Protein related to sex hormones affects risk of stroke in women

What role does sex hormone binding globulin play in strokes in women?

If women have low levels of a particular protein that binds and transports sex hormones in the blood, this may indicate an increased risk of ischemic stroke.

Brown University's recent research found that lower levels of a protein in women that bind and transport sex hormones in women may indicate an increased risk of ischemic stroke. The results of the study were published in the English-language journal “Stroke”.

What is sex hormone binding globulin?

So-called sex hormone-binding globulin (SHBG) is a protein produced by the liver that binds to estradiol (a form of estrogen) and testosterone and transports these hormones in the bloodstream. At high SHBG levels, lower levels of active estrogen and testosterone circulate in the body and the balance between testosterone and estrogen changes.

Effects of low SHBG levels

Conversely, low levels of SHBG mean that more of the hormones are active in body tissues. In addition to affecting estrogen and testosterone levels, SHBG also affects body tissues by binding directly to the cells. In the past, low levels of SHBG have been associated with diabetes and heart disease, and current results confirm this.

How do female hormones affect the risk of stroke?

“In recent years, we've started to learn more about how well-established stroke risk factors such as high blood pressure and diabetes differ between women and men. Unfortunately, we still don't know how female hormones affect lifelong stroke risk for women, ”study author Tracy E. Madsen of Brown University in Providence said in a press release.

More than 13,000 postmenopausal women have been examined

In their study, the researchers examined the occurrence of ischemic strokes in more than 13,000 postmenopausal women with an average age of 62.5 years. Participants were measured for SHBG between 1993 and 1998 when they were accepted into the Women's Health Initiative, a large, nationwide study involving more than 160,000 postmenopausal women.

Lowest SHBG values ​​massively increased the risk of stroke

In the current study, the researchers examined the occurrence of strokes between women with SHBG in the top 25 percent and women with SHBG in the bottom 25 percent of all participating women. Taking age, race, body mass index, hypertension, alcohol consumption and smoking into account, women with the lowest SHBG levels were 51 percent more likely to have a stroke.

The risk of follow-up was 46 percent

Even after considering diabetes, a possible link between low SHBG and stroke, women with the lowest SHBG were still 46 percent more likely to have a stroke in the follow-up period.

More research is needed

"More research is needed before SHBG measurements are included in clinical care and used to assess stroke risk," said Madsen.

Healthy lifestyle can increase SHBG

However, it is known that there are factors that tend to increase SHBG and that are related to an overall healthy lifestyle. This includes, for example, regular exercise, a healthy body weight and a reduction in sugar intake. Drinking coffee in moderation can also help improve your SHBG.

How can women improve stroke prediction?

The researchers are planning further studies in the future to find out whether there is a cause-effect relationship between low SHBG and stroke. They want to evaluate whether adding hormonal biomarker screening to existing stroke risk assessments could improve stroke prediction in women.

Various hypotheses are examined in more detail

There are several possible mechanisms by which low SHBG levels could be associated with an increased risk of stroke. These include, for example, changes in the body's response to sex hormones, changes in the way the body uses insulin (which can cause blood vessels in the brain to malfunction), or changes in inflammation, immune function, or the blood clotting process. The research group is currently working on some of these hypotheses.

Limitations of the investigation

The results of this study in postmenopausal women may not be generalized to either men or pre-menopausal women. Since the Women's Health Initiative was originally not designed to answer questions about SHBG and stroke, the researchers were only able to use data from a fraction of the total study participants. (as)

Author and source information

This text corresponds to the specifications of the medical literature, medical guidelines and current studies and has been checked by medical doctors.


  • Tracy E. Madsen, Xi Luo, Mengna Huang, Ki E. Park, Marcia L. Stefanick, JoAnn E. Manson, Simin Liu: Circulating SHBG (Sex Hormone-Binding Globulin) and Risk of Ischemic Stroke, in Stroke (published 12.02. 2020), stroke
  • Sex hormone-related protein levels may impact stroke risk in women, American Heart Association (Published 02/12/2020), AHA

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