Identification and Management of Radiation-Induced Premature Ovarian Failure

Abstract

Premature ovarian failure (POF) is the dysfunction of ovarian follicles resulting in amenorrhea before the natural age of menopause. For women with locally advanced cervical cancer (LACC), POF is caused by chemoradiation due to the cytotoxic effects of radiation on the ovary. The diagnosis is confirmed with an FSH level in the postmenopausal range. The recommendation is for all patients with POF to take hormone replacement therapy (HRT) through the average age of natural menopause (age 50-51). The goal of this study is to determine how POF was managed in a large cohort of premenopausal women with LACC receiving pelvic RT. We retrospectively reviewed medical charts of premenopausal patients who underwent RT for LACC at an academic hospital from 2010 to 2020. Data regarding the type and duration of RT, demographics, and survival was obtained. The following data points were obtained from clinic notes documented after radiation treatment started: FSH levels, estradiol levels, menstrual history, menopausal symptoms. Additionally, data regarding HRT initiation was extracted, including the type of HRT and the department of the prescribing provider. Descriptive analysis was performed to determine the frequency of each variable of interest including patient characteristics, receipt hormone therapy, type of hormone therapy and menopausal symptoms. A total of 45 premenopausal patients treated for locally advanced cervical cancer with a median age of 39 (range 22- 50 years) were included. 51% (n = 23) of the patients were started on hormone therapy either during or post radiation treatment. 20 patients had documented menopausal symptoms. Most frequently reported symptoms included hot flashes (80%), fatigue (25%) and anxiety (15%). Most (78%) women received combination oral contraceptive pills (OCP) and some also received an estrogen patch/cream. 38% (n = 7) of patients started the HRT post RT while 61% (11) patients started during RT treatment. Of the available data, HRT was prescribed by a radiation oncologist 39% of the time and a gynecologic oncologist 35% of the time. The onset of POF was identified clinically by the onset of hypo-estrogen vasomotor symptoms. FSH levels were not routinely checked prior to prescribing HRT. The most commonly prescribed HRT was the combination oral contraceptive pill, which was prescribed and managed by both radiation oncologists and gynecologic oncologists. Our study illustrates the need for a standardized method to routinely assess the onset of POF while undergoing radiation treatment. With frequent follow-ups, radiation oncologists have the opportunity to identify early signs POF and provide adequate treatment. Additional studies are needed to evaluate if patients initiated and maintained HRT for the recommended length of time.