The Effect of Botulinum on Chronic Pelvic Pain and Sexual Satisfaction in Women with Endometriosis

& Objective: Endometriosis is a chronic gynecological condition affecting approximately 10% of women of reproductive age. Chronic pelvic pain is a common symptom of endometriosis which significantly impacts on a woman's quality of life, including sexual satisfaction. Botulinum toxin injection has been used as a treatment for chronic pelvic pain in endometriosis, but its effect on sexual satisfaction is not well understood. The present study was conducted with aim to investigate the effect of botulinum on chronic pelvic pain and sexual satisfaction in women with endometriosis.

& Methods: This randomized controlled trial study was conducted on 32 wo men with endometriosis who were randomly assigned to receive either botulinum toxin injection or placebo. The primary outcome was a change in chronic pelvic pain assessed using the visual analog scale (VAS) at one month after treatment. Secondary outcome included changes in sexual satisfaction assessed using the Female Sexual Function Index (FSFI) at one month after treatment.

The botulinum toxin injection significantly reduced chronic pelvic pain compared to placebo at one month after treatment (P<0.001). There was also a significant improvement in sexual satisfaction in the botulinum toxin group compared to placebo at one month after treatment (P=0.001).

Botulinum toxin injection in women with endometriosis may be an effective treatment option for chronic pelvic pain and improving sexual satisfaction.

Botulinum, Chronic Pelvic Pain, Endometriosis, Sexual Satisfaction Received: 2023/05/12; Accepted: 2023/08/01; Published Online: 22 Jan 2025; Use your device to scan and read the article online Corresponding Information: Mojgan Asadi, Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran Email: [email protected] Copyright © 2025, This is an original open -access article distributed under the terms of the Creative Commons Attribution-noncommercial 4.0 International License which permits copy and redistribution of the material just in noncommercial usages with proper citation. 1. Introduction Chronic pelvic pain is a common condition affecting many women worldwide. It is characterized by persistent pain in the lower abdomen, pelvis, and genital area lasting for more than six months (1). Endometriosis is one of the leading causes of chronic pelvic pain in women. It is a condition where the tissue that normally lines the uterus grows outside of it, causing inflammation and scarring (2-5). Endometriosis can have a significant impact on a woman's sexual health and satisfaction. It is associated with pain that can make sexual intercourse uncomfortable or even unbearable. This can lead to decreased sexual desire and satisfaction, which can have negative effects on a woman's overall quality of life (6). Botulinum toxin is a neurotoxin which acts by blocking nerve signals to muscles, reducing muscle contractions and spasms. Botulinum toxin injection has been found to be an effective treatment for chronic pelvic pain and sexual dysfunction. In a study conducted on women with vulvodynia, botulinum Fatemeh Davari Tanha et al. 202 Volume 10, March 2025 Journal of Obstetrics, Gynecology and Cancer Research toxin injection was found to significantly reduce pain and improve sexual satisfaction (7). The other studies showed that the injection of botulinum toxin into the pelvic floor muscles reduced muscle tension and spasms, which are often associated with chronic pelvic pain (8, 9). However, there is limited research on the effectiveness of botulinum toxin in treatment of endometriosis. Therefore, it seems necessary to design a study to investigate the effect of botulinum toxin injection on chronic pelvic pain and sexual satisfaction in endometriosis. The study will provide valuable insights into the use of botulinum toxin injection as a treatment option for endometriosis -related symptoms. It will help clinicians make informed decisions about whether to recommend this tr eatment to their patients. Additionally, the study will contribute to the growing body of research on endometriosis and its management, which can lead to improved patient outcomes. 