Part 1 of 3
Nelson Vergel: Hello everybody, Nelson Vergel here with ExcelMale.com and DiscountedLabs.com. I’m very happy here to have Dr. Ramasamy, we’ve done a webinar before, on estradiol and anastrozole, that was very popular, so he’s a great speaker, great researcher. He is in Miami, and he’ll let us know today, about this product called Natesto. It’s a testosterone nasal gel, that you apply in your nostrils. Very interesting data that he has to show us from a study he did with Natesto, and why don’t we start and have Dr. Ramasamy, welcome to the guys, I love you online, so why don’t you tell us a little bit about what you do, and in Miami.
Dr Ramasamy: Sure. Thanks so much, Nelson for the opportunity. And, yes, the previous seminar that we did on an anastrozole, was a total hit, so. thank you very much. So, the goal for today is to somehow discuss this product that’s been FDA approved and has been in the market since 2012. So now, for the last six years, it’s called Natesto. It’s, as the name implies, it’s nasal testosterone. So, since I started the … before I started the clinical trial, honestly, I’ve actually never prescribed Natesto. Things that bothered me about Natesto, where you had to put it up the nose. And I said, you know, most men would not want to have anything put up their nose, and the second thing that bothered me, as it was the FDA prescription, is to do it one pump in each nostril, three times a day.
Dr Ramasamy: And compliance with testosterone therapy in itself, is not that great. And so, I said to myself, I mean, how are men actually going to do it three times a day, and keep up with it. So, I was very averse to prescribing Natesto, as a modality of testosterone therapy, in men with low testosterone. But then after I looked at some of the recent data that were presented at the AUA, showing that the gonadotropins, the FSH and the LH, were decreased, but not completely abrogated.
Dr Ramasamy: I was very curious, and wanted to see if this would be a treatment option for guys that want to maintain their fertility options, and their sperm production options. Now, one of the main focuses of my practice here at the University of Miami, is fertility, and I see a lot of young men with low testosterone who are in their 20s and 30s, who are currently in the process of starting their family, or have not yet completed their family and want to go on to receive exogenous testosterone therapy.
Dr Ramasamy: Because right now, the options for low testosterone in men who want to preserve fertility, are off-label medications such as Arimidex, or anastrozole, clomiphene citrate, and ACG. And all of those three treatment options, albeit very effective, can have long-lasting side effects, such as decreased libido, increased in estrogen, fluid retention, gynecomastia and so on. So, because of all of the negative side effects with those medications, and because they’re off-label, we wanted to see if we can use Natesto, in a clinical trial in men who wish to preserve their sperm production.
Dr Ramasamy: So, one of the biggest problems is low testosterone, that men face. And we estimated that about 10% of men below the age of 40, actually have low testosterone, and men less than 40, typically, have either not started their families, or have not completed their families and want to still keep the option of family building open, and so, therefore, they absolutely seek out options for testosterone therapy, that is FDA approved and wants to use it on label.
Dr Ramasamy: And some of the current treatments for testosterone therapy that’s available on the market, on a very popular, are obviously injections with testosterone cypionate or enanthate, or the long-acting injection with testosterone undecanoate, and the topical testosterone treatment options are either the gel, such as AndroGel for tester and Testim, and testosterone patches such as Androderm and finally testosterone pellets, which can be used every three to six months.
Dr Ramasamy: Now one of the most … go ahead.
Nelson Vergel: Sorry, can I have a question here, because some of my people are going to definitely have a problem with the first statement on dosing cypionate or enanthate, and then every two to four weeks. I know that’s not how you prescribe it. It’s what’s written in the different-
Dr Ramasamy: In the labels, yeah.
