A randomized trial on the safety and efficacy of sensate water-based and silicone-based personal lubricants for relief of intimate discomfort associated with vaginal dryness

Abstract

Background

Personal lubricants with different formulations and properties, including ingredients designed to enhance sensation or feeling, can be used to alleviate vaginal dryness and affect sexual function. Clinical data to support their safety and efficacy are limited.

Aim

Determine safety and efficacy of two sensate personal lubricants for relief of discomfort associated with vaginal dryness in female participants, and report the impact on sexual satisfaction in female participants and male partners.

Methods

A two-arm, parallel design study was performed in women (18–65 years) experiencing vaginal dryness. Participants were randomized to one of two sensate lubricants (water-based [tingling] or silicone-based [warming]), which had to be used during vaginal intercourse at least once a week over a 4-week period.

Outcomes

Primary outcome: change from baseline in total Female Sexual Function Index (FSFI) score after 4 weeks of lubricant use. Secondary outcomes: change from baseline in FSFI domain scores; adverse events (AE); vulvovaginal and oral tolerance; female participant and male partner perception of lubricants; improvement in sexual intimacy (assessed using Subject Perceived Questionnaires [SPQ] and Patient Global Impression of Change).

Results

Sixty-six female participants completed the study. The primary endpoint (prespecified increase in FSFI ≥4 points from baseline) was achieved for both lubricants. A positive change was observed across all six FSFI domains. All AEs were mild in severity; no serious AEs were reported; the discontinuation rate was 1.5% (one female participant; warming lubricant). For both lubricants, vulvovaginal tolerance was “good/very good” and oral tolerance was generally “very good” (“acceptable” for one participant in each treatment arm). For both lubricants, most female participants and their male partners agreed that first penetration during vaginal sex was smoother, and there was an improvement in sexual intimacy.

Clinical implications

Safety and efficacy of both lubricants containing sensate ingredients was demonstrated, giving reassurance that they can be safely recommended by healthcare professionals to relieve vaginal dryness and enhance sexual pleasure.

Strengths/limitations

Evidence is provided for the safety and efficacy of two sensate lubricants for relieving vaginal dryness and improving sexual pleasure in healthy participants across a wide age range. The SPQ is not a clinically validated tool, and the sample of participants was not diverse, which may limit the generalizability of data.

Conclusions

The use of sensate lubricants showed significant improvement in sexual function coupled with improved satisfaction for both male and female participants. No severe or serious AE were reported during the study period.

Introduction

Vaginal dryness, or decreased vaginal lubrication, is generally associated with menopause;¹ however, it can occur at any age.^2,3 Over 15% of premenopausal women experience symptoms of vaginal dryness and dyspareunia,^3–5 which can be caused by many factors, including breastfeeding, certain health conditions, and medications (eg, anti-depressants, progestin-only contraceptive pills).³ Up to 57% of postmenopausal women experience symptoms of urogenital (vaginal/vulval) atrophy, commonly known as genitourinary syndrome of menopause, of which vaginal dryness is a symptom.^2–5

Vaginal dryness can significantly impact quality of life as it affects normal everyday activities and negatively impacts sexual activity.^6,7 Progression of vaginal atrophy, vaginal dryness, and painful intercourse can often cause women to avoid sexual activity due to the anticipation of discomfort. This avoidance can contribute to worsening vaginal atrophy, increasing discomfort during intercourse and initiating a cycle of avoidance, anxiety, and decreased sexual desire,² which can negatively impact relationships.^3,4

Personal lubricants are recommended by the North American Menopause Society, the International Menopause Society, and the American College of Obstetricians and Gynecologists^8–10 as front-line interventions for women suffering from vaginal dryness and associated sexual pain.^8–12 In addition to improving vaginal dryness, personal lubricants can enhance sexual function and pleasure for sexually active individuals across identified genders, regardless of specific health conditions.¹³

A wide variety of personal lubricants are commercially available¹⁴ with varying base formulations (water-, silicone- and glycol-based).¹⁵ The most commonly available personal lubricants are water-based, and should be carefully formulated with osmolality <1200 mOsm/kg.¹⁶ Despite wide availability, there is a lack of published safety and efficacy data on lubricants in the scientific literature. World Health Organization (WHO) guidance highlighted that personal lubricants with high osmolality may be associated with vaginal and epithelial damage.¹⁶ It is important to highlight that a study of five water-based lubricants, four of which met WHO recommendations for osmolality, were all well tolerated and improved sexual function.¹⁷

