The combination of gonadotrophin-releasing hormone (GnRH) antagonist and pulsatile GnRH normalizes luteinizing hormone secretion in polycystic ovarian disease but fails to induce follicular maturation.
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)
Dubourdieu
S
S
Clinique Endocrinologique, Hôtel-Dieu, Nantes, France.
Le Nestour
E
E
Spitz
I M
IM
Charbonnel
B
B
Bouchard
P
P
D000328:Adult; D004359:Drug Therapy, Combination; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors*; D006801:Humans; D007262:Infusions, Intravenous; D007986:Luteinizing Hormone / Q000378:metabolism*; D006080:Ovarian Follicle / Q000187:drug effects*; D011085:Polycystic Ovary Syndrome / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology
C057805:LHRH, N-Ac-2-Nal(1)-4-Cl-Phe(2)-3-Pal(3)-Arg(5)-Glu(6)-AlaNH2(10)-; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone