Dr. Julie Harper discusses adult female acne, hormonal treatment for men, spironolactone safety, and the need for combination treatments.
Julie Harper, MD, is a board-certified dermatologist, Dermatology and Skin Care Center, Birmingham, Alabama.
“It took us a long time to get people to understand that all acne is inflammatory. Even the acne that doesn’t look red. Even the acne that’s just blackheads. It’s inflammatory by nature…. It’s the same thing with hormonal acne,” said Julie Harper, MD, Founding Director of the Acne and Rosacea Society, who discussed hormonal acne in the Update 2022: Acne and Rosacea session at Maui Derm 2022.
“Every hormonal treatment we’ve had, until recently, we can only use in women. …it’s made us look at…the adult woman, and say, she has hormonal acne, because look how well it does when I use a hormonal treatment.”
But hormonal acne isn’t exclusive to women. The pathogenesis includes several hormonal pathways, said Dr. Harper.
“It’s also comedonal acne in a 10-year-old boy. That’s hormonal acne. And mixed acne in a 16-year-old boy. That’s hormonal acne. So I think one huge take home is … remember that, yes, there is a subset of acne that happens in adult females, but let’s just call that adult female acne.”
A Hormonal Treatment for All
The FDA approved Winlevi (clascoterone) cream 1% topical (Sun Dermatology) in August of 2020 and has somewhat equalized the acne treatment opportunities for men and women.
“Clascoterone is a topical androgen receptor inhibitor that doesn’t have really any systemic effects. So we’re going to get all that anti-androgen effect in the skin and none of it in the body, which now means, guess who can use this? The guys,” said Dr. Harper.
In clinical trials,1 1400 participants were randomized into two identical vehicle-controlled studies. Nearly 40% of participants were men. Both men and women had safe and efficacious results with few adverse events.
“We’ve never had an anti-androgen that we could use in men, for obvious reasons. And now we do because it’s topical with limited systemic exposure,” said Dr. Harper.
Clascoterone (BID) is approved to treat acne in men and women 12 years of age and older. For now, twice-a-day treatment is important, said Dr. Harper.
“We’re going to be using it in combinations with other things, other topicals, I realize that. We’re going to be stacking things together. We don’t have a lot of evidence to support that yet but that is the way most of us are going to use it in the clinic. But remember, we can use it in men and women.”
Safety and Spironolactone
The best thing about spironolactone is that it’s not an antibiotic and can be used long term, said Dr. Harper. It’s also inexpensive, generic, and easy to access.
“[The black box warning comes from] animal studies, but we are risk-averse people. We want to do a really good job for our patients and we’re aware that that’s in there.”
While animal studies showed tumor development in rats, human database studies by Mackenzie et al.2 and Biggar et al.3 did not.
“Both of those studies were big database studies where they looked at women who had been treated with spironolactone…to see if they had a higher rate of diagnosis of breast cancer. And the answer was no.”
In a retrospective analysis, Wei et al.4 examined the incidence of recurrence in breast cancer survivors who used spironolactone for hair loss. Researchers found that spironolactone was not independently associated with breast cancer recurrence, said Dr. Harper.
“People are seeing the efficacy of the drug, not seeing safety problems with it, and then we’re getting good information like this that makes us feel better about things like the risk of hyperkalemia and breast cancer.”
Birth Control Pills in the Background
While dermatologists don’t typically prescribe birth control pills as frequently as spironolactone, many acne patients are already on birth control, said Dr. Harper.
“It doesn’t mean that that doesn’t help their acne. It’s sitting there in the background very likely helping.”
And although birth control pills come with risks, including venous thromboembolism, they don’t outweigh that of an unwanted pregnancy, said Dr. Harper. They also offer protection for other types of cancer, including colon, uterine, ovarian, and (perhaps) cervical.
“So if you know somebody also needs contraception, you’ve got a really good risk-benefit ratio.”
There are four brands FDA approved to treat acne: Yaz, Beyaz, Estrostep FE, and Ortho Tri-Cyclen. But that doesn’t limit use, said Dr. Harper.
“Probably every birth control pill, as long as it’s a combination of estrogen and progestin… should help acne. You don’t want to do a progestin only minipill [or] an IUD that is only progestin…,” which could make acne worse.
Importantly, birth control pills are contraindicated in smokers, said Dr. Harper.
“The definitive contraindication, I think, is somebody who’s over the age of 35 [and] who smokes more than 10 cigarettes a day.”
Other exclusions for Dr. Harper include a history of blood clotting or migraines.
“Pretty much everything I’ve said, whether it’s clascoterone, spironolactone, birth control pills—these are not standalone medicines. They’re working on just a part of the pathogenesis of acne. They’re working on, for the most part, sebum and inflammation. And so we’re going to mix them with other products that come in and help clear out that pore or that have an antimicrobial effect, so that we’re really getting the best effect that we can.”
References
- Hebert A, Thiboutot D, Stein Gold L, Cartwright M, Gerloni M, Fragasso E, Mazzetti A. Efficacy and Safety of Topical Clascoterone Cream, 1%, for Treatment in Patients With Facial Acne: Two Phase 3 Randomized Clinical Trials. JAMA Dermatol. 2020 Jun 1;156(6):621-630. doi: 10.1001/jamadermatol.2020.0465. PMID: 32320027; PMCID: PMC7177662.
- Mackenzie IS, Macdonald TM, Thompson A, Morant S, Wei L. Spironolactone and risk of incident breast cancer in women older than 55 years: retrospective, matched cohort study. BMJ. 2012 Jul 13;345:e4447. doi: 10.1136/bmj.e4447. PMID: 22797844; PMCID: PMC3396460.
- Biggar RJ, Andersen EW, Wohlfahrt J, Melbye M. Spironolactone use and the risk of breast and gynecologic cancers. Cancer Epidemiol. 2013 Dec;37(6):870-5. doi: 10.1016/j.canep.2013.10.004. Epub 2013 Nov 1. PMID: 24189467.
- Wei C, Bovonratwet P, Gu A, Moawad G, Silverberg JI, Friedman AJ. Spironolactone use does not increase the risk of female breast cancer recurrence: A retrospective analysis. J Am Acad Dermatol. 2020 Oct;83(4):1021-1027. doi: 10.1016/j.jaad.2020.05.081. Epub 2020 May 21. PMID: 32446820.
Disclosures: Dr. Harper is a consultant, speaker, and/or advisory board member for Cutera, Almirall, Sun, LaRoche-Posay, Ortho, EPI, BioPharmX, Cassiopeia, Cutanea, Vyne, Galderma, Dermira, and Sol Gel.