Conclusion: In this secondary analysis of a randomized clinical trial, a significant, although small, increase in serum estradiol levels was noted after 12 weeks of vaginal estrogen administration. The clinical relevance of this small increase is uncertain.
Key Points
• Source: JAMA Network Open
• Meaning: “Low-dose vaginal estradiol use was associated with a small increase in serum estradiol concentrations of uncertain clinical significance.”
• In the current secondary analysis of randomized clinical trial data involving 174 women who are postmenopausal, U.S. researchers found that 12 weeks of vaginal estradiol, 10 µg, tablet use was related to a higher median serum estradiol concentration compared with placebo. Of note, estrone or SHBG levels were not significantly affected. The number of women who changed from a lower serum estradiol (≤2.7 pg/mL) to a higher (>2.7 pg/mL) risk category was similar in all treatment groups.
• The authors wrote, “Meta-analyses, mostly including studies that used immunoassays, suggest that higher concentrations of serum estradiol in women who are postmenopausal are associated with greater risks for multiple adverse health outcomes, including breast cancer, thromboembolic disease, and heart disease. Multiple cohort analyses have found no significant associations between use of low-dose vaginal estradiol and any of these outcomes, suggesting that the small increases in serum estradiol concentrations seen in our cohort are not clinically significant. However, to our knowledge, no randomized clinical trials have specifically tested this claim.”
• One limitation of the current study is that it is unclear what circulating estradiol cutoffs convey increased risk.
• Source: JAMA Network Open
• Meaning: “Low-dose vaginal estradiol use was associated with a small increase in serum estradiol concentrations of uncertain clinical significance.”
• In the current secondary analysis of randomized clinical trial data involving 174 women who are postmenopausal, U.S. researchers found that 12 weeks of vaginal estradiol, 10 µg, tablet use was related to a higher median serum estradiol concentration compared with placebo. Of note, estrone or SHBG levels were not significantly affected. The number of women who changed from a lower serum estradiol (≤2.7 pg/mL) to a higher (>2.7 pg/mL) risk category was similar in all treatment groups.
• The authors wrote, “Meta-analyses, mostly including studies that used immunoassays, suggest that higher concentrations of serum estradiol in women who are postmenopausal are associated with greater risks for multiple adverse health outcomes, including breast cancer, thromboembolic disease, and heart disease. Multiple cohort analyses have found no significant associations between use of low-dose vaginal estradiol and any of these outcomes, suggesting that the small increases in serum estradiol concentrations seen in our cohort are not clinically significant. However, to our knowledge, no randomized clinical trials have specifically tested this claim.”
• One limitation of the current study is that it is unclear what circulating estradiol cutoffs convey increased risk.