The Genitourinary Syndrome of Menopause (GSM) is caused by the ageing of cells from the genital area and the systemic depletion of estrogens [1–3]. In the transition period to menopause its prevalence is between 15 to 50% and increases up to 70% in postmenopause. Clinical manifestations of the GSM can be divided in two types: vaginal symptoms and lower urinary tract symptoms. Up to 80% of women have vaginal symptoms, such as pruritus and dyspareunia, while up to 30% present urinary symptoms such polyuria, urinary urgency, bladder instability and urinary incontinence [4]–[6]. The Menopause Rating Scale (MRS) is a health-related quality of life (HRQoL) instrument, which measures the severity of ageing symptoms and their impact on the quality of life in a standardized way [7], [8]. MRS comprises 11 items included in three domains: the psychological, somatic and urogenital. The urogenital domain comprises items 9 to 11. Each item evaluates symptom´s severity on a scale that ranges from 0 to 4, getting 0 points for asymptomatic,1 point for mild, 2 points for moderate,3 for severe and ≥ 4 points for extremely severe urogenital symptoms. Item 9 assesses sexual problems, including changes in libido, sexual activity, and dyspareunia. Item 10 evaluates bladder problems such as polyuria, urinary urgency, bladder instability, and urinary incontinence, and item 11 evaluates vaginal dryness [7]–[9].
The vaginal maturation index (VMI) is used to determine the hormonal status of the vaginal epithelium, which quantifies the rates of cell types in the vaginal epithelium [10]. In healthy premenopausal women, the classical VMI is composed by 0% of basal/ parabasal cells, 40–70% of intermediate cells, and 30–60% of superficial cells (0:40–70:30–60) [11]. Women in the transition of menopause have a VMI of 65:30:5. After menopause, the intermediate cells decrease and the rate of maturation can consist entirely of parabasal cells (90:10:0). Moreover, the vaginal mucosa harbours a variable number of immune cells such as neutrophils and polarised type 2 macrophages (M2) that assist in the fix of the mucosa [12]. Both epithelial cells and immune cells are sensitive to local estrogenic stimulation to maintain the function of the epithelial barrier and increase mucopolysaccharides and hyaluronic acid to maintain the urogenital territory and skin moisture [13].
Currently, estrogen-based (ES) hormone therapy remains the gold standard treatment for GSM [14], [15]. However, several studies have shown its low efficiency in treating the GSM. This issue has prompted to investigate the effect of alternative therapies for complementing or replacing ES-based hormone therapy [16], [17].One of the most promising treatments is the use of salmon poly-deoxyribonucleotides (PDRNs). PDRNs are a mix of polynucleotides (PNs) that have an activity in the adenosine A2A, A1, A2A, A2B, and A3 receptors. Immune cells, such as lymphocytes, neutrophils, monocytes, and macrophages, express these adenosine receptors and their stimulation triggers an anti-inflammatory and pro-healing response [18]. However, there is a lack of randomized controlled trials that demonstrate the efficiency of PDRNs to treat the GSM. Palmieri et al. conducted a pilot study on 19 women with postmenopausal vulvovaginal symptoms that received vulval injections with highly concentrated salmon trout gonads polynucleotides (PNs) and sodium hyaluronate (PN/HA) for one year, demonstrating a significant improvement in the Vaginal Assessment Scale (VAS) and the Vulvar Assessment Scale (VuAS) at 21, 35, 50, 70, and 90 days [19]. Another study showed that intradermal PN/HA injections were safe to treat vulvovaginal atrophy (VVA) in postmenopausal women [20]. Nonetheless, these studies had an aesthetic purpose instead of a functional purpose. Thus, the present work aimed to investigate the efficacy of PDRNs-based local therapy using vaginal suppositories to treat GSM in postmenopausal women.