A Pilot Randomized Controlled Trial of Vaginal Cryotherapy for the Treatment of Pelvic Floor Myofascial Pain.

Between March 2019 and September 2021, we enrolled 163 participants, 42 in the single session, in-office group (including cryotherapy and control), 98 in the two-week, at-home group, and 23 in both ( Figure 1 ). Eighty participants were randomized to the cryotherapy intervention and eighty-three to control (N=83). Overall, most participants identified as White (85.9%) and were postmenopausal (88.3%), with a mean age of 53.5±15.1 years. The most reported PFD symptoms were LUTS (90.2%). Demographic and clinical characteristics were generally similar between arms ( Table 1 ), except that at-home therapy participants randomized to cryotherapy had a higher body mass index (31.8 vs. 27.7 kg/m 2 ; p=0.02) and were less likely to report sciatica/low back pain than at-home therapy participants randomized to control (3.1% vs. 25%; p=0.03). Of the 64 participants (42 in the 10-minute, in-office only and 22 in both) enrolled in the 10-minute, in-office treatment, 63 (98.4%; 28 cryotherapy; 35 control) participants completed the treatment and were re-examined; one participant withdrew when randomized to control, and one left before repeat examination was performed. Baseline PFMP on palpation was in the “moderate” range (mean=5.60, range 1–9) on a 0–10-point scale and similar between cryotherapy and control arms (5.13 vs. 5.60; p=0.39). After 10 minutes of in-office therapy, participants in both the cryotherapy (5.13 vs. 4.10; p=0.02) and control (5.60 vs. 4.72; p<0.01) arms noted significant improvement in pain scores; the magnitude of this improvement was similar between arms (−1.03 vs. −0.88 p=0.75). Similar patterns were observed for all individual and combined muscle sites. ( Table 2 ) Of the 121 participants enrolled in the at-home therapy group, 56 (46.3%; 32 cryotherapy and 24 control) completed the at-home treatment and returned for a repeat examination. Sixty-five participants (53.7%; 29 cryotherapy and 36 control) did not complete the study, including 31 lost-to-follow-up and 34 that withdrew. Most participants did not provide a reason for withdrawal (N=22; 64.7%), but of those that did, the most reported reason was discomfort with tube insertion (N=6; 17.6%). Compared to participants that completed the study, those that were lost-to-follow-up or withdrew were more likely to be premenopausal (p=0.05), report a history of anxiety/depression (p=0.01), and have lower pain on palpation at baseline (5.21 vs. 5.93; p=0.05;). Average follow-up time for at-home participants was 3.0±1.6 weeks. Baseline PFMP on palpation was in the “moderate” range (mean=5.72, range: 2–9.5), and was significantly higher in the cryotherapy arm compared to the control arm (6.34 vs. 5.41; p=0.05). After at least 2 weeks of at-home therapy, pain scores were significantly reduced in the cryotherapy arm (6.34 vs. 4.75; p<0.01) and non-significantly reduced in the control arm (5.41 vs. 4.66; p=0.07), resulting in a non-significant difference by arm (−1.59 vs. −0.75; p=0.14). Similar patterns were observed at all individual and combined muscle sites. ( Table 2 ) Of the 56 participants that completed at-home therapy, 46 (82.1%) completed both the baseline and post-intervention UDI-19, PFDI-20, and PFIQ questionnaires. In general, participants in the cryotherapy arm tended to report improved symptoms following therapy, but these findings were statistically significant for the UDI-19 (117.7 vs. 100.4; p=0.05) and CRADI-8 (53.3 vs. 42.4; p=0.05) only ( Table 3 ). In contrast, participants in the control arm noted minimal improvement or worsening in their symptoms following therapy. However, when we compared changes in symptoms across arms, no statistically significant differences were observed. A total of 53 participants completed at least one daily diary (32 cryotherapy; 21 control; Table 4 ). Participants completed an average of 10.8 (SD± 3.66) diary days and 10.3 (SD±3.78) interventions. In general, participants in the cryotherapy arm reported greater improvement in LUTS and pelvic symptoms post-intervention, but only UTI-like symptoms were significantly improved compared to control (−1.93 vs. −0.08; p=value=0.04). Furthermore, less than 10% of participants noted a 2-point worsening of these symptoms post-intervention.

