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


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The pelvic floor: common elements of the physiotherapy and gynecological evaluation

The pelvic floor: common elements of the physiotherapy and gynecological evaluation

Arianna Bortolami – Orcid

Physiotherapist

Consultant in Sexology

Master’s Doctor
in Sciences of the Health Professions of Rehabilitation

Adjunct professor at the University of Milan-Bicocca

arianna.bortolami@gmail.com


DOI: 10.53146/lriog1202121

Abstract

Dysfunction of the pelvic floor muscles can cause urological, gynecological, anorectal, sexual and pain symptoms that can have a negative impact on a woman’s quality of life. Therefore, the evaluation of these muscles and the characteristics of the symptoms is fundamental for their management and treatment. Urological symptoms are related to both bladder filling, such as incontinence, frequency, urgency, nocturia, and emptying, such as urinary hesitation, intermittent, hypovalid, deviated mitt, straining, post voiding drip, sense of incomplete emptying. Anorectal symptoms are identified in anal incontinence and urgency, constipation and a sense of incomplete emptying. Alterations in the gynecological area refer to the prolapse of the pelvic organs. Sexual dysfunctions consist in the impossibility or difficulty in penetration and orgasm, in coital pain, and in the reduction of genital sensations of pleasure. Painlike symptoms refer to chronic/persistent pain in the pelvic area, including persistent vulvar pain. The common elements among professionals in the evaluation of the pelvic floor are identified in the medical history and physical examination. The first identifies symptoms and related risk factors. The latter include pregnancy, childbirth, menopause, syndromes involving persistent pelvic pain, systemic diseases involving connective tissue, skin and peripheral nervous system, oncological diseases, lifestyles that cause frequent increases in abdominal pressure or excessive contraction of the trunk and pelvis muscles, or prolonged sitting. The physical examination identifies the condition of the pelvic floor muscles, which may be excessively or poorly active. Anamnesis and physical examination then allow to plan the therapy, which can be identified in physiotherapy and rehabilitation, in psychological, pharmacological, surgical therapy.

Keywords: physical examination; manual palpation; muscle tone; muscle trophism; voluntary and involuntary motor activity; muscle pain.


Available in LRIOG Nr.2 – 2021

e-ISSN: 1824-0283


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The vagina, oncological target: Vain and therapeutic strategies

The vagina, oncological target: Vain and therapeutic strategies

Francesco Sopracordevole1 – Orcid , Nicolò Clemente1 – Orcid, Anna del Fabro1 – Orcid

1 – SOC of Oncological Gynecology – Oncological Reference Center of Aviano – IRCCS

Corresponding author: Francesco Sopracordevole

fsopracordevole@cro.it


DOI: 10.53146/lriog1202120

Abstract

VaIN (Vaginal Intraepithelial Neoplasia) is a challenge disease for gynecologists: it is often undiagnosed, difficult to treat, with high rate of recurrence and, in some cases, it can progress to invasive vaginal cancer. Multiple treatments are often required, with a potential impairment of women’s quality of life. To get a proper diagnosis and adequate treatment, all the women with abnormal pap smear, should undergo an accurate colposcopic evaluation of vaginal walls. A colposcopy-guided biopsy of suspicious lesions is mandatory. The treatment of VaIN (especially the most complex cases) should be performed by expert colposcopists in referral centres.

Keywords: VaIN; vaginal intraepithelial neoplasia; pap smear; vaginal excision; vaginal surgery.


Available in LRIOG Nr.2 – 2021

e-ISSN: 1824-0283


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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


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The vagina, a sensual and erotic organ: anatomofunctional evidence

The vagina, a sensual and erotic organ: anatomofunctional evidence

Emmanuelle A. Jannini– Orcid, Fiorenza Pesce

1 – Chair of Endocrinology and Medical Sexology (ENDOSEX), Department of Systems Medicine, University of Rome Tor Vergata

Corresponding author: Emmanuelle A. Jannini

eajannini@gmail.com


DOI: 10.53146/lriog1202118

Abstract

In the field of female sexuality, the existence of the so-called “G-spot” represent a topic still anchored to anecdotes and opinions and explained through non-scientific arguments, as well as overused for commercial and mediatic purposes. The scope of the review is to give an update on the current state of the art regarding the G-spot and suggesting potential future directions in the research field of this interesting, albeit controversial, aspect of human sexual physiology. From evolutionary, anatomical and functional points of view, new evidence rebutted the original conceptualization of G-spot, abandoning the idea of a specific anatomical point able to produce exceptional orgasmic experience through the stimulation of the anterior vaginal wall, the site where the G-spot is supposed to stay. From a psychological perspective, only few findings are to date present able to describe the psychological, behavioural and social correlates of the pleasure experience by G-spot induced, or – better – vaginally-induced orgasm (VAO). Recent literature suggests the existence of G-spot but specifying that, since it is not a spot neither anatomically nor functionally, cannot be called G, nor spot, anymore. It is indeed a functional, dynamic and hormone-dependent area (called clitorourethrovaginal, CUV, complex), extremely individual in the development and action due to the combined influence of biological and psychological aspects, which may trigger VAO and in some peculiar cases also female ejaculation (FE).

Keywords: g-spot; clitorourethrovaginal complex; vaginal activated orgasm; female ejaculation.


Available in LRIOG Nr.2 – 2021

e-ISSN: 1824-0283


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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


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