The endometrial response to sequential and continuous combined oestrogen-progestogen replacement therapy

Area of Science:

• Gynecology
• Endocrinology
• Oncology

Background:

• Postmenopausal hormone replacement therapy (HRT) is widely used.
• Sequential HRT regimens involve estrogen with a progestogen component for a portion of the cycle.
• Endometrial hyperplasia is a potential risk associated with unopposed estrogen or inadequate progestogen in HRT.

Purpose of the Study:

• To determine the prevalence of endometrial hyperplasia in postmenopausal women using standard sequential estrogen/progestogen HRT.
• To evaluate the effect of a 9-month oral continuous combined regimen (2 mg 17beta-estradiol and 1 mg norethisterone acetate) on endometrial histology.

Main Methods:

• An open, prospective study involving 2028 postmenopausal women across 54 UK menopause clinics.
• Endometrial aspiration biopsies were performed before and after a 9-month continuous combined HRT treatment period.
• Histological analysis of endometrial biopsies was the primary outcome measure.

Main Results:

• Among 1106 women on sequential HRT, 5.3% had complex endometrial hyperplasia and 0.7% had atypical hyperplasia.
• In 661 untreated women, one (0.2%) showed atypical hyperplasia, with no complex hyperplasia.
• After 9 months of continuous combined HRT, no cases of hyperplasia were observed in 1196 biopsies, and 38 women with prior complex hyperplasia showed normalization.

Conclusions:

• Standard sequential HRT regimens carry a significant risk of endometrial hyperplasia (5.3% complex, 0.7% atypical).
• Continuous combined HRT, specifically the regimen studied, is not linked to an increased risk of endometrial hyperplasia.
• Continuous combined HRT effectively resolves complex hyperplasia in women previously treated with sequential HRT.