What is testosterone?

Testosterone is an androgen hormone which is responsible for many of the physical characteristics of adult males.  Both men and women have testosterone secretion although it is present in much greater levels in adult men than women.  Testosterone is produced by the gonads (the testes in men and ovaries in women) and also small quantities are produced by the adrenal glands in both sexes.   It is called an androgen because it stimulates the development of male characteristics.  Testosterone initiates the development of the male internal and external genitalia during fetal development, and is essential for boys going through puberty and for the production of sperm in adult life.  Testosterone is essential for the changes seen in boys during puberty including increase in height, body and pubic hair, enlargement of the penis, and normal male libido.  Testosterone levels are controlled by the pituitary gland which releases hormones that stimulate the testes to release testosterone. 

What happens if I have low testosterone levels?

Testosterone deficiency (hypogonadism) may present at birth, puberty and during adult life.  If there is deficiency of testosterone in utero then there will be failure of masculinisation of the male fetus.  If there is deficiency of testosterone at puberty then the boy will fail to progress through puberty.  If there is deficiency of testosterone during adult male life then there will be loss of the male secondary sexual characteristics including loss of libido, body hair and low testosterone levels may be associated with an increase in body fat with loss of muscle tone and in long standing deficiency osteoporosis. 

What are the courses of male hypogonadism?

Male hypogonadism can be a result of failure of the testes (primary gonadal failure) or due to failure of stimulation by the pituitary (secondary hypogonadism).  Primary hypogonadism (failure of the testes) can be congenital (inherited) such as Klinefelter’s syndrome in which men are born with an extra X sex chromosome (XXY) or acquired during life due to the variety of causes including failure of the testes to descend into the scrotum, inflammation due to infections such as mumps, chemotherapy or radiotherapy affecting the testes, and following removal of the testes for testicular tumours.  Secondary hypogonadism results usually from a benign tumour of the pituitary gland that causes hypopituitarism.  Secondary hypogonadism may occasionally be congenital such as in Kallmann’s syndrome which is a rare genetic condition where there is loss of development of the nerves that supply the pituitary to stimulate the release of the gonadotrophins.

What of the signs and symptoms of the male hypogonadism?

If this occurs before puberty then delayed puberty is usually the presenting symptoms.  If after puberty then loss of secondary sexual characteristics, low libido and infertility are common presenting symptoms.  Low testosterone levels also result in some breast development in men and increased body fat. 

How common is male hypogonadism?

Classical hypogonadism due to the above causes occurs in approximately 1% of men. Testosterone levels fall after the age of 40 and some reports suggest that hypogonadism is much commoner in older men particularly those with type II diabetes.  However, currently it is not proven that these older patients will benefit from testosterone replacement therapy.

How is male hypogonadism diagnosed?

In patients with a medical history suggesting hypogonadism, testosterone is measured first thing in the morning around 9am fasted with the measurement of the pituitary hormones the gonadatrophins.  The presence of a testosterone level below the normal range at 9am fasted suggests male hypogonadism and the gonadatrophins will define whether or not this is due to testicular failure in which case the gonadatrophins are high or pituitary failure in which case the gonadatrophins are low.

How is male hypogonadism treated?

Testosterone is rapidly metabolised by the liver when taken orally. Thus most currently available treatments for male hypogonadism either come as injections or as gels applied to the skin.  The commonly used injection is given approximately once every three months into a muscle and the gels are usually applied once daily.

Are there any side effects to the treatment?

There are mild side effects of testosterone replacement depending on the form used.  Injectable testosterone may cause pain at the site of injection but this is usually short lived.  Gels occasionally cause skin irritation and patients need to be careful after application not to transfer the gel to their partner’s or child’s skin at risk of them then absorbing testosterone.  Testosterone increases red blood cells and occasionally the dose needs to be reduced to prevent the blood becoming too thick.

What is the Diurnal approach to male hypogonadism?

Diurnal has successfully completed pre-clinical studies of its novel, native testosterone replacement formulation, designed to be administered orally.