Botulinum toxin treatment of refractory vaginismus: a prospective study

Abstract

Background:

Vaginismus is a common sexual dysfunction. A few studies have indicated that botulinum neurotoxin type A (BoNTA) can help treat refractory vaginismus by alleviating muscle tension. However, such studies did not use standardized methodology and BoNTA dosage.

Objective:

The aim is to evaluate the efficacy of intravaginal BoNTA injection in treating refractory vaginismus. Also, we intended to assess the effectiveness and safety of modest doses, that is, 100 to 200 IU of submucosal BoNTA injections.

Methods:

A prospective study was conducted in an outpatient surgical center over 18 months. Twenty patients aged 29 to 49 years (mean, 30.9 years) with refractory vaginismus were enrolled. All patients had been sexually inactive at the time of treatment. All participants had received various treatments such as psychotherapy, vaginal dilatator therapy, muscle relaxants, and lubricants with no relief. A dose of 100 to 200 IU of BoNTA was injected submucosally in the lateral sides of the bulbospongiosus, pubococcygeus, and puborectalis muscle areas. The patients were followed over 4 months posttreatment.

Results:

Nineteen patients (95%) achieved satisfactory intercourse by the end of the 4-month follow-up period. A repeat BoNTA injection was not required as there were no recurrences. None of the participants reported adverse effects.

Limitations:

A small sample size and lack of a control group.

Conclusion:

Injecting submucosally modest BoNTA doses is an effective and safe treatment for refractory vaginismus. When conventional therapies fail, BoNTA can be used to lessen muscle contraction, alleviate pain, and facilitate dilator treatments. Our standardized protocol, which involves a careful submucosal injection technique, can minimize risks and make the procedure easy to perform for daily practice.

What is known about this subject in regard to women and their families?

• Vaginismus is a common sexual dysfunction characterized by involuntary spasms of the perineal muscles surrounding the vagina, which prevents vaginal penetration.

• Treatment of vaginismus can be challenging, with conventional therapies such as vaginal dilator therapy and physical therapy being reported as minimally helpful.

• A few studies have indicated that botulinum neurotoxin type A (BoNTA) can help treat refractory vaginismus by alleviating muscle tension. However, such studies did not use standardized methodology and BoNTA dosage. Also, BoNTA studies are lacking in large geographic areas, and the clinicians’ familiarity with this new modality is limited.

What is new from this article as messages for women and their families?

• Modest doses of BoNTA (ie, 100–200 IU) can effectively treat refractory vaginismus.

• Modest doses of BoNTA were not associated with any adverse effects in this prospective study.

• This is the first BoNTA study in vaginismus in Southeast Asia.

• Our standardized protocol, which involves a careful submucosal injection technique, can minimize risks and make the procedure easy to perform for daily practice.

Introduction

Vaginismus is characterized by recurrent or persistent involuntary contraction of the perineal muscles surrounding the outer third of the vagina when any form of vaginal penetration such as tampons, digit, vaginal dilator, intercourse, or speculum penetration during gynecologic examinations is attempted.¹ Intercourse is often painful or impossible. This painful penetration causes anxiety and fear of having intercourse and can worsen with time. Vaginismus affects about 5 to 17% of women² and is a common female sexual dysfunction (FSD). FSD is prevalent in India. A study showed a prevalence of FSD of 55.5% among Indian fertile females, with pain being present in 85.88% of those with FSD (P < .01 when compared to those without FSD).³ In another study by Singh et al.,⁴ 56% of sexually active, 20- to 45-year-old Indian women had dyspareunia. Most patients with vaginismus do not seek medical help because the condition is still considered taboo in many parts of the world.⁴ It is a very distressing and frustrating condition for the patient and partner and one of the common causes of unconsummated marriages.

Vaginismus can be classified into primary, in which a woman has never been able to experience intercourse, and secondary or acquired vaginismus, which develops in a female who has previously been sexually active or may even have delivered a baby. It may or may not be partner-specific. Lamont classified the severity of vaginismus into 4 grades (Table 1).⁵ Grade 5 was proposed by Pacik et al.⁶

Table 1.

