When you start hormone replacement therapy (HRT) for menopause, you’re not just adding one medication to your routine-you’re changing how your whole body processes drugs. Many women don’t realize that HRT can make other medicines work differently, sometimes dangerously so. It’s not just about side effects like bloating or headaches. It’s about whether your epilepsy drug still controls seizures, if your thyroid pill is doing its job, or if your antidepressant suddenly stops working. These aren’t rare edge cases. They’re documented, real, and often missed by doctors who focus only on menopause symptoms.
How HRT Changes How Your Body Handles Medicines
HRT doesn’t just replace estrogen and progesterone-it changes the enzymes in your liver that break down other drugs. The most well-studied example is lamotrigine, a common epilepsy and mood stabilizer. When estrogen from HRT is present, your liver ramps up a specific enzyme called UGT1A4. This enzyme speeds up the breakdown of lamotrigine, so your blood levels drop. In one case reported by the Netherlands Pharmacovigilance Centre Lareb, a woman on lamotrigine for depression saw her symptoms return after starting Femoston (estradiol/dydrogesterone). Her lamotrigine levels fell by nearly half. When she stopped HRT, her mood improved again. This isn’t a guess-it’s measurable, repeatable, and now officially listed in European HRT product labels.
It’s not just lamotrigine. Other anticonvulsants like carbamazepine and phenytoin can also be affected. Even antibiotics like rifampicin (used for tuberculosis) and some HIV meds can interfere. The mechanism is the same: estrogen tricks your liver into metabolizing these drugs too fast. If you’re on any of these, your doctor needs to know you’re on HRT. Otherwise, you could have a seizure, a depressive relapse, or an infection that won’t clear.
Oral vs. Patches: A Big Difference
Not all HRT is the same. If you’re taking pills or capsules, your hormones go straight to your liver first. That’s where most drug interactions happen. But if you use a patch, gel, or spray, the hormones enter through your skin and bypass the liver. That’s why the NHS and other health bodies say transdermal HRT is less likely to interfere with other medicines.
For example, St. John’s wort-a popular herbal remedy for mild depression-is known to reduce the effectiveness of oral HRT. It does this by activating the same liver enzymes that break down estrogen. But if you’re on a patch? The interaction is much weaker, or sometimes absent. Same goes for other liver-metabolized drugs. If you’re on multiple medications, switching from pills to patches could be one of the safest choices you make.
Hidden Interactions: Cortisol, Testosterone, and More
Some interactions are sneaky because they don’t cause obvious symptoms. Take cortisol, the hormone your body uses to manage stress and inflammation. If you’re on hydrocortisone replacement for adrenal issues, and you start HRT, your blood tests might look normal-but you’re not getting the right amount of active cortisol. Why? Estrogen increases a protein called CBG, which binds cortisol tightly in the blood. The total cortisol level looks high, but the free, active part hasn’t changed. Your doctor might think you’re getting enough, when you’re actually under-treated. This can lead to fatigue, low blood pressure, or even adrenal crisis.
Another hidden risk: combining testosterone with hydrocortisone. The Pituitary Foundation warns this can cause fluid retention-swollen hands, feet, or ankles. It’s not just a nuisance. It can raise blood pressure and strain your heart. If you’re on both, your doctor should check for swelling and adjust doses accordingly.
Even natural products can interfere. Resveratrol, found in red wine and supplements, has a chemical structure similar to synthetic estrogen. While evidence is weak, it could theoretically add to estrogen’s effects. Rosemary extract might speed up estrogen breakdown in the liver, making HRT less effective. These aren’t just internet rumors-they’re documented in peer-reviewed databases like EBSCO. If you’re taking supplements, tell your doctor. Don’t assume they’re safe just because they’re natural.
Who’s at Highest Risk?
Not everyone on HRT needs to worry. But some groups are at much higher risk:
- Women on anticonvulsants (lamotrigine, carbamazepine, phenytoin)
- Those taking blood thinners like warfarin-estrogen can increase clotting risk
- People on thyroid medication-HRT can raise thyroid-binding proteins, making free thyroid hormone drop
- Patients on HIV or TB drugs that rely on liver metabolism
- Anyone using herbal remedies like St. John’s wort, ginseng, or black cohosh
- Women with adrenal insufficiency on hydrocortisone
If you fall into any of these groups, your HRT isn’t just about hot flashes. It’s a drug interaction waiting to happen. Your doctor should check your medication list before starting HRT-and again if you add or change anything.
What to Do Before Starting HRT
Don’t wait for a problem to arise. Here’s what you should do before your first prescription:
- Make a full list of every medication, supplement, and herbal remedy you take-even over-the-counter ones.
- Bring it to your doctor. Don’t assume they’ll ask. Many don’t.
- Ask: “Could this interact with my other medicines?” Be specific about lamotrigine, thyroid meds, blood thinners, or steroids.
