Gender-Affirming Hormone Therapy: What You Need to Know About Medication Interactions and Side Effects

When you start gender-affirming hormone therapy (GAHT), your body begins to change in ways that align with your gender identity. For many, this is life-saving care. But it’s not just about taking estrogen or testosterone - it’s about understanding how those hormones talk to everything else in your medicine cabinet. If you’re on HIV meds, antidepressants, blood pressure pills, or even over-the-counter supplements, there’s a chance they’re talking back to your hormones - and not always in a good way.

How GAHT Works and Why Interactions Matter

Gender-affirming hormone therapy comes in two main forms: feminizing therapy for transgender women and nonbinary people assigned male at birth, and masculinizing therapy for transgender men and nonbinary people assigned female at birth. Feminizing therapy usually includes estradiol - often taken as pills, patches, or gels - along with anti-androgens like spironolactone or cyproterone acetate to block testosterone. Masculinizing therapy uses testosterone, delivered as injections, gels, or pellets.

These hormones don’t work in isolation. They’re broken down by liver enzymes - especially CYP3A4 and CYP2D6 - that also process dozens of other medications. When another drug interferes with these enzymes, it can make your hormone levels too high or too low. Too low? You might not get the physical changes you’re hoping for. Too high? You risk blood clots, liver stress, or mood swings.

According to a 2023 review of over 12,000 transgender patients, serious side effects from GAHT alone are rare - but when combined with other meds, the risk isn’t zero. That’s why knowing what’s in your regimen matters as much as knowing your dose.

Key Interactions with HIV Medications

Transgender people are 3.4 times more likely to be living with HIV than cisgender people. That means many on GAHT are also on antiretroviral therapy (ART). And here’s where things get tricky.

Some HIV drugs boost or block the liver enzymes that handle estrogen. For example:

• Cobicistat-boosted regimens (like darunavir/cobicistat) can raise estradiol levels by 40-60%. That might sound good - until you realize it could increase your risk of blood clots or high blood pressure.
• Efavirenz and other enzyme-inducing NNRTIs can drop estradiol levels by 30-50%. That might mean your breast development stalls or your mood worsens.
• Dolutegravir and other integrase inhibitors show little to no interaction - making them the safest choice for people on feminizing therapy.

For testosterone users, HIV meds rarely interfere. But if you’re on both GAHT and ART, your provider should check your hormone levels 4-6 weeks after starting or switching HIV meds. Don’t assume everything’s fine just because you feel okay.

PrEP and GAHT: No Need to Worry

Pre-exposure prophylaxis (PrEP) - the daily pill that prevents HIV - is safe to take with GAHT. A 2022 study of 172 transgender people on both tenofovir/emtricitabine (Truvada) and hormone therapy found no meaningful change in hormone levels or PrEP effectiveness. Testosterone levels stayed steady. Estradiol levels shifted by less than 5%. The drug levels in blood stayed within protective ranges.

Even the newer long-acting injectable PrEP (cabotegravir) shows no known interactions - though data is still limited. If you’re on PrEP and starting GAHT, you don’t need to stop or switch your prevention plan. Just keep your provider updated.

Psychiatric Medications: The Hidden Risk

Transgender people experience anxiety, depression, and PTSD at rates 2.5 times higher than cisgender people. That means many are on SSRIs, SNRIs, or mood stabilizers - and those can interfere with GAHT in ways few doctors expect.

• Fluoxetine (Prozac) and other SSRIs that block CYP2D6 can raise estradiol levels by slowing its breakdown. One case report showed estradiol levels doubling after starting fluoxetine - leading to breast tenderness and nausea.
• Carbamazepine and phenytoin (used for seizures or bipolar disorder) speed up CYP3A4, which can lower estrogen levels and reduce feminization effects.
• Testosterone doesn’t have clear pharmacokinetic interactions with most antidepressants - but some people report mood changes when starting testosterone. That doesn’t mean the meds are clashing - it might mean your body is adjusting to new hormone levels. Still, if your depression gets worse after starting T, your dose may need tweaking.

Here’s the hard truth: 97% of antidepressant trials never included transgender participants. So when your doctor says, “This should be fine,” they’re guessing. That’s why monitoring your mood and symptoms closely in the first 6-8 weeks is critical.

Other Common Medications to Watch For

You might not think about these, but they can make a difference:

• St. John’s Wort - a popular herbal supplement for mild depression - boosts CYP3A4 and can drop estradiol levels. Skip it.
• Grapefruit juice blocks CYP3A4 and can raise estrogen levels. One glass a day with your pills? It’s not worth the risk.
• Birth control pills - even if you’re on testosterone - can interfere with hormone balance. They’re not needed for pregnancy prevention in most cases, but if you’re using them for acne or cycle control, your provider should reassess.
• Thyroid meds - testosterone can increase thyroid-binding proteins, which may lower free thyroid hormone. If you’re on levothyroxine, your levels might need checking after starting T.

What Your Provider Should Be Doing

Not all clinics are prepared. A 2023 audit found only 41% of U.S. endocrinology clinics had a standard checklist for drug interactions in GAHT patients. That’s changing - but slowly.

Here’s what good care looks like:

1. Review your full medication list - including supplements, OTC drugs, and cannabis - before starting GAHT.
2. Check hormone levels at baseline, then again at 4-6 weeks after starting or changing any other medication.
3. Use therapeutic drug monitoring when possible - especially if you’re on HIV meds or psychiatric drugs.
4. Don’t assume “no interaction” means “no effect.” Sometimes, the body reacts even when the science doesn’t show it yet.

If your provider says, “We’ve never seen a problem,” ask: “Is that because it’s rare - or because no one’s looked?”

What’s New in 2025?

Research is catching up fast. The NIH-funded Tangerine Study, tracking 300 transgender adults on GAHT and psychiatric meds, will release its first results in mid-2025. Gilead Sciences now requires GAHT interaction testing in all new PrEP trials. And the FDA is pushing for more inclusive clinical trials - meaning future drug labels might actually say, “This may affect hormone levels in transgender patients.”

For now, the best advice is simple: keep a list. Write down every pill, patch, and supplement you take. Bring it to every appointment. Ask: “Could this affect my hormones?” Don’t wait for your provider to ask first.

Bottom Line: You’re Not Alone - But You Need to Be Informed

GAHT is safe. GAHT works. But it’s not magic. It’s medicine. And like all medicine, it plays well with some things - and poorly with others. The goal isn’t to scare you off hormones. It’s to help you get the most out of them - without surprises.

If you’re on HIV meds, antidepressants, or even just a daily vitamin - talk to your provider. Get your hormone levels checked. Adjust doses if needed. And know this: you deserve care that sees the whole picture - not just your gender, but every pill you swallow, every condition you live with, every part of your health.

Next Steps: What to Do Today

• Write down every medication, supplement, and herb you take - even the ones you forgot about.
• Call your pharmacy and ask if they’ve flagged any interactions between your hormones and other meds.
• If you’re on HIV meds or antidepressants, schedule a hormone level check in the next 6 weeks.
• Ask your provider: “Do you screen for GAHT-drug interactions? Can you show me your checklist?”
• If they say no - find a provider who does. Your health isn’t a guess.