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Home > Patients > Learn about GnRH deficiency / Kallmann syndrome
                 

Learn about GnRH deficiency / Kallmann syndrome


What is GnRH deficiency?  A Brief Overview

GnRH deficiency can occur in a number of different conditions and are classed collectively as hypogonadotropic hypogonadism (HH).  One type of GnRH deficiency that occurs in conjunction with a lack of sense of smell, called anosmia, is known as Kallmann syndrome.

     

GnRH (gonadotropin releasing hormone) is an essential hormone for sexual development, puberty and fertility.

       

GnRH is released from the hypothalamus gland, located deep inside the brain, and acts directly on the closely associated anterior pituitary gland to release two hormones, luteinising hormone (LH) and follicle stimulating hormone (FSH).  They have a direct action on the ovaries in women and on the testes in men.

  

Any deficiency, whether total or partial, in the production of GnRH can lead to a failure of puberty which in turn can lead to a lack of sexual development and infertility.  Pubertal failure might be total or partial depending on the degree of GnRH deficiency.

   

GnRH deficient conditions can affect both men and women.  Almost invariably they are present from birth and in the majority of cases will require life-long treatment with various hormone replacement therapies.


The specifics

What is GnRH?

GnRH is the abbreviation for gonadotropin releasing hormone.  It is also known as LHRH (luteinising hormone releasing hormone).  A hormone is a substance your body produces which has a direct effect on another part of the body.  The production of hormones is normally tightly controlled by the body to allow the body to function correctly. If hormone levels are too high or too low, certain conditions may develop.  As an example, a very common hormonal condition is diabetes mellitus which is caused by an imbalance in the hormone insulin.

What does "gonadotropin" mean?

The term gonadotropin relates to two very important hormones which have a direct impact on the gonads (reproductive organs) in men and women.  The gonadotropins act on the testes in men and on ovaries in women to allow them to function correctly.  The two gonadotropin hormones are called follicle stimulating hormone (FSH) and luteinising hormone (LH).  These two hormones together play a vital role at puberty to allow the body to reach sexual maturity and to allow men and women to eventually achieve fertility.  Even though the terms follicle stimulating hormone and luteinising hormone relate to their activity in females they are the identical hormones to the hormones found in men.

What does GnRH do?

GnRH causes the production and release of the gonadotropins FSH and LH from the pituitary gland.

Where is GnRH produced?

GnRH is produced by a almond-sized gland called the hypothalamus.  It is located deep within the brain and despite its small size controls a wide variety of functions around the body.  The gonadotropins LH and FSH are produced by a pea-sized gland called the pituitary gland connected directly to the hypothalamus gland.  The pituitary gland also releases other hormones. GnRH deficiency results from a problem with the release of LH and FSH, while the other functions of the pituitary gland remain unaffected.

Why is GnRH important?

Any failure, whether total or partial, in the production of GnRH can cause the failure in the production of adequate levels of FSH and LH, which in turn can lead to a total or partial failure of pubertal development.  This in turn will lead to a lack of secondary sexual development and in most cases, unless treated, infertility.

     

In men, the lack of gonadotropins will mean the testes will not grow at puberty and they will not produce their own testosterone and sperm.

          

In women, the lack of gonadotropins will mean the ovaries will not release mature eggs and they will not produce oestrogen or progesterone and menstruation will not occur.

What causes GnRH deficient conditions?

The underlying cause of GnRH deficient conditions is the inability of the hypothalamus to produce GnRH at the correct time.

      

In order for the hypothalamus to be able to release GnRH it must contain the correct cells to be able to do this.  These cells are specialised nerve cells called neurons.  For the hypothalamus to be able to release GnRH it must contain an adequate number of GnRH releasing neurons.

      

As the brain develops in the first few weeks of life these GnRH neurons have to move into the correct location in order to connect to the hypothalamus.  The majority of GnRH deficient conditions occur because this migration is blocked for some reason and the hypothalamus develops without the GnRH releasing neurons connected to it.

      

The GnRH releasing neurons are in the brain but are not connected to the hypothalamus preventing GnRH release. This in turn prevents the gonadotropin release by the pituitary gland which causes the failure of puberty and subsequent infertility seen in GnRH deficiency cases.

What are GnRH deficiency conditions?

GnRH deficiency leads to a group of conditions known collectively as hypogonadotropic hypogonadism (HH).  In simple terms this means:  A failure in the normal function of the testes or ovaries due to the failure of the production of FSH and LH by the pituitary gland.  This condition has a number of different abbreviations.  Two of the most commonly used ones are CHH and IIHH.

  • CHH or Congenital hypogonadotropic hypogonadism:  "Congenital" means that the condition is present from birth.  The majority of GnRH deficient cases are congenital.  GnRH deficiency can be inherited from either parent or it may occur with no apparent family history.

  • IHH or Idiopathic hypogonadotropic hypogonadism:  "Idiopathic" indicates that the condition has, as yet, an unknown cause.

One form of GnRH deficiency is accompanied by a lack of sense of smell, or anosmia.  This condition is known as Kallmann syndrome.  Franz Kallmann was a German- born American scientist who published a medical paper in 1944 about the cases of 3 families who all had members who failed to enter puberty and had no sense of smell.  He was the first person to propose that this was a genetic condition.  In some countries this condition might also be known as Morsier-Gauthier Syndrome or Kallmann-de Morsier Syndrome.