Triptorelin

General In rare cases, treatment with GnRH agonists may unmask the presence of a previously undiagnosed gonadotroph cell pituitary adenoma. These patients may present with signs of pituitary apoplexy, characterised by sudden headache, vomiting, visual impairment, and ophthalmoplegia. Patients treated with GnRH agonists, such as triptorelin, have an increased risk of developing depression, which may be severe. Patients should be informed of this risk and treated appropriately should depressive symptoms occur. Patients with a known history of depression should be closely monitored during treatment. Treatment with Decapeptyl should be initiated following a thorough diagnostic work-up (e.g. laparoscopy). Pregnancy must be excluded before starting treatment with triptorelin. As menstruation ceases during treatment in women, patients should be instructed to inform their physician if menstrual bleeding persists. Loss of bone mineral density Use of GnRH agonists is likely to cause a reduction in bone mineral density, averaging approximately one percent per month over a six-month treatment period. Every 10% loss in bone density is associated with an approximately two- to threefold increase in fracture risk. Currently available data indicate that recovery of lost bone mineral density occurs in the majority of women following discontinuation of treatment. No specific data are available for patients with established osteoporosis or for those with risk factors for osteoporosis (e.g. chronic alcohol abuse, smoking, long-term therapy with medicinal products that reduce bone mineral density such as anticonvulsants or corticosteroids, family history of osteoporosis, malnutrition, e.g. anorexia nervosa). As the reduction in bone mineral density is likely to be particularly detrimental in these patients, treatment with triptorelin should be considered on a case-by-case basis and only initiated after careful assessment that the anticipated benefits outweigh the risks. Additional measures to counteract loss of bone mineral density should also be considered. Uterine fibroids and endometriosis Triptorelin at the recommended doses induces consistent hypogonadotrophic amenorrhoea. If genital bleeding occurs beyond the first month, plasma estradiol levels should be measured. If these values are below 50 pg/ml, possible organic lesions should be investigated. Following discontinuation of treatment, ovarian function resumes; bleeding returns within 7–12 weeks after the last injection. Non-hormonal contraception should be used throughout treatment and for one month after the last injection. As menstruation should cease during triptorelin therapy, patients should be advised to inform their physician if regular menstrual bleeding persists. During treatment of uterine fibroids, the size of the uterus and fibroids should be monitored regularly, e.g. by ultrasound. In several cases, a disproportionately rapid reduction in uterine volume relative to fibroid volume has resulted in bleeding and sepsis. A few cases of bleeding have been reported following treatment with GnRH analogues in patients with submucosal fibroids. Bleeding usually occurred 6–10 weeks after initiation of treatment. Assisted reproduction Down-regulation and prevention of premature LH surges Assisted reproduction is associated with an increased risk of multiple pregnancy, ectopic pregnancy, and congenital malformations. These risks also apply when Decapeptyl is used as an adjunct in controlled ovarian stimulation. The use of a GnRH agonist in controlled ovarian stimulation may increase the risk of ovarian hyperstimulation syndrome (OHSS) and ovarian cysts. In a minority of predisposed patients, particularly those with polycystic ovary syndrome, follicular recruitment induced by the combined use of GnRH analogues and gonadotropins may be markedly increased. As with other GnRH analogues, cases of ovarian hyperstimulation syndrome have been reported in association with the use of triptorelin concomitantly with gonadotropins. In assisted reproduction, despite prolonged exposure, triptorelin is not expected to be present in the circulation at the time of embryo transfer. Ovarian hyperstimulation syndrome (OHSS) OHSS is a medical event distinct from uncomplicated ovarian enlargement. OHSS is a syndrome that may manifest with increasing degrees of severity. It includes marked ovarian enlargement, elevated serum sex steroid levels, and increased vascular permeability, which can result in fluid accumulation in the peritoneal, pleural, and rarely the pericardial cavities. In severe cases of OHSS, the following symptomatology may be observed: abdominal pain, abdominal distension, severe ovarian enlargement, weight gain, dyspnoea, oliguria, and gastrointestinal symptoms including nausea, vomiting, and diarrhoea. Clinical examination may reveal hypovolaemia, haemoconcentration, electrolyte imbalance, ascites, haemoperitoneum, pleural effusion, hydrothorax, acute pulmonary distress, and thromboembolic events. Excessive ovarian response to gonadotropin therapy rarely results in OHSS unless hCG is administered to trigger ovulation. Therefore, in the event of ovarian hyperstimulation, hCG should be withheld and the patient advised to abstain from sexual intercourse or to use barrier methods of contraception for at least 4 days. OHSS may progress rapidly (within 24 hours to several days) into a serious medical event; patients should therefore be monitored for at least 2 weeks after hCG administration. OHSS may be more severe and prolonged in cases of pregnancy. OHSS most commonly occurs after discontinuation of hormonal treatment and reaches its peak 7–10 days after treatment. OHSS usually resolves spontaneously with the onset of menstruation. In the event of severe OHSS, gonadotropin therapy must be discontinued, the patient hospitalised, and specific treatment for OHSS initiated, e.g. bed rest, intravenous infusion of electrolyte or colloid solutions, or heparin. The risk of OHSS may be higher when GnRH agonists are used in combination with gonadotropins than with gonadotropins alone. Ovarian cysts Ovarian cysts may occur during the initial phase of treatment with GnRH agonists. These cysts are generally asymptomatic and non-functional. This medicinal product contains less than 1 mmol sodium (23 mg) per injection, that is to say essentially "sodium-free".