Hyaluronic Acid: A Valid Therapeutic Option for Early Management of Genitourinary Syndrome of Menopause in Cancer Survivors?

Abstract

Genitourinary syndrome of menopause (GSM) is a chronic condition affecting a large number of women, with a major impact on their urogenital health and sexual function. It occurs at midlife because estrogen levels decline with menopause enhancing aging-related changes of the functional anatomy of the urogenital system. Unfortunately, GSM may occur early in the lifespan of women or be exacerbated following anticancer treatments, such as chemotherapy, ionizing radiation, or surgical removal of reproductive organs. Symptoms of GSM are often under-reported by women, under-estimated and under-diagnosed by health care providers (HCPs), and subsequently under-treated, despite their profound negative impact on the quality of life. The mainstay of vaginal treatments is local estrogen therapy (LET) ensuring an effective management of moderate to severe symptomatic GSM. However, LET is generally contraindicated in women with a history of hormone receptor positive cancer, due to the fear of increased recurrence or possible interference with endocrine adjuvant therapies. Among non-hormonal treatments, hyaluronic acid-based moisturizers have shown promising clinical results both in healthy women and in cancer patients or survivors. Its strong water-binding properties provide lubricating and moisturizing effects, which contribute to maintaining a proper level of hydration and viscoelasticity in several body parts, including the urinary tract and genital tissues. Hyaluronic acid-based moisturizers are effective, safe, and well tolerated; therefore, they may represent a valid option for the early management of GSM-associated symptoms in every woman with a history of cancer who is unable or unwilling to undergo hormone-based therapies. Hence, the aim of this review was to provide an overview of GSM etiology and treatment in women with natural or iatrogenic menopause, with a focus on the use of hyaluronic acid as a prophylactic treatment in the context of an integrated management protocol for cancer patients.

Keywords: genitourinary syndrome; hormone-dependent cancer; hyaluronic acid; menopause; vulvar and vaginal atrophy.

Conflict of interest statement

R.E.N. had past financial relationships (lecturer, member of advisory boards and/or consultant) with Boehringer Ingelheim, Ely Lilly, Endoceutics, Gedeon Richter, HRA Pharma, Merck Sharpe & Dohme, Procter & Gamble Co., TEVA Women’s Health Inc, and Zambon SpA. At present, she has ongoing relationships with Astellas, Bayer HealthCare AG, Exceltis, Fidia, Novo Nordisk, Organon & Co., Palatin Technologies, Pfizer Inc., Shionogi Limited, and Theramex.

Figures

Figure 1

A comparison of the degradation process of hyaluronan and conjugated hyaluronic acid (HA). Both polymers are composed of a variable number of dimers (n dimers) of glucuronic acid and N-acetylglucosamine, linked via alternating β-1,4 and β-1,3 glycosidic bonds. Hyaluronan is the sodium salt of hyaluronic acid (HA) and represents the form that naturally occurs in the human body. The conjugated HA is obtained through the introduction of chemical modifications of the HA backbone. As can be seen from this schematic representation, the presence of a covalently bonded functional group (R) has an impact on the polymer degradation process. If on one hand, the β-1,4 glycosidic bonds of hyaluronan are easily accessible for hyaluronidase, on the other, those of conjugated HA to be such require a preliminary step where an additional hydrolytic enzyme removes the functional group. This difference implies that the degradation products of conjugated HA are released over an extended period, thus ensuring a long-lasting action of the products that contain it. Vaginal moisturizers containing conjugated HA and, therefore, having a prolonged residence time on the mucosa, have been described by Cascone & Lamberti (2019) [85].