Testosterone replacement therapy increases the risk of nonunion after surgical fixation of lower extremity fractures

Most men on testosterone replacement therapy -- TRT -- think about the familiar metrics: energy, libido, muscle, mood, hematocrit, estradiol. What almost nobody discusses before starting, and what almost no TRT clinic mentions at the six-month check-in, is what happens if you break your leg.

A 2025 study indexed on PubMed found a statistically significant association between TRT use and an elevated risk of nonunion following surgical fixation of lower extremity fractures (https://pubmed.ncbi.nlm.nih.gov/42314529/). That is a short sentence with a long set of implications. If you are on TRT and you fracture your femur, tibia, fibula, or ankle and need surgery to repair it, the evidence now suggests your bone may be slower -- or less likely -- to heal cleanly than it would be without exogenous testosterone in the picture.

This does not mean you should stop TRT. It does mean you should understand the biology, know what to disclose to your surgical team, and have a prescribing clinician who monitors enough to catch problems early. Here is what the evidence suggests and how we think about it at NoMi Beach Health.

What nonunion means and why it is serious

When a bone breaks, the body launches a complex repair process. Bone cells, blood vessels, growth factors, and inflammatory signals work together in a sequence that -- when everything goes right -- produces new bone that bridges the fracture gap. Clinicians typically expect meaningful healing progress within several months. When that progress stalls or stops, the result is called nonunion.

Nonunion is not just a delayed inconvenience. It means chronic pain, mechanical instability, and often a second surgery -- sometimes with bone grafts, specialized hardware, or electrical stimulation devices. In the lower extremity specifically (hip, thigh, lower leg, ankle), nonunion can mean months of non-weight-bearing, muscle loss, and a significant quality-of-life hit.

The causes of nonunion are well-studied. Poor blood supply to the fracture site is the most common mechanical factor. Other established contributors include smoking, uncontrolled diabetes, vitamin D deficiency, corticosteroid use, and heavy NSAID use (https://pubmed.ncbi.nlm.nih.gov/8447736/). These are the variables that orthopedic surgeons and anesthesiologists have been asking about for decades. TRT is a newer entry to that list.

How does testosterone affect fracture healing?

The biology here is genuinely complicated, and the honest answer is that researchers are still working it out. Testosterone does not act on bone in a simple, linear way. It exerts effects both directly -- through androgen receptors on bone cells -- and indirectly, through its conversion to estradiol, which has its own important role in bone metabolism (https://pubmed.ncbi.nlm.nih.gov/27031881/).

In the context of bone density and overall skeletal health, the story generally favors testosterone. Hypogonadism (low testosterone) is a recognized risk factor for osteoporosis, and restoring testosterone in deficient men tends to improve bone mineral density. That part of the story is fairly well supported.

Fracture healing, though, is a different biological process than bone maintenance. It involves a specific cascade: an initial inflammatory phase, then a reparative phase where cartilage forms at the fracture site, then a remodeling phase where that cartilage is replaced by bone. Disruptions to any phase -- including hormonal disruptions -- can derail the sequence (https://pubmed.ncbi.nlm.nih.gov/17920534/).

Animal studies and early human data have suggested that supraphysiologic androgen levels -- the kind seen in anabolic steroid use, and potentially in some TRT protocols that push testosterone to the high end of normal or above -- may interfere with the inflammatory signaling that kicks off the repair cascade (https://pubmed.ncbi.nlm.nih.gov/34423884/). The 2025 study in the trending research extends this signal into a real-world surgical population. The association is there. The mechanism is plausible. The clinical implication is that TRT is now something orthopedic teams should know about before operating.

What this means for men currently on TRT

A few things worth being clear about before we go further.

First, this is an association, not a guaranteed outcome. Most men on TRT who fracture a bone will heal. The research suggests the risk of nonunion is elevated -- not that nonunion is inevitable. Risk factors shift probabilities; they do not write fates.

Second, this does not mean TRT is the wrong choice for men with confirmed hypogonadism. The Endocrine Society and the American Urological Association both recognize testosterone deficiency as a real clinical syndrome with real consequences, and TRT -- when properly indicated and monitored -- remains a well-supported treatment (https://www.auanet.org/guidelines-and-quality/guidelines/testosterone-deficiency-guideline) (https://pubmed.ncbi.nlm.nih.gov/29562364/). What this new evidence adds is a risk to weigh and disclose -- not a reason to abandon a protocol that is helping you.

