Buserelin

The peptide buserelin is an analogue of GnRH. Buserelin acts as a gonadotropin-releasing hormone agonist (GnRH agonist or gonadeorelin receptor agonist) and prevents the production of sex hormones by the gonads during long-term therapy. The chemical modification leads to an increased resistance to enzymatic degradation by peptidases and to a long-lasting release of gonadotropin. Buserelin can reduce the sex hormone level in both sexes by about 95%.

Buserelin is a GnRH agonist/ agonist of the GnRH receptor (superagonist of the GnRH receptor). Buserelin 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 buserelin, the GnRH receptor is desensitized and no longer reacts to buserelin as well as to its natural ligand, the endogenous GnRH. This is due to the fact that GnRH is normally released by pulsation, which means that the GnRH receptor remains sensitive. Permanent exposure of the receptor leads to its desensitisation.

The desensitisation of the GnRH receptor leads to a permanent loss of LH and FSH secretion and a resulting interruption of the production of gonadal sex hormones. 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 buserelin 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 approx. 10-20 ng / ml). The resulting values correspond to those of women after menopause.

Buserelin is approved for the treatment of hormone-sensitive prostate cancer and pre-menopausal breast cancer, sex hormone-dependent uterine diseases such as endometriosis, endometriosis and uterine fibroids, and for assisted reproduction in female infertility. It is also used off-label for the treatment of premature puberty, as a puberty blocker in transgender children and as a component of transgender hormone therapy.

For prostate cancer, the dosage of buserelin by subcutaneous injection is 500 μg three times a day for one week (once every 8 hours, a total of 1,500 μg / day) and then 200 μg once a day. If buserelin is used as a nasal spray, the dosage for prostate cancer is 800 μg three times daily.

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 cancer 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.

Buserelin was approved for medical use in 1985.

1. Brogden RN et al (1990). Buserelin. A review of its pharmacodynamic and pharmacokinetic properties, and clinical profile. Drugs 39: 399-437.
2. 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.
3. Rajfer J et al (1986) Comparison of the efficacy of subcutaneous and nasal spray buserelin treatment in suppression of testicular steroidogenesis in men with prostate cancer. Fertil Sterile 46: 104-110.
4. Soloway MS (1988) Efficacy of buserelin in advanced prostate cancer and comparison with historical controls. At J Clin Oncol 11 Suppl 1: 29-32.