Linda Levesque

Altered pulsatile secretion of luteinizing hormone in women with epilepsy

Menstrual disorders and infertility are common among women with epilepsy of temporal lobe origin (TLE). Reproductive endocrine disorders may be the cause. Polycystic ovarian syndrome (PCO) and hypothalamic amenorrhea (hypogonadotropic hypogonadism, HH), in particular, are significantly overrepresented and attributable to hypothalamic dysfunction. We therefore compared the hypothalamic function of 14 women with clinically and electrographically documented TLE with that of eight age-matched normal controls by determining the interictal pulse frequency and amplitude of luteinizing hormone (LH) secretion. Serum for LH measurement was drawn every 15 minutes from 8 AM to 4 PM in both groups. LH pulse frequency values were significantly more variable (p < 0.05) and lower (p < 0.05) among women with TLE than among controls. Women with left temporal EEG foci showed a trend toward higher pulse frequencies compared to women with right foci (p = 0.05 to 0.10). Among five women with reproductive endocrine disorders, the three with PCO had left-sided foci and average LH pulse frequency two times higher than that of the two women with HH, who had right-sided foci. Eight reproductively normal, medically treated women with TLE had significantly lower LH pulse frequencies than did the one reproductively normal, untreated woman with TLE (p < 0.05) and the eight normal controls (p < 0.001). These findings suggest that LH pulse frequencies in women with TLE may be influenced by the laterality of the epileptic focus, the reproductive endocrine status, and the use of antiseizure medications.

Phenytoin‐Induced Elevation of Serum Estradiol and Reproductive Dysfunction in Men with Epilepsy

Summary: Reproductive and sexual dysfunction in men with epilepsy has been attributed to androgen deficiency. Low serum free testosterone (FT) levels occur in both hypogonadotropic and hypergonadotropic hypogonadism. Antiepileptic drugs (AEDs) have been implicated. Proposed mechanisms include induction of increased sex hormone binding globulin (SHBG) resulting in decreased FT, as well as dysfunction or premature aging of the hypothalamopituitary‐gonadal axis. In an investigation comparing serum reproductive steroid levels among 20 men receiving phenytoin (PHT) monotherapy for complex partial seizures, 21 untreated men with complex partial seizures, and 20 age‐matched normal controls, total estradiol levels were significantly higher in the PHT group (56.3 ± 29.4 pg/ml, mean ± SD) than in the untreated (32.4 ± 27.4 pg/ml, p < 0.01) and normal control (34.3 ± 12.7 pg/ml, p < 0.05) groups. The physiologically active non‐SHBG‐bound serum estradiol levels were also significantly higher in the medicated group (45.1 ± 21.7 pg/ml) than in the untreated (29.9 ± 17.2 pg/ml, p < 0.01) and normal control (31.1 ± 11.4 pg/ml, p = 0.05) groups. These findings suggest that PHT may lower FT by induction of aromatase, enhancing FT conversion to estradiol, as well as SHBG synthetase. Estradiol exerts a potent inhibitory influence on luteinizing hormone secretion and has been suggested to play a major role in negative feedback in men as well as women. Suppression of LH secretion results in hypogonadotropic hypogonadism. Chronically low FT leads to testicular failure and hypergonadotropic hypogonadism. Finally, estradiol has been shown to produce premature aging of the hypothalamic arcuate nucleus, which secretes go‐nadotropin‐releasing hormone.

Abnormal pulsatile secretion of luteinizing hormone in men with epilepsy Relationship to laterality and nature of paroxysmal discharges

We compared the pulsatile secretion of luteinizing hormone (LH) between 13 men with clinically and electrographically documented temporal lobe seizures and 8 age-matched controls. Serum for LH measurement was drawn every 15 minutes during 8 hours of EEG telemetry in both groups. The 2 groups did not differ significantly in average mean baseline LH secretion, total LH secretion, or average pulse amplitude. The group with seizures, however, showed a significantly greater (p < 0.05) variability of baseline LH secretion and pulse frequency. Among the men with unilateral paroxysmal EEG findings, pulse frequency was significantly greater (p = 0.05) with right epileptiform discharges or left slowing (6.4 ± 0.4) than with left epileptiform discharges or right slowing (3.0 ± 1.3). The relationship of pulse frequency to the nature and laterality of paroxysmal discharges makes it unlikely that endocrine abnormalities can be attributed to medication alone and strengthens the notion that temporal lobe epileptiform discharges may disrupt hypothalamic regulation of pituitary secretion.

