Cyclic hormone replacement therapy using quarterly progestin

To determine whether cyclic progestin, when part of postmenopausal hormone replacement therapy, can be used quarterly instead of monthly without increasing the risk of endometrial hyperplasia. In addition, we determined whether this hormone replacement therapy regimen produces an acceptable menstrual pattern.

The subjects were 214 postmenopausal women, mean (+/- standard deviation) age 56.2 +/- 5.4 years, who had regularly used hormone replacement therapy (consisting of Premarin 0.625 mg/day with monthly cyclic medroxyprogesterone, 5 or 10 mg) for a mean of 5.4 +/- 4.5 years (minimum 1 year). The study intervention consisted of changing the subjects' treatment from the usual monthly progestin to four 3-month (ie, quarterly) cycles of medroxyprogesterone, 10 mg/day for 14 days. Endometrial histology was evaluated by doing endometrial biopsies at study outset and after 1 year. Scheduled and unscheduled vaginal bleeding was reported in daily diaries.

Endometrial hyperplasia was found in 1.5% of 199 women completing follow-up, a rate similar to the 0.9% prevalence found at baseline. Compared with monthly medroxyprogesterone, quarterly medroxyprogesterone resulted in longer menses (7.7 +/- 2.9 versus 5.4 +/- 2.0 days) and more reports of heavy menses (31.1 versus 8.0%) and unscheduled bleeding (15.5 versus 6.8%). Despite these problems, women preferred the quarterly regimen by nearly four to one.

In a 1-year trial, quarterly medroxyprogesterone appeared as safe as monthly medroxyprogesterone and was preferred by most women. This schedule may be useful for women seeking relief from monthly use of progestin and monthly menses.