Key Points
Question
What are the epidemiologic characteristics associated with acne development in transgender individuals receiving masculinizing hormone therapy?
Findings
In this cohort study, among 988 transgender patients who initiated masculinizing hormone therapy, there was an overall acne prevalence of 31.1% and a 2-year incidence proportion of 25.1%. A younger age at initiation was significantly associated with acne development for individuals receiving masculinizing hormone therapy.
Meaning
In this study, acne appears to be a common condition among transgender patients receiving masculinizing hormone therapy, with younger patients more likely to develop acne.
Abstract
Importance
Acne is a common condition among transgender patients receiving masculinizing hormone therapy (MHT), but the incident risk and predictors of developing acne in this population have not yet been studied on a large scale.
Objective
To assess risk of acne among a large population of transgender patients receiving MHT and clinical risk factors for acne diagnosis.
Design, Setting, and Participants
A retrospective cohort study that included 988 patients who started MHT between January 1, 2014, and December 31, 2017, with at least 1 year of follow-up was performed. Data analysis was conducted from September 1 to 15, 2019. Data were obtained using electronic health records from a community health center serving the sexual and gender minority community. The population included every patient who began receiving MHT during the study period who was aged 18 years or older at the time of MHT initiation and whose assigned sex at birth was female.
Main Outcomes and Measures
The main outcome was acne defined by International Statistical Classification of Diseases, Tenth Revision, Clinical Modification codes for acne. Overall prevalence and incidence proportions over 2 years after initiation of MHT were calculated. Baseline demographic and clinical characteristics were collected at the time of MHT initiation. A series of univariate analyses for all factors was calculated to test for an association with acne diagnosis, followed by multivariate analyses to test for independent predictors.
Results
For 988 patients (median age, 25.8 years; interquartile range, 20.8-28.2 years), there was an overall acne prevalence of 31.1% (n = 307). The 1-year post-MHT acne incidence proportion was 19.0% and the 2-year incidence proportion was 25.1%. A younger age at MHT initiation was associated with a higher likelihood of developing acne, with a median of 22.4 years (interquartile range, 19.7-25.6 years) among patients who developed acne vs 24.7 years (interquartile range, 21.3-29.4 years) among patients who did not (P = .002).
Conclusions and Relevance
Acne is a common condition among transgender patients on MHT, with a prevalence increasing from 6.3% to 31.1% following MHT initiation. Patients aged 18 to 21 years appear to be the most likely to develop acne after MHT initiation.
This cohort study examines the prevalence of acne in transgender individuals initiating masculinizing hormone therapy.
Introduction
Masculinizing hormone therapy (MHT) (ie, testosterone) is given to transgender individuals, defined herein as individuals whose gender identity differs from their assigned sex at birth and including gender nonbinary and genderqueer individuals, to develop male secondary sex characteristics, such as male-pattern hair growth, male body contours, and vocal virilization, as well as suppression of female secondary sex characteristics, including cessation of menses. Various routes of administration are available, including intramuscular, subcutaneous, or transdermal delivery.1
Previous studies suggest that MHT is a risk factor for the development of acne.2,3,4 Although a clear biological pathway exists for MHT to cause or worsen acne, studies thus far have reached varying conclusions regarding the severity, course, and management of MHT-induced acne in the transgender population. While some studies have not shown associations between MHT and acne severity,2,3,4 case reports indicate that MHT-induced acne may require isotretinoin therapy in severe cases.5 In addition, these studies have shown that acne tends to peak 6 to 12 months after initiation of MHT and resolves with long-term use of testosterone.2,4 However, the studies have been limited by small sample sizes.
Acne is associated with decreased self-esteem and overall quality of life, leading to higher rates of depression, poor body image, and social withdrawal.6,7,8 Transgender and sexual minority individuals may be especially susceptible to the psychological effects of acne, as this population has a baseline increased risk of mental health disorders, substance use disorders, depression, and suicide.9 In a cross-sectional study of sexual minority patients aged 18 to 28 years, individuals with acne experienced a greater risk of suicidal ideation and antidepressant use compared with sexual minority patients without acne.10
There remain significant knowledge and practice barriers for the management of acne among transgender patients on MHT, and further exploration is needed to help guide patient counseling and treatment. In this study, we sought to assess the prevalence and incidence of acne, current treatment patterns, and demographic and clinical factors associated with the diagnosis of acne in a large population of gender-diverse patients on MHT.
Methods
We conducted a retrospective cohort study using the electronic health records (EHRs) (Centricity Practice Solutions, AthenaHealth) at Fenway Health, a large, freestanding community health care and research facility serving the needs of the sexual and gender minority community in the greater Boston, Massachusetts, area. Fenway Health has detailed sexual orientation and gender identity data fully integrated into their clients’ EHRs.11 This study was determined to be exempt from institutional review board review by the Fenway Institute of Health, Boston, Massachusetts, owing to meeting criteria set forth at 45 CFR 46.104 [46.104(d)(4)(iii)] pertaining to information collection and analysis involving the investigators’ use of identifiable health information for the purposes of research. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline for cohort studies.
We included patients who started MHT between January 1, 2014, and December 31, 2017, were aged 18 years or older at the time of MHT initiation, and whose assigned sex at birth was female. We excluded patients whose assigned sex at birth was not documented.
The main outcome was the overall prevalence and incidence proportion of acne after initiating MHT. Acne was defined by International Statistical Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes for acne (L70.x). All patients with an acne diagnosis date after their MHT initiation date in the EHR were considered to have post-MHT acne. The analysis was performed from September 1 to 15, 2019, and all patients had been on MHT for at least 1 year at the time of analysis. A search for all listed medications, including topical preparations, oral antibiotics, and oral isotretinoin, was conducted in the EHR and the use of medications specifically prescribed for acne was confirmed by EHR review (eTable 1 in the Supplement).
We defined baseline as the most recent data available before MHT initiation for each patient. Categories for analysis included race/ethnicity, gender identity, sexual orientation, age, body mass index (BMI; calculated as weight in kilograms divided by height in meters squared), insurance status, employment status, partnership status, dermatology visits, comorbidities, and smoking status. Comorbidities were identified by ICD-10-CM codes and included metabolic comorbidities, dermatologic comorbidities, mood disorders, and polycystic ovarian syndrome.
We also examined MHT-related factors, such as total serum testosterone levels, both before and between 1 and 2 years after MHT initiation, MHT modality during maintenance therapy (2 groups: subcutaneous/intramuscular vs noninjectable), and MHT dosage, because higher serum testosterone levels at baseline or during maintenance therapy could potentially be associated with acne. Use of subcutaneous/intramuscular testosterone results in greater fluctuation of serum testosterone levels with higher peak levels of testosterone compared with noninjectable forms.12 We also collected data on medications used before initiation of MHT and within 1 year after initiation of MHT that have been shown to either worsen or alleviate acne, including combined estrogen/progestin and progestin-only contraceptives (oral, implant, and intrauterine device forms), corticosteroids, and lithium.13,14,15
Statistical Analysis
Prevalence was defined as the total number of post-MHT acne cases, both new and preexisting, at the time of analysis. Incidence proportion was defined as the number of new cases of acne occurring within 6-month intervals after MHT initiation up to 24 months. All demographic and clinical factors were tested for an association with acne diagnosis using Stata/SE, version 16.0 (StataCorp LLC). An initial univariate analysis for each variable was conducted followed by multivariate analyses to determine factors associated with acne diagnosis. All patients with acne before MHT initiation were excluded from the acne diagnosis analysis. Analyses using χ2 testing were conducted for all categorical variables and a 2-sample t test was used for all continuous variables. All factors with a univariate P value <.2 were included in a multivariate logistic regression to assess factors associated with post-MHT acne diagnosis. Nonparametric variables were categorized into quartiles (age and total serum testosterone level) or converted to log values (BMI) for multivariate analyses. To correct for multiple comparisons, the Bonferroni correction for P values was applied and P = .002 was considered significant for univariate and multivariate analyses. Patients with missing data for a specific parameter were excluded from analysis in any univariate and multivariate test that included that parameter.
To examine the association of age with acne diagnosis, we created Kaplan-Meier plots based on the cumulative incidence of acne and stratified by age categories in quartiles for all patients who developed acne after initiation of MHT and had an MHT duration of at least 2 years. A log-rank test was used for comparison of the cumulative incidence of acne between the 4 age groups in the Kaplan-Meier analysis. We examined the association of age with other factors found to be significant in the univariate analyses by grouping the age categories and performing analysis of variance and χ2 analyses as appropriate. P < .05 was considered statistically significant for all post hoc analyses.
Results
We identified a total of 988 transgender patients who initiated MHT during the study period and had received MHT for a mean (SD) of 3.4 (1.1) years (Table 1). The patients’ median age was 25.8 years (interquartile range, 20.8-28.2 years); other overall demographic and clinical characteristics, including race/ethnicity, BMI, and comorbidities, are listed in Table 1.
Table 1. Baseline Demographic and Clinical Characteristics at MHT Initiation.
| Variablea | Values |
|---|---|
| No. of patients | 988 |
| Age, median (IQR), y | 25.8 (20.8-28.2) |
| Age, range | 18-66.5 |
| BMI (n = 938) | |
| Median (IQR) | 26.0 (22.5-31.8) |
| Range | 11.8-69.3 |
| <35, No. (%) | 774 (82.5) |
| ≥35, No. (%) | 164 (17.5) |
| Dermatology visits, No. (%) | |
| Yes | 70 (7.1) |
| No | 918 (92.9) |
| Race/ethnicity, No. (%) (n = 967) | |
| White | 763 (78.9) |
| Hispanic | 32 (3.3) |
| Black/African American | 47 (4.9) |
| Asian | 28 (2.9) |
| Undefined/multiracial | 97 (10.0) |
| Sex assigned at birth, No. (%) | |
| Female | 988 (100) |
| Gender identity, No. (%) | |
| Male | 723 (73.2) |
| Genderqueer/not exclusively male or female | 265 (26.8) |
| Sexual orientation, No. (%) | |
| Straight/heterosexual | 188 (20.5) |
| Gay/lesbian/homosexual | 182 (19.8) |
| Bisexual | 175 (19.1) |
| Other | 372 (40.6) |
| Partnership status, No. (%) | |
| Married/partnered | 216 (23.5) |
| Single/divorced/separated/widowed | 705 (76.5) |
| Employment status (n = 775), No. (%) | |
| Employed or student | 684 (88.3) |
| Unemployed | 91 (11.7) |
| Smoking status (n = 632), No. (%) | |
| Current | 99 (15.7) |
| Past | 102 (16.1) |
| Never | 431 (68.2) |
| Comorbidities at baseline, No. (%) | |
| Hypertension | 21 (2.1) |
| Hyperlipidemia | 33 (3.3) |
| Diabetes | 11 (1.1) |
| Anxiety | 289 (29.3) |
| Depression | 299 (30.3) |
| Alopecia | 4 (0.4) |
| Polycystic ovarian syndrome | 31 (3.1) |
| Hyperhidrosis | 1 (0.1) |
| Hidradenitis suppurativa | 3 (0.3) |
| Rosacea | 1 (0.1) |
| MHT duration, mean (SD), y | 3.4 (1.1) |
| MHT type at maintenance, No. (%) | |
| Intramuscular/subcutaneous injection | 824 (83.4) |
| Implant | 31 (3.1) |
| Transdermal | |
| Gel | 120 (12.1) |
| Patch | 13 (1.3) |
| Overall dose/weight at maintenance, median (IQR), mg/wk/kg | 0.91 (0.70-1.29) |
| Intramuscular/subcutaneous injection | 0.86 (0.68-1.10) |
| Implant | 1.83 (1.13-2.44) |
| Transdermal gel | 4.68 (1.13-2.44) |
| Transdermal patch | 0.35 (0.29-0.49) |
| Total serum testosterone before MHT, median (IQR), ng/dL | 38 (27-58.5) |
| Total serum testosterone 1 y post MHT, median (IQR), ng/dL | 548 (370-761) |
| Insurance, No. (%) (n = 967) | |
| Private | 763 (78.9) |
| Public | 204 (21.1) |
| Acne treatment before MHT, No. (%) (n = 62) | |
| No prescribed medication | 28 (45.2) |
| Topical medication | 15 (24.2) |
| Oral antibiotics | 13 (21.0) |
| Isotretinoin | 6 (9.7) |
| Nonacne medications used before and within 1 y post MHT, No. (%) | |
| Combined oral contraceptives | 54 (5.5) |
| Progestin-only contraceptives | 69 (7.0) |
| Corticosteroids | 30 (3.0) |
| Lithium | 13 (1.3) |
Abbreviations: BMI, body mass index (calculated as weight in kilograms divided by height in meters squared); IQR, interquartile range; MHT, masculinizing hormone therapy.
SI conversion: To convert testosterone to nanomoles per liter, multiply by 0.0347.
The following parameters contained missing data: race (21 [2.1%]), sexual orientation (16 [1.6%]), employment status (213 [21.6%]), smoking status (356 [36.0%]), partnership status (67 [6.8%]), and insurance type (21 [2.1%]).
The total number of patients with acne was 307 of 988 (31.1%), including 62 patients (6.3%) who were diagnosed with acne before starting MHT. Excluding the 62 patients with pre-MHT acne diagnoses, the total prevalence of post-MHT acne was 26.5% (245 of 926 patients). The incidence proportion was 11.8% (109 of 926) for the first 6 months of MHT, 8.2% (67 of 817) at 7 to 12 months, 4.1% (31 of 750) at 13 to 18 months, and 2.3% (14 to 618) at 19 to 24 months. The incidence proportion at 1 year was 19.0% (176 of 926). The 2-year post-MHT acne incidence proportion was 25.1% overall, with 29.6% (76 of 257) among patients aged 18.00 to 20.75 years, 24.4% (53 of 217) among patients aged 20.83 to 23.92 years, 26.1% (54 of 207) among patients aged 24.00 to 28.17 years, and 17.1% (26 of 152) among patients aged 28.25 to 66.5 years (Figure).
Figure. Acne Diagnosis After Initiation of Masculinizing Hormone Therapy (MHT).
Age by quartile was rounded using the following values: first quartile, 18.00 to 20.75 years; second quartile: 20.83 to 23.92 years; third quartile, 24.00 to 28.17 years; and fourth quartile, 28.25 to 66.5 years.
In the univariate analysis, younger age was associated with a higher likelihood of acne diagnosis (t statistic, 5.5; mean 25.9; 95% CI, 25.4-26.4; P < .001) (Table 2). Baseline median BMI was also lower among those who developed acne compared with those without an acne diagnosis (24.9; interquartile range, 21.8-29.6 vs 26.6; interquartile range, 22.8-33.0; P < .001). In the multivariate analysis, age at MHT initiation was the only factor found to be significantly associated with post-MHT acne diagnosis, with a median of 22.4 years (interquartile range, 19.7-25.6 years) among patients who developed acne vs 24.7 years (interquartile range, 21.3-29.4 years) among patients who did not (P = .002). The post hoc analysis of age and MHT acne incidence using a Kaplan-Meier log-rank test showed a significant difference in acne incidence by age group (χ2, 32.2; 95% CI, 9.7-54.6, P < .001) (Figure). The post hoc analysis of age on different clinical factors found an association of younger ages with lower BMIs (F, 7.2; mean, 28.0; 95% CI, 27.5-28.5: P < .001), lower pre-MHT total serum testosterone level (F, 8.2; mean, 109.5; 95% CI, 89.2-129.7; P < .001), and a higher rate of injectable vs noninjectable forms of MHT (χ2, 10.5; 95% CI, –3.1 to 13.7; P = .01) (eTable 2 in the Supplement).
Table 2. Demographic and Clinical Factors and Post-MHT Acne Diagnosis.
| Demographic/clinical factor | Univariate | Multivariate | |||
|---|---|---|---|---|---|
| t Statistic | Mean/χ2 value (95% CI) | P value | OR (95% CI) | P value | |
| Age at MHT initiation, y | 5.5 | 25.9 (25.4-26.4) | <.001 | NA | |
| 18.00-20.75 | NA | NA | NA | 1 [Reference] | .002 |
| 20.83-23.92 | NA | NA | NA | 0.41 (0.20-0.84) | |
| 24.00-28.17 | NA | NA | NA | 0.65 (0.31-1.34) | |
| 28.25-66.5 | NA | NA | NA | 0.20 (0.08-0.47) | |
| Pre-MHT BMI | 3.6 | 28.0 (27.5-28.5) | <.001 | 0.09 (0.01-1.05) | .06 |
| Smoking status, No. (%) | NA | 5.9 (–4.4 to 16.1) | .06 | NA | .16 |
| Never smoker | NA | NA | NA | 1 [Reference] | |
| Past smoker | NA | NA | NA | 0.77 (0.35-1.71) | |
| Current smoker | NA | NA | NA | 0.44 (0.19-1.03) | |
| MHT type | NA | 5.3 (–3.5 to 14.1) | .02 | 0.54 (0.24-1.19) | .13 |
| Total serum testosterone before MHT, median (IQR), ng/dL | 2.8 | 109.5 (89.2-129.7) | .006 | NA | |
| 1.88-27 | NA | NA | NA | 1 [Reference] | .29 |
| 28-38 | NA | NA | NA | 1.55 (0.75-3.22) | |
| 39-59 | NA | NA | NA | 1.19 (0.57-2.46) | |
| 60-1585 | NA | NA | NA | 0.68 (0.28-1.65) | |
| Combined oral contraceptives | NA | 2.3 (–2.9 to 7.5) | .13 | 0.28 (0.03-2.53) | .26 |
| Progestin-only contraceptives | NA | 3.0 (–2.7 to 8.6) | .09 | 0.68 (0.18-2.67) | .58 |
Abbreviations: BMI, body mass index (calculated as weight in kilograms divided by height in meters squared); IQR, interquartile range; MHT, masculinizing hormone therapy; NA, not applicable.
SI conversion: To convert testosterone to nanomoles per liter, multiply by 0.0347.
Discussion
In this large, retrospective cohort study including 988 transgender patients initiating MHT, we found that overall acne prevalence increased from 6.3% before MHT initiation to 31.1% after a mean MHT duration of 3.4 years. Among all patients, there was an incidence proportion of 25.1% over 2 years, with a rate of acne diagnosis that was greatest in the first 6 months of therapy and steadily decreased over each successive 6-month period for the first 2 years. Age at MHT initiation was the only demographic or clinical factor examined in this study that was significantly associated with the overall development of acne after MHT was started, with younger patients more likely to be diagnosed after MHT initiation.
The prevalence of acne found in our study among transgender individuals on MHT is lower than reported in previous prospective studies. A study of 16 transgender patients undergoing testosterone therapy revealed that 15 patients (94%) developed facial acne and 14 patients (88%) developed back acne after 4 months of MHT, compared with baseline rates of 29% for facial acne and 17% for back acne.2 Another prospective study of 20 transgender patients beginning MHT showed an increase of facial acne from 35% to 82% and chest/back acne from 15% to 88% after 6 months of therapy.4 In a cross-sectional analysis of 50 transgender patients within that study who had already been receiving MHT for a mean of 10 years, 63% had mild acne, 6% had moderate acne, and none of the patients had severe acne.4 The higher prevalence reported in these studies may be due to an increased detection of mild acne cases, because these studies used physician global assessments or patient self-report of acne for their outcome measures. Our study only included patients who had received an ICD-10-CM coded diagnosis of acne. Many of our patients may have developed mild acne that did not worsen to the level of clinical significance or have chosen not to discuss acne with their health care clinician. To our knowledge, the only other retrospective study of transgender patients receiving MHT to use acne diagnosed in clinic to measure incidence found a 2-year cumulative incidence rate of 38% among 55 transgender men, closer to the findings of our study.16 Although we found the highest prevalence of acne in the youngest age group (age 18-21 years), total serum testosterone levels before starting MHT and 1 to 2 years following MHT initiation were lowest in this group.
These findings suggest that the higher acne prevalence among younger patients may be related to factors other than just serum levels or exogenous administration of testosterone. It is well established that acne is not necessarily related to serum testosterone levels or serum testosterone production.17,18 However, there may be local overproduction of active androgens. Testosterone can be converted to 5α-dihydrotestosterone in sebocytes, and increased rates of 5α-dihydrotestosterone have been reported in acne skin.19 Other hormones, including growth hormone and insulinlike growth factor-1 reach peak levels in adolescence. Increased serum levels of insulinlike growth factor-1 are associated with severity of acne, and increased serum levels of growth hormone are associated with increased sebum production in acromegaly.20,21,22 The delivery of MHT may also play a role in acne prevalence. Injectable forms of MHT were more commonly prescribed to younger patients in our study. Injectable forms of MHT are more widely available and less expensive than noninjectable forms; however, the troughs and peaks in serum hormone levels via this mode of delivery may be wider than those with noninjectable formulations and thus contribute to acne development.23,24
Limitations
The study has limitations. This was a retrospective cohort study that cannot determine causation. Because the cohort included transgender patients found in 1 community health center in New England, our findings may not be representative of all transgender patients; moreover, most patients in our sample were of White race, a group whose acne presentation and severity are known to differ from other racial groups.25 It is possible that we did not identify all cases of acne, especially if mild, because ascertainment was limited to ICD-10-CM diagnoses in the EHR. Because we examined the most recent testosterone delivery modality used, it is possible we did not accurately capture the maintenance therapy modality for patients who recently switched to a new drug formulation.
Conclusions
Acne can be a debilitating condition for many patients and may be especially harmful for individuals of gender and sexual minorities who already experience stigma and discrimination. Transgender patients who are about to undergo MHT, especially those who are younger, should be counseled on the increased risk of acne and the treatments available. In addition, guidelines of care for the treatment of acne should be expanded to include transgender patients.26 The association between various testosterone formulations, doses, and routes of administration and the development of acne among transgender patients is likely complex and further studies are needed.
eTable 1. Acne Medications and Acne Severity
eTable 2. Demographic and Clinical Factors by Age
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Associated Data
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Supplementary Materials
eTable 1. Acne Medications and Acne Severity
eTable 2. Demographic and Clinical Factors by Age
