At one time, teachers forced pencils into right hands because they considered being lefthanded a pathology to be suppressed. We find that attitude hard to understand today, when handedness is considered a natural variation. A similar transition is occurring in attitudes toward people uncomfortable with the gender they were born into.

Even the terminology is evolving quickly: “Gender dysphoria” displaced “gender identity disorder” in the Diagnostic and Statistical Manual of Mental Disorders (DSM-V). The new term softens the implication that any pathology is involved and recognizes that sexuality involves a continuum rather than neat categories.

“There has been an enormous paradigm shift away from the notion that we have two sexes and people have to fit into one or the other,” Eli Coleman, PhD, director of the program in human sexuality at the University of Minnesota, told a standing-roomonly crowd at a session on transgender medicine at ENDO 2013. He said that a growing recognition that a “broad spectrum of people cross or transcend culturally defined notions of what it means to be a male or female” has led to the belief that gender incongruence should “no longer be called a disorder because gender variance is normal.” For people who do not fit comfortably into their assigned gender’s looks and roles, their distress originates primarily from the stigmatization that society imposes.

Gender dysphoria differs a great deal from handedness, however, because of the role of medical treatment — modern medicine has the power to bring patients’ physical bodies in line with their psychology. “Gender nonconformity is not pathological, yet gender dysphoria is a specific distress that can be alleviated through medically necessary treatment,” Coleman said. “Untreated or undertreated gender dysphoria leads to increased morbidity and mortality. We are negligent if we do not treat these cases. Hormone treatment can be very effective. It is not an experiment but a valid and well-researched treatment option, medically necessary for many people.”

Barrier to Treatment

A medical approach is needed because “gender identity is hardwired and unlikely to be overcome through external coercion,” according to Joshua D. Safer, MD, associate professor of medicine and molecular medicine at Boston University School of Medicine.

The success of treatment is illustrated by a high level of patient satisfaction. One large study found that more than 99% of patients were happy with their gender change decision. Despite the existence of care guidelines from the World Professional Association of Transgender Health (WPATH) and the Endocrine Society, Safer said that “the largest barrier to care for transgender patients right now is a lack of physician comfort with the topic.”

Role of Endocrinology

Endocrinologists play a central role in a multidisciplinary approach to treatment, according to Wylie Hembree, MD, of the College of Physicians and Surgeons at Columbia University Medical Center in New York. Hembree chaired the committee that wrote the Endocrine Society guideline, “Endocrine Treatment of Transsexual Persons,” (see box, below).

The Endocrine Society guideline recommends that a mental health professional with a thorough grounding in the DSM-V or the International Classification of Diseases-10 criteria make the diagnosis of gender dysphoria. But even with this referral, given the import of the condition, an endocrinologist should independently confirm that the patient fulfills the diagnostic criteria before initiating treatment.

The treatment is unique because most patients begin with normal hormone levels for their birth sex, and the endocrinologist’s goal is to replace these hormones with the normal levels of the opposite sex. Although this sounds like a radical change, Hembree says, “The goals of treatment are extremely simple and straightforward for endocrinologists. First, we need to medically ablate the endogenous hormone secretion, and there are many ways of doing that. Second, [we] administer the crossgender hormones.”

The process boils down to a variation on the kind of treatment that endocrinologists provide regularly, applying a wealth of knowledge about treating abnormal hormone levels in both men and women by raising or lowering them.

Hembree says that a two-step process starting with suppression is needed because simply giving estrogen or testosterone “results in incomplete endogenous hormone suppression the great majority of the time. That then gives rise to the need for high doses of hormones, which may, in fact, lead to complications not in the best interest of the patient.”

The guideline calls for aiming to match the normal levels found in native members of the new sex. For women transitioning to men, clinicians should aim for the middle of the normal range for testosterone, which can be achieved using an approach of incremental increases, Hembree says. In man-to-woman transitions, clinicians need to keep the testosterone levels low to avoid its masculinizing effects, while aiming for mid-level estrogen levels.

In the early days of gender transition medicine, the tendency to use high doses of hormones led to worries about the dangers of cross-gender hormones. Those worries have been alleviated by the use of appropriate doses. The practice of gender transition has now reached a maturity — along with its earliest patients — so researchers are studying the effects of continuing hormone treatments as patients age.

Of course, the need for continued suppression of endogenous hormones is obviated if the patient continues on to surgical reassignment with removal of sexual organs.

Many Cases Resolve Themselves

An important caution in the Endocrine Society guidelines concerns the age to begin treatment. Some 80% to 90% of very young children who experience distress about their gender identity grow out of these feelings, with their discomfort often resolving during puberty. The gender dysphoria of the remaining 10% to 20% significantly worsens during puberty, when their bodies start turning inexorably into what they feel is the wrong gender.

Clinicians can buy time for distressed adolescents to consider their options by arresting puberty using gonadotropin-releasing hormone (GnRH) analogues, while counseling continues. The suppression is reversible, enabling full pubertal development if the patient decides to remain in the natal gender. In contrast, if puberty is not stopped, the sexual characteristics that develop are irreversible, which can cause considerable distress for those who will choose to change genders. This approach has proven successful in identifying patients who will be satisfied with continuing to a transition.

Rising to the Endocrine

Although most clinicians consider gender dysphoria to be very rare, Hembree says that it may be more common than one might think from reading reported statistics. His experience from giving presentations at endocrinology meetings is that the sessions are always full and a surprising number of physicians tell him they have been approached by patients interested in treatment.

Coleman and Hembree recommended that physicians spend some time getting to know transgender patients better — more than the standard office visit allows — in order to lessen their own discomfort, to better grasp the condition, and to increase their understanding of their patients’ needs. That would help remove one of the biggest barriers to treatment.

Safer urged endocrinologists to learn more about gender dysphoria because the treatment is not “a narrow specialized thing” but lies at the heart of their specialty: “Hormone treatment for transgender patients follows a conventional endocrinology paradigm.”

— Seaborg is a freelance writer based in Charlottesville, Va. He
wrote about endocrinologists and osteoporosis in the April issue.

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