The effect of sequential administration of octreotide alone and octreotide/growth hormone simultaneously on buserelin stimulated ovarian steroid secretion in women with polycystic ovary syndrome.
OBJECTIVE
GH increases oestradiol secretion and promotes oocyte development in women with polycystic ovary syndrome (PCOS). However, there are no data on ovarian androgen production after GH treatment. We have therefore assessed the effect of sequential treatment with a long-acting somatostatin analogue (octreotide) alone and octreotide/GH simultaneously on ovarian steroid levels in PCOS and non-PCOS normal women.


METHODS
Twenty-six PCOS and 12 non-PCOS women, aged 18-35 years, were studied. Ten of the PCOS and six of the non-PCOS women received sequential treatment with octreotide alone and followed by octreotide + GH together, while another eight PCOS and six non-PCOS women received saline instead of octreotide-octreotide + GH. The remaining eight PCOS women received GH alone.


METHODS
The octreotide-octreotide + GH and saline studies lasted 12 days, the GH alone 7 days. Octreotide (100 micrograms, s.c., t.d.s.) was given from the 2nd to the 10th and octreotide + GH (4 IU, s.c. at 2300h) from the 7th to the 10th day of the study. The GH alone treatment was given from the 2nd to the 5th day. On the 1st day, two tests were performed: (1) an oral glucose tolerance test (OGTT, 75 g, orally) at 0830h and (2) a buserelin (long-acting GnRH agonist) test (100 micrograms, s.c.) at the end of the OGTT. Both tests were repeated on the 6th and 11th days in the octreotide-octreotide + GH or on the 6th day only in the GH alone study.


METHODS
Blood glucose, insulin (IRI), C-peptide and IGF-I (at time 0 only) were measured before glucose administration and at 30-minute intervals for 3 hours and LH, FSH, delta 4-androstenedione (delta 4A), testosterone (TT), free testosterone (FT) and oestradiol (E2) before buserelin and at 1,2,6,10,14 and 18 hours.


RESULTS
Octreotide alone significantly reduced the basal IGF-I stimulated LH and both basal and stimulated IRI, delta 4A, TT, FT and E2 levels in all PCOS women tested. Both octreotide + GH and GH alone increased significantly the basal IGF-I and both basal and stimulated IRI and E2 levels in all PCOS women, while the basal and stimulated LH, delta 4A, TT and FT levels were completely unaffected. In contrast, octreotide-octreotide + GH treatment did not modify either basal or stimulated gonadotrophin or ovarian steroid levels in non-PCOS women. No changes in either basal or stimulated hormone levels were observed in those PCOS women who received saline. Although both basal and stimulated levels of all ovarian androgens were significantly reduced by octreotide-octreotide + GH treatment in PCOS women, they still remained significantly higher than in the non-PCOS women.


CONCLUSIONS
The data show that (1) octreotide is a potent inhibitor of ovarian steroid secretion, (2) GH increases oestradiol secretion, possibly by stimulating ovarian aromatase activity, and (3) the combined treatment with octreotide and GH significantly improves ovarlan function in women with PCOS and may thus have important clinical implications for the management of infertile women with this syndrome.
Piaditis
G P
GP
Department of Endocrinology and Diabetes, General Hospital of Athens, Greece.
Hatziioanidis
A H
AH
Trovas
G P
GP
Misichronis
G S
GS
Kounadi
T G
TG
Devetzaki
O A
OA
Andronis
C K
CK
Rangou
D B
DB
Chlouverakis
C S
CS
D000293:Adolescent; D000328:Adult; D000735:Androstenedione / Q000097:blood; D002064:Buserelin; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004958:Estradiol / Q000097:blood; D005260:Female; D005951:Glucose Tolerance Test; D006728:Hormones / Q000008:administration & dosage / Q000627:therapeutic use; D019382:Human Growth Hormone / Q000008:administration & dosage* / Q000627:therapeutic use; D006801:Humans; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D015282:Octreotide / Q000008:administration & dosage* / Q000627:therapeutic use; D011085:Polycystic Ovary Syndrome / Q000097:blood / Q000188:drug therapy*; D013739:Testosterone / Q000097:blood
D006728:Hormones; D007328:Insulin; D019382:Human Growth Hormone; D013739:Testosterone; D000735:Androstenedione; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D007986:Luteinizing Hormone; D002064:Buserelin; D015282:Octreotide