Personal lubricants containing ingredients that provide an enhanced sensation in addition to improving vaginal dryness are commercially available. However, an anonymous online survey completed by a random sample of obstetricians/gynecologists, physician assistants/nurse practitioners and physicians specializing in menopausal populations at The Menopause Society’s 2023 Annual Meeting, revealed that some healthcare professionals have expressed concerns regarding the safety and lack of clinical data supporting the use of personal lubricants containing sensate ingredients.¹⁸

This study aimed to investigate the safety and efficacy of two personal lubricants with sensate ingredients for the relief of intimate discomfort associated with vaginal dryness, and assess the perception of both lubricants in women and their male partners.

Materials and methods

Study design

This two-arm, open-label, parallel-design study ran from February to May 2023 at a clinical investigation center in Hamburg, Germany. This study was conducted according to the clinical investigation plan and the principles set out in the Declaration of Helsinki. It complied with the International Council for Harmonization’s guidelines for Good Clinical Practice, ISO 14155:2020, and applicable regulatory requirements. The trial was registered at the US National Institutes of Health (Clinicaltrials.gov: NCT05644444). All participants and their male partners provided written consent prior to study enrollment.

The study followed a similar design to a previous published study,¹⁷ and included a tolerance phase (consisting of a 7-day washout period) (Supplementary Figure 1) and a treatment phase (Supplementary Figure 2). The methodology was almost identical (eg, frequency of visits and study assessments), except for the following. In female participants, oral tolerance assessments (tolerance phase) at baseline, 30 minutes, 2 and 24 hours were conducted and improvements in intimacy (visit 3) assessed. In male partners, assessments of the perception of lubricants (screening and visit 3), adverse events/adverse device events (AEs/ADEs) (all visits), and improvements in intimacy (visit 3) were conducted in the treatment phase.

At screening, patients were asked to rate the intensity of their vaginal dryness and dyspareunia. Both were rated using a 4-point verbal rating scale ranging from “No pain/dryness [0]” to “Severe pain/dryness [3]”.

Eligible participants were randomized in a 1:1 ratio to one of two lubricants assessed through permuted blocks of fixed size of 4. The randomization was stratified by menopausal status, namely premenopausal for strata 1 or postmenopausal for strata 2. The randomization schedule was generated in SAS version 9.4. For complete participation in the study (tolerance and treatment phase), participants received an expense allowance of €970 (maximum), which was paid on the last trial visit. Participants who did not complete the trial in full received an expense allowance that corresponded to the progress of the study. The study followed the European Union General Data Protection Regulation.

Study population

Full inclusion and exclusion criteria are included in Supplementary Table 1. In brief, self-identified heterosexual, premenopausal and postmenopausal women in monogamous relationships (aged 18–65 years) who had self-reported mild-to-moderate vaginal dryness and dyspareunia in the past 3 months using a 4-point verbal rating scale were enrolled, along with their male partners (aged ≥18 years).

Study products

There were two personal lubricants investigated: one water-based (tingling) lubricant reformulated to meet WHO standards for osmolality, and one silicone-based (warming) lubricant that was a reformulation of a glycerine-based (warming) lubricant. The sense of warmth, tingling, or cooling on the skin and mucous membranes from active sensate ingredients occurs via chemesthesis.¹⁹ The two lubricants investigated in this study contain the following active ingredients: vanillyl butyl ether (present in <1%) in the warming lubricant and a cyclic carboxamide (present in <1%) in the tingling lubricant. These active ingredients produce the chemesthetic sensations via activation of transient receptor potential ion channels, which detect different active agents that range from cooling through to warming and irritation.^20,21 Between individuals, there is natural variation in the distribution of receptors and their sensitivity, meaning reactions to sensory ingredients (actual perception and intensity) vary.^20,21

Participants were trained by the Principal Investigator (PI), and any other clinical site staff authorized by the PI to perform the training, on how to apply the study product to the vagina and intimate area and study lubricants were provided at the clinical site to the participants. No blinding was necessary as the two products were not intended to be compared. Participants were asked to make a single application of lubricant at the clinical site for the vulvovaginal assessment (tolerance phase). For the oral assessments (tolerance phase), the clinical site staff applied a pea-sized application of the study product to the inner linings of the upper and lower lips on both sides of the mouth. The allocated study product was weighed prior to being dispensed for the participant to use at home during the 4-week treatment period and after the treatment phase. Participants were subject to various restrictions during the investigation, to minimize the impact on results. This included a limit to time spent bathing and a restriction on the use of hygiene products in the intimate area.

