Acne risk in transgender and gender diverse populations: A retrospective, comparative cohort study

Abstract

To the Editor: Acne is a common dermatologic condition that may be particularly problematic for transgender and gender diverse (TGD) individuals.1Motosko C. Zakhem G. Pomeranz M. Hazen A. Acne: a side-effect of masculinizing hormonal therapy in transgender patients.Br J Dermatol. 2019; 180: 26-30Crossref PubMed Scopus (24) Google Scholar Both masculinizing gender-affirming hormone therapy (mGAHT [ie, testosterone]) and feminizing gender-affirming hormone therapy (fGAHT [ie, estrogen or antiandrogens]) have been linked to the worsening and improvement of acne, respectively, but existing studies have been limited by the size and lack of comparison groups.1Motosko C. Zakhem G. Pomeranz M. Hazen A. Acne: a side-effect of masculinizing hormonal therapy in transgender patients.Br J Dermatol. 2019; 180: 26-30Crossref PubMed Scopus (24) Google Scholar, 2Giltay E. Gooren L. Effects of sex steroid deprivation/administration on hair growth and skin sebum production in transsexual males and females.J Clin Endocrinol Metab. 2000; 85: 2913-2921Crossref PubMed Scopus (140) Google Scholar, 3Wierckx K. Van de Peer F. Verhaeghe E. et al.Short- and long-term clinical skin effects of testosterone treatment in trans men.J Sex Med. 2014; 11: 222-229https://doi.org/10.1111/jsm.12366Abstract Full Text Full Text PDF PubMed Scopus (82) Google Scholar, 4Thoreson N. Park J.A. Grasso C. et al.Incidence and factors associated with acne among transgender patients receiving masculinizing hormone therapy.JAMA Dermatol. 2021; 157: 290-295Crossref PubMed Scopus (9) Google Scholar In this study of 46,507 patients, we examined the overall prevalence and risk ratios of acne in TGD patients receiving mGAHT (TGD-mGAHT) or fGAHT (TGD-fGAHT) compared with those in cisgender men, cisgender women, and TGD patients not receiving gender-affirming hormone therapy who were assigned female or male at birth.We conducted a retrospective cohort study using electronic health records of all TGD and cisgender adults who had at least 1 medical visit at Fenway Health, a community health center in Boston, between August 2014 and August 2020. This study was determined to be exempted from review by the institutional review board of Fenway Institute of Health. We excluded patients without recorded gender identity, birth sex, or body mass index data; cisgender women prescribed testosterone; and cisgender men prescribed birth control or menopause medications. Acne was defined based on International Statistical Classification of Diseases, Ninth and Tenth Revisions, Clinical Modification codes for acne (706.1 and L70.x, respectively). The use of gender-affirming hormone therapy was elicited based on prescription data. We collected data on demographics and other clinical factors that affect acne (Table I). Prevalence was defined as the total number of acne cases, both new and pre-existing, identified based on the diagnostic codes at the time of analysis. Unadjusted risk ratios and adjusted risk ratios (aRRs) with 95% CIs for association with acne were calculated using log-binomial regression. Multivariate models included age, body mass index, diabetes, hyperlipidemia, hypertension, corticosteroid use, lithium or amoxapine use, and smoking status.Table IBaseline demographics and clinical characteristicsCharacteristicOverallTGD-fGAHTTGD-mGAHTCisgender menCisgender womenTGD-nGAHT, AFABTGD-nGAHT, AMABPatients, N46,5071394157625,59416,961535447Acne diagnosis, n (%)3517(7.6%)73(5.2%)415(26.3%)1345(5.3%)1621(9.6%)45(8.4%)18(4.0%)Age Median (IQR), y27(22-39)25(21-32)23(20-28)30(24-44)25(21-32)25(20-27)30(21-35) Range, y18-9518-7118-6618-9518-9318-7018-74BMI Median (IQR)25.3(22.6-29.0)25.3(22.0-30.1)26.6(22.9-32.3)25.9(23.4-29.1)24.2(21.6-28.4)28.8(22.8-33.2)26.4(21.8-29.3) Range(2.0,81.8)(2.1,68.1)(2.5,73.7)(2.0,67.6)(2.0,81.8)(5.3,57.0)(16.6,74.6) 18.5-24.9, n (%)20,762(44.6%)622(44.6%)608(38.6%)10,133(39.6%)8994(53.0%)182(34.0%)223(49.9%) <18.5, n (%)1038(2.2%)46(3.3%)36(2.3%)329(1.3%)600(3.5%)16(3.0%)11(47.7%) ≥25.0, n (%)24,707(51.1%)726(52.1%)932(59.1%)15,132(59.1%)7367(43.4%)337(63.0%)213(2.5%)Race, n (%) Caucasian/White30,972(66.6%)1014(72.7%)1295(76.5%)17,479(68.3%)10,557(62.2%)398(74.4%)319(71.4%) Asian4741(10.2%)64(4.6%)59(3.7%)2226(8.7%)2349(13.9%)22(4.1%)21(4.7%) Black3127(6.7%)64(4.6%)88(5.6%)1669(6.5%)1258(7.4%)23(4.3%)25(5.6%) Multiracial2296(4.9%)110(7.9%)126(8.0%)1187(4.6%)780(4.6%)61(11.4%)32(7.2%) Other1370(3.0%)40(2.9%)28(1.8%)709(2.8%)562(3.3%)17(3.2%)14(3.1%) Unknown or missing4001(8.6%)102(7.3%)70(4.4%)2324(9.1%)1455(8.6%)14(2.6%)36(8.1%)Smoking status, n (%) Current4491(9.7%)165(11.8%)182(11.6%)2945(11.5%)1101(6.5%)47(8.8%)51(11.4%) Past7448(16.0%)293(21.0%)303(19.2%)4746(18.5%)1935(11.4%)91(17.0%)80(17.9%) Never28,143(60.5%)854(61.3%)998(63.3%)14,597(57.0%)11,079(65.3%)337(63.0%)278(62.2%) Unknown or missing6425(13.8%)82(5.9%)93(5.9%)3306(12.9%)2846(16.8%)60(11.2%)38(8.5%)Comorbidities, n (%) Diabetes1660(3.6%)60(4.3%)41(2.6%)1115(4.4%)413(2.4%)12(2.2%)19(4.3%) Hyperlipidemia6978(15.0%)171(12.3%)224(14.2%)5088(19.9%)1414(8.3%)30(5.6%)51(11.4%) Hypertension6053(13.0%)113(8.1%)112(7.1%)4388(17.1%)1370(8.1%)27(5.1%)43(9.6%)Other medication use Oral corticosteroids7776(16.7%)207(13.1%)156(11.2%)4997(19.5%)2311(13.6%)51(9.5%)54(12.1%) Lithium or amoxapine529(1.1%)29(2.1%)46(2.9%)271(1.1%)154(0.9%)17(3.2%)12(2.7%)AFAB, Assigned female at birth; AMAB, assigned male at birth; BMI, body mass index; IQR, interquartile range; TGD-fGAHT, transgender/gender diverse patients receiving feminizing gender-affirming hormone therapy; TGD-mGAHT, transgender/gender diverse patients receiving masculinizing gender-affirming hormone therapy; TGD-nGAHT, transgender/gender diverse patients not undergoing gender-affirming hormone therapy. Open table in a new tab Both unadjusted and adjusted analyses revealed that TGD-mGAHT patients were significantly more likely to have acne than cisgender women (aRR = 2.41; 95% CI, 2.18-2.67), cisgender men (aRR = 4.09; 95% CI, 3.67-4.56), and TGD patients not receiving gender-affirming hormone therapy. TGD-fGAHT patients were not significantly less likely to have acne than cisgender men (aRR = 0.85; 95% CI, 0.66-1.09) but were significantly less likely to have acne than cisgender women (aRR = 0.51; 95% CI, 0.40-0.65) and TGD patients not receiving gender-affirming hormone therapy who were assigned female at birth (aRR = 0.56; 95% CI, 0.39-0.81) (Table II). Sensitivity analyses restricting the cisgender comparison groups to only those not receiving hormonal treatments—ie, testosterone, birth control, or menopause therapy—did not significantly affect these findings.Table IIUnadjusted, multivariate, and sensitivity analyses for acne∗aRR was adjusted for age by quartile, body mass index category, race, diabetes or hyperlipidemia, hypertension, corticosteroid or lithium or amoxapine use, and smoking status.Comparison groupCisgender womenCisgender menCisgender women†Only included cisgender women not receiving hormonal birth control or menopausal hormone therapy.Cisgender men‡Only included cisgender men not receiving testosterone therapy.TGD not receiving GAHT who were assigned female at birthTGD not receiving GAHT who were assigned male at birthExposed groupTGD receiving masculinizing GAHTRR95% CIRR95% CIRR95% CIRR95% CIRR95% CIRR95% CI2.76(2.51-3.03)5.01(4.54-5.52)3.59(3.23-4.00)5.03(4.56-5.55)3.13(2.34-4.19)6.54(4.13-10.36)aRR95% CIaRR§For the comparison between TGD patients receiving masculinizing GAHT versus cisgender men, we did not control for corticosteroid, lithium, or amoxapine use because convergence was unable to be achieved when this variable was included.95% CIaRR95% CIaRR§For the comparison between TGD patients receiving masculinizing GAHT versus cisgender men, we did not control for corticosteroid, lithium, or amoxapine use because convergence was unable to be achieved when this variable was included.95% CIaRR95% CIaRR95% CI2.41(2.18-2.67)4.09(3.67-4.56)2.89(2.57-3.25)4.11(3.69-4.56)2.70(2.02-3.62)6.64(3.94-11.20)TGD receiving feminizing GAHTRR95% CIRR95% CIRR95% CIRR95% CIRR95% CIRR95% CI0.55(0.44-0.69)1.00(0.79-1.25)0.71(0.57-0.90)1.00(0.80-1.26)0.62(0.44-0.89)1.30(0.79-2.12)aRR95% CIaRR95% CIaRR95% CIaRR95% CIaRR95% CIaRR95% CI0.51(0.40-0.65)0.85(0.66-1.09)0.62(0.48-0.80)0.86(0.67-1.11)0.56(0.39-0.81)1.32(0.75-2.32)aRR, Adjusted relative risk; GAHT, gender-affirming hormone therapy; RR, relative risk; TGD, transgender/gender diverse.