Transgender patients seek endocrinology care more often, require more information

Throughout human history, there have been people who were transgender, individuals whose gender identity and expression differ from the sex they appear to be at birth. Some cultures accepted these differences, whereas others violently opposed them. The current world culture is in the midst of a sea change with regard to gender. And although there is still open hostility in some sectors, in many places, there is an increased openness toward people who are gender-nonconforming.

“The media has [started to present] the story of kids and adults who are transgender … as real people who do not do this for some kind of fetishism,” Norman P. Spack, MD, an endocrinologist and associate professor of pediatrics at Harvard Medical School, told Endocrine Today.

Access to medical care for transgender patients is becoming easier. “You have to account for the fact that it wasn’t long ago that we didn’t have programs [to help these people],” Spack said.

After opening the first US multidisciplinary gender clinic at his institution in 2007, Spack saw a fourfold increase in the number of transgender people seeking medical interventions.

Currently, there are about 21 such centers in North America that are training pediatric residents and fellows in the care of transgender patients.

In addition, because information on transgender issues and medical care is more easily accessible, more patients are seeking interventions earlier in life, leading to better results.

“It might just be that it’s all presenting earlier in life because it’s easier for kids to figure it out and it’s more acceptable,” said Daniel Metzger, MD, a pediatric endocrinologist and a clinical professor of pediatrics at the University of British Columbia in Vancouver.

As a result, endocrinologists around the world are seeing more patients in their offices who are considering or undergoing medical interventions to affirm their gender. Experts discussed with Endocrine Today how to best provide the safe, effective care required for transgender patients.

Consequences of gender dysphoria

Some transgender people do not seek medical interventions and live well as gender non-conformists, whereas others experience significant distress or confusion when their brain and genitals do not match, which also is known by the clinical term gender dysphoria.

Gender dysphoria varies by individual and generation, according to Diane Ehrensaft, PhD, a developmental and clinical psychologist and the director of mental health for the Child and Adolescent Gender Center in San Francisco. “For example, we’d have to talk differently about the cohort of gender-nonconforming people who are 10 years and younger right now vs. those who are in their 50s and 60s. A lot of it has to do with the social environment in which they’ve grown up.”

Formerly known in the Diagnostic and Statistical Manual of Mental Disorders (DSM) as gender identity disorder, gender dysphoria can manifest as anxiety, depression, aggression or social withdrawal.

“In teenagers, you might see suicidality,” Ehrensaft said. “You see acting out. You might see substance abuse. In young children, you might see an inability to concentrate in school and the misdiagnosis of having attention-deficit disorder.”

The suicide risk is high; 41% of transgender adults in the United States have attempted suicide, according to the findings of the National Transgender Discrimination Study.

Etiology most likely multifactorial

Although researchers are actively studying the etiology of nonconforming gender, not much is known yet. “There [are] areas in the brain that seem to be important for gender identity,” Vin Tangpricha, MD, PhD, an associate professor of medicine in the division of endocrinology at Emory University, told Endocrine Today. “[Researchers are] focused on the hypothalamus. We may not find an exact cause; it’s probably multifactorial.”

Current investigations are headed in the direction of considering differences in the brains of transgender or gender-nonconforming people which may be caused by constitutional and fetal environmental factors, according to Ehrensaft. “We know also that nurture plays a strong part and culture plays a strong part in gender nonconformity,” she said. “For transgender people, increasingly we’re finding as we have around gay individuals, that there is a strong nature element to it; it’s not a choice, but rather simply who they are.”

To help endocrinologists with the management of transgender patients, the Endocrine Society published clinical guidelines in 2009 for the endocrine treatment of transgender people. The guidelines, which the organization plans to update next year, recommend the provision of a “safe and effective hormone regimen that will suppress endogenous hormone secretion determined by the person’s genetic/biologic sex and maintain sex hormone levels within the normal range for the person’s desired gender.”

Psychological assessment

The first step for the patient is to get psychological counseling. “If [the patients] don’t have some support behind them, my giving them medications may just lead to all sorts of troubles,” said Michael Kleerekoper, MD, MACE, a professor in the department of internal medicine and section chief of the endocrinology division at the University of Toledo in Ohio.

Although the assessment is strongly encouraged as the initial part of treatment now, that may change when the society updates the guidelines. Getting access to a psychologist qualified to treat transgender patients has proved difficult for some.

