Evaluation of safety and efficacy of micronized progesterone in induction of secretory conversion of endometrium and withdrawal bleeding in women with secondary amenorrhea

Abstract

OBJECTIVE: To evaluate 1) the efficacy of 300 mg/day and 400 mg/day dose of micronized progesterone (MP) in induction of secretory conversion of the endometrium and rate of withdrawal bleeding in women with secondary amenorrhea, and 2) the safety of MP 300 mg/day and 400 mg/day.DESIGN: A multicenter, parallel group, randomized, and open-label trial.MATERIALS AND METHODS: Women, aged 18-45, with secondary amenorrhea were randomized to receive MP at 300 mg/day (n=122) or 400 mg/day (n=118). The study period consisted of three consecutive 28-day (4 weeks) treatment cycles. Subjects received conjugated estrogens 0.625 mg/day on Days 1-84 and MP 300 mg/day or 400 mg/day on Days 19-28, 47-56, and 75-84. Withdrawal bleeding was evaluated within 2 weeks after 1st and 2nd treatment cycle of MP. Clinical safety including lab, PAP-smear and TVUS were also evaluated. Endometrial biopsies were performed at baseline and end of 12 weeks.RESULTS: Secretory conversion of the endometrium was observed in 23 (21.5%) women in the 300 mg/day MP group and 28 (28.3%) women in the 400 mg/day MP groups. Withdrawal bleeding after 1st and/or 2nd cycle was observed in 93 (86.9%) women in the 300 mg/day MP group and 90 (90.9%) women in the 400 mg/day MP group respectively, based on last observation carry forward (LOCF) analysis. Three subjects experienced serious adverse events (SAEs) including one hydrocephalus and one adnexal mass (300 mg/day) and one pregnancy (400 mg/day). All SAEs were reported as unrelated to study medication. There were no remarkable differences in treatment emergent AEs (TEAEs) between the treatment groups and the majority of TEAEs were mild or moderate in severity.CONCLUSION: Treatment with MP at 300 mg/day and 400 mg/day demonstrated similar efficacy in induction of secretory conversion of the endometrium and rate of withdrawal bleeding in women of reproductive age with secondary amenorrhea. The safety profile for both MP doses was similar. OBJECTIVE: To evaluate 1) the efficacy of 300 mg/day and 400 mg/day dose of micronized progesterone (MP) in induction of secretory conversion of the endometrium and rate of withdrawal bleeding in women with secondary amenorrhea, and 2) the safety of MP 300 mg/day and 400 mg/day. DESIGN: A multicenter, parallel group, randomized, and open-label trial. MATERIALS AND METHODS: Women, aged 18-45, with secondary amenorrhea were randomized to receive MP at 300 mg/day (n=122) or 400 mg/day (n=118). The study period consisted of three consecutive 28-day (4 weeks) treatment cycles. Subjects received conjugated estrogens 0.625 mg/day on Days 1-84 and MP 300 mg/day or 400 mg/day on Days 19-28, 47-56, and 75-84. Withdrawal bleeding was evaluated within 2 weeks after 1st and 2nd treatment cycle of MP. Clinical safety including lab, PAP-smear and TVUS were also evaluated. Endometrial biopsies were performed at baseline and end of 12 weeks. RESULTS: Secretory conversion of the endometrium was observed in 23 (21.5%) women in the 300 mg/day MP group and 28 (28.3%) women in the 400 mg/day MP groups. Withdrawal bleeding after 1st and/or 2nd cycle was observed in 93 (86.9%) women in the 300 mg/day MP group and 90 (90.9%) women in the 400 mg/day MP group respectively, based on last observation carry forward (LOCF) analysis. Three subjects experienced serious adverse events (SAEs) including one hydrocephalus and one adnexal mass (300 mg/day) and one pregnancy (400 mg/day). All SAEs were reported as unrelated to study medication. There were no remarkable differences in treatment emergent AEs (TEAEs) between the treatment groups and the majority of TEAEs were mild or moderate in severity. CONCLUSION: Treatment with MP at 300 mg/day and 400 mg/day demonstrated similar efficacy in induction of secretory conversion of the endometrium and rate of withdrawal bleeding in women of reproductive age with secondary amenorrhea. The safety profile for both MP doses was similar.