Sex and gender are essential components of person-centered care. This article presents and discusses four important tenets regarding sex and gender health that should be incorporated into dental education and oral health care to foster inclusivity and improve care for all patients, including a sex and gender-diverse patient population.
Key points
- •
Sex and gender are integral to person-centered care.
- •
Interprofessional sex and gender health tenets (competencies) were recently published for health sciences education and are applied here for dentistry.
- •
Oral health curricula should ensure that graduates understand sex and gender differences and can apply this knowledge to the comprehensive care of patients.
- •
Evidence-based care depends on health sciences research including sex and gender considerations.
- •
Sex and gender health advocacy will help improve health outcomes and reduce health disparities.
Introduction
Sex, Gender, and Health
Sex and gender are essential components of oral and systemic health. Adopting a sex and gender lens is paramount in providing person-centered and evidence-based care. “Sex” (female, male, intersex, or non-dichotomous sex) is a biologic variable determined by the presence and/or combination of sex chromosomes, sex hormones, and reproductive organs. A person’s sex directly impacts the function of their cells and has broad physiologic and pathophysiologic implications relevant to all organ systems. “Gender” (man, woman, transgender, and nonbinary genders) is a sociocultural spectrum associated with certain roles, habits and behaviors, identities, and power relations , that occur in a social, cultural, and historic context. These may influence the risk of disease and a person’s interactions with the health care system. The interaction between biologic sex and sociocultural gender has an impact on health.
Evolution of Sex and Gender in Dental Education
Key events in the development of sex and gender core educational competency statements, or “tenets,” that apply to all health profession programs are outlined in Fig. 1 .
In the early 1990s, increased awareness of sex differences in health and disease propelled the incorporation of women’s health issues into research and clinical practice. In 1996, the US Department of Health and Human Services concluded that all health professionals should competently provide care to women across the life span. In response, a 1997 dental curricular survey explored topics in women’s health, serving as the impetus for the subsequent survey report and for a discussion of women’s oral health in a 2001 Dental Clinics of North America (DCNA) publication. , A second comprehensive dental curricular survey on closely parallel subject areas followed over a decade later, in 2011 ( Box 1 ). It indicated that gender-related topics were incorporated into dental curricula at many institutions. Participants agreed the information was important but that faculty needed resources and guidelines on content, sequencing, and/or assessment of these topics. The report recommended establishing national educational and fellowship programs and resources related to women’s health; incorporating “clinical simulations” for teaching women’s health topics into dental curricula; promoting interprofessional dialogue to address sex and gender factors in health and disease; and developing core competencies related to sex and gender health (SGH). A second DCNA issue focused on these emerging perspectives.
| 1997 Survey Topic Areas | 2011 Survey Topic Areas |
|---|---|
| General Social Themes and Gender | General Themes |
| Biological and Basic Science Considerations | Biological Considerations |
| Developmental and Psychological Themes | Developmental and Social Issues |
| Health Behavior and Health Promotion | Approaches to Health Behavior/Health Promotion in Women |
| Sexual and Reproductive Function | Sexual and Reproductive Function |
| Selected Conditions Prevalent in Women | Etiology, Prevalence, Course Treatment, and Prevention of Particular Conditions/Disorders in Women |
| Impact of Medications | Impact of the Use of Medications |
| History, Physical Examination, and Communication Skills | History, Physical Examination, and Patient Communication Skills |
| Selected Topics of Concern to Women | N/A |
A series of interprofessional SGH Education Summits in 2015, 2018, 2020, and 2021 broadened the approach from a focus on women to include all genders and sexes. At the 2020 SGH Education Summit, facilitated discussion groups composed of members representing health disciplines including dentistry drafted four interprofessional SGH core competency statements, or “tenets,” for educational programs in all health professions. A smaller interprofessional working group revised, finalized, and published the tenets ( Box 2 ).
-
Tenet 1: Demonstrate knowledge of sex and gender health.
-
Tenet 2: Evaluate literature and the conduct of research for incorporation of sex and gender.
-
Tenet 3: Incorporate sex and gender considerations into decision-making.
-
Tenet 4: Demonstrate patient advocacy with respect to sex and gender.
Discussion: the sex and gender health education tenets
The integration of SGH tenets in dental education will help dental schools incorporate SGH topics into dental curricula. This will establish best practices and calibration of education, support interprofessional collaboration, improve patient care, reduce bias, and advance inclusivity. Each tenet is outlined and discussed later, along with some applications for dentistry. Exhaustive discussion of all SGH topics is well beyond the scope of this article, so we recommend reviewing prior and emerging publications on this subject to further guide incorporation of SGH in dental education and practice. , ,
Tenet 1: Demonstrate Knowledge of Sex and Gender Health
The intent of Tenet 1 is summarized in Box 3 .
-
Dental practitioners should be able to
- •
Define sex and gender as variables that impact health and influence risk for disease at all stages of life.
- •
Describe and explain sex differences and the interaction between sex and gender in anatomy, physiology, and pathophysiology.