This is a pilot randomized controlled trial at a single tertiary center with the primary objectives of determining the effects of vaginal cryotherapy on pelvic floor myofascial pain intensity in patients with PFMP on palpation: 1) as an immediate, 10-minute, in-office treatment modality, and 2) as a two-week, at-home therapy. Our secondary objective was to determine the effect of two weeks of at-home vaginal cryotherapy on patient-reported PFD symptoms. All new patients presenting to our urogynecology practice are screened for PFMP with palpation using a standardized pelvic floor myofascial examination. 21 Patients are asked to rate their pain on palpation of pelvic floor and hip muscles (bilateral LA and OI) on 11-point verbal rating scales. Between March of 2019 and September of 2021, eligible patients with a pain score of ≥4/10 in ≥1 of the four muscle groups were invited to participate in this pilot trial. Patients were ineligible if they were <18 years of age, non-English speaking, had a diagnosis of dementia or limited mobility that prevented them from performing the intervention, had an active gynecologic malignancy, or were within 6 weeks postpartum or postoperative from gynecologic surgery. Patients with chronic pain were also avoided. Following written informed consent, participants were invited to participate in the immediate therapy group, two-week therapy group, or both. They were then randomized 1:1 to either intervention or control by a research assistant using a randomization program in REDCap (version 7). Participants were aware of the group assignment but the physician performing the repeat examination was blinded. This registered clinical trial ( ClinicalTrials.gov , NCT03885791 ) was approved by the Washington University in St. Louis Institutional Review Board. Participants randomized to the intervention group were provided with a 15 mL conical centrifuge tube prepared with a mixture of water (10 mL) and rubbing alcohol (5 mL) that had been stored in the freezer overnight. The control group was provided with an identical empty tube at room temperature. Both groups were instructed to place the tube intravaginally for a total of 10 minutes. Participants were reexamined immediately by a provider blinded to treatment arm using the same pelvic floor myofascial examination as at baseline. The at-home intervention group was provided with two 15 mL centrifuge tubes and standardized instructions on how to prepare their tubes. Control group participants were provided with two 15 mL centrifuge tubes and instructed to keep them empty at room temperature. Participants were asked to place one tube intravaginally, cold or empty, based on their randomization, for a total of 10 minutes daily for two weeks or until their follow-up appointment (up to four weeks after baseline). A repeat examination was performed at their follow-up visit by a provider blinded to treatment arm. As a secondary outcome, participants enrolled in at-home treatment provided self-reported information on PFD symptoms using validated self-administered questionnaires including the Urogenital Distress Inventory (UDI-19), 22 Pelvic Floor Distress Inventory (PFDI-20), 23 Pelvic Floor Impact Questionnaire (PFIQ-7), 23 and Pelvic Organ Prolapse/Urinary incontinence Sexual Questionnaire (PISQ-IR) 24 at baseline and after completing the intervention 2–4 weeks from their baseline visit. Questionnaires assessed degree of bother from LUTS, impact on quality of life, sexual function associated with urinary incontinence, voiding dysfunction, pelvic organ prolapse (POP) symptoms, and defecatory dysfunction. Questionnaires were scored based on published protocols. 22 – 24 All data were collected in REDCap. 25 , 26 In addition to patient-reported outcome instruments, participants were asked to report their daily intensity of lower urinary tract and pelvic symptoms (i.e., urgency, frequency, urinary tract infection [UTI]-like symptoms, pelvic pressure/heaviness, and vaginal burning) on scales of 0–10 (0=none and 10=severe) both before and during the intervention. Participants were sent the daily diary through REDCap. Student’s t-tests and Wilcoxon rank-sum tests were used to compare mean (or the full distribution of): 1) individual site-specific (bilateral OI and LA) and overall pain scores, 2) PFD symptom scores, and 3) changes in pain and PFD symptom scores over time by arm. Paired t-tests and Wilcoxon signed rank-sum tests were used to compare these values within arm. SAS version 9.4 (Cary, NC) was used for statistical analysis. A reduction of 2-points on an 11-point verbal rating scale or a 50% reduction in pain is regarded as clinically significant. 27 To detect this magnitude of difference between arms, we initially estimated a total sample size of 66 participants (33 per arm), assuming 80% power, an α-level of 0.05, and 20% loss-to-follow-up. However, as loss-to-follow-up during the trial was closer to 50%, we increased the sample size to a total of 163 participants.

