Abstract
A prodigious increment of scientific evidence in both preclinical and clinical studies is narrowing a major gap in knowledge regarding sex-specific biological responses observed in numerous branches of clinical practices. Some paradigmatic examples include neurodegenerative and mental disorders, immune-related disorders such as pathogenic infections and autoimmune diseases, oncologic conditions, and cardiovascular morbidities. The male-to-female proportion in a population is expressed as sex ratio and varies eminently with respect to the pathophysiology, natural history, incidence, prevalence, and mortality rates. The factors that determine this scenario incorporate both sex-associated biological differences and gender-dependent sociocultural issues. A broad narrative review focused on the current knowledge about the role of hormone regulation in gender medicine and gender peculiarities across key clinical areas is provided. Sex differences in immune response, cardiovascular diseases, neurological disorders, cancer, and COVID-19 are some of the hints reported. Moreover, gender implications in occupational health and health policy are offered to support the need for more personalized clinical medicine and public health approaches to achieve an ameliorated quality of life of patients and better outcomes in population health.
Highlights
Deliberate contemplation of sex-biased data in preclinical and clinical studies was initiated only in the last few decades, howbeit a historical assertion of sex differences in the manifestation of diseases and response to treatment was already stated by Hippocrates more than 2000 years ago
Nuclear acting estrogen receptors (ERs) can function as transcription factors and regulate gene expression on a slow time range. These moderately long processes had been puzzling scientists as they could not explain the observed rapid changes in neurological or immune system behavior, alluding to the presence of another type of ERs. This hypothesis was initially experimented by investigators who realized that estradiol provision in the tissue of the uterine cavity resulted in rapid increment of cAMP, which was due to estradiol binding to cell membrane hormone receptors
Numerous studies have agreed that circulating sex hormones and neurosteroids influence the inhibitory GABAergic synapses and the excitatory glutamatergic transmission that are greatly involved in seizures
Summary
Deliberate contemplation of sex-biased data in preclinical and clinical studies was initiated only in the last few decades, howbeit a historical assertion of sex differences in the manifestation of diseases and response to treatment was already stated by Hippocrates more than 2000 years ago. Sex refers to the biological and genetic features of individuals, whereas gender is intended as the social perspective of human beings concerning expressions, behaviors, and social roles The latter is considered a personal choice and can generate a nonbinary range of gender identities. While some inter-relationship between the hormonal and genetic milieu and gender identity selection may exist, the exact mechanisms are still unknown This phenomenon is rather troublesome to investigate due to the fact that humans present consciousness, a trait that is still at least unclear in animals, and research in this area is limited [1]. Gender-dependent sociocultural issues affect the epidemiology and the diseases’ course, such as in the case of risky lifestyle attitudes or access to healthcare This narrative review deals with biological substrata of gender differences in health and gender peculiarities across key clinical areas. An overview of gender implications in occupational health and health policymaking is provided
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