2. Materials and Methods This randomized controlled trial study was conducted on women with endometriosis between July 2021 and July 2022 at a tertiary care university hospital (Yas Hospital Complex). The study included 32 women with endometriosis who were randomly assigned to receive either botulinum toxin injection or placebo . The sample size was calculated using the clinical trial superiority design formula and the reported values in the previous study (10), the study power of 80%, and the two -tailed significance level of 5%. The sample size was determined to be 16 in each gr oup. The inclusion criteria for the patient group were age between 18 and 50 years, history of endometriosis at surgery, persistent pelvic pain for at least 6 months and pelvic floor spasm. The exclusion criteria were other causes of chronic pelvic pain in cluding gastrointestinal, psychological disorders, infectious, fibromyalgia and chronic fatigue syndrome, untreated severe cervical dysplasia, history hysterectomy and bilateral salpingo -oophorectomy, allergy to botulinum toxin, history of myasthenia gravis or Eaton -Lambert syndrome, history of urinary or fecal incontinence, pelvic prolapse, pregnancy, lactation, and menopause. The patients did not receive hormonal drugs for at least two months before the study. The primary outcome measure was change in chronic pelvic pain assessed using the visual analog scale (VAS) at one month after treatment. Secondary outcome measures included changes in sexual satisfaction assessed using the Female Sexual Function Index (FSFI) at one month after treatment. Before enrollment in the study, all participants underwent vaginal sonography or laparascopy for diagnosis and staging of endometriosis (11) . They were excluded if they had any contraindications to botulinum toxin injection or if they had undergone previous surgery for endometriosis within the past 6 months. First, muscle spasm and pain in the pelvic region were evaluated by vaginal finger examination, and the presence and location of the spasm was recorded. Then, after randomization by block randomization method, people were placed in botulinum injection group (intervention group) and control group (saline injection). The women were placed in the lithotomy position, and then single digit palpation was used to assess the presence of muscle spasm in the pelvic floor musc les. After the examination and 20 to 30 minutes before the injection, up to 10 mg of diazepam was administered orally, and 4% lidocaine cream was applied to the spasm site in the vaginal mucosa. In the intervention group, a vial of 100 units of Anabotulinu m toxin A (Botox) was placed in 4 ml of saline (final concentration of 25units/ml). A total of 100 units of botulinum were injected into the spasmodic muscles. The injections were made using a 27-gauge needle at a depth of 5 -10 mm by a gynecologist with experience in the field of endometriosis using a sterile technique. In fact, a total dose of 100 units was divided among three to four marked areas of muscle spasm. The researcher noted that the injection method was well -tolerated by the participants. Bilateral injections in muscles including pubococcygeus, iliococcygeus and internal obtrator were performed through transvaginal. Participants were followed up at one month after treatment to assess changes in chronic pelvic pain and sexual satisfaction over tim e. Out of 50 participants assessed for eligibility, 14 were excluded (10 did not meet criteria, 4 declined), and 36 were randomized equally into two groups: botulinum injection (n=18) and saline injection (n=18). Both groups were assessed for changes in chronic pelvic pain (VAS) and sexual satisfaction (FSFI) at 4 weeks, with 2 participants from each group lost to follow-up. Ultimately, data from 16 participants in each group were analyzed (Figure 1 ). Independent and paired T-test was used in parametric distribution and Wilcoxon and Mann -Whitney U was used in non -parametric distribution to evaluate the differences in means. All analyses were performed using SPSS 24 (IBM Corp., Armonk, NY, USA) software at a significant level of less than 0.05. 