Classification of vaginismus severity⁵

Degree	Description
First	Perineal and levator spasms, relieved with reassurance
Second	Perineal spasm, maintained throughout pelvic examination
Third	Levator spasm and elevation of buttocks
Fourth	Levator and perineal spasm, elevation; adduction and retreat
Fifth6	Visceral reaction manifested by increased adrenaline output and resulting in any of the following: increased heart rate, palpitations, hyperventilation, trembling, shaking, nausea or vomiting, crying uncontrollably, a feeling of light headedness and fainting, a desire to jump off the table, run away, or even attack the doctor

Research does not support evidence in differentiating between “dyspareunia” and “vaginismus.” These entities belong to a nosologic continuum. They are included under the category “genito-pelvic pain/penetration disorder” as per the Diagnostic and Statistical Manual of Mental Disorders, fifth edition based on 5 dimensions: percentage success of vaginal penetration over 6 months, pain with vaginal penetration, fear of vaginal penetration or genito-pelvic pain during penetration, and pelvic floor muscle dysfunction.⁷

The etiology of vaginismus remains elusive; however, a psychological overlay can be involved. Factors that can play a role in vaginismus include a strict sexual upbringing, religious emphasis on chastity, cultural taboos, viewing sex as sinful, and lack of comprehensive sexual education, all of which may lead to a negative attitude toward sex. Sexual molestation and rape have also been identified as potential contributing factors. Surface and needle electromyography studies show increased muscle tone and poor pelvic muscle strength in patients who suffer from vaginismus.^8,9 To diagnose vaginismus, it is important to rule out other causes of dyspareunia that are not related to involuntary contraction of the perineal muscles, such as dryness, trauma, infection, anatomic anomalies, and endometriosis before labeling a case as vaginismus.

Established treatment options include sex counseling, psychotherapy, vaginal dilator therapy, physical therapy, Kegel’s exercises, the use of lubricants, muscle relaxants, or local anesthesia.¹⁰ Still, almost 10% of patients do not respond to these treatments.

Injection of botulinum neurotoxin type A (BoNTA) in the perivaginal muscles is a newer therapeutic approach for this condition, indicated in cases that have not responded to the modalities mentioned earlier. BoNTA, produced by the bacterium Clostridium botulinum, prevents the presynaptic release of acetylcholine and blocks neuromuscular transmission, thus causing muscle paresis.¹¹ Brin¹² first described the use of BoNTA for vaginismus in a case report in 1997. There are a few studies on the effectiveness of this technique in treating this neglected condition.^13–19 However, such studies used different methodologies and BoNTA dosages; a standardized protocol is lacking, making applying the procedure in daily practice difficult. Also, BoNTA studies have not been performed in large geographic areas, such as India and Southeast Asia, and the clinicians’ familiarity with this new therapy is limited. The US Food and Drug Administration has not approved intravaginal BoNTA injection therapy for vaginismus.

Objective

This study aimed to evaluate the efficacy of intravaginal BoNTA injection in treating refractory vaginismus. Also, we intended to assess the effectiveness and safety of modest doses, that is, 100 to 200 IU of submucosal BoNTA injections.

Methods

Study design

This prospective study was conducted in an outpatient surgical center over an 18-month period (September 2021–May 2023). Patients with refractory vaginismus were enrolled after signing an informed consent. The study was exempt from institutional review board approval as the investigators recorded and disclosed deidentified information. A thorough counseling was provided, detailing the benefits and risks of the procedure and that the success was dependent on maintaining the postprocedure vaginal dilatation, and only those women who were willing to use dilators were enrolled in the study. All patients had failed vaginal dilator therapy and received various treatments such as psychotherapy, muscle relaxants, and lubricants with no relief. Women with hypersensitivity to botulinum toxin, pregnant women, women with coagulopathies, or women with any known contraindication to botulinum toxin were excluded from the study.

