25 - Pharmacodynamics and Pharmacokinetics of Gonadotrophins

Summary

INTRODUCTION

Exogenous hormone supplementation has been used to treat infertility for nearly 100 years (1). Compounds extracted from urine and serum have been used in pharmacotherapeutic preparations as the mainstay of exogenous hormone supplementation until recently. These preparations enabled clinicians to manipulate the hypothalamic-pituitary-ovarian axis to induce follicular recruitment and subsequent ovulation in otherwise anovulatory infertile patients. A resurgence of interest in the treatment of infertility occurred with the birth of the first infant following successful in vitro fertilization (IVF), baby Louise Brown. It is interesting that this pregnancy did not result from exogenous hormone supplementation but rather from a noninduced ovulation (2). Nevertheless, with this successful pregnancy came renewed interest in treatment of infertility. This interest has resulted in the development of new technologies for the production of better, safer, and more affordable treatment options for the infertile female patient.

Ovulation of a single healthy oocyte in a natural cycle is a carefully orchestrated event modulated by secretion of several glycoproteins that act on the ovary and other reproductive tissues to stimulate changes in functional morphology and to stimulate steroidogenesis (Table 25.1). Follicle-stimulating hormone (FSH) is secreted from the anterior pituitary gland in response to the secretion of gonadotropin-releasing hormone from the hypothalamus. Circulating FSH stimulates follicular growth in the ovary by acting on specific FSH receptors in the cell membranes of granulosa cells.