- If you’re on a high-risk drug, request a blood test before and 4-6 weeks after starting HRT to check levels.
- Consider transdermal HRT if you’re on multiple liver-metabolized drugs.
- Never stop or change a medication without talking to your doctor-especially epilepsy or antidepressant drugs.
The NHS and other health agencies stress: Always tell your prescriber about all medicines you’re taking. This isn’t just good advice-it’s essential for safety.
When to Call for Help
Some interactions cause sudden, dangerous symptoms. If you start HRT and notice any of these, contact your doctor immediately:
- Sudden, severe headache or dizziness
- Loss of vision, blurred vision, or seeing flashing lights
- Difficulty speaking or slurred speech
- Chest pain or shortness of breath
- Swelling in hands, feet, or ankles (especially if on hydrocortisone)
- Return of depression, anxiety, or seizures
These aren’t normal side effects. They could mean a blood clot, stroke, or medication failure. Don’t wait. Get help right away.
The Bottom Line
HRT can be life-changing for menopausal symptoms. But it’s not a simple hormone fix. It’s a complex drug that changes how your body handles everything else you take. The science is clear: estrogen-based HRT can lower levels of lamotrigine, thyroid meds, and other critical drugs. Transdermal options are safer. Herbal supplements aren’t risk-free. And ignoring interactions can lead to serious health events.
If you’re considering HRT-or already on it-talk to your doctor about every medication you use. Ask for blood tests if you’re on a narrow-therapeutic-index drug. Don’t assume your pharmacist or GP knows all the risks. Most don’t. The September 2022 update to HRT labels in Europe was a wake-up call. It’s time women started treating HRT like the powerful drug it is-not just a quick fix for hot flashes.
Can HRT make my antidepressant stop working?
Yes, especially if you’re taking lamotrigine, which is used for both epilepsy and depression. Estrogen in HRT can speed up how fast your body breaks down lamotrigine, lowering its blood levels. This can cause depression symptoms to return or worsen. Other antidepressants may also be affected, though evidence is less clear. If you notice your mood changing after starting HRT, get your medication levels checked.
Are HRT patches safer than pills when taking other meds?
Yes. Patches, gels, and sprays deliver hormones through the skin, bypassing the liver. This avoids the enzyme activation that causes most drug interactions. If you’re on epilepsy meds, antibiotics, HIV drugs, or thyroid medication, transdermal HRT is often the safer choice. Pills are more likely to interfere with other drugs.
Does St. John’s wort affect HRT?
Yes, especially with oral HRT. St. John’s wort activates liver enzymes that break down estrogen, making HRT less effective. This can bring back hot flashes or other menopause symptoms. It may also increase the risk of breakthrough bleeding. Avoid it while on HRT unless your doctor approves it after checking your specific regimen.
Can HRT interfere with thyroid medication?
Yes. Estrogen increases a protein that binds thyroid hormone, lowering the amount of free, active hormone in your blood. This can make your thyroid medication less effective. You may need a higher dose after starting HRT. Always have your thyroid levels checked 6-8 weeks after beginning HRT.
What should I do if I’m on hydrocortisone and want HRT?
Don’t start HRT without talking to your endocrinologist. Estrogen raises cortisol-binding proteins, so your blood tests will show high total cortisol-but your active, free cortisol may be unchanged. This can trick your doctor into thinking you’re getting enough hydrocortisone. You may need more hydrocortisone, or different monitoring methods like ACTH stimulation tests. Swelling in hands or feet is another red flag.
Is it safe to take HRT with blood thinners like warfarin?
It’s possible, but risky. Estrogen increases clotting factors, which can reduce warfarin’s effectiveness. This raises your risk of blood clots. If you’re on both, your INR levels must be checked more often-especially when starting or stopping HRT. Your doctor may need to adjust your warfarin dose. Transdermal HRT is preferred over pills in these cases.
How long should I wait after stopping HRT before surgery?
The U.S. National Library of Medicine recommends stopping estrogen and progestin at least 4 to 6 weeks before major surgery or prolonged bed rest. This reduces the risk of blood clots, especially if you smoke, are overweight, or have a history of clots, stroke, or heart disease. Always tell your surgeon you’ve been on HRT-even if you stopped it weeks ago.
Next Steps
If you’re on HRT and other medications, schedule a medication review with your doctor or pharmacist. Bring your complete list-prescription, OTC, and supplements. Ask specifically about lamotrigine, thyroid meds, blood thinners, and steroids. If you’re on oral HRT and take multiple liver-metabolized drugs, ask if switching to a patch is an option. Keep a symptom journal: note mood changes, seizure frequency, swelling, or new fatigue. These are clues to hidden interactions. Don’t wait for a crisis. A simple conversation today could prevent a hospital visit tomorrow.
