Effects of ultra-low dose hormone therapy on biochemical bone turnover markers in postmenopausal women

Abstract

Ultra-low dose hormone therapy (Ultra-LD HT) with daily administration of 0.5 mg 17β-estradiol and 0.1 mg norethisterone acetate (E2 0.5/NETA 0.1) is available in some countries and the approval of this formulation was based in CHOICE trial. E2 0.5/NETA 0.1 have been shown beneficial effects on vasomotor symptoms with a good tolerability profile. Regarding the effect of HT on bone, there is a dose-dependent effect of E2 and the addition of NETA seems to enhance the response in bone mineral density (BMD). Although BMD assessment using dual-energy X-ray absorptiometry (DXA) scan is the current gold standard test for the diagnosis of osteoporosis, the evaluation of biochemical bone turnover markers (BTMs) are tools which rapidly detect the dynamics of bone remodeling with respect to bone formation and resorption during therapies for osteoporosis. This multicenter, double-blind, randomized, placebo-controlled study evaluated the effects of E2 0.5/NETA 0.1 versus placebo on BTMs in postmenopausal women. Subjects were randomized to one of the two treatment groups. Participants received one tablet daily for 24 weeks. Bone-specific alkaline phosphatase (BSAP) and N-terminal propeptide of type I collagen for bone formation (P1NP), and C-telopeptide crosslinked type I collagen (CTX-1) and N-telopeptide crosslinked of type I collagen (NTX) for bone resorption were assessed before and at 12 and 24 weeks of treatment. A total of 118 women were randomized and efficacy assessments were performed in 107 subjects, 52 in the active group and 55 in the placebo group. In the Ultra-LD HT treated women, the NTX showed a significant (p = 0.0011) reduction (44.8 ± 18.9 nM/mM and 33.4 ± 14.7 nM/mM), at baseline and at week 24, respectively. P1NP showed a significant (p < 0.0001) reduction (58.5 ± 21.1 μg/L and 48.3 ± 21.0 μg/L) and (58.5 ± 21.1 μg/L and 38.1 ± 15.9 μg/L), at baseline and at week 12 and 24, respectively. In the placebo group, the NTX and P1NP did not differ significantly. The analysis of the BSAP indicated a significant (p = 0.0013) increase (13.8 ± 5.1 μg/L and 16.3 ± 4.3 μg/L) at baseline and at week 24 (p = 0.0013) in placebo group. In the active group the values did not change. In the analysis of CTX-1 no significant change in values was found throughout the study in both groups. Women receiving E2 0.5/NETA 0.1 experienced reductions in bone resorption and formation markers, suggesting a positive bone effect with the Ultra-LD HT.