What is hormone therapy for prostate cancer?
Hormone therapy for prostate cancer uses the androgen dependence of prostate cancer for therapeutic purposes. Androgens, such as testosterone, are male sex hormones that are produced in the testicles and to a small extent in the adrenal gland. Among other things, they lead to the growth and proliferation of prostate cancer cells.
More precisely, hormone therapy is a hormone withdrawal therapy in which the growth stimulus for the tumor cells is reduced by suppressing the hormone release. Hormone therapy is also known as chemical castration because it has the same effect as castration by surgical removal of both testicles. Hormone therapy uses various active ingredients that intervene at different points in the process of androgen release.
For whom is hormone therapy suitable?
The therapy of prostate cancer is divided into curative, i.e. curative, treatment options and palliative, i.e. palliative, treatment options. Curative therapy includes a radical removal of the prostate (prostatectomy) with removal of the lymph nodes, which can be supplemented by radiation if necessary.
Alternatively, radiation can be performed externally. These two treatment options are equivalent. Hormone therapy is performed both curatively and palliatively.
Within the framework of a curative therapy, hormone therapy is used in addition to external radiation. It can help to improve the outcome of radiation therapy for prostate cancer. If a decision is made against curative therapy or if distant metastases are present, hormone therapy is used as part of a palliative therapy concept. As an alternative to hormone therapy, a palliative approach can be used as an observational wait-and-see approach. This means that the progression of the tumor is only observed until symptoms occur.
Which hormones are used?
Strictly speaking, no hormones are used. Drugs are used that act as if they were hormones. The regular release of testosterone works in the following way.
In a part of the diencephalon (hypothalamus), the release of the luteinizing hormone releasing hormone (LH-RH or GnRH) takes place. This leads to the release of the luteinizing hormone (LH) in the pituitary gland (hypophysis). The LH in turn leads to the production of the androgen testosterone in the testes.
The testosterone slows down the release of LH by a feedback mechanism. The drugs used in hormone therapy for prostate cancer are divided into different groups according to their site of action. These are: LH-RH analogs LH-RH antagonists Antiandrogens Direct testosterone synthesis inhibitors A combination of several drugs from different groups is also possible.
The drugs used for hormone therapy can be administered in the form of intermittent or continuous treatment. With continuous treatment, patients receive the drugs permanently. In the case of intermittent treatment, the therapy is continued until a control value (PSA value) falls below a defined lower limit.
The therapy is then paused until the control value exceeds the upper limit again. The advantages of intermittent treatment are on the one hand the less frequent occurrence of side effects and a longer treatment period until castration resistance occurs.
- LH-RH-Analogues
- LH-RH antagonists
- Antiandrogens
- Direct testosterone synthesis inhibitors
LH-RH analogues, also called LH-RH agonists, act like the LH-RH itself.
They lead to the release of LH in the pituitary gland. This in turn leads to an increase in testosterone production in the testicles. This initial increase in testosterone is called the flare-up phenomenon.
Continued stimulation causes the number of receptors for LH-RH on the pituitary gland to decrease, resulting in insensitivity to LH-RH. As a result, testosterone levels also decrease and the tumor cells lose their growth stimulus. LH-RH analogs are applied in the form of depot injections into the muscle or under the skin.
LH-RH antagonists work in the opposite direction to LH-RH. They block the receptor for LH-RH on the pituitary gland. Consequently, less LH is secreted and less androgens are produced in the testes.
The growth of prostate cancer cells is slowed down. In contrast to the LH-RH analogs, LH-RH antagonists do not initially produce elevated testosterone concentrations.LH-RH antagonists are also administered as depot syringes. Antiandrogens, also called androgen receptor antagonists, have a similar structure to androgens themselves.
They can block the androgen receptors on the prostate cancer cells and thus prevent the local effect of the hormone. Antiandrogens also inhibit the release of LH at the pituitary gland to a small extent and consequently also reduce testosterone release. They are often used in combination with LH-RH analogs.
The combination is called complete androgen blockade. This is especially helpful at the beginning of the therapy to reduce the initial androgen increase in LH-RH analogs Antiandrogens are taken as tablets. Newer substances in this group of active ingredients are still effective even after the tumor has become resistant to castration, i.e. the hormone therapy is not effective.