Amenorrhea and endometrial atrophy with continuous oral estrogen and progestogen therapy in postmenopausal women

An oral regimen of continuous conjugated equine estrogens (Premarin 0.625 or 1.25 mg daily) and low-dose progestogen (Norethisterone 0.35 to 2.1 mg daily) have been used to treat 95 nonhysterectomized postmenopausal women for up to 2.5 years. This method of hormone replacements was undertaken in an attempt to avoid the withdrawal bleeding and progestogenic side effects associated with conventional cyclical therapy with estrogen and progestogen, while simultaneously protecting the endometrium from estrogenic over-stimulation. With the lower dose of estrogen, amenorrhea was achieved immediately in 30 of 46 patients (65%), and after adjustments to the dose of the progestogen in all ten patients observed for at least one year (maximum 2.5 years). With the higher dose of estrogen, irregular spotting during the first three months resulted in the cessation of treatment by six of the 49 patients (12%), but 23 (47%) women had no bleeding during that time; by 15 months, all 13 patients who had remained in treatment had become amenorrheic (maximum 2.25 years). Endometrial biopsy specimens after six months of combined treatment in 56% of patients revealed atrophic histology regardless of the dose of the estrogen.