Human Reproduction, Vol. 9, No. 7, pp. 1237-1242, 1994
© 1994 European Society of Human Reproduction and Embryology
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Endocrinology: Recombinant human follicle-stimulating hormone and ovarian response in gonadotrophin-deficient women
1Section of Reproductive Endocrinology and Fertility, Department of Obstetrics and Gynaecology, Dijkzigt University Hospital Dr Molewaterplein 40, 3015 GD Rotterdam, The Netherlands 2Department of Obstetrics and Gynaecology, Karolinska Hospital Stockholm, Sweden 3Department of Obstetrics and Gynaecology, Kaplan Hospital Rehovot, Israel 4Medical Research & Development Unit, Organon International Bv Oss, The Netherlands 5Fondation de Recherche en Hormonologie Fresnes, France 6Service d'Endocrinologie et de Maladies de la Reproduction, Hôpital Bicêtre Le Kremlin Bicêtre, France
Correspondence: 7To whom correspondence should be addressed
Seven women suffering from hypogonadism due to previous hypophysectomy, isolated gonadotrophin deficiency, or Kallman's syndrome [median age 39 years (range 24–45)] volunteered to participate in a study to assess ovarian response following multiple-dose administration of recombinant human follicle-stimulating hormone (rhFSH; Org 32489). Baseline serum FSH and luteinizing hormone (LH) concentrations were 0.25 (<0.05–1.15) IU/l and 0.06 (<0.05–0.37) IU/l, respectively. Subjects received daily i.m. injections of rhFSH for 3 weeks (week 1: 75 IU/day, week 2: 150 IU/day, week 3: 225 IU/day). Blood sampling and sonographic investigations were performed on alternate days. Steady-state FSH concentrations were reached 
3–5 days after alterations of the doses administered. Maximum FSH concentrations were between 7.1 and 11.8 IU/l, whereas serum LH concentrations remained unchanged. Due to absent follicle development and lack of a rise in immunoreactive inhibin (INH) (response failure possibly due to early ovarian failure or resistant ovary syndrome) in two subjects, analysis of ovarian response was restricted to five volunteers. Serum androstenedione levels showed no significant changes during rhFSH administration. Although serum immunoreactive INH concentrations reached normal late follicular values [659 (388–993) IU/l], serum oestradiol revealed only a minor increase [77 (18–210) pmol/I]. Moreover, growth of (multiple) ovarian follicles was observed up to pre-ovulatory sizes (>15 mm) in these patients. It may be concluded from the present study that (i) rhFSH exhibits no intrinsic LH activity; (ii) rhFSH stimulation in hypogondotrophic women resulted in an immunoreactive INH rise which was similar to that in normal women, whereas in contrast only a minor increase in oestradiol concentrations was observed (suggesting normal granulosa cell function and low availability of androgens as a substrate for aromatization); (iii) despite the minimal oestrogen increase, ovarian follicles developed normally to the pre-ovulatory stage.
Key words: follicle development/hypogonadism/inhibin/oestrogen/ovarian response
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