Recombinant LH (lutropin alfa) for the treatment of hypogonadotrophic women with profound LH deficiency: a randomized, double-blind, placebo-controlled, proof-of-efficacy study.
OBJECTIVE
To confirm the safety and efficacy of 75 IU lutropin alfa with concomitant follitropin alfa in inducing follicular development in women with profound gonadotrophin deficiency.


METHODS
Double-blind, randomized, placebo-controlled trial conducted in 25 medical centres in four countries.


METHODS
Thirty-nine patients with LH < 1.2 IU/l and FSH < 5.0 IU/l were treated with concomitant 75 IU lutropin alfa and 150 IU follitropin alfa or concomitant placebo and 150 IU follitropin alfa.


METHODS
Primary efficacy end-point (intent-to-treat): follicular development defined by (i) at least one follicle >or= 17 mm; (ii) serum E(2) level >or= 400 pmol/l on day of hCG administration (DhCG); and (iii) mid-luteal phase progesterone level >or= 25 nmol/l.


RESULTS
In the analysis of evaluable patients, 66.7% (16 of 24) of patients given lutropin alfa achieved follicular development compared with 20.0% (2 of 10) of patients receiving placebo (P = 0.023). In the intent-to-treat analysis, follicular development was achieved in 65.4% (17 of 26) of patients receiving lutropin alfa and 15.4% (2 of 13) of patients receiving placebo (P = 0.006). The statistical difference between treatment groups was preserved when over-response leading to cycle cancellation was analysed as a failed response (P = 0.034). Lutropin alfa was well tolerated.


CONCLUSIONS
Subcutaneous co-administration of 75 IU lutropin alfa with follitropin alfa is safe and effective in inducing follicular development in women with profound gonadotrophin deficiency.
Shoham
Z
Z
Department of Obstetrics and Gynecology, Kaplan Medical Center, Rehovot, Israel.
Smith
H
H
Yeko
T
T
O'Brien
F
F
Hemsey
G
G
O'Dea
L
L
D000293:Adolescent; D000328:Adult; D004311:Double-Blind Method; D004958:Estradiol / Q000097:blood; D005260:Female; D020249:Hormone Replacement Therapy; D006801:Humans; D007006:Hypogonadism / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D007986:Luteinizing Hormone / Q000009:adverse effects / Q000172:deficiency* / Q000627:therapeutic use*; D006080:Ovarian Follicle / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D010919:Placebos; D011247:Pregnancy; D018873:Pregnancy Rate; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult
D010919:Placebos; D011994:Recombinant Proteins; D004958:Estradiol; D007986:Luteinizing Hormone