A Study on the Timing of Resumption of Menstruation After Interruption/Termination of GnRH Agonist Therapy in Premenopausal Breast Cancer Patients

<b><i>Purpose:</i></b> In hormone therapy for premenopausal breast cancer (BC), gonadotropin-releasing hormone (GnRH) agonist (GnRHa) formulations, especially long-acting formulations, are often used in combination with tamoxifen (TAM). On the other hand, in recent years, endocrine therapy is increasingly interrupted to achieve pregnancy. Here, we examined ovarian function and the timing of resumption of menstruation after the interruption of GnRHa therapy. <b><i>Methods:</i></b> Fertility preservation patients with BC who visited our hospital between January 2010 and August 2023 and who interrupted endocrine therapy with a GnRHa formulation were included. Information on 22 cases (24 cycles), including two interruptions due to the desire for a second child, was collected from medical records and examined retrospectively. <b><i>Results:</i></b> Three cases started assisted reproductive technology treatments before menstruation resumed and were excluded from the analysis. Menstruation resumed at approximately 7, 9, and 12 months from the last dose of the 1-, 3-, and 6-month GnRHa formulations, respectively. The long delay of menstruation resumption was presumably caused by the use of (1) the 3-month formulation in the 6 months before the last GnRHa dose, (2) the 6-month formulation in the 12 months before the last dose, and (3) TAM when menstruation resumed. <b><i>Conclusions:</i></b> In BC patients who may seek pregnancy after interrupting endocrine therapy, it may be easier to estimate the timing of resumption of menstruation if the use of long-term GnRHa depot formulations is avoided for >6 months before the interruption. BC endocrine therapy should be optimized to achieve pregnancy and childbirth as soon as possible during its interruption.