January 25, 2016 | Special HTA Reports
Diagnostic criteria for gender dysphoria in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition(DSM-5) includes "a marked incongruence between one's experience/expressed gender and assigned gender, of at least 6 months duration and manifested by a strong desire to be of the other gender or an insistence that one is the other gender or some alternative gender different than the assigned gender" (see the Ghosh article: "Gender Identity"). The diagnosis requires that at least five additional criteria be met, including a strong dislike of one's sexual anatomy, a strong preference for playmates of the other gender, and a strong desire for the primary and/or secondary sex characteristics that match one's experienced gender. The American Psychiatric Association (APA) notes that the condition is typically associated with "clinically significant distress or impairment in social, school, or other important areas of functioning." See APA's: Gender Dysphoria – DSM5.
According to the World Professional Association for Transgender Health (WPATH), children as young as two years may show features of gender dysphoria. Such features may include expressing a wish to be the other gender, unhappiness with physical characteristics, and preference for clothes/toys commonly associated with the other gender. While gender dysphoria will disappear in most children, feelings may intensify for some or just begin developing in others during puberty as secondary sex characteristics develop. Treatment approaches for gender-discordant adolescents include puberty suppression, cross-sex hormone treatment, and gender reassignment surgery. Adolescents may be eligible for puberty-suppressing hormones as soon as pubertal changes occur (may be as early as nine years of age). Puberty suppression therapy may continue for a few years, at which time a decision is made to either discontinue all hormone therapy or transition to a feminizing/masculinizing hormone regimen. Surgery may involve changing primary and/or secondary sex characteristics such as breasts/chest, external and/or internal genitalia, facial features, and body contouring. See WPATH Standards of Careand the ECRI Institute Hotline: Candidate selection criteria and surgical procedures for treating gender identity disorder.
Hormonal therapy for transwomen (individuals who were assigned male at birth but identify and live as women) may include estrogen, androgen-reducing medications or "anti-androgens" (e.g., spironolactone, cyproterone acetate, gonadotropin-releasing hormone agonists, 5-alpha reductase inhibitors), and progestins. Hormonal therapy for transmen (individuals who were assigned female at birth but identify and live as men) include testosterones and progestins (to assist in menstrual cessation). See WPATH Standards of Care.
Risks associated with feminizing hormones include venous thromboembolic disease, gallstones, elevated liver enzymes, weight gain, and hypertriglyceridemia. Risks associated with masculinizing hormones include polycythemia (increase in red blood cells), weight gain, acne, androgenic alopecia (balding), and sleep apnea. See WPATH Standards of Care. See the Drugs@FDA database for drugs and/or drug regimens used for hormone therapy for treating gender dysphoria.
For transwomen, surgical intervention involves removal of the testicles (orchiectomy) and creation of a clitoris (clitoroplasty) and vagina (vaginoplasty), as well as procedures to enhance facial femininity (frontal bone remodeling) and vocal characteristics (glottoplasty). For transmen, surgical interventions include removal of the breasts (mastectomy), ovaries (oophorectomy/adnexectomy), uterus (hysterectomy), and vagina (vaginectomy), along with creation of male genitalia. Surgical creation of a penis and scrotum can be achieved through phalloplasty, for which various techniques exist, including metoidioplasty. In many of these techniques, surgeons use skin grafts from the forearm or leg and also implant a penile prosthesis. See WPATH Standards of Care.
This Special Report systematically reviews clinical studies on gender dysphoria and treatments for this condition to assess their effectiveness and to determine how many of these studies have been approved by an institutional review board (IRB) and to examine the process by which individuals in these subjects are protected. Our searches looked for studies published between January 1, 2010, and January 8, 2016. We identified limited evidence from mostly low-quality retrospective studies. We did not identify any studies that met our inclusion criteria (see Methodology section) on the topic of puberty suppression therapy in adolescents. Evidence on cross-sex hormone therapy (one systematic review and three primary studies) reported on psychological- and sexual-related outcomes, quality of life, risk of breast cancer, and adverse events. Evidence on sexual reassignment surgery (three systematic reviews and four primary studies) was mostly limited to evaluations of male-to-female (MTF) individuals undergoing vaginoplasty, facial feminization surgery, and breast augmentation. Outcomes included mortality, patient satisfaction, physical well-being, psychological- and sexual-related outcomes, quality of life, suicide, and adverse events. None of the included studies reported any serious adverse events.
Study authors called for the need for standardized protocols and prospective studies using standardized measures for correct interpretation and comparability of data.
Puberty suppression therapy: We did not identify any studies that met inclusion criteria for this topic.
Cross-sex hormone therapy: One systematic review and 3 primary studies (1 nonrandomized controlled/comparison, 2 database reviews) evaluating 3,392 transgender individuals addressed this topic. Outcomes reported in these...