Higher Estradiol Dose Improves Metabolic Profile in Early But Not Late Postmenopausal Women

Higher estradiol doses had significant benefits for cardiovascular risk factors in early postmenopausal women, but these effects were attenuated in late postmenopausal women.

Estradiol dose affects metabolic measures differentially in early and late postmenopausal women, according to study results presented at the North American Menopause Society Annual Meeting, held September 25 to 28, 2019, in Chicago, Illinois.

The study researchers aimed to identify the association between estradiol dose during hormone therapy and serum estradiol levels on metabolic measures in early and late postmenopausal women from the phase 3 randomized double-blind placebo-controlled multicenter REPLENISH trial (ClinicalTrials.gov Identifier: NCT01942668).

A total of 1216 early (<6 years since menopause) and 297 late (≥10 years since menopause) postmenopausal women received either a combined dose of estradiol and progesterone (1/100 mg, 0.5/100 mg, 0.5/50 mg, or 0.25/50 mg) or placebo. Metabolic outcomes included total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, and glucose levels over the course of 12 months.

In early postmenopausal women, a 0.25-mg higher estradiol dose was associated with a 1.34 mg/dL lower total cholesterol level (95% CI, -2.45 to -0.24; P =.02) and a 1.49 mg/dL lower low-density lipoprotein cholesterol level (95% CI, -2.41 to -0.56; P =.002), as well as a 0.39 mg/dL higher high-density lipoprotein cholesterol level (95% CI, 0.01-0.77; P =.04). These associations were attenuated with longer time since menopause. There was no significant association found between estradiol dose and metabolic measures in late postmenopausal women.

Higher serum estradiol levels were also associated with lower total cholesterol (P =.004), low-density lipoprotein cholesterol (P =.0001), and fasting blood glucose levels (P =.003) and higher triglyceride levels (P =.002) in early postmenopausal women. Although the direction and magnitude of changes in metabolic measures were similar between early and late postmenopausal women, there were no significant associations found with serum estradiol levels in late postmenopausal women.

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“While there were significant beneficial associations of higher [estradiol] dose among early postmenopausal women, there was no effect among late postmenopausal women,” the investigators wrote. “As these metabolic parameters are risk factors for cardiovascular events, these results support the timing hypothesis of [estradiol] therapy and cardiovascular benefits.”

Disclosure: This study was funded by TherapeuticsMD.

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Sriprasert I, Hodis H, Bernick B, Mirkin S, Mack W. Effect of estradiol dose and serum estradiol level on metabolic measures in early and late postmenopausal women in the REPLENISH trial. Presented at: North American Menopause Society 2019 Annual Meeting; September 25-28, 2019; Chicago, IL. Abstract S-18.