Testosterone and prostate cancer: an evidence-based review of pathogenesis and oncologic risk

Testosterone and prostate cancer: an evidence-based review of pathogenesis and oncologic risk

Testosterone plays a central role in male development and health. Likewise, androgen deficiency, or hypogonadism, is associated with a variety of symptoms including decreased energy, diminished libido and erectile dysfunction, among others. Male androgen levels steadily decline with age, and, in a subset of symptomatic older men, can result in late-onset hypogonadism (LOH). Over the last decade, increased awareness of hypogonadism among patients and providers has led to a significant rise in the use of testosterone replacement therapy (TRT) for hypogonadism, and especially in LOH. Accompanying the rise in TRT are concerns of potential adverse effects, including cardiovascular risks and the promotion of prostate cancer. The ‘androgen hypothesis’ asserts that prostate cancer development and progression is driven by androgens, and thus TRT has the theoretical potential to drive prostate cancer development and progression. In this review, we examine existing data surrounding testosterone and prostate cancer. There is significant evidence that androgens promote prostate cancer in experimental systems. However, there is no clear evidence that elevations in endogenous testosterone levels promote the development of prostate cancer in humans. As a result of experimental and historical data on the progression of prostate cancer following TRT, there has been widespread belief that TRT will promote disease progression in prostate cancer patients. Despite these fears, there are a growing number of studies demonstrating no increase in prostate cancer incidence among men on TRT. Furthermore, in studies involving a small number of patients, there has been no discernable increase in disease progression in prostate cancer patients on TRT. While data from large, prospective, randomized, controlled trials are absent, TRT in select prostate cancer patients is likely safe. In the end, the use of TRT in prostate cancer patients is still considered experimental and should only be offered after well-informed shared decision making and with close monitoring.

Erectile Dysfunction: an Early Sign of Cardiovascular Disease

Identification of vasculogenic erectile dysfunction (ED) should be used to focus preventive efforts on reducing the risk of future cardiovascular events. For younger men 40 to 60 years old believed to have predominantly vasculogenic ED, we recommend an algorithm for further assessment of cardiovascular disease modified from the 2013 American College of Cardiology (ACC)/American Heart Association (AHA) risk assessment guidelines. We propose that all men with confirmed vasculogenic ED and no overt cardiovascular disease symptoms undergo noninvasive evaluation using a coronary artery calcium (CAC) score. For men with low to intermediate risk (atherosclerotic cardiovascular disease (ASCVD) risk score 0–10 %), CAC score can be used to guide decisions regarding initiation of therapies, and in patients with high CVD risk, after referral to a cardiologist for a full evaluation, CAC can be used to guide intensity of therapies. We recommend that men with ED be evaluated using this modified risk assessment to incorporate factors otherwise excluded from the ACC/AHA calculator. © 2015, Springer Science+Business Media New York.

All Men with Vasculogenic Erectile Dysfunction Require a Cardiovascular Workup

All Men with Vasculogenic Erectile Dysfunction Require a Cardiovascular Workup

An association between erectile dysfunction and cardiovascular disease has long been recognized, and studies suggest that erectile dysfunction is an independent marker of cardiovascular disease risk. Therefore, assessment and management of erectile dysfunction may help identify and reduce the risk of future cardiovascular events, particularly in younger men. The initial erectile dysfunction evaluation should distinguish between predominantly vasculogenic erectile dysfunction and erectile dysfunction of other etiologies. For men believed to have predominantly vasculogenic erectile dysfunction, we recommend that initial cardiovascular risk stratification be based on the Framingham Risk Score. Management of men with erectile dysfunction who are at low risk for cardiovascular disease should focus on risk-factor control; men at high risk, including those with cardiovascular symptoms, should be referred to a cardiologist. Intermediate-risk men should undergo noninvasive evaluation for subclinical atherosclerosis. A growing body of evidence supports the use of emerging prognostic markers to further understand cardiovascular risk in men with erectile dysfunction, but few markers have been prospectively evaluated in this population. In conclusion, we support cardiovascular risk stratification and risk-factor management in all men with vasculogenic erectile dysfunction.

