort study of almost 250,000 Danish patients with ischemic heart disease who were followed for 18 years found no association between coprescription of nitrates with PDE-5 inhibitors and the risk of major cardiovascular outcomes (ie, cardiac arrest, cardiogenic shock, MI, angina, ischemic stroke, or need for acute coronary angiography) [73].

●Patients who never or infrequently use nitrates – We consider deprescribing nitrates in individuals who are asymptomatic, never or infrequently use nitrates, and do not have a separate indication for nitrate therapy (eg, heart failure).

●Patients with acute chest pain – When patients present with acute chest pain, we ask if they have taken a PDE-5 inhibitor before we administer nitroglycerin. Nitrates should not be administered within 12 hours (or longer in patients with kidney or hepatic dysfunction) of avanafil, 24 hours of sildenafil or vardenafil, or 48 hours of tadalafil [31,71,74,75].

This approach is consistent with 2023 Princeton IV consensus guidelines on the use of PDE-5 inhibitors in individuals with CVD [23].

Coadministration with antihypertensive medications

●Use with alpha blockers – Lower urinary tract symptoms from benign prostatic hypertrophy commonly coexist with male sexual dysfunction. In individuals who want to take PDE-5 inhibitors who also require alpha-1 receptor antagonists, we typically use a uroselective alpha blocker, such as tamsulosin, rather than nonselective agents, such as doxazosin. We first ensure that these patients can tolerate a low-dose, uroselective alpha blocker (eg, tamsulosin 0.4 mg) without symptoms of lightheadedness or low blood pressure. They should then initiate a short-acting PDE-5 inhibitor at the lowest possible dose (eg, sildenafil 25 mg) and monitor closely for side effects [10].

Individuals who take nonselective alpha-blocking agents (eg, doxazosin) generally should not use PDE-5 inhibitors because this can lead to symptomatic hypotension [31,71]. In a small study, tadalafil potentiated the hypotensive effects of doxazosin but not tamsulosin [76].

●Can combine with antihypertensive medications – Patients can safely combine PDE-5 inhibitors with other classes of antihypertensive medications.

•In a study of patients using sildenafil, the adverse side effects of hypotension, dizziness, and syncope were not more common among those concomitantly taking antihypertensive medications compared with those who did not [77].

•Individuals with hypertension on either single-drug or combination regimens with most antihypertensive agents (eg, ACE inhibitors, angiotensin II receptor blockers, calcium channel blockers, beta blockers, and diuretics) generally tolerate PDE-5 inhibitors with only minor reductions in blood pressure [78,79].

•The decrease in systolic blood pressure observed with PDE-5 inhibitors is not more pronounced when given with antihypertensive drugs with vasodilator activity, such as amlodipine [80].

Caveats in other high-risk patient populations

●Heart failure, obstructive cardiomyopathy, and aortic stenosis – Clinicians should exercise extreme caution in prescribing PDE-5 inhibitors to individuals whose cardiac output depends on preload. This includes patients with hypertrophic obstructive cardiomyopathy (HCM) and some individuals with aortic stenosis and heart failure.

In individuals with HCM, the decrease in preload and afterload caused by PDE-5 inhibitors could increase outflow obstruction and potentially culminate in hemodynamic instability [81] (see "Hypertrophic cardiomyopathy: Morphologic variants and the pathophysiology of left ventricular outflow tract obstruction"). Patients with moderate to severe aortic stenosis may also be susceptible.

Individuals with heart failure with severe left ventricular dysfunction accompanied by low blood pressure may be adversely affected by even the modest reduction in blood pressure associated with PDE-5 inhibitors and should avoid their use if possible. (See "Drugs that should be avoided or used with caution in patients with heart failure", section on 'PDE-5 inhibitors'.)

