lhrh--n-ac-2-nal(1)-4-cl-phe(2)-trp(3)-hci(6)-alanh2(10)- and Polycystic-Ovary-Syndrome

To evaluate the role of altered luteinizing hormone (LH) release in the mechanism of polycystic ovarian disease (PCOD) anovulation, we have co-administered a gonadotrophin-releasing hormone (GnRH) antagonist and pulsatile GnRH therapy to two clomiphene citrate-resistant PCOD patients. The aim was to correct their inappropriate gonadotrophin secretion. Nal-Glu was administered s.c. every 72 h to both subjects for 3 weeks. On day 7 after commencing the study, intravenous pulsatile GnRH therapy was initiated (10 micrograms/pulse) every 90 min for 15 days to both subjects. In one subject, Nal-Glu treatment was continued and the GnRH dose was increased to 20 micrograms/pulse for 10 additional days. Prior to Nal-Glu, mean serum LH levels were 10.4 +/- 1.6 and 9.3 +/- 1.3 mIU/ml (mean +/- SEM) and mean interpulse intervals were 67.1 and 60 min in patients 1 and 2, respectively. Mean serum FSH levels were 4.9 +/- 0.4 and 4.2 +/- 0.2 mIU/ml for patients 1 and 2, respectively. LH pulsatility was abolished following Nal-Glu, mean serum LH decreased to 1.1 +/- 0.1 and 1.3 +/- 0.5 mIU/ml and mean FSH to 1.8 +/- 0.1 and 2 +/- 0.1 mIU/ml in the two subjects. On the 4th day of the combined therapy, mean serum LH increased to 5.4 +/- 1.3 and 3.9 +/- 0.9 mIU/ml with a mean interpulse interval of 72 and 80 min, respectively. Mean FSH levels increased to 3 +/- 0.1 and 2.8 +/- 0.1 mIU/ml, respectively and to 5.5 +/- 0.2 mIU/ml after the GnRH dose was increased in patient 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Drug Therapy, Combination; Female; Gonadotropin-Releasing Hormone; Humans; Infusions, Intravenous; Luteinizing Hormone; Ovarian Follicle; Polycystic Ovary Syndrome

A study was initiated to delineate the neuroendocrine characteristics of hyperandrogenic adolescent girls with the aim of discerning features that may relate to the pubertal onset of the polycystic ovarian syndrome. Thirteen 11- to 18-yr-old girls with mild to moderate signs of hyperandrogenism (HA) and increased ovarian volume and 28 age-matched normal girls were recruited for the study. LH pulsatility and FSH levels were analyzed based on serum concentrations measured with sensitive immunofluorometric assays in samples taken at 10-min intervals for 24 h under basal conditions, GnRH antagonist (Nal-Glu) suppression, and dexamethasone suppression. Adrenal and ovarian contributions to serum cortisol, dehydroepiandrosterone, androstenedione, testosterone (T), estrone (E1), estradiol (hourly), 17-hydroxypregnenolone, and 17-hydroxyprogesterone (17PO) concentrations were compared during basal and suppression conditions and after gonadotropin and adrenal stimulations by bolus GnRH (10 micrograms) and CRF (1 microgram/kg). The progression from sleep-augmented pulsatile LH secretion to higher LH levels during wake than sleep observed during normal pubertal development occurred 2 yr earlier in the HA group. The number of LH pulses was significantly higher in the HA group during both sleep and waking, whereas pulse amplitude was higher only during the awake time. Thus, mean LH was 2.0-fold higher during the awake time and only 1.6-fold higher during sleep in the HA group compared to the normal group. The elevation of FSH in HA was small relative to that of LH, resulting in an increased LH/FSH ratio (P < 0.008). The HA group had higher concentrations of 17PO (1.8-fold), androstenedione (1.9-fold), T (2.4-fold), and E1 (1.7-fold) than the normal group (all P < 0.001), with no alteration in circadian rhythm. These elevated steroid levels were significantly correlated with LH levels in the basal state and decreased in proportion to the change in LH during Nal-Glu suppression. During adrenal suppression with dexamethasone, concentrations of cortisol, dehydroepiandrosterone, and 17-hydroxypregnenolone decreased in both groups (P < 0.001), but significant suppression of 17PO, T, and E1 occurred only in the normal girls, indicating the ovarian origin of the increased levels of these steroids with enhanced expression of 17 alpha-hydroxylase activity in HA girls.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Adolescent; Androstenedione; Child; Circadian Rhythm; Dexamethasone; Estrone; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Hyperandrogenism; Luteinizing Hormone; Ovary; Periodicity; Polycystic Ovary Syndrome; Puberty; Testosterone

To determine if fluoroimmunoassay (FIA) of serum luteinizing hormone (LH) is more useful clinically than a conventional radioimmunoassay (RIA) because it has been suggested that FIA closely reflects biological activity.. Comparison of serum LH measurements by RIA and FIA during various perturbations in normal ovulatory women and in women with polycystic ovarian syndrome (PCOS).. Normal ovulatory subjects were healthy volunteers and women with PCOS were untreated and newly diagnosed outpatients in our Reproductive Endocrinology/Infertility Clinic, Women's Hospital, at the Los Angeles County+University of Southern California Medical Center.. Fifty-three normal ovulatory women, ages 20 to 35, and 27 women with PCOS, ages 21 to 35. All were in good health and received no other medications during the study period.. Fluoroimmunoassay of serum LH reflected status of known altered bioactivity better than with a conventional RIA. This was most evident during conditions of gonadotropin suppression and in patients with PCOS. An excellent correlation was found between values of FIA and RIA.. The measurement of LH by FIA is clinically useful, specifically when a change in biological activity of LH is sought.

Topics: Adult; Evaluation Studies as Topic; Female; Fluoroimmunoassay; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Luteinizing Hormone; Norethindrone; Polycystic Ovary Syndrome; Pulsatile Flow; Radioimmunoassay; Reference Values; Time Factors