Procedure

The participants were counseled about the procedure and signed an informed consent. The patient was placed in a dorsal lithotomy position. The procedure was carried out under short conscious sedation (intravenous propofol). A vaginal examination with the index finger was performed. A 100 IU BoNTA (onabotulinumtoxinA) dose was diluted in 2 mL of bacteriostatic saline. BoNTA was injected using a tuberculin syringe submucosally in the lateral sides of the bulbospongiosus, pubococcygeus, and puborectalis muscle areas (Figs. 1 and 2), sparing the anterior (suburethral) and posterior regions to minimize the risk of urinary or anal incontinence, respectively. The needle was bent 30° at the hub to ease injections and ensure the submucosal toxin placement. A 100 to 200 IU BoNTA dose was used in each patient. The dose depends on the width of the tight gripping perivaginal muscles as determined during a vaginal examination. If the width is ≤2 cm, a 100 to 150 IU dose is administered, but broader (>2 cm) muscle bands require a 200 IU BoNTA dose.

Fig. 1.

Submucosal BoNTA injections to each bulbospongiosus using hymenal fragments as a landmark. The needle is bent 30° at the hub to ease injections and ensure the submucosal toxin placement. The position of the puborectalis and pubococcygeus muscles is shown. Reproduced, with permission, from Pacik PT, Geletta S. Vaginismus treatment: clinical trials follow up 241 patients. Sex Med 2017;5:e114–23. BoNTA, botulinum neurotoxin type A.

Fig. 2.

Submucosal BoNTA injection in the area of the right lateral bulbospongiosus muscle. BoNTA, botulinum neurotoxin type A.

After the BoNTA injection, 20 cc of local anesthesia was injected circumferentially intravaginally. The vagina was then serially dilated using a set of dilators, starting from the smallest to largest. The patient woke up with the dilator in place and felt comfortable with it, which is encouraging to her. Patients were discharged after a few hours once they could use the dilator. They were counseled about possible soreness for a week and feeling dry posttreatment. Also, they were counseled to use dilators twice a day from then on and attempt intercourse at any time after a week of treatment, once they were comfortable. The use of generous water-based lubricants was encouraged. Failure of successful complete penetration over a period of 4 months was considered treatment failure. Patients were followed up for 12 months posttreatment.

Results

Patient characteristics

Twenty Indian patients aged 29 to 49 years (mean, 30.9 years) participated in the study (Table 2). Thirteen patients were married (65%), and the remainder were single. All patients were sexually inactive before BoNTA treatment. Eighteen patients (90%) had primary (ie, never had penovaginal intercourse), and the remainder had secondary vaginismus (ie, they had not engaged in penovaginal intercourse for a year). Regarding vaginismus severity (Table 1), 7 patients had grade 1 or 2, 6 patients had grade 3, 5 patients had grade 4, and 2 patients had grade 5 vaginismus (Table 2).^5,6

Table 2.

Clinical data

Patient no.	Age	Gender/marital status	Quantity (IU)	Sexual activity	Sexual activity post-BoNTA	Retreatment	Vaginismus type	Severity classification5,6
1	33	Female/single	100	None	Active	No	I	3
2	28	Transgender/single	100	None	Active	No	II	2
3	28	Female/married	200	None	Active at 4 days	No	I	1
4	49	Female/married	200	None	Active at 15 days	No	II	4
5	26	Female/single	100	None	Active	No	I	1
6	27	Female/single	100	None	Active	No	I	4
7	36	Female/married	100	None	Inactive; loose at 3 months (on dilator #3 of 5)	No	I	2
8	27	Female/married	100	None	Active	No	I	5
9	35	Female/married	100	None	Active	No	I	3
10	33	Female/married	100	None	Active	No	I	3
11	33	Female/married	200	None	Active	No	I	4
12	37	Female/married	200	None	Active	No	I	3
13	32	Female/married	150	None	Active	No	I	4
14	25	Female/single	100	None	Active	No	I	2
15	28	Female/single	200	None	Active	No	I	3
16	24	Female/single	150	None	Active	No	I	4
17	33	Female/single	100	None	Active	No	I	2
18	26	Female/married	200	None	Active	No	I	3
19	30	Female/married	150	None	Active	No	I	5
20	29	Female/married	100	None	Active	No	I	2

BoNTA, botulinum neurotoxin type A; I, primary vaginismus; II, secondary vaginismus.

