Medical Treatment for Gender Dysphoria: A Review of Risks and Benefits

//Medical Treatment for Gender Dysphoria: A Review of Risks and Benefits

Medical Treatment for Gender Dysphoria: A Review of Risks and Benefits

2019-01-30T02:41:12-07:00 September 26th, 2016|Health and Medicine|

By Elizabeth Gore; Neurobiology, Physiology, and Behavior; ’17

Author’s Note:

“This is my literature review for UWP 104F. I chose the topic of transgender medical treatment outcomes because of the recent increase in transgender inequity in the media. In the last 10 years, with the emergence of World Professional Association for Transgender Health (WPATH), there has been an increase in studies and resources available to clinicians. This emergence, while promising, is new and few clinicians feel comfortable treating these patients. This paper focuses on the outcomes of treatment on the wellbeing of patients struggling with gender dysphoria (GD). I originally chose this topic because of my connection with several transgender individuals. I was also curious as to what could be done to alleviate GD because I had heard about the prevalence of mental disorders and suicide rates among these patients. I do not focus on the treatments themselves in my literature review but on the wellbeing of the patient after receiving treatment. I thought that this was the important emphasis because the overall goal of these treatments is to improve the wellbeing of the patient.”


Individuals experiencing gender dysphoria (GD) have a marked incongruence between their assigned and experienced gender, resulting in great distress1. Issues, such as transgender bathroom policies, are exposing transgender rights to the mainstream media, highlighting this population’s lack of equity. Social marginalization can cause high rates of depression, anxiety, self-harm and suicide in this population2. In addition, barriers to health care leave these individuals at high risk for negative health outcomes2.

GD is accompanied by a desire to transition to an individual’s gender identity1. An increasing number of gender nonconforming youth are seeking medical intervention, yet in many cases few providers feel educated about and comfortable with treating these patients, making this population vulnerable2,4. There are guidelines for transitioning developed by respected organizations, such as the World Professional Association for Transgender Health (WPATH) and the Endocrine Society4. These guidelines, which were developed after conducting clinical and academic research, are meant to guide clinicians to provide evidence-based medicine for their transgender patients, but it is important to note that there is not a universal consensus within the medical community4 . There is disagreement among clinicians on whether the risks of transitioning or withholding treatment result in worse outcomes4. The purpose of this literature review is to analyze the benefits and risks of medical intervention to the wellbeing of patients experiencing GD in order to provide guidance to general practitioners. This literature review will first discuss the eligibility for beginning the transitioning process, followed by the outcome of  the medical stages of transitioning, and finally, the risks associated.


To be eligible for treatment in the following studies, patients must meet the standards established by WPATH5. These standards include a presence of GD that is intense and long lasting, an increase in GD when beginning puberty, an absence of any mental or physical problems that would affect treatment, and patient consent contingent on parental support5. Each guideline is essential to providing accurate care for these patients. For example, it is important to wait until GD increases during puberty because GD in prepubertal children often desists, while GD in adolescents during puberty have high rates of persistence5,9. Another WPATH standard for transitioning is parental support, which was shown in a study to be linked with buffering mental health illness in adolescents with GD6. These factors are all necessary to ensure a positive transitioning experience5,8.

Medical Interventions

Puberty Suppression

Puberty suppression can be used as both a diagnostic tool and a medically valuable treatment option for youth experiencing GD7,8,9. Puberty suppressors are drugs that prevent puberty from starting. Because puberty suppression tends to be fully reversible, it gives youth time to explore their gender identity while preventing their body from irreversibly changing during puberty7,8,9. It also makes surgery less redundant7. The following studies investigated the effects that puberty suppression had on psychological functioning and patient well-being after undergoing psychological support.

A study that tested puberty suppression and psychosocial functioning compared two groups of adolescents experiencing GD8. In this study, psychologists and psychiatrists conducted clinical interviews, psychological assessments, and questionnaires in order to evaluate the effects of psychological support on GD adolescents8. In the group with adolescents eligible for puberty suppression, six months of psychological support did not improve their psychosocial functioning 8. In contrast, the adolescents’ psychosocial functioning significantly improved to levels equivalent to their  peers without GD after being on puberty suppressants for 12 months8. The second group of adolescents had their puberty suppression delayed due to not meeting the WPATH standards8. This group improved in psychosocial functioning with psychological therapy, but there was no further improvement after six months, and they scored lower in psychosocial functioning than their GD peers even after 18 months of therapy8. Although psychological support improved functioning, puberty suppression is associated with further overall improvement and is argued to be an effective treatment for youth experiencing GD8.

