Pulsatile gonadotropin-releasing hormone: clinical applications of a physiologic paradigm

Abstract

Gonadotropin-releasing hormone (GnRH) is a fundamental driver of human reproduction. A pulsatile pattern of GnRH secretion is essential to achieve pituitary stimulation, gonadotropin secretion, and normal gonadal function. Pulsatile GnRH administration is used to treat anovulation and male hypogonadotropic hypogonadism. Pulsatile GnRH ovulation induction is effective and safe because it allows to avoid ovarian hyperstimulation syndrome and reduce the occurrence of multiple pregnancies. This physiology-inspired therapeutic tool has also permitted to elucidate several pathophysiologic features of human reproductive disorders.

Keywords: GnRH; LH; gonadotropins; ovulation induction; pulsatile.

Figure 1

Luteinizing hormone (LH) measurements in blood samples obtained at 5-minute intervals for 12 consecutive hours in a patient with polycystic ovary syndrome. Data points were then progressively omitted to simulate blood sampling conducted at 10-, 15-, and 20-minute intervals. The asterisks indicate significant LH peaks identified by computer algorithm. (From Crowley et al. (6). Reprinted by permission of the publisher.)

Figure 2

Daily gonadotropin and gonadal steroid levels throughout a normal spontaneous menstrual cycle (left panels) and during pulsatile gonadotropin-releasing hormone (GnRH) ovulation induction in a patient with hypothalamic primary amenorrhea (right panels). E₂ = estradiol; FSH = follicle-stimulating hormone; LH = luteinizing hormone; P = progesterone. (From Filicori et al. (13). Reprinted by permission of the publisher.)

Figure 3

Daily gonadotropin and gonadal steroid levels (mean ± standard error) in patients with primary hypogonadotropic amenorrhea receiving 60 μg/day of GnRH at 60-minute intervals (closed circles) or 120-minute intervals (open circles). E = estradiol; FSH = follicle-stimulating hormone; LH = luteinizing hormone; P = progesterone. (From Filicori et al. (16). Reprinted by permission of the publisher.)

Figure 4

Daily gonadotropin and steroid levels (mean ± standard error) during pulsatile gonadotropin-releasing hormone (GnRH) administration (5 μg/bolus at 1-hour intervals) in the ovulatory cycles of patients with idiopathic hypogonadotropic hypogonadism (IHH) (O), polycystic ovary disease (PCOD) without GnRH agonist suppression (pre-A [•]), and PCOD after GnRH agonist suppression (post-A [∗]). Hormone data are centered around the midcycle gonadotropin surge. E = estradiol; FSH = follicle-stimulating hormone; LH = luteinizing hormone; P = progesterone. (From Filicori et al. (18). Reprinted by permission of the publisher.)