I like to start with a story…In the first years of the past century, a young woman, whose name was Yentl, disguised herself as a boy, to have the opportunity to study. In 1991, this story became the “Yentl syndrome”, based on the idea of an American cardiologist. She observed that women were less hospitalized than men. This is not all, women had less therapeutic attention and were less represented in trials. This story caused a stir at that time, but they started reflecting on a new medicine, or rather a transversal medicine: the Gender Medicine.
The World Health Organization (WHO) defines Gender Medicine, or Gender-specific Medicine, as the study of how (sex-based) biological and (gender-based) socioeconomic and cultural differences influence people’s health.
At the start it was only a question of biological sex.
Data say that in addition to being socially disadvantaged compared to men, women tend to become ill more often, take more medications and are more likely to experience adverse reactions.
For a long time, clinical studies enrolled predominantly male subjects, pre-clinical in vitro studies (on cell lines or isolated cells) failed to include information on the sex of the organism from which the cells originated, and in vivo studies (on experimental animals) only used male animals.
The term ‘gender medicine’ was first introduced in the late 1990s. Gender medicine is the study of how diseases differ between men and women in terms of prevention, clinical manifestation, diagnostic and therapeutic approaches, prognosis, psychosocial effects, and interactions with the health-care system.
So, the terms “sex” and “gender” were often exchanged, but it’s inappropriate.
Now it’s a question of both sex and gender.
Nowadays, the Gender Medicine is not an independent branch of medicine, but its interdisciplinary dimension should permeate all areas of medical science to help understand how sex and also gender influence human physiology, pathology and pathophysiology (the development of diseases and their symptoms), as well as their prevention, diagnosis and treatment in both men and women.
Gender is a multidimensional and dynamic construct that refers to the sociocultural dimension of being a woman, a man or a gender-diverse person in a given society. Gender comprises four dimensions, including gender roles, gender relations, institutionalized gender and gender identity. Gender is not identical to the sex of the individual but is strongly associated with sex.
In health care, gender comprises the interaction of patients with their social environment (health-care staff) and physical environment (environmental stimuli and toxins) as well as access to and use of the health-care system. A holistic approach to health involves a “patient-centered” focus and “personalized treatments” to provide appropriate care. For the correct diagnosis and management of a condition, the biological sex of the patient should therefore be considered, as well as other parameters, such as: gender identity, age, ethnicity, level of knowledge, religious beliefs, sexual orientation, social and economic conditions.
What we know now?
Recent studies in Gender Medicine concentrate the attention on several diseases. Below only few examples are reported, in particular, cardiovascular diseases (CVD), pharmacology, oncology, liver diseases, osteoporosis and allergy.
CVD disease
Clear evidence indicates that sex-related and gender-related factors interact in generating differences in CVD outcomes in women and men and might even have opposite effects on clinical manifestations and outcomes. The influence of biological sex on CVD manifestations frequently favours females, such as the relative protection from obstructive coronary artery disease in premenopausal females or the more favourable left ventricular remodeling observed in females with heart failure compared with males. Conversely, gender-related factors, including a higher prevalence of anxiety in women with CVD, a stronger association between mental stress and disease manifestations in women, poorer communication with health-care representatives, a lack of consideration of sex-specific and gender-specific pathophysiology in medical research, and the underrepresentation of the female population in drug development, more adversely affect women than men [1].
Pharmacology
For what concerns pharmacology, while gender-related pharmacodynamic data are limited, evidence suggests that women are more prone to the development of side effects and different pharmacological response to drug treatment that could translate into a different clinical outcome [2].
Cancer
Studies on cancer are very extended, but it emerges that gender differences are deeply underestimated in clinical practice for the treatment of the main types of cancer. It is necessary to encode and improve the knowledge about tumor variability based on gender differences, to identify all the variables that can influence prognosis, choice of treatment and possible related toxicities [2].
Liver disease
The field of liver disease also shows several differences among gender. An interesting observation, for example, concerns the liver fibrosis. It has been shown that long-term benefits of estrogen exposure (premenopausal women) have a slow progression in liver fibrosis. The reduced rate of fibrosis among women disappears after menopause; in fact, post-menopausal women have accelerated progression of fibrosis compared with men that is slowed by long-term estrogen exposure with hormone replacement therapy. The fertile age is indeed a crucial point when a female patient with chronic hepatitis C is treated with antiviral therapy [2].
Osteoporosis
Another field of interest is the osteoporosis disease, that is an important public health problem both in women and men. Overall, far more epidemiologic, diagnostic, and therapeutic data are currently available for women. In clinical practice, if this disease remains underestimated in women, patients’ and physicians’ awareness is even lower for male osteoporosis [2].
Allergy
Finally, there’s the need of more observations data for allergy disease. It is known that even though the risk of being allergic is greater for boys in childhood, almost from adolescence onwards it seems that women are more affected by allergy problems. Asthma, food allergies and anaphylaxis are more frequently diagnosed in females. In turn, asthma and hay fever are associated with irregular menstruation. Pointing towards a role of sex hormones, an association of asthma and intake of contraceptives, and a risk for asthma exacerbations during pregnancy have been observed [3].
It’s now difficult to draw a conclusion, but it’s clear that treatments must personalized. It is desirable that in the future the multidisciplinary medicine will be improved to put the patient at the center.
I like to end with the word of the Nobel peace prize Bernard Lown:
“Medicine is the art of engagement with the human condition rather than with the disease.”
[1] Gender medicine: effects of sex and gender on cardiovascular disease manifestation and outcomes; Vera Regitz-Zagrosek & Catherine Gebhard; Nature Reviews Cardiology – Volume 20 | April 2023 | 236–247.
[2] Gender medicine: A task for the third millennium; Giovannella Baggio , Alberto Corsini , Annarosa Floreani , Sandro Giannini and Vittorina Zagonel; lin Chem Lab Med 2013; 51(4): 713–727.
[3] Gender-medicine aspects in allergology; E. Jensen-Jarolim, E. Untersmayr – Allergy: European Journal of Allergy and Clinical Immunology – 2008, 63 (5), 610-615.
