Takeaways from key testosterone enanthate study presented at SMSNA 2021

Jesse N. Mills, MD, also highlights a few other key studies that were also presented at the 2021 Sexual Medicine Society of North America Fall Scientific Meeting

In a recent interview with Jesse N. Mills, MD, the findings of the study, “Subcutaneous testosterone enanthate and the effect of body mass index on serum testosterone in men with testosterone deficiency,” are examined from an expert’s point of view.1 Mills also highlights a few other key studies that were also presented at the 2021 Sexual Medicine Society of North America Fall Scientific Meeting.2,3 Mills is an associate clinical professor of urology at the David Geffen School of Medicine, the director of the UCLA division of Andrology, the director of the Men’s Clinic, and the chief of UCLA Santa Monica Urology, University of California, Los Angeles.

Please discuss the findings of the study, “Subcutaneous testosterone enanthate and the effect of body mass index on serum testosterone in men with testosterone deficiency" and their significance for providers and patients.

This new study really dovetails on we already know about men who are overweight, how they metabolize, and how you monitor the biochemistry of testosterone in the bloodstream. We know that heavyset men have larger circulating volume of blood that we call effective circulating volume, or ECV. And so, the heavier you get, the more dilute whatever molecule you're studying, whether it's testosterone, estrogen, or [prostate-specific antigen]. There's a little bit of a compensation that we have to do for weight. The critical thing about this study is they took 3 groups of men, which were men that had normal body mass index, men that were considered overweight, and then men that were considered obese. By putting them on a testosterone enanthate subcutaneous delivery mechanism for testosterone, they looked at what their average testosterone levels would be. What they found—no surprise—is that the heavier the man was, the lower the effective volume of testosterone levels that you're going to see in their bloodstream. That's super important because when you're finding a good, accurate delivery system for a man, the take-home message is that you need to account for body mass index and realize that you're probably going to be having to titrate up.

This was an industry-sponsored study by Antares Pharmaceuticals, which has a testosterone enanthate subcutaneous molecule in the hunt and there are 3 different levels of dosing for it: 50, 75, and 100. So, this does provide you with a mechanism for titration if you're going to be using that in your patients. What is a little bit limited with the study, of course, is that they were just looking at levels. They weren't monitoring symptoms. Their critical questions were, "If a man has a lower testosterone level and he's on testosterone replacement therapy, does that actually correlate to worsening symptoms? And do you have to then titrate based on his serum levels?" These days, especially since around 2013, when the FDA stopped asking us to screen for symptoms of low testosterone and base it purely on serology or blood levels, it changes our clinical management a little bit. I think most of your audience, the urologists that really specialize in sexual medicine, is still trying to treat patients and not blood values. And so, I think for them it's going to be a much more important factor to decide how to accurately assess these men and treat them effectively. It's a nice thing to think about in the back of your head if you're seeing a very heavy man in your practice. Think about titrating up or monitoring those levels more closely. That's the main gist of it, as well as the main limitation.

One thing that I would love to see in the follow-up studies is, for those men who were in a weight loss program or a vigorous exercise program, and their body mass index went down, whether their need for testosterone replacement would go down as well. The best therapy for testosterone is for increasing nutrition and dietary interventions before you start a drug therapy in the first place, so it'd be really great to see that and I'd love to see if they have any follow-up studies to look more at symptomatology as well as decreasing body mass index.

What distinguishes testosterone enanthate from other testosterone products or formulations?

There are 2 things to consider here. Not just the drug, the testosterone enanthate, but also the delivery mechanism. Most of the testosterone injectable products are an intramuscular delivery system, meaning you take a big needle, you stick it right through the skin and into a big muscle in the thigh or the gluteus, and that changes the kinetics a little bit. So, this product has been around for 50 years probably. It's an old generic drug, but the novelty of this is that it's a subcutaneous dosing, and there are differences between a subcutaneous delivery mechanism and an intramuscular one. What we find is that the kinetics change a little bit. So, if you look at the traditional testosterone enanthate, or testosterone cypionate—they're very similar esters and they have very similar kinetics—we typically think of those as a 2-week delivery system. Most physicians would say the starting dose for testosterone enanthate or testosterone cypionate would be 1 cc, which is 200 milligrams of testosterone, every 14 days. This, in the subcutaneous delivery mechanism, changes to 100 mg being the highest dose. So, we have 50, 75, 100, but you're doing it every week. The idea is by going subcutaneously, you can lower the dose, but you have to also increase the frequency of delivery. What that does is it mellows out the peaks and troughs of injectable testosterone.

If you look at the other ways that we have testosterone to prescribe to patients, there's everything from pills to long-acting pellets that that last over 4 months. The pills last about 12 hours because it's a twice-a-day dosing, and then you've got gels that are 24 hours. So, this injectable of testosterone enanthate hasn't changed for years and years. It's just how they deliver it and the fact that they decided to go into sub-q dosing, which is what they went to the FDA with. Now, you have an FDA-approved subcutaneous dosing. For the practicing urologist, this is really important because I've been doing subcutaneous dosing of testosterone cypionate or enanthate generically for years, because most of us know that it's a cleaner, better monitored delivery system. But, we still get angry notes from pharmacists saying we're not doing or prescribing it right since we're doing an intramuscular drug subcutaneously, which is completely safe and completely effective. And now, we have FDA-approved data to show that it is.

