Sex-Specific Research Striving for Optimal Healthcare

In the beginning, it's a coincidence: A chromosome determines whether a person is born biologically as male or female. As life progresses, this happenstance becomes pivotal for survival. Numerous illnesses exhibit sex-specific symptoms, such as women with diabetes facing a heightened risk of heart attacks compared to men. Scientists at Helmholtz Munich are delving into the molecular intricacies behind these sex-specific differences, aiming to enhance overall life expectancy for both men and women.

In medicine, certain drugs do not differentiate according to biological sex. However, for other medications, substantial variations in effectiveness, both in terms of intensity and duration, are observed between men and women. Consequently, package inserts should ideally include precise dosage recommendations for both sexes. Regrettably, many drug manufacturers lack essential sex-specific data to formulate accurate guidelines. It is a well-established fact that drugs and therapies undergo insufficient testing on women, with a significant portion of available data, at times all of it, originating from male test subjects. Urgent measures are imperative to address this gap and promote more comprehensive, sex-specific research and development in the pharmaceutical field.

Research has long acknowledged that the distinction between women and men extends beyond mere chromosomal differences. “In addition to individual genetic predispositions and life influences, both of which significantly shape our disease potential, the physiological functions of men's and women's bodies differ. There are reasons why men are more likely to accumulate body fat in the abdominal area, while women are more likely to store it on their hips and thighs. Moreover, sex-specific variations in pain perception and heart attack symptoms exist. It is crucial to better understand these causes at a molecular level. Only through this in-depth understanding can we integrate our findings directly into the development of advanced, personalized medicine,” says Susanna Hofmann.

Metabolism, Immune System, and Sport – A Matter of Sex

Susanna Hofmann is an expert on sex-specific differences in metabolism and the immune system and works intensively on associated diseases such as obesity and diabetes. In her research, she places particular emphasis on the therapeutic significance of lifestyle changes through sport. In addition to her scientific work, she is a deputy board member of the German Society for Gender-Specific Medicine.

In this video, Susanna Hofmann explores the influence of sex on metabolic diseases, the immune system, losing weight through exercise, and offers insights on personalized medicine.

Martin Heni and his research group reveal distinct hormonal responses between women and men. The researchers at the Institute of Diabetes Research and Metabolic Diseases have discovered that the menstrual cycle strongly influences the brain's reaction to the pancreatic hormone insulin. In their study involving eleven women, a nasal spray containing insulin was administered before and after ovulation. The focus was on understanding the participants' insulin responses compared to a placebo spray and throughout their menstrual cycles. Martin Heni observed noteworthy differences in insulin sensitivity between the phases of the menstrual cycle. Before ovulation, sensitivity was markedly higher compared to post-ovulation, where the insulin response was significantly decreased. These findings bear significant implications for women dealing with diabetes.

Insulin sensitivity refers to the body's responsiveness to insulin, a hormone that regulates blood sugar levels. High insulin sensitivity means cells efficiently respond to insulin, promoting effective glucose uptake and utilization. On the other hand, low insulin sensitivity, known as insulin resistance, implies reduced cell responsiveness, leading to elevated blood sugar levels and contributes to potential health issues like type 2 diabetes.

The findings were further validated through magnetic resonance imaging (MRI). Brain scans of further participants revealed heightened insulin sensitivity in the hypothalamus during the first half of the cycle (follicular phase) compared to the second half (luteal phase). In clinical practice, women with type 1 diabetes, who require insulin injections, often adjust their dosage based on their menstrual cycle phases due to significant blood sugar level fluctuations. Thanks to Martin Heni and his colleagues' study, a possible mechanism has been discovered that could explain these variations in blood sugar levels along the menstrual cycle through changes in the brain.

Insulin is not the sole protagonist in the genesis of metabolic diseases. Before menopause, women are less likely to develop metabolic diseases than men, which suggests a protective role for sex hormones. Nevertheless, the precise mechanisms through which sex-specific hormones influence metabolism remain incompletely researched. Insights from mouse model studies indicate that female mice of a specific genetic lineage (C57BL/6) enjoy greater protection against obesity during reproductive age than their male counterparts. Cristina García-Cáceres and her research group at the Institute for Diabetes and Obesity have investigated this in more detail.

Estradiol is the most important hormone in the female body and belongs to the estrogens. In the mouse model, researchers were able to determine that oestradiol regulates energy balance, for example by sending satiety signals. Problems with energy balance are a major cause of obesity.

In their study, female mice showed a higher risk of obesity when they lacked the protein Cited1. The absence of Cited1 in the female mice's hypothalamus meant that they could no longer react as strongly to the satiety hormone leptin as before. Their leptin sensitivity dropped to the level of male mice. Cristina García-Cáceres explains: “Research results like these help us to better understand sex-specific differences in obesity. This lays the foundation for new drugs that can treat severe obesity more individually and with fewer side effects.”

Some scientists at Helmholtz Munich delve into sex-specific research even before birth. Prof. Hubert Preissl and his team specialize in investigating prenatal and newborn brain development. Leveraging their expertise in metabolic neuroimaging, Preissl utilizes a non-invasive and highly sensitive fetal magnetoencephalography (fMEG) machine to monitor fetal and newborn neuronal activity. Worldwide only two fMEG machines are operational. In a recent study conducted by the Institute for Diabetes Research and Metabolic Diseases, the researchers aimed to elucidate how brain activity evolves before and after birth, particularly concerning sex differences. Initially hypothesizing that brain complexity would increase with gestational age, their findings unveiled a surprising trend: a notable decrease in neural complexity as infants matured, with male infants exhibiting a more rapid decrease compared to females.

Personalized medicine needs sex-specific research to do justice to the individual differences between men and women. At present, a substantial data gap exists in both fundamental research and clinical studies. “The ideal scenario would involve gathering data that facilitates an even more precise and personalized characterization of patients in the future. A promising blueprint for this can be found in cancer research, where the accurate identification of subtypes enables targeted treatments with newly developed agents,“ notes Susanna Hofmann. Extending this paradigm to other medical domains could pave the way for tailored medicine that not only considers sex-specific distinctions but also addresses the unique needs of individual patients—ultimately turning the vision of personalized medicine into reality.

Latest update: March 2024.