Androgen Deprivation Therapy Tied to Increased Cardiovascular Death

Some patients diagnosed with prostate cancer undergo androgen deprivation therapy (ADT) to treat the disease. The therapy is commonly used to treat locally advanced prostate cancer or cancer that has spread too far to be treated with radiation or surgery. ADT is an umbrella term for the suppression of androgens. Most commonly, ADT administers gonadotropin-releasing hormone (GnRH) agonists that suppress androgens. Other drug classes for this therapy include antagonists and antiandrogen receptor agents.

Androgens—testosterone and dihydrotestosterone (DHT) are two primary ones—can activate prostate cancer cells to grow. ADT is a fast-acting method to reduce or stop that action by robbing cancer cells of fuel.

ADT is a proven method to help patients treat prostate cancer symptoms. A recent study, however, suggests it may cause significant health problems within a few years of its use.

The study's findings

A recent five-year study by researchers in Lithuania indicated an association between ADT and the increased risk of cardiovascular disease (CVD) and death among prostate cancer patients. The research team, led by Justinas Jonušas, performed a retrospective cohort study of 13,343 prostate cancer patients ages 40 to 79 from January 2012 to December 2016.

"The study found that androgen deprivation therapy as a prostate cancer therapy is associated with increased cardiovascular-related mortality risks, especially with ischemic heart disease and stroke, compared to other patients with prostate cancer that were treated with non-androgen deprivation therapy," said Aleece Fosnight, M.S.P.A.S., a board-certified physician assistant and a medical advisor at Aeroflow Urology in Arden, North Carolina, in an email conversation.

Additionally, patients who had the highest cardiovascular-related mortality rate were between 70 and 79 years old when treated with ADT.

"This is particularly interesting, as androgen deprivation therapy is considered the main therapy for [patients] with advanced, metastatic and high-risk localized prostate cancer," Fosnight added. "This helps us better understand how testosterone can be cardioprotective for AMAB [assigned male at birth] individuals."

Possible implications

The study's results create a concern for potential cardiovascular health problems for patients who continue to use ADT. Androgen ablation, another term for ADT, has been known to increase symptoms associated with chronic health conditions. These include type 2 diabetes, stroke, myocardial infarction and cardiovascular disease.

"The mechanism of heart disease with androgen ablation is increased visceral adipose tissue, insulin resistance and atherosclerotic plaque growth," said Russel Williams, M.D., the founder and CEO of the Y Factor, a men's urology and fertility practice in Houston, in an email conversation. "Since men can live 10 years on androgen deprivation therapy, comorbid health conditions like heart disease become significant sources of morbidity."

The significance of the relationship between ADT and CVD

Results of the study suggest a significant difference in the cardiovascular mortality rates among prostate cancer patients using ADT compared to non-ADT patients. In addition, there was a twofold increase in the risk of cardiovascular-related mortality in the research team's unadjusted and adjusted Cox proportional-hazards model. This model is a statistical tool used to investigate the association between the survival time of patients and one or more predictor variables.

"According to the study findings, the increased cardiovascular risk was almost twofold with the group treated with antiandrogen deprivation therapy compared to those with other treatment therapy," Fosnight said. "This is a significant increase and should be counseled with patients receiving antiandrogen therapy."

Immediate risks vs. long-term outcomes

Does the immediate threat of prostate cancer outweigh the risks of potential future cardiovascular death?

The presumed dangers of ADT compared with those of prostate cancer vary with each case. That's why physicians look at whether the patient is in the advanced stages of the disease and their age when they begin ADT.

One of the study's findings was surprising: There was no association between a higher risk of cardiovascular death during the first year after prostate cancer diagnosis for men receiving ADT treatment. The research team hypothesized that this finding is due to ADT primarily being administered to patients in the advanced stages of prostate cancer.

Men diagnosed in the earlier stages of prostate cancer often receive other types of treatment, such as radiation therapy or radical prostatectomy, rather than ADT. However, the longer a patient is on ADT, the higher their risk of cardiovascular death within the first four years of treatment for prostate cancer.

Likewise, another finding from the study suggested the risk of cardiovascular death due to ADT is higher among older patients with prostate cancer. The study's results show an almost fivefold increase in cardiovascular-related mortality in patients ages 65 and older who received ADT treatment.

For older patients with prostate cancer, hormone therapy may pose more risks than cancer. Therefore, the researchers suggest older patients be screened before beginning ADT treatment. This is a crucial point to emphasize because ADT is an important option for patients with advanced prostate cancer and should be discussed with a doctor on an individual basis.

"The authors recommend that ADT be started on men with advanced prostate cancer on a case-by-case basis," Williams said. "There is less benefit of starting ADT on older men with cardiac risk factors with a lower volume of metastasis versus younger men with metastatic disease."

ADT is a standard treatment method for prostate cancer patients. However, the risks associated with this hormone therapy may cause more harm than cancer itself. Therefore, depending on the cancer stage and the patient's age, screening tests should be performed for ADT before treatment.