“Only when we understand the differences can we provide more targeted treatment”
In this interview, Professor Susanna Hofmann explains why women and men develop metabolic diseases differently and what that means for the future of medicine.
Interview: Marita Fuchs, freelance journalist
Ms. Hofmann, you conduct research on human metabolism. In reality, however, there isn’t just one type of metabolism—it differs between women and men. Why is it so important to understand these differences more closely?
Susanna Hofmann: Today we know that metabolism doesn’t function the same way in everyone. Men and women differ in many biological aspects. Hormones play an important role here, but they aren’t the only factor. The distribution of body fat, muscle mass, and the way sugars and fats are processed also differ.
The so-called weight-loss injections impressively demonstrate the potential of metabolic research. But at the same time, they raise new questions: Do such therapies work equally well for women and men?
GLP-1 medications are indeed a striking example of what basic research on metabolism can achieve. They did not emerge overnight but are based on decades of research into how active ingredients that activate hormone receptors regulate metabolism and appetite. This shows that scientific findings that initially seem very theoretical can lead to very concrete therapies years later.
There is preliminary evidence that women and men respond differently to GLP-1 therapies. On average, women lose slightly more weight, but they also report side effects more frequently. We don’t yet know why this is the case. That’s exactly what we’re investigating: We want to identify the biological mechanisms behind it—from sex hormones to body composition to the regulation of hunger and energy expenditure. Only when we understand these differences can we provide more targeted treatment. Only this knowledge enables truly individualized therapy.
Sex hormones influence fat and sugar metabolism—when did you first recognize this connection?
As a postdoctoral fellow at the Mount Sinai School of Medicine in New York—where I was conducting diabetes research—I noticed that almost exclusively male mice of the C57/Bl6 strain were being studied. There were very pragmatic reasons for this: Female mice of this strain were less suitable because they gained significantly less weight on a high-fat diet than the male mice, and they hardly developed any pronounced insulin resistance.
For me, that was precisely the key observation. If female mice are apparently better protected against metabolic disorders than male mice, then that is not a confounding factor but a biological signal. Since then, I have been researching how sex hormones influence fat and sugar metabolism and why women and men develop metabolic diseases differently.
Can this be explained using cardiovascular disease as an example?
Yes. One important difference concerns fat metabolism: Before menopause, women have, on average, lower LDL and higher HDL cholesterol levels than men. Put simply, LDL cholesterol is deposited in the blood vessels, while HDL transports excess cholesterol back to the liver. Estrogens also help protect the blood vessels and have a beneficial effect on lipid metabolism. That is why women, on average, develop coronary heart disease eight to ten years later than men.
Does this protective effect disappear after menopause?
Yes, LDL levels often rise, and cardiovascular risk increases significantly. Although women continue to have higher average HDL levels than men even after menopause, a high HDL level alone is not a reliable form of protection. What matters is how well the HDL particles function—and this function is influenced by factors such as gender, genes, and lifestyle.
Adipose tissue also plays an important role in metabolism. What do we know about it today?
Another area of my research is the role of various fat deposits in the body. Today we know that visceral fat in the abdominal cavity, in particular, plays a crucial role: It is highly metabolically active and contributes significantly to metabolic disorders that substantially increase the risk of diabetes and cardiovascular disease.
However, another fat deposit is now coming into sharper focus: intermuscular fat. What role does it play?
We are studying what is known as intermuscular adipose tissue (IMAT)—that is, fat stored between the muscles. IMAT can have a similar inflammatory effect to abdominal fat and thereby impair insulin action—with potential consequences for metabolism. The latest findings also suggest that IMAT is an independent prognostic risk factor for microvascular dysfunction in the heart. This condition, also known as coronary microvascular dysfunction (CMD), is more common in women and can cause symptoms even in the absence of narrowing of the major coronary arteries. Since CMD is associated with an increased cardiovascular risk, early diagnosis and consistent management of risk factors are crucial.
About the Author
Prof. Dr. med. Susanna Hofmann is a professor of lipid metabolism and metabolic diseases at the School of Medicine at Ludwig Maximilian University of Munich (LMU) and heads the “Women and Diabetes” research group at Helmholtz Zentrum München.
The physician and scientist is investigating why women and men develop metabolic diseases such as diabetes differently and how gender-specific differences can be used to tailor prevention and treatment to individual patients. A key focus of her work is on the molecular mechanisms of diabetes, lipid metabolism disorders, and cardiovascular diseases.
After completing her clinical training at LMU, she conducted research as a postdoctoral fellow at the Mount Sinai School of Medicine in New York. Today, she advocates for greater consideration of gender differences in medical research and treatment.
