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In the Clinic – Transgender Medicine

When Transgender Medicine Meets Neurology

What's Known, What's Not

Fallik, Dawn

doi: 10.1097/01.NT.0000526511.36909.50
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ARTICLE IN BRIEF

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The field of transgender medicine is in its infancy, experts acknowledge, but a new review of existing literature spotlights specific concerns related to treating transgender patients with epilepsy.

There is a dearth of research on how to treat neurologic conditions in patients who are transgender, experts in a small of growing field of so-called transgender medicine acknowledged in interviews with Neurology Today. What is known, however, but not completely understood, is that certain therapies may interact with commonly used treatments for transitioning to an identified gender.

In particular, this could be the case for transgender patients with epilepsy, according to an analysis of the medical literature published in the August 3 online issue of Epilepsia.

“The goals of this analysis were to draw attention to the specific needs of transgender patients, to make neurologists aware of the specific common regimens for gender-affirming treatment, and to highlight the need for epidemiological and prospective studies to characterize the numbers of transgender patients with epilepsy,” study author Emily Johnson, MD, an assistant professor of neurology at Johns Hopkins School of Medicine, told Neurology Today. “Prospective observational studies in this population could provide a valuable opportunity to learn more about the effects of exogenous hormones on seizure control.”

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She said that epilepsy treatments might affect groups differently depending on whether they are transitioning from female to male or male to female. Other studies have reported interactions of estrogen with antiepileptic drugs, she said, and potentially seizure control could worsen in male-to-female patients taking the hormone. In female-to-male patients, there may be improvement of catamenial epilepsy, where seizures are affected by the menstrual cycle. When menses stop, the effects of additional testosterone are not as well-characterized as those of estrogen/progesterone, where there is information from hormonal birth controls.

The higher rate of HIV among transgender patients should also be a concern, she said, because enzyme-inducing AEDs could impact antiretrovirals. Dr. Johnson said that, although there are no data currently studying this specific impact, neurologists should be aware of these interactions, and preferentially prescribe non-inducing AEDs when possible. Good communication with the patient's other providers — particularly those managing the antiretrovirals and the gender-affirming treatment — will be key, she said.

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HORMONAL TREATMENTS

Joshua D. Safer, MD, FACP, medical director for the Center for Transgender Medicine and Surgery at Boston Medical Center, said that the most common concern that has been verified through research is that estrogen therapy does increase the number of blood clots, and that's true whether the therapy is for post-menopausal treatment, birth control, or transition therapy.

Testosterone in transgender men may make female reproductive cancer worse, he said, like endometrial cancer in a female-to-male transition.

“There are a lot of things we think are associated with hormones, but we don't actually know [much about it],” Dr. Safer said. “So I think people are going to start questioning how much is hormone dependent, and as people change hormones we may see less difference, or no difference, than we thought.”

Dr. Safer said that if physicians believe that the hormone treatment will affect another medical condition, such as epileptic seizures, they should not tell the patient to stop the hormones, and the transition.

Instead, he said, the standard procedure should be to accept that someone who is transgender is transgender and requires a hormone profile, whatever that may be, and adjust the other medications as needed.

That's exactly what Peter Crino, MD, PhD, saw when he was a neurologist at the University of Pennsylvania more than a decade ago. He had a patient come to him from another practice in the city to address her epileptic seizures. Before going on hormone replacement, she'd been able to modestly control her seizures with medication, but the estrogen aggravated the situation, sending the seizures “out of control.”

The other practice wanted to stop the hormones, and the patient felt that she was not being heard and that they were being insensitive to her specific situation. When she met Dr. Crino, now chair of neurology at the University of Maryland School of Medicine, it was his first time meeting a transgender patient.

But instead of asking her to stop the transition process, he began adjusting her seizure medications so that she could continue the hormone therapy.

“It was complicated because she was already on a medication that caused the liver to metabolize the hormone more rapidly, so she wasn't really getting all of the desired estrogen effects and at the same time, her epilepsy was much worse,” said Dr. Crino. “We did a complete re-evaluation of her epilepsy with EEG and trials of different medications. We'd taper down one and try another, and if that didn't fully help, we tried another all the while allowing her to stay on estrogen supplementation.”

