Abstract
Introduction and Hypothesis:
Pelvic floor myofascial pain (PFMP) is a common but underrecognized component of chronic pelvic pain and pelvic floor disorders symptoms with limited, well-studied treatment modalities. Our objective was to determine the effect of vaginal cryotherapy on PFMP with palpation.
Methods:
Following a standardized PFMP screening examination, individuals with a pain score ≥4/10 in ≥1 of four muscle groups were invited to participate in a randomized controlled trial comparing vaginal cryotherapy to control. Participants in both arms could choose to participate in a single in-office treatment; a two-week, at-home daily treatment; or both.
Results:
Between 3/2019–9/2021, 163 participants were enrolled and randomized: 80 to cryotherapy, 83 to control. Sixty-three (28 cryotherapy; 35 control) completed in-office treatment and 56 (32 cryotherapy; 24 control) completed at-home therapy. In the in-office comparison, mean pain scores decreased significantly in both arms: cryotherapy (5.13 vs. 4.10; p=0.02) and control (5.60 vs. 4.72; p<0.01), with a similar magnitude of reduction between arms (p=0.75). In the at-home comparison, mean pain scores decreased significantly in the cryotherapy arm (6.34 vs. 4.75; p<0.01), and non-significantly in the control arm (5.41 vs. 4.66; p=0.07), resulting in a non-significant difference between arms (p=0.14).
Conclusion:
PFMP pain with palpation improved following both a single cryotherapy session and two weeks of daily cryotherapy. Interestingly, pain scores also improved with room temperature therapy. Whether these findings reflect a therapeutic effect of both cold and room temperature intravaginal therapy, or a placebo effect is unclear but should be explored in larger studies.
Keywords: pelvic floor myofascial pain with palpation, cryotherapy, pelvic floor disorder symptoms
Brief Summary
A simple, home-based regimen of vaginal cryotherapy is a safe, accessible adjunct therapy with potential to improve pelvic floor myofascial pain and symptoms.
Introduction:
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 injections12,13 (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.
Materials and Methods:
Study design and population:
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.
Cryotherapy intervention:
Single session, in-office treatment:
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.
Two-week, at-home treatment:
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.
Assessment of PFD symptoms:
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.
Statistical analysis:
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.
Sample size calculation:
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.
Results:
Study population:
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/m2; 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).
Figure 1. Consort flow diagram.
Table 1.
Demographic and clinical characteristics of participants in a pilot randomized, placebo-controlled trial of vaginal cryotherapy for the treatment of pelvic floor myofascial pain
| In-office therapy (N=63) | At home therapy (N=56) | Participants that withdrew or were lost-to-follow-up from the at-home therapy group (N=65) | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Control (N=35) | Cryotherapy (N=28) | P-Value1† | Control (N=24) | Cryotherapy (N= 32) | P-Value2† | Control (N=36) | Cryotherapy (N=29) | P-Value3† | P-value4† | |
| Age (years, mean, SD) | 55.60(16.3) | 48.46(14.5) | 0.07 | 57.3 (12.6) | 54.5 (15.3) | 0.50 | 53.0 (13.0) | 50.0 (15.7) | 0.40 | 0.12 |
| Body Mass index (Kg/m2, mean, SD) | 29.9(7.8) | 28.75(5.9) | 0.52 | 27.7 (4.9) | 31.8 (7.7) | 0.02 | 30.2 (7.9) | 30.1 (7.6) | 0.95 | 0.93 |
