Gonodatropin-Releasing Hormone (GnRH)

Take-home points

• The gonadotropin-releasing hormone regulates the production of sex hormones such as testosterone.
• It is rare for the gonadotropin-releasing hormone to be measured in clinical settings due to various practical challenges.
• Low levels of luteinising hormone and follicle-stimulating hormone can indicate an issue with producing enough gonadotropin-releasing hormone.
• If an issue with the gonadotropin-releasing hormone is suspected, a healthcare professional may recommend various treatments.

What is gonadotropin-releasing hormone and what does it do?

If the body were an orchestra, hormones would be the conductors, orchestrating the symphony of bodily functions. Among these, gonadotropin-releasing hormone (GnRH), produced deep within the brain, controls the downstream production of gonadotropin hormones in the gonads (the testicles in males). These gonadotropins are the luteinising hormone and the follicle-stimulating hormone, which stimulate the production of sex hormones such as testosterone.  

Under healthy conditions, your body makes less gonadotropin-releasing hormone when your testosterone levels are high and more when testosterone is low. As such, the gonadotropin-releasing hormone is linked with many of testosterone's functions: sexual function, sperm production, fertility, muscle mass and energy levels.¹  

Note: Gonadotropin-releasing hormone (GnRH) can sometimes be referred to as luliberin or the luteinising hormone-releasing hormone (LHRH).

Can gonadotropin-releasing hormone be measured?

It is challenging to measure gonadotropin-releasing hormone levels directly because it is released in short pulses throughout the day and metabolised in blood within minutes.² Consequently, a single measurement may not capture the dynamic changes in the secretion of this hormone. For this reason, measuring gonadotropin-releasing hormone is not a common practice in clinical settings.¹

Instead of directly measuring gonadotropic-releasing hormone levels, clinicians typically assess the levels of downstream hormones regulated by the gonadotropin-releasing hormone, such as luteinising hormone and follicle-stimulating hormone.³ Abnormal levels of luteinising hormone and follicle-stimulating hormone are a sign of disruptions in the secretion of gonadotropin-releasing hormone and downstream signalling pathways.

What are normal levels of gonadotropin-releasing hormone in men?  

Due to various challenges with measuring gonadotropin-releasing hormone levels, normal levels of this hormone are not well defined. However, gonadotropin-releasing hormone levels are considered naturally low in children and rise during puberty.⁴

One common test, particularly in children, is the gonadotropin stimulation test.³ This checks how well the pituitary gland is working. It works by a healthcare professional injecting a gonadotropin-releasing hormone agonist (leuprolide) and then drawing blood 30-60 minutes later to measure levels of luteinising hormone and follicle-stimulating hormone. Low levels of one or both of these hormones can indicate an issue with gonadotropin-releasing hormone levels.

Please refer to our articles on the luteinising hormone and follicle-stimulating hormone to learn more about normal levels for these hormones.

What do high and low levels of gonadotropin-releasing hormone indicate?

High levels of gonadotropin-releasing hormone, known as hypergonadotropic states, are considered rare. If suspected, this can indicate^5,6,7:

• Hypothalamic dysfunction: A problem in a part of the brain called the hypothalamus.
• Primary gonadal failure: A lack of sex hormone production from the testicles.
• Pituitary adenomas: A noncancerous (benign) tumor.
• Precocious (early) puberty: When a child’s signs of sexual maturity develop too soon.

Low levels of gonadotropin-releasing hormone can indicate^1,8,9:  

• Testosterone deficiency: clinically known as hypogonadism when combined with various signs and symptoms.
• Delayed sexual maturation and puberty.
• Low sex drive.
• Male infertility, low sperm count or azoospermia (no sperm in the ejaculate).
• Kallman syndrome.

What are gonadotropin-releasing hormone (GnRH) analogues?

The GnRH analogues are synthetic compounds that are structurally similar to the natural gonadotropin-releasing hormone produced in the body. They are made to replicate the effects of GnRH and are typically prescribed as androgen deprivation therapy for some prostate cancers. GnRH analogues are also used off-label for precocious puberty, gender dysphoria and infertility. ¹⁰

References

1. Physiology of GnRH and Gonadotropin Secretion.  
2. Moenter SM & Evans NP. J Neuroendocrinol 2022;34(5):e13065.
3. Kim HK et a. Korean J Lab Med 2011;31(4):244–249.
4. Abreu AP et al. Lancet Diabetes Endocrinol 2017;4(3):254–264.
5. Marshall JC et al. Mol Cell Endocrinol 183(1-2):29–32.
6. Guarda FJ et al. Pituitary 2021;24(5):681–689.
7. Bertelloni S et al. Expert Opin Pharmaotherapy 2013;14(12):1627–1639.
8. Georgopoulous NA et al. Hormones (Athens) 2018;17(3):383–390.
9. Nachtigall LB et al. N Engl J Med 1997;336(6):410–415.
10. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. 2012-. Gonadotropin Releasing Hormone (GnRH) Analogues.