[Pulsatile administration of LH-RH: diagnostic and therapeutic applications]. / Administration pulsatile de la LH-RH: applications diagnostiques et thérapeutiques.

Hypothalamic hypogonadotropic hypogonadism (HHH), a disorder occurring in both sexes, is characterized by a partial or complete inability to synthesize and/or release LH-RH from the hypothalamus which result in absence or defects of amplitude and frequency of gonadotropin secretion. Long term substitution by pulsatile exogenous LH-RH usually result in complete normalization of both pituitary and gonadic hormones. Such a treatment allows differentiation between hypothalamic and pituitary causes of hypogonadotrophic hypogonadism. Ovulation and fertility can be achieved in most of women with hypothalamic amenorrhea treated with pulsatile LH-RH using i.v. bolus doses of 25-100 ng/kg at 1-2 h intervals. In opposite LH-RH therapy yields inferior results to human menopausal gonadotropin (hMG) in chronic anovulatory patients with persistent LH secretion or polycystic ovary syndrome (PCOS) as shown by one randomized and several non-controlled studies. Successful pulsatile LH-RH treatment following a 2 months LH-RH analog suppression in PCOS previously refractory to LH-RH alone represents a new promising approach. The majority of men with complete HHH begin to produce sperm only after 1 year of therapy. Both the testicular volume and the mean sperm concentrations were below the normal values after 2 years of treatment in spite of normalization of testosterone, LH and FSH levels. Pulsatile LH-RH does not seem significantly improve the treatment of infertile HHH men compared to hMH/hCG.

Influence of the frequency of gonadotropin-releasing hormone (GnRH) administration on ovulatory responses in women with anovulation.

In attempt to optimize gonadotropin-releasing hormone (GnRH) treatment of anovulation, we compared the effect of intravenous GnRH administration at three pulse intervals (PI) during 63 cycles in 30 anovulatory patients who had: (1) amenorrhea secondary to anorexia nervosa (group I: 10 patients, 21 cycles); (2) unexplained anovulation with normal to high luteinizing hormone plasma levels (group II: 12 patients, 24 cycles); and (3) polycystic ovarian disease (PCOD) (group III: 8 patients, 18 cycles). Ovulation was achieved more frequently in group I (85%) than in group II (41%) or in group III (50%). In both groups I and II, the frequency of ovulatory responses was not different with the PI used, and 6 of the 17 women treated for infertility conceived; 3 with 90-minute PIs, 2 with 64-minute PIs, and 1 with 128-minute PIs. In women with PCOD, seven of the nine ovulatory responses and three pregnancies were obtained with 128-minute PIs. The overweight women with PCOD did not respond reliably to GnRH at the doses used, i.e., 4 to 15 micrograms per pulse. In all groups, the urinary estrone and estradiol preovulatory peak, duration of luteal phase, progesterone levels, and preovulatory follicle diameter were unrelated to the frequency of GnRH administration.