203 The Effect of Botulinum Toxin in Endometriosis Volume 10, March 2025 Journal of Obstetrics, Gynecology and Cancer Research Figure 1. CONSORT flow diagram illustrating the allocation of patients to the study groups 3. Results The demographic characteristics of the studied population are shown in Table 1 . The results showed that botulinum toxin injection significantly reduced chronic pelvic pain compared to placebo at one month after treatment (P<0.001). The mean sedative drug usage in the intervention group was lower than the control group, but the difference between the two groups was not significant (P=0.12) ( Table 2 ). There was also a significant improvement in sexual satisfaction in the botulinum toxin group compared to the placebo group at one month after treatment (P=0.001) ( Table 3 ). The comparison of sexual satisfaction after the intervention between the two groups showed that the scores of the compon ents of satisfaction (P<0.001), dyspareunia (P<0.001), and orgasm (P=0.001) were significantly higher in the botulinum toxin group than the placebo group. However, there was no statistically significant difference between the two groups regarding the score of libido (P=0.32), psychological stimulation (P=0.09), and wetness (P=0.11) ( Table 4 ). In general, the total score of sexual satisfaction after the intervention Excluded (n=14) ♦ Not meeting inclusion criteria (n=10) ♦ Declined to participate (n=4) ♦ Other reasons (n=0) Lost to follow -up (lack of communication with patients) (n=2) Review changes in chronic pelvic pain by VAS and sexual satisfaction by FSFI at 4 week Lost to follow -up (patient non-compliance) (n=2) Review changes in chronic pelvic pain by VAS and sexual satisfaction by FSFI at 4 week Assessed for eligibility (n=50) Analysed (n=16) Allocated to intervention (n=18) ♦ Received botulinum injection (n=18) Allocated to intervention (n=18) ♦ Received saline injection (n= 18) Analysed (n=16) Allocation Analysis Follow-Up Enrollment Randomized (n=36) Fatemeh Davari Tanha et al. 204 Volume 10, March 2025 Journal of Obstetrics, Gynecology and Cancer Research showed a statistically significant difference between the two groups (P=0.001). No side effects (urinary retention, constipation, urinary and fecal incontinence, back pain, etc.) caused by botulinum injection were reported in this study. Table 1. Demographic characteristic of the studied population Demographic characteristic Group Mean Std. Deviation P-value Age control 37.38 6.70 0.897 case 36.94 5.26 BMI control 25.34 5.08 1.000 case 24.44 4.00 Chronic pelvic pain control 7.13 1.45 0.056 case 8.06 1.12 Dysmenorrhea control 2.81 1.04 0.051 case 2.25 0.93 Table 2. Comparison of pain components in case and control groups Pain component Group Mean Std. Deviation P-value Chronic pelvic pain control 3.37 0.62 0.001 case 2.25 0.93 Dysmenorrhea control 2.81 1.04 0.051 case 2.25 0.93 Daily need for pain medication control 1.18 0.83 0.128 case 0.68 0.60 Table 3. Comparison of pain components in control group before and after intervention Case Group Mean Std. Deviation P-value Chronic pelvic pain before intervention 8.06 1.12 <0.001 Chronic pelvic pain after intervention 2.25 0.93 Dysmenorrhea before intervention 7.50 1.51 <0.001 Dysmenorrhea after intervention 2.25 0.93 Daily need for pain medication before intervention 3.88 1.20 <0.001 Daily need for pain medication after intervention 0.69 0.60 Table 4. Comparison of female sexual function index in the two groups of case and control FSFI domain Group Mean Std. Deviation P-value Desire control 4.09 0.39 0.323 case 4.28 0.48 Arousal control 4.05 0.31 0.094 case 4.22 0.35 lubrication control 3.90 0.41 0.110 case 3.90 0.41 Orgasm control 4.13 0.38 0.003 case 3.70 0.34 Satisfaction control 4.03 0.47 <0.001 case 4.70 0.31 205 The Effect of Botulinum Toxin in Endometriosis Volume 10, March 2025 Journal of Obstetrics, Gynecology and Cancer Research FSFI domain Group Mean Std. Deviation P-value Pain control 3.70 0.18 <0.001 case 1.75 0.29 Total score control 23.89 1.01 0.001 case 23.89 1.01 4. Discussion Chronic pelvic pain caused by endometriosis can lead to discomfort during menstruation, sexual intercourse, and other activities. Sexual satisfaction can also be affected by endometriosis due to pain during intercourse and decreased libido (12 -14). Botulin um toxin acts through blocking the release of acetylcholine, a neurotransmitter that causes muscle contractions (15) and can help reduce pain and improve sexual function. Some studies have shown that botulinum toxin injection can relieve chronic pelvic pain and women who received botulinum toxin injection reported a 50% reduction in pain compared to those who received a placebo injection (16, 17) . Tandon, Stratton (16) investigated the effect of botulinum toxin injection on chronic pelvic pain in women with endometriosis. Their case series included 13 women who received botulinum toxin injections into their pelvic floor muscles. The results showed that the treatment significantly improved muscle spasms and pelvic pain at 4 -8 weeks post -treatment (16). Stratton et al (17) also evaluated the efficacy of botulinum toxin injection in 30 women with endometriosis-associated chronic pelvic pain. The

