Wednesday, April 27, 2011

Hormonal Therapy For Prostate Cancer: Understanding The Risks To Your Heart

If you have been diagnosed with prostate cancer, chances are you have been told about hormonal therapy.  Nearly 70 years ago, the management of prostate cancer was revolutionized by the discovery that prostate cancer is fueled by the male hormone testosterone.  Prior to this discovery, numerous men languished in hospital beds suffering from the pain of advanced prostate cancer.  After the discovery, men with advanced prostate cancer started undergoing orchiectomy (surgical removal of the testicles).  Because the testicles naturally produce most of the testosterone in men, removing them effectively removes most of the testosterone from the body.  With the “food” gone, the prostate cancer moves much more slowly and sometimes decreases in size.  While not a cure, such hormonal manipulation has led to significantly decreased symptoms for men with advanced prostate cancer.

Hormonal therapy was further advanced about 30 years ago with the development of “medical castration.”  Rather than removing the testicles, doctors could give medicine which would effectively prevent the body from producing testosterone.  This approach was significantly more appealing for most men as it avoided the psychological trauma of castration.  Initially, medical castration or hormonal therapy was used just for men with prostate cancer which had spread to the bones and other distant organs.  Studies demonstrated that the treatment, although not a cure, could allow men with metastatic prostate cancer to live symptom free for many years.  More recently, the use of hormonal therapy has been further expanded to men with localized disease.  Numerous studies demonstrated that hormonal therapy given in combination with radiation therapy for men with locally advanced prostate cancer is superior to radiation alone.  As a result many doctors now give at least a short course of hormonal therapy at the start of radiation therapy while others give hormonal therapy up to 2 years following radiation therapy for men with localized disease.  Other doctors also give early hormonal therapy for men with a PSA recurrence after radical prostatectomy.  With these expanded indications, more and more men are currently treated with hormonal therapy. 

The problem with such widespread use of hormonal therapy is that this treatment modality, like all medicines, is no free lunch.  As more and more men have been treated with hormonal therapy, more and more risks have been discovered.  The risk of osteoporosis, for example, is very well known to urologists and patients alike and is often very carefully monitored and treated.  Recently, however, the very real impact of hormonal therapy on the heart has been demonstrated.  Studies have demonstrated that treatment with hormonal therapy often leads to metabolic changes such as increases in blood sugar and cholesterol.  As a result, a very real increase in heart attacks and heart related deaths have been attributed to the use of hormonal therapy.  While radiation oncologists and urologists are very well trained to evaluate and treat prostate cancer, they are generally not as great at looking at the big picture.  As a result, the treatment of prostate cancer often takes priority over heart health, particularly when a primary care doctor is not part of the decision making process.  The goal of this post is to review the real metabolic consequences of hormonal therapy and the subsequent heart risks that they then create.



Metabolic Consequences of Hormonal Therapy

  1. Blood Sugar:  The loss of testosterone and estrogen due to hormonal therapy has been demonstrated to cause a resistance to the hormone Insulin.  Insulin is the prime regulator of blood sugar in the body.  As a result, men who start hormonal therapy often demonstrate a rise in their blood sugar and Hemoglobin A1C (a measure of diabetes control).  As a result, studies have demonstrated that men undergoing hormonal therapy have a 28-50% HIGHER risk of developing diabetes than equally aged men not receiving the treatment.

  1. Lipids:  Hormonal therapy has also been demonstrated to have a significant impact on lipids (fats) in the blood stream.  One study evaluating men on hormonal therapy demonstrated that after about a year on therapy, these men demonstrated an increase in total cholesterol of 9% and an increase in triglycerides (fat in the bloodstream) of 26%. 

  1. Arterial Stiffness:  The decrease in testosterone experienced during hormonal therapy has also been thought to increase the stiffness of the arteries carrying blood to the heart.  This increased stiffness is thought to decrease blood flow to the heart and potentially cause a heart attack.

