Effects of two different regimens of continuous hormone replacement therapy on endometrial histopathology and postmenopausal uterine bleeding

Objective: To compare the effects of frequently used two different regimens of combined continuous hormone replacement therapy; 0.625 mg conjugated equine estrogen (CEE) + 2.5 mg medroxyprogesterone acetate (MPA) and 1 mg 17β estradiol (E2) + 0.5 mg norethindrone acetate (NETA), on endometrial histopathology and postmenopausal uterine bleeding. Materials and methods: Two hundred and forty-six outpatient subjects aged 41–57 years were enrolled in the study conducted at the menopause clinic between November 2003 and November 2004. One hundred and thirty-nine patients were assigned to receive 0.625 mg conjugated equine estrogen + 2.5 mg medroxyprogesterone acetate (CEE/MPA), whereas 107 patients were to receive 17β estradiol + 0.5 mg norethindrone acetate (E2/NETA). Inclusion criteria of the study were: normal values of endometrial thickness at basal evaluation, women with intact uterus, at least 12 months of amenorrhea, normal vaginal smear, bilateral mammography and biochemical blood parameters. All women were questioned every 3 months for vaginal bleeding/spotting. Endometrial sampling was performed by Pipelle catheter in the 12th month of therapy. Results: For the first 3 months, vaginal bleeding/spotting rate for the CEE/MPA group was 38.7%, whereas it was higher (45%) in the E2/NETA group. For the second 3-month period, vaginal bleeding/spotting frequencies were 41.1 and 37.8%, respectively. In the third 3-month period 30.6 and 29.6%, and in the fourth 3-month period, 18.5 and 12.5% of the patients reported vaginal bleeding or spotting. None of the results of endometrial sampling have shown findings of cancer histopathology. Conclusion: Compared to CEE/MPA regimen, E2/NETA therapy has not shown more favorable effects on postmenopausal bleeding abnormalities. Irregular endometrial proliferation was seen more with the E2/NETA regimen.