Menopause, Hormones, and Epilepsy: What You Need to Know
- Nov 24, 2024
- 9 min read
I recently had the privilege of seeing a remarkable, intelligent patient with epilepsy who sought my expertise as a menopause specialist to address concerns about vaginal dryness and low libido. She was understandably cautious about using menopausal hormone therapy (MHT), particularly estrogen, due to fears it might exacerbate her seizures—a concern rooted in earlier studies suggesting a potential link between estrogen and increased seizure activity. But what does the most recent research reveal?
What We Know About Hormones and Seizures
Epilepsy and Hormonal Changes: Hormones like estrogen and progesterone can influence seizures. Some women with epilepsy experience more seizures around their menstrual cycles (called catamenial epilepsy), often linked to hormone fluctuations.
Menstrual Cycle Old Research: Much of the concern about estrogen and seizures comes from older studies using high doses of synthetic estrogen, which isn't the same as the bio-identical estradiol commonly prescribed today. For example:
A 1959 study found that high doses of synthetic estrogen increased seizure activity in some women.
Research from the 1970s suggested that higher estrogen and lower progesterone levels might increase seizures.
Newer Insights: Bio-identical progesterone, often used in modern MHT, has anti-seizure properties, unlike synthetic progestins. Small studies suggest that low-dose, stable forms of bio-identical estradiol and progesterone might not have the same risks.
What About Menopause?
Hormonal changes during perimenopause (when hormones fluctuate) might temporarily worsen seizures for some women. But after menopause, when hormone levels stabilize, many women with epilepsy report fewer seizures.
What Does This Mean for MHT?
Modern MHT typically uses low, stable doses of bio-identical hormones, like 17-beta estradiol and micronized progesterone. These forms are very different from synthetic hormones used in older studies or high-dose birth control pills.
Research on MHT in women with epilepsy is limited, but international epilepsy organizations suggest that body-identical hormones are likely safe when carefully managed.
Things to Consider:
Personalized Care: If you have epilepsy, MHT might still be an option. Your menopause specialist can work with you and your neurologist to make sure your treatment is safe and effective.
Medication Interactions: Some anti-seizure medications can interact with hormone therapy so it is important to work closely with your doctor to monitor medication levels when necessary.
Stable Hormone Levels: Low, steady doses of bio-identical hormones are less likely to cause problems than high-dose or fluctuating synthetic hormones.
Final Thought:
When deciding on MHT, I often ask, "Would this patient be safe to become pregnant?" During pregnancy, estradiol levels can be 100 times higher than in MHT. If a patient can safely tolerate those levels, low-dose MHT might be worth considering, provided it’s monitored closely.
If you're a woman with epilepsy navigating menopause, know that you're not alone. We're here to explore all options and find a solution that works best for your health and quality of life.
Going back to my patient:
Her seizures flared around her menstrual cycle (when estrogen and progesterone levels were low).
She had more seizures during perimenopause (a time when estrogen levels fluctuate wildly and progesterone levels tend to run low).
She experienced more seizures after becoming postmenopausal (when estrogen and progesterone levels are essentially zero).
My next questions would be:
Did she ever take a birth control pill (which contains high doses of synthetic estrogen and progesterone)? If so, how did her seizures behave during that time (more frequent, less frequent, or no change)?
Did her seizure frequency change during pregnancy (when estrogen and progesterone levels are naturally very high)?
Looking at all this information together, I feel confident that I could guide my patient to confidently consider whether menopausal hormone therapy is right for her. If she decides to try it, I would recommend first consulting with her neurologist. After that, if she still wants to go ahead, we would start with a lower dose of bio-identical estradiol, paired with a slightly higher dose of progesterone, and monitor her response to adjust as needed.
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Below is a summary of the data I found in order to make the best recommendation I can for my patient:
Buckle up, folks, because this is a bit dry but worth your while if this affects you or someone you love.
Like so much in menopause, the studies are sparse and often weak, and they do not provide information about the bio-identical (aka body-identical) hormones (17-beta estradiol and progesterone) that are prescribed in my clinic. Rather, they are mostly based on synthetic estrogen (Premarin or conjugated equine estrogen). What I found was that the oldest study on the subject, from which much of the understanding of estrogen's effects on epilepsy is derived, was done back in 1959. This study showed that with high doses of synthetic estrogen, seizure frequency increased.
