The vagina: emerging evidence on the anti-inflammatory role of testosterone
Linda Vignozzi1,2– , Elisa Maseroli1 – , Ilaria Cellai2, Sandra Filippi3, Paolo Comeglio2, Sarah Cipriani2 – , Irene Scavello2 – , Giulia Rastrelli2 – , Margherita Frison2, Mario Maggi2 –
1 – SODc Andrology, Female Endocrinology and Gender Incongruence, Careggi University Hospital, Florence
2 – Department of Biomedical, Experimental and Clinical Sciences “Mario Serio”, University of Florence
3 – Department of Neuroscience, Psychology, Pharmaceutical and Child Health Area, University of Florence
Corresponding author: Linda Vignozzi
The female genitourinary tract is constantly exposed to infectious and inflammatory insults. Inflammation is an essential mechanism, usually able to restore tissue homeostasis; however, uncontrolled and self-maintaining inflammation can lead to dysfunctional processes, which may contribute to the onset of chronic conditions affecting the female genitourinary tract. These include the Genitourinary Syndrome of Menopause (GSM), characterized by vulvovaginal atrophy and symptoms of the lower urinary tract. The primary cause of GSM is a drop of estrogen levels at menopause; however, a decline in androgen level and chronic inflammation also play a pathogenic role. Androgen signaling generally suppress the activity of immune cells. In recent years, androgens have been described to play a key role in maintaining vaginal health, by positively regulating vascular and non-vascular smooth muscle and collagen growth and function, nerve density and function, and genital hemodynamics. Recent in vitro evidence also suggests an anti-inflammatory action of androgens within the vagina. In fact, it has been shown that hu- man vagina smooth muscle cells are able to be involved in the inflammatory response, behaving as resident nonprofessional antigen presenting cells and producing cytokines, chemokines and growth factors. Testosterone, ac- ting through its more active metabolite DHT (Dihydrotestosterone), seems to exert a relevant anti-inflammatory effect on vagina smooth muscle cells, blunting their ability to respond to inflammatory stimuli and to perpetuate inflammation. In particular, DHT counteracts the secretion of Interferon (IFNg), the most potent Th1 cytokine, which plays a key role in development of autoimmunity and chronic, self-perpetuating inflammatory diseases. These data suggest that androgens represent a potential therapeutic strategy for the GSM and other inflammatory conditions of the female genitourinary tract, to be further investigated in clinical studies.
Keywords: androgens; menopause; vagina; inflammation; infection.
Available in LRIOG Nr.2 – 2021