The assessment of vascular risk in men with erectile dysfunction: the role of the cardiologist and general physician

The assessment of vascular risk in men with erectile dysfunction: the role of the cardiologist and general physician

Erectile dysfunction (ED) and cardiovascular disease (CVD) share risk factors and frequently coexist, with endothelial dysfunction believed to be the pathophysiologic link. ED is common, affecting more than 70% of men with known CVD. In addition, clinical studies have demonstrated that ED in men with no known CVD often precedes a CVD event by 2-5 years. ED severity has been correlated with increasing plaque burden in patients with coronary artery disease. ED is an independent marker of increased CVD risk including all-cause and especially CVD mortality, particularly in men aged 30-60 years. Thus, ED identifies a window of opportunity for CVD risk mitigation. We recommend that a thorough history, physical exam (including visceral adiposity), assessment of ED severity and duration and evaluation including fasting plasma glucose, lipids, resting electrocardiogram, family history, lifestyle factors, serum creatinine (estimated glomerular filtration rate) and albumin:creatinine ratio, and determination of the presence or absence of the metabolic syndrome be performed to characterise cardiovascular risk in all men with ED. Assessment of testosterone levels should also be considered and biomarkers may help to further quantify risk, even though their roles in development of CVD have not been firmly established. Finally, we recommend that a question about ED be included in assessment of CVD risk in all men and be added to CVD risk assessment guidelines.

Erectile Dysfunction and Testosterone Deficiency as Gender Specific Markers of Cardiometabolic Risk in Minority and Non-Minority Men: Potential Role of Social Determinants

Evaluation of cardiometabolic risk has become vital in the primary prevention of adverse vascular events (coronary artery disease, heart attack, stroke or congestive heart failure), particularly in younger middle-aged men (aged 40–60 years old). To discern the prevalence of events in these men, clinicians often stratify cardiovascular risk and treat according to traditional Framingham risk criteria. The Framingham Risk Score (FRS) is a useful and often used tool for estimating the 10-year risk for myocardial infarction or coronary death of an individual. It is supported by the 2010 ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic adults. The FRS is based on data obtained from the Framingham Heart Study and it incorporates age, gender, total and high-density lipoprotein (HDL) cholesterol, smoking, systolic blood pressure (BP), and use of antihypertensive medications. However, it is important to note that the Framingham study includes few data from patients <40 years of age and few minority patients (African American and Hispanic). Thus, the FRS may not adequately estimate risk in younger patients and minorities. The FRS also lacks some important risk factors (e.g., family history, fasting glucose, testosterone) that should be considered when estimating cardiovascular risk in the man with ED. It is evident that the traditional Framingham risk assigned to intermediate and low-risk men will miss several of these individuals deemed at high “cardiometabolic risk”, also known as residual cardiovascular risk. This review will elaborate the definition of cardiometabolic risk, and apply the use of erectile dysfunction and testosterone deficiency as gender-specific surrogate markers for cardiovascular risk stratification in men in addition to the traditional Framingham-based markers. Lastly, it will examine minority men's health, racial differences and the need to include the role of social determinants in future research studies of cardiovascular risk.

The Princeton III Consensus Recommendations for the Management of Erectile Dysfunction and Cardiovascular Disease

The Princeton III Consensus Recommendations for the Management of Erectile Dysfunction and Cardiovascular Disease

The Princeton Consensus (Expert Panel) Conference is a multispecialty collaborative tradition dedicated to optimizing sexual function and preserving cardiovascular health. The third Princeton Consensus met November 8 to 10, 2010, and had 2 primary objectives. The first objective focused on the evaluation and management of cardiovascular risk in men with erectile dysfunction (ED) and no known cardiovascular disease (CVD), with particular emphasis on identification of men with ED who may require additional cardiologic work-up. The second objective focused on reevaluation and modification of previous recommendations for evaluation of cardiac risk associated with sexual activity in men with known CVD. The Panel’s recommendations build on those developed during the first and second Princeton Consensus Conferences, first emphasizing the use of exercise ability and stress testing to ensure that each man’s cardiovascular health is consistent with the physical demands of sexual activity before prescribing treatment for ED, and second highlighting the link between ED and CVD, which may be asymptomatic and may benefit from cardiovascular risk reduction.