Epilepsia, 47(9):1452–1459, 2006 Blackwell Publishing, Inc. C  2006 International League Against Epilepsy Interictal and Postictal Circadian and Ultradian Luteinizing Hormone Secretion in Men with Temporal Lobe Epilepsy ∗ Mark Quigg, ∗ James M. Kiely, †Michael L. Johnson, †Martin Straume, ∗ Edward H. Bertram, and †William S. Evans ∗ Department of Neurology, University of Virginia, Charlottesville, VA, U.S.A., and †Department of Internal Medicine, Division of Endocrinology, University of Virginia, Charlottesville, VA, U.S.A. Summary: Purpose: Hypothalamic regulation of the repro- ductive axis in temporal lobe epilepsy (TLE), represented by the ultradian pulsatile secretion of luteinizing hormone (LH), has been shown to be altered interictally and postictally. Our objective is to determine if epilepsy or seizures disrupt normal circadian fluctuations of LH as well as circadian organization of ultradian bursts of LH. Methods: We characterized LH secretion in 10 men with TLE during two 24-h blocks: an interictal epoch and a postictal epoch initiated by a seizure. Serum LH was measured every 10 min and characterized by circadian and ultradian patterns with cosinor and deconvolution analysis. Results: Mean peak serum concentrations of LH occurred at ∼0400 in controls, were significantly delayed ∼5 h interictally, and were randomly distributed postictally. Burst amplitudes dif- fered significantly by phase among controls, with the largest amplitudes between 0101 and 0700 and the smallest between 1301 and 1900. No phase differences were present in interic- tal or postictal epochs. Burst frequency weakly but significantly was slowest between 0101 and 0700 in controls, but did not dif- fer significantly by phase in either interictal or postictal epochs. Postictal LH burst frequencies, but not amplitudes, were signif- icantly decreased immediately postictally. Conclusion: The pulsatile secretion of LH in TLE is ab- normal both in the circadian as well as the ultradian domain. Interictal effects consist mainly in loss of circadian fluctua- tions in LH burst amplitude, whereas postictal effects consist of altered burst timing. Altered daily patterns of neuroen- docrine signals may underlie other disorders of homeostasis in TLE. Key Words: Chronobiology—Luteinizing hormone— Epilepsy—Hormonal regulation—Hippocampal sclerosis. Partial epilepsy is associated with reproductive system dysfunction such as dysfertility (1), poor libido and im- potence (2,3), disorders of menstrual regulation (4), and polycystic ovary syndrome (5). One hypothesis to account for these observations is that the interictal state of epilepsy or the acute postictal effects of seizures may alter se- cretion of hypothalamic gonadotropin releasing hormone (GnRH). GnRH drives the pulsatile secretion of luteinizing hor- mone (LH). LH secretory bursts, in turn, stimulate the secretion of gonadal sex hormones. Normal secretion of LH requires pulsatile, rather than continuous, exposure to GnRH (6,7). Because the hypothalamus and limbic system have functional connections (8,9), limbic epilepsy may disrupt normal activity of hypothalamic neurons. Assum- ing that LH bursts reflect activity of GnRH neurons, pat- Accepted February 14, 2006. Address correspondence and reprint requests to Dr. Mark Quigg, Department of Neurology, University of Virginia, Charlottesville, VA 22908, U.S.A. E-mail: quigg@virginia.edu doi: 10.1111/j.1528-1167.2006.00617.x terns of LH bursts should provide a surrogate measure of central hypothalamic regulation. Previous studies on the dynamics of LH secretion in epilepsy focus on the ultradian (cycle length <24 h) fre- quency of LH bursts measured in patients with temporal lobe epilepsy (TLE, the most common medically in- tractable partial epilepsy). An ∼100–120 min ultradian cycle of LH bursts can be measured in sera of healthy adults (10,11). In patients with partial epilepsy, abnor- malities in ultradian patterns of LH secretion attributable to interictal dysfunction include increased (12–15) or de- creased (16) burst frequencies and increased burst ampli- tudes (16). Postictal abnormalities of LH secretion include entropic disorderliness of bursts (a measure of the regu- larity of timing) and a tendency to slower burst frequency (16). The pulsatile secretion of LH also has a circadian component in addition to ultradian components, with peak concentrations occurring nocturnally in men (17,18). The circadian rhythms of LH secretion are predomi- nantly modulated by changes in burst amplitude rather than burst frequency (18). Circadian dysregulation of LH 1452