Sunday, April 8, 2012

Hot Flashes and Prostate Cancer: Treating One of the Most Dreaded Side Effects of Androgen Deprivation Therapy

One of the earliest and most bothersome side effects of androgen deprivation therapy for prostate cancer is the hot flash.  Very similar to those experienced by women during menopause, hot flashes can be debilitating for men receiving medications such as Lupron.  Many are too embarrassed by hot flashes to even mention them to their physician.  Others don’t discuss them because they feel that these hot flashes cannot be treated or prevented.  In reality, this could not be further from the truth.  In this post, I will describe hot flashes and discuss what causes them.  In addition, I will review the most common medications employed to prevent and treat hot flashes experienced by men undergoing androgen deprivation therapy for prostate cancer.

What Is a Hot Flash?

A hot flash is a sudden overwhelming sensation of warmth usually experienced in the face, neck, upper chest and back.  This feeling is often accompanied by redness or blotching of the skin as well as heavy sweating.  This constellation of symptoms can occur to varying degrees, with some being so severe that they require a change of clothing or a shower.  Other associated symptoms can include nausea, rapid heartbeat, anxiety, and even trouble breathing.  Hot flashes can last from less than 5 minutes to over 30 minutes.  They can also occur with varying frequency, from once in a few days to several times per hour.

Why Does Androgen Deprivation Therapy Cause Hot Flashes?

Men undergoing androgen deprivation therapy (ADT) with medicines such as Lupron to treat their prostate cancer often get hot flashes.  In fact, studies have demonstrated that 60-80% of men undergoing ADT experience hot flashes at some point during treatment.  For most men, this first occurs within the first few months of treatment .  Interestingly, nearly a third of men who experience hot flashes during ADT for prostate cancer state that these symptoms are the most debilitating side effects of the treatment.  Nearly half of men experiencing hot flashes report a significant decrease in their quality of life.

Recent research has helped determine why men undergoing ADT actually experience hot flashes.  As you may remember from my previous post,  ADT fights prostate cancer by removing its food, testosterone, from the blood stream.  It turns out that testosterone, like other sex hormones, is an important regulator of the “thermostat” of the human body.  This “thermostat” is actually located in a part of the brain called the hypothalamus.  By causing a rapid drop of testosterone in the bloodstream, ADT confuses the “thermostat.”  Without its usual input from testosterone, the “thermostat” believes that the body is too hot.  As a result, the “thermostat” tries to cool the body off by making the blood vessels near the skin dilate, which allows for the release of heat on the skin surface.  This, in turn, leads to the characteristic blotching of the skin, feeling of warmth, and perspiration. 

How Do You Treat Hot Flashes?

1.     Hormonal Treatments:  As you would imagine, if a lack of hormones is the cause of hot flashes, replacing these hormones can help to treat these bothersome symptoms.  Certainly, we cannot simply replace the testosterone removed by ADT as this would defeat the purpose of the treatment: starving the prostate cancer.  However, studies have shown that other hormones, aside from testosterone, can also be used to regulate the “thermostat” and, thus, prevent hot flashes.  The first of these hormones to be tested was the female hormone, estrogen.  While estrogen did, indeed, reduce the incidence of hot flashes, it also increased the incidence of life threatening blood clots and painful breast tenderness.  As a result, estrogen has not been used as a mainstream treatment for hot flashes.  Other hormones, however, have been demonstrated to improve hot flashes while avoiding the risks of estrogen.  Two of the most popular treatments for hot flashes are derived from just such a hormone: progesterone.

A.     Megestrol Acetate – A study of 66 men undergoing ADT for prostate cancer were given either Megestrol Acetate (20 milligrams twice a day) or a placebo(sugar pill) for 4 weeks.  The study found that 79% of men receiving Megestrol Acetate reported a 50% decrease in hot flashes as opposed to only 12% of men receiving placebo pills.  The time to achieve the maximal effect of the drug was 2-3 weeks and the most common side effects were weight gain, fluid retention, and headaches.

B.     Medroxyprogesterone Acetate – A study of over 100 men undergoing ADT for prostate cancer were given Medroxyprogesterone Acetate (20 milligrams daily) for 4 weeks.  The study reported that 84% of men demonstrated a greater than 50% improvement in hot flashes while 37% enjoyed a complete resolution of hot flash symptoms.  Side effects of the medication included intestinal upset, water retention, and increased blood pressure.
2.     Non-Hormonal Treatments:  As more research has been carried out about hot flashes, studies have found that hormones are not the only substances in the body that control the “thermostat.”  These discoveries have provided more treatment options for men with prostate cancer suffering from hot flashes from ADT.

A.     Venlafaxine – Also known as Effexor, this drug is part of a class of antidepressant drugs known as serotonin norepinephrine reuptake inhibitors (SNRI).  The utility of this drug for treating hot flashes was discovered when postmenopausal women taking Venlafaxine for depression were found to have fewer and less intense hot flashes.  Subsequent studies confirmed the benefit of this drug in treating hot flashes in men treated with ADT.  One small study of 16 men demonstrated that taking 25 milligrams of Venlafaxine daily for 4 weeks decreased hot flashes by 50% in 63% of men.  A larger study of 97 men taking 75 milligrams of Venlafaxine daily confirmed the benefit, demonstrating a 47% decrease in hot flashes.  Of note, however, this same study demonstrated that medroxyprogesterone was more effective, reducing hot flashes by 84%.  The most common side effects of the drug are gastrointestinal in nature, including dry mouth, nausea, and decreased appetite.

B.     Gabapentin – The mechanism by which Gabapentin, a drug used to alleviate nerve pain, relieves hot flashes is unknown.  Nonetheless, a study of 350 women with hot flashes demonstrated a 46% decrease in hot flashes for women taking 900 milligrams of the drug daily versus a 15% decrease for those women taking a placebo drug.  To my knowledge, no specific study has looked at the benefits of Gabapentin for treating hot flashes in men on ADT.

3.     Alternative Therapies:  Small studies have also demonstrated that hot flashes can also be treated without taking medications at all. 

A.      Acupuncture – A very small study of 7 men with prostate cancer evaluated the effects of acupuncture on hot flashes.  The men in the study underwent 30 minutes of acupuncture treatment twice a week for 2 weeks and then once a week for 10 weeks.  The study reported that the men enjoyed a 50% reduction in hot flashes at 3 months following the final treatment.
B.      Electroacupuncture – A study of 15 postmenopausal women undergoing electroacupuncture demonstrated at least a 50% decrease in hot flashes in 73% of women as late as 6 months following the final treatment.

Take Home Message

Hot flashes are very common side effects of androgen deprivation therapy for men fighting advanced prostate cancer.  While most men reluctantly accept these debilitating symptoms and their subsequent impact on quality of life, they should not.  Numerous medications and alternative therapies are available to significantly decrease hot flashes.  While these treatments have their own side effects, they are often worth trying for men with severe hot flashes.  Of course, the various medications and treatments I have discussed in this post may not be for everyone.  Certain people have medical conditions that preclude the use of some or all of these medications.  As always, never start any medicine without first discussing it with your doctor. 

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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