Transcription
In today's video, I wanted to dial into the use of hormone therapy, or more specifically androgen deprivation therapy, which we call ADT for short, to try and highlight for you the pros and cons and where this can be utilized.
If you stick around for the video, I'll also give you towards the end some information with what men can do to try to mitigate any potential side effects that they're experiencing from taking this type of treatment to manage their prostate cancer. I'm a urologist and director of the prostate clinic located on the Gold Coast in Australia.
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What is androgen deprivation therapy, or ADT? In essence, broadly speaking, it is a collection of different treatments with a specific aim to lower a man's androgen levels. And the key androgen in a man's body is testosterone. Testosterone is predominantly produced from a man's testicles. One is to produce sperm and the other one is to produce testosterone. The aim of ADT effectively is to significantly lower the body's production of testosterone so that we have castrate levels of that hormone.
Now, the reason we do this is because we know that prostate cancer, at the early stage of the disease, is what we call castrate-sensitive or hormone-sensitive. And in essence, what that means is that we can control and lower testosterone levels, and through the process of doing that, we can stop the progression of someone's cancer. Now, it's important to note at this stage that ADT on its own does not effect cure. So, this is not a curative treatment, but it is a treatment that can be used in different ways, as we'll see in a moment, to try and put someone into remission or to improve the benefit from local therapy.
Okay. So, how does ADT work? Well, in essence, there are three crude ways that ADT can be delivered. Number one is that it can be used in a way to try and reduce, as I've said, testosterone production, and that can be done with a couple of different drugs. One group is called LHRH, or luteinizing hormone-releasing hormone agonists, and the other one is LHRH antagonists. They work in slightly different ways. The LHRH agonist basically stimulates the release of a chemical in the brain that has a feedback loop whereby transiently it increases testosterone production, which then circles back to the brain and then switches off further production. Examples of LHRH analogues include things like, uh, luprolide or goserelin. If we look now at LHRH antagonists, now these basically work by blocking LHRH function. So immediately, it stops the stimulation of testicular production of testosterone. And examples of this would include something like degarelix.
Okay, so that's the first group, those that reduce androgen testosterone production. The second group is a group of drugs that basically prevent androgen, uh, action. It should be noted that if you have a drug to, to prevent testicular production of testosterone, there still can be a small amount of adrenal testosterone production. The adrenal glands, small little glands located above the kidneys. There are two of them, one on each side. And so there can still be small amounts of androgens that are produced. The second group of drugs basically blocks any activity of androgens that can be produced from this site, and traditional examples of this would include something like bicalutamide, or the trade name is Casodex. There are more modern forms of what we call androgen receptor pathway inhibitors, and they include things like enzalutamide, darolutamide, or apalutamide. Now, there will be different trade names for these drugs depending on which country you're actually watching this video in.
The second situation that we might use ADT is in the context of a man who has had localized therapy. So, he's had primary treatment for localized prostate cancer, and at some stage in the future, that man relapses. And the way that we determine if someone relapses is by monitoring their PSA following treatment, whether that initial treatment was either surgery or radiotherapy, but we see what's called biochemical recurrence, in that the PSA test increases with time and is a sign that we have recurrent disease. Now, in that context, we may just watch for a period of time, but at some point in the future, again, we may give that man ADT.
Now, the third setting that we might use ADT is in the context of a man who has localized prostate cancer. He is awaiting external beam radiotherapy as his choice for definitive local therapy. And the pathology characteristics highlight to us that there are some adverse aspects to his pathology. And therefore, we want to combine both radiation and also the ADT to improve the overall effectiveness and reduce the probability of recurrence. We tend to use ADT when men are having radiotherapy if, for example, they have a Gleason score of 3+4=7 or a Gleason score of 4+3=7, or if their PSA, for example, is above 10, or if they were to have an abnormality that was palpable or could be felt on the prostate examination.
The fourth example of when we may use radiotherapy is in the context of what we call either neoadjuvant, which is where they have hormone therapy before radiotherapy, or potentially adjuvant, which is where it is continued after radiotherapy for a period of time. For example, if men have more aggressive features, then sometimes we may continue hormone therapy for a year, and in some settings, two years after that man has actually had his localized therapy with radiation. So, those are the four scenarios in which we tend to use ADT in the context of treating prostate cancer.
