Effects of progesterone therapy on serum sclerostin levels in healthy menopausal women: a 3-month randomized, placebo-controlled clinical trial



Sclerostin, a natural hormone made in bone, suppresses bone formation. Sclerostin is also decreased by estrogen. Progesterone, estrogen’s menstrual partner, stimulates bone formation. It is unclear whether progesterone influences sclerostin. This study showed that progesterone did not change sclerostin using serum remaining from a randomized progesterone hot flush therapy trial.


Progesterone and sclerostin are both endogenous hormones acting through osteoblast-origin cells and promote or suppress bone formation, respectively. Estradiol suppresses sclerostin, but progesterone, its menstrual cycle partner hormone, has unclear sclerostin relationships. We postulated that progesterone therapy would influence serum sclerostin levels.


We obtained sclerostin levels for an ethics-approved post hoc analysis. Fasting sclerostin was measured in all remaining sera from a previous 12-week randomized controlled trial (RCT) of oral micronized progesterone (progesterone) for menopausal (> 1 year after last flow) vasomotor symptoms (VMS). Women in the RCT took 300 mg progesterone at bedtime or placebo (1:1) in a trial showing progesterone significantly decreased VMS.


Participants were healthy menopausal, primarily Caucasian (91.2%) community-dwelling women (± SD), 55.2 ± 4.6 years old with BMI 24.9 ± 2.9 kg/m2. The baseline sclerostin level in 60 women was 28.41 ± 10.47 pmol/L. Baseline sclerostin was not correlated with the run-in VMS score (r = 0.143, P = 0.294). Paired baseline and 12-week RCT data for 52 women showed serum sclerostin levels did not change related to experimental therapy (P = 0.504). Changes in final sclerostin values adjusted for baseline were progesterone (− 1.07 ± 7.96 pmol/L) and placebo (− 2.64 ± 8.70 pmol/L). In observational data (n = 60), baseline sclerostin levels correlated with the General Framingham Cardiovascular (CVD) Risk score (r = − 0.398, P = 0.003) and self-reported health by SF-36 quality of life instrument (QoL, r = − 0.331, P = 0.016).


Physiological oral micronized progesterone did not stimulate nor suppress serum sclerostin levels based on post hoc analysis of RCT data. Exploratory results, however, showed sclerostin negatively correlated with CVD risk and QoL. ClinicalTrials.gov #NCT0146469.

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We thank the Endocrine Society for the Summer Student Scholarship awarded to Y.BY. (UBC Med 2021), supervised by J.C.P. As well, we appreciate the Government of Canada for assisting with funding for the summer studentship which made this manuscript possible. We deeply appreciate the contribution of Professor Socrates E Papapoulas whose laboratory analyzed blinded sera from our RCT without charge in the interests of science. We thank the donors to the Centre for Menstrual Cycle and Ovulation Research (CeMCOR) that funded the randomized controlled trial from which these results were drawn. We also appreciate the arms-length donation of active drug (Prometrium®) and identical placebo for this RCT by Besins Healthcare International.


Grant support: This work was supported by an Endocrine Society Summer Student Scholarship in 2018 to Y.Y., with supervisor, J.C.P.

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Correspondence to J. C. Prior.

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Y.Y., A.G., D.K., C.L.H., A.H.v.L., and J.C.P. have no conflicts of interest with these data or with for-profit entities. The funding sources for this project had no influence on the study design, data collection, analysis, or interpretation, writing, or decision for submission of the article.

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Yang, Y.B., Goshtasebi, A., van Lierop, A.H. et al. Effects of progesterone therapy on serum sclerostin levels in healthy menopausal women: a 3-month randomized, placebo-controlled clinical trial. Osteoporos Int (2020). https://doi.org/10.1007/s00198-020-05505-x

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  • Anabolic
  • Hormone therapy
  • Progesterone
  • Randomized controlled clinical trial
  • Sclerostin