When you start Hormone Replacement Therapy (HRT) for menopause, you’re not just adding one medication to your routine-you’re introducing a powerful hormonal shift that can change how your body handles other drugs. Many women don’t realize that the estrogen and progestin in HRT can interfere with medications they’ve been taking for years, sometimes with serious consequences.
Why HRT Changes How Other Drugs Work
HRT doesn’t just replace hormones-it affects your liver’s ability to process other medicines. Estrogen, especially in oral form, triggers enzymes like UGT1A4 that break down certain drugs faster. This means those drugs leave your system sooner, dropping below the level needed to work properly.For example, if you’re taking lamotrigine for epilepsy or depression, adding HRT can cause your lamotrigine levels to crash. A case reported by the Netherlands Pharmacovigilance Centre Lareb in 2022 showed a woman’s depression returned after starting Femoston (a combination of estradiol and dydrogesterone). Her lamotrigine blood levels had dropped by nearly half. When she stopped HRT, her symptoms improved and her lamotrigine levels returned to normal.
This isn’t rare. Estrogen-based HRT is now known to reduce the effectiveness of several anticonvulsants, including carbamazepine and phenytoin. If you’re on any of these, your seizure control or mood stability could be at risk.
Drugs That Definitely Interact with HRT
Some medications are well-documented to clash with HRT. Here’s what you need to watch for:- Lamotrigine - Used for epilepsy and bipolar disorder. Estrogen can cut its levels by up to 50%.
- Antibiotics - Rifampicin and rifabutin (used for tuberculosis) speed up HRT breakdown, making it less effective.
- HIV meds - Some protease inhibitors and non-nucleoside reverse transcriptase inhibitors interfere with hormone metabolism.
- St. John’s wort - This popular herbal remedy for low mood can make HRT tablets useless by boosting liver enzymes that break down estrogen.
- Thyroid meds - Estrogen increases thyroid-binding proteins, which can lower free thyroid hormone levels. You may need a higher dose of levothyroxine.
Even over-the-counter supplements aren’t safe. Resveratrol, found in red wine and grapes, has a chemical structure similar to synthetic estrogen. It may compete with HRT or alter its effects. Rosemary extract might speed up estrogen breakdown in the liver-though evidence is weak, it’s not worth the risk.
What About Corticosteroids and HRT?
If you’re on hydrocortisone for adrenal insufficiency, HRT can mess with your test results. Female hormones increase a protein called corticosteroid-binding globulin (CBG), which binds to cortisol in your blood. This makes your total cortisol levels look high-even though your active, free cortisol hasn’t changed.This is dangerous. Doctors rely on cortisol tests to adjust your hydrocortisone dose. If you’re on HRT, those tests become misleading. You could end up under- or over-treated. The Pituitary Foundation recommends using alternative monitoring methods, like ACTH stimulation tests, instead of relying on cortisol blood levels alone.
Transdermal Patches vs. Pills: A Big Difference
Not all HRT is the same. If you’re on oral pills, your liver processes the hormones first. This is where most drug interactions happen.Transdermal patches, gels, or sprays deliver hormones directly into your bloodstream, bypassing the liver. That means they’re far less likely to interfere with other medications.
The NHS confirms that skin patches are less affected by St. John’s wort, antibiotics, and anticonvulsants. If you’re on multiple medications, switching from pills to patches could reduce your interaction risk significantly. It’s not a magic fix-but it’s often the smartest first step.
Who’s at Highest Risk?
Some women are more vulnerable to HRT interactions than others:- Those taking drugs with a narrow therapeutic index-like warfarin, digoxin, or antiseizure meds-where even small changes in blood levels can cause harm.
- People with epilepsy, depression, or autoimmune conditions on immunosuppressants.
- Women on multiple medications-especially older adults managing several chronic conditions.
- Those using herbal remedies or supplements without telling their doctor.
The NIH warns that with any drug, there’s potential for interaction-but it’s especially risky when you’re on HRT plus other meds that need precise dosing. One missed interaction could mean a seizure, a blood clot, or a depressive relapse.
What You Should Do Before Starting HRT
Don’t assume your doctor knows everything on your list. Many women forget to mention vitamins, teas, or herbal drops. Here’s your checklist:- Make a full list of every medication, supplement, and herb you take-including dosages and how often.
- Bring it to your appointment. Don’t rely on memory.
- Ask: “Could this interact with HRT?” Be specific about what you’re taking.
- If you’re on lamotrigine, anticonvulsants, or hydrocortisone, request a blood level test before and 4-6 weeks after starting HRT.
- Consider transdermal HRT if you’re on multiple meds-it’s safer.
Some GPs still think HRT is just “a pill for hot flashes.” But the science shows it’s a systemic hormone intervention with wide-reaching effects. You deserve a doctor who treats it that way.
Signs Something’s Wrong
If you start HRT and notice any of these, don’t wait-call your doctor:- Your seizures become more frequent or severe.
- Your depression returns or worsens.