●Patients at high risk of arrhythmia

•Vardenafil – We suggest that patients with congenital long QT syndrome or taking drugs that can cause the long QT syndrome (table 6) avoid the use of vardenafil [71]. Vardenafil (but not sildenafil or tadalafil) may slightly prolong the QT interval, although the clinical importance of this finding is uncertain [82].

•Sildenafil – At high doses, sildenafil exhibits class III antiarrhythmic properties (ie, prolongation of cardiac repolarization) [83]. Consequently, clinicians should use sildenafil with caution in patients at risk for arrhythmia who have concomitant hepatic or kidney impairment or are on concurrent therapy with another cytochrome P450 3A substrate/inhibitor (table 7).

Other pharmacotherapies for males with sexual dysfunction

●Testosterone – Testosterone replacement therapy can be used cautiously in males with CVD who have indications for androgen replacement (eg, hypogonadism). We suggest using testosterone gel for males with CVD who also have indications for androgen replacement.

A large, randomized noninferiority trial of males with established CVD (55 percent) or multiple CVD risk factors (45 percent) and established symptoms and laboratory evidence of hypogonadism found similar rates of cardiovascular events with testosterone replacement (transdermal gel), compared with placebo [84]. A prespecified subgroup analysis of males with established CVD also demonstrated comparable rates of cardiovascular events with testosterone replacement and placebo (HR 0.99, 95% CI 0.77-1.26). Testosterone replacement resulted in higher rates of nonfatal arrhythmias (5.2 versus 3.3 percent), including atrial fibrillation (3.5 versus 2.4 percent).

The use of testosterone replacement therapy in males with hypogonadism and risks in the general population are discussed separately. (See "Testosterone treatment of male hypogonadism".)

●Other treatments – Other treatment options for male sexual dysfunction can be pursued in patients with stable cardiac disease, including alprostadil intracavernosal injections, penile prostheses, and vacuum-assisted erection devices. PDE-5 inhibitors may be safer than alprostadil in this patient population. In an observational study of 16,548 males with coronary disease, use of PDE-5 inhibitors was associated with a lower risk of death than alprostadil [85]. The possibility of unmeasured confounding and small number of participants taking alprostadil (n = 1994) limit the certainty of these findings. (See "Treatment of male sexual dysfunction".)

●Over-the-counter products and supplements – We advise patients to avoid supplements and nonprescription medications to treat sexual dysfunction because surveillance studies suggest that some of these products may contain PDE-5 inhibitors [23].

Pharmacotherapy for sexual dysfunction in females

For genitourinary syndrome of menopause (vaginal atrophy) — Vaginal dryness and pain with intercourse are common symptoms of sexual dysfunction in females with CVD. Topical estrogen therapy and vaginal lubricants are considered safe to use in this population [10]. Treatment of genitourinary syndrome of menopause is discussed elsewhere. (See "Genitourinary syndrome of menopause (vulvovaginal atrophy): Treatment".)

For sexual interest/arousal disorder — Bupropion and flibanserin (for premenopausal patients only) can be used to treat sexual interest/arousal disorder in females with CVD. Bremelanotide, which is US Food and Drug Administration-approved for this indication in premenopausal females, can transiently increase blood pressure in some females and should not be used to treat sexual dysfunction in females with CVD. Although transdermal testosterone gel appears safe in males with CVD, it is less commonly used to treat sexual dysfunction in females, and safety in females with CVD is uncertain. Data on PDE-5 inhibitors are mixed, with some positive data on antidepressant-induced sexual dysfunction [23,86]. These medications are discussed separately. (See "Overview of sexual dysfunction in females: Management", section on 'Sexual interest/arousal disorder'.)

INFORMATION FOR PATIENTS — 

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Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Heart attack – Discharge instructions (The Basics)" and "Patient education: Coronary artery bypass graft surgery – Discharge instructions (The Basics)")

●Beyond the Basics topics (see "Patient education: Heart attack recovery (Beyond the Basics)" and "Patient education: Recovery after coronary artery bypass graft surgery (CABG) (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Addressing sexual concerns – Clinicians should routinely ask their patients with cardiovascular disease (CVD) about sexual concerns and function (table 1). Sexual dysfunction is common in individuals with CVD, and many patients have fears or concerns about engaging in sexual activity, particularly after an acute cardiac event (table 2). (See 'Discussing patients' sexual concerns' above.)

