RECOMBINANT HUMAN FOLLICLE-STIMULATING-HORMONE AND OVARIAN RESPONSE IN GONADOTROPIN-DEFICIENT WOMEN

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 asse ss ovarian response following multiple-dose administration of recombin ant human follicle-stimulating hormone (rhFSH; Org 32489). Baseline se rum 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 receive d 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 inv estigations were performed on alternate days. Steady-state FSH concent rations were reached similar to 3-5 days after alterations of the dose s administered. Maximun FSH concentrations were between 7.1 and 11.8 I U/l, whereas serum LH concentrations remained unchanged. Due to absent follicle development and lack of a rise in immunoreactive inhibin (IN H) (response failure possibly due to early ovarian failure or resistan t ovary syndrome) in two subjects, analysis of ovarian response was re stricted to five volunteers. Serum androstenedione levels showed no si gnificant changes during rhFSH administration. Although serum immunore active INH concentrations reached normal late follicular values [659 ( 388-993) IU/l], serum oestradiol revealed only a minor increase [77 (1 8-210) pmol/l]. Moreover, gro,vth 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 intrin sic LH activity; (ii) rhFSH stimulation in hypogondotrophic women resu lted in an immunoreactive INH rise which was similar to that in normal women, whereas in contrast only a minor increase in oestradiol concen trations was observed (suggesting normal granulosa cell function and l ow availability of androgens as a substrate for aromatization); (iii) despite the minimal oestrogen increase, ovarian follicles developed no rmally to the pre-ovulatory stage.