“Many cities don’t have a gender specialist,” Tangpricha said. And this has been a barrier to treatment for some patients. “So any endocrinologist who feels comfortable enough treating someone who is gender-nonconforming, they can go ahead and treat them. I suspect that the majority of endocrine specialists don’t yet have that comfort level and may need some input from a mental health provider who has some expertise.”

In most cases, the mental health professional plays a crucial role in shepherding the patient through this process.

“All I do is help [the patients] with medications,” said Kleerekoper, who is also an Endocrine Today Editorial Board member.

The psychological assessment gauges level of distress, if there is any, and how to help the transgender person. “We’re looking to assess if there’s a gender dysphoria and, if yes, how to support this child,” Ehrensaft said. “What we find is that people who get support, either social or medical, have better mental health outcomes.”

The mental health professional can use standardized measures or clinical interviewing to determine whether the patient has gender dysphoria.

“A combination of the two usually works best in documenting that this person is really struggling around their gender,” Ehrensaft said. “Not every gender-nonconforming person is struggling. But if they’re struggling, we use those protocols to identify if they’re struggling and also to recommend what should come next in terms of mental health and/or medical interventions and strengthening of social supports.”

Although the main focus of the counseling is to support the patient, the family needs help as well.

“The other really big thing that we all know is a need to support the parents and the family,” Metzger said. Although starting treatment is often a huge relief for patients, some parents may need time to adjust.

“They are still mourning the loss of their little boy, but their little boy is already becoming a woman,” Metzger said. “We focus on the patient, but we really need to keep our focus on the parents because they are often struggling.” Family support is lacking in many treatment centers, he added.

Medical interventions

If the psychologist determines that the patient is ready, the individual can pursue cross-hormone treatment under the supervision of an endocrinologist or any physician who has expertise in prescribing sex hormones.

The current Endocrine Society guidelines recommend against hormone treatment in prepubertal patients, given how often children change their minds after the onset of puberty.

“[For] prepubertal kids, everybody would agree that it’s much more of a wait-and-see kind of thing,” Metzger said. “We do know that not all kids will have persistence of gender nonconformity after puberty starts.

“But that doesn’t mean that [these children] don’t benefit from counseling, from being with other kids or from family interventions just to make sure that they’re safe,” Metzger said.

Questions remain about the most appropriate way of supporting prepubertal children. “Do you let them wear what they want to school?” Metzger said. “Do you call them by their new name? What pronouns do you use?” For patients this young, the caregivers need to determine how much support is appropriate and how much the child’s local society will allow that to safely happen.

There are three schools of thought among psychologists. Some operate from the gender-affirmative model, in which they “support the social transition of a prepubertal child after collaborative evaluation with the family,” Ehrensaft said. Some follow a wait-and-see approach, whereas the third group works to get the child to accept the sex label on their birth certificate.

Puberty defines who is transgender

Caregivers must take special care with pubertal children, too. “Puberty … actually defines who is really transgender,” Spack said. “The work of Kenneth Zucker and others has shown that prior to puberty, a very high percentage of kids who act in a cross-gender way actually accept the puberty that comes with their genotype.

“The other 20% to 25% of kids, who absolutely decompensate at the initiation of puberty, whose fantasy that with puberty they will turn into their affirmed gender is shattered, often have major psychological problems with the beginning of puberty,” Spack said.

For these patients and adolescents who are unsure of the path they wish to follow, the endocrinologist can prescribe puberty blockers. These gonadotropin-releasing hormone (GnRH) analogues, which are typically used to halt puberty in patients with central precocious puberty, block the pituitary gland’s ability to release luteinizing hormone and follicle-stimulating hormone, Spack said.

“[Puberty blockers] put [children] on hold for a while, while they’re getting their counseling … while they’re perhaps doing a bit of social transition,” Metzger said. “It gives everyone a bit of breathing room to figure out what the longer-term plan should be.”

Puberty blockers have a record of demonstrated safety and efficacy. A study by Delemarre-van de Waal and colleagues showed that GnRH analogues suppressed puberty without negatively affecting bone health in transgender adolescents. Of the 127 patients in this study, those who began treatment late in puberty had higher bone density and their bone mass stabilized during treatment. Although patients in early puberty had bone mass increases during treatment, these increases were less than they would have been if the patients had experienced their own puberty. Overall, the results demonstrated that bone development catches up once cross-sex hormones are administered.

