Factors associated with endometrial bleeding in continuous hormone replacement therapy

To identify clinical and laboratory parameters associated with the occurrence of endometrial bleeding within the first 6 months of treatment in postmenopausal women taking continuous hormone replacement therapy.

We performed a prospective study of 55 postmenopausal women who had amenorrhea for at least 12 months before baseline screening and were taking 0.625 mg conjugated estrogen and 5 mg medroxyprogesterone acetate daily on a continuous basis. Postmenopausal duration was defined as the interval, in months, between the last menstruation and the commencement of treatment. All subjects were instructed to monitor bleeding episodes in a diary and were followed up monthly for at least 12 months.

Thirty-four women (62%) experienced bleeding within the first 6 months of treatment. Using a multivariate approach, a woman with a postmenopausal duration of 24 months or less had a relative risk of 8.2 (95% confidence limits: 1.3, 53.1) of bleeding, as compared with those with a postmenopausal duration of more than 24 months. Furthermore, pretreatment endometrial thickness greater than 5 mm (p < 0.05) and serum estradiol levels greater than 25 pg/mL (p < 0.01) were noted to be significantly correlated with the occurrence of bleeding in women with a postmenopausal duration of more than 24 months.

Women with a postmenopausal duration of 24 months or less, a pretreatment endometrial thickness greater than 5 mm, and serum estradiol level greater than 25 pg/mL are at risk to have endometrial bleeding within the first 6 months of continuous hormone replacement therapy.