Endocrine Abstracts

JOINT3514

Introduction: Reproductive function in women with sickle cell disease can be compromised by various mechanisms, including the direct impact of vaso-occlusive crises on the ovaries, endocrine dysfunction due to iron overload in chronically transfused patients, and iatrogenic factors such as hydroxyurea treatment. Several studies suggest that hydroxyurea may contribute to a decline in ovarian reserve. In this context, we report a case of premature ovarian insufficiency(POI) in a 26-year-old woman treated with hydroxyurea.

Case presentation: A 26-year-old female patient was referred to our department for secondary amenorrhea. The patient has a family history of homozygous sickle cell anemia in one sister and peripheral hypothyroidism in another. She has been treated for sickle cell disease since age 4 and has been on Hydroxyurea for several years, with infrequent need for transfusions and rare vaso-occlusive crises. Her menarche occurred at age 14, followed by 10 years of oligomenorrhea. Over the past year, she developed secondary amenorrhea, unresponsive to dydrogesterone, which had previously been effective. At presentation, she was receiving 500mg of Hydroxyurea twice daily and her hemoglobin was 9.8 g/dl. Hormonal tests revealed elevated FSH (144.34 mUI/ml), LH (80 mUI/ml), and low estradiol (24 ng/L), while thyroid hormones, prolactin, and testosterone were normal. AMH was < 0.05 ng/ml, confirming POI. Genetic testing showed a normal 46XX karyotype. Autoimmune screening showed a slightly positive TPO antibodies but negative anti-21 hydroxylase antibodies, making autoimmune ovaritis less likely given the strong suspicion of iatrogenic cause. Bone mineral density (BMD) tests revealed spinal and femoral osteopenia as a complication of hypogonadism. The patient was started on hormone replacement therapy, and her hematologist was consulted to explore alternative treatments to hydroxyurea in the hope of reversing ovarian function, although it seems very unlikely.

Discussion: Although several studies have reported a decline in ovarian function associated with hydroxyurea, its impact remains controversial. It is still unclear whether this decline can lead to ovarian insufficiency as severe as in our case or whether it is reversible after discontinuation of treatment. Further research is needed to clarify these effects. Meanwhile, these findings highlight the importance of considering fertility preservation for women of childbearing age before initiating hydroxyurea therapy.