Increasing Estrogen Concentrations Reduces Cholesterol Expansion With Crystallization

Investigators assessed the impact of estrogen and testosterone on cholesterol crystallization and volume expansion as they relate to atherosclerotic plaque rupture.

Estrogen, but not testosterone, was found to inhibit expansion of cholesterol during the crystallization process, according to results of a study presented at the National Lipid Association Scientific Sessions in Scottsdale, Arizona, from June 2nd to 5th, 2022.

Estrogen and testosterone hormones are formed by a cholesterol-based molecule, and the 2 hormones only differ by one OH side branch and methyl group. However, despite their similar chemical structures, their effects differ greatly.

Cholesterol crystallization has been implicated in atherosclerotic plaque destabilization and can lead to rupture and cardiovascular events. Estrogen has been associated with protective effects against cardiovascular events among premenopausal women.

In order to evaluate the potential mechanisms behind estrogen’s beneficial effects, investigators from Michigan State University performed a scanning electron microscopy study. Graded concentrations of estradiol or testosterone of 13, 130, and 1300 mg were mixed with 3 g of cholesterol power in 1 mL of water. The mixtures were allowed to crystalize at room temperature (22°C). Changes in volume expansion between liquid and crystalline phases were compared against water alone.

The change in cholesterol volume expansion decreased significantly with greater estradiol concentrations (P <.01). This trend was not observed for testosterone (P =.64), in which the change in volume expansion was similar to water alone regardless of the concentration of testosterone.

Scanning electron microscopy imaging demonstrated the cholesterol crystals that were exposed to estrogen to be dissolving compared with intact crystals in the absence of estrogen.

This study found that the volume expansion with cholesterol crystallization from liquid to solid was inhibited with the addition of estrogen. This pattern was not observed with testosterone. These findings are consistent with clinical observations that support the protective effect of estrogen in decreasing the frequency of cardiovascular events among premenopausal women.

Disclosure: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Wang E, Al-Abcha A, Osman H, Oladeji A, Boumegouas M, Abela GS. The effect of estrogen and testosterone on cholesterol crystallization. Presented at: National Lipid Association 2022 Scientific Sessions; June 2-5, 2022; Scottsdale, Arizona. Abstract #56.