Hello, I'm Dr. Michael Holick. And I'm here today to tell you a little bit about my background and my journey with prostate cancer. I'm Professor of medicine, physiology, biophysics and molecular medicine at Boston University School of Medicine. I am the Chief of endocrinology, nutrition and diabetes at Boston City Hospital. Back in 1987 and when they merged with Boston Medical Center, remained Chief of endocrinology, nutrition and diabetes. I set up a metabolic bone clinic for infants, children and adults at Boston City Hospital. They did not have that type of expertise. And then continued that role as Director of the Bone Health Care Clinic at Boston Medical Center until recently.
A little bit more of my background and why I'm interested in metabolic bone disease, because I've seen over 25,000 patients with metabolic bone disease, infants, children and adults. And I happened to be in the right place at the right time when I was in graduate school, University of Wisconsin. And I was interested in getting my PhD. And at the time, I was interested in the hottest topic, which was DNA and RNA. It just had been discovered, but there were a lot of postdocs, they weren't interested in a young graduate student.
So they sent me to Dr. Deluca who was working in Vitamin D. And I said, "I have no interest in working in Vitamin D." And they said, "It doesn't matter what you're interested in. This is what you're going to be working on." And it turned out that I made basically a [inaudible 00:01:58] into a golden purse because back then we couldn't understand that when you took Vitamin D, it took 24 hours to begin to work. And so, why would that be? And so, the thinking was that maybe it was activated. And so, for my master's degree, I was the person first in the world to identify 25-hydroxy Vitamin D as the major circulating form of Vitamin D. This is the Vitamin D that when you go to your doctor is what they measure to tell you if you have adequate Vitamin D or if you're Vitamin D deficient or even intoxicated.
And then after I got my master's degree, I was given the task of identifying the active form of Vitamin D. It turns out that I'm the first in the world to have identified it as 1,25-dihydroxy Vitamin D. Why is that important? Because it turns out that your kidneys activate Vitamin D. Back in the 1950s and '60s, they couldn't understand why patients with kidney disease had severe bone disease, aching bone disease, and that caused them to be wheelchair bound because they couldn't respond to Vitamin D. Well, it instantly made sense that if you can't activate Vitamin D, you can't use calcium in your diet and you wind up with bone disease.
Well, now that we knew what the active form was, it needed to be chemically made. Well, I'm an organic chemist. And my roommate and I were the first in the world to make 1,25-dihydroxy Vitamin D3, known as calcitriol. And the material that we made in the test tube, we gave to doctors around the world. And it began treating kids with rare diseases causing rickets where they were wheelchair bound. They began walking again. Patients with kidney disease, wheelchair bound, aching bone pain, started walking again. That was my introduction to translational medicine.
Why am I here today? Because I have a new title, which is prostate cancer survivor. And I'm going to share with you my journey. And being a scientist, I wasn't willing to just simply accept that I'm going to be getting treatment without understanding the treatment, understanding the consequences of that treatment, and most importantly, to think about intervention, how to prevent many of the complications associated with it.
In November of last year, I went to my PCP, hadn't seen him for over a year and a half because of COVID. And he sent me a letter back saying that my PSA was 13 and that you should see your urologist. Well, being at Boston Medical Center and seeing men with prostate cancer, I went to my urologist friend and I said, "I have a PSA of 13." He did an exam. He said that the gland was a little bit enlarged, but it was totally smooth, that most men, they have hyperplasia, and that the PSA can be elevated. Not to worry, but we definitely should do a biopsy just to be on the safe side. So he did a biopsy.
Two weeks later, frantically gives me a call to tell me that seven out of 12 biopsies were positive and that I had a Gleason score of four plus five, which is nine. Now you would think that if you're a nine or a 10, this is a good thing, right? But not when you have a Gleason score of nine. It's one of the most deadliest forms of prostate cancer and it basically eats you from the inside out.
Then I went immediately, this is now on December 30th, to see my oncologist friend at Boston Medical Center because I had been seeing her prostate and breast cancer patients because bone disease is associated with this hormone deprivation therapy. And so, I had been treating patients with breast cancer and prostate cancer for a very long time. And the first word out of her mouth when she saw me was, "Holick, this is curable." Now, that was incredibly important to me because for any of you, when you get the diagnosis of prostate cancer, your whole life flashes in front of you and you realize that, "My gracious, I have so many other things to do. And now I have a disease that's likely to limit my existence and I need to do something about it."