●Risk stratification for safety of sexual activity

•Patients with chronic cardiovascular disease – Clinicians should evaluate and risk stratify patients with CVD to determine their safety to engage in sexual activity (algorithm 1). Although sexual activity can modestly increase the risk of myocardial infarction (MI), most patients with CVD are at low risk of MI related to sexual activity. (See 'Low risk of MI for most patients' above.)

-Patients with stable disease and adequate exercise tolerance – Patients with asymptomatic or stable CVD who can exercise more than four (older patients) or six (younger patients) metabolic equivalents (METs) without symptoms or evidence of ischemia can safely engage in sexual activity. Such individuals are at low risk of MI associated with sexual activity. (See 'Asymptomatic coronary artery disease' above and 'Stable angina' above.)

-Patients with unstable or severe disease – Individuals with unstable or severe CVD (eg, unstable angina, New York Heart Association class IV heart failure, atrial fibrillation with rapid ventricular response) should defer sexual activity and the treatment of sexual dysfunction until their condition is stabilized and optimally managed. (See 'Acute coronary syndromes' above and 'Other disease-specific recommendations' above.)

-Patients with unknown exercise tolerance – Patients with unknown exercise tolerance at high risk of CVD (advanced subclinical atherosclerosis with unclear symptoms, recent MI, prior incomplete coronary revascularization, or chronic stable coronary disease) should generally undergo additional risk stratification with exercise testing. (See 'Risk stratification and modification' above.)

•After acute events – Individuals who have recovered from the acute event, are asymptomatic, and can tolerate at least four to six METs of activity can safely resume sexual activity at least one week after MI, two to three days after percutaneous coronary intervention, and six to eight weeks after cardiac surgery. (See 'Acute coronary syndromes' above and 'After coronary revascularization' above.)

●Phosphodiesterase 5 inhibitors to treat erectile dysfunction in males – In males with erectile dysfunction and CVD, we suggest the phosphodiesterase 5 (PDE-5) inhibitor sildenafil rather than other PDE-5 inhibitors (Grade 2C). Although other PDE-5 inhibitors appear safe and effective, sildenafil has a shorter duration of action and more extensive safety record in this population. Patients should avoid taking PDE-5 inhibitors within 24 to 48 hours of nitrate use. PDE-5 inhibitors should not be routinely used with nonselective alpha blockers and should be used cautiously with drugs that block cytochrome P450 3A and in individuals with active ischemia, high arrhythmia risk, hypertrophic obstructive cardiomyopathy, aortic stenosis, or heart failure with low blood pressure. (See 'Use of PDE-5 inhibitors in males with CVD' above.)

●Testosterone replacement therapy in males – In males with hypogonadism and CVD, we suggest using testosterone gel rather than other forms of testosterone, as this formulation has data regarding its safety specifically in males with CVD (Grade 2C). (See 'Other pharmacotherapies for males with sexual dysfunction' above.)

●Pharmacotherapy for females with CVD and sexual dysfunction – Females with sexual dysfunction caused by genitourinary syndrome of menopause can safely use topical (vaginal) estrogen. Limited data inform the safety of current medications for the treatment of sexual interest/arousal disorder in females with CVD, but potential options include bupropion; flibanserin (for premenopausal persons); and, possibly, PDE-5 inhibitors. (See 'Pharmacotherapy for sexual dysfunction in females' above.)

ACKNOWLEDGMENTS — 

The UpToDate editorial staff acknowledges Stephen E Kimmel, MD, MS, and William H Sauer, MD, who contributed to earlier versions of this topic review.