COSA:AYA cancer fertility preservation/Options for fertility preservation/Ovarian suppression with GnRH analogues during chemotherapy
Ovarian suppression with GnRH analogues during chemotherapy
Ideally GNRH analogues for ovarian protection should be used within the context of a clinical trial setting.
Where this is not possible, administration is supported provided the patient and family are fully informed of the lack of large randomised trials addressing the potential benefit.
The use of gonadotrophin-releasing hormone analogues (GnRH), administered throughout the time of chemotherapy treatment, may reduce the gonadotoxic effects of chemotherapy on ovarian function.
Options include depot preparations (which are preferred because of ease of administration and prolonged activity) and formulations administered daily, either by injection or intranasal administration.
When used for durations longer than six months, additional low-dose oestrogen support should be considered to reduce the consequences of protracted hypooestrogenism, unless the patient has an oestrogen-sensitive tumour.
Likelihood of success
There is evidence that GnRH agonists reduce the risk of acute and more prolonged ovarian failure, although there is still controversy about the magnitude of benefit. It appears that the risk of ovarian failure may be reduced by approximately 40%. However there is no evidence that GnRH analogues provide benefit in the context of very high dose chemotherapy as part of pretreatment for bone-marrow transplant.
A single well-conducted study in patients with lymphoma did not show any benefit with GnRh agonist. However recent evidence, including a systematic review of randomised trials, has suggested that GnRH agonists do provide some ovarian protection. The heterogeneity of studies and results, and the fact that most trials only assessed ovarian function in the short term (8 months to 2.5 years) means that there is not yet conclusive evidence of benefit.
Risks and side effects
The side effects of GnRH analogues relate predominantly to the induced hypooestrogenic state and so include hot flushes and reduction in vaginal secretions. When used for prolonged periods (i.e. > 6 months) without add-back oestrogen treatment, there is a risk of bone depletion.
There is no evidence that use of GnRH analogues during chemotherapy reduces the efficacy of the cancer treatment.
Currently in Australia, use of GnRH analogues for ovarian protection during chemotherapy is not an indication supported by the PBS, so administration is either self-funded (approximately $340 to $400 per injection for goserelin monthly injections, and usually 3 to 4 injections required for duration of chemotherapy) or provided by the treating institution.
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