The temporal relationship between the luteinizing hormone surge and human oocyte maturation

The temporal relationship of oocyte maturation to endogenous luteinizing hormone (LH) in vivo throughout the preovulatory period has not been previously reported. In order to study in vivo oocyte maturation follicular aspiration was carried out from 4 to 38 hours after the onset of the LH surge. Oocytes were obtained in 72% of cases. If oocytes were harvested more than 18 hours after the onset of the LH surge, resumption of meiosis had occurred. Twenty-eight to thirty-eight hours after the onset of the LH surge preovulatory oocytes in metaphase II were obtained. A corpus luteum was found 38 hours after the onset of the LH surge.

Clinical use of a solid-phase radioimmunoassay specific for human chorionic gonadotropin

Abstract A rapid radioimmunoassay specific for human chorionic gonadotropin (hCG) has been developed. Elimination of cross-reactivity with luteinizing hormone (hLH) was obtained by utilizing an antiserum with a specificity for the beta subunit of hCG. A solid-phase system, in which the antibody was bound to CNBR-activated sepharose in a preliminary step, reduced the minimum incubation time of the assay to two hours. The assay has been found to be of particular value in those conditions where in the concentration of hCG as measured by previously described assays would be affected by circulating levels of hLH: i.e., early implantation, unruptured ectopic pregnancy, threatened abortion, and trophoblastic disease under chemotherapy.

Levels Of Serum Follicle-Stimulating Hormone, Luteinizing Hormone, And Plasma Progestin During Microdose Chlormadinone Treatment *

Results of daily LH FSH progestin and basal body temperature measurements in 6 women for one normal menstrual cycle and 1 or 2 cycles while taking .5 mg chlormadinone acetate continuously are presented as individual graphs. Gonadotropins were assessed by double antibody radioimmunoassay and progestin by petroleum-ether extraction. In the 6 women 3 treatment cycles were definitely ovulatory as judged by LH curve luteal progestin levels and temperature rise. 6 cycles were classed as nonovulatory although equivocal temperature rise or low LH surges were present in some. 2 cycles were questionable.

Timing of Ovulation by a Rapid Luteinizing Hormone Assay

A rapid solid phase assay for serum luteinizing hormone (LH) invol ving a single antigen antibody reaction and a 2-hour incubation period was evaluated. Preparation of the assay materials is described in detail. The assay was tested in 6 normally menstruating women over the menstrual cycle and was found to compare favorably with a 6-day double antibody method in delineating the pattern of serum LH. Although a longer incubation period would most likely yield more precise results it is thought that this assay system is capable of demonstrating the preovulatory peak of LH.

A Rapid Solid-Phase Radioimmunoassay for the Measurement of Serum Luteinizing Hormone-Human Chorionic Gonadotropin (LH-HCG) Activity in very early Pregnancy * †

A rapid solid-phase radioimmunoassay (RIA) method for the quantitative measurement of luteinizing hormone-human chorionic gonadotropin (LH-HCG) in serum in very early pregnancy is decribed. The technique is a rapid modification of an immunadsorbent method originally described by Wide and Porath (1966). The method has been used for the diagnosis of pregnancy as early as the 26th day of the menstrual cycle. It has also proven useful in detecting pregnancy in patients being treated for secondary infertility and in the study of various disorders of early pregnancy.

A Rapid Radioimmunoassay Method for Serum Luteinizing Hormone Utilizing Polyethylene Glycol and A Double-Antibody Method of Separation

A method is described utilizing polyethylene glycol (PEG) combined with a double antibody for separation for rapid radioimmunoassay (RIA) of human luteinizing hormone(hLH). The total assay time is 3 hours with a 1-hour incubation period. Reliable comparisons with the 3-day assay have been shown. The average between-assay coefficient of variation was 11%, whereas the average within-assay coefficient of variation was 6%. The sensitivity of the assay was 7.5 mIU/ml. It is suggested that this reliable and rapid RIA for hLH will prove to be a valuable adjunct in the treatment of patients when timing of ovulation is imperative, such as for artificial insemination and harvesting of maturing human oocytes.