∗ aRR was adjusted for age by quartile, body mass index category, race, diabetes or hyperlipidemia, hypertension, corticosteroid or lithium or amoxapine use, and smoking status.† Only included cisgender women not receiving hormonal birth control or menopausal hormone therapy.‡ Only included cisgender men not receiving testosterone therapy.§ For the comparison between TGD patients receiving masculinizing GAHT versus cisgender men, we did not control for corticosteroid, lithium, or amoxapine use because convergence was unable to be achieved when this variable was included. Open table in a new tab Prior studies examining acne among TGD patients have been limited in size and scope. Our large-cohort study expands upon existing literature, corroborates the association of mGAHT with increased acne, and helps establish the decreased risk of acne in TGD-fGAHT patients.1Motosko C. Zakhem G. Pomeranz M. Hazen A. Acne: a side-effect of masculinizing hormonal therapy in transgender patients.Br J Dermatol. 2019; 180: 26-30Crossref PubMed Scopus (24) Google Scholar,2Giltay E. Gooren L. Effects of sex steroid deprivation/administration on hair growth and skin sebum production in transsexual males and females.J Clin Endocrinol Metab. 2000; 85: 2913-2921Crossref PubMed Scopus (140) Google Scholar,4Thoreson N. Park J.A. Grasso C. et al.Incidence and factors associated with acne among transgender patients receiving masculinizing hormone therapy.JAMA Dermatol. 2021; 157: 290-295Crossref PubMed Scopus (9) Google Scholar Our study’s limitations include the inability to determine causation and the direction of association, lack of generalizability, and undercounting of cases, which were identified based only on the diagnostic codes and only included adults.Acne can be detrimental to well-being, especially for gender minority individuals who already experience discrimination. TGD patients starting mGAHT should be counseled about potentially increased acne risk and treatment options; however, fGAHT may decrease acne risk. To the Editor: Acne is a common dermatologic condition that may be particularly problematic for transgender and gender diverse (TGD) individuals.1Motosko C. Zakhem G. Pomeranz M. Hazen A. Acne: a side-effect of masculinizing hormonal therapy in transgender patients.Br J Dermatol. 2019; 180: 26-30Crossref PubMed Scopus (24) Google Scholar Both masculinizing gender-affirming hormone therapy (mGAHT [ie, testosterone]) and feminizing gender-affirming hormone therapy (fGAHT [ie, estrogen or antiandrogens]) have been linked to the worsening and improvement of acne, respectively, but existing studies have been limited by the size and lack of comparison groups.1Motosko C. Zakhem G. Pomeranz M. Hazen A. Acne: a side-effect of masculinizing hormonal therapy in transgender patients.Br J Dermatol. 2019; 180: 26-30Crossref PubMed Scopus (24) Google Scholar, 2Giltay E. Gooren L. Effects of sex steroid deprivation/administration on hair growth and skin sebum production in transsexual males and females.J Clin Endocrinol Metab. 2000; 85: 2913-2921Crossref PubMed Scopus (140) Google Scholar, 3Wierckx K. Van de Peer F. Verhaeghe E. et al.Short- and long-term clinical skin effects of testosterone treatment in trans men.J Sex Med. 2014; 11: 222-229https://doi.org/10.1111/jsm.12366Abstract Full Text Full Text PDF PubMed Scopus (82) Google Scholar, 4Thoreson N. Park J.A. Grasso C. et al.Incidence and factors associated with acne among transgender patients receiving masculinizing hormone therapy.JAMA Dermatol. 2021; 157: 290-295Crossref PubMed Scopus (9) Google Scholar In this study of 46,507 patients, we examined the overall prevalence and risk ratios of acne in TGD patients receiving mGAHT (TGD-mGAHT) or fGAHT (TGD-fGAHT) compared with those in cisgender men, cisgender women, and TGD patients not receiving gender-affirming hormone therapy who were assigned female or male at birth. We conducted a retrospective cohort study using electronic health records of all TGD and cisgender adults who had at least 1 medical visit at Fenway Health, a community health center in Boston, between August 2014 and August 2020. This study was determined to be exempted from review by the institutional review board of Fenway Institute of Health. We excluded patients without recorded gender identity, birth sex, or body mass index data; cisgender women prescribed testosterone; and cisgender men prescribed birth control or menopause medications. Acne was defined based on International Statistical Classification of Diseases, Ninth and Tenth Revisions, Clinical Modification codes for acne (706.1 and L70.x, respectively). The use of gender-affirming hormone therapy was elicited based on prescription data. We collected data on demographics and other clinical factors that affect acne (Table I). Prevalence was defined as the total number of acne cases, both new and pre-existing, identified based on the diagnostic codes at the time of analysis. Unadjusted risk ratios and adjusted risk ratios (aRRs) with 95% CIs for association with acne were calculated using log-binomial regression. Multivariate models included age, body mass index, diabetes, hyperlipidemia, hypertension, corticosteroid use, lithium or amoxapine use, and smoking status. AFAB, Assigned female at birth; AMAB, assigned male at birth; BMI, body mass index; IQR, interquartile range; TGD-fGAHT, transgender/gender diverse patients receiving feminizing gender-affirming hormone therapy; TGD-mGAHT, transgender/gender diverse patients receiving masculinizing gender-affirming hormone therapy; TGD-nGAHT, transgender/gender diverse patients not undergoing gender-affirming hormone therapy. Both unadjusted and adjusted analyses revealed that TGD-mGAHT patients were significantly more likely to have acne than cisgender women (aRR = 2.41; 95% CI, 2.18-2.67), cisgender men (aRR = 4.09; 95% CI, 3.67-4.56), and TGD patients not receiving gender-affirming hormone therapy. TGD-fGAHT patients were not significantly less likely to have acne than cisgender men (aRR = 0.85; 95% CI, 0.66-1.09) but were significantly less likely to have acne than cisgender women (aRR = 0.51; 95% CI, 0.40-0.65) and TGD patients not receiving gender-affirming hormone therapy who were assigned female at birth (aRR = 0.56; 95% CI, 0.39-0.81) (Table II). Sensitivity analyses restricting the cisgender comparison groups to only those not receiving hormonal treatments—ie, testosterone, birth control, or menopause therapy—did not significantly affect these findings. aRR, Adjusted relative risk; GAHT, gender-affirming hormone therapy; RR, relative risk; TGD, transgender/gender diverse. Prior studies examining acne among TGD patients have been limited in size and scope. Our large-cohort study expands upon existing literature, corroborates the association of mGAHT with increased acne, and helps establish the decreased risk of acne in TGD-fGAHT patients.1Motosko C. Zakhem G. Pomeranz M. Hazen A. Acne: a side-effect of masculinizing hormonal therapy in transgender patients.Br J Dermatol. 2019; 180: 26-30Crossref PubMed Scopus (24) Google Scholar,2Giltay E. Gooren L. Effects of sex steroid deprivation/administration on hair growth and skin sebum production in transsexual males and females.J Clin Endocrinol Metab. 2000; 85: 2913-2921Crossref PubMed Scopus (140) Google Scholar,4Thoreson N. Park J.A. Grasso C. et al.Incidence and factors associated with acne among transgender patients receiving masculinizing hormone therapy.JAMA Dermatol. 2021; 157: 290-295Crossref PubMed Scopus (9) Google Scholar Our study’s limitations include the inability to determine causation and the direction of association, lack of generalizability, and undercounting of cases, which were identified based only on the diagnostic codes and only included adults. Acne can be detrimental to well-being, especially for gender minority individuals who already experience discrimination. TGD patients starting mGAHT should be counseled about potentially increased acne risk and treatment options; however, fGAHT may decrease acne risk. Dr Dommasch reported serving as co-chair of the American Academy of Dermatology Expert Resource Group on Lesbian, Gay, Bisexual, Transgender, Queer/Sexual and Gender Minority Health. Dr Modest and Authors Gao and King have no conflicts of interest to declare. This work was conducted with support from Harvard Catalyst | The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award UL1 TR002541) and financial contributions from Harvard University and its affiliated academic health care centers. The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University, and its affiliated academic health care centers or the National Institutes of Health.