Besides being safe, puberty blockers are completely reversible. “We don’t think of them as having long-term effects,” Metzger said.

At the initial endocrine consultation, Kleerekoper thoroughly reviews the patient’s medical history and discusses the available treatment options. In addition, Kleerekoper has an open discussion with the patient about their desires.

“Generally, they open widely and tell me how long they’ve wanted to do this, why they’ve wanted to do this,” Kleerekoper said. “They’re not quite sure why this has happened, but they’ve known since they were kids.”

Irreversible changes

When the patient is ready for cross-sex hormones, which is age 16 years, according to the clinical guidelines, it is critical that the endocrinologist counsel them about what is reversible and irreversible with regard to hormone therapy. Puberty blockers are easily reversible, but many of the changes related to cross-sex hormones are not. For example, breast tissue may be irreversible. “There may be changes in their genitalia that won’t reverse, like clitoromegaly, voice changes,” Tangpricha said.

In addition, cross-sex hormones may reduce fertility, which may be permanent, even if the medications are withdrawn.

“We’re talking about either banking up sperm or saving eggs,” Tangpricha said.

The clinical guidelines recommend surgery for adolescents who desire it when they have achieved a satisfactory societal role change and they are satisfied with the effects of their hormones. However, the guidelines suggest deferring surgery until patients are aged 18 years.

For adults, there is no upper age limit for pursuing medical interventions. “Any adult who is healthy enough to receive hormones can be seen,” Tangpricha said.

It is important in adults to evaluate any medical conditions that may be worsened by hormone depletion or cross-sex hormone therapy before starting treatment, according to the guidelines.

Treatment for girls and women affirming a male gender is the androgen testosterone, which can be delivered parenterally or transdermally, according to the clinical guidelines.

For men and boys affirming a female gender, hormone treatment is more complex and generally combines an antiandrogen and an estrogen. Estrogen can be administered orally as a conjugated estrogen or estradiol, as transdermal estrogen or parenteral estrogen esters.

Kleerekoper monitors his patients every 3 to 6 months. “It takes a while to make those changes,” he said.

For adults, surgery is recommended only after a year or more of hormone treatment. The endocrinologist and mental health provider must approve and indicate that surgery is advisable for the patient.

Issues related to long-term hormone use

Some risks are associated with long-term hormone use. Genetic men and boys who affirm a female gender have some risk for breast cancer that is lower than genetic women but higher than genetic men who are not transgender, according to Spack.

Transgender patients could be at risk for diabetes and cardiovascular problems.

“Genetic females who affirm a male identity tend to redistribute their fat in a more female way, which may not be good for things like diabetes if they don’t exercise,” Spack said. “Females-to-males are at higher risk for cardiovascular disease, if they shift their weight to their abdomen. Testosterone treatment also lowers their HDL-cholesterol levels.”

The endocrinologist should also measure bone mineral density if the patient has osteoporosis risk factors, according to the guidelines.

In addition, there is a link between oral estrogen and blood clots. “Probably more and more patients will switch to other forms of estrogen, particularly as they come out of their 20s and 30s and are moving toward midlife to decrease the risk for blood clots,” Metzger said.

With about 21 centers in North America available to treat transgender patients, and new centers opening monthly, access to care is greatly improved. Now, the hope is that more endocrinologists will expand their knowledge base and their comfort level in treating transgender patients.

“Every endocrinologist should know about this condition, and in an ideal world, every endocrinologist should feel comfortable treating [transgender] patients,” Tangpricha said. “If they don’t feel comfortable, they should at least know what the resources out there are and know people who they can refer these patients to for proper treatment.”

The endocrinologist must “educate themselves, know that this condition exists and know that there are available resources,” Tangpricha said. — by Colleen Owens

Can transgender teens fully understand the loss of fertility that comes from administration of cross-sex hormones?

Transgender teens grasp that biological children are unlikely

We have 300 transgender kids in the practice, who range in age from 4 to 25. For the kids who are starting puberty and going on to blockers or cross-sex hormones, fertility is a large part of the conversation. My experience of it has been that transgender teenagers have incredible insight about the structure and nature of families. They understand that biological children are unlikely in their future, especially now that we are moving into blocking earlier and moving into cross-sex hormones later. I think that by the time young people reach 13 or so they have a very good understanding of what that means.

