In-vivo ovarian androgen responses to recombinant FSH with and without recombinant LH in polycystic ovarian syndrome.
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 micro g 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, 17alpha-hydroxyprogesterone (17-OHP), androstenedione (DeltaDelta(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, DeltaDelta(4) and testosterone levels fell following nafarelin treatment. Dexamethasone further suppressed 17-OHP, DeltaDelta(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, DeltaDelta(4) and testosterone suppression, comparable E(2) 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.
D019326:17-alpha-Hydroxyprogesterone / Q000097:blood; D000328:Adult; D000728:Androgens / Q000378:metabolism*; D003907:Dexamethasone / Q000008:administration & dosage; D005260:Female; D005640:Follicle Stimulating Hormone / Q000008:administration & dosage* / Q000097:blood; D005938:Glucocorticoids / Q000008:administration & dosage; D006801:Humans; D007247:Infertility, Female / Q000209:etiology / Q000628:therapy; D007700:Kinetics; D007986:Luteinizing Hormone / Q000008:administration & dosage*; D017274:Nafarelin / Q000008:administration & dosage; D010053:Ovary / Q000187:drug effects / Q000378:metabolism*; D010062:Ovulation Induction; D011085:Polycystic Ovary Syndrome / Q000150:complications / Q000503:physiopathology*; D011247:Pregnancy; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000008:administration & dosage; D013739:Testosterone / Q000097:blood
D000728:Androgens; D005938:Glucocorticoids; D011994:Recombinant Proteins; D017274:Nafarelin; D013739:Testosterone; D019326:17-alpha-Hydroxyprogesterone; D003907:Dexamethasone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone