Gender Diverse Patients With Acne

Dr. Klint Peebles discusses considerations for dermatologists who treat acne in gender diverse individuals taking testosterone, including risk factors, treatment nuances, and the iPLEDGE program.

Klint Peebles, MD, Dermatologist, Mid-Atlantic Permanente Medical Group, Washington, DC, and suburban Maryland.

“Why does this matter? First of all, any dermatologist knows that acne is one of the most common conditions that we see. The vast majority of patients ages 12 to 25 (about 85%) are impacted by acne to some degree, which is the most common condition seen in this age group in the outpatient dermatology setting.1, 2 At the same time, we’re seeing consistent increases in the number of people in the U.S. identifying as transgender or gender diverse. [About] 0.6% of U.S. adults identify as transgender based on recent estimates,”3 said Klint Peebles, MD, who presented on managing acne in gender diverse individuals who are taking testosterone during the “Advances and Quandaries in Isotretinoin Management: Cases and Discussions with the Experts” session at the 2023 AAD Innovation Academy in Tampa, Florida.

“To put that into perspective, it is more than the number of individuals in the U.S. who have type 1 diabetes.”4

According to Dr. Peebles, the number of Americans identifying as sexually and gender diverse* is increasing, likely due to numerous factors including growing social comfort and visibility. Recent surveys show that one in five Gen Z adults identifies as LGBT.5 Gender expansive identities are also more frequent among younger people with almost 2% of children in the US identifying as transgender and similarly roughly 2% of high-school-age people identifying as gender diverse, which may be an underestimate in some areas of the nation.6

Testosterone, Acne & Trans Men

Dr. Peebles specifically addressed masculinizing hormone therapy, or testosterone, in trans men or non-binary persons seeking masculinizing effects. 

“In the United States, testosterone is usually given as a weekly intramuscular injection, though other routes of administration are also available. Testosterone has many effects, one of which is on the skin. We can see skin oiliness and acne develop as well as body fat redistribution, facial and body hair growth, deepening of the voice, etc.” 

Acne is very common in gender diverse patients taking testosterone, and dermatologists are essentially guaranteed to encounter them, said Dr. Peebles. In general, there is limited data on acne specifically in the transgender population, with much of the current management approach extrapolated from cisgender individuals. Historically, it was commonly believed that acne would develop within several months of starting testosterone, plateau, and then gradually decrease in severity over the next year or two. However, research shows that this natural history might be more complex. 

“More recent data…  tells us that testosterone-induced acne may in some cases be more delayed in onset and tends to be more persistent than originally thought.”

Dr. Peebles cited a study of almost 1,000 patients at a large Boston center showing that acne prevalence increased from 6% before testosterone to more than 31% after a mean testosterone duration of 3 years.7

Still other research suggests long-lasting effects from testosterone on acne in trans-men. In one study, almost 70% of patients reported ongoing mild to moderate acne after an average of 10 years of testosterone, said Dr. Peebles.8,9

“Some of the risk factors that we’ve seen for acne in this population would be individuals who had preexisting acne before starting testosterone therapy, starting testosterone at a younger age (it seems the risk is greater between age 18 and 25 but more data is needed), potentially higher BMI, high serum testosterone levels, and current smoking.” 

But the role of testosterone levels in driving acne remains unclear, said Dr. Peebles. 

“There has only been a single study looking at serum testosterone levels in this context, and it did not evaluate the dose of testosterone used. The study concluded that a serum level of greater than 630 ng/dL was associated with a higher odds of acne after 2 years.”10

It may be important in some cases to assess blood testosterone levels, but it’s also important to know when to do that, said Dr. Peebles. 

“With the weekly injection of testosterone, it’s ideal to get that level done between injections so that you are not getting an artificially low dose right before the injection or an artificially high one immediately after the injection. If in doubt, coordinate with the patient’s primary gender-affirming care clinician to ensure the level is obtained at the most appropriate time.”

Managing Acne

In general, managing acne in trans men taking testosterone mirrors acne management in cisgender people, especially when they have mild or mild-to-moderate acne. But there are nuances, said Dr. Peebles.  

  1. Oral spironolactone should not be used in the setting of testosterone, as it will antagonize the gender-affirming effects. 
  2. Topical clascoterone may be an ideal option topical. This hasn’t been studied explicitly in transgender individuals, but it is something being currently used and can be considered. 
  3. Contraception can be considered as acne therapy, but the selection of the agents should be discussed carefully in the context of the patient’s gender affirmation goals and current regimen.
  4. Isotretinoin is often indicated and has several unique considerations, Dr. Peebles said. 

