The vagina as an endocrine organ: clinical implications
Linda Vignozzi1 – , Sarah Cipriani1 – , Elisa Maseroli2 – , Irene Scavello1 – , Vincenza Di Stasi1 – , Ilaria Cellai1, Sandra Filippi3 – , 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
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