What are some key studies being presented at SMSNA this year that our audience should be aware of?

I think the most exciting thing in the sexual medicine sphere is the strategy for equity, diversity, and inclusion. I hate to use the bully pulpit for our great work at UCLA, but we have a few abstracts being presented by one of my former fellows, Denise Asafu-Adjei [MD, MPH] who's at Loyola now in Chicago on faculty, and Dr. Alvaro Santamaria [MD] who's still a fifth-year resident in urology at UCLA. They looked at, over the last year and a half to 2 years, how people in underrepresented communities access the health care system.

Dr Asafu-Adjei's talk looked at the differences between how men in Los Angeles are able to engage in health care, men's health, and sexual health on the west side of town, which is the more affluent side of Los Angeles, vs the south side of town.2 The shocking, wonderful, and surprising thing about this is that on the west side, on the swankier side of town, it turns out that most people are still going to sexual medicine experts via referrals from their primary care physicians—about a 70-30 split. And on the south side of town, it's about a 90% male-patient-generated access to care, which to me shows that there is something there, and if we build it, then we can have access to world-class men’s health on this side too because the patients want it. The primary care physicians are, like any primary care physicians, so bogged down with monitoring blood pressure, monitoring cholesterol levels, stroke risks, all the things that are incredibly important for men’s health and to overall sexual health, because these are all risk factors for sexual disease. However, they don’t have the time, nor do they have that referral base to actually deal with some of the sexual matters that mean the most to the patients. I think that changes a lot. That’s a paradigm-shifting abstract because what you’re saying is that people want the care. Unfortunately, the stereotype in minority communities is that they don’t want to see the doctor, but 90% of them are doing it on their own. And so, I think building out that platform is going to be huge, as well as just getting rid of 1 more barrier and 1 more stereotype in medicine that somehow these men are wary of going to the doctor. They just need to have the access. I think it is going to be very important and, certainly, is going to change the way that we approach health care in Los Angeles, at UCLA, and within the system at large.

Dr Santamaria’s paper shifts gears to look at access to sexual health in solid organ transplant men and realize that there is a huge unmet need in this population, which is not surprising because you’re waiting for a lifesaving operation and the physicians that are doing those operations and monitoring the transplant have enough on their plate.3 But the fact is that there’s a huge unmet demand that these men do want access to high-quality sexual care because these transplant surgeons are giving the life back to these patients and the transplant nephrologist and hepatologist are monitoring these men so that they can have a long, healthy, productive life. What’s better for a long, healthy, productive life than a long, healthy, productive sex life as well? So, because of his studies showing that the need is there, and the access is poor, again this is launching an initiative to have a free-standing sexual medicine referral clinic so that men who are going through solid organ transplant have much easier access to high quality sexual health as part of their recovery and even as part of their overall transplant evaluation. It's a great thing if you think about it from a men's health perspective as well as from a public health perspective because a lot of these men already have some sort of public health assistance. They're either on Medicaid, Medi-Cal, or Medicare, and so they are an insured population that we can take care of, and that we can provide incredibly high access to care. When you think about the end result of a lot of men with solid organ transplant disease, it's atherosclerotic, especially in the kidney transplant population. We know that atherosclerosis causes heart disease, renal problems, and sexual dysfunction, so a lot of these men are going to potentially benefit if no other conservative therapies help from a penile implant. And we have really good data that doing penile implants in men on immunosuppressive therapy is just as safe and effective as in men who are not on that therapy. And those are all covered benefits, at least in Medicare, so I think that was really exciting that we have another market and about 30% of the population, at least in Los Angeles, are Latinx as well. So, you again have an inroad into a community that is typically underrepresented in medicine to help bring up their level of care so that they're getting the same highest level of care on the west side of town as in the state of California at large.

Those are probably the most exciting things for me because we are trying to start to move the needle and make a much more equitable, inclusive stance in sexual medicine as it pertains to male health in general.

References

1. Miner M, Amy T, Gollen R, et al. Subcutaneous testosterone enanthate and the effect of body mass index on serum testosterone in men with testosterone deficiency. Paper presented at: 2021 Sexual Medicine Society of North America Fall Scientific Meeting; October 21-24, 2021; Scottsdale, Arizona. Abstract #002

2. Asafu-Adjei. Racial and other social disparities in the treatment of sexual dysfunction. Lecture presented at: 2021 Sexual Medicine Society of North America Fall Scientific Meeting; October 21-24, 2021; Scottsdale, Arizona

3. Santamaria A, Yoffe DA, Modiri N, et al. Racial disparities in sexual health care received by kidney transplant recipients in a metropolitan area. Paper presented at: 2021 Sexual Medicine Society of North America Fall Scientific Meeting; October 21-24, 2021; Scottsdale, Arizona. Abstract #148