The primary role of sebum in the pathophysiology of acne vulgaris and its therapeutic relevance in acne management

Figures & data

Figure 1. Contribution of sebum to acne pathophysiology. Acne pathophysiology is driven by 4 key factors: alteration in sebaceous immunobiology (excessive sebum production and alterations in sebum composition), inflammation, follicular hyperkeratinization, and colonization of Cutibacterium acnes (6,47,48). Solid lines indicate an impact of sebum on the other 3 acne pathogenic factors, whereas dashed lines indicate the inverse.

Figure 2. Sebum production trends by facial region. Sebum levels are highest on the nose, followed by the forehead and chin (comprising the T-zone), and are lowest on the cheeks (comprising the U-zone), regardless of the presence of acne lesions (86,87). Differences in sebum production have also been noted based on patient age and sex (85,87).

Table 1. Overview of pharmacologic therapies for patients with acne and the impact on sebaceous immunobiology.

Therapy	Route of administration	Indication	Impact on sebaceous immunobiology
COCs	Oral (18,19,93,94)	Ortho Tri-Cyclen and Estrostep Fe: Females ≥15 years of age with moderate acne that is unresponsive to topical anti-acne treatment (93,94) Yaz and Beyaz: Females ≥14 years of age with moderate acne (18,19)	Inhibits ovarian androgen production and lowers circulating testosterone concentration and sebum production (7)
Isotretinoin	Oral (21)	Patients with severe recalcitrant nodular acne (21). Female patients of childbearing potential must be on 2 simultaneous forms of effective contraception	Reduces sebocyte differentiation, proliferation, and sebum production (7)
Spironolactone	Oral (1,17)	Used off label to treat moderate-to-severe acne in adult female patients (1,17)	Acts as a competitive inhibitor of sebocyte ARs, thereby reducing AR activation and excessive sebum production (1,95)
Clascoterone	Topical cream (96)	Patients ≥12 years of age with acne (96)	Acts as a competitive inhibitor of sebocyte ARs, thereby reducing AR activation, increased sebum production, and proinflammatory cytokine production (97,98)

AR: androgen receptor; COC: combined oral contraceptive.

Baldwin H, Farberg A, Frey C, et al. Unmet needs in the management of acne vulgaris: a consensus statement. J Drugs Dermatol. 2023;22(6):582–587. doi: 10.36849/JDD.7587.

 PubMedGoogle Scholar

Li X, He C, Chen Z, et al. A review of the role of sebum in the mechanism of acne pathogenesis. J Cosmet Dermatol. 2017;16(2):168–173. doi: 10.1111/jocd.12345.

 PubMed Web of Science ®Google Scholar

Makrantonaki E, Ganceviciene R, Zouboulis C. An update on the role of the sebaceous gland in the pathogenesis of acne. Dermatoendocrinol. 2011;3(1):41–49. doi: 10.4161/derm.3.1.13900.

 PubMedGoogle Scholar

Park SG, Kim YD, Kim JJ, et al. Two possible classifications of facial skin type by two parameters in korean women: sebum excretion rate (SER) and skin surface relief (SSR). Skin Res Technol. 1999;5(3):189–194. doi: 10.1111/j.1600-0846.1999.tb00130.x.

 Web of Science ®Google Scholar

Choi CW, Choi JW, Park KC, et al. Facial sebum affects the development of acne, especially the distribution of inflammatory acne. J Eur Acad Dermatol Venereol. 2013;27(3):301–306. doi: 10.1111/j.1468-3083.2011.04384.x.

 PubMed Web of Science ®Google Scholar

Spigariolo CB, Giacalone S, Nazzaro G. Maskne: the epidemic within the pandemic: from diagnosis to therapy. J Clin Med. 2022;11(3):618. doi: 10.3390/jcm11030618.

 PubMed Web of Science ®Google Scholar

YAZ® (Drospirenone and ethinyl estradiol) tablets [prescribing information]. Whippany (NJ): Bayer HealthCare Pharmaceuticals Inc; 2023.

 Google Scholar

BEYAZ® (drospirenone/ethinyl estradiol/levomefolate calcium tablets and levomefolate calcium tablets), for oral use [prescribing information]. Whippany (NJ): Bayer HealthCare Pharmaceuticals Inc.; 2023.

 Google Scholar

ORTHO TRI-CYCLEN® tablets (norgestimate/ethinyl estradiol) [prescribing information]. Tulsa (OK): Physicians Total Care, Inc.; 2012.

 Google Scholar

ESTROSTEP® Fe (norethindrone acetate and ethinyl estradiol tablets, USP and ferrous fumarate tablets) [prescribing information]. Irvine (CA): Allergan USA, Inc.; 2017.

 Google Scholar

Zouboulis CC, Piquero-Martin J. Update and future of systemic acne treatment. Dermatology. 2003;206(1):37–53. doi: 10.1159/000067821.

 PubMed Web of Science ®Google Scholar

ACCUTANE® (isotretinoin) [prescribing information]. Nutley (NJ): Roche Laboratories Inc.; 2008.

 Google Scholar

Costa CS, Bagatin E, Yang Z, et al. Systemic pharmacological treatments for acne: an overview of systematic reviews (protocol). Cochrane Database Syst Rev. 2021;2021(11):1.

 Google Scholar

Zaenglein AL, Pathy AL, Schlosser BJ, et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol. 2016;74(5):945–973 e33. doi: 10.1016/j.jaad.2015.12.037.

 PubMed Web of Science ®Google Scholar

Layton AM, Eady EA, Whitehouse H, et al. Oral spironolactone for acne vulgaris in adult females: a hybrid systematic review. Am J Clin Dermatol. 2017;18(2):169–191. doi: 10.1007/s40257-016-0245-x.

 PubMed Web of Science ®Google Scholar

WINLEVI® (clascoterone) cream, for topical use [prescribing information]. Cranbury (NJ): Sun Pharmaceutical Industries, Inc.; 2022.

 Google Scholar

Rosette C, Rosette N, Mazzetti A, et al. Cortexolone 17α-propionate (clascoterone) is an androgen receptor antagonist in dermal papilla cells in vitro. J Drugs Dermatol. 2019;18(2):197–201.

 PubMed Web of Science ®Google Scholar

Rosette C, Agan FJ, Mazzetti A, et al. Cortexolone 17α-propionate (clascoterone) is a novel androgen receptor antagonist that inhibits production of lipids and inflammatory cytokines from sebocytes in vitro. J Drugs Dermatol. 2019;18(5):412–418.

 PubMed Web of Science ®Google Scholar

Data availability statement

Data sharing is not applicable to this article as no data sets were generated or analyzed during the current study.