Hormonal Therapy in Acne: DHT, Spironolactone, and Clascoterone

Dr Lawrence Green discusses how androgens and DHT contribute to acne pathogenesis through sebum production, inflammation, and abnormal keratinization. Learn when to incorporate hormonal therapies like spironolactone and clascoterone, why serum androgen levels may not correlate with acne severity, and how anti-androgen strategies offer a more comprehensive, mechanism-based approach to acne management.

Transcript:

Hi, my name is Larry Green. I'm a clinical professor of dermatology at George Washington University School of Medicine in Washington, D.C.

How do androgens—particularly DHT—drive key pathways in acne pathogenesis, and why don’t serum androgen levels always correlate with disease severity?

Dr Green: Androgens are intricately involved in the creation of acne, and they're involved in all the inflammatory process when you think about it. Androgens promote sebum production, so high sebum production increases the amount of C acnes that come in the pore, so it's inflammatory. They also cause abnormal desquamation, which can create comedones. So they're involved intimately, multifactorially, I should say, in acne processes. So having the approach of an anti-androgen therapy really makes sense.

Androgen levels have not been found to be correlated with acne. However, there was one smaller study in China from a few years ago that showed the ratio of androgens to estrogens does correlate to the amount of acne someone has. That study has not been replicated, but that does show the ratio may be making a difference, not the actual amount, which can be so variable from person to person.

With growing interest in hormonal therapies, how should clinicians decide when to incorporate anti-androgen treatments like spironolactone or clascoterone into acne management?

Dr Green: So let's start with topical hormonal therapy, with clascoterone. It's the only FDA-approved antiandrogen that we have. And it's approved for men and women to treat acne. I think it should be an integral part of acne therapy in a different way. It does not supplement the need for benzoyl peroxides or other anti -inflammatory products for acne. But when I like to use clascoterone is when someone has more oily skin or there's more hormonal acne, especially in a female patient. So because antiandrogens help squelch up that sebum, they stop sebum secretion, that's going to help dry the person out and also improve their acne. Bottom line, topical: I like it for people with oilier skin and hormonally induced acne in women, in addition to my regular therapy.

When it comes to oral treatments, spironolactone is used a lot for women who have acne. It's not used for men, not at this time. It's not been studied in men. But it's used for women who have a lot of inflammatory acne. Now, it used to be that I used, and most of the world used spironolactone for women who have menstrual-related acne. In other words, when women have that premenstrual flare of inflammatory lesions, especially on the jawline and chin, when that happens, they only get acne inflamed once a month, spironolactone was a great choice, and it still is for that. But there are more and more studies that show that spironolactone is also a great choice for women with any type of inflammatory acne, whether it's menstrual-related or not. In fact, there are studies that show it works just as well as doxycycline. I find that I'm using spironolactone more and more because it's something we can use long-term to control inflammatory acne, unlike doxycycline, which is recommended just for a few months at a time.

Given that many current therapies target only one or two pathways, what opportunities exist for more comprehensive, mechanism-based treatment approaches in acne?

Dr Green: I think hormonal therapies for acne target more factors that create acne than any other product. They lessen sebum production, they correct abnormal keratinization, and they also lessen inflammation. Whereas other products that are FDA-approved for acne, for example, such as doxycycline, just target the inflammation in the C acnes component. They don't do anything for sebum secretion or abnormal keratinization. So we have, when we look at hormonal therapy, we have the opportunity to really go after the main pathogenic factors in acne. And we don't have any other therapies that do it in the same way. And that's why I like the idea of using hormonal therapy to treat acne.