Gonadotropin-Releasing Hormone Agonist for the Prevention of Chemotherapy-Induced Ovarian Failure in Patients With Lymphoma: 1-Year Follow-Up of a Prospective Randomized Trial

Abstract

A B S T R A C T PurposeTo assess the efficacy of gonadotropin-releasing hormone agonist (GnRHa) in preventing chemotherapy-induced ovarian failure in patients treated for Hodgkin or non-Hodgkin lymphoma within the setting of a multicenter, randomized, prospective trial. Patients and MethodsPatients age 18 to 45 years were randomly assigned to receive either the GnRHa triptorelin plus norethisterone (GnRHa group) or norethisterone alone (control group) concomitantly with alkylating agents containing chemotherapy. The primary end point was the premature ovarian failure (POF) rate (follicle-stimulating hormone [FSH] Ն 40 IU/L) after 1 year of follow-up. ResultsEighty-four of 129 randomly assigned patients completed the 1-year follow-up. The mean FSH values were higher in the control group than in the GnRHa group during chemotherapy; however, this difference was no longer observed after 6 months of follow-up. After 1 year, 20% and 19% of patients in the GnRHa and control groups, respectively, exhibited POF (P ϭ 1.00). More than half of patients in each group completely restored their ovarian function (FSH Ͻ 10 IU/L), but the anti-Mü llerian hormone values were higher in the GnRHa group than in the control group (1.4 Ϯ 0.35 v 0.5 Ϯ 0.15 ng/mL, respectively; P ϭ .040). The occurrence of adverse events was similar in both groups with the exception of metrorrhagia, which was more frequently observed in the control group than the GnRHa group (38.4% v 15.6%, respectively; P ϭ .024). ConclusionApproximately 20% of patients in both groups exhibited POF after 1 year of follow-up. Triptorelin was not associated with a significant decreased risk of POF in young patients treated for lymphoma but may provide protection of the ovarian reserve.J Clin Oncol 30.

Adolescent and Young Adult Oncology, Version 2.2018, NCCN Clinical Practice Guidelines in Oncology

“…122 Some studies, including randomized trials, have evaluated the role of menstrual suppression with gonadotropin-releasing hormone (GnRH; also known as LH-releasing hormone [LHRH]) agonists to preserve ovarian function during chemotherapy. [123][124][125][126][127][128][129][130][131] Some meta-analyses have shown that GnRH agonist may be beneficial for fertility preservation. [132][133][134] However, the impact of these meta-analyses are limited by flaws such as only examining women with breast cancer and only including trials that were not adequately powered and did not use blinding and/ or a placebo condition.…”

Gonadotropin-Releasing Hormone Agonist Cotreatment During Chemotherapy May Increase Pregnancy Rate in Survivors

“…Another methodological error, possibly leading to inaccurate conclusions in this equivocal issue, is premature evaluation of ovarian function [1, 5-7, 10, 11, 16]. Indeed, Demeestere et al [16], who initially did not find a difference in POF rate after 1 year, have presented the 2-year follow-up of their patients [16] claiming that "the number of patients who totally restored their ovarian function was significantly higher in the GnRHa group (p 5 .049) confirming results of [anti-Müllerian hormone (AMH)]" [16]. This supports the possibility that short follow-up may be responsible for the discrepancy between studies and lead to incorrect conclusions [1].…”

Possible applications analogues of gonadotropin-releasing hormone puberty in girls with cancer

“…В мировой литературе все больше внимания уделя-ется медикаментозным методам сохранения фертиль-ности, а именно использованию аГРГ с целью подав-ления овариальной функции в период проведения противоопухолевой терапии [2,4,13,16,[20][21][22][23].…”

“…Наиболее частыми побочными эффектами являются: головные боли, частая смена настроения, бессонница, депрессия, сухость слизистых, акне, мы-шечные боли. Согласно результатам исследования, проведенного Demeestere et al, симптомы гипоэстро-гении отмечались у 75,5 % пациенток на фоне терапии аГРГ [20]. Высоковероятное снижение костной плот-ности (остеопения), развивающееся в результате гипо-эстрогенного статуса пациенток, должно учитываться при назначении препаратов данной группы, и являет-ся одним из наиболее серьезных побочных эффектов аГРГ, что в сочетании с применением стероидных гор-монов в схемах ХТ у больных лейкозами и лимфомами может стимулировать развитие аваскулярных некрозов.…”

“…Относительный риск наступления беременности при использовании аГРГ составил 1,45 [48]. По результа-там исследования, проведенного Demeestere et al, оценивающего эффективность аГРГ для предотвра-щения ХТ-индуцированной овариальной недостаточ-ности у пациенток с лимфомой Ходжкина, авторы сделали вывод об отсутствии значимого снижения ри-ска развития ПИЯ [20].…”