For the oral assessment, comparators in the form of a non-sensate water- and silicone-based lubricant were included to compare objective and subjective responses to lubricants containing sensate ingredients versus those without. Oral assessment in the tolerance phase was performed by a dermatologist who remained blinded, in order to minimize any evaluation bias.

Study endpoints and assessments

Primary and secondary study endpoints and assessments are outlined in Table 1.

For the endpoint of transition from sexual dysfunction to sexual function, a cut-off score of 26.55 on the FSFI was used. This has been determined in previous studies as being the most appropriate boundary for differentiating women with and without sexual dysfunction.²²

Sample size

This clinical investigation was powered for the primary endpoint and key secondary endpoint. The sample size calculation considered two previous clinical trials^23,24 and advice from key opinion leaders. As outlined previously, a change of 4 in the total Female Sexual Function Index (FSFI) score was considered a minimally clinically important change from baseline. Assuming a standard deviation of 5.2 for FSFI, a sample size of 24 participants completing the 4-week treatment period in each of the two treatment groups was planned to achieve 90% power for assessment of the primary endpoint. For the key secondary endpoint, to preserve the power of the clinical investigation, the FSFI domain that detected the smallest average effect size (desire: 0.623) was used for the calculation, resulting in 30 participants required to complete the study in each treatment group. A 10% attrition rate per treatment group was accounted for.

Statistical analysis

For the primary endpoint, the total FSFI score at 4 weeks was compared to baseline using a paired t-test. For the determination of the statistical significance of each comparison, an adjustment for multiple testing was made according to the Bonferroni–Holm method to ensure the family-wise error was controlled at 5%. The mean change from baseline in total FSFI was presented with Bonferroni-corrected 97.5% confidence intervals to account for the two treatment comparisons. If within-participant differences were not normally distributed, a Wilcoxon signed rank test was used to compare change from baseline. In this case, Hodges–Lehmann 97.5% confidence intervals were calculated. The number and percentage of participants achieving ≥4-point improvement in total FSFI at 4 weeks and moving from sexual dysfunction to sexual function between baseline and 4 weeks were presented by treatment group and overall. Individual FSFI domain scores at 4 weeks were compared to baseline using a paired t-test or Wilcoxon signed rank test. All AEs/ADEs from the tolerance and treatment phases were summarized together.

Results

Study population

In total, 66 female participants were randomized by menopausal status and used the study products, 22 of whom were included in the tolerance phase (21 of these continuing in the treatment phase). Only one participant dropped out due to an AE (reported “burning, itching, and erythema directly after application”) before the start of the treatment phase; the participant recovered by the end of the study. Overall, 65 participants completed the treatment phase (Figure 1).

The demographics of participants are presented in Table 2.

Change in FSFI

The primary endpoint was met for both lubricants. This was seen as a statistically significant change in the full analysis set (FAS) and per protocol (PP) population (Table 3).

From baseline to the end of the 4-week treatment phase, 52% (FAS) and 53% (PP) of female participants in the tingling arm and 67% (FAS and PP) in the warming arm achieved ≥4-point improvement in total FSFI score. Meanwhile, 52% (FAS) and 53% (PP) of female participants in the tingling arm and 53% (FAS) and 54% (PP) in the warming arm experienced an increase in the total FSFI score from ≤26.55 to >26.55.

For all six individual domains of the FSFI, a positive change was observed for both lubricants. The changes were statistically significant for all domains except for arousal (FAS and PP: tingling), desire (PP: tingling; FAS and PP: warming) (Table 4).

Subject perceived questionnaire (male and female [tingling n = 33, warming n = 32])

Most female participants agreed that first penetration during vaginal sex was smoother and more comfortable with both products after initial use and after 4 weeks of use, respectively (tingling: 97% and >87%; warming: >87% and >84%). Similarly, the majority of male partners agreed that first penetration during vaginal sex was smoother with both products after initial use and 4 weeks of use, respectively (tingling: 97% at both timepoints; warming: 94% and 91%).