| Gravidity (median, IQR) | 2(2–3) | 2(1–3) | 1.00 | 3 (2–4) | 3 (2–3.5) | 0.73 | 3 (2–4) | 2 (1–5) | 0.93 | 0.93 |
| Parity (median, IQR) | 2(1–3) | 2(1–3) | 0.52 | 2 (1.5–3) | 2 (2–3) | 0.81 | 2 (2–3) | 2(1–4) | 0.80 | 0.98 |
| Race [n(%)] | ||||||||||
| White | 31 (88.6) | 25 (89.3) | 1.00 | 22 (91.7) | 29 (90.6) | 0.45 | 30 (83.3) | 23 (79.3) | 0.77 | 0.60 |
| Black | 3 (8.6) | 2 (7.1) | 1 (4.2) | 3 (9.4) | 5 (13.9) | 4 (13.8) | ||||
| Other | 1 (2.9) | 1 (3.6) | 1 (4.2) | 0 | 1 (2.78) | 2 (6.9) | ||||
| Menopausal Status [n(%)] | ||||||||||
| Pre | 9 (25.7) | 10 (35.7) | 0.24 | 3 (12.5) | 8 (25.0) | 0.29 | 9 (25.0) | 11 (37.9) | 0.73 | 0.05 |
| Post | 23 (65.7) | 14 (50.0) | 18 (75.0) | 23 (71.9) | 21 (58.3) | 13 (44.8) | ||||
| Peri/uncertain/not reported | 3 (8.6) | 4 (14.3) | 3 (12.5) | 1 (3.1) | 6 (16.7) | 5 (17.2) | ||||
| Presenting symptom | ||||||||||
| Prolapse | 11 (31.4) | 9 (32.1) | 0.95 | 7 (29.2) | 11 (34.4) | 0.68 | 10 (27.8) | 4 (13.8) | 0.23 | 0.19 |
| Lower urinary tract symptoms | 18 (51.4) | 17 (60.7) | 0.46 | 16 (66.7) | 23 (71.9) | 0.67 | 23 (63.9) | 17 (58.6) | 0.66 | 0.35 |
| Pelvic pain | 5 (14.3) | 3 (10.7) | 0.72 | 1 (4.17) | 4 (12.5) | 0.38 | 7 (19.4) | 7 (24.1) | 0.64 | 0.06 |
| Fecal incontinence | 0 | 0 | - | 0 | 2 (6.3) | 0.50 | 2 (5.6) | 1 (3.5) | 1.00 | 1.00 |
| Other | 2 (5.7) | 0 | 0.50 | 0 | 1 (3.1) | 1.00 | 2 (5.6) | 4 (13.8) | 0.39 | 0.12 |
| Medical history [n(%)] | ||||||||||
| Sciatica/low back pain | 1 (2.9) | 1 (3.57) | 1.00 | 6 (25.0) | 1 (3.1) | 0.03 | 3 (8,3) | 5 (17.2) | 0.45 | 0.97 |
| Degenerative disc disease/OA | 8 (22.9) | 5 (17.9) | 0.63 | 7 (29.2) | 9 (28.1) | 0.93 | 10 (27.8) | 10 (34.5) | 0.56 | 0.79 |
| Rheumatologic disease | 0 | 3 (10.7) | 0.09 | 1 (4.2) | 0 | 0.43 | 4 (11.1) | 2 (6.9) | 0.68 | 0.12 |
| Chronic pain/fibromyalgia | 5 (14.3) | 1 (3.6) | 0.21 | 1 (4.2) | 1 (3.1) | 1.00 | 1 (2.8) | 2 (6.9) | 0.58 | 1.00 |
| Chronic pelvic pain/endometriosis | 4 (11.4) | 2 (7.14) | 0.68 | 2 (8.3) | 0 | 0.18 | 4 (11.1) | 2 (6.9) | 0.68 | 0.28 |
| Inflammatory bowel disease | 0 | 0 | - | 0 | 3 (9.4) | 0.25 | 1 (2.8) | 1 (3.45) | 1.00 | 0.66 |
| Irritable bowel syndrome | 3 (8.6) | 0 | 0.25 | 1 (4.2) | 2 (6.3) | 1.00 | 3 (8.3) | 0 | 0.25 | 1.00 |
| Anxiety/depression | 14 (40.0) | 10 (35.7) | 0.73 | 5 (20.8) | 8 (25.0) | 0.71 | 16 (44.4) | 14 (48.3) | 0.76 | 0.01 |
| Surgical history [n(%)] | ||||||||||
| Hysterectomy | 15 (42.9) | 9 (32.1) | 0.38 | 10 (41.7) | 9 (28.1) | 0.29 | 16 (44.4) | 8 (27.6) | 0.16 | 0.73 |
| Prolapse Surgery | 2 (5.7) | 2 (7.1) | 1.00 | 2 (8.3) | 2 (6.3) | 1.00 | 1 (2.8) | 4 (13.8) | 0.16 | 1.00 |
| Incontinence surgery | 3 (8.6) | 1 (3.6) | 0.62 | 1 (4.2) | 3 (9.4) | 0.63 | 4 (11.1) | 3 (10.3) | 1.00 | 0.54 |
| Vaginal mesh removal/revision | 0 | 0 | - | 0 | 0 | - | 0 | 2 (6.9) | 0.20 | 0.50 |
| Pelvic Floor symptoms [n (%)] | ||||||||||
| Prolapse Symptoms | 16 (45.7) | 12 (42.9) | 0.82 | 8 (33.3) | 13 (40.6) | 0.58 | 15 (41.7) | 7 (24.1) | 0.16 | 0.72 |
| Urinary symptoms | 31 (88.6) | 26 (92.9) | 0.68 | 23 (95.8) | 29 (90.6) | 0.63 | 34 (94.4) | 25 (86.2) | 0.39 | 0.75 |
| Bowel Symptoms | 15 (42.9) | 17 (60.7) | 0.16 | 19 (79.2) | 21 (65.6) | 0.27 | 15 (41.7) | 21 (72.4) | 0.01 | 0.07 |
| History of sexual abuse | ||||||||||
| No | 23 (65.7) | 17 (60.7) | 0.61 | 15 (62.5) | 17 (53.1) | 0.62 | 15 (41.7) | 15 (51.7) | 0.55 | 0.12 |
| Yes | 3 (8.57) | 5 (17.9) | 3 (12.5) | 3 (9.4) | 10 (27.8) | 6 (20.7) | ||||
| Not reported | 9 (25.7) | 6 (21.4) | 6 (25.0) | 12 (37.5) | 11 (30.6) | 6 (20.7) | ||||
P-value comparing baseline demographic and clinical characteristics between arms in the 10-minute in-office treatment group calculated by Fisher’s exact test, chi-squared as appropriate.
