Are we assessing genitourinary syndrome of menopause properly?

Keywords:

• Genitourinary syndrome of menopause
• Vaginal Health Index
• assessment tools
• Vaginal Maturation Index
• Female Sexual Function Index
• visual analog scales

Genitourinary syndrome of menopause (GSM) comprises an aggregate of symptoms occurring in the external genitalia, pelvic floor tissues, bladder and urethra related to hypoestrogenism, where urinary tract symptoms, vaginal dryness, painful intercourse and loss of sexual function are highlighted. GSM affects from 27% to 84% of postmenopausal women, causing impairment of their sexuality and quality of life [1]. During the last decade, new therapeutic options have appeared to treat GSM symptoms, ranging from ospemifene and prasterone to vaginal laser, all positioned as potential alternatives for those patients in whom estrogenic therapies are not recommended or when moisturizers and lubricants provide poor relief [2].

Recently, we have seen a large number of scientific papers discussing treatment of GSM, mostly related to vaginal laser, evaluating the safety and efficacy of these new options. Unfortunately, there remains no clear consensus in the scientific community regarding the role of energy-based therapies for GSM, as seen in the North American Menopause Society position statement of 2020 concluding that energy-based therapies required long-term, sham-controlled safety and efficacy studies before their routine use could be recommended [3].

In 2020, Mitchell asked the question ‘How do we measure success in the treatment of GSM?’ [4], underlining the lack of consensus in the literature regarding how to evaluate clinically relevant improvement of GSM. Concerning this issue, in 2003 the US Food and Drug Administration outlined possible end points for studies assessing topical estrogen to treat GSM: change in severity of symptoms, change in vaginal pH and change in the Vaginal Maturation Index [5]. To date, the most used assessment tools to quantify severity and improvement of GSM are the visual analog scale of GSM symptoms, the Vaginal Health Index (VHI) and the Female Sexual Function Index. From our point of view, the GSM assessment tools can be divided into two groups: subjective outcomes and objective outcomes.

Regarding subjective outcomes, we must differentiate those that depend on the patient perception of the problem from those that depend on the medical subjective quantification of the problem. In the first group, the visual analog scale of GSM symptoms and different tests such as the Female Sexual Function Index or the Short Form-12, among others, are included. Second, there is controversy about whether or not some aspects of the clinical medical evaluation are subjective or objective tests. Some articles report the VHI as an objective measure, but from our point of view it is a medical subjective evaluation of the genital tract status in four out of five variables of the index (vaginal elasticity, fluid volume, epithelial integrity and moisture) and one objective variable, which is vaginal pH measurement [6].

Regarding objective outcomes, the most used is vaginal pH measurement, part of the VHI calculation, which is not always expressed as an individual outcome, and may be biased by other variables when included in the VHI [7].

The Vaginal Maturation Index assesses the relative proportion of parabasal, intermediate and superficial vaginal epithelial cell types in a vaginal cytology sample, defining a cut-off for premenopausal and postmenopausal women with vulvovaginal atrophy [8].

Other objective outcomes have been described, such as vaginal epithelial thickness, composition of the lamina propia and vaginal compliance [9], but they have been scarcely used, reporting contradictory results and only in case-series studies. Finally, few authors have attempted to evaluate objectively the vaginal wall thickness in GSM by ultrasound, although this measurement could be as effective as histological measurement [10].

To conclude, we are beginning to see new and interesting target outcomes to evaluate GSM, but there is an urgent need to bring consistency to new studies to facilitate systematic reviews and meta-analysis, and to provide the best evidence on this matter. The overall lack of meaningful objective outcomes assessing GSM across literature is also cause for concern. There is a need to evaluate whether the current pH measurement and Vaginal Maturation Index are enough to bring objectiveness to scientific assessment of GSM, or whether other objective methods are necessary to achieve this goal. Finally, from our point of view, subjective and objective variables to evaluate GSM should be differentiated. There is the possibility that some therapies present only subjective improvement, suggesting a possible placebo effect of these therapies when subjective improvement is not supported by objective assessment of improvement.

Source of funding

Nil.

Potential conflict of interest

Nil.