Tolerance

Gynecologists rated vulvovaginal tolerance (signs of vulvovaginal irritation [subjective observation]) for all participants as “good” or “very good” for both lubricants. Most female participants agreed that the tingling and warming lubricants were gentle on skin in the vagina (75% and 89%, respectively) and of the vulva (75% and 100%, respectively).

For both products, dermatologists did not observe signs of irritation on the lips or oral mucosa. Oral tolerance for both lubricants was “very good” for all participants, except for one in each treatment group where tolerance was rated as “acceptable”. Most female participants agreed that the tingling and warming lubricants felt gentle on mucosa inside the oral cavity and lips (92% and 100%, respectively).

Patient global impression of change

For both lubricants, an improvement in sexual intimacy was observed. Around 50% of female participants recorded a ≥ 2-point improvement in patient global impression of change (PGIC), while <50% of males showed a ≥ 2-point improvement in PGIC (Table 5).

Safety

Of identified AEs (assessed by investigators), 12 and 18 AEs had a causal relationship to the tingling and warming lubricants, respectively. All other AEs were unrelated to the lubricants (Table 6).

No serious AEs were reported; all AEs were mild in severity, and in total, only 17.4% of male and female participants in the safety population experienced a mild AE (Table 7).

Notably, there were no AEs in a male partner that led to discontinuation. Overall, the discontinuation rate was 1.5%. This occurred in the warming lubricant treatment arm, where one female participant reported “burning, itching, and erythema directly after application”. Their male partner was subsequently withdrawn, and the participant had recovered at the end of the study.

Discussion

Our study assessed the safety and efficacy of two personal lubricants with sensate ingredients, one water-based tingling lubricant and one silicone-based warming lubricant. This study provides evidence that both sensate lubricants are effective for improving sexual function in women with vaginal dryness, as demonstrated by a significant change from baseline in the total FSFI score. The products were also associated with no oral and vulvovaginal tolerance concerns and few AEs. Sexual health is integral to overall well-being and vitality of individuals and couples,²⁵ and there is a need for products that improve and enhance sexual function and well-being in those without specific medical conditions.²⁶

Personal lubricants can provide relief from vaginal dryness and discomfort.^11,12 They can also enhance overall orgasmic response, as demonstrated by the significant increase in change from baseline orgasm score to 4 weeks, which may ultimately improve overall sexual pleasure.¹³ However, they should be formulated carefully in line with current guidelines on pH and osmolality for water-based lubricants.^14–16 To our knowledge, this novel study represents the first in vivo data examining the safety and efficacy of lubricants with a sensory ingredient as an additive. The study significantly contributes to the limited but growing body of published evidence on the safety and effectiveness of lubricants for the relief of intimate discomfort associated with vaginal dryness.^12,17,27,28

A statistically significant improvement of the mean total FSFI score was observed for both lubricants after 4 weeks of use, indicating an improvement in sexual function and supporting the effectiveness of the lubricants for relief of dyspareunia associated with vaginal dryness. Our findings are consistent with results from two aforementioned studies that used water-based lubricants without sensate ingredients in women with vaginal dryness.^17,27 Those studies similarly reported a significant improvement in sexual function, as indicated by the overall FSFI score (P < 0.001), resulting from lubricant use.^17,27

In this study, over half of participants experienced an improvement of ≥4 points in the total FSFI, which is considered a clinically important change.²⁴ The same was reported in a previous study, with more than 50% of participants for each of the five water-based lubricants investigated experiencing such an improvement.¹⁷

Most participants entered the study with a total FSFI score of ≤26.55 (indicating sexual dysfunction). However, at the end of the 4-week treatment period, >50% of participants had a total FSFI score of >26.55, suggesting an improvement in sexual function to a functional level. This highlights the importance of effectively treating pain associated with sex and indicates the potential of these lubricants to help with sexual dysfunction. There was also a positive change for both lubricants across all six domains of the FSFI. In particular, there were statistically significant increases across all domains except for desire in the warming lubricant (FAS and PP) and tingling lubricant (PP) arms and for arousal in the tingling lubricant (FAS and PP) arm. Overall, these findings indicate that the lubricants can not only provide relief from vaginal dryness, but may also improve overall sexual well-being and pleasure. The results align with findings from two previous studies that utilized the FSFI to assess sexual function in women with vaginal dryness who used water-based lubricants, demonstrating significant improvements across all six domains.^17,27 Furthermore, a prospective study that used a daily diary to record sexual pleasure and satisfaction among healthy women found higher ratings of sexual pleasure or satisfaction when using water- and silicone-based lubricants during sexual intercourse.²⁸

After 4 weeks of use, both female participants and their male partners had a positive perception of both lubricants, as expressed by agreement with questions about “smoother first penetration” and making “vaginal sex feel more comfortable”. Interestingly, a higher proportion of female participants reported an improvement in sexual intimacy than their male partners. Women often receive more emotional and affective education than men, which can influence how they perceive and communicate improvements in sexual intimacy.^29,30 This may explain the observed differences between females and males in our study.

