EP1391 - ECE_3025 - Xeroderma pigmentosum: an underrecognized cause of premature ovarian insufficiency

Abstract Introduction Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder caused by mutations affecting one of seven genes involved in the DNA repair pathway, leading to hypersensitivity to the deleterious effects of ultraviolet (UV) radiation on DNA. From a gynecological and endocrine perspective, women with XP appear to be at increased risk of developing premature ovarian insufficiency (POI). We report the case of a 29-year-old woman with XP who presented with secondary amenorrhea, in whom investigations revealed POI. Case Report A 29-year-old woman with xeroderma pigmentosum diagnosed in childhood presented with secondary amenorrhea of one year's duration. Menarche occurred at the age of 13 years, with regular menstrual cycles until the age of 24 years, followed by the onset of oligo-spaniomenorrhea and subsequently secondary amenorrhea associated with hot flashes from the age of 28 years. Hormonal evaluation revealed hypergonadotropic hypogonadism with low estradiol and markedly elevated FSH and LH, associated with a severely reduced ovarian reserve (AMH <0.01 ng/mL), consistent with premature ovarian insufficiency. Karyotype analysis was normal. Discussion This case highlights a rarely described association between xeroderma pigmentosum, a DNA repair–deficiency disorder, and premature ovarian insufficiency, highlighting the essential role of genomic stability in preserving normal ovarian function. The ovaries, due to their high proliferative activity, exhibit particularly high expression levels of the XPC gene, likely reflecting an increased requirement for correction of replication errors and repair of endogenous DNA damage. Murine models of XP demonstrate reduced reproductive performance, associated with increased apoptosis of germ cells. Merideth et al. (2019) evaluated 60 women with xeroderma pigmentosum and found that 31% of these patients had experienced menopause, with 78% meeting criteria for premature menopause; the median age at menopause was 29.5 years, approximately 20 years earlier than in the general population. Conclusions Awareness of the increased risk of premature menopause in women with xeroderma pigmentosum warrants early surveillance to detect declining ovarian reserve and to guide reproductive management. When indicated, initiation of hormone replacement therapy is essential to prevent skeletal and cardiovascular complications.