Another study from 1976 found "a positive correlation between the number of secondary generalized seizures and the mean estrogen/progesterone (E/P) ratios and a negative correlation to plasma progesterone levels. Three periods without ovulation showed an increase in the number of fits during days of high estrogen. The number of fits seemed not to be correlated to changes in body weight." This is interesting and concerning. This suggests that when estrogen levels are high and progesterone levels are relatively low (such as when a woman has anovulatory cycles), seizures are more likely.
Well that is concerning.... I see why my patient is worried about using menopausal hormone therapy.
As a non-neurologist, my first go-to resource when looking for information about epilepsy and hormones is called UpToDate, which is a fantastic resource for many topics. UpToDate states that it provides "the latest information to support better patient outcomes across the entire healthcare ecosystem." UpToDate is a fantastic resource, and I use it every day at work. When I researched epilepsy and menopause on UpToDate, I found that the evidence available there is based on a 1999 questionnaire study (which is not considered great evidence at all) of 42 women. It concludes that synthetic HRT may be associated with an increase in seizure frequency.
Realizing there must be more information out there, I began searching the internet, and the following is a summary of what I found:.
Realizing that there must be more information out there, I began searching the internet and the following is a summary of what I found:
First of all, I learned about a type of epilepsy that affects up to 70% of women, known as catamenial epilepsy, which is epilepsy influenced by a woman's menstrual cycle. This certainly fits with the idea that estrogen and progesterone can influence seizures. For example, many women have more seizures around their period, consistent with low estrogen and progesterone levels.
According to Epilepsy Action Australia: "If you have catamenial epilepsy, you may experience an increase in seizures during your perimenopause and menopause due to fluctuating hormones, and you may have fewer seizures after your menopause."
According to the American College of Obstetrics and Gynecology: "Periovulatory catamenial exacerbation has been attributed to the midcycle surge of estrogen that is relatively unopposed by progesterone. Patients have the fewest seizures during the midluteal phase in ovulatory cycles when progesterone levels are the highest."
In a 2011 study published in Epilepsy and Menopause: "The frequency of catamenial type of epileptic seizures may increase during perimenopause due to hyperestrogenism and subside after menopause. Sexual dysfunction can be severe depending upon the effect of lack of estrogen in menopause and epilepsy itself. Osteoporosis and fractures may increase due to hypoestrogenism in menopause and cytochrome P450-inducing anti-epileptic drugs. According to the current data, conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate may increase the frequency of epileptic seizures....A combination of a single estrogenic compound such as 17-β-estradiol along with natural progesterone could be considered in these patients."
My research led me to confirm something I suspected: there is minimal recent data on menopausal hormone therapy and women with epilepsy. So, I researched what I could find about transgender women with epilepsy. This was interesting. According to the Journal Epilepsia, for males with epilepsy transitioning to female: "Typical treatment is with oral 17-β-estradiol, starting at 5 ug/kg per day and increasing up to an adult dose of 2 mg/day.... Estrogen may be administered orally or transdermally, and serum levels checked for a target range of <200 pg/ml (although synthetic estrogens or conjugated estrogens cannot be monitored)."
Of note, for my patients, the goal range for bioidentical 17-beta estradiol in women is 50-150. Also: "Long-term studies (up to 18 years) have not shown an increase in cardiovascular-related deaths, except for transwomen continuing to use ethinyl estradiol rather than other preparations of estrogen."
Later in the article, it notes: "Estrogen has proconvulsant properties in some patients with epilepsy, vividly demonstrated in 1959 by Logothetis et al., when intravenous infusion of estrogen increased epileptic spikes and sharp waves in 11 of 16 women with epilepsy. Therefore, when transwomen with epilepsy begin treatment with estrogen, an exacerbation of seizure activity is possible, and the patient may need medication adjustment. Although natural progesterone is a neurosteroid and has anticonvulsant properties (through the progesterone metabolite, allopregnanolone), the synthetic medroxyprogesterone most commonly used for gender-affirming treatment is not metabolized to allopregnanolone and does not offer the same protection."
What stands out to me in the above paragraph is that the old 1959 study, which uses synthetic estrogen, is again referenced, and natural (bio-identical) progesterone has anti-seizure properties compared to synthetic progestins.