“Prior to the most recent changes to iPLEDGE, the iPLEDGE program for isotretinoin was inherently discriminatory to transgender people, meaning that the only way to identify a patient’s pregnancy potential was to register them as female, which marginalized transgender men and other nonbinary patients not identifying as women yet retaining pregnancy potential.”

Today, iPLEDGE includes two categories—those who can become pregnant and those who cannot become pregnant, but there remain important nuances to consider when having that conversation, Dr. Peebles said. 

“When determining a patient’s pregnancy potential, we have to understand what their anatomy is. Do they have a uterus and a functioning ovary? If so, they would have to be registered as a patient who can become pregnant. But in terms of whether or not they would need contraception, this is really something that depends on their sexual behaviors and whether or not they are engaging in sexual behaviors that would put them at risk for pregnancy.”

It’s important to have a comprehensive understanding of those behaviors, said Dr. Peebles. And a patient’s expressed identity doesn’t necessarily give you that fully reliable understanding. 

“If someone identifies as a transgender man but they have a uterus and ovaries capable of producing a pregnancy, then we would want to know whether they are engaging in receptive penile-vaginal intercourse with someone who makes sperm. That’s part of the history taking.  If someone is not engaging in those kinds of sexual behaviors that could result in pregnancy, then abstinence is appropriate for their registration in iPLEDGE.”

Remember, too, that testosterone is not contraception, said Dr. Peebles. 

“Additionally, testosterone itself is not an absolute contraindication to any form of hormonal or nonhormonal contraception, but again therapeutic choices must be made in a patient-centered context.”

Still, progestin-based options alone may worsen acne and are not considered primary contraception per iPLEDGE. But combined oral contraceptives with estrogen and progestin can be used for contraception in transgender individuals on testosterone, Dr. Peebles said. 

“… if your patient needs contraception, definitely coordinate with their primary gender clinician to really figure out the best contraceptive choice for them.”

It’s also important when starting isotretinoin in a transgender person to discuss surgical affirmation goals, especially because of the potential concerns about delayed wound healing and the preferences of the surgeon, said Dr. Peebles. 

“Transgender men who are imminently considering top surgery, or chest surgery, may need to coordinate with their surgeon prior to starting isotretinoin just to make sure we get their opinion and pearls as far as when to start isotretinoin and when to stop before surgery. We certainly wouldn’t want to unnecessarily disrupt their affirmation therapy timeline, if possible.”

Consider psychiatric comorbidities and balance risks and benefits when considering such things as anxiety and depression, Dr. Peebles said. 

“Oftentimes, I find that just treating severe acne really increases wellbeing, makes mood better and lessens anxiety and depression. But obviously transgender individuals… have higher rates of anxiety and depression so it’s important to have that comprehensive history and have an understanding of that before we start the isotretinoin.” 

There’s no significant evidence that the lab monitoring should differ from that of cisgender individuals, said Dr. Peebles. 

“In terms of dosing for isotretinoin, we don’t have any evidence specifically in the transgender population yet, and the approach mirrors that of cisgender individuals. I tend to use lower dosing for longer periods of time to prevent side effects and to maintain compliance, but certainly cumulative dosing is reasonable as well. Sometimes I’ll even do pulse therapy, for instance 20 mg per day, 3 days a week depending on the trajectory and overall affirmation goals in light of acne treatment progress.” 

Maintaining a Safe Space

Gender neutrality is important. That includes using appropriate language, echoing the patient’s language, and using gender-neutral terms when possible. It also includes using a trauma-informed care approach when asking about sexual history, said Dr. Peebles. 

The legislation involving transgender care is evolving, Dr. Peebles said. 

“Many states have moved to legislatively block gender-affirming care, depending on the state. But there are many different ongoing court cases that are challenging the legality of those legislative actions. It’s very state-specific at this point. It’s possible, depending on the language of some of these laws, that dermatologic care of transgender people could be implicated. Especially in the current legislative and political environment, it’s increasingly more important that we establish safe spaces for transgender and gender-diverse people in our clinics.” 

“Dermatologic education is minimal when it comes to the standardization of curricula focused on gender-affirming care in dermatology. A study from a few years ago showed that almost half of dermatology residency programs had zero sexual and gender-diverse content hours.”11

There are multiple resources for gender-affirming care including acne management in gender diverse populations. The American Academy of Dermatology (AAD.org) has a sexual and gender-diverse dermatology module on its Basic Dermatology Curriculum page.

