Non-hormonal approaches for the treatment of vulvovaginal atrophy: the choice between hyaluronic acid and glycerin

Symptoms of vulvovaginal atrophy (VVA) can be managed successfully using a variety of prescription and over-the-counter treatments, and the choice of therapy depends on the severity of the symptoms, the safety and effectiveness of each option, as well as to patient’s individual preference. Several scientific societies consider continuous administration of vaginal moisturizers as the first-choice approach to VVA [1], owing to their demonstrated effectiveness on the vaginal mucosa, through which they reduce dryness and dyspareunia [1]. The most common components of vaginal moisturizers are hyaluronic acid or glycerin.

Hyaluronic acid belongs to the broad glycosaminoglycan family, which are the main components of the extracellular matrix. The unique characteristics that distinguish hyaluronic acid from other glycosaminoglycans are its simple structure and high molecular weight. Its characteristics make hyaluronic acid suitable for use in medicines, cosmetics, and foods. The physical properties and physiological activities of hyaluronic acid differ with molecular weight. High-molecular-weight hyaluronic acid is used in medicine owing to the advantages of its high viscosity and water-retaining properties [2].

Of 27 studies identified through PubMed search using the words hyaluronic acid, vagina, and atrophy, 1 was a systematic review, 3 were narrative reviews, and 13 were clinical trials, of which 7 were randomized. The first study was performed in 2011 [3] and aimed to compare the effectiveness of vaginal hyaluronic acid tablets with that of estradiol for the treatment of VVA. Symptoms were relieved significantly in both groups (p < 0.001); however, it was significantly better in the estradiol group (p < 0.05). A second study was performed in 62 postmenopausal women who were randomly allocated to receive 0.97 μg of genistein (n = 31) or 5 mg of hyaluronic acid (n = 31) intravaginally every day for 15 consecutive days per month over 3 months. Both treatments improved genital symptoms, colposcopy findings, and the vaginal maturation index [4].

Grimaldi et al. [5] performed a double-blind, placebo-controlled randomized study of 36 postmenopausal women distributed evenly between two groups (placebo and active treatment with hyaluronic acid). Participants were asked to apply the gel (hyaluronic acid or placebo) daily for 7 months. Both treatments significantly reduced vaginal atrophy (p < 0.001), erythema (p < 0.01 placebo and p < 0.001 hyaluronic acid), and vaginal dryness (p < 0.001).

A non-comparative study evaluated liposomal hyaluronic acid in 47 patients with vulvovaginal dryness. Women applied hyaluronic acid three times per week for 84 days. At the end of the study, a significant clinical improvement was observed for dryness and pain (p < 0.001) [6]. In one study carried out by Dinicola et al. [7], cervical cancer women, who were to receive after surgery 4 weeks of radiotherapy and 4 weeks of brachytherapy plus chemotherapy, were assigned to receive for 4 months 2 daily vaginal suppositories (hyaluronic acid with vitamins A and E, n = 23) or no treatment (n = 22, control). Treatment with hyaluronic acid was effective in terms of decreasing severity of pain.

A recently published randomized pilot study of 57 postmenopausal women with early stage breast cancer who started treatment with aromatase inhibitors randomly assigned patients to three treatment groups. The two active treatment groups received for 6 months, vaginal hyaluronic acid or a vaginal prebiotic, as well as a lubricant with a vaginal dilator. The active treatments groups displayed less dyspareunia (p = 0.07) and sexual distress (p = 0.02) at 6 months as compared to control group. At 6 months, the hyaluronic acid group had improved sexual function (total FSFI score) significantly more than the prebiotic group (p = 0.04) [8]. In another study, Serati et al. [9] compared the efficacy of topical vaginal estrogens with that of hyaluronic acid for treatment of dyspareunia in sexually active women who took oral contraceptives. The authors concluded that vaginal supplementation with estriol 50 μg/g or hyaluronic acid could reduce dyspareunia associated with hormonal oral contraceptive use and that both treatments improved sexual relations.

Glycerin serves many functions in the human body, as it is the main unit of triglycerides and phospholipids, which are in turn the main way of storing energy and is an essential component of cell membranes. Glycerin is a viscous liquid with a high boiling point. It is colorless, odorless, and hygroscopic. Glycerin can undergo selective transformations and is easily manipulated, since it is a small molecule and highly flexible. Glycerin is widely used in the pharmaceutical and cosmetic industries as an additive (plasticizer, thickener, emollient, demulcent, humectant, bodying agent, and lubricant) because of its physical properties [10]. The main property of glycerin is its moisturizing capacity, since it absorbs and retains water, together with its emollient capacity (softener). Glycerin is used mainly to hydrate the skin and for vaginal lubrication [10].

Of the two studies identified through PubMed search using terms glycerin, vagina, and atrophy, one was a clinical trial that demonstrated the efficacy of glycerin gel in diabetic women with vaginal dryness and recurrent candidiasis [11], and the other examined polyacrylic acid aiming at evaluating female sexual function after using topical estrogens, testosterone, oil-based lubricant, or polyacrylic acid. After 12 weeks of treatment, polyacrylic acid and topical testosterone generated the highest scores in the ‘Desire’, ‘Lubrication’, ‘Satisfaction’, and ‘Pain’ domains as compared to lubricant alone [12].

The examined data show that the scale tips clearly in favor of vaginal hyaluronic acid as opposed to glycerin. Hyaluronic acid has been studied as a moisturizer in VVA [3–9]; however, the quality, concentration, and formulation (vehicle) can play a key role and highlight significant differences. For example, a noisome-based vehicle is not the same as a liposome-based vehicle; indeed, although both have similar chemical and physical properties, niosomes exhibit greater permeability for small ions/solutes, thus making them attractive as drug delivery systems for all types of molecules.

In conclusion, compared to glycerin, the use of hyaluronic acid as a vaginal moisturizer in women with VVA is supported by more clinical trials and scientific data. However, further randomized trials are necessary, particularly those that compare both products. Nevertheless, both, hyaluronic acid and glycerin, are safe therapeutic options free of adverse effects.