Okay, let's have a little look now at some of the side effects that we can see when men have ADT. And the challenge really with ADT, and one of the reasons why we sometimes limit the use or the duration of ADT, is because of the potential for side effects. Now, it should be noted that some men actually don't experience any side effects at all when they have ADT. Other men find it a, a, a terrible experience to go through.
Now, the most common side effects that we see and that men report to me is that they can experience hot flushes, or if you're in the States watching this, hot flashes. Many men can feel washed out. They have no energy. They struggle with normal day-to-day tasks. From a sexual function point of view, men can notice that their libido goes and that their erections go. If men are on ADT for a longer period of time, it can also promote characteristics associated with metabolic syndrome. And in essence, what that means is it can promote weight gain. And men tend to get weight gain centrally in the abdominal region. There can be changes in their sugar control, changes in their cholesterol control.
So, what are the things that men can do to try to mitigate the risks of these side effects? Whether we're looking at the short-term side effects of ADT or longer-term problems that can accompany its use. Well, the, the first thing from an overall well-being standpoint is that it's imperative that men continue to remain as active as possible. In my practice, I try and encourage men, get out, have a walk every day. It doesn't need to be anything particularly strenuous, but certainly get out, see the sunlight, breathe in fresh air, and walk as regularly as possible, and with time, try to increase the duration of the walk that you undertake.
If we look at particular or specific exercises, of which there is increasing data to support its use, and that really comes down to resistive exercises or weight training. And weight training does several things. Not only is it good from a cognition point of view, and there's some data to support, but the most important thing that we can all be doing to try to prevent that, that gradual slow cognitive decline that we can all experience as we go through life, really, is, is, is lifting weights. So, not only does it protect us from a cognitive point of view, but lifting weights also prevents something called sarcopenia. Now, sarcopenia is that process whereby we lose muscle mass. And as we get older and lose muscle mass, we're more prone to falling with a simple trip or just getting the stairs wrong. And a trip and a fall, which results in a broken bone as we progress through life, can be a significant and potential life-ending event. So, lifting weights to prevent sarcopenia and also to improve outcomes from a metabolic point of view is really key.
There's also more and more data that's highlighting that as we progress through life, one of the things that we certainly need to make sure is, is center stage in our diet is that we consume enough protein. Many Western diets contain far too much processed carbohydrate and not enough protein. And it's protein really, which is the building blocks of muscle. And that, in combination with resistive exercises, can certainly go a long way to preventing significant muscle mass loss. If you're unsure about which diets you should be consuming, please talk to your local doctor or have a chat with a dietitian to try and come up with a dietary plan that is going to be ideally suited for you and your specific circumstance.
In terms of the hot flushes that men can experience, well, certainly here in Australia, we've got fairly significant difference in seasons. And in the summer and in the summer months, the hot, uh, weather can certainly precipitate, uh, hot flushes. When men are being managed with what we call intermittent androgen blockade, which means that they have an injection of ADT periodically, we try, if possible, if their disease allows it, to synchronize that injection in the winter, cooler months, to try and remove that environmental trigger that can precipitate hot flushes. Simple things by such as identifying triggers for hot flushes, which can be something as simple as a cup of tea or a cup of coffee, any kind of hot drink, really, and seeing if we can avoid that or remove that from the diet to try and remove that as a potential stimulus. Other things that can make a difference are simple things like taking evening primrose oil, and there are some reports that acupuncture can also help. If all of this fails, have a t, have a discussion with your local doctor about juggling around the different forms of ADT, some of which are less prone to causing hot flushes.
When it comes to longer-term issues such as bone density loss, the technical term is osteopenia or osteoporosis. In essence, having a high protein diet, doing resistive exercises, and monitoring and being aware of your bone mineral density with scans such as DEXA scans can also play an invaluable role in being aware of your specific situation and trying to prevent further bone mineral density loss. But certainly, weight training, regular exercise is going to be key.
If you have any questions, if you'd like to share your story, please leave it in the comments section down below.