Synthetic progestins may be the major cause of harmful side effects reported with hormone replacement therapy. University of South Florida researchers used a novel imaging technique to show that progestins caused toxicity while natural progesterone and estrogen did not show toxicity to blood vessels in live animals. "Our findings can lead to the development and screening of synthetic hormones to find a safe progestin that will ultimately give women safer options than are currently available for hormone replacement therapy," said Tom Thomas, lead author of the study published in Climacteric, the Journal of the International Menopause Society.
"This is experimental evidence that supports scientists who believe estrogen with the right formulation is good for some women, depending on their other risk factors."
The novel imaging technique was developed by Thomas and Johannes Rhodin, co-investigator. It took three years for Thomas and Rhodin to combine video microscopy with fluorescence and electron microscopy. By labeling blood cells with a fluorescent tag, the team observed blood flow, blood vessel structure and activities of various blood cells in real time in a live animal. After one dose of medroxy progesterone acetate (MPA), the most widely used synthetic progestin in estrogen prepaparations and oral contraceptives, the rats had visible damage to the periphery and brain blood vessels, endothelial and smooth muscle damage, inflammation and blood clot formation and impeded blood flow.
"These vascular reactions to synthetic progestin can lead to increases in heart attacks, blood clots, strokes and dementia - problems that were observed in the Women's Health Initiative," Thomas said.
The USF researchers' findings may shed light on the current reassessment of the Women's Health Initiative.
Using the same video microscopic techniques the research team found that either estrogen alone or the natural progesterone did not cause such vascular toxicity.
They also showed that estrogen protects blood vessels of the brain and surrounding areas and prevents inflammation and clot formation.
In a related study the team showed that estrogen might protect blood vessels in the brain from beta-amyloid, a key factor contributing to memory loss in Alzheimer's disease. The article "In vivo cerebrovascular actions of amyloid B-peptides and the protective effect of conjugated estrogens" was published in the Journal of Alzheimer's Disease 5 (2003).
"This supports recommendations to use estrogen early and in low doses to protect the brain," Dr. Thomas said.
