Improved bleeding profile and tolerability of tibolone versus transdermal E2/NETA treatment in postmenopausal women with female sexual dysfunction

Objectives To compare the incidence of vaginal spotting/bleeding events and breast pain between therapy with tibolone 2.5mg and continuous combined transdermal estradiol (E2)/norethisterone acetate (NETA) 50g/140g after 24 weeks of treatment. Methods A double-blind, double-dummy, randomized, controlled trial was performed and assessments were performed at baseline, week 12 and week 24. Bleeding/spotting events were recorded in a daily diary. Breast signs and symptoms were collected as adverse events. Results A total of 403 women (mean age 56 years) were randomized. Bleeding/spotting events during weeks 1-12 with tibolone and E2/NETA were experienced by 16% and 56% of women, respectively (p0.001). The corresponding percentages during weeks 13-24 were 12% and 51%, respectively (p0.001). E2/NETA was significantly more likely than tibolone to be associated with vaginal hemorrhage (11% vs. 0%; p0.001) and breast signs and symptoms (11% vs. 4%; p=0.015). Early discontinuations resulting from adverse events were significantly more common in the E2/NETA group than in the tibolone group (20% vs. 12%), primarily related to withdrawal due to vaginal hemorrhage (8% vs. 0%). Conclusions Tibolone has a significantly better tolerability profile than transdermal E2/NETA as measured by vaginal bleeding, breast pain and treatment continuation.