Increased levels of CA 125 and CA 19.9 serum tumour markers following cyclic combined hormone replacement therapy

We report a case of increase in serum tumour markers CA 125 and CA 19.9 induced by cyclic combined hormone replacement therapy (HRT). A 52-year-old Caucasian post-menopausal woman presented with a slight enlargement of the right ovary and uterine fibromyomatosis. She was taking HRT for 4 years in a cyclic combined regimen of 2 mg oestradiol with 1 mg cyproterone acetate. The serum tumour markers occasionally measured were in normal range except CA 19.9 (997 U/mL; normal values 0.0-37) and CA 125 (85 U/mL; normal values 0.0-35). However, on one occasion, the CA 19.9 and CA 125 were high and then showed persistently high values (1005 and 81.3 U/mL, respectively). Radiodiagnostic investigations excluded any malignancies and a hysteroscopy showed endometrial thickening. After discontinuation of HRT, CA 125 levels returned to normal after 1 month, whereas CA 19.9 took 6 months to do so. Four months after the beginning subsequent therapy with over-the-counter phyto-oestrogens a new serum test showed an increase in CA 19.9 but CA 125 remained within the normal range. Phyto-oestrogen therapy was then interrupted and 1 month later CA 19.9 returned to normal. In this case, cyclic HRT was the probable cause of CA 19.9 and CA 125 increase. Positive dechallenge and subsequent CA 19.9 increase after phyto-oestrogen intake seem to confirm the role of oestrogens as the cause of the endometrial thickening through hormonal imbalance. Increased CA 19.9 and CA 125 levels in benign gynaecological conditions may be a source of misdiagnosis of malignant disease.