Effects of estrogen with micronized progesterone on cortical and trabecular bone mass and microstructure in recently postmenopausal women

Abstract

Context: In women, cortical bone mass decreases significantly at menopause. By contrast, loss of trabecular bone begins in the third decade and accelerates after menopause.

Objective: The aim of the study was to investigate the effects of estrogen on cortical and trabecular bone.

Design: The Kronos Early Estrogen Prevention Study is a double-blind, randomized, placebo-controlled trial of menopausal hormone treatment (MHT) in women, enrolled within 6-36 months of their final menstrual period.

Setting: The study was conducted at the Mayo Clinic, Rochester, Minnesota.

Intervention: Subjects were treated with placebo (n = 31), or .45 mg/d conjugated equine estrogens (n = 20), or transdermal 50 μg/d 17β-estradiol (n = 25) with pulsed micronized progesterone.

Main outcome measures: Cortical and trabecular microarchitecture at the distal radius was assessed by high-resolution peripheral quantitative computed tomography.

Results: At the distal radius, cortical volumetric bone mineral density (vBMD) decreased, and cortical porosity increased in the placebo group; MHT prevented these changes. By contrast, MHT did not prevent decreases in trabecular microarchitecture at the radius. However, MHT prevented decreases in trabecular vBMD at the thoracic spine (assessed in a subset of subjects; n = 51). These results indicate that MHT prevents deterioration in radial cortical vBMD and porosity in recently menopausal women.

Conclusion: The maintenance of cortical bone in response to estrogen likely has important clinical implications because cortical bone morphology plays an important role in bone strength. However, effects of MHT on trabecular bone at the radius differ from those at the thoracic spine. Underlying mechanisms for these site-specific effects of MHT on cortical vs trabecular bone require further investigation.

Trial registration: ClinicalTrials.gov NCT00154180.

Figure 1.

CONSORT flow diagram describing the enrollment, randomization, and progress of the KEEPS participants through the trial by randomization group at the Mayo Clinic site. Complete follow-up and inclusion in the ITT (intention to treat) analysis is defined as completion of the primary endpoint (HRpQCT) and acceptable scan quality. Inclusion in the secondary adherence to treatment analysis is further defined as completion of 4 years of treatment.

Figure 2.

Percentage change in cortical (A) and trabecular (B) bone parameters at the distal radius in placebo compared with E-treated subjects. Data are shown as mean (±SE) of the percentage change after 4 years of treatment. *P < .05 for change from baseline to 4 years.

Figure 3.

Percentage change in thoracic spine vBMD (mg/cm³) at the trabecular (A) and central (B) zones of the T8 and T9 vertebrae in placebo compared with E-treated subjects. Data are shown as mean (±SE) of the percentage change after 4 years of treatment. **P < .01; ***P < .001 for change from baseline to 4 years.