As prescribing clinicians, we're no strangers to off-label use—it's an everyday part of practicing medicine. From managing migraines with beta blockers to using antidepressants for chronic pain, much of what we do involves applying evidence-based treatments beyond their FDA-approved indications. Gender affirming care is no exception. Most medications used for gender affirmation—like testosterone, estradiol, and puberty blockers—are prescribed off-label, not because they’re unproven or unsafe, but because the FDA approval process is lengthy, costly, and designed for pharmaceutical companies, not clinicians or patients. With transgender people comprising roughly 1% of the population, there’s little financial incentive for manufacturers to seek FDA labeling for gender affirming indications when they can already profit from these prescriptions without it. The vast majority of medical treatments used in transgender medicine are technically off-label.

Let’s break that down.

What Does Off-Label Mean?

“Off-label” prescribing refers to using an FDA-approved medication in a way not specifically listed on its label. This could be for a different:

• Condition

• Population (like age group or gender)

• Route or dosage

Importantly: off-label does not mean illegal, inappropriate, or unsafe. In fact, off-label prescribing is both common and often necessary in many areas of medicine.

How Common Is Off-Label Prescribing?

Off-label use is deeply embedded in clinical practice. Here’s what the data show:

• A 2006 study published in Archives of Internal Medicine found that approximately 21% of all prescriptions in the U.S. are off-label, and for some categories—like anticonvulsants or antipsychotics—up to 75% of use is off-label (Radley, Finkelstein & Stafford, 2006).

• Among pediatric populations, estimates range from 50% to 80% of prescriptions being off-label, due to fewer clinical trials involving children (Cuzzolin et al., 2006; Wharton, 2008).

• In oncology, critical care, and rare disease management, off-label prescribing is not just common—it’s standard.

So when we talk about off-label use in transgender medicine, we are not in rogue territory. We are right where much of medicine lives: applying best-available evidence to meet individual patient needs.

Transgender Medicine and Off-Label Prescribing

Gender affirming hormone therapies—like testosterone, estradiol, and puberty blockers (GnRH analogs)—are FDA-approved medications. However, none of them are FDA-labeled for gender affirmation. The same goes for many surgical interventions, voice therapy modalities, or progesterone use.

Why?

Because the FDA doesn’t regulate medical care—it regulates medications for specific indications. The Endocrine Society, WPATH SOC-8, most major medical societies and countless clinical experts support hormone therapy as medically necessary for many TGD people.

In practical terms, that means:

• Testosterone is FDA-approved for hypogonadism—not transgender medicine.

• Estradiol is labeled for menopausal symptoms—not for gender affirming care.

• GnRH agonists (like leuprolide) are labeled for precocious puberty or prostate cancer—not for pausing puberty in TGD youth.

Yet, these same medications are recommended by major medical bodies, including:

• The Endocrine Society Clinical Practice Guidelines (Hembree et al., 2017)

• WPATH Standards of Care, Version 8 (Coleman et al., 2022)

And more importantly, they save lives, reduce gender dysphoria, and improve mental health outcomes.

Why This Matters for Clinicians

We’re not doing something wrong by prescribing off-label for transgender medicine.

In fact, by staying current with evidence-based guidelines and engaging in shared decision-making with our patients, we are:

✅ Practicing safe, effective medicine
✅ Upholding principles of autonomy and informed consent
✅ Disrupting harmful, cis-centered care models that deny access under the guise of "safety"

Off-label doesn’t mean off-track—it means on the frontlines of patient-centered, justice-driven care.

Don’t Let “Off-Label” Stop You From Providing Care

At QueerCME, we provide AMA Category 1 CME, expert-led content, clinical toolkits, and real-talk about how to show up for TGD patients with confidence. We also address legal, ethical, and documentation practices around off-label prescribing, so you can feel equipped and empowered.

Ready to Learn More?

✨ Subscribe to QueerCME’s Premium tier for advanced training on topics like:

• How to document off-label prescriptions legally and ethically

• Hormone therapy protocols for youth and adults

• How to explain off-label care to patients and colleagues

Let’s raise the bar in queer and gender affirming healthcare—together.

References:

• Radley, D. C., Finkelstein, S. N., & Stafford, R. S. (2006). Off-label prescribing among office-based physicians. Archives of Internal Medicine, 166(9), 1021–1026. https://doi.org/10.1001/archinte.166.9.1021 

• Hembree, W. C., et al. (2017). Endocrine Treatment of Gender-Dysphoric/Gender-Incongruent Persons. Journal of Clinical Endocrinology & Metabolism, 102(11), 3869–3903. https://doi.org/10.1210/jc.2017-01658 

• Coleman, E., et al. (2022). Standards of Care for the Health of Transgender and Gender Diverse People Version 8. International Journal of Transgender Health, 23(sup1), S1–S258. https://doi.org/10.1080/26895269.2022.2100644 

• Cuzzolin, L., et al. (2006). Off-label and unlicensed prescribing for newborns and children in different settings. Acta Paediatrica, 95(6), 744–750.

• Wharton, G. T. (2008). Off-label drug use in children. American Family Physician, 77(6), 847–849.