Women with partial epilepsy often complain of an irregular menstrual cycle-usually prolonged but sometimes shortened (or both). These irregularities may be related to several reproductive endocrine disorders, especially polycystic ovary syndrome (PCOS) and hypothalamic hypogonadism (HH). Of course, if a woman complains of secondary amenorrhea, pregnancy or menopause should not be forgotten as a possible cause.

Here is a suggested approach to the evaluation of a woman with epilepsy and reproductive dysfunction:

1. History and examination
• Rule out pregnancy and menopause.
• Evaluate for PCOS, HH, and hyperprolactinemia:
• hirsutism, acne (for PCOS-associated hyperandrogenism)
• galactorrhea (for hyperprolactinemia)
2. Endocrine evaluation
• During the follicular phase (e.g., menstrual cycle day 4), test:
• LH
• FSH
• estradiol
• total testosterone
• free testosterone
• androstenedione (A)
• dehydroepiandrostenedione sulfate (DHEAS)
• prolactin
• thyroid function

In PCOS, one or more of the androgens (FT, A, or DHEAS) are elevated, the usual LH/FSH ratio of 1 is increased to > 2.5, and prolactin may be increased (in about 25%). Both total testosterone and free testosterone and should be checked because total testosterone may be affected by several antiepileptic drugs and free testosterone is the functionally relevant parameter.

In HH, LH, FSH, and estradiol are all low.

In hyperprolactinemia, remember that psychotropic medications (including benzodiazepines when used as AEDs [e.g., clonazepam]) and temporal lobe epilepsy are possible causes.

Hypothyroidism is a common cause of menstrual irregularities.

During the midluteal phase (e.g., menstrual cycle day 22), test:

• progesterone
• estradiol

In inadequate luteal phase syndrome (regardless of cause), the progesterone level is less than the normal 5 ng/mL. In PCOS, estradiol is normal.

In HH, both estradiol and progesterone are low.

3. Radiologic evaluation
• Pelvic ultrasound for PCOS, if indicated by laboratory values.
• MRI of the brain (coronal views of the hypothalamus and pituitary) for HH and hyperprolactinemia, if the history and examination point to a structural cause unrelated to temporal lobe epilepsy.

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).
Reviewed and revised May 2004 by Cynthia Harden, MD, Weill Cornell Medical College.