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The vagina: therapeutic role of estrogen

Editor , , , , ArticlesLRIOG 2021-4 , , , .
The vagina: therapeutic role of estrogen
Vincenza Di Stasi 1 – Orcid, Irene Scavello1 – Orcid , Elisa Maseroli 1,2 – Orcid, Sarah Cipriani1,2– Orcid, Linda Vignozzi1,2 – Orcid

1 -Department of Experimental and Clinical Biomedical Sciences “Mario Serio”. University of Florence

2 -Andrology, Female Endocrinology and Gender Incongruence. Careggi University Hospital, Florence

Corresponding Author: Linda Vignozzi

linda.vignozzi@unifi.it

DOI: 10.53146/lriog1202146

Abstract

Estrogen plays a fundamental role in women’s well-being in general and par- ticularly in vaginal health. After menopause there is a gradual reduction in circulating estrogen levels which often results in the onset of symptoms of the Genitourinary Syndrome of Menopause (GSM). In the absence of con- traindications, local estrogens are among the most used drugs in relieving signs and symptoms of GSM. There are different formulations available and the choice of one over the other depends on the severity of the symptoms, the preferences of the patients and the risk / benefit ratio of each. In women with a history of hormone-responsive cancer or at high risk for this disease, the decision to undertake local estrogen-based hormone therapy to treat GSM should be assessed on a case-by-case basis and after appropriate multi- disciplinary counseling with the oncologists.

Keywords: estrogens; vagina; menopause; local therapies.

Available in LRIOG Nr.4 – 2021

e-ISSN: 1824-0283

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The vagina: therapeutic role of prasterone

Editor , , , , ArticlesLRIOG 2021-2 , , , .
The vagina: therapeutic role of prasterone

Linda Vignozzi1,2 – Orcid, Irene Scavello1 – Orcid, Elisa Maseroli1 – Orcid, Vincenzo Di Stasi1 – Orcid, Sarah Cipriani1,2 – Orcid

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

2 – SODc Andrology, Female Endocrinology and Gender Incongruence, Careggi University Hospital, Florence

Corresponding author: Linda Vignozzi

linda.vignozzi@unifi.it

DOI: 10.53146/lriog1202123

Abstract

Genitourinary menopause syndrome (GSM) is a chronic, progressive condition, which results from the effects of estrogenic and androgenic deficiency typical of menopausal age. It involves the genitourinary district and occurs with an extremely wide range of signs and symptoms. Dyspareunia, both superficial and deep, is among the main and most distressing symptoms of the GSM. Over the decades, different therapeutic approaches have been developed, aimed at improving the symptomatology and thus the quality of life of women, such as local estrogenic therapy, which until now has been considered the gold standard of GSM treatment. A new Prasterone formulation has recently been approved, which is biochemically and biologically identical to that of the endogenous human DHEA, an inactive steroid precursor that can be converted into estrogen and androgen into vaginal cells. The rationale of the use of prasterone is the theory of intracrinology, which is the proven ability of vaginal cells to convert an inactive compound into an active form. This molecule, absorbed locally, determines only a minimum increase in circulating hormonal values, which remains be- low the threshold of physiologic levels for menopausal women.

Keywords: prasterone; genitourinary syndrome; menopause; atrophy.

Available in LRIOG Nr.2 – 2021

e-ISSN: 1824-0283

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

Editor , , , , , , , , , ArticlesLRIOG 2021-2 , , , , .
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 vagina as an endocrine organ: clinical implications

Editor , , , , , , , ArticlesLRIOG 2021-2 , , , , , .
The vagina as an endocrine organ: clinical implications

Linda Vignozzi1 – Orcid, Sarah Cipriani1 – Orcid, Elisa Maseroli2 – Orcid, Irene Scavello1 – Orcid, Vincenza Di Stasi1 – Orcid, Ilaria Cellai1, Sandra Filippi3 – 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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