Triptorelin

The decapeptide triptorelin is an artificial analogue of GnRH. At position 6 the amino acid glycine was replaced by D-tryptophane. Triptorelin acts as a gonadotropin-releasing hormone agonist (GnRH agonist or gonadorelin receptor agonist) and prevents the production of sex hormones by the gonads during long-term therapy. Triptorelin is more effective than natural GnRH. The chemical modification leads to an increased resistance to enzymatic degradation by peptidases and to a long-lasting release of gonadotropin. Triptorelin can lower sex hormone levels by about 95% in both sexes.

Triptorelin is an injectable GnRH agonist/ agonist of the GnRH receptor (superagonist of the GnRH receptor). Triptorelin is able to increase the secretion of luteinizing hormone (LH) and follicle stimulating hormone (FSH) to 20 to 170 times the physiological stimulation by GnRH itself.

However, with chronic administration of triptorelin, the GnRH receptor is desensitized and no longer reacts to triptorelin itself as well as to its physiological ligand (GnRH). This is due to the fact that GnRH is normally released by pulsation. This means that the GnRH receptor remains sensitive. In contrast, continuous exposure to the artificial ligand leads to desensitisation of the receptor and thus to a loss of LH and FSH secretion from the pituitary gland with interruption of gonadal sex hormone production.

In men, approximately 95% of circulating testosterone is produced by the testicles, while the remaining 5% comes from the adrenal glands. Accordingly, GnRH analogues such as triptorelin can reduce testosterone levels in men by about 95%. Sex hormone levels, including estradiol and progesterone, are similarly suppressed in pre-menopausal women. The suppression of oestradiol levels is 95% and progesterone levels are less than 1 ng / ml (normal range during the luteal phase about 10-20 ng / ml); the resulting values correspond to those in post-menopausal women.

Triptorelin is indicated for the treatment of locally advanced or metastatic hormone-dependent prostate cancer and localized high-risk or locally advanced hormone-dependent prostate cancer in combination with radiotherapy.

Before the GnRH receptors are significantly downregulated, testosterone levels are elevated. In carcinoma patients this can lead to a temporary tumor activation with bone pain (in patients with metastases) and urinary retention. Other side effects that occur later during treatment are mainly due to low sex hormone levels and include decreased libido, erectile dysfunction, hot flashes, vaginal dryness, vaginal atrophy, menorrhagia, osteoporosis, depression, asthenia, emotional instability, headache, dizziness and application local reactions.

Pamorelin®

1. Jacobi GH (1990) LH-RH agonist monotherapy in patients with carcinoma of the prostate and reflections on the so-called total androgen blockade. Recent Results Cancer Res 118:174-185.