Endometrial Histology in Subjects on a Continuous-Use Regimen of Levonorgestrel/Ethinyl Estradiol: Results of a Phase 3 Study

Abstract

Levonorgestrel 90 μg/ethinyl estradiol 20 μg administered as a novel continuous-use regimen (LNG/EE Continuous) was evaluated for its effect on endometrial histology. Endometrial histology was evaluated at baseline and after up to13 pill packs of continuous-use daily oral LNG 90 μg/EE 20 μg. The histology substudy, conducted at 6 sites, was part of a phase 3 open label 1-year trial that was conducted at 92 sites in the United States and Canada Healthy sexually active women aged 18 to 49 years were enrolled in the phase 3 trial. Subjects took 1 pill daily of LNG 90 μg/EE 20 μg starting on the first day of their menstrual cycle (first pill pack only) and continuing for 12 months (13 pill packs); there were no pill-free intervals. Subjects who participated in the endometrial histology study were scheduled to have an endometrial biopsy at the pretreatment visit and during pill pack 13. Biopsies were read by a central lab. Frequency tables were used to illustrate overall changes in the endometrial histology findings from pretreatment to the last on-therapy evaluation. Tabled 1 The mean age (± SD) of the endometrial histology study population (n =146) was 28.45 (± 6.60) years and the mean weight (± SD) was 70.53 (± 16.60) kg. Subjects with a baseline biopsy who completed at least 6 pill packs of study drug use (n = 93) were included in the endometrial biopsy analysis that compared baseline with last on-therapy visit findings. The table presents baseline and on-treatment histology for all 93 subjects. At baseline, the most common sample (60%; n = 56) was classified as “weakly/proliferative endometrium”. At the last on-treatment visit, the most common sample (52%; n = 48) was classified as “other”, for which the histologic diagnosis included inactive and/or benign endometrium (n = 42), few proliferative glands (n = 3), and no histologic diagnosis (n = 3) due to scant endometrium or crush artifact. There was no evidence of endometrial hyperplasia or malignancy. LNG/EE Continuous has a good endometrial safety profile. The histologic changes in the endometrium were consistent with a decrease in endometrial growth and decidualization. There were no findings of hyperplasia or malignancy in any of the biopsies.