Triptorelin is a gonadotropin releasing hormone (GnRH) agonist that is a potent inhibitor of the synthesis of testosterone (in men) and estrogen (in women) and is used to treat advanced prostate cancer. Triptorelin is associated with a low rate of transient serum enzyme elevations during therapy, but has not been linked convincingly to cases of clinically apparent acute liver injury.
Triptorelin (trip" toe rel' in) is a decapeptide analogue of gonadotropin releasing hormone (GnRH) that acts on the pituitary to cause the synthesis and release of luteinizing hormone (LH) and follicle stimulating hormone (FSH), two gonadotropins that act on the male testes to stimulate the production of testosterone and on the female ovaries to induce synthesis of estrogen. Triptorelin and other GnRH agonists cause an initial surge of gonadotropin release, but then lead to down-regulation of their synthesis and secretion which results in a decline in testosterone and estrogen production. Triptorelin, alone or in combination with other antiandrogens, has been found to be palliative in advanced prostate cancer and as effective as surgical castration. Triptorelin was approved for use in the United States for prostate cancer in 2000 and is still widely used, being considered a first line treatment of this hormone responsive malignancy. Triptorelin is available generically and under the brand name Trelstar in an injectable suspension for intramuscular depot administration every 4 weeks (3.75 mg), 12 weeks (11.25 mg) or 24 weeks (22.5 mg). Triptorelin and the other GnRH analogues cause a profound hypogonadism ("chemical castration") and its common side effects are typical of androgen deprivation, including hot flashes, loss of libido, erectile dysfunction, depression, nausea, diarrhea, weight gain and fluid retention. Rare, but potentially severe adverse events can include immediate hypersensitivity reactions, pituitary apoplexy and, with long term use, weight gain, metabolic changes, diabetes and osteoporosis.
Long term triptorelin is associated with serum enzyme elevations in 2% to 5% of patients, although the elevations are rarely above three times the upper limit of normal (<1%). The enzyme elevations are usually mild, asymptomatic and resolve even without dose modification or drug discontinuation. Triptorelin has not been linked convincingly to cases of acute, clinically apparent liver injury with jaundice.
Likelihood score: E (unlikely cause of clinically apparent liver injury).
Mechanism of Injury
The cause of the minor serum enzyme elevations that can occur during triptorelin therapy is unknown. Triptorelin is a decapeptide similar to GnRH and is metabolized locally in tissue and not by the hepatic cytochrome P450 system. Some serum enzyme elevations may be caused by nonalcoholic fatty liver arising because of weight gain or metabolic changes caused by the androgen deprivation state induced by the GnRH agonist.
Outcome and Management
The serum enzyme elevations during triptorelin therapy rarely require dose modification or drug discontinuation and should instead lead to investigation of other possible causes of liver injury. There is no evidence to indicate that there is cross sensitivity to liver injury among the various GnRH analogues.
REPRESENTATIVE TRADE NAMES
Triptorelin – Generic, Trelstar®
Product labeling at DailyMed, National Library of Medicine, NIH
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References updated: 22 March 2018
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