Clinical profiling of recombinant follicle stimulating hormone (rFSH; Puregon): Relationship between serum FSH and efficacy

Abstract

Single-dose and multiple-rising dose studies of recombinant follicle stimulating hormone (rFSH) in hypogonadotrophic male and female volunteers demonstrated that the rate of FSH absorption after i.m. injection is higher in men than in women. In the absence of endogenous FSH, a correlation between serum FSH and body weight became apparent. The elimination half-life of rFSH was not different between the sexes and was comparable with urinary FSH. However, the in-vitro bio:immuno ratio of serum FSH was significantly higher after the administration of rFSB than after urinary FSH. When rFSH was administered daily with a fixed dose, steady state levels were reached within 3-5 days. Serum FSH concentrations increased in a dose-dependent manner when the daily dose was increased weekly over 3 weeks from 75 to 225 IU. In hypogonadotrophic women, rFSH induced normal follicular growth whereas oestrogen synthesis was impaired. In women pituitary suppressed by a high-dose oral contraceptive, the daily administration of 150 IU rFSH for 1 week induced more and larger antral follicles than the same regimen with urinary FSH, whereas the serum immunoactive FSH concentrations measured 24 h after each dosing were similar. It is concluded that even though equal or lower serum immunoactive FSH concentrations were obtained following the administration of rFSH compared with urinary FSH, circulating bioactive FSH concentrations were higher. Therefore, the conventional idea that serum immunoreactive FSH correlates positively with the magnitude of the ovarian response should be reconsidered.