Randomized cross-over study of a 21-day versus a 28-day hormone replacement therapy (HRT)

Objective: To compare the occurrence of climacteric symptoms at two points in the cycle, identified as minE (phase of minimum estrogen effect) and MaxP (phase of maximum progesterone effect). Methods: Prospective randomized cross-over study in postmenopausal women currently on HRT comparing two opposed, sequential formulations: a regimen of 21 tablets containing estradiol valerate (EV) opposed with cyproterone acetate (CPA) in the last 10 tablets, versus a regimen of 28 tablets of conjugated equine estrogens (CEE), the last 12 tablets of which were taken together with norgetrel (NG). Outcome measures: Incidence of 24 climacteric complaints assessed at the specified days of the cycle corresponding to minE (day 6 or 7) and MaxP (day 27 or 28) Results: Contrary to the hypothesis that estrogen-dependent symptoms will recur at minE of the 21-day regimen, no significant differences were noted with the regimen containing 28 days of CEE, which served as the control. There were more complaints with the CEE + NG formulation at both minE and MaxP. Of the 38 patients, 63% preferred the EV + CPA regimen, 18.4% the CEE + NG regimen and 18.4% rated both preparations as equal. Conclusions: The 7-day pause in the 21-day formulation containing EV + CPA did not affect efficacy; it was as effective in relieving climacteric symptoms as the regimen containing 28 days of estrogen. Based on the frequency of complaints both at minE and MaxP, the EV + CPA formulation induced a more acceptable symptom and mood profile.