GnRH (gonadotropin-releasing hormone), also called LHRH (luteinizing hormone releasing hormone, or gonadorelin (in the pharmaceutical role) is a hypothalamic decapeptide with the physiological role of inducing luteinizing hormone (LH) and follicle stimulating hormone (FSH) release from the pituitary. GnRH is the first step in the hypothalamic-pituitary-gonadal axis, and is instrumental in pubertal development, follicle growth, spermatogenesis, and ovulation. Exogenous GnRH initially enhances sex hormone production upon acute administration, but with chronic frequent administration (or repeated administration of long-acting analogs) desensitizes the hypothalamic-pituitary-gonadal axis and blunts the release of sex hormones. GnRH and its analogs are used as to test hormonal production via provocation, fertility treatment for women, and also for chemical castration and to combat certain hormone-responsive cancers. Occasionally GnRH is used to induce spermatogenesis and testosterone production in males, and its analogs have been used infrequently to treat hypogonadism. GnRH also plays secondary and lesser-understood roles outside of the hypothalamic-pituitary axis, such as in the testes. The peptide amino acid structure of GnRH is pyroGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2.
Pulse frequency or waveform influences the pituitary effect of GnRH: lower-frequency pulsatility of GnRH induces FSH release, while higher-frequency pulsatility induces LH release.
Unaltered synthetic GnRH is effective, but not frequently used, for treating secondary hypogonadism and infertility. In a study by Skarin, et al, a 23-year-old male was successfully treated for hypogonadism with chronic treatment with GnRH:
Spermatogenesis became close to normal and the subject 's wife became pregnant after 181 days of treatment. The prolonged treatment with the small infusion pump was well accepted and did not interfere with the patient's daily life activities. Thus, chronic pulsatile low dose GnRH treatment can restore normal pituitary-gonadal function in idiopathic male hypogonadotropic hypogonadism.
Compared to longer-acting agonists, which may work without a pump, synthetic gonadorelin’s short half-life makes it a less common choice for restoring gonadal function over longer periods of time.
GnRH may also play a role in male birth control in the future, outside of cases where the reduction in sex drive (as in chemical castration) is desired; when coadministered with testosterone, infertility occurs without hypogonadism. Bhasin et al find that "superactive analogues of gonadotrophin releasing hormone and testosterone, when administered together, synergistically inhibit gonadotrophin secretion and spermatogenesis in the rat."
GnRH, whether in the presence of absence of exogenous testosterone or not, results in an initial spike in fertility and hormone levels that reduces over ten days before dropping below the initial baseline, provided administration is frequent enough and dosage is sufficient:
Daily administration of both 10 and 100 μg of GnRH-A alone resulted in an early phase of stimulation followed by progressive decline in LH, FSH and testosterone to levels below baseline by day 10 despite continued administration of GnRH-A. Addition of testosterone to 10 μg of GnRH-A resulted in hormonal responses identical to those seen with GnRH-A alone. Combined treatment of testosterone with 100 μg of GnRH-A did not blunt the peak LH and FSH responses on day 2, but resulted in significantly lower LH (mean integrated responses: 187 ± 30 vs. 234 ± 42 mIU-d/ml) and FSH (mean integrated responses: 20·6 ± 3·3 vs. 32·8 ± 4·2 mIU-d/ml) responses from days 3 to 11. By day 11, all subjects receiving combined treatment (GnRH-A 100 μg+testosterone oenanthate) had undetectable serum FSH levels....We conclude that addition of a suppressive dose of testosterone to an appropriate dose of GnRN-A significantly enhances gonadotrophin suppression by GnRH-A in the human male. Combined use of testosterone and GnRH-A might be of importance in the development of a male contraceptive to achieve the desired suppression of spermatogenesis while avoiding androgen deficiency.
Counis et al (2009) discuss the important role played by fluctuations in pulse form:
Brain control of the reproductive system is mediated through hypothalamic gonadotropin-releasing hormone (GnRH) which activates specific receptors (GnRHR) present at the surface of the pituitary gonadotropes to trigger secretion of the two gonadotropins LH and FSH. A unique feature of this system is the high dependence on the secretion mode of GnRH, which is basically pulsatile but undergoes considerable fluctuations in pulse frequency pattern in response to endogenous or external factors. 
Compared to other diurnal or circadian hormonal cascades, the production of GnRH is exceptionally sensitive to external cues or acute physiological changes. For example, in a study performed on healthy young men in a nutrient-deprived state, Aloi et al (1997) concluded that nutrient deprivation decreases endogenous GnRH output and that further, exogenous GnRH "rescue[s]...hypogonadism".
 Campbell RE, Gaidamaka G, Han SK, Herbison AE. "Dendro-dendritic bundling and shared synapses between gonadotropin-releasing hormone neurons". Proc. Natl. Acad. Sci. U.S.A..
 Brown RM. An introduction to Neuroendocrinology. Cambridge, UK: Cambridge University Press, 1994.
G. Skarin, SJ Nillius, L. Wibell, and L. Wide. Chronic Pulsatile Low Dose GnRH Therapy for Induction of Testosterone Production and Spermatogenesis in a Man with Secondary Hypogonadotropic Hypogonadism. Journal of Clinical Endocrinology & Metabolism Vol. 55, No. 4 723-726.
S. Bhasin, D. Heber, B. Steiner, M. Peterson, B. Blaisch, L. A. Campfield, R. S. Swerdloff, Hormonal effects of GnRH agonist in the human male: Testosterone enhances gonadotrophin suppression induced by GnRH agonist. Clinical Endocrinology, Volume 20 Issue 2, Pages 119 - 128.
Counis R, Garrel G, Laverriere JN, Simon V, Bleux C, Magre S, Cohen-Tannoudji J. Folia. The GnRH receptor and the response of gonadotrope cells to GnRH pulse frequency code. A story of an atypical adaptation of cell function relying on a lack of receptor homologous desensitization. Histochem Cytobiol. 2009;47(5):S81-7.
 Aloi JA, Bergendahl M, Iranmanesh A, Veldhuis JD. Pulsatile intravenous gonadotropin-releasing hormone administration averts fasting-induced hypogonadotropism and hypoandrogenemia in healthy, normal weight men. J Clin Endocrinol Metab. 1997 May;82(5):1543-8.