What are the guidelines for using transdermal progesterone (Hormone Replacement Therapy (HRT)) in patients with a history of seizures?

From the Guidelines

Transdermal progesterone therapy should be used with caution in patients with a history of seizures, as progesterone and its metabolites can affect seizure thresholds. When considering Hormone Replacement Therapy (HRT) for patients with a history of seizures, it's essential to weigh the potential benefits against the risks. While there is limited direct evidence on the use of transdermal progesterone in patients with seizure disorders, studies suggest that physical activity, which can be influenced by hormone levels, may improve epileptic seizure control 1.

For patients requiring HRT who have seizure disorders, lower starting doses are recommended, typically beginning with 100 mg daily of transdermal progesterone cream applied to thin-skinned areas like the inner wrist or inner thigh. Key considerations include:

• Dose adjustments should be made gradually, with careful monitoring for seizure activity.
• Patients should maintain consistent application timing to avoid fluctuations in hormone levels that might trigger seizures.
• Close collaboration between the prescribing physician and the patient's neurologist is essential, with regular follow-up appointments to assess seizure frequency and severity.
• Patients should be instructed to keep a seizure diary during the initial treatment period and report any changes in seizure patterns immediately.

It's also important to note that while progesterone's metabolites (particularly allopregnanolone) generally have anticonvulsant properties that may benefit some patients with seizures, individual responses vary significantly 1. Some patients might experience seizure improvement, while others could have worsening symptoms. If seizures worsen, dose reduction or discontinuation may be necessary. Blood level monitoring of progesterone may be helpful in these patients to ensure therapeutic levels without excessive fluctuations.

From the Research

Guidelines for Using Transdermal Progesterone in Patients with a History of Seizures

• The use of transdermal progesterone as a form of Hormone Replacement Therapy (HRT) in patients with a history of seizures has been explored in several studies 2, 3, 4, 5.
• Progesterone has been found to have an anti-seizure effect, particularly in women with catamenial epilepsy, which affects 31-60% of epileptic women 2.
• A study published in 2013 found that progesterone therapy resulted in a significant reduction of seizure frequency in the majority of patients with catamenial epilepsy, with a decline in the frequency of primary and secondary generalized seizures by 20-96% 2.
• Another study published in 2011 discussed the role of reproductive hormones, including progesterone, in the pathogenesis and treatment of seizures, highlighting the potential benefits of hormonal therapy in patients with epilepsy 3.
• A case report published in 2000 found that HRT, including transdermal estradiol and oral medroxyprogesterone acetate, was associated with a decreased incidence of seizures in a postmenopausal woman with epilepsy 4.
• However, a randomized clinical trial published in 2012 found that progesterone therapy was not effective in reducing seizure frequency in women with intractable partial epilepsy, although post hoc analysis suggested that a subset of women with higher levels of perimenstrual seizure exacerbation may benefit from treatment 5.

Key Considerations

• The effectiveness of transdermal progesterone in reducing seizure frequency may depend on the individual patient's level of perimenstrual seizure exacerbation 5.
• Progesterone therapy may be more effective in women with catamenial epilepsy, who experience seizures related to their menstrual cycle 2.
• The use of HRT, including transdermal progesterone, should be carefully considered in patients with a history of seizures, taking into account the potential benefits and risks of treatment 4.