Pubertal Suppression for Transgender Youth and Risk of Suicidal Ideation

Abstract

BACKGROUND AND OBJECTIVES:

Gonadotropin-releasing hormone analogues are commonly prescribed to suppress endogenous puberty for transgender adolescents. There are limited data regarding the mental health benefits of this treatment. Our objective for this study was to examine associations between access to pubertal suppression during adolescence and adult mental health outcomes.

METHODS:

Using a cross-sectional survey of 20 619 transgender adults aged 18 to 36 years, we examined self-reported history of pubertal suppression during adolescence. Using multivariable logistic regression, we examined associations between access to pubertal suppression and adult mental health outcomes, including multiple measures of suicidality.

RESULTS:

Of the sample, 16.9% reported that they ever wanted pubertal suppression as part of their gender-related care. Their mean age was 23.4 years, and 45.2% were assigned male sex at birth. Of them, 2.5% received pubertal suppression. After adjustment for demographic variables and level of family support for gender identity, those who received treatment with pubertal suppression, when compared with those who wanted pubertal suppression but did not receive it, had lower odds of lifetime suicidal ideation (adjusted odds ratio = 0.3; 95% confidence interval = 0.2–0.6).

CONCLUSIONS:

This is the first study in which associations between access to pubertal suppression and suicidality are examined. There is a significant inverse association between treatment with pubertal suppression during adolescence and lifetime suicidal ideation among transgender adults who ever wanted this treatment. These results align with past literature, suggesting that pubertal suppression for transgender adolescents who want this treatment is associated with favorable mental health outcomes.

According to the Centers for Disease Control and Prevention’s Youth Risk Behavior Surveillance System, ∼1.8% of adolescents in the United States identify as transgender.¹ These youth suffer mental health disparities that include higher rates of internalizing psychopathology (ie, anxiety and depression) and suicidality, theorized to be due to a combination of dysphoria toward their bodies and minority stress.^2–5 In a large study of transgender adults in the United States, 40% endorsed a lifetime suicide attempt.⁶

Over the past 2 decades, protocols have been developed to provide transgender adolescents with gender-affirming medical interventions that align their bodies with their gender identities. Most prominent among these are the Endocrine Society guidelines⁷ and the World Professional Association for Transgender Health (WPATH) Standards of Care.⁸ Both sets of guidelines recommend that transgender adolescents be offered gonadotropin-releasing hormone analogues (GnRHas), colloquially referred to as “puberty blockers,” once they reach Tanner 2 of puberty. These medications are provided as subcutaneous implants or are administered as either 1- or 3-month depot injections. GnRHa therapy effectively halts the production of gonadal sex steroids (testosterone and estrogen) by persistently activating and thereby desensitizing the gonadotropin-releasing hormone receptor, which in turn leads to suppression of luteinizing hormone and follicle-stimulating hormone release from the anterior pituitary gland.⁹ This process inhibits endogenous puberty for the duration of GnRHa use. Once further pubertal development is delayed, youth are able to explore gender identities without the pressure of dysphoria associated with gender-incongruent physical development.¹⁰ GnRHa therapy is unique among gender-affirming medical interventions in that the resultant pubertal suppression is fully reversible, with the resumption of endogenous puberty after their discontinuation.^7,8

Since the publication of the WPATH Standards of Care and the Endocrine Society guidelines, the use of pubertal suppression for transgender youth has become more common in the United States⁹ There are limited data, however, regarding the mental health outcomes of pubertal suppression. To date, there have been 2 published studies in which the effects of this treatment on the mental health of transgender youth were examined. In the first study, the authors assessed changes in mental health among 55 Dutch adolescents who received pubertal suppression.¹¹ This study, which notably lacked a control group, revealed that internalizing psychopathology improved after treatment with pubertal suppression. In the second study, researchers followed a group of 201 adolescents with gender dysphoria and found that those who received pubertal suppression in addition to psychological support (n = 101) had superior global functioning, measured by the Children’s Global Assessment Scale, when compared with those who received psychological support alone (n = 100).¹²

In the current study, we use the largest survey of transgender people to date, a community-recruited sample of transgender adults in the United States, to conduct the first-ever investigation into associations between pubertal suppression and suicidality.

Transgender youth present to clinicians with a range of concerns. Some have minimal body dysphoria and do not desire pubertal suppression, whereas others report significant dysphoria around the physical changes related to puberty. Because not all transgender and gender-diverse youth desire medical interventions, we examined only those youth who desired pubertal suppression because these are the young people who would present to care and for whom clinicians would need to decide about whether to initiate pubertal suppression. We specifically examined measures of past-year suicidality, lifetime suicidality, past-month severe psychological distress, past-month binge drinking, and lifetime illicit drug use. We hypothesized that among those who wanted pubertal suppression, those who received it would have superior mental health outcomes when compared with those who wanted but did not receive it.

METHODS

Study Design and Data Source

The 2015 US Transgender Survey (USTS) was conducted over a 1-month period in 2015 by the National Center for Transgender Equality (NCTE). It is, to our knowledge, the largest existing data set of transgender adults and includes data regarding demographics, past gender-affirming medical treatment, family support, and mental health outcomes. Participants were recruited through community outreach in collaboration with >400 lesbian, gay, bisexual, and transgender organizations and were provided with a Web address to complete the survey online. Details regarding outreach efforts are further described in the NCTE report on the survey.⁶ The USTS protocol was approved by the University of California, Los Angeles Institutional Review Board. For the purposes of the current study, data were obtained via a data-sharing agreement with the NCTE, and the current protocol was reviewed by The Fenway Institute Institutional Review Board and determined to not comprise human subjects research.

Study Population

The USTS data set contains responses from 27 715 US transgender adults, with respondents from all 50 states, the District of Columbia, American Samoa, Guam, Puerto Rico, and US military bases overseas. Given that pubertal suppression for transgender youth was not available in the United States until 1998,⁴ only participants who were 17 or younger in 1998 would have had health care access to GnRHa for pubertal suppression. We thus restricted the analysis to participants who were 36 or younger at the time of the survey, resulting in a sample of 20 619 participants. Data were further restricted to those who selected “puberty blocking hormones (usually used by youth ages 9–16)” in response to the question “Have you ever wanted any of the health care listed below for your gender identity or gender transition? (Mark all that apply).” Response options for this question were “counseling/therapy,” “hormone treatment/HRT,” “puberty blocking hormones (usually used by youth ages 9–16),” or “none of the above.” This resulted in a sample of 3494 individuals between the ages of 18 and 36 who ever wanted pubertal suppression as part of their gender-affirming medical care.

Exposures

Exposure to pubertal suppression was defined as selecting “puberty blocking hormones (usually used by youth ages 9–16)” in response to the question “Have you ever had any of the health care listed below for your gender identity or gender transition? (Mark all that apply).” Response options for this question were “counseling/therapy,” “hormone treatment/HRT,” “puberty blocking hormones (usually used by youth ages 9–16),” and “none of the above.” Participants who reported having pubertal suppression were also asked, “At what age did you begin taking Puberty Blocking Hormones?” Those who reported beginning treatment after age 17 were excluded to only include participants who likely had pubertal suppression during active endogenous puberty. The vast majority of adolescents would have reached Tanner 5, the final stage of puberty, by age 17.^13,14

Outcomes

Comparing those who received pubertal suppression with those who did not, we examined past-month severe psychological distress (defined as a score of ≥13 on the Kessler Psychological Distress Scale [K6], a cutoff previously validated among US adults¹⁵), past-month binge drinking (operationalized as drinking ≥5 standard alcoholic beverages during 1 occasion; the rationale for this threshold when studying alcohol use among transgender people has been discussed previously¹⁶), lifetime illicit drug use (not including marijuana), past-year suicidal ideation, past-year suicidal ideation with a plan, past-year suicide attempts, past-year suicide attempts resulting in inpatient care, lifetime suicidal ideation, and lifetime suicide attempts.

Control Variables

Demographic variables collected included age, age of social transition, age of initiation of gender-affirming hormone therapy, current gender identity, sex assigned at birth, sexual orientation, race, education level, employment status, relationship status, total household income at the time of data collection in 2015, family support for gender identity, and current hormone treatment.

Statistical Analysis

Data were analyzed by using SPSS software version 25 (IBM SPSS Statistics, IBM Corporation, Armonk, NY). Descriptive statistics were conducted and are presented as frequency (percentage) or mean (SD). Analysis of variance and χ² tests were used to assess significance by age, gender identity, sex assigned at birth, race, education level, employment status, relationship status, total household income, family support for gender identity, and current hormone treatment between those who received pubertal suppression and those who did not. We used univariate logistic regression to examine associations between receiving pubertal suppression and each mental health outcome, as well as between age and both ever wanting and receiving pubertal suppression. P < .05 defined statistical significance. Multivariable logistic regression models were adjusted for using the demographic variables associated with each outcome at the level of P ≤ .20. Because all outcomes were associated with level of family support, sexual orientation, education level, employment status, and total household income, all models were adjusted for these variables. Lifetime suicide attempts were associated with gender identity, and this model was therefore additionally adjusted for this variable. Past-month severe psychological distress and past-year suicidal ideation were additionally associated with age, gender identity, and relationship status, and therefore models were adjusted for these variables as well. Race was found to be associated with lifetime suicidal ideation and lifetime suicide attempts; therefore models were therefore additionally adjusted for race.

RESULTS

Of the 20 619 survey respondents 18 to 36 years of age, 3494 (16.9%) reported that they had ever wanted pubertal suppression. Of those who wanted pubertal suppression, only 89 (2.5%) had received this treatment. The following variables were found to be associated with those who wanted and received pubertal suppression compared with those who wanted pubertal suppression but did not receive it: younger age, age of social transition, age of initiation of hormone therapy, feminine gender identity, male sex assigned at birth, heterosexual sexual orientation, higher total household income, and greater family support of gender identity (Table 1).

TABLE 1.

Sample Demographics

		Have You Ever Had [Pubertal Suppression] for Your Gender Identity or Gender Transition?
	All (N = 3494)	Yes (n = 89; 2.5%)	No (n = 3405; 97.5%)	F	P
n (%)n (%)n (%)
Age	23.4 (5.0)	21.7 (4.7)	23.4 (5.0)	10.3	.001*
Age of social transition	20.0 (5.5)	15.2 (4.5)	20.1 (5.5)	67.5	<.001*
Age began hormone therapy	22.1 (4.5)	15.7 (2.4)	22.5 (4.3)	217.4	<.001*
Gender identity				25.5a	<.001*
Woman		23 (25.8)	617 (18.2)
Man		19 (21.3)	383 (11.3)
Transgender woman		25 (28.1)	720 (21.3)
Transgender man		16 (18.0)	795 (23.5)
Nonbinary or genderqueer		6 (6.7)	866 (25.6)
Sex assigned at birth				4.4a	.04*
Female		39 (43.8)	1874 (55.0)
Male		50 (56.2)	1531 (45.0)
Sexual orientation				36.5a	<.001*
Heterosexual or straight		27 (30.3)	350 (10.3)
Asexual		9 (10.1)	437 (12.8)
Pansexual or queer		36 (40.4)	1784 (52.4)
Gay or lesbian		12 (13.5)	539 (15.8)
Not listed		5 (5.6)	295 (8.7)
Race, n (%)				3.5a	.06
Racial minority		28 (31.5)	782 (23.0)
Not racial minority (white or European American)		61 (68.5)	2623 (77.0)
Education level				2.9a	.41
Less than high school		9 (10.1)	220 (6.5)
High school graduate or GED		20 (22.5)	683 (20.1)
Some college or associate degree		39 (43.8)	1729 (50.8)
Bachelor’s degree or higher		21 (23.6)	773 (22.7)
Employment status				0.6a	.45
Employed		51 (79.7)	1976 (75.6)
Unemployed		13 (20.3)	638 (24.4)
Relationship status				0.5a	.47
Partnered		35 (40.2)	1447 (44.1)
Unpartnered		52 (59.8)	1834 (55.9)
Total household income, $				21.9a	<.001*
<25 000		21 (26.3)	1153 (38.3)
25 000–49 999		13 (16.3)	652 (21.7)
50 000–99 000		14 (17.5)	630 (20.9)
>100 000		32 (40.0)	574 (19.1)
Family support for gender identity
Supportive		71 (81.6)	1551 (55.8)	24.3a	<.001*
Neutral		11 (12.6)	573 (20.6)
Unsupportive		5 (5.7)	658 (23.7)
Current hormone treatment		87 (97.8)	1617 (96.3)	0.5a	.48

Descriptive statistics for transgender adults in the United States who ever wanted pubertal suppression for their gender identity or gender transition when comparing those who received this treatment with those who did not receive this treatment (total N = 3494). Percentages were calculated from the total of nonmissing values.

