What Cardiovascular Risks Does Androgen Deprivation Therapy Cause for Prostate Cancer Patients?

Research-informed explainer — last updated April 12, 2026

Androgen deprivation therapy is the backbone of prostate cancer treatment for hundreds of thousands of men. But ADT suppresses testosterone to near-zero levels — and testosterone is cardioprotective. Clinical evidence shows that men on ADT face meaningfully higher rates of heart attack, stroke, diabetes, and sudden cardiac death. Yet most urology practices don't routinely co-manage cardiovascular risk during ADT, and many patients aren't warned before they start. This is a second-opinion article for men on ADT who haven't seen a cardiologist, haven't had a baseline cardiovascular workup, and haven't been offered a conversation about statins or blood pressure management.

This explainer draws on research from three urologists in the Convene directory. Neal Shore at Grand Strand Medical Center was a co-investigator on the ARCHES trial, the phase III randomized study that established enzalutamide plus ADT as the standard regimen for metastatic hormone-sensitive prostate cancer. Paul Morris at Northeast Alabama Regional Medical Center has contributed to research on testosterone deficiency and cardiovascular mortality — including data showing that low serum testosterone is independently associated with increased mortality in men with coronary heart disease. Christopher Kane, Professor of Urology at UC San Diego, contributed to both the NCCN Clinical Practice Guidelines for Prostate Cancer and the AUA/ASTRO guidelines for clinically localized prostate cancer, which now explicitly recommend cardiovascular risk assessment and monitoring during ADT.

What is androgen deprivation therapy?

ADT is a broad term for treatments that reduce testosterone to castrate levels — typically defined as below 50 ng/dL, compared to normal levels of 300 to 1,000 ng/dL in adult men.

The most commonly used agents are GnRH agonists — leuprolide (Lupron) being the most familiar. These drugs initially cause a surge of testosterone before shutting down production entirely, which is why short-term antiandrogen coverage is needed at the start. They are typically given as depot injections every one, three, or six months.

GnRH antagonists — degarelix (Firmagon) — work differently. They block the GnRH receptor directly without the initial testosterone flare, achieving castrate levels within days rather than weeks. A 12-month comparative randomized study co-authored by Neal Shore showed that degarelix achieved testosterone and PSA suppression significantly faster than leuprolide, without requiring antiandrogen supplements to prevent clinical flare [2].

Next-generation antiandrogens — enzalutamide (Xtandi) and abiraterone (Zytiga) — work further downstream. They don't suppress testosterone production the way GnRH agents do; instead, they block androgen signaling even at castrate testosterone levels. The ARCHES trial, a randomized phase III study with Neal Shore as a co-investigator, compared enzalutamide plus ADT against placebo plus ADT in men with metastatic hormone-sensitive prostate cancer. Enzalutamide significantly reduced the risk of metastatic progression or death — establishing combination therapy as the current standard for most men with hormone-sensitive metastatic disease [1].

All of these agents — GnRH agonists, GnRH antagonists, and next-generation antiandrogens — carry the same underlying cardiovascular risk: prolonged suppression of testosterone.

Why does suppressing testosterone affect the heart?

Testosterone is not just a sex hormone. It plays a significant role in maintaining vascular health — specifically in preserving endothelial function, the ability of blood vessel walls to dilate and regulate blood flow appropriately.

When testosterone falls to castrate levels, several things happen simultaneously:

• Endothelial cells lose a key vasodilatory signal, leading to stiffened, less responsive blood vessels
• Insulin sensitivity decreases, driving higher blood glucose and eventually diabetes or pre-diabetes
• Body composition shifts — men on ADT typically gain fat mass (especially visceral fat) and lose lean muscle within months
• LDL cholesterol and triglycerides rise; HDL cholesterol falls
• Inflammatory markers increase

Research on low serum testosterone and cardiovascular outcomes, including work contributed to by Paul Morris, has shown that testosterone deficiency is independently associated with increased mortality in men with existing coronary heart disease [4]. A European Society of Cardiology consensus paper on endothelial function — also contributed to by Paul Morris — established that endothelial dysfunction is a measurable, clinically meaningful intermediate step on the path from cardiovascular risk factors to overt heart disease, and that it reverses when pathological stimuli are removed [3]. In the case of ADT, the stimulus is not removed — it is the treatment itself, often maintained for months to years.

What are the specific cardiovascular risks?

Clinical data has now accumulated over more than a decade to characterize the cardiovascular hazards of ADT:

• Myocardial infarction (heart attack): Studies have reported risk increases of approximately 20–30% in men on GnRH agonist therapy compared to prostate cancer patients not on ADT, with higher absolute risk in men who already have cardiovascular disease.
• Stroke: Risk of stroke appears similarly elevated, with some population-based studies reporting hazard ratios in the range of 1.2 to 1.6 in men on ADT versus age-matched controls.
• Sudden cardiac death: Risk of sudden cardiac death is increased, particularly in men with pre-existing cardiac arrhythmias or QT prolongation — a known effect of some ADT regimens.
• Diabetes and metabolic syndrome: Up to 40% of men develop diabetes or pre-diabetes within a year of starting ADT. Metabolic syndrome — the cluster of abdominal obesity, high triglycerides, low HDL, high blood pressure, and high blood glucose — develops in a substantial proportion of men within three to six months.
• Atrial fibrillation: Some analyses have found significantly higher rates of atrial fibrillation among men on ADT, which independently increases stroke risk.

