ORLANDO – In the case of transgender youth and adults – those with what is now called gender dysphoria – physicians are faced with treating individuals who generally have no physical disease or abnormalities.
Endocrinologists are the professionals who are often tasked with the medical aspects of treating gender dysphoria. In an effort to help them understand the underpinnings and aspects of the conditions, Dr. Stephen Rosenthal, professor of pediatrics and medical director of the Child and Adolescent Medical Gender Center at the University of California, San Francisco, reviewed current knowledge about the biological basis for gender identity, current treatment models, and barriers to care of patients with gender dysphoria.
Dr. Stephen Rosenthal
Speaking at the annual meeting of the American Association of Clinical Endocrinologists, Dr. Rosenthal said the dysphoria derives from the significant emotional distress that may be associated with a transgender identity, essentially from the social and psychological pressures of being born and living in a body (the “natal sex”) that does not match an individual’s gender identity, defined as one’s fundamental sense of self as male or female. “It’s not always limited to those two choices, and it’s not always binary,” he said, since individuals may identify with aspects of both or, at times, neither gender.
He defined some terms, such as transgender, which refers to a transient or persistent identification with gender different from the one others assume based on physical sex characteristics at birth. That gender becomes the one of rearing, which may not be how the individual feels growing up. Gender identity should not be confused with sexual identity or orientation because people of any gender can have any sexual orientation.
“Gender Identity Disorder,” a term used in the DSM IV (Diagnostic and Statistical Manual of Mental Disorders IV) has been replaced by “Gender Dysphoria in Children” in DSM 5. And even that term may be revised since transgender identity in itself is not a pathology.
In one survey of 28,176 people, 0.5% self-identified as transgender. Another survey showed statistically significant risks associated with being transgender. Comparing 180 transgender youth with 180 non–transgender youth (average age, 19.6 years; range, 12-29 years), researchers found a two- to threefold increased risk of depression, anxiety disorder, suicidal ideation, suicide attempt, and self- harm without lethal intent among the transgender youths. Parental support helped alleviate some of these risks, especially suicide attempts, but did not eliminate them entirely; that support also contributed to better mental and physical health, improved self-esteem, and even adequate food and housing for transgender adolescents.
Clues to biological influences
A complex interplay of biological, environmental, and cultural factors affect the determination of gender identity. Evidence points to the role of biology in gender identity development through studies of genetics, hormones, and the brain, but none of these is a “litmus test” for gender identity, Dr. Rosenthal said.
A study of 23 monozygotic twin pairs, 21 same-sex dizygotic twin pairs, and 7 opposite-sex twin pairs showed a 39.1% concordance for gender dysphoria among the monozygotic twins but none for the other sets.
Most transgender individuals do not have any obvious disorder of sexual development, but that is not to rule out a role of prenatal or postnatal androgens (specifically enzymes of the steroid pathways), androgen insensitivity, or extragonadal sources of androgen, as in congenital adrenal hyperplasia (CAH). Among 250 46XX females with CAH raised as female, 5.2% had male gender identity or gender dysphoria (a 10- to 20-fold increased risk vs. controls), suggesting a possible role for prenatal androgens in gender identity development.
A neurobiological basis for transgender is supported by some studies of sexually dimorphic brain structures but is by no means conclusive. Numerous studies of gray and white matter showed that sexually dimorphic structures are more closely aligned with gender identity than with physical sex (even before cross-sex hormones have been applied). But morphometry on areas of the brain that show the largest sex differences found that variability was more prevalent than was consistency in the 1,400 brains studied.
Tests of “functional sexual dimorphism” used PET or MRI to measure changes in regional blood flow in the anterior hypothalamus when control adolescent girls or boys or those with gender dysphoria were asked to smell substances containing pheromones of the opposite sex (for girls: androstadienone in a mixture of male sweat and semen; for boys: estrogen-like compounds in urine of pregnant women). Both girls and boys with gender dysphoria had responses significantly different from those of their respective controls.
Natural history of gender dysphoria