References:

  1. American Academy of Dermatology. Skin Conditions by the Numbers. www.aad.org. Accessed September 11, 2023.
  2. Lynn DD, Umari T, Dunnick CA, Dellavalle RP. The epidemiology of acne vulgaris in late adolescence. Adolesc Health Med Ther. 2016; 7:13-25. doi:10.2147/AHMT.S55832
  3. Herman JL, Flores AR, O’Neill KK. How Many Adults and Youth Identify as Transgender in the United States? UCLA School of Law Williams Institute. Report. June 2022. Accessed September 11, 2023.
  4. Bullard KM, Cowie CC, Lessem SE, et al. Prevalence of Diagnosed Diabetes in Adults by Diabetes Type — United States, 2016. MMWR Morb Mortal Wkly Rep 2018;67:359–361. DOI: http://dx.doi.org/10.15585/mmwr.mm6712a2
  5. Jones JM. LGBT Identification in U.S. Ticks Up to 7.1%. Gallup. February 17, 2022. Accessed September 11, 2023.
  6. Johns MM, Lowry R, Andrzejewski J, et al. Transgender Identity and Experiences of Violence Victimization, Substance Use, Suicide Risk, and Sexual Risk Behaviors Among High School Students — 19 States and Large Urban School Districts, 2017. MMWR Morb Mortal Wkly Rep 2019;68:67–71. DOI: http://dx.doi.org/10.15585/mmwr.mm6803a3.
  7. Thoreson N, Park JA, Grasso C, et al. Incidence and Factors Associated With Acne Among Transgender Patients Receiving Masculinizing Hormone Therapy. JAMA Dermatol. 2021;157(3):290-295. doi:10.1001/jamadermatol.2020.5347
  8. Nakamura A, Watanabe M, Sugimoto M, et al. Dose-response analysis of testosterone replacement therapy in patients with female to male gender identity disorder. Endocr J. 2013;60(3):275-281. doi:10.1507/endocrj.ej12-0319.
  9. Stuyver I, Somers S, Provoost V, et al. Ten years of fertility treatment experience and reproductive options in transgender men. Int J Transgend Health. 2020;22(3):294-303. Published 2020 Oct 13. doi:10.1080/26895269.2020.1827472
  10. Park JA, Carter EE, Larson AR. Risk factors for acne development in the first 2 years after initiating masculinizing testosterone therapy among transgender men. J Am Acad Dermatol. 2019;81(2):617-618. doi:10.1016/j.jaad.2018.12.040.
  11. Jia JL, Nord KM, Sarin KY, Linos E, Bailey EE. Sexual and Gender Minority Curricula Within US Dermatology Residency Programs. JAMA Dermatol. 2020;156(5):593–594. doi:10.1001/jamadermatol.2020.0113.

*Terminology Notes

It’s important to note that terminology is fluid, and these pearls are general rules of thumb, said Dr. Peebles. Ultimately the key to appropriate, affirming terminology is to echo the terms each patient or individual uses. 

“Sex” is a biological term and is also known as sex assigned at birth. It tends to be based on observation of external genitalia at birth. In rare cases, genital ambiguity may exist in which a sex assignment is more complex. In such cases, individuals may not fit typical binary notions of male and female, which can describe intersex conditions, also known as differences in sex development or variations of sex characteristics.  

“Gender” is a social construction often based on and extrapolated from sex assigned at birth. While sex is a biological term, gender is a more complex sociocultural term describing the numerous roles, attributes, behaviors, and norms expected of individuals based on their gender, said Dr. Peebles. 

“Sex and gender are distinct concepts that do not inherently define each other.” 

While this may be a major conceptual paradigm shift for many, it is critical to understand that societal expectations of an individual based upon gender are not innate to biological sex. 

The terms “nonbinary,” “transgender,” “genderqueer,” and “gender-nonconforming,” refer to the diversity of identities and lived experiences of those who do not identify as cisgender, said Dr. Peebles. 

“In other words, their gender identify differs from their sex assigned at birth. And you may hear terms intended to promote broader inclusion, such as ‘gender diverse,’ ‘gender expansive,’ or ‘gender minority.’”

Sexual behaviors are distinct from all these terms as well, Dr. Peebles said. 

A patient with “gender dysphoria” is one who experiences distress as a result of their gender identity not aligning with their sex assigned at birth, according to Dr. Peebles. Not all transgender people experience dysphoria, and those who do often experience it in different ways and in different contexts. 

“We use various interventions or decisions known as gender affirmation to help mitigate dysphoria. Such measures encompass a scope of interventions, ranging from psychological, social, and legal affirmation to medical and surgical affirmation. Medical affirmation can include hormone therapy such as testosterone, estrogen, and anti-androgenic medications depending on the specific needs of the individual.”