No oral and vulvovaginal tolerance concerns were identified for both lubricants in the tolerance phase. In addition, all AEs related to the lubricants were symptoms of localized mild severity and were resolved by the end of the study. Healthcare professionals should be aware that AEs of mild severity are likely to happen, are often self-limiting, and rarely lead to discontinuation. It remains critical to adequately counsel patients about these AEs. The robust safety and tolerability profile and very low discontinuation rates of the lubricants indicate they could enhance patients’ overall sexual experience, without safety concerns.

Strengths and limitations

The randomized, controlled design is a strength of this study. Further, vaginal dryness and discomfort affects premenopausal and postmenopausal women²; however, most previously published studies on vaginal dryness have focused on postmenopausal women. Therefore, the inclusion of a wide age range in the current study means that the data are applicable to a wider population and should provide confidence that lubricants are relevant throughout adulthood. The FSFI questionnaire is a widely accepted and clinically validated study instrument to measure female sexual function. The study investigated oral mucosal tolerance, which is novel as previous studies have not included these assessments. Finally, inclusion of subject perceived questionnaire (SPQ) and PGIC data from male partners is novel.

This study has several limitations. Firstly, reporting and recall bias may have affected data accuracy as participants were required to recall and report their sexual experiences over a 4-week period. The SPQ is not a clinically validated tool, limiting the validity of these results. Furthermore, the tolerance analysis only included a small number of participants (n = 22), which may limit the generalizability of the results. It should be noted that the female population was primarily composed of Caucasian participants and thus lacked racial and geographic diversity. The results are specific to self-identified cis male and cis female heterosexual couples engaging in vaginal/penile intercourse, and therefore may not be applicable to individuals of different ethnicities, sexual identities, or orientations. Finally, it is important to note that the dichotomous classification of the total FSFI score (sexual dysfunction [≤26.55] versus sexual function [>26.55]) fails to capture the full range of scores that reflect varying levels of female sexual dysfunction.³¹

Conclusions

In a wide age range of female participants who had reported vaginal dryness but were otherwise healthy, both sensate personal lubricants can be considered effective, as demonstrated by a clinically and statistically significant improvement in sexual function. Few AEs were reported and all were mild and localized. Beyond the relief of vaginal dryness, the results show that both lubricants can enhance overall sexual experience and function in women and their male partners.

Acknowledgments

The authors would like to thank Sammi Iveson and Janet Warren for review of the manuscript and Alice Switonski for statistical consultation, data interpretation and review of relevant sections in the manuscript. Medical writing support was provided by Abby Armitt and Honey McElhill of Obsidian Healthcare Group Ltd, UK.

Author contributions

Michael Krychman (Conceptualization [equal], Methodology [equal], Supervision [equal], Writing—review & editing [equal]), Sarah Hood (Conceptualization [equal], Funding acquisition [lead], Methodology [equal], Supervision [equal], Writing—review & editing [equal]), Karishma Hemmady (Methodology [equal], Writing—review & editing [equal]), Lingyao Su (Investigation [equal], Project administration [lead], Supervision [equal], Writing—review & editing [equal]), Snezhana Gaifieva (Investigation [equal], Methodology [equal], Writing—review & editing [equal]), Santiago Palacios (Conceptualization [equal], Methodology [equal], Supervision [equal], Writing—review & editing [equal]).

Funding

Funding for this research and medical writing assistance was provided by Reckitt Healthcare Ltd.

Conflicts of interest

Michael Krychman, Karishma Hemmady and Santiago Palacios are paid consultants for Reckitt Healthcare and contributed to the study design and concept review. They did not receive payment or financial support for the creation of this manuscript.

Lingyao Su and Sarah Hood are employees of Reckitt Healthcare Ltd. Snezhana Gaifieva was an employee of Reckitt Healthcare Ltd. at the time of the study.

References

Author notes