An additional study showed promising effects of puberty suppression by testing psychological functioning and well-being in 55 transitioning young adults9. Using questionnaires, participants were evaluated 3 times: before puberty suppression, at the introduction of cross-sex hormones (CSH), and at least 1 year after gender-reassignment surgery (GRS)9. Researchers in the study found that puberty suppression did not alleviate GD 9. Puberty suppression does alleviate distress, but to fully remit GD, additional actions were required, such as CSH and GRS9.

Cross-Sex Hormones and Gender-Reassignment Surgery

Unlike puberty suppression, CSH and GRS are irreversible treatments10. CSH has a physical impact on both transmen and transwomen, eliciting changes that assist in presenting as their preferred gender10. GRS alters an individual’s sex to resemble their experienced gender. The following three studies focus on different aspects of patient’s well-being after CSH and GRS treatments.

A study that included 55 young transgender adults with similar representation of transmale and transfemale participants, observed that GD was alleviated after the start of CSH and GRS treatments9. In this group, the patients who  received treatment of CSH and GRS improved their body image satisfaction and psychological functioning to values similar to that of the general population9. These patients also showed particular improvement with anger, anxiety, and behavioral and emotional problems9. None of the participants regretted going through the transitioning process9. These results suggest that medical intervention may produce overall global functioning improvements for individuals experiencing GD.

A defining aspect of GD is distress. A study was conducted to test the stress level in transsexual individuals before and after starting CSH therapy11. At the beginning of the study, patients with GD who had not received hormone therapy had high levels of stress, insecurity, and anxiety11. Before they began treatment, participants had their level of cortisol measured11. Cortisol is a hormone released in response to stress, and can be used to measure perceived stress. Cortisol level was measured by taking a blood sample one hour after waking up for three days and perceived stress was determined using a self-reported evaluation11. It was found that all participants had higher levels of cortisol and perceived stress before CSH therapy, compared to levels found in the general population11. Patients treated with CSH therapy for one year reduced their cortisol levels equivalent to the general population11. It was also found that patterns of stress, such as insecurity and anxiety, were alleviated11. The data suggests that patients benefited from CSH therapy9,11.

In contrast to the studies previously mentioned that focused on short-term results, a long-term follow-up study assessed overall evaluation of participant’s transitions, 15. 71 participants first underwent a clinical interview, and then were required to fill out a separate  follow-up questionnaire with periodic standardized questionnaires to keep a record of their changes over a long time frame15. The evaluations reported that using medical interventions reduced their GD15. Individuals reported high levels of well-being, with most employed, and sustaining satisfactory social lives15. The only common regret was wishing to have made the transition earlier in life7,9,15. It was found that most participants were in steady relationships and assessed their satisfaction with their relationships, on average 4.52 out of 515. Similar results were found when evaluating friendships and relationships with their parents, which were 4.3 and 4.08 out of 5 respectively15.  There were three main themes that researchers found in participants: they felt positive about their decision to pursue treatment, none wished to reverse their decision, and they overall had a high level of life satisfaction15.  The long term effects of medial intervention seems promising for improving the wellbeing of individuals with GD 4,15.

Risk Assessment

Due to the lack of abundant long-term studies on the risks of transitioning, there is some concern about long-term medical implications4,7. This section will review studies that investigated potential risks for individuals who pursue medical intervention.

In a case report, a 22-year follow-up was conducted with a patient, B, a transman who began puberty suppression at age 13, and later followed up with CSH and SR7. At age 35, he presented a healthy blood pressure, height, weight, bone mineral density above the 50th percentile, normal serum values for lipids and showed no signs of diabetes7. In this case report, there was no observed negative risk7.

Additionally, since puberty suppression occurs during a time of major brain development, a study investigated the effects that puberty suppression has on executive functions to identify any risk associated12. They compared two groups of GD adolescents: one group treated with puberty suppression and the other group left untreated12. When data from the two groups were compared, the findings suggested that there is no difference in executive functioning of the patients12.

This next study focuses on the effects of CSH. It analyzed the physiological effects of 106 individuals with GD treated with CSH13. It found that 2% of the participants developed erythrocytosis and elevated liver enzymes. Transmen did see a large increase in acne and hair loss due to the increase in testosterone from their therapy13. Despite some negative outcomes, overall data showed that CSH was effective and carries a low risk  of side effects and severe negative outcomes13 . An additional report on CSH in transsexuals suggests that treatment is safe and there is low risk for osteoporosis, cardiovascular disease, and cancer14. These findings predict that there is low short-term risk associated with transitioning, but clinical data for long-term risks is insufficient.


