Gender-Affirming Hormone Therapy: How Other Medications Affect Your Hormone Levels

When you're on gender-affirming hormone therapy (GAHT), your body is changing in ways that matter deeply to your identity and well-being. But what happens when you're also taking other medications-antibiotics, antidepressants, HIV drugs, or even over-the-counter supplements? These aren't just background details. They can change how well your hormones work, or even push your body into dangerous territory.

How Hormones and Medications Talk to Each Other

Your body doesn’t treat hormones and other drugs as separate things. They all use the same metabolic pathways, especially enzymes in your liver. The most important one is called CYP3A4. It’s like a busy factory worker that breaks down drugs so your body can get rid of them. Estradiol-the main hormone used in feminizing therapy-is processed mainly by this enzyme. So if something else slows down or speeds up this factory, your hormone levels can swing wildly.

For example, if you're taking cobicistat (part of some HIV treatments like Stribild or Descovy), it shuts down CYP3A4. That means your estradiol doesn’t get broken down as fast. Studies show estradiol levels can jump by 40% to 60% within two weeks. That’s not just a small change-it can lead to blood clots, high blood pressure, or mood swings. On the flip side, efavirenz (used in older HIV regimens) turns on CYP3A4. That speeds up estradiol breakdown, dropping levels by 30% to 50%. You might start feeling like your hormones aren’t working anymore: less breast development, more fatigue, or a return of unwanted body hair.

Testosterone, used in masculinizing therapy, is handled differently. It’s mostly broken down by enzymes called 5-alpha reductase and aromatase. That means fewer drug interactions overall. But if you're on carbamazepine (a seizure or mood stabilizer), it still activates CYP3A4 and can lower testosterone levels enough to reduce its effects. You might notice less muscle gain, lower energy, or decreased libido-even if you’re taking the right dose.

HIV Medications and GAHT: A Delicate Balance

Transgender people are 3.4 times more likely to be living with HIV than cisgender people. That means many people on GAHT are also on antiretroviral therapy (ART). The good news? Most modern HIV drugs play nicely with hormones. But the old ones? Not so much.

NNRTIs like efavirenz and nevirapine are the biggest red flags. They can slash estradiol levels so hard that some people stop seeing the benefits of hormone therapy. In one study, 8 out of 12 case reports showed this drop. If you're on one of these, your provider should check your estradiol levels every 3 months after starting ART. You might need a higher hormone dose-or switch to a different HIV drug.

The newer HIV drugs are much safer. Integrase inhibitors like dolutegravir (Tivicay) actually raise estradiol by 25% to 35%. That’s usually not a problem, but it’s still worth monitoring. If you’re on a boosted protease inhibitor like darunavir/cobicistat, your estradiol will likely rise. No need to panic-but do tell your doctor. They might reduce your estradiol dose slightly to avoid side effects.

The one exception? GnRH agonists like leuprolide. These are often used to block puberty in teens or to suppress natural hormones in adults. They don’t interact with any HIV drugs. That’s one of the few clear-cut answers in this whole field.

PrEP and Hormones: No Need to Worry

If you’re on PrEP to prevent HIV, you might be anxious about whether it’ll interfere with your hormones. The good news? It doesn’t. A major 2022 study followed 172 transgender people taking tenofovir/emtricitabine (Truvada or Descovy) while on GAHT. The results? Hormone levels changed by less than 5%. Tenofovir levels didn’t budge either. You can take PrEP and GAHT together without adjusting either.

Even the newer long-acting injectable PrEP, cabotegravir (Apretude), shows no known interactions in early data. But because it’s so new, there aren’t many studies yet. If you’re starting it, your provider should still track your hormone levels for the first few months just to be safe.

Psychiatric Medications: The Hidden Risk

Transgender people are 2.5 times more likely to have depression, anxiety, or PTSD. That means many are on antidepressants, mood stabilizers, or antipsychotics. And here’s where things get murky.

SSRIs like fluoxetine (Prozac) and sertraline (Zoloft) can block CYP2D6, another liver enzyme that helps break down estradiol. That means your estradiol might build up-possibly leading to side effects like breast tenderness, nausea, or mood swings. It’s not always obvious, and most doctors don’t check for it.

The real danger comes from drugs that speed up metabolism. Carbamazepine (Tegretol), phenytoin (Dilantin), and rifampin (an antibiotic for TB) all crank up CYP3A4. If you’re on one of these, your estradiol levels can crash. One study found 17 cases where testosterone therapy made antidepressants less effective. That doesn’t mean the antidepressants stopped working-it means the body’s hormonal shift changed how the brain responded. Some people needed their antidepressant dose raised by 25% to 50% within six weeks.

Here’s the problem: almost no psychiatric drug trials include transgender people. A 2021 analysis found only 3% of antidepressant studies included trans participants. That means we’re guessing a lot. If you’re starting GAHT and already on psychiatric meds, watch for changes in mood, sleep, or energy. Don’t assume it’s just "adjusting to hormones." It might be a drug interaction.

What You Should Do Right Now

This isn’t about fear. It’s about control. You deserve to know what’s happening in your body. Here’s what to do:

• Make a full list of everything you take-prescription, over-the-counter, herbal, vitamins. Even melatonin or St. John’s wort can interfere.
• Bring it to every appointment. Don’t assume your doctor knows. Only 41% of U.S. endocrinology clinics have standardized screening for these interactions.
• Ask for hormone level checks after starting or changing any new medication. Estradiol and testosterone levels should be checked 4 to 6 weeks after a new drug is added.
• Know your HIV meds. If you’re on efavirenz, talk to your provider about switching. If you’re on cobicistat, ask if your estradiol dose needs adjusting.
• Track your symptoms. Did your breasts stop growing? Did your mood drop? Did your energy vanish? These aren’t "just in your head." They could be drug interactions.

What’s Changing in 2025

The science is catching up. The NIH-funded Tangerine Study is tracking 300 transgender adults on GAHT and 12 common psychiatric drugs. Preliminary results are due in mid-2025. That’s the first large-scale look at how antidepressants, antipsychotics, and mood stabilizers interact with hormones.

The FDA now encourages drug companies to include transgender people in clinical trials. Gilead Sciences, maker of Truvada and Descovy, now requires GAHT interaction testing in all new PrEP trials after their 2022 study proved it was possible-and necessary.

But until then, you’re still the most important part of your care. You know your body better than any chart or study. If something feels off, speak up. Your hormones aren’t just chemicals-they’re part of your identity. And you deserve treatment that respects that.