Article Impact Level: HIGH Data Quality: STRONG Summary of Obstetrics & Gynecology, 145(4), 357–367. https://doi.org/10.1097/AOG.0000000000005862 Dr. Matthew Nudy et al.
Points
- The study from the Women’s Health Initiative (WHI) trials evaluated long-term cardiovascular biomarker changes in postmenopausal women receiving hormone therapy (HT), comparing conjugated equine estrogens (CEE) with or without medroxyprogesterone acetate (MPA).
- Results showed that CEE alone and CEE+MPA reduced LDL-C by 11% and 12%, respectively, increased HDL-C by 13% and 7%, while triglycerides increased by 7% in both treatment groups.
- Lipoprotein(a) decreased by 15% in the CEE group and 20% in the CEE+MPA group, while insulin resistance (HOMA-IR) decreased by 14% with CEE alone and 8% with CEE+MPA.
- CEE and CEE+MPA therapies improved lipoprotein(a), LDL-C, and insulin resistance. They increased HDL-C compared to placebo, but triglycerides increased in both treatment groups, highlighting potential benefits and risks.
- The study suggests that HT may have cardiovascular benefits for younger menopausal women but emphasizes the need for further research on other progestogens and their effects on cardiovascular biomarkers.
Summary
This study from the Women’s Health Initiative (WHI) trials evaluated long-term cardiovascular biomarker changes in postmenopausal women receiving hormone therapy (HT), specifically conjugated equine estrogens (CEE) alone or CEE combined with medroxyprogesterone acetate (MPA). Participants were randomized to receive either the active treatment or placebo and were followed for up to 6 years. Blood samples were collected at baseline and years 1, 3, and 6 to measure biomarkers, including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, lipoprotein(a), glucose, insulin, and insulin resistance (HOMA-IR). The study used repeated-measures regression models to analyze changes in these biomarkers over time.
Results showed that CEE alone reduced LDL-C by 11% over 6 years (geometric mean ratio 0.89, 95% CI 0.88-0.91, P<0.001), with similar reductions seen in the CEE+MPA group (0.88, 95% CI 0.86-0.89, P<0.001). HDL-C increased by 13.0% and 7.0% for CEE alone and CEE+MPA, respectively, compared to placebo. Triglycerides increased in both treatment groups, with CEE alone showing a 7.0% increase, while CEE+MPA participants also had a 7.0% rise. Lipoprotein(a) decreased by 15.0% and 20.0% in the CEE and CEE+MPA groups, respectively. HOMA-IR decreased by 14.0% for CEE alone and 8.0% for CEE+MPA.
In conclusion, both CEE and CEE+MPA therapies were associated with improved lipoprotein(a), LDL-C, and insulin resistance, and increased HDL-C compared to placebo. However, triglycerides increased in both treatment groups. These findings highlight the potential benefits and risks of HT for younger menopausal women, helping inform decisions on initiating oral HT, especially regarding cardiovascular event rates. Further research is needed to explore the effects of other progestogens on cardiovascular biomarkers.
Link to the article: https://journals.lww.com/greenjournal/fulltext/2025/04000/long_term_changes_to_cardiovascular_biomarkers.1.aspx
References Nudy, M., Aragaki, A. K., Jiang, X., Manson, J. E., Shadyab, A. H., Jung, S. Y., Martin, L. W., Wild, R. A., Womack, C., Mouton, C. P., Rossouw, J. E., & Schnatz, P. F. (2025). Long-term changes to cardiovascular biomarkers after hormone therapy in the women’s health initiative hormone therapy clinical trials. Obstetrics & Gynecology, 145(4), 357–367. https://doi.org/10.1097/AOG.0000000000005862
