madman
Super Moderator
* Androgens play a central role in the development of acne vulgaris (acne). Testosterone and its more potent metabolite, dihydrotestosterone (DHT), bind to androgen receptors in sebocytes [1,2]. They activate sebaceous gland activity, inducing a significant increase of sebum production with a modification of the composition of sebum [3].Sebaceous gland hyperplasia, under androgenic control and via the activation of lipogenic pathways (SREBP-1, PPARγ), leads to hyperseborrhoea associated with a qualitative alteration of sebum (increased triglycerides, relative decrease in linoleic acid, oxidation of squalene) [4,5]. This lipid alteration disrupts keratinocytes differentiation in the follicular canal by promoting hyperkeratinisation and impairment of the epithelial barrier (tight junctions, abnormal cornification) and in addition proliferation of keratinocytes of the epithelial barrier of the sebaceous gland. This ultimately results in an obstruction of the sebaceous gland canal and the development of retentional lesions.
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Figure 1: Physiopathology of acne with a focus on increased androgen levels.
Introduction
Androgens play a central role in the development of acne vulgaris (acne). Testosterone and its more potent metabolite, dihydrotestosterone (DHT), bind to androgen receptors in sebocytes [1,2]. They activate sebaceous gland activity, inducing a significant increase of sebum production with a modification of the composition of sebum [3].Sebaceous gland hyperplasia, under androgenic control and via the activation of lipogenic pathways (SREBP-1, PPARγ), leads to hyperseborrhoea associated with a qualitative alteration of sebum (increased triglycerides, relative decrease in linoleic acid, oxidation of squalene) [4,5]. This lipid alteration disrupts keratinocytes differentiation in the follicular canal by promoting hyperkeratinisation and impairment of the epithelial barrier (tight junctions, abnormal cornification) and in addition proliferation of keratinocytes of the epithelial barrier of the sebaceous gland. This ultimately results in an obstruction of the sebaceous gland canal and the development of retentional lesions. The follicular microenvironment becomes more anaerobic and rich in lipid substrates, promoting follicular dysbiosis and the production of bacterial lipases, which generate pro-inflammatory free fatty acids. Concurrently, oxidized lipids (peroxidized squalene) activate keratinocytes and immune cells via TLR2 and the inflammasome (NLRP3), amplifying the local inflammatory response [6]. These androgen-induced changes in sebum production contribute to follicular dysbiosis, characterized by a reduction in the diversity of the six major Cutibacterium acnes (C. acnes) phylotypes and the predominance of phylotype IA1. Alterations in sebum composition also favour the emergence of a more virulent C. acnes phenotype, associated with the release of pro-inflammatory antimicrobial peptides and extracellular vesicles. This virulent phenotype appears to be driven, at least in part, by bacteriophage-mediated acquisition of virulence-associated genes in phylotype IA1. Together, these microbial and host interactions promote persistent activation of innate immunity and contribute to the chronic inflammatory process characteristic of acne [7,8].
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In conclusion, long-term management and prevention of exogenous androgen-driven acne relapse require an integrated, interdisciplinary approach that considers pharmacological, hormonal, metabolic, environmental, and behavioural factors. As persistent androgenic signalling and hormonal fluctuations can influence sebaceous activity and treatment response, management should focus on maintaining follicular homeostasis and preventing the re-establishment of a pro-inflammatory, dysbiotic microenvironment. Long-term relapse prevention should prioritize non-antibiotic strategies, sustained normalization of follicular biology, and preservation of microbial diversity to reduce recurrent disease and limit the emergence of resistant microbial communities.
==========
Figure 1: Physiopathology of acne with a focus on increased androgen levels.
Introduction
Androgens play a central role in the development of acne vulgaris (acne). Testosterone and its more potent metabolite, dihydrotestosterone (DHT), bind to androgen receptors in sebocytes [1,2]. They activate sebaceous gland activity, inducing a significant increase of sebum production with a modification of the composition of sebum [3].Sebaceous gland hyperplasia, under androgenic control and via the activation of lipogenic pathways (SREBP-1, PPARγ), leads to hyperseborrhoea associated with a qualitative alteration of sebum (increased triglycerides, relative decrease in linoleic acid, oxidation of squalene) [4,5]. This lipid alteration disrupts keratinocytes differentiation in the follicular canal by promoting hyperkeratinisation and impairment of the epithelial barrier (tight junctions, abnormal cornification) and in addition proliferation of keratinocytes of the epithelial barrier of the sebaceous gland. This ultimately results in an obstruction of the sebaceous gland canal and the development of retentional lesions. The follicular microenvironment becomes more anaerobic and rich in lipid substrates, promoting follicular dysbiosis and the production of bacterial lipases, which generate pro-inflammatory free fatty acids. Concurrently, oxidized lipids (peroxidized squalene) activate keratinocytes and immune cells via TLR2 and the inflammasome (NLRP3), amplifying the local inflammatory response [6]. These androgen-induced changes in sebum production contribute to follicular dysbiosis, characterized by a reduction in the diversity of the six major Cutibacterium acnes (C. acnes) phylotypes and the predominance of phylotype IA1. Alterations in sebum composition also favour the emergence of a more virulent C. acnes phenotype, associated with the release of pro-inflammatory antimicrobial peptides and extracellular vesicles. This virulent phenotype appears to be driven, at least in part, by bacteriophage-mediated acquisition of virulence-associated genes in phylotype IA1. Together, these microbial and host interactions promote persistent activation of innate immunity and contribute to the chronic inflammatory process characteristic of acne [7,8].
========
In conclusion, long-term management and prevention of exogenous androgen-driven acne relapse require an integrated, interdisciplinary approach that considers pharmacological, hormonal, metabolic, environmental, and behavioural factors. As persistent androgenic signalling and hormonal fluctuations can influence sebaceous activity and treatment response, management should focus on maintaining follicular homeostasis and preventing the re-establishment of a pro-inflammatory, dysbiotic microenvironment. Long-term relapse prevention should prioritize non-antibiotic strategies, sustained normalization of follicular biology, and preservation of microbial diversity to reduce recurrent disease and limit the emergence of resistant microbial communities.
