European Journal of Endocrinology paper on reversal cases of Kallmann syndrome / CHH.

This is a very interesting area of research I think.

There are basically two types of KS / CHH. One is where the GnRH releasing neurones have been blocked in their migration into the hypothalamus during early development, which normally results in KS cases as the olfactory nerves are blocked as well.

The other type is where the action of the hypothalamus is impaired. The GnRH neurones are in the right place but for some reason they do not fire in the correct manner to allow GnRH to be released correctly (called a pulse generator). This normally results in CHH where the olfactory nerves are unaffected and there is a normal sense of smell.

Whether you get a case of KS or CHH will depend on which gene or genes have been affected and where in the developmental process they have an effect.

An active area of research at the moment is looking in how the genes involved in the action of the hypothalamus operate and how they are influenced by external factors such as nutrition, stress, environment or even sexual activity. This is known as epigenetics,

There are research groups looking to see if the reproductive cycle can be restored by switching on genes that are present but are not active by modifying external factors. It is certainly early days in terms of research but the more reversal cases they find the more chance they have of finding out crucial information which will increase the understanding of KS / CHH.

Reversal is less common in KS cases where there are less GnRH nerve cells inside the hypothalamus but reversal cases have be reported. There is a theory that GnRH neurones continue to grow / move throughout life and if the eventually reach the hypothalamus in sufficient numbers the reproductive cycle can start later in life.

The reversal is always fragile and the hypogonadal state can return in some cases but it does provide a little bit of hope.

It is good to know research is ongoing in this area.