Hi, I’m Dr. Scholz. A common question we get at the PCRI is “how do you counteract fatigue from hormone blockade?”

Hormone blockade otherwise known as androgen deprivation or we call it testosterone inactivating pharmacuticals—these are medicines like Lupron, Casodex, Zytiga, Xtandi—fatigue is far and away the most common complaint, and this occurs primarily because low testosterone causes loss of muscle.

Think of muscles as the engines of your body. So if you’ve been driving around with a V8 all your life and all of sudden they’ve put a 4-cylinder in your car, you’re going to wonder why when you hit the gas nothing happens. There is a way to counteract muscle weakness from hormone blockade and it takes a fanatical, diligent, consistent commitment to exercise. And not just any kind of exercise; I’m not talking about running and stretching; I’m talking about weightlifting. Weightlifting can compensate for the muscle loss that occurs when testosterone levels are low. But this usually means visiting the gym 2 or 3 times a week and really stressing the muscles so they become fatigued and sore. This will cause them to increase in size and restore your normal strength. When testosterone levels are low under therapy muscle loss can occur incredibly quickly—within a couple of weeks. So people can diligently do exercise month after month after month, and feel reasonably well and then take a two week holiday, and all of a sudden they feel horribly fatigued because of all the rapid muscle loss. So not only does exercise need to be regular, it needs to be totally consistent. There can’t be any holiday periods. In my experience, regular fitness training like I’m describing will cause about an 80% reduction in the amount of fatigue that men face when they’re on these treatments.

There are a few other tricks that people can consider as well.

One, of course, is to realize that there are other causes of fatigue beside the treatment. People can have low thyroid levels or low B12 levels, and so a medical examination by a skilled doctor should be done to make sure there’s not something else going on. If people are just told it’s always from the Lupron, sometimes some of these other things are going to be missed. One medical condition that is less common, but can also occur with low testosterone levels is the development of anemia—low red blood cell counts. If anemia becomes severe then cardiorespiratory reserve is reduced, and you’re left with getting shorter breath rather easily with minimal exercise. Most of the anemia from low testosterone levels is mild and does not need treatment, but if it becomes severe—which would probably be signaled by a hemoglobin less than 10 or a hematocrit under 30%—pharmacutical intervention with a medicine such as Aranesp or Procrit can restore blood levels back up into an acceptable range. Transfusions are not indicated. There is always some risk with transfusions, and unless the anemia was horribly severe one would not consider giving transfusions just to correct the anemia of low testosterone.

So what other tricks can people consider if these measures don’t seem to be enough?

Well, medicine such as Provigil, also called modafinil, which is a medicine that has been FDA approved for the treatment of narcolepsy seems to be a nice stimulant that can help people. Some men rely on caffeine—an extra cup of coffee now and then. These measures have some benefit, but as is the case with many pharmaceuticals continued successive use leads to less of a benefit over time. It’s better to use these agents for certain special occasions or days that you need extra energy and then allow your body acclimatized to the absence of these medicines so it reestablishes their benefit when you use them again.

Lastly, in men with ongoing hormone blockade treatment (TIP Therapy, Androgen Deprivation) there’s always some flexibility in what medicines are being used and how long the treatment is continued. Often times TIP is giving for a four-month period for men with Teal, an 18 month period for men with Azure, and maybe a 12 month period for men with Indigo, but when men are more elderly or perhaps they have a milder form of disease, [then] shorter treatment periods should be discussed, especially in men that are having a lot of serious fatigue. Another possibility is to use less intense therapy. One medicine in particular, Xtandi, is more associated with fatigue. Another competitor called Zytiga is equally effective but less likely to cause fatigue. So you can talk about switching the Xtandi to the Zytiga, and that may reduce the problem with the fatigue when Xtandi is the cause. Another shift to consider when men are really hurting from Lupron (I use Lupron sort of like the Kleenex of the prostate world. There’s Eligard, Firmagon, and all these medicines can induce the fatigue of low testosterone) but Casodex, an oral hormone blockade agent, is definitely associated with less fatigue than these other injectable forms. Casodex is probably not quite as potent in its anti-cancer effects, so some of the anti-cancer effect is probably being sacrificed by using Casodex instead of Lupron or one of its analogs, but in severe cases, Casodex can be considered as a substitute for Lupron to help people get some degree of treatment. In my own patients, I tend to use Casodex in my elderly patients that in their 80s to extract some benefit from the testosterone blockade therapy, but minimize the fatigue that comes from this type of treatment.

So in summary, there’s a panoply of options to help men who are suffering from fatigue. You need to put all this information into context depending on how serious the disease and how serious the fatigue is different measures can be implemented to try and reduce this troublesome side effect and improve a person’s quality of life.