“Finally, we found a good regimen for her – she wasn't completely seizure free, but she was able to return to work in her office job.”

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SHIFTING MEDICAL NEEDS

It's that kind of patience and attention to detail — on both the patient and doctor's behalf — that's particularly important when treating transgender patients, said Matthew McCaskill, DO, assistant professor and neurohospitalist at Oregon Health & Science University in Portland.

He has a significant number of transgender patients in his practice, often referred by members of the community or by other doctors who are familiar with Dr. McCaskill's knowledge and comfort level.

Transgender patients present a constantly changing situation, he said, because so many neurologic conditions are hormonally affected. Their hormone therapies could change month-to-month, resulting in a domino reaction to their other medications.

“Each one of them is usually so unique in that moment of what is happening with their hormonal process and neurologic function that you have to constantly tailor the treatment to what they're doing,” said Dr. McCaskill. “I try to educate patients that every time they change their hormone regimen or even if they lose sleep for multiple nights, that's going to have an impact on their neurologic problem as well, and to keep me abreast because I will need to adapt their regimen accordingly.”

It's also important to realize that there may be something going on beyond the transition process. He recalled one patient who had transitioned from male to female, and had complained of vague neurologic issues, but it was always attributed to psychiatric issues or to the trans process. When the patient came to Dr. McCaskill, after taking a complete history, they realized that the seizures had started after intramuscular estrogen therapy. However, the underlying issue turned out to be mesial temporal sclerosis, which had been undiagnosed because no one investigated the seizures, only the treatment.

Holly E. Hinson, MD, MCR, an assistant professor who specializes in neurocritical care at Oregon Health & Science University and is the founding member of the AAN's new Lesbian, Gay, Bisexual, Queer, Transsexual, Intersex Section, said that taking an inclusive history has proved challenging because electronic medical records are not inclusive about sexual orientation or gender identification. Only recently, she said, have sexual orientation and gender identification intake forms become integrated with electronic data. [Read more about the new AAN Section here: http://bit.ly/NT-transgender.]

She said the Section, among other goals, hopes to ensure that neurologists have access to cultural competency training programs. In a 2010 survey of medical students, the majority of students rated their programs as fair or worse, if they had any cultural curriculum at all, she said.

“Neurologists in general are very benevolent about wanting to be sensitive and caring and inclusive,” she said. “And, like most physicians, they want their patients to feel respected and to provide the best of care. I think many would welcome guidance on how to do this.”

All the physicians interviewed said it was helpful to initiate the conversation about special circumstances regarding transgender patients, but emphasized the need for data collection.

S. Andrew Josephson, MD, FAAN, the founder and director of the University of California, San Francisco (UCSF) Neurohospitalist program as well as chair of UCSF's neurology department, said that this is a field “completely in its infancy.”

“We just don't know most of the answers about the different rates of disorders and different responses to treatments in our transgender community, particularly in those conditions which are potentially influenced by exogenous hormones,” he said. “There's an incredible need for research to see if we can fill in some of these gaps.”

At UCSF, Dr. Josephson and colleagues, under the leadership of Nicole Rosendale, MD, are studying at a large cohort of transgender patients and the prevalence of neurologic disorders, including migraines.

“The goal is to always practice patient-centered medicine, and there's an importance to this topic whether you're in an area with a large transgender community like New York or California, or if you are a doctor in areas where only a handful of trans patients may live; we need to know how to best care for this population.”

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LINK UP FOR MORE INFORMATION:

•. Johnson E, Kaplan P. Caring for transgender patients with epilepsy http://onlinelibrary.wiley.com/doi/10.1111/epi.13864/full. Epilepsia 2017; Epub 2017 Aug 3.
    •. Hurley D. Medical societies, including the AAN, move to address care of LGBTQI patients http://journals.lww.com/neurotodayonline/pages/articleviewer.aspx?year=2017&issue=04060&article=00010&type=FullText. Neurology Today 2017; 17(7): 21–23.
      © 2017 American Academy of Neurology