The objective of our pilot study was to examine the effect of vaginal cryotherapy on PFMP with palpation and PFD symptoms in patients with pelvic floor disorders after both single session, in-office, and daily two-week treatments. We found that, although cryotherapy was associated with reduced PFMP with palpation after a single 10-minute treatment and two weeks of at-home treatment, this reduction was not statistically significantly different from control. Similar findings were observed for PFD symptoms following two weeks of at-home treatment. Our null trial findings could potentially be interpreted in several different ways, each of which warrants further consideration and discussion. First, it is possible that both vaginal cryotherapy and the tactile stimulation provided by an empty tube in the vagina have a therapeutic effect on PFMP with palpation, leading to similar improvements in symptoms by arm. Cryotherapy has already shown promise in managing myofascial and chronic musculoskeletal disorders in other areas of the body 28 and thus could possibly be effective for the muscles of the pelvic floor. Cryotherapy is hypothesized to act by reducing inflammation and edema, and consequently muscle spasm. 29 Additional mechanisms by which it may act include increasing pain threshold and tolerance, and reducing nerve conduction velocity, 19 , 30 with evidence to support a cumulative analgesic effect. 16 Although used as a control in our trial, it is possible that vaginal placement of a room temperature tube could contribute to reduced pain through tactile stimulation. This mechanism is not clearly understood in humans, but some data suggest that even light touch can produce an anti-nociceptive response through stimulation of nerve fibers that compete with nocioreceptors. 31 Therefore, future trials may need to consider including a third arm to distinguish between these two mechanisms – cryotherapy and tactile stimulation – and to control appropriately for a placebo response. Another possible explanation for our null findings is a placebo response in both the cryotherapy and control arms. Data from previous trials suggest that placebo responses typically account for 35% of observed improvement, 32 with higher values reported for conditions such as interstitial cystitis/bladder pain syndrome (45–50%) 33 , 34 and low back pain (65–70%). 35 Other possible explanations for our observed improvement in both arms include an associative learning process or reduction in anticipatory anxiety on repeat examination in both arms, as well as a simple regression to the mean, whereby pain with palpation improved on its own, irrespective of treatment. Also, while we have heard anecdotal testimonials by patients about the effect of daily cryotherapy on their lower urinary, bowel, and prolapse symptoms, this effect is usually observed after 6–8 weeks of treatment; thus, the two weeks designated in the study protocol may not have been long enough to observe the anticipated effect. In addition, in clinical practice, patients often use two tubes in sequential order for a total of 14–15 minutes and may repeat the treatment more than once per day. Therefore, future studies might consider testing a longer-duration intervention. A secondary objective of our trial was to assess the impact of at least two weeks of vaginal cryotherapy on self-reported PFD symptoms. In general, we observed similar findings for PFD symptoms as for PFMP with palpation. Even though there were no statistical significant differences in change scores by arm, cryotherapy was associated with a clinically significant reduction in UDI-19 36 and PFDI-20 scores. 37 It is unlikely that vaginal cryotherapy, or the control in this study, induced an anatomic or physiologic “correction” in the bladder and bowel function or vaginal support that could directly improve PFDs. Rather, this change is more likely to reflect improvement in the underlying associated symptoms 19 (i.e. LUTS, prolapse, bowel) due to PFMP that is detectable on palpation. Viscerosomatic convergence and the anatomic proximity of the urinary bladder, bowel, uterus and vagina to the pelvic floor and hip muscles are possible explanations for the overlap between PFMP and dysfunction and these visceral organ-related symptoms. While this study was being conducted, an important and tremendously helpful terminology report was published by the Frawley et al on behalf of the International Continence Society. 38 The goal of this terminology report was to update and comprehensively document the terms and related definitions of PFM assessment, to describe assessment methods and interpretation of findings, to standardize assessment procedures, and aid diagnostic decision making related to PFM function and dysfunction. 38 Within this report, definitions for pelvic floor tension myalgia, pelvic floor myofascial pain syndrome, and pelvic floor myalgia were thoroughly described and characterized. 