Third, this is exactly why the details of your TRT protocol matter. Where your total testosterone actually lands on labs -- whether your clinic is targeting a physiologic range or an aggressive high end -- is relevant information for your surgeon. A protocol that keeps you at 550 ng/dL is a different conversation than one that has you running at 1100 ng/dL. We track this because it matters for more than just your hematocrit.

If you fracture a lower extremity bone and need surgery while you are on TRT, here is what we recommend discussing with your surgical team and with us:

• Your current total and free testosterone levels, and where your protocol is targeting
• Your most recent hematocrit (elevated hematocrit can affect healing through blood viscosity)
• Any other factors that increase nonunion risk: smoking status, vitamin D level, diabetes control, NSAID use
• Whether a temporary hold on TRT perioperatively is appropriate for your specific case -- this is a decision for your clinician and surgeon together, not something to do unilaterally

For a deeper look at what a well-structured TRT protocol looks like and what monitoring should include, see our post on understanding testosterone replacement therapy.

Why this is the kind of thing most TRT clinics will not tell you

High-volume, single-vertical TRT clinics are built around volume and convenience. That is not a conspiracy -- it is a business model. The problem is that a business model built around rapid intake and easy refills does not naturally generate time for conversations about emerging research on fracture biology.

The clinician who saw you for 12 minutes last year, ordered one lab panel, and wrote your prescription is probably not following the orthopedic surgery literature. They are not going to flag this finding the next time you refill. And if you tear your ACL skiing or fracture your ankle stepping off a curb -- both more common than people think for active men in their 40s and 50s -- your surgical team may not think to ask about your testosterone protocol either.

This is the gap that concierge, integrative medicine is designed to fill. Not because we are trying to complicate things, but because your hormones do not live in a silo. They interact with your cardiovascular system, your bone biology, your liver enzymes, your fertility, and -- as this research makes clear -- your surgical outcomes. When we manage TRT at NBH, we are managing a hormone system inside a whole person, not a single lab value.

If you want context on how we think about men's health holistically after 35, our concierge men's health after 35 post covers the broader picture.

What we look for and how we monitor

At NoMi Beach Health, Dr. Jezwah Harris (NP, JD, MBA, FNP-BC, MEP-C) structures TRT protocols around AUA guidelines and monitors at defined intervals because the evidence requires it -- not as an upsell.

What clinicians look for at the six-week and three-month marks includes total testosterone, free testosterone, hematocrit, estradiol, and a metabolic panel. PSA is added for men over 40. For men with any bone-related risk factors -- a family history of osteoporosis, prior fractures, low vitamin D, or corticosteroid use -- we also look at vitamin D levels and may recommend a DEXA scan baseline.

If you fracture a bone while on our protocol, we coordinate. That means communicating your current labs and protocol details to your surgical team on request, discussing whether a perioperative hold is appropriate, and following up after surgery to re-evaluate the protocol in light of your healing trajectory.

This is not standard care at most TRT clinics. It is standard care here.

The TRAVERSE trial, published in the New England Journal of Medicine in 2023, gave us important cardiovascular safety data on long-term TRT in older men (https://www.nejm.org/doi/full/10.1056/NEJMoa2215025). The 2025 nonunion finding adds another data point that belongs in the risk-benefit conversation. Neither finding kills the case for TRT in men with confirmed deficiency. Both findings make the case for TRT managed by someone who reads the literature and adjusts accordingly.

The honest bottom line

If you are on TRT -- or considering it -- the nonunion finding is not a reason to panic. It is a reason to be informed. Here is what it actually changes:

• Before starting TRT: Your full medical history should include fracture risk factors, bone density concerns, and activity level. If you are a skier, a runner, or work in a physical job, your odds of ever needing orthopedic surgery are not trivial. That context belongs in your intake.
• While on TRT: Your protocol should target a physiologic range, not an aggressive ceiling. Your labs should be reviewed regularly, and your vitamin D and hematocrit should not be ignored.
• If you fracture a bone: Your surgical team needs to know you are on TRT. Bring your most recent labs. Ask your prescribing clinician to communicate with your surgeon. Do not make decisions about stopping or continuing the protocol without that conversation.

The men who do best on long-term TRT are not the ones who got on it fastest. They are the ones who had the right conversation at the start, with a clinician who did not stop paying attention after the prescription was written.

If you are managing TRT on your own, through a clinic that has stopped checking, or without a provider who keeps up with the research, our men's health services page explains what a more thorough approach looks like. You can also call us directly at (786) 744-5152 to ask whether your current protocol is set up to protect you -- not just in the gym, but in every clinical scenario that might come up over the years you are on it.