She told me that good news because I had a PET scan and MRI. MRI showed total involvement of the prostate with extension, but no evidence of lymph node involvement. PET scan was negative. So I did not have metastatic bone disease or any evidence in the lymph nodes. That was the good news.
And so, now I was transferred to Dana-Farber and had an opportunity to meet Dr. Alicia Morgans and Dr. Paul Nguyen. But before doing that, when I knew that I was going to be on androgen deprivation therapy, when I met my oncologist friend on December 30th, I made as my New Year's resolution that I am not going to suffer the consequences of being hypogonadal, i.e. because I had treated a lot of patients with low testosterone levels. Causes muscle weakness, causes muscle atrophy. But you don't wake up one day being hypogonadal and then losing your muscle mass and being fatigued.
And so, I made the decision on January one of this year that I was going to start walking five miles every day and have at least 10 to 15,000 steps a day because this, A, will maintain my heart function. And B, it helps actually maintain your bone density because the pounding on the pavement maintains both hip and bone density, which I recommended to my patients. And also, it keeps your muscles working. I had been seeing a personal trainer once a week doing weight training. And I got to see her and she said, "You should probably be doing this twice a week." And so, I initiated weight training twice a week.
So now I meet with Dr. Nguyen and I also meet with a surgeon because your options are that you can have surgery and radiation therapy and also fondly known as ADT, androgen deprivation therapy.
And so, I weighed the pros and the cons. And the surgeon told me, "Yes, you're 75. And so, typically, we don't do surgery on anyone over the age of 70, but you're a young 75, so you could still have surgery, but the complications from that are quite significant, including incontinence and, of course, ED and possibly other consequences." And so, my option therefore was to go by using ADT as well as radiation therapy. So I made the decision to do this and met with Dr. Alicia Morgans. She was outstanding. She gave me all of the various options available to me. And the first option, of course, is that you got to shut down your testosterone production. And how do you do that? Well, what you do is you take what's called Lupron and you get this in your butt every three months.
What is Lupron, right? Being a biochemist, I knew very well because I've seen lots of my patients on this medication. It's a medication that was discovered back in early 1970s and it's made by your hypothalamus. It's called gonadotropin-releasing hormone. And that what it does, it goes to your pituitary gland to make FSH and LH, which then goes to your gonads to both make estrogen, it helps in puberty, and also makes testosterone. But what's really interesting about Lupron is that the body doesn't like to see it all the time. And so, when you initially get Lupron, what you will do is you will stimulate FSH and LH, you will stimulate testosterone production. But when you're on it for a long period of time, it shuts down the effectiveness of your pituitary gland to make FSH and LH, which is why you then become hypogonadal, because you're not any longer making testosterone.
I did get the Lupron, but there's a slight problem with this because Lupron, like I said, initially will stimulate your pituitary gland to make FSH and LH, which will go to your testes to increase testosterone production. Well, if you have an aggressive prostate cancer, this monster in your body, you don't want to feed it. And so, what she then did was to put me on bicalutamide. Now, this medication specifically prevents any testosterone in your body from getting to the prostate cancer cells, prevents it. And as a result, is a way to make sure that at least for that first month or so, that even though the testosterone is going up, that you're able to prevent that from happening.
And then after the month, that medication was stopped. And then I was put on abiraterone. What is abiraterone? Abiraterone is a medication that now regulates the adrenal glands because, yes, your testes make testosterone, but we know that your adrenal glands also make androgens. And so, part of the problem has been that if just being on Lupron that you still could have the cancer take off again because it can take advantage of the androgens produced in your adrenal gland.
So I started the abiraterone and it's 250 milligrams, four of them. And you take it sometime in the late night or early morning because you have to be ... Have an empty stomach when you're taking it because it affects how you absorb it in your intestine. I routinely was getting up at around two, three o'clock in the morning and taking it and then waiting for breakfast for another two to three hours. And that works quite well.
