Does Testosterone Help Orthobiologics Procedures?

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The same patient who asked the question about PRP vs BMC and ligament healing yesterday also asked about whether taking testosterone could help with healing after an orthobiologic procedure. That same prolotherapy physician who launched teh last blog had also claimed that there was no doubt that the science showed that testosterone supplementation helped his chances of healing after a ligament procedure. Again, that topic is really too long for an email response, so let’s go into this in more depth in a blog.

Regen Med + Testosterone

As men and women get older, testosterone levels drop. In men, once they hit middle age and beyond, that’s called andropause. Hence, physicians will often offer age management services like testosterone injections, pellets, or creams to help that problem.

From what I’ve observed, about 1 in 5 medical practices out there that offer interventional orthobiologics like PRP injections also offer age management services. I have also heard from a good chunk of colleagues that you must correct hormone issues like “low T” (low testosterone) to maximize a patient’s chance of success after a procedure.

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The Multiple Levels of this Idea

I’m going to approach this on a few different levels. First, is the basic science of whether testosterone can help ligaments heal and what we know from animal models. Next, we’ll see if there is any clinical research from patients who were treated for low testosterone and whether their outcomes from an orthobiologic procedure were compared to those who didn’t have that treatment. Finally, I’ll go into my personal experience and general recommendations on this topic.

The Basic Science

The effect of testosterone on ligament healing and maintenance is not well understood. We do know that ligament specimens from young people have androgen receptors in both sexes. This could mean that ligaments respond to testosterone levels (1,2). Small research studies have shown that testosterone levels correlate with knee ACL stiffness, meaning that lower testosterone levels could cause ligaments to become less protective of joints (3,4). While more research is needed to characterize the pathways that testosterone uses to act on ligaments, the influence of sex steroid hormones (testosterone, estrogen, and progesterone) has been proposed as one possible reason that women are more likely to injure the knee ACL (5).

Is there anything else? Banerjee et al performed an interesting lab-based study where testosterone was added to platelets and aggregation was measured (the ability of platelets to form a clot, which is the first step in healing) (6). The authors did find that adding testosterone to male platelets only, caused more aggregation. Regrettably, the focus of this study was to see if testosterone could lead to the type of clots that cause heart attacks and had nothing to do with PRP injections.

Clinical Research

Is there actual research on how testosterone may impact the outcomes from PRP or BMC injections? Nothing for PRP and testosterone was identified in the US National Library of Medicine. In addition, nothing was found for BMC treatment and testosterone either.

In fact, the only study ever conducted in orthobiologics that I know about with regard to testosterone supplementation is a study we performed but never published. Several years ago, we wanted to know if our middle-aged and elderly male patients with low testosterone would benefit from a simple 3-month testosterone supplementation program before a bone marrow concentrate procedure. Meaning, could we make their stem cells better or increase the number?

Basically, in 20 men that were BMC candidates and who had low-T we first took their bone marrow aspirate and froze that down into cryopreservation. We then placed them in a testosterone and thyroid supplementation program for 3-months (Testosterone IM and oral thyroid) with the goal of bringing testosterone levels back to youthful levels. We then performed another BMA which we also cryopreserved. We then thawed both samples and cultured the cells in either the patient’s own pre-testosterone platelet lysate (PL) or their post-supplementation PL.

We did all sorts of tests on their stem cells including:

  • The ability of their stem cells to make cartilage
  • The ability of their stem cells to recover from excessive inflammation
  • The total number of cells grown

What did we observe?

Without getting too deep in the weeds, based on our lab testing results, as shown above, a short course of supplementing testosterone didn’t help the participant’s stem cells.

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My Personal Experience

I am a big personal believer in male and female hormone supplementation in aging. Meaning as someone gets into their late 40s and early 50s and testosterone and growth hormone levels predictably drop and that patient goes into metabolic syndrome, then supplementing testosterone and growth hormone, based on what I have seen in the clinic can help reduce weight and keep that person active.

Hence, if a patient asks me if they should supplement their testosterone because they have “low T”, my answer is “absolutely”. However, that’s a very different question than, “Will supplementing testosterone improve my chances of a successful orthobiologics procedure?” On that subject, right now the answer is either “we don’t know” or “no” depending on how you interpret the scant data we have.

The upshot? The statement that we definitely know based on the science that supplementing testosterone will help ligaments heal from a PRP or BMC procedure is not supported by the available data. That could change as more research is performed but for now, if you have Low T, then by all means correct that problem. However, I wouldn’t expect that testosterone supplementation to increase your chances of a great outcome after an orthobiologic procedure.

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References:

(1) Hamlet WP, Liu SH, Panossian V, Finerman GA: Primary immunolocalization of androgen target cells in the human anterior cruciate ligament. J Orthop Res 1997;15:657-663.

(2) Lovering RM, Romani WA: Effect of testosterone on the female anterior cruciate ligament. Am J Physiol Regul Integr Comp Physiol 2005;289:R15-R22.

(3) Romani WA, Belkoff SM, Elisseeff JH: Testosterone may increase rat anterior cruciate ligament strength. Knee 2016;23:1069-1073.

(4) Tipton CM, Tcheng TK, Mergner W: Ligamentous strength measurements from hypophysectomized rats. Am J Physiol 1971;221:1144-1150.

(5) Griffin LY, Agel J, Albohm MJ, et al.: Noncontact anterior cruciate ligament injuries: Risk factors and prevention strategies. J Am Acad Orthop Surg 2000;8:141-150.

(6) Banerjee D, Mazumder S, Bhattacharya S, Sinha AK. The sex specific effects of extraneous testosterone on ADP induced platelet aggregation in platelet-rich plasma from male and female subjects. Int J Lab Hematol. 2014 Oct;36(5):e74-7. doi: 10.1111/ijlh.12188. Epub 2014 Jan 16. PMID: 24428876.

Chris Centeno, MD is a specialist in regenerative medicine and the new field of Interventional Orthopedics. Centeno pioneered orthopedic stem cell procedures in 2005 and is responsible for a large amount of the published research on stem cell use for orthopedic applications.
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NOTE: This blog post provides general information to help the reader better understand regenerative medicine, musculoskeletal health, and related subjects. All content provided in this blog, website, or any linked materials, including text, graphics, images, patient profiles, outcomes, and information, are not intended and should not be considered or used as a substitute for medical advice, diagnosis, or treatment. Please always consult with a professional and certified healthcare provider to discuss if a treatment is right for you.

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