Nelson Vergel: … Labels, but just real quick to clarify that sentence, there-
Dr Ramasamy: Sure. So, that’s what’s in the label and that we have to write these in talks like these. But, when I give testosterone cypionate or enanthate, I usually use 100 to 200 milligrams. IM or subcutaneously if the patients don’t want to use IM injections, on a weekly basis. Because when you give it two to four weeks, then patients experienced the troughs, and when they bottom out on their testosterone levels, it’s not such a great feeling. So, I usually try and cut back on the dose, but give it more frequently. So, not only are their peaks not that high leading to all of the side effects but their troughs and also not low, so they don’t experience the symptoms of low testosterone.
Nelson Vergel: All right, thank you for clarifying that.
Dr Ramasamy: So, some of the common side effects of testosterone therapy, I think we all know this. It’s unfortunately received a lot of bad press lately because of its possible increased risk in cardiovascular events, with MI stroke and pulmonary embolism. Obviously, some of the other side effects which we commonly know are hypertension and edema, and an increase in hematocrit or polycythemia. And the most important side effect of the topical gels is the risk of transference. The patients are often concerned that they would pass it on to their wife or their kids. And so that’s a big issue with trying to use topical gels.
Dr Ramasamy: And of course, the biggest risk with this … you can go to the next slide … The biggest risk of testosterone therapy is it causes infertility. And why does testosterone therapy cause infertility? So, testosterone therapy blocks the production of GnRH, from the hypothalamus, which blocks the production of FSH and LH, from the pituitary gland and FSH is a very important hormone for sperm production, and LH is a very important hormone for intratesticular testosterone production. So, if you don’t have FSH, then you’re not going to make sperm, and most likely your sperm count is going to be either low or going to be zero. Whereas, if you don’t have LH, then your body’s own natural testosterone production is also going to get shut down.
Dr Ramasamy: So, any testosterone therapy that we currently have on the market, both including the gels, the injections, and the pellets, all basically do one thing. They shut down GnRH, the shutdown FSH, they shut down LH, thereby both blocking sperm production, as well as blocking your own natural testosterone production. And that’s basically what these exogenous testosterone products do. The one other important thing is, as we made more and more advances in testosterone therapy, we went from shorter acting testosterone preparations, testosterone propionate, as some of you may know, is probably the shortest acting testosterone injection.
Dr Ramasamy: It’s currently not FDA approved, they took it off the market, but that’s what was the first testosterone preparation that was available back in the 50s, 60s and the 70s. And then we went from propionate to cypionate, and enanthate was a version of this, and then we went on to undecanoate, and then we went on to making pellets. Somehow, we went from very short-acting preparations to much longer acting testosterone preparations, because we wanted to make the patients more compliant. We wanted to see if this would be less cumbersome for men to be on testosterone therapy, potentially, for basically their whole lives.
Dr Ramasamy: Now, Natesto is actually the total opposite. It’s actually the shortest acting testosterone preparation, and the peaks are achieved in a very short time and the [inaudible 00:09:20] fertility, is maintained. Let’s go to the next slide. And so, how common are fertility problems? You know men always ask me this. They are like, Doc, fine, I’m going to go on injections, I’m going to go on gels. What are my chances that I’m going to become infertile? And a very nice study that done back in the 90s, and army recruits, that basically showed that if you take testosterone cypionate, 200 milligrams, intramuscular injection, once a week, at the end of three months, there’s a 65 % chance you’re going to have zero sperm count.
Dr Ramasamy: You know, people think that it’s a very good contraceptive, it’s actually not. So, 35% of the time men will still have sperm production, but two-thirds of the time you will have zero. And so, it’s a contraceptive, but it’s a terrible contraceptive. So, men who are wanting to take testosterone therapy and think they’re not going to make sperm, there is a 33% chance you’re going to get your wife pregnant because there is a chance that you will still have sperm. But two-thirds of the time, you’re going to have zero sperm count, and there’s a 5% chance that the sperm count may never recover.
