A combination of low doses of 17 beta-estradiol and norethisterone acetateprevents bone loss and normalizes bone turnover in postmenopausal women

The effects of 17 beta-estradiog (E-2) 1 mg combined with low doses of nore thisterone acetate (NETA) on postmenopausal bone loss and turnover were inv estigated in a 2-year, randomized, double-masked, placebo-controlled trial. A total of 135 postmenopausal women with a lumbar spine bone mineral densi ty (BMD) T-score between -2 and +2 were randomized to daily treatment with an oral tablet of either placebo, E-2 1 mg/NETA 0.25 mg, or E-2 1 mg/ NETA 0.5 mg. Significant (p<0.001) increases in BMD at the lumbar spine (L1-4) w ere observed with E-2 1 mg/ NETA 0.25 mg (5.2%) and E-2 1 mg/NETA 0.5 mg (5 .4%) compared with placebo (-0.9%). The total hip BMD increased significant ly in the E-2 1 mg/NETA 0.25 mg (3.1%) and E-2 1 mg/NETA 0.5 mg groups (3.3 %) compared with placebo. At the femoral trochanter, the increase in BMD in the E-2 1 mg/NETA 0.5 mg group (6.3%) was significantly different from the placebo group (0.8%), while that in the E-2 1 mg/NETA 0.25 mg group (3.3%) was not. No statistical differences were found between the active groups a nd placebo for the change in BMD at the femoral neck. Significant increases in BMD at the distal radius and total body were found for both E-2 1 mg/NE TA 0.25 mg (0.9% and 2.5%, respectively) and E-2 1 mg/NETA 0.5 mg (2.1% and 3.0%, respectively) compared with placebo (- 0.7% and 0.4%, respectively). At the end of the treatment, urinary pyridinoline type I collagen C-telopep tide had decreased by 65% and 60% in the E-2 1 mg/NETA 0.25 mg and E-2 1 mg /NETA 0.5 mg groups, respectively, while the mean serum concentrations of o steocalcin had decreased by 39% and 34%, bone-specific alkaline phosphatase by 32% and 29%, and C-terminal propeptide of type I collagen by 21% and 19 % had decreased by 34-39%, 29-32%, and 19-21% in the E-2 1 mg/NETA 0.25 mg and E-2 1 mg/ NETA 0.25 mg groups, respectively. In conclusion, combinations of E-2 1 mg and NETA 0.25 or 0.5 mg prevent bon e loss in postmenopausal women at the lumbar spine, hip, distal radius and total body, and normalize bone turnover.