^*Indicates statistical significance.

^aχ².

In univariate analyses, when comparing those who received pubertal suppression with those who did not, receiving pubertal suppression was associated with decreased odds of past-year suicidal ideation, lifetime suicidal ideation, and past-month severe psychological distress (Table 2). After controlling for demographic variables from Table 1, pubertal suppression was associated with decreased odds of lifetime suicidal ideation. Raw frequency outcomes are presented in Table 3.

TABLE 2.

Mental Health Outcomes Among Those Who Received Pubertal Suppression

	Univariate Analyses		Multivariable Analyses
	OR (95% CI)	P	aOR (95% CI)	P
Suicidality, past 12 mo
Ideation	0.6 (0.4–0.8)	.006*	0.6 (0.3–1.1)	0.09
Ideation with plan	0.9 (0.5–1.6)	.73
Ideation with plan and attempt	1.2 (0.6–2.3)	.64
Attempt resulting in inpatient care	2.8 (0.8–9.4)	.09
Suicidality, lifetime
Ideation	0.3 (0.2–0.5)	<.001*	0.3 (0.2–0.6)	0.001*
Attempts	0.7 (0.4–1.0)	.08
Mental health and substance use
Past-month severe psychological distress, K6 ≥13	0.5 (0.3–0.8)	.001*	0.8 (0.4–1.4)	0.38
Past-month binge drinking	0.3 (0.8–2.0)	.29
Lifetime illicit drug use	1.1 (0.7–1.8)	.67

Univariate and multivariable analyses of mental health outcomes among transgender adults in the United States who ever wanted pubertal suppression when comparing those who received this treatment with those who did not. Multivariable logistic regression models were adjusted for using the demographic variables associated with each outcome at the level of P ≤ .20. Because all outcomes were associated with family support, sexual orientation, education level, employment status, and total household income, all models were adjusted for these variables. Lifetime suicide attempts were associated with gender identity, and this model was additionally adjusted for this variable. Past-month severe psychological distress and past-year suicidal ideation were additionally associated with age, gender identity, and relationship status, and thus these models were adjusted for these variables as well. Race was found to be associated with lifetime suicidal ideation and lifetime suicide attempts, and thus these models were additionally adjusted for race. Models for psychological distress and past-year suicidal ideation were also adjusted for age, gender identity, and relationship status. aOR, adjusted odds ratio.

^aIndicates statistical significance.

TABLE 3.

Raw Frequencies of Outcome Variables

	Have You Ever Had [Pubertal Suppression] for Your Gender Identity or Gender Transition?
	Yes (n = 89; 2.5%)	No (n = 3405; 97.5%)
	n (%)	n (%)
Suicidality (past 12 mo)
Ideation	45 (50.6)	2204 (64.8)
Ideation with plan	25 (55.6)	1281 (58.2)
Ideation with plan and attempt	11 (24.4)	473 (21.5)
Attempt resulting in inpatient care	5 (45.5)	108 (22.8)
Suicidality (lifetime)
Ideation	67 (75.3)	3062 (90.2)
Attempts	37 (41.6)	1738 (51.2)
Mental health and substance use
Past-month severe psychological distress (K6 ≥13)	32 (37.2)	1847 (55.1)
Past-month binge drinking	26 (29.2)	825 (24.3)
Lifetime illicit drug use	24 (27.3)	850 (25.3)

Raw frequencies of mental health outcomes among transgender adults in the United States who ever wanted pubertal suppression. Percentages were calculated from the total of nonmissing values.

To examine associations between age, ever wanting, and ever receiving pubertal suppression, we divided participants into 2 age groups with the cutoff point at the median, 18 to 22 and 23 to 36, in light of the skewed distribution of age.¹⁷ The younger age group had increased odds both of ever wanting pubertal suppression (odds ratio [OR] = 1.4, P< .001, 95% confidence interval [CI]: 1.3–3.5) and of receiving pubertal suppression (OR = 2.1, P = .001, 95% CI: 1.4–3.4).

