The vagina: emerging evidence on the anti-inflammatory role of testosterone

The vagina: emerging evidence on the anti-inflammatory role of 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 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

linda.vignozzi@unifi.it


DOI: 10.53146/lriog1202122

Abstract

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

e-ISSN: 1824-0283


Download the pdf   download_pdf


The vagina and its microbiota (resident and dynamic)

The vagina and its microbiota (resident and dynamic)

Francesco De Seta1,2 – Orcid, Gabriella Zito1 – Orcid, Giuseppe Ricci1,2, Simona Franzo2

1 – Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste

2 – Department of Medicine, Surgery and Health Sciences, University of Trieste

Corresponding author: Francesco De Seta

fradeseta@gmail.com


DOI: 10.53146/lriog1202119

Abstract

The vaginal microbiota and the immunologic milieu that derives are a dynamic and complex ensemble. A normal vaginal microbiota is mainly constituted by Lactobacillus sp.. This bacterium, thanks to the production of metabolites (lactic acid, hydrogen peroxide, bacteriocin) and stimulating the immune system toward an anti-inflammatory switch, can maintain the stability of vaginal microbiota and inhibit pathogen bacteria proliferation. Multiple factors affect vaginal microbiota composition. They can lead to high diversity and rise of anaerobic bacteria that enhance chronic inflammation, vaginal epithelial barrier damage, risk of STI transmission, infertility, preterm labor, PID. Research about this issue has intensified in the last decade, due to the development of molecular biology techniques that allow to isolate specific species of bacteria and analyse their specific functions. However, the understanding of the mechanisms through which the shifts in the microbiota can affect the health state and the immune system of the individual is still far. This constitutes a frontier for the development of prevention, diagnosis and therapeutic strategies.

Keywords: microbiome; bacteria, vagina; lactobacilli; dysbiosis.


Available in LRIOG Nr.2 – 2021

e-ISSN: 1824-0283


Download the pdf    download_pdf


The vagina as an endocrine organ: clinical implications

The vagina as an endocrine organ: clinical implications

Linda Vignozzi– Orcid, Sarah Cipriani– Orcid, Elisa Maseroli– Orcid, Irene Scavello– Orcid, Vincenza Di Stasi– Orcid, Ilaria Cellai1, Sandra Filippi– Orcid, Paolo Comeglio1

1 – Department of Biomedical, Experimental and Clinical Sciences “Mario Serio”, University of Florence

2 – Careggi University Hospital, Florence

3 – Department of Neuroscience, Psychology, Pharmaceutical and Child Health Area, University of Florence

Corresponding author: Linda Vignozzi

linda.vignozzi@unifi.it


DOI: 10.53146/lriog1202117

Abstract

Vagina is an androgens-responsive organ since the early weeks of pregnancy. Although androgens have always been recognized as key hormones for male sexuality, recent preclinical and clinical evidence suggests a fundamental role exerted particularly by testosterone (T) also in female genital tissues. As a matter of fact, T has been demonstrated to be involved in the physiologic functional contractile and relaxant machinery of clitoral smooth muscle cells, as well as in clitoral vascularization, that is essential for genital arousal. Even more groundbreaking is the demonstration of the anti-inflammatory role of androgens in the vagina, that becomes a key aspect if related to the inflammatory process characterizing the genitourinary syndrome of menopause (GSM). As a matter of fact, our research team observed that pre-treatment of human vagina smooth muscle cells (hvSMCs) with dihydrotestosterone (DHT) significantly reduced gene expression of different pro-inflammatory mediators induced by inflammatory stimuli such as lipopolysaccharide or interferone-g. This effect was significantly blunted by co-treatment with androgen receptor antagonist bicalutamide. Interestingly, we demonstrated that hvSMCs own the enzymatic machinery which is necessary to synthesize more biologically active androgens, that seems to be therefore as important as estrogens to maintain a functional vaginal muscle tissue, exerting a local anti-inflammatory effect, as well. Consequently, vagina appears to be as a real endocrine organ, with the ability of synthesizing more potent androgens from upstream precursors (e.g. DHT from dehydroepiandrosterone, DHEA) according to intracrinology principles, thus supporting the use of topical androgens such as Prasterone (synthetic DHEA) against symptoms of GSM.

Keywords: vagina; genitourinary syndrome of menopause; intracrinology; female sexual dysfunction; steroidogenesis; chronic inflammation.


Available in LRIOG Nr.2 – 2021

e-ISSN: 1824-0283


Download the pdf   download_pdf


The vagina: clinical questions and unfulfilled therapeutic needs

The vagina: clinical questions and unfulfilled therapeutic needs

Alessandra Grazziottin1,2 – Orcid

1 – Alessandra Graziottin Foundation for the treatment of pain in women – Onlus

2 – Gynecology and Medical Sexology Center, H. San Raffaele Resnati, Milan

direzione@studiograziottin.it


DOI: 10.53146/lriog1202116

Abstract

This monograph was meant to share with colleagues a cultural, scientific and clinical perspective that is stimulating and of immediate impact for daily gynecological practice. In detail, we will analyze the sensitivity to many hormones and the close correlations between endocrine and sexual health; the factors that influence the variability of the vaginal ecosystem and in particular of the microbiota; the essential role of the pathogen biofilm that covers the mucosa and colonizes the vaginal environment and their correlation with vulnerability to sexually transmitted diseases. We then move on to the analysis of the vulnerability to birth trauma and iatrogenic damage; the evaluation of the correlation between vaginal health and pelvic floor tone up to the correlation of specific factors with vulnerability to sexual abuse.

Keywords: vagina; microbiota; hormonal sensitivity; sexual health.


Available in LRIOG Nr.2 – 2021

e-ISSN: 1824-0283


Download the pdf  download_pdf