Endocrine Abstracts

Introduction: Immune checkpoint inhibitors have become well-established in the treatment of various cancers. Immune-related adverse effects (irAEs) are well recognised, particularly of the endocrine system. There is limited information on how they may impact sex hormones. A small study demonstrated increased oestradiol levels in men, but there have been no reported cases in women. Timing of onset of irAEs is highly variable and can occur up to 27 months after their use. Our case raises the question of whether the observed changes in estradiol levels are simply due to normal perimenopausal fluctuations or a delayed effect induced by immunotherapy.

Clinical case: A 43-year-old woman was diagnosed with breast cancer in May 2023. Her obstetric history was G1P0+1, which ended in abortion. From the age of 18, she was on the Evra contraceptive patch, which was discontinued following her cancer diagnosis. She described brief interruptions in contraception use, which was usually accompanied by resumption of menstruation. Her cancer treatment, including Pembrolizumab was discontinued in November 2023 due to severe colitis and development of primary hypothyroidism. In June 2025, she suddenly had a menstrual period. Her bloods showed an FSH 43IU/l, LH 86IU/l and oestradiol 927pmol/l. Both pituitary MRI and adrenal CT were normal. Transvaginal ultrasound showed two right-sided ovarian cysts measuring 13 and 26mm. CA-125 was negative. After two menstrual periods, she did not experience further bleeding and repeat biochemistry showed raised gonadotropins with an undetectable oestradiol level.

Discussion: The onset of menstrual periods occurred 19 months after Pembrolizumab was discontinued. We question whether the two delayed menstrual periods occurred as a form of irAE transient ovarian hyperstimulation or impending primary ovarian failure either masked by contraception or induced by immunotherapy. This case highlights the importance of careful biochemical monitoring when on immunotherapy and need of further studies.