Endocrine treatment of seizures may rationally be aimed at those endocrinologic aspects of seizures that act either to exacerbate or to ameliorate them. Because progesterone has anticonvulsant effects and estrogen has proconvulsant effects, treatment with progesterone or estrogen antagonists may prove to be useful adjunctive treatments in appropriate patients.


Low progesterone levels or rapid withdrawal of progesterone may be a factor in the increased seizure frequency seen during the premenstrual and early follicular phase of women with catamenial epilepsy and normal ovulatory cycles, and during the entire luteal phase of women with anovulatory cycles.14,15 Progesterone may be expected to be beneficial in these women.

Synthetic progestin therapy may be considered. Little or no benefit has been noted with oral forms in a number of studies16,17 although occasional benefits have been described in single case reports.

In one study of women with refractory partial seizures and normal ovulatory cycles, a medroxyprogesterone dose large enough to induce amenorrhea (120 to 150 mg every 6 to 12 weeks intramuscularly or 20 to 40 mg orally daily) resulted in a 40% average seizure reduction.16 Weekly doses of 400 mg of intramuscular depo medroxyprogesterone may be more effective.

Potential side effects include depression, sedation, and breakthrough vaginal bleeding. The use of depo medroxyprogesterone also may delay the return of regular menstrual cycles.

Natural progesterone may be a more effective treatment. In a study of 25 women with catamenial exacerbation of complex partial seizures of temporal lobe origin, 72% of the women improved.18 The average decline in seizure frequency was 55%. Of the 25 women in the study, 14 had anovulatory cycles or an inadequate luteal phase. These women took progesterone lozenges (200 mg tid) on days 15 through 25 of each menstrual cycle, with taper over days 26 through 28. The 11 women with normal cycles and perimenstrual seizure exacerbation took the same type and dose of progesterone on days 23 through 25 of each menstrual cycle.18

The natural and synthetic progestins are not equivalent because natural progesterone is metabolized to allopregnanolone, which has very potent GABA-a mimetic and anticonvulsant action,19,20 whereas synthetic progestins are not metabolized in this way.

Potential side effects of progesterone treatment may include:

  • sedation
  • depression
  • weight gain
  • breast tenderness
  • breakthrough vaginal bleeding

All of these effects are readily reversed if the hormone is stopped or the dose is lowered.

Medication adjustments

If low AED levels are found during certain phases of the woman's menstrual cycle, it may be helpful to increase the dose slightly around that time, or in some cases to add a low dose of another AED, such as a benzodiazepine.

Adapted from: Klein P and Herzog AG. Endocrine aspects of partial seizures. In: Schachter SC, Schomer DL, eds. The comprehensive evaluation and treatment of epilepsy. San Diego, CA: Academic Press; 1997. p. 207-232.
With permission from Elsevier (www.elsevier.com).

Authored By: 
Pavel Klein MD
Andrew G. Herzog MD
Reviewed By: 
Cynthia L. Harden MD
Sunday, February 1, 2004