The vagina: therapeutic role of estrogen

The vagina: therapeutic role of estrogen
Vincenza Di Stasi 1 Orcid, Irene ScavelloOrcid , Elisa Maseroli 1,2 Orcid, Sarah Cipriani1,2Orcid, 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

DOI: 10.53146/lriog1202146


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 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

DOI: 10.53146/lriog1202117


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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