What is abiraterone doing now? Now, not only is your Lupron shutting down totally your testosterone production, but now abiraterone not only shutting down androgen production, but it's down regulating the production of cortisol, which is really important for you because when you get up in the morning, what's happening is that your brain making ACTH, adrenocorticotropin hormone, is going to your adrenal gland to tell the adrenal gland to make cortisol so that when you wake up in the morning, you feel very active and ready to go. But abiraterone shuts that down. And so, as a result, it's one of the reasons that many cancer patients on these medications, including me, when I get up in the morning, I don't want to get up because I have no cortisol.
Being an endocrinologist, I ask Dr. Morgans, "Can you get me a blood level and 8:00 AM cortisol?" This is what you typically get on endocrinologist orders to see if you're adrenally sufficient. My blood level, 1.1. So I knew that I'm adrenally insufficient. My blood testosterone levels, zero. I am hypogonadal. But now I'm on this, the prostate gland has shrunk significantly, and now I need to have radiation therapy. And met with Dr. Nguyen and he said it's going to be five and a half weeks of intensive therapy, lots of complications from this. You can get GI bleeding, you can have dysuria, pain on urination, you can have difficulty in urinating, just to name a few complications.
Again, my thinking was that how can you help mitigate or prevent many of these? Well, one of the ways of course is, and that they recommend, is that you go on miralax. And so, what it does is it's a material that when you're swallowing it, you don't absorb it, but it absorbs water in your colon so that it makes your stool very kind of loose. And so, when you go for the radiation therapy, that your colon is not really full so that when you're getting blasted by radiation therapy, you're not affecting it as much, less likely to have GI complications, including pain and GI bleeding.
And then I thought you have to also take 16 ounces of water before you have your therapy because what you want to do is have a full bladder. Now, you would think if you have a full bladder that that would even make it worse, but no. What it does is it actually raises your bladder. And so, as a result, when you're being irradiated around the pelvis, the prostate and the lymph nodes, then the bladder being elevated minimizes the complications associated with it.
Well, what I did was I took it to the next step because my thinking was, A, if I walked three to ... About five to eight miles, which I did every morning, so I got to the hospital at Brigham Women's Hospital around 5:00 in the morning. I was scheduled at 8:30 in the morning, so I walked for two hours around the campus. Or when it was snowing outside, in the hospital. It does two things. One is it actually increases bowel movement activity. I also took an hour before, not 16 ounces, but 32 ounces of water because I wanted to make sure my bladder was completely full. And so, 10 minutes before my appointment, I would then have complete elimination of my colon and have a very full bladder.
I started going through radiation therapy. And what they have is that you meet a radiation oncologist once a week and you have to fill out all of what symptoms that you're experiencing as a result of the radiation therapy. And I said, "I don't have any symptoms at all," first week and second week and third week, fourth week, fifth week. And so, the final meeting, he said, "It's amazing that you've not had any symptoms. You've really sailed through this very well." And I said, "Wait a second. Are you sure that you turned the machine on?" And he said, "Oh, don't you know? Your insurance company doesn't cover that. You have to pay extra for that." And so, that was kind of the joke. But I had zero complications from the radiation therapy. And I think it's because I was fully prepared every day. And so, as a result, for men thinking about the consequences of radiation therapy, which are really, when you listen to these, can be quite severe, at least for me, I was able to get through this.
But that's not the end of the story because Dr. Nguyen said, "Okay, after you have the radiation therapy, we need to blast your prostate gland for any evidence of cells that didn't fully respond to the therapy that you're on." And it's called brachytherapy. And what that means is that they will be putting in these little tubes into your prostate, and then they put in super radioactive material just for a short period of time and it blasts the whole area. And again, lots of potential complications. And went through the therapy, sailed through it, and really had minimum complications.
But in the meantime, now I'm beginning to continue to wonder about my muscle function and bone health. And so, I did a bone density. And since I ran the Bone Health Care Clinic, I knew very well what bone density means. And so, they did a bone density at a local hospital and I had what's called a T-score of minus 1.4 in my hip. And what that means is that I have osteopenia. By definition, a T-score of minus one to minus 2.5 means that you have less bone mass than you would like, but it's not osteoporosis. Minus 2.5 and greater is considered to be osteoporosis.