- •
Identify and describe psychosocial factors and behaviors that influence the risk of disease or health outcomes.
- •
Biomedical, behavioral, and clinical courses should highlight diseases and conditions with a sex and/or gender prevalence or differences in clinical presentation, treatment, or prognosis. This should accompany instruction related to screening, evaluation, risk assessment, diagnosis, treatment, health promotion, and disease prevention strategies. Some examples include eating disorders, head and neck cancer, osteoporosis, sleep apnea, temporomandibular disorders, autoimmune diseases, and developmental anomalies. Pregnancy and prenatal care should also be addressed. Additional examples are provided in Table 1 .
| Male Predominant Oral Pathologic Conditions and Lesions | Male: Female Ratio |
|---|---|
| Blastomycosis | 9:1 |
| Kaposi sarcoma | 9:1 |
| Lymphatic malformations | 2:1 |
| Nasopharyngeal angiofibroma | Almost exclusively in male individuals |
| Necrotizing sialometaplasia | Approaching 2:1 |
| Oral leukoplakia | 4:1 |
| Oral squamous cell carcinoma | 2.7:1 |
| Orthokeratinized odontogenic cyst | 2.6:1 |
| Paracoccidioidomycosis | 13:1 |
| Stafne bone defect | 8:1–9:1 |
| Warthin tumor | 10:1 |
| Female Predominant Oral Pathologic Conditions and Lesions | Female: Male Ratio |
|---|---|
| Proliferative Verrucous Leukoplakia | 4:1 |
| Sjögren syndrome | 9:1–20:1 |
| Polymorphous low-grade adenocarcinoma | 2:1 |
| Oral focal mucinosis | 2:1 |
| Granular cell tumor | 3:1 |
| Congenital epulis | 9:1 |
| Alveolar soft-part sarcoma | 2:1 |
| Rheumatoid arthritis | 2:1–3:1 |
| Focal osteoporotic bone marrow defect | 3:1 |
| Periapical cemento-osseous dysplasia | 10:1–14:1 |
| Florid cemento-osseous dysplasia | 9:1 |
| Adenomatoid odontogenic tumor | 2:1 |
| Mucous membrane pemphigoid | 2:1 |
| Systemic lupus erythematosus | 10:1 |
| Hyperthyroidism (Grave’s disease) | 5:1–10:1 |
| Hyperparathyroidism | 2:1–4:1 |
| Trigeminal neuralgia | 3:1 |
| Giant cell arteritis | 2:1–3:1 |
The remainder of this section on Tenet 1 will focus on a discussion of sex and gender differences in the underlying mechanisms of pain and disease. Currently, little information exists in the scientific literature on the effects of exogenous hormones on pain and disease in transgender persons.
Sexual dimorphism in pain mechanisms
Pain is commonly encountered in dental practice. Female individuals tend to be more sensitive to pain (lower pain threshold and tolerance) and experience pain more intensely than male individuals. Physiologic mechanisms underlying pain in male individuals are significantly different than those producing pain in female individuals. Estrogen and androgen receptors are found on many cells including neurons, glial cells, and immune cells. Sex hormones influence pain by binding to those receptors. Tissue-specific co-regulating proteins are sometimes involved. In general, testosterone appears to have antinociceptive effects, whereas the effects of estrogen and progesterone on pain vary and are less clear. For premenopausal female individuals, pain intensity may also parallel normal fluctuations in estrogen and progesterone during the menstrual cycle. Prolactin, which has numerous functions beyond lactation, is also linked to sex differences in pain. Estrogen promotes expression of prolactin receptor isoforms that are linked with pain.
Immune cells play an important role in pain and studies show sex differences in immune modulation of pain. , , Macrophages can induce pain or increase pain sensitivity via the release of proinflammatory cytokines. Microglia in the spinal cord increase pain in male mice but not females through testosterone-dependent binding of a lipopolysaccharide ligand to its toll-like receptor 4 (TLR4). TLR4 is linked to chronic pain and sepsis in male individuals, but not in female individuals. In female individuals, pain is preferentially modulated by a subset of helper T cells with proinflammatory properties (CD4+ Th1). , Female individuals exhibit a predominance of CD4+ Th1 T cells, whereas male individuals show higher levels of anti-inflammatory CD4+ Th2 T cells. These differences appear to be mediated by estrogen and progesterone levels in female individuals and testosterone in male individuals.
Sex hormones influence the stress-induced analgesia (SIA) system, a centrally mediated innate defensive mechanism that suppresses pain in response to a stressful stimulus. It involves opioid and glutamate receptors as well as neurotransmitters such as beta-endorphin and results in the inhibition of descending pain pathways. The N-methyl- d -aspartate (NMDA) glutamate receptor is involved in activation of SIA in male individuals but not female individuals. However, when estrogen production is significantly reduced, female individuals “switch” to the NMDA pathway. Exposure to testosterone during the neonatal period appears critical to this sex difference. A female-specific SIA pathway involves the melanocortin-1 receptor (MC1R), widely expressed in melanocytes and glial cells of the brain. Mutations that render MC1R nonfunctional also result in a “switch” to the NMDA system. ,
Gender and pain
Chronic pain (CP), a leading cause of disability worldwide, affects 20% of adults. Women suffer from CP conditions at higher rates than men. Biologic differences affect how pain is experienced, but the influence of sociocultural, psychological, and gender factors on pain sensitivity, experience, coping, and reporting cannot be overlooked. , In women who have experienced traumatic life events such as violence and abuse, the emotional context of pain and stress can lead to modifications in nervous, endocrine, and immune function, increased sensitivity to nociceptive stimuli, and greater susceptibility to CP conditions.
