Tranexamic acid treatment for heavy menstrual bleeding: a randomized controlled trial.

OBJECTIVE: To assess the efficacy and safety of an oral formulation of tranexamic acid for the treatment of heavy menstrual bleeding. METHODS: Adult women with heavy menstrual bleeding (mean menstrual blood loss 80 mL or more per cycle) were enrolled in a double-blind, placebo-controlled study. After two pretreatment menstrual cycles, women were randomized to receive tranexamic acid 3.9 g/d or placebo for up to 5 days per menstrual cycle through six cycles. To meet the prespecified three-component primary efficacy end point, mean reduction in menstrual blood loss from baseline with tranexamic acid treatment needed to be 1) significantly greater than placebo, 2) greater than 50 mL, and 3) greater than a predetermined meaningful threshold (36 mL or higher). Health-related quality of life was measured using a validated patient-reported outcome instrument. RESULTS: Women who received tranexamic acid (n=115) met all three primary efficacy end points: first, a significantly greater reduction in menstrual blood loss of -69.6 mL (40.4%) compared with -12.6 mL (8.2%) in the 72 women who received placebo (P<.001); reduction of menstrual blood loss exceeding a prespecified 50 mL; and last, reduction of menstrual blood loss considered meaningful to women. Compared with women receiving placebo, women treated with tranexamic acid experienced significant improvements in limitations in social or leisure and physical activities, work inside and outside the home, and self-perceived menstrual blood loss (P<.01). The majority of adverse events were mild to moderate in severity, and the incidence of gastrointestinal adverse events was comparable with placebo. CONCLUSION: In this study, a new oral tranexamic acid treatment was well tolerated and significantly improved both menstrual blood loss and health-related quality of life in women with heavy menstrual bleeding. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00386308. LEVEL OF EVIDENCE: I.

The effects of progestins on bone density and bone metabolism in postmenopausal women: a randomized controlled trial.

OBJECTIVE: The purpose of this study was to evaluate the action of progestins on bone metabolism in early menopausal women. STUDY DESIGN: One hundred thirty-two menopausal women were randomized into a 2-year double-blinded, placebo-controlled clinical trial. There were 6 treatment groups: micronized progesterone (P 4 ) 300 mg/day; medroxyprogesterone acetate (MPA) 10 mg/day; norethindrone (NET) 1 mg/day; micronized estradiol (E 2 ) 1 mg/day; E 2 1 mg/day + MPA 10 mg/day; and placebo. All subjects received 1000 mg of calcium and 400 IU of vitamin D/day. Primary outcome variables were bone mineral density (BMD) changes at the spine and hip. Secondary variables were bone turnover markers. RESULTS: With E 2 or E 2 +MPA treatment, BMD at L2-L4 increased by 2% to 4% over 2 years. Bone mineral density (BMD) at the spine followed a decreasing trend with MPA, P 4 , and placebo treatments. With NET treatment, BMD did not change from baseline. At the femoral neck site, BMD did not change significantly for any treatment group. Bone resorption and bone formation markers decreased with E 2 or E 2 +MPA treatment, and did not change appreciably with all 3 progestin-alone treatments. There were no vertebral or hip fractures observed during the trial. CONCLUSION: Estrogen remains the primary bone active agent in hormone therapy, while progestins have significantly less activity. The selection of the appropriate progestin in hormone therapy should be based on criteria other than bone activity.