Dr Ramasamy: So, what’s happening why is infertility a problem? I think men are now fathering children at older, and older ages. We’ve seen this over the last decade, wherein the average age of new fathers has now increased to more than 35. And we do know that testosterone declines naturally with age, and it starts declining after the age 20. So, it declines about point five to one percent of what you started with, once you reach 20 and above, which is very sad, because, for men that start off with a lower level, their decline is much faster with age, compared to men that start off at a much higher level.
Dr Ramasamy: And so, therefore, trying to target this population of young men, who still want to have kids, but have consistent testosterone decline, is a big problem that we’re facing, which is what we’re trying to address with this clinical trial. So, we went over the current medications that are now used to increase testosterone in men that want to preserve fertility. Three medicines that we discussed were a clomiphene citrate, anastrozole, and HCG.
Dr Ramasamy: One of the nice things about anastrozole, it blocks the conversion of testosterone to estrogen, so therefore, it increases your own natural testosterone. Clomiphene citrate blocks the estrogen receptor in the pituitary, thereby increasing FSH, LH and therefore it increases testosterone, and therefore estrogen production, and HCG has been used a lot in men that want to preserve their testes size, as well as those that want to preserve sperm production. It’s just very similar to LH, it increases your own natural testosterone production from the testicles.
Nelson Vergel: Doctor, one more product, FSH, what do you think?
Dr Ramasamy: FSH, so exogenous FSH has been used to increase spermatogenesis. It’s expensive, and it has to be used three times a week. But in guys that cannot make FSH, so in people … in adolescents who have hypogonadotropic hypogonadism, wherein their pituitary is not functioning, and they cannot make FSH, then using FSH to try and increase their sperm production, is absolutely useful.
Dr Ramasamy: In some patients who come off of anabolic steroid use, or testosterone therapy for a long time, if you try them on clomiphene citrate and HCG, for about three to six months, and their FSH doesn’t improve and their sperm production doesn’t improve, then trying to put them on FSH, and trying to see if we can get some sperm production back, is very useful. But those are the only two indications where I try and use exogenous FSH.
Dr Ramasamy: Why are we concerned about these treatments? All of these medications have side effects. Anastrozole can cause hypertension, back pain, dyspnea, edema, and blocking estrogen for a long time is not good because estrogen is a very important hormone for the bones and some of the doses of Anastrozole that was used basically being down the estrogen to almost negligible and so, therefore, it has to be carefully titrated to make sure the estrogen decreases, but at the same time doesn’t become negligent.
Dr Ramasamy: Clomiphene Citrate, Clomid, I’m sure people have taken Clomid and have had their own side effects with flushing, weight gain, and fatigue and with HCG it also has side effects because it increases testosterone that converts to estrogen. But again, it’s an injection, it’s expensive, and often not covered by insurance and has to be used on a weekly, if not bi-weekly basis.
Nelson Vergel: Let me add something about HCGs. It’s not expensive. It’s only expensive if you use the pharmaceutical grade-
Dr Ramasamy: Correct-
Nelson Vergel: But compounding pharmacies make it cheaply.
Dr Ramasamy: That’s exactly right, yes.
Nelson Vergel: And so all the other ones do … are made by … can be sold by company pharmacies for people-
Dr Ramasamy: Correct.
Nelson Vergel: Because insurance, like you said, these are off-label-
Dr Ramasamy: Correct.
Nelson Vergel: Insurance companies don’t like to pay for it because it is off label for men so it’s usually a cash kind of a deal where the-
Dr Ramasamy: Correct.
Nelson Vergel: Have to pay.
Dr Ramasamy: That’s exactly right, yes.
Nelson Vergel: Thanks a lot.
Nelson Vergel: Okay, so yeah. What you just said about the fact that it’s off-label meaning not FDA approved in males, only females. But there’s nothing illegal about using them off-label.
Dr Ramasamy: Absolutely, yes.
Nelson Vergel: Alright, good.
Dr Ramasamy: When I meant expensive I meant that it’s just not covered by insurance, that patients often have to pay cash from compounding pharmacies as opposed to testosterone therapy which will actually get covered by insurance as long as you have a low T.
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