ADMINISTRATION OF HORMONAL ADD-BACK THERAPY (ABT) COUNTERACTS THE UTERINE VOLUME REDUCING EFFECTS OF ORAL GnRH ANTAGONIST THERAPY

To assess the effect of administration of ABT (estradiol (E2) 1mg/norethindrone acetate 0.5 mg) on uterine volume in women with symptomatic uterine fibroids (UF) receiving the oral GnRH antagonist, linzagolix (LGX). Women with heavy menstrual bleeding due to UF were treated with once daily doses of 100 or 200 mg LGX, both with or without ABT for 52 weeks in 2 randomized, double-blind, placebo-controlled trials. Women receiving LGX 200 mg alone or placebo were switched to LGX 200 mg + ABT after 24 weeks, except for a group of placebo subjects in one study who continued placebo until 52 weeks. Uterine volumes were measured using transvaginal ultrasound at baseline, 24 and 52 weeks. Change from baseline was analyzed using a mixed model with repeated measures. Serum E2 levels were measured using a validated sensitive assay (tandem mass spectrometry HPLC). Overall mean baseline uterine volume was 328 (median: 241; Q1, Q3: 160, 396) cm3. At 24 weeks, the mean change from baseline in uterine volume was 0.61 (95% CI 0.57,0.65), corresponding to a 39% reduction, in the LGX 200 mg without ABT group associated with full suppression of serum E2 (median 9 pg/mL). There were smaller reductions in volume (<15%) in the other LGX groups where median serum E2 was in the range of 40–50 pg/mL. At 52 weeks, after the LGX 200 mg group were switched to LGX 200 mg + ABT, median serum E2 increased to 43 pg/mL and the mean change from baseline in uterine volume increased to 0.79 (95% CI 0.73,0.86) corresponding to a 21% reduction from baseline.Tabled 1*Estimated mean ratio to baseline uterine volumePlaceboPlacebo/LGX 200mg+ ABTLGX 100mgLGX 100mg+ ABTLGX 200mg/200mg+ ABTLGX 200mg+ ABTN31123140144163149Week 24Median E2 pg/mL101104.54147.58.840.5*Mean (95% CI)0.98 (0.83,1.16)1.04 (0.96,1.13)0.84 (0.78,0.91)0.93 (0.86,1.00)0.61 (0.57,0.65)0.84 (0.77,0.90)Week 52Median E2 pg/mL6837535342.543*Mean (95% CI)1.09 (0.90,1.32)0.88 (0.80,0.97)0.97 (0.89,1.06)0.93 (0.85,1.02)0.79 (0.73,0.86)0.89 (0.82,0.97) Open table in a new tab Once daily LGX 200 mg fully suppressed serum E2 leading a 39% decrease in uterine volume after 12 weeks. Co-administration of hormonal ABT either starting concurrently with LGX or starting after 24 weeks reduced the effect of LGX 200 mg on uterine volume.