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. INTRODUCTION: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Estrogen-progestin therapy causes a greater increase in spinal bone mineral density than estrogen therapy - a systematic review and meta-analysis of controlled trials with direct randomization.

OBJECTIVE: To assess whether progesterone (P4) or osteoblast P4 receptor-acting progestin (P) contributed to estrogen (E) therapy-related increased areal bone mineral density (BMD) in randomized controlled trials (RCT) with direct randomization to estrogen (ET) or estrogen-progestin (EPT) therapy. METHODS: Systematic literature searches in biomedical databases identified RCT with direct randomization and parallel estrogen doses that measured spinal BMD change/year. Cyclic P4/P was included in this random effects meta-analysis only if for ≥ half the number of E-days. RESULTS: Searches yielded 155 publications; five met inclusion criteria providing eight dose-parallel ET-EPT comparisons in 1058 women. Women averaged mid-50 years, ⟨five years into menopause and took conjugated equine E daily at 0.625 mg with/without 2.5 mg medroxyprogesterone acetate (MPA). The weighted mean EPT minus ET percentage difference in spinal BMD change was +0.68%/year (95% CI 0.38, 0.97%) (P=0.00001). This result was highly heterogeneous (I²=81%) but this may reflect the small number of studies. CONCLUSION: Estrogen with an osteoblast P4R-acting progestin (EPT) in these five published RCT provides Level 1 evidence that MPA caused significantly greater annual percent spinal BMD gains than the same dose of ET. These data have implications for management of vasomotor symptoms and potentially for osteoporosis treatment in menopausal women.

Impact of twice weekly versus daily iron supplementation during pregnancy on maternal and fetal haematological indices: a randomized clinical trial.

A randomized clinical trial examined the efficiency and tolerability of twice weekly versus daily iron supplementation during pregnancy. A total of 370 pregnant women were randomly assigned to receive either daily or twice weekly iron supplementation during pregnancy. There were no significant differences in initial and delivery haemoglobin and haematocrit levels between the 2 groups. Ferritin concentrations were significantly lower in the twice weekly group at delivery, but hypoferritinaemia (ferritin < 15 microg/L) was not observed in either group. The frequency of nausea, vomiting and constipation were significantly lower in the twice weekly group. Birth weight and length were significantly higher in the daily supplemented group. In non-anaemic mothers, a smaller dose of iron may be sufficient and also might prevent the complications of iron excess.

Impact of twice weekly versus daily iron supplementation during pregnancy on maternal and fetal haematological indices: a randomized clinical trial

A randomized clinical trial examined the efficiency and tolerability of twice weekly versus daily iron supplementation during pregnancy. A total of 370 pregnant women were randomly assigned to receive either daily or twice weekly iron supplementation during pregnancy. There were no significant differences in initial and delivery haemoglobin and haematocrit levels between the 2 groups. Ferritin concentrations were significantly lower in the twice weekly group at delivery, but hypoferritinaemia [ferritin < 15 microg/L] was not observed in either group. The frequency of nausea, vomiting and constipation were significantly lower in the twice weekly group. Birth weight and length were significantly higher in the daily supplemented group. In non-anaemic mothers, a smaller dose of iron may be sufficient and also might prevent the complications of iron excess