Follicular development induced by recombinant luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in anovulatory women with LH and FSH deficiency: evidence of a threshold effect.
OBJECTIVE
To assess the requirement for luteinizing hormone (LH) in women deficient in LH and follicle-stimulating hormone (FSH).


METHODS
A prospective, randomized, parallel-group, multicentre study was carried out in tertiary care and academic medical centres. Women with anovulatory amenorrhoea > or = 1 year, serum oestradiol (E(2)) < 60 pg/mL (< 220 pmol/L) and low normal serum gonadotrophins were randomized in cycle A to a fixed daily dose of recombinant human (r-h) FSH (150 IU) and r-hLH 0, 25, 75 or 225 IU. Cycles B and C were not randomized.


METHODS
Follicular development, ovulation and luteinization.


RESULTS
In cycle A, follicular development was achieved by 63.6% (7/11), 100% (9/9), 72.7% (8/11) and 66.7% (6/9) of patients who received r-hFSH and r-hLH 0, 25, 75 or 225 IU/day, respectively (p = not significant). Among patients with basal serum LH of < 1.2 IU/L, a dose-response relationship of r-hLH to follicular development was observed (p = 0.039). Fourteen of 34 patients (41.2%) wishing to conceive became pregnant. Among patients with hypogonadotrophic hypogonadism (HH) treated with r-hFSH alone, a transition from LH dependence to independence was observed between basal LH values of > or = 1.2 IU/L and < or = 1.6 IU/L. The r-hLH was well tolerated and no serious adverse events occurred during treatment. The most common treatment-related events were related to the reproductive system and the gastrointestinal tract.


CONCLUSIONS
Recombinant human LH provides a safe treatment option for women with HH. This small study also provided evidence suggestive of an LH threshold: follicular development was suboptimal when less than 75 IU/day r-hLH was administered.
O'Dea
Louis
L
Radius Health, Inc., Cambridge, MA, USA.
O'Brien
Fanny
F
Currie
Karen
K
Hemsey
George
G
D000293:Adolescent; D000328:Adult; D000568:Amenorrhea / Q000097:blood / Q000188:drug therapy*; D000858:Anovulation / Q000097:blood / Q000188:drug therapy*; D004958:Estradiol / Q000097:blood; D005260:Female; D043373:Follicle Stimulating Hormone, Human / Q000009:adverse effects / Q000172:deficiency* / Q000627:therapeutic use*; D020249:Hormone Replacement Therapy; D006801:Humans; D007986:Luteinizing Hormone / Q000009:adverse effects / Q000172:deficiency* / Q000627:therapeutic use*; D006080:Ovarian Follicle; D011247:Pregnancy; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use
D043373:Follicle Stimulating Hormone, Human; D011994:Recombinant Proteins; D004958:Estradiol; D007986:Luteinizing Hormone