Catamenial Epilepsy

How do we break the cycle of epilepsy in women?

US researchers have made an important discovery about a form of epilepsy that affects women most severely during menstruation. The findings could lead to a new treatment based on manipulating levels of the hormone progesterone.

Epilepsy affects about 40 million people worldwide, with a proportion of sufferers being women where their symptoms are related to the menstrual cycle, so-called catamenial epilepsy. In at least 72% of catamenial epilepsy sufferers, menstruation exacerbates their seizures. Women with catamenial epilepsy tend to have seizures clustered around their monthly cycle, sometimes as many as three or four a day. Seizures are generally mild, partial seizures, but some women experience severe generalized seizures and lose consciousness. Scientists have learned that the hormone progesterone provides some protection from the seizures, and it may be that as levels of that hormone fall near the end of the menstrual cycle that women are suddenly more vulnerable to a seizure.

According to Doodipala Reddy of North Carolina State University, catamenial epilepsy is an often neglected area but they are hoping to improve the options available to sufferers through their research. They have discovered how progesterone is involved in protecting against seizures and identified how the protection happens. “Scientists have known for many decades that progesterone has anti-convulsive properties, but we didn’t fully understand how,” Reddy explains. Recent developments in transgenic mouse technology and availability of specific 5a-reductase enzyme inhibitors made it possible to elucidate the biochemical mechanisms of progesterone in seizure susceptibility.

Reddy and his colleagues have worked with Bert O’Malley of the Baylor College of Medicine and Michael Rogawski from the National Institute of Neurological Disorders and Stroke (NINDS) to elucidate the protective role of progesterone. Progesterone plays two important roles in brain function, they explain. First, it binds to progesterone receptors and helps regulate reproductive functions. Secondly, it is metabolized to the neurosteroid allopregnanolone. “It had been thought that the progesterone binding to the progesterone receptor is what provided the protection from seizures, but we discovered that it’s the neurosteroid allopregnanolone that actually provides the protection” Reddy explains.

The team used a model to show that allopregnanolone also activates another brain receptor GABA-A. This is a subtype of the receptors that usually control inhibitory neurotransmission in the brain, when it malfunctions, seizures can result as excitatory neurotransmission goes out of control. The researchers found that the neurosteroid acts as a “positive allosteric modulator” for this receptor, it binds to it and temporarily opens this chloride ion channel and thereby causes hyperpolarization. This stops the runaway neuronal activity and precludes the seizure. Reddy explains that withdrawal from this neurosteroid, which occurs naturally during menstruation, removes the controlling factor and allows a seizure to occur.

Currently, there are no approved drugs specifically for treating catamenial epilepsy. “We tested the traditional anti-convulsants like Valproate and Diazepam, but they don’t work well in this disorder,” Reddy says. Progesterone is not the answer either, as administering it during susceptible periods of the menstrual cycle could disturb the reproductive system causing breakthrough bleeding, breast tenderness, and other side-effects.

Reddy now proposes that neurosteroid replacement could be used at times when the allopregnanolone metabolite of progesterone tapers off. “If you can maintain those levels, that should take care of the seizure problem,” he explains. Allopregnanolone may produce some hormonal side effects. An allopregnanolone analog, ganaxolone, overcomes this limitation.

Ganaxolone is a synthetic neuroactive steroid that was originally discovered at CoCensys for the treatment of epilepsy. It was acquired by Purdue Pharma in 1999 for further clinical evaluation (phase III). This drug was developed as a result of an elegant series of studies by Kelvin Gee and colleagues in the 1990s, which was turn based on some clues from earlier studies of progesterone in 1940s. “There’s still a lot more for us to learn about this disease,” adds Reddy. “It’s a very ambitious goal, but we’d like to try and find novel treatment options for prevention or cure of this disease.”

The researchers also suggest that their findings could have implications for understanding the symptoms of premenstrual syndrome, such as mood swings and headaches, which are also associated with fluctuations in neurosteroids during the menstrual cycle.

Research Blogging IconReddy, D. (2004). Anticonvulsant Activity of Progesterone and Neurosteroids in Progesterone Receptor Knockout Mice Journal of Pharmacology and Experimental Therapeutics, 310 (1), 230-239 DOI: 10.1124/jpet.104.065268

Author: David Bradley

Post by David Bradley Science Writer. You can get in touch with David via email or check out his CV on the Sciencebase.com site.