Let's re-visit the 1959 study which uses the synthetic estrogen Premarin: "Intravenous (i.v.) injections of the estrogenic substance, Premarin, were administered to 16 female epileptic patients, of whom eleven patients showed increased epileptogenic activity and four experienced frank seizures. Of the four patients that received the highest dose, three patients experienced fits, indicating a dose-dependent effect of estrogen on seizure excitability. In contrast to estrogen, progesterone infusions in epilepsy patients reduce seizure susceptibility." Synthetic estrogen causes seizures, bio-identical progesterone reduces seizures.
A common theme throughout my research was that it is very important to be aware of possible drug interactions between anti-seizure medications and hormone therapies. That said, all women of childbearing age taking anti-seizure medications should be advised about the risk of birth defects potentially caused by these medications. Because of this, it is advised that they take birth control. Importantly for my particular research about the safety of estrogen and seizure disorders, women are frequently prescribed birth control pills, which contain very high doses of synthetic estrogen and progesterone. They do recommend consideration of progesterone-only birth control, but combined oral contraception with synthetic estrogen and progesterone is also recommended. It is best to take a continuous regimen that keeps hormone levels constant.
According to ACOG: "There is no conclusive evidence that combination hormonal contraception increases epileptic seizures, and epilepsy itself poses no increased risk of an adverse outcome for those using combined OCPs, the contraceptive patch, or a contraceptive ring. Combination hormonal contraceptive methods are considered category 1 (no restriction for the use of the contraceptive method) according to the Centers for Disease Control and Prevention’s U.S. Medical Eligibility Criteria (USMEC) for women with epilepsy."
So, as a menopause specialist, I must wonder: Why is it that post-menopausal women cannot take estrogen due to risks of seizures, but every reproductive-aged female should be on some form of birth control, estrogen-containing or otherwise? It seems that the very high doses of estrogen and progesterone in birth control that shut down the ovaries would be more dangerous than the low doses prescribed by your menopause specialist. According to EarlyMenopause.Com "The estrogen in birth control pills is most commonly a synthetic form called ethinyl estradiol. It's a potent form of estrogen that is roughly four to ten times stronger than that used in differnt types of HRT."
Finally, one question that a leader in menopause care always asks when we are thinking about whether menopause hormone therapy is safe for a particular patient: "Would I allow this patient to become pregnant?" If the answer is yes, we are saying that we are comfortable allowing this patient to have estradiol (the same estradiol used in bio-identical HRT) levels as high as 17,500 pg/ml. So if that is the case, why can't this same patient take menopausal hormone therapy at 50-150 pg/ml? It seems we should use caution caring for patients with epilepsy based on what we think we know (synthetic estrogen may cause seizures), but we should also use our highly educated brains to make an educated recommendation for our patients.
A few international epilepsy groups seem to feel the same way as I do. Also according to Epilepsy Action Australia "One study suggests 17-beta estradiol or transdermal estrogen, alongside micronised progesterone, is unlikely to increase the frequency of seizures. Body-identical HRT is likely to be safe and not affect seizures as the dose is stable and constant."
There have been very few studies on HRT and epilepsy, and there is not enough evidence to conclusively say HRT can trigger seizures, so more research is needed.
In addition, according to the European Journal of Epilepsy "A risk of increased seizures with HRT consisting of CEE and MPA (which are synthetic estrogen and progesterone) appears to be present in postmenopausal WWE. This was found in a cross-sectional questionnaire as well as a randomized, double-blinded, placebo-controlled clinical trial. Yet WWE will need to take HRT at times, for symptomatic relief and to allow adequate sleep when 'hot flushes' are disruptive. The author suggests that a combination of a single estrogenic compound such as 17-β-estradiol along with natural progesterone be considered in this clinical scenario."
Finally, according to the Epilepsy Society "During the menopause, a woman’s body stops making natural hormones and this can cause symptoms such as hot flushes and mood swings. Hormone replacement therapy (HRT) is sometimes used to treat these symptoms.
HRT contains either oestrogen or a combination of oestrogen and progestogen. Although oestrogen is known to have a pro-convulsant (seizure causing) effect for some women, the amount of oestrogen prescribed in HRT is usually matched to the amount of oestrogen in your body before the menopause. So it is usually not enough to cause seizures to happen. However, if you take HRT and you do have more seizures than usual, this could be related to the oestrogen in HRT.
If this happens it might be helpful to discuss the HRT with your neurologist to consider any possible alternatives or different combinations of oestrogen and progestogen.
Having information and regular medical reviews with your neurologist or GP can be important during the menopause. This is an opportunity to discuss any concerns you may have."
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