La vagina: evidenze emergenti sul ruolo anti-infiammatorio del testosterone

La vagina: evidenze emergenti sul ruolo anti-infiammatorio del testosterone

Linda Vignozzi1,2 – Orcid, Elisa Maseroli1 – Orcid, Ilaria Cellai2, Sandra Filippi3, Paolo Comeglio2, Sarah Cipriani2 – Orcid, Irene Scavello2 – Orcid, Giulia Rastrelli2 – Orcid, Margherita Frison2, Mario Maggi2 – Orcid

1 – SODc Andrologia, Endocrinologia Femminile e Incongruenza di Genere, Azienda Ospedaliero-Universitaria Careggi, Firenze

2 – Dipartimento di Scienze Biomediche Sperimentali e Cliniche “Mario Serio”, Università degli Studi di Firenze

3 – Dipartimento di Neuroscienze, Psicologia, Area del Farmaco e Salute del Bambino, Università degli Studi di Firenze

Autore di riferimento: Linda Vignozzi

DOI: 10.53146/lriog1202122


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.

Presente in LRIOG Nr.2 – 2021

e-ISSN: 1824-0283

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Androgeni e sindrome genitourinaria della menopausa

Androgeni e sindrome genitourinaria della menopausa. Perché, quando e per chi sono indicati

Alessandra Graziottin – Orcid

Direttrice del Centro di Ginecologia e Sessuologia Medica, H. San Raffaele Resnati, Milano

Fondazione Alessandra Graziottin per la cura del dolore nella donna – Onlus

DOI: 10.53146/lriog120212


Why androgens – testosterone and dehydroepiandrosterone (DHEA) – can play a role in the treatment of the Genitourinary Syndrome of the Menopause? What evidence supports this? Androgens are essential sex hormones for women’s health. Biological evidence (“bio-evidence”) indicates the following: androgens reach high plasma levels in childbearing age; have cell receptors in major organs; the hormone-receptor interaction mediates androgen-mediated, somatic (brain, muscle, bone), sexual and reproductive functions; their deficiency causes symptoms of androgenic insufficiency. They have a trophic, sexual, anti-inflammatory, and reconstructive functions. DHEA launches puberty (adrenarche). Androgens reach their plasma peak at twenty years of age, then they undergo an age-dependent gradual fall. At the age of fifty, women have lost about 50% of testosterone and 60-70% of DHEA. Bilateral ovariectomy reduces testosterone by 80%. Their age-
dependent reduction, worsened by estrogen deficiency, contributes to systemic and genital aging and to the “low grade inflammation” typical of post-menopause. Genitourinary Syndrome of the Menopause includes vulvo-vaginal symptoms.

Keywords: androgens; prasterone; testosterone; genitourinary syndrome of the menopause (GSM).

Presente in LRIOG Nr.1 – 2021

e-ISSN: 1824-0283

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