Among those who had ever received pubertal suppression, 60% reported traveling, 25 miles for gender-affirming health care, 29% traveled between 25 and 100 miles, and 11% traveled .100 miles.

DISCUSSION

This study is the first in which the association between access to pubertal suppression and measures of suicidality is examined. Treatment with pubertal suppression among those who wanted it was associated with lower odds of lifetime suicidal ideation when compared with those who wanted pubertal suppression but did not receive it. Suicidality is of particular concern for this population because the estimated lifetime prevalence of suicide attempts among transgender people is as high as 40%.⁶ Approximately 9 of 10 transgender adults who wanted pubertal suppression but did not receive it endorsed lifetime suicidal ideation in the current study (Table 3). Access to pubertal suppression was associated with male sex assignment at birth, heterosexual sexual orientation, higher total household income, and higher level of family support for gender identity.

Results from this study suggest that the majority of transgender adults in the United States who have wanted pubertal suppression did not receive it. Of surveyed transgender adults in the current study, 16.9% reported ever desiring pubertal suppression as part of their gender-related care; however, only 2.5% of these respondents indicated they had in fact received this wanted treatment. This was the case even for the youngest survey respondents, who were 18 years old at the time of data collection in 2015. Only 4.7% of 18-year-olds who wanted the treatment reported receiving it.

Although rates both of desiring and of receiving pubertal suppression were higher among younger respondents, results from the current study indicate that still only 29.2% of the youngest participants in the study (ie, those who were 18 years of age in the year 2015) reported ever desiring pubertal suppression as part of gender-related care. No individuals <18 years of age were captured by this data set; future research should investigate the rate of desiring pubertal suppression among younger populations. Some respondents may have simply never been aware of the possibility of puberty suppression while still within the range of developmentally suitable candidates for receiving this treatment, or they may have believed that they were not suitable candidates. This finding may also reflect the diversity of experience among transgender and gender-diverse people, highlighting that not all will want every type of gender-affirming intervention.^7,8 Future research is needed to understand why younger participants reported desiring pubertal suppression at higher rates; we hypothesize that this is likely due in part to recent increased public awareness about and access to gender-affirming interventions.⁵

Access to pubertal suppression was associated with a greater total household income. Without insurance, the annual cost of GnRHa therapy ranges from $4000 to $25 000.¹⁸ Among adolescents treated with pubertal suppression at the Boston Children’s Hospital Gender Management Service before 2012, <20% obtained insurance coverage.¹⁹ More recently, insurance coverage for these medications has increased: a study from 2 academic medical centers in 2015 revealed that insurance covered the cost of GnRHa therapy in 72% of cases.¹⁸ This is 1 potential explanation for why younger age was found to be associated with accessing pubertal suppression in the current study (Table 1). It is also plausible that those who receive pubertal suppression experience more improvement in mental health, which in turn may contribute to greater socioeconomic advancement.²⁰ This study’s cross-sectional design limits further interpretation.

Participants who endorsed a heterosexual sexual orientation were more likely to have received pubertal suppression. This is in line with past research revealing that nonheterosexual transgender people are less likely to access gender-affirming surgical interventions.²¹ Some clinicians may be biased against administering pubertal suppression to patients whose sexual orientation identities do not align with society’s heteronormative assumptions.²¹ In the current study, nonbinary and genderqueer respondents were also less likely to have accessed pubertal suppression, suggesting that clinicians may additionally be uncomfortable with delivering this treatment to patients whose gender identities defy more traditional binary categorization. Of note, because research on gender-affirming hormonal interventions for adolescents has been focused on transgender youth with binary gender identities,¹¹ some clinicians have reservations about prescribing pubertal suppression interventions to nonbinary youth in the event of a potentially prolonged state of low sex-steroid milieu.

Family support was also associated with receiving pubertal suppression among those who wanted this treatment. This finding is unsurprising given that most states require parental consent for adolescents to receive pubertal suppression.²² Past studies have revealed that family support of gender identity is associated with favorable mental health outcomes.⁶ Of note, treatment with pubertal suppression in the current study was associated with lower odds of lifetime suicidal ideation, even after adjustment for family support (Table 2).