And so, the patients that I saw with breast cancer and prostate cancer, to prevent bone loss, I had them on adequate amount of Vitamin D. Now, the Endocrine Society recommends that men and women, all adults should be on 1,500 to 2,000 units of Vitamin D a day. And you need an adequate amount of calcium, 1,000 milligrams a day. And so, many of my patients that followed my advice did very well and maintained their bone density. But men and women with metastatic bone disease often are placed on what's called xgeva, also known as zometa. And what it does, this drug has an effect on your bone cells to possibly help reduce the activity of the metastatic disease in your bones.
And so, I had been treating patients for more than a decade for this. And so, I am on ... I personally take 5,000 units of Vitamin D a day. My 25-hydroxy Vitamin D level, the Endocrine Society recommends should be at least 30 nanograms per ml. And the preferred range is 40 to 60 nanograms per ml. And so, I'm on 5,000 units a day. My blood level's 72 nanograms per ml. I drink three glasses of milk a day. There's 300 milligrams and eight ounces of skim milk. And so, I am adequate calcium and adequate Vitamin D.
I was also concerned, of course, about the muscle function and loss. And so, by being in the physical therapy, basically weightlifting twice a week, I continue to lift the same amount of weight I did before I started therapy. So my message to you is that if you intervene and you are aggressive in your health, that you don't have to experience a lot of these side effects that are usually associated with androgen deprivation therapy and radiation therapy.
There's another complication, however, from radiation therapy and androgen deprivation therapy. And that is testosterone plays a role in blood cell production in your bone marrow. And your bone marrow in your pelvic area is very important for producing red blood cells. So now you're blasting your bone marrow with radiation and you have no testosterone. And so, yep, I'm anemic. Normally your hematocrit, the percentage of red blood cells, should be in the range of about 42 to 45 for a male. Mine's 36, so now I'm anemic, I am adrenally insufficient, and I'm hypogonadal.
And so, trust me, you feel exhausted when you get up in the morning, and even throughout the day. And sometimes huffing and puffing because being anemic is certainly a significant issue.
But with all of these, they pale in comparison to hot flashes that are associated with being on androgen deprivation therapy. And this is the same thing for women, breast cancer, on hormone deprivation therapy. Post-menopausal women, I saw thousands of them in my clinic. They told me about hot flashes and I was sympathetic. There really is very little that can be done. And I do apologize to many of my female patients because as a physician, male physician especially, and listening to this woman telling me that she's having hot flashes and that it's really disruptive of her life, my response is, "How bad can a hot flash be? You feel a little bit warm, so what's the big deal? And five minutes later it's gone." No.
And so, now I know what a hot flash is, a severe hot flash. When you have a hot flash, you can feel it. You could instantly feel it coming on. And all of a sudden, from your belly button up, you start profusely sweating and your blood vessels basically almost are exploding. They're expanding in size because the body thinks that you're having a heat stroke. And as a result, it's doing everything that it can to try to prevent that from happening. You're sweating so profusely. Normal activity, it's very disruptive. You basically stop. You can't function. And I was having at least a dozen hot flashes every day. But what was worse for me was I was having them at night. And when I was in bed, if I moved my blankets, for example, or got up and had to go to the bathroom and came back, I had an intense hot flash. And that keeps you awake.
And so, I then decided, "Wait a second. There has to be a way of helping to control them." So I went on the internet and I found a product called Kulkuf. And what this ... And there were a bunch of anecdotes from post-menopausal women saying that this has changed their life. So I figured, "What the heck, why not try it?" And so, I purchased it. And it's basically a device that you wrap around your wrist with a Velcro sleeve. And when you turn it on, it ... And you could probably see the blue. This is a mini heat pump. It instantly decreases the temperature of your wrist to 47 degrees, and it lasts for five minutes.
Now, why is that important? Because the inventor of this thought about this and realized that if you're having a hot flash, there's some signal going to your brain saying that you're hot. Well, what if you could block that signal by now having a signal saying that you actually are cold? And so, when I put this on as a hot flash is being initiated, it instantly shut it off. And so, now throughout the day, I wear this, turn it on whenever I'm aggravated, which can certainly initiate a hot flash, or if the temperature in the room changes, it really has helped tremendously. And even at night, if I have a hot flash, I can turn it on.