They express incredible thoughts and tremendous insight about their fertility, acknowledging that they will likely not be able to bear, or biologically contribute to children, should they choose to have families in the future. They recognize that as part of the decision making that goes along with deciding what to do when their gender is not aligned with their assigned gender.

Where the confusion often comes is that people believe that what transgender individuals are deciding about is their gender. They are not deciding their gender; they are deciding what to do when their gender identity is not aligned with their assigned birth gender. Sometimes that entails decisions between bad and bad, and that makes people desperately uncomfortable. Most people want to make a choice between good and bad; they don’t want to make a choice between bad and bad. For teenagers who want to transition early, they have to choose between the incredible benefits of an early transition and not being able to have biological children. That is a hard decision, a bad one.

Transgender teens have great recognition about that. Some of them may regret that decision. A lot of young people experience great sadness about it. They recognize that it is a loss.

There are others who say, “Well, I was adopted and I recognize the importance of providing love in a home for a child who doesn’t have love in a home.” There are kids who say things like, “Well, there are a lot of ways to have a family, Dr. Olson.” They’re trying to prove it to me as I’m asking about it.

I found that in my work, most of the mourning really comes from the parents of the young person; it is the parents who have a story that they are mourning, and that story usually includes biological grandchildren. Sometimes, they are the ones who have more work to do around this topic than the young person.

Johanna Olson, MD, is the medical director for the Center for Transyouth Health and Development at Children’s Hospital Los Angeles and an assistant professor of Clinical Pediatrics at the Keck School of Medicine in Los Angeles. Olson reports no relevant financial disclosures.

Some transgender teens may not understand the full ramifications

Is any teenager capable of understanding the ramifications of decisions regarding reproduction? Many people do not recognize the importance of fertility until much later — until they have a partner, until they have the means to support a child, etc. While most young people do not need to consider this question, young transgender adolescents must think about it.

These youngsters must try to imagine a life of not passing in their affirmed gender role if they avoid treatment now for the sake of their fertility, facing the possibility of a lifetime of stigma, as people who do not appear to be male or female. These are problems that can be easily avoided with early treatment.

Yet, we do not want young people embarking on irreversible procedures that they will regret later on. An adolescent treated with cross-gender hormones may become a transgender adult who has forfeited their right to reproduce, although it was done with medical help that was provided with the best of intentions.

The reality is that transgender youngsters are asking for cross-sex hormonal interventions at a young age, during a narrow window of opportunity, treatments that will prevent fertility down the road. But these treatments will also provide the possibility of living a full life without stigma and one that fits with their self-concept. By preventing the development of the despised secondary sex characteristics from the assigned gender, the treatments offer the possibility of a lifetime of radically reduced gender dysphoria, a life where the adolescent can move in circles of their affirmed gender pretty much invisible to their cohorts. They have the opportunity to be like everybody else. But they will not be able to reproduce.

Many transgender adults envy the opportunities afforded young transgender kids today, the loss of fertility notwithstanding. Many regret that they did not transition earlier. They grieve about the pain, suffering and the misgendering they endured that could have been avoided had they had early and appropriate interventions.

How then do we ensure reproductive rights of transgender young people even if they themselves are not concerned?

One, we can make sure they have quality, informed medical care and in most cases, parental support, so that all affected persons receive informed consent. Second, we can make sure to put them on reversible puberty blockers until they are mature enough to make more decisions about how best to move forward. And third, we can provide them with information on sperm and egg banking so that they have the opportunity at the appropriate time to have their own biological children.

In summary, even though most young people may not be able to understand the full ramifications of lost fertility, that shortcoming cannot be the only concern mitigating their eligibility for treatment. Their wish for early treatment and its obvious positive outcome, the strong support from older trans people who found themselves in similar circumstances but without the opportunity for intervention, and the existence of other reproductive options such as banking need to be taken into account. Technology may also be developing new opportunities in the future allowing even more options.

Lin Fraser, EdD, is in private practice with a 35-year subspecialty working with transsexual, transgender and gender nonconforming people. She is also the immediate Past-President of the World Professional Association for Transgender Health (WPATH). Fraser reports no relevant financial disclosures.