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The synthesis of numerous LHRH analogues and the production of easy to use galenic forms (injections with depot properties) has transformed the hormonotherapy of prostate cancer (and to a lesser extent breast cancer)

These drugs have many non-cancer-related indications (endometriosis, uterine fibroma, ovarian polycystosis, hirsutism).

The main drugs are:

• buserelin,

• goserelin,

• leuprorelin,

• triptorelin.

The mechanism of action of these LHRH agonists is explained by the down-regulation in the pituitary gland: pituitary receptors for LHRH are totally saturated and then down-regulated with loss of sensitivity to any further stimuli. The gonad receptors for LH and FSH are then reduced. High dosage of LHRH agonists induces inhibition of pituitary and gonad functions (sex steroid deprivation).

The pituitary cells, will initially respond to the stimulation of hypothalamic hormone analogues by increased LHRH secretion. The testis will respond to this secretion by increased testosterone synthesis.

Action of the agonists of LH RH: first step

It is very important to be aware of the ‘flush’ effect, since, at the beginning of treatment, it may lead to the aggravation of pain, paralysis or prostate symptoms.

Treatment by LHRH agonists should therefore not be initiated without previous antiandrogen treatment (or antioestrogen for breast cancer) over a few days.

It is quite possible that these agonists have a direct action on tumour cells, since rare observations of responses in castrated men (or women) have been described.

The secondary effect of agonists involves chemical castration by the exhaustion of the pituitary gland. Hot flushes are frequently observed and castration leads to impotence (in almost all patients), loss of libido and major hypogonadism.

Treatment by agonist of LH-RH : second step.

One of the constraints of this treatment is the necessity to indefinitely pursue the monthly (or tri-monthly) subcutaneous injection. If the treatment is stopped, the castration effect will slowly regress (in particular when treatment duration is short).

In prostate cancer, up to 70% of remissions are obtained using this treatment and their mean duration is around one to three years (and much longer among certain patients).

In breast cancer, this treatment is often instituted in order to obtain non-definitive castration for young patients in the hope of a return of normal menstruation.