- You feel unusually swollen in your hands, feet, or ankles (could mean water retention from steroid interactions).
- You have a sudden, severe headache, vision loss, or trouble speaking (signs of stroke or blood clot).
- Your mood swings or energy levels change drastically.
These aren’t normal side effects of HRT. They’re red flags that another drug isn’t working right.
What’s Not Well Known (Yet)
The truth? We don’t know everything about HRT interactions. Most data comes from case reports or biological plausibility-not large clinical trials. The PubMed review from 2023 says evidence is “scarce and mainly indirect.”That means:
- Interactions with newer drugs (like certain antidepressants or GLP-1 weight loss meds) aren’t well studied.
- Bioidentical HRT products have almost no interaction data.
- Long-term effects on drug metabolism in women over 70 are still unclear.
This isn’t a reason to avoid HRT. It’s a reason to be cautious, informed, and proactive.
Regulatory Changes Are Happening
In September 2022, the Netherlands Pharmacovigilance Centre Lareb flagged the lamotrigine-HRT interaction. Within months, European regulators updated the product labels for all estrogen-based HRT to include this warning. That’s rare. It shows how seriously the medical community now takes these interactions.But the changes are slow. Many prescriptions are still written without checking for interactions. That’s why you need to be your own advocate.
Final Advice: Don’t Guess, Test
HRT can be life-changing for menopausal symptoms. But it’s not a simple fix. When you’re on other meds, it becomes a balancing act.Your best move? Talk to your doctor, pharmacist, or a menopause specialist. Ask for blood tests before and after starting HRT if you’re on critical meds. Choose patches over pills if possible. And never stop or change a drug without professional advice.
The goal isn’t to scare you off HRT. It’s to make sure you get the relief you need-without risking your other treatments.
Can HRT make my epilepsy worse?
Yes, if you’re taking oral estrogen-based HRT and anticonvulsants like lamotrigine, carbamazepine, or phenytoin. Estrogen increases liver enzymes that break down these drugs, lowering their levels in your blood. This can lead to more seizures. If you notice increased seizures after starting HRT, get your medication levels checked right away. Switching to a transdermal patch may help reduce this risk.
Is it safe to take St. John’s wort with HRT?
No. St. John’s wort strongly activates liver enzymes that break down estrogen. This can make your HRT pills ineffective, bringing back hot flashes, night sweats, and mood swings. Even if you feel fine, your hormone levels may be too low. The NHS and multiple medical guidelines warn against combining them. If you’re using St. John’s wort for low mood, talk to your doctor about safer alternatives.
Do HRT patches have fewer interactions than pills?
Yes. Patches, gels, and sprays deliver hormones through the skin, bypassing the liver. This means they don’t trigger the same enzyme changes that oral HRT does. As a result, they’re much less likely to interfere with epilepsy meds, antibiotics, or antidepressants. If you’re on multiple medications, transdermal HRT is often the safer choice.
Can HRT affect my thyroid medication?
Yes. Estrogen increases a protein that binds to thyroid hormone, making less of it available to your body. If you’re on levothyroxine, your thyroid levels may drop after starting HRT. You might need a higher dose. Your doctor should check your TSH and free T4 levels about 6-8 weeks after starting HRT to make sure your thyroid treatment is still working.
Should I stop HRT before surgery?
If you’re at risk for blood clots-due to smoking, obesity, history of clots, or other factors-your doctor may advise stopping HRT 4 to 6 weeks before surgery. Estrogen increases clotting risk, and surgery adds more. This is especially important if you’re on oral HRT. Patches carry less risk, but your surgeon will still want to know you’re on HRT. Never stop without medical advice.
Can HRT interfere with cortisol tests for adrenal problems?
Yes. HRT increases a protein called CBG, which binds to cortisol in your blood. This makes your total cortisol levels look high-even if your active cortisol is normal. If you’re on hydrocortisone for adrenal insufficiency, your doctor can’t rely on standard cortisol tests. They’ll need to use other methods, like ACTH stimulation tests, to adjust your dose safely.
Are bioidentical HRT products safer with other drugs?
No. Bioidentical HRT (like compounded estradiol or progesterone) is often marketed as safer, but there’s almost no research on how it interacts with other medications. Just because it’s “natural” doesn’t mean it’s safer. It still contains estrogen or progesterone, which can trigger the same liver enzyme changes as synthetic HRT. Stick to regulated, tested products unless your doctor has a specific reason to recommend otherwise.
Next Steps: What to Do Today
If you’re on HRT and another medication:- Review your list of all drugs and supplements.
- Check if any are on the high-risk list: lamotrigine, anticonvulsants, antibiotics for TB, St. John’s wort, hydrocortisone.
- If yes, book a quick appointment with your GP or pharmacist. Ask: “Could this interact with my HRT?”
- Ask if switching to a patch would help.
- If you’re on lamotrigine or hydrocortisone, request a blood test before and after starting HRT.
Small steps now can prevent serious problems later. You’re not being overly cautious-you’re being smart.