Hormonal Therapy and Risks to the Heart

With the metabolic changes mentioned above, it probably does not seem surprising that studies have demonstrated that taking hormonal therapy may pose a substantial risk to the heart.  Large studies ( 37,000- 73,000 men) have demonstrated that hormonal therapy results in a 16-19% increased risk of coronary artery disease, an 11-28% increased risk of heart attack, and a 16-35% increased risk of sudden death when compared with men not undergoing the treatment.  Another study demonstrated a 20% increased risk of heart complications within 1 year of starting hormonal therapy.  Not surprisingly, higher risk was seen in older men, with one study demonstrating that men over age 65 undergoing hormonal therapy have over 2 times the risk of heart related death within 5 years of starting therapy (5.5% vs 2%) as compared with those that do not undergo the therapy.

The impact of hormonal therapy for men with preexisting heart disease is even more dramatic.  A recent study published in the Journal of the American Medical Association studied men with localized prostate cancer undergoing 4 months of hormonal therapy in combination with radiation therapy.  The study specifically looked at men with a prior history of a heart attack or heart failure.  In this group, the study found that 26% of men undergoing hormonal therapy died within an average of 5 years as compared to 11% of men who did not undergo the therapy.  That represents TWICE the risk of death for men with prior heart disease who underwent hormonal therapy plus radiation therapy as compared to the men that underwent radiation therapy alone.  Interestingly, the authors of the study did not demonstrate an increased risk of death for those men undergoing hormonal therapy who did not have significant underlying heart disease or risk factors for heart disease. 

Take Home Message

So what do we conclude from this worrisome information?  Should hormonal therapy no longer be offered to men with prostate cancer?  Should men already on hormonal therapy stop the treatment?  Of course not.  Hormonal therapy has been vital in the fight against prostate cancer, particularly for men with advanced disease.  Instead, this data should make us rethink who should receive hormonal therapy and what precautions should be taken when the therapy is administered.  The problem with many urologists and radiation oncologists is that they often get caught up with prostate cancer and, sometimes, miss the big picture.  While they see the potential benefits of hormonal therapy in terms of prostate cancer, they don’t pay enough attention to the impacts of this treatment on other vital aspects of a patient’s health.  As a result, as the patient, you need to make sure that a few steps get taken prior to proceeding with hormonal therapy:

  1. Tailor Your Prostate Cancer Treatment To YOU:  Not ALL men need hormonal therapy to treat prostate cancer, particularly localized prostate cancer that has not spread. While, indeed, studies have demonstrated improved outcomes with the addition of hormonal therapy to radiation therapy for aggressive, localized disease, the extent of these benefits need to be weighed against the potential risks.  For example, older men with significant heart problems (or risk factors for heart disease) and low grade prostate cancer, may want to consider avoiding hormonal therapy in conjunction with radiation.  They will probably do just as well from the cancer standpoint while avoiding the heart risks.  At the very least, you should have your doctor go over the specific risks and benefits of hormonal therapy in your particular situation.

  1. Assemble Your Team: Some men really need hormonal therapy in treating their prostate cancer.  If you are one of those men, make sure that your ENTIRE medical team is involved.  Most men who undergo hormonal therapy are managed for this by just their urologist and/or radiation oncologist.  The problem with this arrangement, as I mentioned before, is that while these specialists are great at managing prostate cancer, they are not quite as adept at taking care of diabetes, cholesterol, and heart disease.  As a result, if you are started on hormonal therapy, you may want to make sure that you are followed by your primary doctor as well.  Your primary doctor can check baseline labs like blood sugar and cholesterol levels as well as a baseline blood pressure. He or she can then check on you every 3-4 months with repeat labs and exams to see if you are experiencing any of the metabolic changes described above and make appropriate adjustments to your other medicines, if necessary.  If you already have heart disease, you may want to discuss hormonal therapy with your cardiologist prior to starting and to have him or her follow you to look for any early changes to your heart as a result of the therapy. Because the damage done by hormonal therapy usually occurs in the first year of treatment, this rigorous follow up only needs to be carried out for a short period of time.  Having a COMPLETE team follow you, however, may be the key to avoiding serious heart problems for years to come.