BoNTA therapy and follow-up

Eleven patients were treated with 100 IU, 3 with 150 IU, and 6 with 200 IU BoNTA (onabotulinumtoxinA) (Table 2). Nineteen patients (95%) achieved satisfactory intercourse by the end of the 4-month period posttreatment. One patient had successful intercourse on day 4 posttreatment, and another patient at 2 weeks posttreatment. One patient was comfortable up to the third dilator at 3 months follow-up but had not attempted penovaginal penetration. A repeat injection was not required for any patients as there were no recurrences. Participant age, marital status, and vaginismus severity did not have any effect on the outcome (Table 2). No complications were encountered during or after the procedure. None of the patients reported side effects such as urinary or anal incontinence. All patients expressed high satisfaction with the treatment at follow-up visits.

Discussion

Principal findings

Our study demonstrates that BoNTA injection yields significant improvement in patients suffering from recalcitrant vaginismus. There were no complications or adverse effects, and appropriately injected modest BoNTA doses, as detailed here, are safe. The effect of BoNTA (onabotulinumtoxinA) begins 48 to 72 hours after the injection and usually lasts for an average of 4 months. By this time, the patient can have intercourse comfortably and overcome the fear of penetration. Counseling about the postprocedure use of dilators is of utmost importance. Couples should be advised to use dilators before initiating intercourse. Partners/husbands should be motivated to help with the use of dilators.

There have been a few relevant studies. Fageeh treated 5 women with third to fourth-degree vaginismus with a 300 to 400 IU BoNTA dose.¹³ All had satisfactory intercourse on the day of treatment, but one experienced recurrence and had repeat BoNTA treatment after 2 months. Ghazizadeh and Nikzad¹⁴ completed a study of 24 patients with vaginismus grades 3 and 4 who received 150 to 400 IU intravaginal BoNTA (abobotulinumtoxinA) injection. Most patients (95.8%) experienced significant improvement after BoNTA injection. Pacik¹⁵ administered a dose of 100 to 150 IU BoNTA in 12 patients with primary and 5 with secondary vaginismus. He reported that 16 patients (94%) experienced pain-free intercourse posttreatment.

Hamdy and Elsheikh¹⁶ conducted a study in 42 Egyptian women with vaginismus grade ≥3 that compared the female sexual function index (FSFI) scores pre- and post-BoNTA treatment. A dose of 50 IU BoNTA was injected submucosally in each bulbocavernosus area. After treatment, 37 patients (88.1%) achieved painless intercourse at a mean of 5.3 weeks. The authors showed that 1 year posttreatment, the average FSFI scores significantly improved compared to baseline (P < .001). The study by Bertolasi et al.¹⁷ included women with vaginismus secondary to vestibulitis who received several cycles of BoNTA injections in levator ani. Of 33 patients who completed the study, 27 (63.23%) recovered from vaginismus and vulvar vestibular syndrome; their sexual intercourse normalized after a mean ± standard deviation of 2.7 ± 1.5 treatment cycles (range, 1–7). However, the patient selection and methodology preclude comparisons with the results of other studies. Yaraghi et al.¹⁸ compared the efficacy of BoNTA to physiotherapy in a limited sample of patients with primary vaginismus. Although two-thirds of patients treated with BoNTA managed to have successful intercourse, the efficacy of physiotherapy was superior (P = .014). The reduction of sexual dysfunction frequency in the BoNTA group was 26.6% (P = .008) and 50% (P < .001) in the physiotherapy group.

