Illustration of 27HC blocking estrogen's heart-protective effects in postmenopausal women.

Estrogen's Hidden Foe: How a Cholesterol Molecule May Sabotage Heart Health in Postmenopausal Women

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Jordan Keane in Health & Wellness August 2025 • 4 min read.

"New research reveals how 27-hydroxycholesterol (27HC) can counteract the protective effects of estrogen, potentially increasing cardiovascular risk after menopause."


For years, scientists have observed a stark contrast in cardiovascular health between pre- and postmenopausal women. Before menopause, women enjoy a lower risk of heart disease compared to men of the same age. However, this advantage diminishes after menopause, coinciding with a significant drop in estrogen levels. This decline has long been suspected as a key contributor to the increased cardiovascular risk, prompting research into how estrogen protects the heart.

Estrogen's protective effects are partly attributed to estrogen receptors (ERs) found on various cells throughout the body, including platelets. These receptors allow estrogen to influence platelet function, potentially reducing the risk of blood clot formation. However, the picture is complicated by the presence of other molecules that can interact with these same estrogen receptors, either enhancing or hindering estrogen's effects.

One such molecule is 27-hydroxycholesterol (27HC), a byproduct of cholesterol metabolism. 27HC is a known ligand for ERs, meaning it can bind to these receptors. Unlike estrogen, 27HC has been shown to block both the genomic and non-genomic actions of E2, leading some scientist to believe that 27HC could block the natural effect of estrogen to function and do its job.

The 27HC Factor: Blocking Estrogen's Protective Action

Illustration of 27HC blocking estrogen's heart-protective effects in postmenopausal women.

Recent research has shed light on how 27HC may undermine estrogen's beneficial effects on platelet function. A new study published in Rev Med Chile investigated the impact of 27HC on platelets from postmenopausal women. The researchers focused on platelet aggregation, a crucial step in blood clot formation. They found that while estrogen effectively inhibited platelet aggregation, this effect was significantly reversed in the presence of 27HC.

The study involved isolating platelets from postmenopausal women and pre-incubating them with varying concentrations of 27HC, both with and without estrogen (specifically, estradiol, or E2). The platelets were then stimulated with collagen, a substance that triggers aggregation. The degree of aggregation was measured using turbidimetry.

Here's a breakdown of the key findings:
  • Estrogen (E2) significantly inhibited collagen-stimulated platelet aggregation.
  • The inhibitory effect of E2 was reversed when platelets were pre-incubated with 27HC.
  • 27HC appeared to counteract the anti-aggregatory effects of estrogen, suggesting it acts as an estrogen antagonist in platelets.
These results suggest that 27HC can interfere with estrogen's ability to protect against excessive platelet aggregation, a process that can contribute to cardiovascular events. The study highlights a potential mechanism by which elevated cholesterol levels, and the subsequent increase in 27HC, may increase cardiovascular risk in postmenopausal women.

Implications and Future Directions

This research provides valuable insights into the complex interplay between estrogen, cholesterol, and cardiovascular health in postmenopausal women. By demonstrating 27HC's ability to counteract estrogen's protective effects on platelets, the study identifies a potential therapeutic target for reducing cardiovascular risk in this population.

While the study used pharmacologic values of 27HC, future research needs to investigate the precise physiological levels of 27HC within platelets and their impact on estrogen signaling. This could involve exploring ways to modulate 27HC production or its interaction with estrogen receptors in platelets.

Ultimately, understanding the role of 27HC in cardiovascular disease could pave the way for new preventative strategies, such as targeted dietary interventions or pharmacological approaches, to help postmenopausal women maintain optimal heart health.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.4067/s0034-98872016001100002, Alternate LINK

Title: Efecto Del 27- Hidroxicolesterol En La Acción Antiplaquetaria De Estradiol En Mujeres Postmenopáusicas

Subject: General Medicine

Journal: Revista médica de Chile

Publisher: SciELO Agencia Nacional de Investigacion y Desarrollo (ANID)

Authors: Gladys Rocha, Walter Sierralta, Luis Valladares

Published: 2016-11-01

Everything You Need To Know

1

What is the main finding about 27-hydroxycholesterol?

The research highlights how 27-hydroxycholesterol (27HC), a byproduct of cholesterol metabolism, interferes with estrogen's heart-protective actions in postmenopausal women. Estrogen, through its receptors (ERs), normally inhibits platelet aggregation, reducing the risk of blood clots. However, 27HC counteracts this effect. This is significant because it explains a mechanism contributing to increased cardiovascular risk after menopause.

2

How does estrogen normally protect the heart?

Estrogen receptors (ERs) are found on various cells, including platelets. These receptors allow estrogen to influence platelet function, which reduces the risk of blood clot formation. The presence of 27-hydroxycholesterol (27HC) complicates this process. 27HC can bind to these same receptors and block the beneficial actions of Estrogen. This interference is a key aspect of how 27HC undermines estrogen's protective effects.

3

What is the role of 27-hydroxycholesterol (27HC) in relation to estrogen?

27-hydroxycholesterol (27HC) is a byproduct of cholesterol metabolism. It acts as an estrogen antagonist in platelets. The research demonstrates that when platelets from postmenopausal women are pre-incubated with 27HC, the inhibitory effect of estrogen (specifically, estradiol, or E2) on platelet aggregation is reversed. This means that 27HC counteracts estrogen's ability to prevent blood clot formation, potentially increasing cardiovascular risk.

4

Why is this research about 27-hydroxycholesterol (27HC) important?

The significance lies in understanding how cardiovascular risk increases after menopause. Before menopause, women have a lower risk of heart disease due to estrogen's protective effects. The decline in estrogen after menopause increases this risk. This research shows that 27-hydroxycholesterol (27HC) can interfere with estrogen's protective effects on platelets, increasing the risk of blood clot formation and, consequently, cardiovascular events in postmenopausal women. This suggests that increased 27HC levels may play a key role in this increased risk.

5

What are the implications and future directions of this research?

The research suggests potential therapeutic targets to reduce cardiovascular risk. By demonstrating 27-hydroxycholesterol's (27HC) ability to counteract estrogen's protective effects on platelets, the study identifies a potential target for intervention. Future directions might include strategies to lower 27HC levels or mitigate its impact on estrogen receptors, thereby reducing cardiovascular risk in postmenopausal women. This could lead to new preventative strategies or treatments.

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