  1. Change Your Lifestyle:  I am sure most if not all of you have heard of simple ways you can decrease your risk of developing heart disease.  These lifestyle modifications become particularly important when on hormonal therapy.  Simple changes to your diet like decreasing the amounts of fat and sugar you consume can go a long way in battling the metabolic changes brought about by hormonal therapy.  In addition, any amount of aerobic exercise such as walking can decrease the risk of heart problems in the future.  As always, make sure you carry out any diet or exercise regimens under the supervision of your doctor, particularly if you already have heart disease.



As with many other aspects of prostate cancer treatment I have discussed on this blog, hormonal therapy, again, proves that there is no such thing as a free lunch.  While hormonal therapy has been shown to be beneficial for many patients with varying extents of prostate cancer, this benefit does not come without risk.  The development of significant heart disease can negate any prostate cancer benefits in SOME men.  As a result, before agreeing to hormonal therapy, make sure that your doctor weighs the relative risks and benefits in YOUR case.  If you and your doctor conclude that hormonal therapy is right for you, make sure that you put together the right team and plan to manage the potential risks.  As a urologist, I am committed to battling prostate cancer with all the medical and surgical tools available to me.  As a patient, you need to make sure that your doctors keep your overall health in mind while fighting this battle.


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This blog is not a medical practice and cannot provide specific medical advice. This information should never be used to replace or discount the medical advice you receive from your physician.

7 comments:

  1. Does orchidectomy have the same side effects as horomonal therapy?

    Does Abiraterone have the same side effects as hormonal theray?

    thank you
    JJ Mermod

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  2. jean-jacques: generally, the side effects of orchiectomy are similar to those of hormonal therapy. A certain type of hormonal therapy, the non-steroidal antiandrogens( i.e. Casodex) do not have as many cardiac risks but are also not as effective when given as monotherapy. As for Abiraterone, it also has cardiac effects as well as effects on the liver and on fluid retention. Remember, though, that Abiraterone is usually given after standard hormonal therapy has already failed and the side effects of hormonal therapy have already taken effect.

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  3. Doc - any thoughts about alternatives to traditional hormone treatments, such as DES or estradiol patches (transdermal estrogen)? Maybe fewer side effects?

    Also, for those who are going to take an LHRH agonist, any thoughts on how to decide which one to use? (Does it matter, so long as the one you pick is keeping T level at or below castrate level?)

    Finally, what are your thoughts on ADT3 (combination of LHRH agonist, antiandrogen, and 5-alpha-reductase inhibitor)? Seems to me some independent prostate cancer specialist oncologists have been using this, but the types of institutions that look for level one evidence before making a treatment recommendation may be more reluctant becuase of the absence of randomized controlled studies showing ADT3 works better than alternatives. Am I right about that? Any thoughts on the merits of ADT3?

    Thanks.

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  4. When HT is used as an adjunct to RT or SRT, is there any agreement as to the most effective length of time HT is administered? Is two years any better than 6 months? This has MAJOR QL ramifications.

    I have real problems with Radiation Oncologists putting their patients on HT for two years, completely masking whether the RT worked..When they take you off and discover the PSA quickly doubling, how much time before the PC becomes refractory? I guess one just has to accept the studies that show the combined treatment is more effective...

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  5. chamorgadol: estrogen was actually the first hormone therapy tried. It was stopped after a VA study demonstrated significantly high rates of blood clots and heart attacks, even more so than the LHRH agonists. As for the LHRH agonists, it is really dealer's choice. I am not aware of one being superior to another. That being said, nonsteroidal antiandrogens(Casodex) have been shown to be inferior to LHRH agonists when given in isolation. As for combo therapy, there have been conflicting studies, none of which are excellent. Until better evidence exists, I would not subject my patients to the added risks of the additional therapy without a proven benefit.

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  6. Fairwind: a short answer to your question is no. There are excellent but conflicting studies. European studies tend to favor long term therapy(36 months) while American studies have advocated 6 months. Several readers have asked me this question and I will dedicate my next post to at least presenting all of the data so that you can see the data for yourselves and get a glimpse of what urologists and radiation oncologists rely on in making their decisions.

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  7. <>

    My sense was that maybe the blood clot problem was less severe with transdermal estrogen, and that some of the side effects of LHRH agonists, such as hot flashes and diminished bone mineral density, where less likely to occur with estradiol. My guess is most docs do not even discuss this option with their patients.

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