Gonadorelin
Gonadorelin (synthetic GnRH)
Synthetic gonadotropin-releasing hormone, historically approved for diagnosis and fertility and now used to preserve testicular function during testosterone therapy.
Overview
Gonadorelin is the synthetic form of gonadotropin-releasing hormone (GnRH), the hypothalamic signal that drives pituitary LH and FSH release. It was previously FDA-approved for diagnostic and fertility uses. In men on testosterone replacement it is increasingly used to preserve testicular volume and fertility by maintaining natural signaling. Its action must be pulsatile, since continuous stimulation paradoxically shuts hormone release down.
Mechanism of action
Stimulates pituitary release of LH and FSH when given in pulses, mimicking natural GnRH signaling; continuous exposure instead desensitizes and suppresses it.
Key studies & citations
- Animal1978
Hypophysial responses to continuous and intermittent delivery of hypothalamic gonadotropin-releasing hormone
In monkeys with hypothalamic lesions, hourly GnRH pulses restored LH and FSH secretion while continuous infusion failed and desensitized the pituitary.
Science - Human1982
Induction of puberty in men by long-term pulsatile administration of low-dose gonadotropin-releasing hormone
Pulsatile subcutaneous GnRH by pump normalized gonadotropins within a week, raised testosterone from 77 to 520 ng/dL in one month and produced spermatogenesis in three of six hypogonadotropic men.
New England Journal of Medicine
Frequently asked questions
Why must gonadorelin be given in pulses?
The pituitary responds to pulses of GnRH. Continuous exposure desensitizes the receptors and paradoxically shuts down LH and FSH release, which is how drugs like leuprolide suppress hormones.