Pacik and Geletta¹⁹ studied the use of a multimodal vaginismus treatment program in 241 patients. The investigators’ protocol included submucosal injections of BoNTA and bupivacaine to each bulbospongiosus, progressive dilation under conscious sedation, indwelling dilation, follow-up and support with office visits, phone calls, e-mails, and dilation logs, and sexual function evaluation with FSFI tool. They used the BoNTA dosage detailed earlier.¹⁵ Hundred seventy-one patients (71%) had pain-free intercourse at a mean of 5.1 weeks. The change in total FSFI score at 3 months, 6 months, and 1 year post-BoNTA treatment was statistically significant compared to baseline. One patient required retreatment followed by successful coitus.

Only 2 studies have compared the efficacy of different BoNTA dosages. The study by Helmi²⁰ showed that a dose of 150 IU was as efficacious as a dose of 200 IU. The study by Ghazizadeh et al.²¹ showed that a dose of 500 IU BoNTA (abobotulinumtoxinA) was more effective than 250 IU in treating severe vaginismus.

Clinical implications

BoNTA effectively treats recalcitrant vaginismus that is explained by a relationship between muscular spasms and the severity of vaginismus.⁶ Our streamlined injection protocol simplifies the procedure, ensuring ease of use. BoNTA is a safe and rapid treatment that can be administered in an inpatient or outpatient setting, which clinicians appreciate.²⁰ Adverse events, such as urinary or anal incontinence, were reported in 17.2 and 2% of patients that received BoNTA injections for vaginismus, respectively,²⁰ but were not observed in our series. We suggest carefully performing submucosal injections with the appropriate technique, as detailed here, to help minimize the risk of adverse events.

BoNTA treatment can serve as second-line therapy when conventional therapies fail. BoNTA injections can facilitate dilator therapy and increase compliance with the latter. Effective counseling, reassurance, and confidence building play a vital role in the success of this treatment. Education is critical, and healthcare organizations and policymakers should increase information and advocacy to raise public awareness about vaginismus and the beneficial effects of BoNTA therapy.

Research implications

Powered studies will determine the longevity of the BoNTA effect on vaginismus and whether some commercially available BoNTA products have better longevity than others. Head-to-head comparisons of BoNTA with other therapies should be performed, especially as the efficacy of several conventional treatments has not been studied in well-designed studies. Multimodal protocols have been effective.^19,22 BoNTA can be incorporated into such protocols.¹⁹ Research studies are needed to determine the efficacy of such approaches.

Strengths and limitations

This is the first study of refractory vaginismus treatment with BoNTA injection in East and South Asia. Vaginismus is a common FSD in India. Therefore, the present study contributes to better managing a prevalent disease in this population. Our results indicate that a modest BoNTA dose can be efficacious in achieving complete temporary vaginal relaxation. Providers can quickly adopt the simplified dosage approach in our study. However, the procedure requires familiarity with vaginal anatomy, and the provider should perform pelvic examinations regularly. The modest BoNTA dose utilized in this series increases the safety of treatment. The study is limited by its small size. Another limitation is the lack of a control group, such as a placebo arm. However, the placebo effect has not been studied in vaginismus,²³ and a meta-analysis of a few randomized controlled trials showed a trend toward higher efficacy of active treatment versus controls in vaginismus.²⁴

Conclusion

Intravaginal BoNTA injection is a safe and effective treatment option in patients with vaginismus who have failed conventional therapies. The procedure is tolerated well by the patients. Our standardized protocol, which involves a careful submucosal injection technique, can minimize risks and make the procedure easy to perform for daily practice. BoNTA injection can facilitate dilator treatments and can be considered in a multimodal approach to challenging vaginismus.

Conflicts of interest

None.

Funding

None.

Study approval

N/A

Author contributions

SAD: Conceptualization, data curation, and writing – review. BS: Formal analysis, writing – original draft, and writing – review. GK: Conceptualization, formal analysis, writing – original draft, and writing – review and editing.