The risk profile is not uniform across all ADT regimens. There is emerging evidence that GnRH antagonists like degarelix may carry a lower cardiovascular risk than GnRH agonists like leuprolide — particularly in men with pre-existing cardiovascular disease — possibly because they avoid the initial testosterone flare and have different downstream effects on the cardiovascular system. This remains an area of active research.

What do the guidelines say?

Both major guideline bodies in urology now explicitly address cardiovascular risk during ADT — and both recommend proactive monitoring.

The NCCN Clinical Practice Guidelines in Oncology for Prostate Cancer, to which Christopher Kane contributed, include recommendations to assess and manage cardiovascular risk factors in men undergoing ADT [5]. The AUA/ASTRO guidelines for clinically localized prostate cancer, co-developed by Kane, similarly address the cardiovascular monitoring needs of men on prolonged hormonal therapy [6].

Specific guideline-recommended practices include:

• Baseline cardiovascular risk assessment before initiating ADT
• Monitoring blood glucose and HbA1c during ADT (to detect diabetes)
• Blood pressure monitoring
• Lipid panel monitoring
• Referral to cardiology for men with pre-existing cardiovascular disease or significant risk factors
• Discussion of statin therapy and antihypertensive medications when indicated

The gap between what guidelines recommend and what happens in practice is real. Urology visits are focused on cancer — PSA trends, imaging, treatment decisions, and side effect management. Cardiovascular co-management is not always part of the urology workflow, and many patients are discharged into ADT without a plan for the metabolic and cardiac consequences.

Who is at highest risk?

Not every man on ADT will have a cardiac event. Risk is highest in men who combine ADT with pre-existing vulnerabilities:

• Pre-existing cardiovascular disease — prior heart attack, stent, bypass surgery, heart failure, or stroke
• Older age — men over 65 have a substantially higher baseline cardiovascular risk, and ADT compounds it
• Metabolic syndrome or type 2 diabetes at baseline
• Hypertension — already present in a large proportion of men with prostate cancer given the age overlap
• Obesity — especially visceral adiposity, which accelerates the metabolic shifts caused by testosterone suppression
• Long duration of ADT — men on continuous ADT for two or more years face a longer cumulative exposure to castrate testosterone levels than men on intermittent or short-course ADT
• Next-generation antiandrogens added to ADT — enzalutamide and abiraterone are effective but further suppress androgen signaling, and their long-term cardiovascular profile in the real world is still being characterized

What patients should do

ADT is often the right treatment — and for many men with advanced or high-risk prostate cancer, the benefit to cancer control far outweighs the cardiovascular risk. The goal is not to avoid ADT. It is to not receive ADT without a cardiovascular risk plan.

Before starting ADT:

• Ask your urologist for a baseline cardiovascular workup — at minimum a blood pressure reading, fasting glucose or HbA1c, and a lipid panel
• If you have any pre-existing cardiovascular disease, ask for a referral to a cardiologist before starting
• Discuss your baseline metabolic syndrome risk

During ADT:

• Make sure someone — your urologist, primary care physician, or cardiologist — is monitoring your blood glucose, blood pressure, and lipids on a regular schedule (typically every 3 to 6 months)
• Ask whether statin therapy is appropriate given your lipid profile
• Ask whether your blood pressure warrants treatment or adjustment
• Consider cardiac rehabilitation or structured exercise — physical activity during ADT has been shown in clinical studies to blunt the metabolic effects of testosterone suppression

Questions to bring to your next urology visit:

• "Will you refer me to a cardiologist before I start ADT?"
• "What is my baseline cardiovascular risk, and how will we monitor it during treatment?"
• "Given my cardiac history, is a GnRH antagonist like degarelix a better choice than a GnRH agonist?"
• "Should I be on a statin? What about a blood pressure medication?"
• "Who on my care team is responsible for managing my cardiovascular health while I'm on ADT?"

The bottom line

ADT is a powerful and often necessary treatment for prostate cancer. But suppressing testosterone to castrate levels carries real cardiovascular consequences — increased risk of heart attack, stroke, diabetes, atrial fibrillation, and sudden cardiac death — that are now well-documented in the research literature and acknowledged in NCCN and AUA/ASTRO guidelines. Most men starting ADT should have a baseline cardiovascular assessment, and men with pre-existing heart disease should see a cardiologist before treatment begins. If your care team has not discussed cardiovascular monitoring with you, that is the conversation to start.