Human Reproduction, Vol. 17, No. 10, 2540-2547,
October 2002
© 2002 European Society of Human Reproduction and Embryology
In-vivo ovarian androgen responses to recombinant FSH with and without recombinant LH in polycystic ovarian syndrome
1 Department of Obstetrics and Gynaecology, University of Alberta, Edmonton and 2 Department of Obstetrics and Gynaecology, University of British Columbia, Vancouver, Canada
BACKGROUND: Effects of exogenous LH on ovarian androgen secretion during ovulation induction have not been clearly characterized in polycystic ovarian syndrome (PCOS). The purpose of this study was to compare androgen secretion in PCOS women during ovarian stimulation with either recombinant FSH (rFSH) alone or combined with recombinant LH (rLH). METHODS: Clomiphene-resistant women with PCOS were allocated, in a factorial study design, to receive either daily injections of rFSH (n = 24) or rFSH + rLH (n = 24) in a 1:1 ratio starting: (i) on day 2–3 of progestogen-induced menses (n = 8); (ii) after 6 weeks of GnRH agonist treatment (nafarelin, 400 µg twice daily; n = 8); or (iii) after nafarelin treatment as in (ii) plus dexamethasone (n = 8). The effects of rFSH with rFSH + rLH under these three hormone conditions on serum LH, 17
-hydroxyprogesterone (17-OHP), androstenedione (
4) and testosterone were contrasted by analysis of variance with specific treatment days as a repeated measures factor. RESULTS: Pre-study hormone levels were similar for all groupings. Nafarelin significantly suppressed LH levels, which remained at the lower limit of assay sensitivity (0.5 IU/l) during stimulation with rFSH but increased significantly to >1 but <2 IU/l when rLH was added. As expected, 17-OHP, 4 and testosterone levels fell following nafarelin treatment. Dexamethasone further suppressed 17-OHP, 4 and testosterone levels and unmasked a small but significant rise in these ovarian steroids 24 h following the first dose of rFSH + rLH, a rise that was absent with rFSH alone. Secretion of these steroids then appeared to ‘catch-up’ after 5 days of rFSH stimulation. CONCLUSIONS: Despite profound LH, 17-OHP, 4 and testosterone suppression, comparable E2 response, follicle development and successful pregnancies in PCOS subjects receiving rFSH alone to those receiving rFSH + rLH would argue that circulating LH at levels as low as 0.5 IU/l are sufficient to sustain adequate follicle development and function when FSH is present in abundance. Whether the observed dichotomy between rFSH and rFSH + rLH treatment in temporal secretion patterns reflects a greater reliance on evolving paracrine mechanisms as the follicles mature under profound LH suppression remains to be explored but may influence the optimal LH threshold for ovulation induction in PCOS.
Key words: androgens/ovarian stimulation/PCOS/recombinant FSH/recombinant LH
3 To whom correspondence should be addressed at: Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, University of British Columbia, 2nd Floor, Willow Pavilion, Vancouver Hospital and Health Sciences Centre, 855 West 12th Avenue, Vancouver, B.C. Canada V5Z 1M9. E-mail: apcheung{at}interchange.ubc.ca
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