Effect of Obesity on Recombinant Follicle-stimulating Hormone Absorption: Subcutaneous Versus Intramuscular Administration

Objective: To determine whether recombinant follicle-stimulating hormone (rFSH) should be administered intramuscularly (i.m.) or subcutaneously (s.c.) to obese women.

Design: Randomized, single-center, two-way crossover study.

Setting: Academic clinical research center.

Subject(s): Nineteen healthy women of reproductive age with body mass indices of 19.9 kg/m(2)-42.8 kg/m(2).

Intervention(s): Leuprolide acetate 3.75 mg i.m. to achieve pituitary down-regulation as determined by serum E(2) levels. Subjects were then given a single dose of 300 IU rFSH either i.m. or s.c.. Multiple blood sampling was performed over the next two weeks, and after retreatment with leuprolide, a second 300 IU rFSH dose was given via the other administration route.

Main Outcome Measure(s): Serum samples were analyzed in duplicate for follicle-stimulating hormone (FSH) using a standard radioimmunoassay in a single run. Maximum concentrations (C(max)), times to C(max) (T(max)), and extent of absorption (area under curve [AUC]) with i.m. vs. s.c. administration were compared using paired analysis.

Result(s): Maximal concentrations were achieved within 24 hours with both s.c. and i.m. routes. No significant differences were found in C(max), T(max), or AUC with s.c. vs. i.m. administration. A decline of AUC occurred among subjects of higher body mass index (BMI) with rFSH given either s.c. or i.m.. Subcutaneous administration achieved AUCs comparable to i.m. administration in both normal-weight and obese subjects.

Conclusion(s): Our data indicate that the s.c. administration of rFSH is appropriate for women regardless of body mass.