8 thoughts on “Catamenial Epilepsy”

  1. Thank you for the information on neurosteroid replacement. After 36 years living with intractable catamenial epilepsy it is a joy to read about new research with promise.

  2. I suffered seizures at menopause and now my daughter has catamenial epilepsy that is still not under control. Thank you for your continued research on this disease and I pray for your success for my daughter and the thousands of women just like her. Progesterone has not helped. We’re still searching. Maybe Ganaxolone is next?

  3. I am 29 in June, from Ireland and always suffer around my period.I have had epilepsy since I was nine & have never found a drug that worked. I afraid to go to work around my period.
    Please just continue your good work, as I am to married next year and to have a wedding day without a seizure.

  4. My daughter now 16 has had an increase in seizure activity from the age of 12. Many medications have been tried but without any luck. She would have seizures two days before her cycle or right after her cycle began. Seven months ago her doctor added another medication called Diamox to her current medications and knock on wood she has been seizure free for almost seven months now. It is very important to keep track of your cycle and keep a seizure diary so you can give this information to your neurologist. This sounds weird coming from a guy but I love my daughter and I did what was necessary to help her.

  5. My name is Sabrina. My daughter Maritess started her seizures when she was 12yrs old when she started her menstruation. She is on 3 combination of meds and still not controlling her seizures. she gets seizures everyday. She feel good if she doesn’t get a seizure for 2 days. Her menstrual period is very irregular and that affected her so much. Her seizure gets severe once a month during her cycle. Hope and pray that you will find a cure soon. Thank you

  6. In 1994 as I approached menopause, I started to have Grand Mal Seizures. At that time, I was uninsured, and going to a clinic for help. After several seizures, I was put on Tegretol. I stopped the meds, because I didn’t like the side effects. More seizures. Went back on the meds, but reduced the amount. I highly recommend that anyone who is not seizure free, work closely with their neurologist as this was dangerous and I didn’t realize it. Menopause became unbearable for me. I had hot flashes all night long and couldn’t sleep. My memory was affected, my hands swelled, vision was blurry and the anxiety was awful. I would feel faint. I was put on HRT by my gynecologist. After two weeks, I was a new woman. Slowly and gracefully I went through menopause and MY SEIZURES STOPPED. After several years of taking Tegretol and HRT (Prempro) I eliminated the Tegretol………..slowly, slowly and slowly. In 2003, I stopped the HRT after the womens health initiative said their study showed ill effects of long term use of HRT. It is 2010. I have not had a seizure since 1997. I don’t know if it was the HRT, fate, or the combo, but I am so grateful and it gives me hope that others out there can be helped too. Please, DON’T GIVE UP. If one medication doesn’t work, try another and another. Until it stops. Be proactive, keep charts, take vitamins, and talk to your Dr.’s. They need to hear our voices. Best wishes to all of you, Linda

  7. My Girl and I have decided to give Progesterone a go after many years of Her having siezures, They began when she was pregnant, second trimester… She had never noted the connection of her siezures and her periods, but I keep a journal one result of which was, I knew when she was due, partly to be forewarned and to when to adopt best behaviour. The regularity of her attacks, full mal-grande, usually only one, was apparent 3 days before and the same after. Usually before. She has never taken any medicine for the ailment as she would rather put up with the siezures than the side effects.After a particularly bad fit in the shower involving hot water, she finally gave in to my patient nagging and we got a prescription for Progesterone. We had to sign a waiver (We’re in Australia)to say that we did not recieve this scrip in any connection with the prevention of epileptic siezures… Progesterone was widely used up to the 1940’s for the treatment of epilepsy in both men and women, ( they’ve know about it since 1881 ) but when thousand of men began to come home badly wounded,many with head injuries and severely epileptic, they took the shotgun approach… Progesterone was dumped for the following reasons. They didn’t know how much to give MEN, also it COULDN’T be patented, (That’s what they said) Have a pill instead, Fred. As my girl has NOT been on any other medicine for the treatment of her Epilepsy we look forward to the next few months knowing that what is happening is the Progesterone alone… Shall keep you posted, Seamus D. Australia.

  8. The majority of people just dont understand the severity or complexity of an epileptic seizure. It’s posts like this I’m hoping will change peoples understanding of the disease.

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