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

• Published in: Current medical research and opinion Vol. 24; no. 10; pp. 2785 - 2793
• Main Authors: O'Dea, Louis, O'Brien, Fanny, Currie, Karen, Hemsey, George
• Format: Journal Article
• Language: English
• Published: England Informa UK Ltd 01.10.2008; Taylor & Francis; Informa Healthcare
• Subjects: Adolescent; Adult; Amenorrhea - blood; Amenorrhea - drug therapy; Anovulation; Anovulation - blood; Anovulation - drug therapy; Estradiol - blood; Female; Follicle Stimulating Hormone, Human - adverse effects; Follicle Stimulating Hormone, Human - deficiency; Follicle Stimulating Hormone, Human - therapeutic use; Follicular development; Hormone Replacement Therapy; Humans; Hypogonadotrophic hypogonadism; Luteinizing Hormone - adverse effects; Luteinizing Hormone - deficiency; Luteinizing Hormone - therapeutic use; Ovarian Follicle; Pregnancy; r-hFSH; r-hLH; Recombinant luteinizing hormone; Recombinant Proteins - adverse effects; Recombinant Proteins - therapeutic use; Threshold effect
• ISSN: 0300-7995; 1473-4877
• DOI: 10.1185/03007990802374815

ABSTRACT Objective: To assess the requirement for luteinizing hormone (LH) in women deficient in LH and follicle-stimulating hormone (FSH). Research design and methods: A prospective, randomized, parallel-group, multicentre study was carried out in tertiary care and academic medical centres. Women with anovulatory amenorrhoea ≥ 1 year, serum oestradiol (E2) < 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. Main outcome measures: 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 ≥ 1.2 IU/L and ≤ 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.