For example, symptomatic temporomandibular disorders (TMDs) are reported disproportionally by women. , Unraveling the relative contributions of sex and gender to symptomatic TMD is complex. Genetic predisposition has been linked to polymorphisms in certain pain-related genes. Estrogen receptors (ERs) abound in the temporomandibular joint, and polymorphisms in ER-alpha are associated with an increased risk of TMD. Additionally, blockage of ERs in synovial cells appears to inhibit cartilage and bone destruction in temporomandibular joint osteoarthritis. Estrogen levels also may explain the higher prevalence of TMD in women of reproductive years and a 30% increase in TMD in women taking estrogen-containing oral contraceptives. ,
Women are more likely to seek medical care than men. This could contribute to sex and gender disparities in the reported prevalence of some painful conditions including TMD. Depending on culture-specific gender roles and expectations, women may be more likely to report and outwardly express pain. , Coping mechanisms may also differ between men and women and can impact the CP experience. These psychosociocultural factors may also alter the pain experience itself.
The X chromosome: X-linked and autoimmune disorders
Most human cells have 46 chromosomes, including two sex chromosomes (XX for females/XY for males). In euploid female individuals, one of the two X chromosomes is randomly inactivated (“silenced”) during early embryologic development. The silencing process usually results in a relatively equal distribution of maternal versus paternal X chromosomes; however, skewing toward one allele may occur. The inactivation process is also imperfect, and some genes on the inactivated chromosome may “escape” silencing. These epigenetic phenomena may partially account for female-predominant diseases.
The Y chromosome contains 106 active protein-coding genes; many primarily involved in male sex determination and development. In contrast, the X chromosome contains 1098 active, protein-coding genes, with a wide array of potential gene products and functions. Sex-linked disorders occur when a mutated gene implicated in a particular disease is located on the X or Y chromosome. Given the large number of genes located on the X chromosome, most sex-linked disorders are X linked. X-linked recessive disorders, such as hemophilia A and B, primarily affect male offspring, although female offspring may also be affected in rare cases, when skewing or gene activation imbalances exist.
Sex chromosomes also appear to be responsible for fundamental physiologic differences that influence the risk of autoimmune diseases. The X chromosome holds many immune genes, which may help explain the greater prevalence of autoimmune disorders among female individuals. While the exact mechanism is not entirely clear, extreme skewing and activation of “escaped” genes are plausible explanations. Sjögren’s syndrome, up to 20 times more common in women, is a useful model to study the role of X chromosome genes such as toll-like receptor 7 (immune response initiation), CD40 ligand (B cell activation), C-X-C motif chemokine receptor (chemokine expression), and interleukin-1 receptor associated kinase (proinflammatory pathways activation). Other autoimmune diseases with a strong female predilection include systemic lupus erythematosus, systemic sclerosis, rheumatoid arthritis, autoimmune thyroiditis, Grave’s disease, and multiple sclerosis.
Sex differences in immunity
Female individuals exhibit a more vigorous immune response to infections and vaccination, which has been linked to sex hormones. Testosterone in male individuals is generally anti-inflammatory as it appears to inhibit the differentiation of B cells and helper T cells and the release of cytokines from T cells. , This may explain both the lower prevalence of autoimmune disorders and also the more attenuated immune response to vaccination and infection in male individuals. In contrast, estrogen’s effects on immune cells are typically but not always proinflammatory. Estrogen directly enhances the function of several immune cells, such as T cells, natural killer cells, and macrophages. Progesterone’s effects on immune function are less studied; however, it appears to reduce inflammation.
Bone health
Bone is formed, resorbed, and maintained by osteoblasts, osteoclasts, and osteocytes, respectively. In female individuals, bone mass and bone density sharply decrease following menopause. Nearly 20% of female individuals aged over 50 years are diagnosed with osteoporosis and more than 50% show low bone mass. Estrogen inhibits osteoblast expression of a ligand that activates osteoclasts (receptor activator of nuclear factor kappa B ligand [RANKL]). When estrogen levels drop after menopause, RANKL expression increases. In contrast, testosterone promotes bone mineral density through incompletely understood mechanisms. , The risk of medication-related osteonecrosis of the jaws is elevated in patients taking bisphosphonates and/or other antiresorptive agents for the management of osteoporosis.
Tenet 2: Evaluate Literature and the Conduct of Research for Incorporation of Sex and Gender
The intent of Tenet 2 is summarized in Box 4 .
