**1. Introduction**

Urogenital atrophy, also referred to as genitourinary syndrome of menopause (GSM) [1], is caused by decreased estrogen levels in women's urogenital tissues. Symptoms include vulvovaginal discomfort described as dryness, itching, burning, irritation, and soreness; sexual dysfunction due to decreased lubrication and dyspareunia; and urinary complaints such as urgency, frequency, and recurrent urinary tract infections [2,3].

Among menopausal women, prevalence of GSM is estimated at approximately 50–60%, making it one of the most frequent causes of genital complaints in this age group [4]. The diagnosis is clinical, based on a combination of symptoms and signs upon physical examination, including thin, pale, smooth, and shiny vaginal epithelium with diminished elasticity [2]. Estrogen supplementation (topically or systemically) is considered the most efficient treatment [5,6]. Following estrogen administration, epithelial maturation occurs, with subsequent changes in epithelial thickness, pH level, and tissue elasticity [6,7].

Treatment efficacy is evaluated in clinical trials using a range of measurements that represent the changes occurring in the vagina in response to the presence or absence of estrogen. The commonly used measures include pH level, vaginal health index (VHI, Table 1) and the vaginal maturation index (VMI) [8]. Other tools used to assess treatment are a variety of questionnaires or scores, relying on patient's self-report, assessing symptoms' severity or quality of life parameters. Available questionnaires include the Most Bothersome Symptoms (MBS), the Day-to-Day Impact on Vaginal Aging (DIVA) Questionnaire,

**Citation:** Gabrieli, D.; Suissa-Cohen, Y.; Jaber, S.; Lev-Sagie, A. "Modified Schirmer Test" as an Objective Measurement for Vaginal Dryness: A Prospective Cohort Study. *Diagnostics* **2022**, *12*, 574. https://doi.org/ 10.3390/diagnostics12030574

Academic Editors: Fabio Bottari and Anna Daniela Iacobone

Received: 28 January 2022 Accepted: 21 February 2022 Published: 23 February 2022

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the Vulvovaginal Symptoms Questionnaire (VSQ), and the Vulvar Pain Assessment Questionnaire (VPAQ) [8]. Alternatively, an array of scores rate severity of symptoms, enabling subjective comparison. Available scores include the Vaginal and Vulvar Assessment Scale, the Female Sexual Function Index (FSFI), and the Female Sexual Distress Scale-Revised (FSDS-R) [8].

As many women with GSM are reluctant to use local estrogen due to various concerns [9], alternatives for topical hormonal treatment are sought. Studies have been evaluating the effectiveness of alternative therapies that do not include estrogen, such as hydrating agents, hormonal non-estrogens including DHEA [6], and energy based treatments, such as the fractional CO<sup>2</sup> laser [9,10], non-ablative vaginal Er:YAG laser (VEL) [11] and radiofrequency procedures [12].

Introduction of energy-based treatments for GSM in recent years resulted in studies evaluating the efficacy of these treatments. These modalities are claimed to improve GSM in an estrogen independent mechanism, such as connective tissue remodulation and neovascularization [9,11–14]. Nevertheless, most of the published research evaluated treatment outcomes using one or more estrogen-dependent measures (i.e., pH, VMI, and VHI). Despite reporting positive effects on symptoms and a relative improvement in the VHI index, pH levels and cytological measures, unsurprisingly, often do not show a clinically significant difference [15–19].

As none of the currently available parameters allow a direct and objective measurement of the vaginal condition and moisture, there is a need for such tools. Ideally, such measures should be objective, allow assessment of GSM-associated signs, and incorporate parameters relevant to new treatment modalities, which do not depend on estrogen or its effects on the vaginal tissue.

Considering patients' reports of increased vaginal secretions following estrogen supplementation as well as following laser treatment, we opted to develop and test a vaginal dryness/moisture measurement tool. The tool we used was a calibrated filter paper strip, similar to the one used to perform the ophthalmic "Schirmer test" for eye moisture measurement.

Our goal was to evaluate the validity of this objective measurement tool for vaginal moisture by comparing measurements in symptomatic women suffering from GSMassociated vaginal dryness to measurements in healthy women without vaginal dryness.