P-value comparing baseline demographic and clinical characteristics between arms in the at home treatment group calculated by Fisher’s exact test, chi-squared as appropriate.
P-value comparing baseline demographic and clinical characteristics between arms among participants that withdrew or were lost to follow up calculated by Fisher’s exact test, chi-squared as appropriate.
P-value comparing baseline demographic and clinical characteristics between participants that completed the at home therapy and those participants that withdrew or were lost to follow up calculated by Fisher’s exact test, chi-squared as appropriate.
Bolded p-values represent statistical significance
Single session (10-minute), in-office treatment:
Pelvic floor myofascial pain on palpation
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)
Table 2.
Change in mean pelvic floor myofascial pain scores on standardized examination after a single session and two weeks of vaginal cryotherapy vs. control
| Comparison of single session, in-office intervention and control | Comparison of two-week, at-home intervention and control | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Site | Cryotherapy (N=28) | Control (N=35) | Change in pain score | Cryotherapy (N=32) | Control (N=24) | Change in pain score | ||||||||||||
| Baseline | Follow-up | P-Value1† | Baseline | Follow-up | P-Value1† | Cryo-therapy | Control | P-Value2† | Baseline | Follow-up | P-Value1† | Baseline | Follow-up | P-Value1 | Cryo-therapy | Control | P-Value2† | |
| Individual sites | ||||||||||||||||||
| ROI | 5.82 | 4.36 | 0.02 | 5.97 | 4.49 | <0.01 | −1.46 | −1.49 | 0.97 | 6.41 | 4.72 | <0.01 | 6.04 | 5.38 | 0.36 | −1.69 | −0.67 | 0.23 |
| RLA | 4.61 | 3.54 | 0.09 | 5.26 | 4.34 | 0.02 | −1.07 | −0.91 | 0.83 | 6.28 | 4.44 | 0.01 | 4.42 | 3.63 | 0.13 | −1.84 | −0.79 | 0.22 |
| LLA | 4.82 | 3.71 | 0.14 | 5.06 | 4.69 | 0.20 | −1.11 | −0.37 | 0.36 | 5.50 | 4.44 | 0.06 | 5.00 | 4.42 | 0.31 | −1.06 | −0.58 | 0.55 |
| LOI | 5.25 | 4.79 | 0.45 | 6.11 | 5.37 | 0.05 | −0.46 | −0.74 | 0.70 | 7.16 | 5.41 | <0.01 | 6.17 | 5.21 | 0.11 | −1.75 | −0.96 | 0.32 |
| Combined sites | ||||||||||||||||||
| Right | 5.21 | 3.95 | 0.01 | 5.61 | 4.41 | <0.01 | −1.27 | −1.20 | 0.90 | 6.34 | 4.58 | <0.01 | 5.23 | 4.50 | 0.18 | −1.77 | −0.73 | 0.12 |
| Left | 5.04 | 4.25 | 0.18 | 5.59 | 5.03 | 0.02 | −0.79 | −0.56 | 0.71 | 6.33 | 4.44 | <0.01 | 5.58 | 4.81 | 0.09 | −1.41 | −0.77 | 0.31 |
| LA | 4.71 | 3.63 | 0.04 | 5.16 | 4.51 | 0.01 | −1.09 | −0.64 | 0.43 | 5.89 | 4.44 | <0.01 | 4.71 | 4.02 | 0.17 | −1.45 | −0.69 | 0.27 |
| OI | 5.54 | 4.57 | 0.03 | 6.04 | 4.93 | 0.01 | −0.96 | −1.11 | 0.76 | 6.78 | 5.06 | <0.01 | 6.10 | 5.29 | 0.11 | −1.72 | −0.81 | 0.15 |
| Mean score | 5.13 | 4.10 | 0.02 | 5.60 | 4.72 | <0.01 | −1.03 | −0.88 | 0.75 | 6.34 | 4.75 | <0.01 | 5.41 | 4.66 | 0.07 | −1.59 | −0.75 | 0.14 |
ROI=Right obturator internus, RLA = Right levator ani, LLA = Left levator ani, LOI = Left obturator internus, Right = Both right obturator internus and levator ani, Left = Both left obturator internus and levator ani, LA = Both right and left levator ani combined, OI = Both right and left obturator internus combined.
