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Randomized Controlled Trial
. 2022 Sep;28(3):149-157.
doi: 10.1177/20533691221116769. Epub 2022 Aug 7.

Effects of ultra-low dose hormone therapy on biochemical bone turnover markers in postmenopausal women: A randomized, placebo-controlled, double-blind trial

Lucia Costa-Paiva  1 , Maria Celeste O Wender  2 , Rogerio B Machado  3 , Luciano M Pompei  4 , Eliana A Nahas  5 , Jorge Nahas-Neto  5 , Sonia Y Del Debbio  6 , Mariangela Badalotti  7 , Achilles M Cruz  8
Affiliations
Randomized Controlled Trial

Effects of ultra-low dose hormone therapy on biochemical bone turnover markers in postmenopausal women: A randomized, placebo-controlled, double-blind trial

Lucia Costa-Paiva et al. Post Reprod Health. 2022 Sep.

Abstract

Objective: Evaluate the effects of ultra-low-dose hormone therapy (Ultra-LD HT) with 17β-estradiol 0.5 mg and norethisterone acetate 0.1 mg (E2 0.5/NETA 0.1) versus placebo on bone turnover markers (BTM) in postmenopausal women.

Study design: A multicenter, double-blind, randomized, placebo-controlled study was performed with 107 participants who received one tablet daily of E2 0.5/NETA 0.1 or placebo for 24-weeks. Bone formation markers-N-terminal propeptide of type I procollagen (PINP) and Bone-specific alkaline phosphatase (BSAP), and bone resorption markers-C-telopeptide of type I collagen (CTX-I) and N-telopeptide crosslinked of type I collagen (NTX) were assessed before and at 12 and 24-weeks of treatment.

Results: Women treated with E2 0.5/NETA 0.1 had a significant reduction in the PINP marker from baseline (58.49 ± 21.12 μg/L) to week 12 (48.31 ± 20.99 μg/L) and week 24 (39.16 ± 16.50 μg/L). Placebo group, the PINP marker did not differ significantly. The analysis of the BSAP indicated a significant increase in the placebo group (13.8 ± 5.09 μg/L and 16.29 ± 4.3 μg/L, at baseline and week 24, respectively), whereas in the treatment group the values did not change. The analysis of the NTX marker showed a significant reduction only in the treatment group (43.21 ± 15.26 nM/mM and 33.89 ± 14.9 nM/mM, at baseline and week 24, respectively). CTX-I had a significant decrease in the treatment group from baseline (0.3 ± 0.16 ng/L) to week 12 (0.21 ± 0.14 ng/L) and week 24 (0.21 ± 0.12 ng/L).

Conclusion: Women receiving E2 0.5/NETA 0.1 experienced reductions in bone resorption and formation markers, an expected effect during the anti-resorptive therapy, suggesting a protective bone effect with the Ultra-LD HT.

Keywords: bone mineral density; bone turnover marker; estrogen; menopause; ultra-low-dose hormone therapy.

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Conflict of interest statement

Declaration of conflicting interests: All author(s) received consultancy fees or research grants as a study investigator from Libbs Farmacêutica Ltda (Brazil). AMC is a medical advisor at Libbs Farmacêutica Ltda and reports funding while conducting the study.

Figures

Figure 1.
Figure 1.
Flowchart of participants through the trial. E2 0.5/NETA 0.1 = 17β-estradiol 0.5 mg + norethisterone acetate 0.1 mg; ITT: Intention to treat analysis; ITTe: Intention to treat efficacy analysis.
Figure 2.
Figure 2.
PINP marker on the baseline, week 12 and week 24 in placebo and treatment groups. The values are mean ± SD. *p < .001 compared to baseline of the same group. PINP: N-terminal propeptide of type I procollagen; SD: standard deviation.
Figure 3.
Figure 3.
BSAP marker on the baseline, week 12 and week 24 in placebo and treatment groups. The values are mean ± SD. *p < .001 compared to baseline of the same group. BSAP: Bone-specific alkaline phosphatase; SD: standard deviation.
Figure 4.
Figure 4.
NTX marker on the baseline, week 12 and week 24 in placebo and treatment groups. The values are mean ± SD. *p < .001 compared to baseline of the same group. NTX: N-telopeptide crosslinked of type I collagen; SD: standard deviation.
Figure 5.
Figure 5.
CTX-I marker on the baseline, week 12 and week 24 in placebo and treatment groups. The values are mean ± SD. *p < .001 compared to baseline of the same group. CTX-I: C-telopeptide of type I collagen; SD: standard deviation.
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