Time to address the knowledge gap regarding female-specific responses to disease

Historically, medical research has been dominated by the “reference man” model, rooted in the assumption that male physiology adequately represents the human experience. For years, this led to the exclusion of women from clinical trials due to concerns about hormonal fluctuations, potential pregnancy, and the perceived complexity of the female reproductive system. This exclusion resulted in a significant knowledge gap regarding female-specific responses to treatments and disease progression. This World Health Day, Dr. Ramakanta Panda of the Asian Heart Institute highlights the urgent need to bridge this gap.

The underrepresentation of women in medical research, a historical oversight that continues to cast a long shadow, is a complex issue with deep-rooted societal and scientific origins. As a cardiac surgeon, I’ve witnessed firsthand the consequences of this disparity, particularly in the realm of heart disease.

For instance, the impact of hormonal changes during menopause on cardiovascular risk has been inadequately studied. While it’s known that estrogen plays a protective role, the complexities of hormone replacement therapy and its effects on cardiovascular health remain debated, partly due to the historical exclusion of women from pivotal trials. Microvascular disease, a condition affecting the small blood vessels of the heart, is more prevalent in women, yet its mechanisms and optimal treatment strategies are still poorly understood—a direct result of the historical focus on males.

Further, In cardiovascular research, this bias has been particularly damaging. For decades, the understanding of heart attack symptoms, diagnostic criteria, and treatment protocols was primarily based on male patients. Women often present with atypical symptoms, such as nausea, shortness of breath, and back pain, which are frequently dismissed or misdiagnosed. This delay in diagnosis, stemming from a lack of awareness rooted in male-centric research, contributes partly to higher mortality and complication rates in women following a heart attack.

A similar challenge exists in research around maternal mortality. Pregnancy induces profound physiological changes, impacting cardiovascular, renal, and metabolic systems. Yet, the study of these changes and their potential complications has been significantly limited. Preeclampsia, a severe hypertensive disorder of pregnancy, remains a leading cause of maternal mortality worldwide. The pathophysiology of preeclampsia, optimal management strategies, and the long-term cardiovascular risks for women who have experienced it are still not fully understood.

Beyond cardiovascular health, conditions such as osteoporosis, autoimmune diseases like lupus, and even drug metabolism have been skewed by the lack of female representation. Dosage adjustments, drug interactions, and the efficacy of treatments vary significantly between men and women.

Fortunately, regulatory bodies, such as the National Institutes of Health (NIH), are now mandating the inclusion of women in clinical trials. Researchers are increasingly recognizing the importance of sex-disaggregated data and the need for studies specifically designed to address female-specific health concerns.

However, challenges remain; funding for women’s health research is still disproportionately low compared to other areas. We need a paradigm shift that prioritizes the inclusion of women in all phases of research, from basic science to clinical trials. Only then can we truly understand the complexities of female physiology and develop effective, personalized treatments that address the unique health needs of women. One north star to guide all of us, should be that good medicine must be inclusive medicine.

Dr. Ramakanta Panda, Renowned Heart Surgeon and Chairman, Asian Heart Institute, Mumbai.