showed that the treatment significantly reduced pain scores one month post-treatment (17). A systematic review analyzed data from 5 randomized controlled trials and 12 observational studies that investigated the effect of botulinum toxin injection on chronic pelvic pain. All observational studies found that botulinum toxin injection was effective in reducing chronic pelvic pain with the greatest change in visual analog scale from 8.69 at baseline to 3.07 at 24 months post-injection. However, only one of the five randomized controlled trials reported improved chronic pelvic pain after the treatment (18). On the other hand, some other studies do not support the use of this treatment method. The study conducted by Petersen el investigated the effect of Injection of 20 I.E. Botox in the vestibule of women diagnosed with vestibulodynia. Botox was not effective on reducing pain, improving sexual functioning, or the quality o f life compared to the placebo group (19). Yaraghi et al (20) compared the effectiveness of functional electrical stimulation of pelvic floor muscles for treating sexual dysfunction with botulinum treatment. The results found that physiotherapy procedure was more effective than botulinum treatment (20). The present study focused on the use of botulinum toxin injection as a potential treatment option for endometriosis - related chronic pelvic pain and sexual satisfaction. The women who received botulinum toxin injections had significantly lower levels of pain during intercourse and higher levels of sexual satisfaction compared to those who did not receive the injections. However, botuli num toxin has some potential side effects, such as urinary retention and constipation (21). These side effects can affect quality of life and may need to be managed with additional treatments. It is important to note that botulinum toxin injection is not a cure for endometriosis. It only provides temporary relief from symptoms such as chronic pelvic pain and painful intercourse (22) . Women with endometriosis should work closely with their healthcare provider to develop an individualized treatment plan that addresses their specific needs. Overall, our study provides valuable insight into the potential benefits of botulinum toxin injection for endometriosis patients suffering from chronic pelvic pain and sexual dysfunction. Other treatments such as hormonal t herapy or surgery may also be considered depending on individual circumstances. 5. Conclusion Chronic pelvic pain associated with endometriosis can have a significant impact on a woman's sexual health and satisfaction. Botulinum toxin injection may be an effective treatment option for reducing pain during intercourse and improving sexual function in women with endometriosis. However, further research is needed to fully understand the long- term effects of this treatment option on sexual health and overall quality of life in women with endometriosis. 6. Declarations Acknowledgments The authors would like to express their gratitude to all participants enrolled in this project. Ethical Considerations The study was approved by the Research Ethics Committee of Tehran University of Medical Sciences, Tehran, Iran (IR.TUMS.MEDICINE.REC.1400.258). This research was also registered with the code (IRCT20091012002576N20) in the Clinical Trial Registration Center of Iran. Fatemeh Davari Tanha et al. 206 Volume 10, March 2025 Journal of Obstetrics, Gynecology and Cancer Research Authors' Contributions Fatemeh Davari Tanha conceived and designed the study; Mojgn Asadi designed the study and wrote paper; Faeze Mirbagheri collected the data; Elham Feizabad performed the analysis; Zahra kaveh edited the paper and Kazem Mousavizadeh developed project. 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