With an increasing number of individuals presenting with GD, it is important to understand the outcomes of transitioning2,3. It appears that pubertal suppressants are a helpful aid for adolescents experiencing GD2,3,4,5,6,7,8,9,10,11,12,13,14,15. Furthermore, CSH and GRS has been shown to alleviate GD2,3,4,5,6,7,8,9,10,11,12,13,14,15. While these studies show promising results, there is little data available on the long-term risks of treatments. Despite this, immediate risks of delaying treatment include depression, self-harm, and suicidality2,3,5,6,7.  While there may not be a consensus in the medical community, some professionals believe that withholding medical interventions for GD does more harm than good and can cause great distress and poor health outcomes4. As shown by the increase of transgender issues in the media, there is also little consensus by the public.

Another aspect of healthcare that can improve GD patients’ health outcomes is providing culturally competent care. Clinicians who care for these patients have a responsibility to provide medical care that is nonjudgmental and comprehensive. Being an ally is especially important for patients in this population, because they experience higher instances of health care inequity. The increase of the quality of life, coupled with the little known risk, suggests that medical intervention is a good option for patients with GD. To provide the best quality care, it is important that health care providers consult the Endocrine Society and WPATH guidelines when treating GD patients.

Table 1. Definitions
Gender Dysphoria (GD) Long-standing distress resulting from incongruence between one’s experienced and assigned gender
Gender The inherent sense of masculinity and femininity
Gender Identity Identification as male, female, or anywhere in between on the gender spectrum
Gender Nonconforming Atypical gender expression for assigned gender
Transition Period in which transgender individuals learn to live as a member of their gender
Cross-Sex Hormone (CSH) Sex hormones administered to alter an individual’s secondary sex characteristics

(Androgens for transmen and estrogens for transwomen)

Gender-Reassignment Surgery (GRS) Surgical procedures to alter an individual’s sex to resemble their experienced gender
Transgender Umbrella term that embraces the full diversity of people who live differently than their birth assigned sex
Transmen/FtM Transition from female to male
Transwomen/MtF Transition from male to female
Transsexual Subset of transgender, with the desire to transition to their experienced gender

Works Cited

  1. American Psychiatric Association. “Diagnostic and Statistical Manual of Mental Disorders” (5th, ed.) 2013
  2. Olson J, et al. Baseline Physiological and Psychological Characteristics of Transgender Youth Seeking Care for Gender Dysphoria. J Adolesc Hea. 2015:57:374-380
  3. de Vries AL, Cohen-Kettenis PT. Clinical management of gender dysphoria in children and adolescents: the Dutch approach. J Homosex. 2012;59(3):301–320
  4. Vrounraets LJ, et al. Early Medical Treatment of Children and Adolescents with Gender Dyshporia: An Empirical Ethical Study. J Adol Hea. 2015:57:367-373
  5. Coleman E, Bockting W, Botzer M, et al. Standards of Care for the Health of Transsexual, Transgender, and Gender-Nonconfroming People, Version 7. International Journal of Transgenderism 2012:
  6. Simons L, et al. Parental Support and Mental Health Among Transgender Adolescents. J Adol Health 2013:53:791-793
  7. Cohen-Kettenis PT, Schagen SE, Steensma TD, et al. Puberty Suppression in a Gender- Dysphoric Adolescent: A 22-Year Follow-Up. Arch Sex Behavior 2011:40:843-847
  8. Costa R, Dunsford M, Skagerber E, et al. Psychological Support, Puberty Suppression, and Psychological Functioning in Adolescents with Gender Dysphoria. J Sex Med 2015;12:2206-2214
  9. de Vries, AL, et al. Young Adult Psychological Outcome After Puberty Suppression and Gender Reassignment. Am Aca of Peds 2014
  10. Smith, KP, et al. Gonadal Suppressive and Cross-Sex Hormone Therapy for Gender Dysphoria in Adolescents and Adults. Pharmacotherapy . 2014:34:1282-1297
  11. Colizzi M, et al. Hormonal Treatment Reduces Psychobiological Distress in Gender Identity Disorder, Independently of Attachment Style. J Sex Med 2013:10:3049-3058
  12. Staphorsius AS, et al. Puberty Suppression and Executive Functioning: An fMRI-study in Adolescents with Gender Dysphoria. Psychoneuroendocrinology. 2015:56:190-199
  13. Wierckx k, et al. Cross-sex Hormone Therapy in Trans Persons is Safe and Effective at Short-Time Follow-up: Results from the European Network for the Investigation of Gender Incongruence. J Sex Med. 2014:8:1999-2011
  14. Gooren LJ, et al. Long-Term Treatment of Transsexuals with Cross-Sex Hormones: Extensive Personal Experience. Journal of Clinical Endocrinology and Metabolism. 2009:93
  15. Ruppin U, Pfafflin F. Long-Term Follow-Up of Adults with Gender Identity Disorder. Arch Sex Beh 2015:44:1321-1329