Effect of initial gestagen treatment on bleeding patterns in postmenopausal women receiving continuous combined hormone replacement therapy

Objective: The purpose of this prospective study was to investigate the association of initial gestagen treatment with future breakthrough bleedings during continuous combined hormone replacement therapy. The predictability of progesterone challenge test on bleeding has also been investigated. Design: Eighty-six naturally postmenopausal women, of whom 38 received initial gestagen treatment (5 mg medroxyprogesterone acetate, twice daily, for 10 days) and 48 did not, were included in this prospective study. Patients were followed for 6 months, and any bleeding occurring during therapy was recorded. Results: Of the 48 patients who received continuous combined hormone replacement therapy without initial gestagen treatment, 23 (48%) had a bleeding episode. Of the 38 patients who received the same therapy with initial gestagen treatment, 13 (34.2%) had bleeding. There was a trend toward decreased breakthrough bleeding in the second group, which did not achieve significance. The mean time before bleeding was 6.76 weeks in the first group and 11.75 weeks in the second group; the difference was statistically significant (p < 0.05). Of the 28 patients with a negative progesterone challenge test at the onset of therapy, eight (28.6%) had bleeding during hormone replacement therapy. Of the 10 patients with a positive challenge, five (50%) had bleeding. The difference was not statistically significant. Conclusions: Patients who receive gestagen treatment before the onset of continuous combined hormone replacement therapy tend to experience breakthrough bleeding less frequently and later during the therapy. The response to progesterone challenge does not predict future bleeding during continuous combined hormone replacement therapy.