P-value comparing baseline pelvic floor myofascial pain score on standardized exam to follow-up pelvic floor myofascial pain score on standardized examination within arm. Calculated using paired t-test.
P-value comparing baseline pelvic floor myofascial pain score on standardized exam to follow-up pelvic floor myofascial pain score on standardized examination by arm. Calculated using independent t-test.
Two-week, at-home treatment:
Pelvic floor myofascial pain on palpation
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)
Pelvic floor disorder symptoms
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.
Table 3.
Change in pelvic floor disorder symptoms after two weeks of vaginal cryotherapy vs. control
| Cryotherapy (N=28) | Control (N=18) | Change in score | |||||||
|---|---|---|---|---|---|---|---|---|---|
| Baseline | Follow-up | P-Value1† | Baseline | Follow-up | P-Value1† | Cryotherapy | Control | P-Value2† | |
| UDI-19 | 117.7 | 100.4 | 0.05 | 112.5 | 101.6 | 0.31 | −17.3 | −10.9 | 0.64 |
| PFDI-20 | 181.6 | 161.8 | 0.12 | 174.1 | 173.4 | 0.96 | −19.8 | −0.8 | 0.33 |
| POPDI-6 | 62.8 | 55.1 | 0.21 | 49.0 | 56.7 | 0.29 | −7.6 | 7.6 | 0.11 |
| UDI-6 | 65.5 | 64.3 | 0.85 | 70.6 | 62.9 | 0.37 | −1.3 | −7.8 | 0.54 |
| CRADI-8 | 53.3 | 42.4 | 0.05 | 54.4 | 53.8 | 0.99 | −10.9 | −0.6 | 0.23 |
| PFIQ | 72.4 | 63.9 | 0.09 | 67.4 | 67.7 | 0.97 | −12.4 | 0.3 | 0.23 |
UDI = Urogenital distress inventory, PFDI-20 = Pelvic floor distress Inventory,
POPDI-6 = Pelvic organ prolapse distress inventory, UDI-6 = Urogenital distress inventory short form,
CRADI-8 = Colorectal-Anal Distress Inventory, PFIQ = Pelvic floor Impact Questionnaire
P-Value comparing baseline and follow up scores within arm. Calculated by paired t-test
P-Value comparing mean change in scores between arms. Calculated by independent t-test
Bolded p-values represent statistical significance
Daily symptoms
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.
Table 4.
Mean change in lower urinary tract symptoms (LUTS) on daily dairy from baseline after at-home vaginal cryotherapy vs. control
| n=53 | Cryotherapy (n=32) | Control (n=21) | p-value within arm | P-Value for change in mean score by arm | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Pre-intervention | Post-intervention | Change | 2-point symptoms increase (%) | p-value within arm | Pre-intervention | Post-intervention | Change | 2-point symptoms increase (%) | |||
| Urgency (n=25) | 3.24 | 2.86 | −0.38 | 4 (8%) | 0.54 | 2.90 | 2.85 | −0.05 | 0 | 0.92 | 0.67 |
| Frequency (n=22) | 3.63 | 2.51 | −1.12 | 1 (2%) | 0.08 | 2.55 | 2.20 | −0.35 | 1 (2%) | 0.62 | 0.40 |
| UTI like symptoms (n=9) | 4.30 | 2.37 | −1.93 | 0 | 0.04 | 3.58 | 3.50 | −0.08 | 0 | 0.42 | 0.04 |
| Pelvic Pressure (n=35) | 3.28 | 2.20 | −1.08 | 1 (2%) | 0.03 | 3.50 | 3.42 | −0.26 | 1 (2%) | 0.65 | 0.25 |
| Vaginal Burning (n=16) | 2.62 | 3.42 | 0.80 | 2 (4%) | 0.27 | 0.58 | 2.61 | 0.2.03 | 5 (9%) | <0.01 | 0.19 |
Discussion
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 body28 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-1936 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 symptoms19 (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.
Disclosures and Source of Funding:
Dr. Morsy was funded by grant #T32 DK120497-01A1 and Dr. Sutcliffe was funded by the Barnes-Jewish Hospital Foundation, the Alvin J. Siteman Cancer Center (P30CA091842), and the Institute for Clinical and Translational Sciences. The remaining authors report no disclosures.
Footnotes
FINANCIAL DISCLAIMER/CONFLICT OF INTEREST: NONE
This work was presented at the International Continence Society 2022 meeting in Vienna, Austria, September 7–10, 2022.
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