The hypothalamic–pituitary–gonadal axis (HPG axis) refers to the hypothalamus, pituitary gland, and gonadal glands as if these individual endocrine glands were a single entity. Because these glands often act in concert, physiologists andendocrinologists find it convenient and descriptive to speak of them as a single system.

The HPG axis plays a critical part in the development and regulation of a number of the body’s systems, such as the reproductive and immune systems. Fluctuations in this axis cause changes in the hormones produced by each gland and have various local and systemic effects on the body.

The axis controls development, reproduction, and aging in animals. Gonadotropin-releasing hormone (GnRH) is secreted from the hypothalamus by GnRH-expressing neurons. The anterior portion of the pituitary gland produces luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and the gonads produce estrogen and testosterone.

In oviparous organisms (e.g. fish, reptiles, amphibians, birds), the HPG axis is commonly referred to as the hypothalamus-pituitary-gonadal-liver axis (HPGL-axis) in females. Many egg-yolk and chorionic proteins are synthesized heterologously in the liver, which are necessary for oocyte growth and development. Examples of such necessary liver proteins are vitellogenin and choriogenin.

The HPA, HPG, and HPT axes are three pathways in which the hypothalamus and pituitary direct neuroendocrine function.

Genetic mutations and chromosomal abnormalities are two sources of HPG axis alteration.[15] Single mutations usually lead to changes in binding ability of the hormone and receptor leading to inactivation or over activation. These mutations can occur in the genes coding for GnRH, LH, and FSH or their receptors. Depending on which hormone and receptor are unable to bind different effects occur but all alter the HPG axis.

For example, the male mutation of the GnRH coding gene could result in hypogonadotrophic hypogonadism. A mutation that cause a gain of function for LH receptor can result in a condition known as testotoxicosis, which cause puberty to occur between ages 2–3 years. Loss of function of LH receptors can cause male pseudohermaphroditism. In females mutations would have analogous effects. Hormone replacement can be used to initiate puberty and continue if the gene mutation occurs in the gene coding for the hormone. Chromosomal mutations tend to affect the androgen production rather than the HPG axis.


The HPG axis can be suppressed by hormonal birth control administration. Although often described as preventing pregnancy by mimicking the pregnancy state, hormonal birth control is effective because it works on the HPG axis to mimic the luteal phase of a woman’s cycle. The primary active ingredients are synthetic progesterones, which mimic biologically derived progesterone. The synthetic progesterone prevent the hypothalamus from releasing GnRH and the pituitary from releasing LH and FSH; therefore it prevents the ovarian cycle from entering the menstrual phase and prevents follicle development and ovulation. Also as a result, many of the side effects are similar to the symptoms of pregnancy. Alzheimer’s has been shown to have a hormonal component, which could possibly be used as a method to prevent the disease.[16]

The HPG axis can also be suppressed by GnRH antagonists or continuous administration of GnRH agonist, such as in the following applications

Environment can have large impact on the HPG axis. One example is women with eating disorders suffer from oligomenorrhea and secondary amenorrhea. Starvation from anorexia nervosa or bulimia causes the HPG axis to deactivate causing women’s ovarian and uterine cycles to stop. Stress, physical exercise, and weight loss have been correlated with oligomenorrhea and secondary amenorrhea.[17] Similarly environmental factors can also affect men such as stress causing impotence. Prenatal exposure to alcohol can affect the hormones regulating fetal development resulting in foetal alcohol spectrum disorder.

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