38 In our study we describe the physical examination finding of “pelvic floor myofascial pain with palpation” in women with pelvic floor disorder symptoms and report the change in both pain with palpation scores and PFD symptoms after cryotherapy. Of note, using current terminology “pain” could be replaced with “tenderness”. The participants in our study could have had any of the three diagnoses described above as our participants were enrolled based on their physical examination finding not a diagnosis. Strengths of our study include the innovative nature of our intervention - a simple, accessible, and conservative potential therapy for PFMP on palpation; the randomized design, with blinding of providers; and the use of validated questionnaires. Limitations include our small sample size and above average attrition rate, which was greater in the control than the cryotherapy arm, and our lack of a true placebo or control. Our higher than average attrition rate is consistent with rates observed in other complementary and alternative medicine trials and likely relates to the un-blinded status of participants, 39 higher prevalence of anxiety and depression, and lower perceived utility of vaginal cryotherapy in the context of significantly lower pain on palpation at baseline. Additionally, our treatment duration (10 minutes), treatment frequency per day, and follow-up time (two weeks) may not have been sufficiently long to observe an effect, as certain providers recommend up to15 minutes of cryotherapy per day, 1–3 times per day based on pain severity, and in our clinical practice we often see patients after 6–8 weeks of treatment. In conclusion, although we observed improvement in PFMP with palpation in both arms of our small pilot randomized controlled trial – cryotherapy and room temperature tube – we believe that future larger studies are warranted, including a non-intervention control arm, given the biologic plausibility and potential of this accessible vaginal therapy.

Pelvic floor myofascial pain (PFMP) is characterized by muscle tenderness, trigger points and hypertonicity in the muscles of the pelvic floor (levator ani, LA) and internal hip (obturator, OI). 1 The pathogenesis of PFMP is not clearly understood, but hypotheses related to repetitive trauma to the pelvic floor and internal hip muscles from direct and indirect physiological and psychological stress have been proposed due to the musculoskeletal function and centralized location of these muscles. 2 The prevalence of PFMP on palpation in the general population is largely unknown, mainly due to the paucity of providers that screen for PFMP on routine gynecologic examination. 2 , 3 PFMP is estimated to affect 60–85% of women with chronic pelvic pain and up to 78% of women with interstitial cystitis/painful bladder syndrome. 4 , 5 Interestingly, pain on palpation of the pelvic floor muscles has been found in 17.2%−25% of pain-free controls and up to 85% of women presenting with non-pain pelvic floor disorder (PFD) symptoms. 6 – 8 Positive correlations have also been observed between PFMP and several non-pain symptoms and conditions, including defecatory dysfunction, 3 lower urinary tract symptoms (LUTS), subjective pelvic organ prolapse (POP) symptoms, 6 and degree of bother and impact on quality of life from POP. 7 , 8 The treatment of PFMP is challenging and typically requires a multimodal approach including medications, 9 , 10 pelvic floor muscle therapy, 11 as well as trigger point injections 12 , 13 (i.e. anesthetics, steroids, botulinum toxin). While these treatment modalities are often effective, they may have significant side effects and are not always readily available or covered by insurance. Therefore, alternative accessible therapies are needed. Cryotherapy, or tissue cooling, has been widely used for thousands of years to treat musculoskeletal injuries. 14 , 15 More recently, cryotherapy has been accepted as a simple and effective intervention for treating myofascial and chronic pain in other areas of the body. 16 – 18 It is thought to reduce pain by decreasing tissue metabolism and blood flow to injured tissue, thereby reducing inflammation, edema, and ultimately muscle spasm and pain. 19 Additionally, the analgesic effect of cryotherapy may be augmented by its effect on neural conductance velocity and nocioreceptors. 19 , 20 Despite widespread use of cryotherapy for myofascial pain throughout the body, its effect on PFMP with palpation has not, to our knowledge, been studied. The pelvic floor muscles are easily accessible through the transvaginal route; therefore, vaginal cryotherapy could be performed readily with a cool test tube. In the present pilot randomized controlled trial, we sought to determine the effect of vaginal cryotherapy on PFMP and PFD symptoms.