Buserelin was first patented in 1974 and approved for medical use in 1985.[13] It is not available in the United States, but is marketed widely elsewhere in the world, including in the United Kingdom, Canada, and many other countries.[14][8][15] The medication is one of only two medically used GnRH analogues that are available as nasal sprays, the other being nafarelin.[16] Buserelin is available as a generic medication.[17][18]
For prostate cancer, the dosage of buserelin by subcutaneous injection is 500 μg three times per day (once every 8 hours, 1,500 μg/day total) for one week and then 200 μg once daily thereafter.[20][21] If buserelin is used as a nasal spray, the dosage for prostate cancer is 800 μg sprayed into the nostrils three times per day (once every 8 hours, 2,400 μg/day total) for one week followed by 400 μg sprayed into the nostrils three times per day (once every 8 hours, 1,200 μg/day total) thereafter.[21][20] For endometriosis, buserelin is used specifically as a nasal spray and the dosage is the same as that used for prostate cancer.[20] These dosages of buserelin for both subcutaneous injection and nasal spray have been found to decrease testosterone levels to near-castrate levels in men with prostate cancer, although suppression was more complete with subcutaneous injection presumably due to suboptimal absorption with intranasal administration.[22]
Available forms
Buserelin is available in the form of a 1 mg/mL solution for use as a nasal spray or subcutaneous injection once every 8 hours (three times per day) and as 6.3 mg and 9.45 mg implants for subcutaneous injection once every two and three months, respectively.[1][2][23][24]
With chronic administration of buserelin however, the GnRH receptor becomes desensitized and completely stops responding both to buserelin and to endogenous GnRH.[3][1] This is because GnRH is normally released from the hypothalamus in pulses, which keeps the GnRH receptor sensitive, whereas chronic buserelin administration results in more constant exposure and desensitization of the receptor.[3][1] The profound desensitization of the GnRH receptor results in a loss of LH and FSH secretion from the anterior pituitary and a consequent shutdown of gonadal sex hormone production, markedly diminished or abolished spermatogenesis in men, and anovulation in women.[3][1]
In men, approximately 95% of circulating testosterone is produced by the testes, with the remaining 5% being derived from the adrenal glands.[9] In accordance, GnRH analogues like buserelin can reduce testosterone levels by about 95% in men.[9][22] Sex hormone levels, including those of estradiol and progesterone, are similarly profoundly suppressed in premenopausal women.[10] The suppression of estradiol levels is 95% and progesterone levels are less than 1 ng/mL (normal range during the luteal phase approximately 10–20 ng/mL); the resulting levels are equivalent to those in postmenopausal women.[10][11]
Buserelin has been found to suppress testosterone levels in men with prostate cancer from 426 ng/dL to 28 ng/dL (by 93.4%) with 200 μg by subcutaneous injection once per day and from 521 ng/dL to 53 ng/dL (by 89.8%) with 400 μg by nasal spray once every 8 hours (1,200 μg/day total).[25] The difference in suppression may have been due to poor compliance.[25] A few small studies have also assessed the suppression of testosterone levels with buserelin nasal spray twice a day instead of three times a day.[26][27] One such study found that testosterone levels in men with prostate cancer were suppressed during treatment with buserelin from 332 ng/dL to 215 ng/dL (28.9% lower than controls) with 200 μg by nasal spray twice a day (400 μg/day total), from 840 ng/dL to 182 ng/dL (71.4% lower than controls) with 500 μg by nasal spray twice a day (1,000 μg/day total), and from 598 ng/dL to 126 ng/dL (80.4% lower than controls) with 50 μg by subcutaneous injection once a day.[26]
Buserelin was first described in 1976 and was introduced for medical use in 1984.[29][30] Intranasal buserelin was the first GnRH agonist demonstrated to achieve medical castration in humans.[31] This was initially observed via a marked decrease in circulating testosterone levels in a single patient in 1980.[31]
Society and culture
Generic names
Buserelin is the generic name of the drug and its INNTooltip International Nonproprietary Name and BANTooltip British Approved Name, while buserelin acetate is its USANTooltip United States Adopted Name, BANMTooltip British Approved Name, and JANTooltip Japanese Accepted Name, buséréline is its DCFTooltip Dénomination Commune Française, and buserelina is its DCITTooltip Denominazione Comune Italiana.[32][8][33][14] While under development by Hoechst AG, buserelin was also known as HOE-766.[32][8][33][14]
Brand names
Buserelin is marketed by Sanofi-Aventis primarily under the brand names Suprefact, Suprefact Depot, and Suprecur.[8][14] It is also available under a number of other brand names including Bigonist, Bucel, Buserecur, Fuset, Metrelef, Profact, Profact Depot, Supremon, and Zerelin.[8][14] CinnaFact is a generic version of the medication that is produced by CinnaGen.[18] Buserelin is marketed for use in veterinary medicine primarily under the brand name Receptal, but is also available under the brand names Buserol, Busol, Porceptal, and Veterelin.[8][14]
The steroidal antiandrogencyproterone acetate has been studied for blocking the testosterone flare at the start of buserelin therapy in men with prostate cancer.[35][36] While cyproterone acetate for two weeks eliminates the biological and biochemical signs of the flare, no benefits on prostate cancer outcomes were observed.[35]
^Tolis G, Faure N, Koutsilieris M, Lemay A, Klioze S, Yakabow A, Fazekas AT (July 1983). "Suppression of testicular steroidogenesis by the GnRH agonistic analogue Buserelin (HOE-766) in patients with prostatic cancer: studies in relation to dose and route of administration". Journal of Steroid Biochemistry. 19 (1C): 995–998. doi:10.1016/0022-4731(83)90045-6. PMID6411994.
^Kuhl H, Kaplan HG, Taubert HD (March 1976). "[Effects of a new analogue of LH-RH, D-Ser(TBU)6- EA10-LH-RH, on gonadotropin liberation in males (author's transl)]". Deutsche Medizinische Wochenschrift. 101 (10): 361–364. doi:10.1055/s-0028-1104089. PMID129323. S2CID260086614.
^Klosterhalfen H, Jacobi GH (1988). "Long-term results of an LH-RH agonist monotherapy in patients with carcinoma of the prostate and reflections on the so-called total androgen blockade with pre-medicated cyproterone acetate". In Klosterhalfen H (ed.). Endocrine Management of Prostatic Cancer. pp. 127–137. doi:10.1515/9783110853674-014. ISBN9783110853674.
^Matsumiya K, Kitamura M, Kishikawa H, Kondoh N, Fujiwara Y, Namiki M, Okuyama A (July 1998). "A prospective comparative trial of a gonadotropin-releasing hormone analogue with clomiphene citrate for the treatment of oligoasthenozoospermia". International Journal of Urology. 5 (4): 361–363. doi:10.1111/j.1442-2042.1998.tb00367.x. PMID9712445. S2CID24680327.
Trabant H, Widdra W, de Looze S (1990). "Efficacy and safety of intranasal buserelin acetate in the treatment of endometriosis: a review of six clinical trials and comparison with danazol". Progress in Clinical and Biological Research. 323: 357–382. PMID2106146.