We did not detect a difference in the odds of lifetime or past-year suicide attempts or attempts resulting in hospitalization. It is possible that we were underpowered to detect these differences given that suicide attempt items were less frequently endorsed than suicidal ideation items (Table 3). Given this study’s retrospective self-report survey design, we were unable to capture information regarding completed suicides, which may have also reduced the number of suicide attempts we were able to account for. Given that suicidal ideation alone is a known predictor of future suicide attempts and deaths from suicide, the current results warrant particular concern.²³

This study adds to the existing literature^11,12 on the relationship of pubertal suppression to favorable mental health outcomes. The theoretical basis for these improved mental health outcomes is that pubertal suppression prevents irreversible, gender-noncongruent changes that result from endogenous puberty (eg, bone structure, voice changes, breast development, and body hair growth) and that may cause significant distress among transgender youth. Pubertal suppression allows these adolescents more time to decide if they wish to either induce exogenous gender-congruent puberty or allow endogenous puberty to progress.^7,8 Some have also theorized that gender-affirming medical care may have mental health benefits that are separate from its physical effects because it provides implied affirmation of gender identity from clinicians, which may in turn buffer against minority stress.²⁴

Strengths of this study include its large sample size and representation of a broad geographic area of the United States. It is the first study in which associations between pubertal suppression for transgender youth and suicidality are examined. Limitations include the study’s cross-sectional design, which does not allow for determination of causation. Longitudinal clinical trials are needed to better understand the efficacy of pubertal suppression. Because the 2015 USTS data do not contain the relevant variables, we were unable to examine associations between access to pubertal suppression and degree of body dysphoria in this study. Notably, past studies have revealed that body image difficulties persist through pubertal suppression and remit only after administration of gender-affirming hormone therapy with estrogen or testosterone.¹¹ It is also limited by its nonprobability sample design. Future researchers should work toward the collection of population-based survey data that include variables related to gender-affirming medical interventions. Of note, because pubertal suppression for transgender youth is a relatively recent intervention, some participants might not have known that these interventions existed and thus would not have reported ever wanting them. Had these individuals known about pubertal suppression, it is possible that they might have desired it. Because we do not have data on whether individuals who did not desire pubertal suppression would have wanted it had they known about it, we restricted our analysis to those who reported ever desiring pubertal suppression. Reverse causation cannot be ruled out: it is plausible that those without suicidal ideation had better mental health when seeking care and thus were more likely to be considered eligible for pubertal suppression. The Endocrine Society guidelines for pubertal suppression eligibility recommend that other mental health concerns be “reasonably well controlled.”⁷ Because this study includes only adults who identify as transgender, it does not include outcomes for people who may have initiated pubertal suppression and subsequently no longer identify as transgender. Notably, however, a recent study from the Netherlands of 812 adolescents with gender dysphoria revealed that only 1.9% of adolescents who initiated pubertal suppression discontinued this treatment without proceeding to gender-affirming hormone therapy with estrogen or testosterone.²⁵

CONCLUSIONS

Among transgender adults in the United States who have wanted pubertal suppression, access to this treatment is associated with lower odds of lifetime suicidal ideation. This study strengthens recommendations by the Endocrine Society and WPATH for this treatment to be made available for transgender adolescents who want it.

WHAT’S KNOWN ON THIS SUBJECT:

Gonadotropin-releasing hormone analogues are commonly used to suppress endogenous puberty for transgender adolescents. Small studies have revealed that pubertal suppression results in favorable mental health outcomes. No studies to date have examined associations between pubertal suppression and suicidality.

WHAT THIS STUDY ADDS:

In this study, using the largest survey of transgender adults to date, we show that access to pubertal suppression during adolescence is associated with lower odds of lifetime suicidal ideation among transgender young adults.

ABBREVIATIONS

CI

confidence interval

GnRHa

gonadotropin-releasing hormone analogue

K6

Kessler Psychological Distress Scale

NCTE

National Center for Transgender Equality

OR

odds ratio

USTS

US Transgender Survey

WPATH

World Professional Association for Transgender Health