But then I started asking the question, why do you get a hot flash? And in the daytime, you're wearing clothing and it's likely that it's a slight temperature change in your skin that's sending the signal to your brain. So at night, I thought if you lived in a cool room and in your underwear and under a blanket, that that would be the ideal circumstance. But it turns out, at least for me, it's just the opposite. It's counterintuitive. That actually what you want to do is to have your skin temperature always at a constant. Because when you're in bed and you're taking your covers off and on, you're changing imperceptibly skin temperature. But it's enough to send a signal to your brain thinking that you are in kind of a state where you need to be responsive and that you need to start sweating to cool the body down.
So I started wearing pajamas thinking that by putting on pajamas that that would help to control my skin temperature. And it worked reasonably well, but still was getting up two to three times at night with hot flashes. I would definitely wear the ... Use this and it would help definitely. As soon as you feel it coming on, I could shut it off.
But then I realized would be ideal is to be in a cocoon, right? Or be inside your mother's womb where the temperature of your whole body is constant. And so, I decided what about a sleeping bag? And so, I rolled out my sleeping bag and started using it. And now I don't have any hot flashes at night in the sleeping bag until I get up and have to go to the bathroom and take my abiraterone. I usually wind up with a hot flash and then I turn on Kulkuf, K-U-L-K-U-F. And you can go to Kulkuf.com for more information about this.
And just an FYI, I have no conflict of interest. I have no relationship with this company other than I convinced them that it would be really worthwhile to do a clinical trial. There's never been a clinical trial for this.
And so, they've agreed. They're going to provide me with the devices. And I'm in the process of getting IRB approval at Boston University School of Medicine to initiate a clinical trial to see if it helps prostate cancer and breast cancer patients on hormone deprivation therapy and their hot flashes. They also developed another device, a hat. And it turns out that they have a plate in the hat. And when you turn on the hat, it goes down to 50 degrees and it lasts for about three quarters of an hour.
So for me, having hot flashes all the time, initially keeping this on really kept them at bay. If you touch it again, it goes up to 60 degrees. And if you touch it again, it goes up to 77 degrees. And so, now it's 77 degrees, it's not using as much of the battery. It lasts for almost two hours.
You can wear this throughout the day and basically eliminate the hot flash so that now you no longer have to worry about putting this device on when you're initiating a hot flash, you can actually prevent them as well.
And so, this gives you kind of an overview on how I've been dealing with the various complications. But last but not least, which to me is most important, is that androgen deprivation therapy plays with your head. It can cause you just to be kind of in a dark cloud and feel like you're in a maze that you can't get out of. And it's well documented that men with prostate cancer have a three to four times higher risk of committing suicide. There is no question, even for me, that this ADT medication induces suicide ideation. It's incredibly important to have a partner. I just celebrated my 50th anniversary with my wonderful wife, and she has been incredibly helpful to me. Both of my children have been as well. It's really important to talk to family members.
It's also documented that men with prostate cancer living alone, having no kind of family support, are much more likely not to just have suicide ideation, but to then take it to the next step and to commit suicide. So it's incredibly important for probably breast cancer patients as well as men with prostate cancer. You need that support from family. Feel free to talk to them. Or you could always have ... There's a hotline, suicide hotline. You need to talk to somebody. You need to get out of that dark cloud because it can be overwhelming. And I've had that experience.
Finally, what I've been doing, because I really wanted to know what was going on, is I have a diary. I have been keeping a diary on a daily basis. I document how many steps I have every day so I know. It kind of forces me to make sure I'm walking at least five miles a day. I'm also counting the days that I'm in therapy and I'm counting the days that it will finally end. And that really kind of gives you hope because your things are moving along. And I also document temperature and other events in the day, and also hot flashes and how I was dealing with them.
Long story short is as a doctor treating patients with breast cancer and prostate cancer, now, like I said, having the title of having the most aggressive form of prostate cancer, I fully now can appreciate the importance of physicians really understanding all of the complications, all of the biochemistry, endocrinology that's associated with these medications, radiation therapy, so that you can be more sympathetic to your patient. And like I said, definitely make sure that that patient has some kind of a network that he or she can go to to explain what they're going through. Incredibly important.
And I thank you for your kind attention.