Practical Guidance on the Use of Vaginal Laser Therapy: Focus on Genitourinary Syndrome and Other Symptoms

Background

Genitourinary syndrome of menopause (GSM) is the term used to describe symptoms of oestrogen deficiency related to changes in the vulva, vagina and lower urinary tract.^1,2 Prior to the introduction of this consensus terminology in 2014, these changes were commonly referred to as vulvovaginal atrophy.²

GSM is characterised by a number of clinical symptoms including: genital symptoms of dryness (up to 100%), burning (57%), itching (57%), and irritation (77%); sexual symptoms of lack of lubrication and dyspareunia (78%); and urinary symptoms of dysuria (6%), urgency and recurrent urinary tract infections.^2–4 Although women may present with one or multiple symptoms, the most common symptom of GSM is vaginal dryness.^5–8

A high concentration of oestrogen receptors exist in the vagina, vestibule, and trigone of the bladder. The decline of circulating oestrogen leads to a reduced collagen content, decreased elastin, thinning of the epithelium, altered function of smooth muscle cells and fewer blood vessels. This results in anatomical changes including regression and thinning of the labia minora, retraction of the introitus with reduced elasticity (often leading to entry dyspareunia), prominence of the urethral meatus (making it vulnerable to physical irritation and trauma), reduction in vaginal blood flow and diminished lubrication. Increased friability may predispose to epithelial damage with vaginal penetration, leading to vaginal pain, fissuring and bleeding after sex.²

In the pre-menopausal state, the stratified squamous vaginal epithelium is thick with rugae.⁹ As epithelial cells exfoliate and die, they release glycogen, which is subsequently transformed to lactic acid by the action of a normal vaginal commensal organism, lactobacillus. At menopause, the epithelium becomes thinner, leading to a reduction in the shedding of glycogenated cells and subsequent loss of lactobacilli, resulting in an increased pH and change to the microbiome.² This leads to an increased growth of pathogenic bacteria such as streptococci, staphylococci, and coliforms, which in turn, can cause vaginal inflammation and urogenital infections.¹⁰

GSM is a chronic and often progressive condition, impacting the quality of life of up to 50% of postmenopausal women.^2,11 The average age of menopause is 51–52 years; with increasing life expectancy, many women will live 40% of their lives after menopause, potentially suffering with these symptoms.¹²

Treatment of GSM includes vaginal moisturisers (for use at any time) and lubricants (for symptomatic relief during sex). However, these have limited efficacy as they do not restore the local physiology. The gold standard treatment is vaginal oestrogen replacement.¹³ It is well recognised that local oestrogen therapy restores vaginal pH, thickens the epithelium, induces collagen synthesis and increases vaginal secretions.^14–16 However, local oestrogen treatment is associated with a high recurrence rate of symptoms, once treatment is discontinued.¹⁷ Alternatives including prasterone and ospemifene (selective oestrogen receptor modulator) are licensed in the treatment of GSM but have not been tested against vaginal oestrogen.^18,19

GSM can affect up to 70% of postmenopausal breast cancer patients and symptoms appear to be more severe, especially for those requiring pharmacological cancer treatment.^20–25 Aromatase inhibitors (AIs) are frequently prescribed to those with endocrine sensitive tumours as they reduce peripheral conversion of androgen to oestrogen, thus resulting in vulvovaginal atrophy.^10,20 Up to 93% of women on AI therapy report sexual dysfunction and 28% report the intention to discontinue treatment due to side effects.^26,27 Chemotherapy may also lead to iatrogenic premature ovarian failure.^23,28

Improved treatment and screening for female breast cancer in developed countries has resulted in higher survival rates, with current five-year survival rates around 90%. As a result, there are many millions of breast cancer survivors living in Western countries, many of whom are suffering with symptoms of GSM.²³

In these patients, treatment options for GSM are limited. Vaginal moisturisers and lubricants are safe and indicated but are less effective than hormonal therapies and perhaps due to poor efficacy are associated with low compliance.²⁹ Vaginal oestrogen is generally not advised, particularly for oestrogen receptor positive tumours, as it can be absorbed into the bloodstream in small amounts and potentially stimulate occult breast cancer cells. Current data do not show an increase in cancer recurrence with local oestrogen therapy; however, some studies do demonstrate elevated serum oestradiol levels with certain preparations, which may reverse the effects of AIs.^30–32 Current recommendations suggest an individual risk:benefit assessment via the oncology team, but there is often both clinician and patient reluctance to use topical oestrogen due to fear of cancer recurrence.^33,34 The safety of intravaginal dehydroepiandrosterone and oral ospemiphene after breast cancer have not been established.²³

In recent years, it has been suggested that laser therapy may offer a nonhormonal alternative to the management of GSM.^35–38

What is Laser?

The word LASER (amplification of light by stimulated emission of radiation) was created in 1959, when the first publications appeared in the literature.³⁹ Since then, medical applications have multiplied and laser is now widely used in dermatology, dentistry and aesthetic surgery.^1,40–42

Laser light has three unique properties. First, it travels in one direction with very little divergence, unlike natural light that spreads and loses its intensity/power. Second, laser light is monochromatic: consisting of a narrow wavelength/colour range, allowing it to have very specific effects on the tissues. Third, laser light is coherent: all the light waves move in phase, allowing laser energy to be delivered accurately.¹

Lasers are named according to the medium that is activated eg CO2, Erbium:YAG. Each medium produces light waves of a specific wavelength, giving it a characteristic colour.⁴³

Three parameters determine the amount of energy delivered to the tissue; wattage, duration of application and the spot size of the beam. The duration of application can be altered by selecting an intermittent timed pulse mode, while spot size is altered by moving closer to the target. The combination of watts and spot size determines the rate of tissue treatment, known as power density and expressed as watts/cm.^2,43

The mechanism of action of laser therapy is essentially to heat tissue, which in turn stimulates angiogenesis, collagen synthesis, formation of dermal papillae and epithelial thickening.^1,40,43

Types of Laser

There are three types of energy device currently in use for vaginal therapy, although there are a number of different manufacturers within each category.⁴⁴ Two of these are laser in nature (CO2 and Erbium:YAG), whilst the third is radiofrequency based. Radiofrequency devices, in contrast to laser, emit focused electromagnetic waves that generate heat upon meeting tissue impedance.⁴³

Laser sources can be ablative or non-ablative. Ablative sources vaporise tissue layers and are more destructive, whereas non-ablative lasers leave the epithelial surface intact. In terms of vaginal lasers; CO2 is ablative in nature, whereas Erbium:YAG is non-ablative.⁴³

In vaginal treatment, fractionated energy devices are used. Non-fractionated energy devices act on the entire projected surface of the skin, whereas fractionated devices target an equally distributed portion of the projected area in a pixelated fashion. This produces small columns of thermal injury, involving both the epidermis and dermis in ablative lasers, or just the dermis in non-ablative lasers.⁴³

The technique for performing vaginal laser therapy involves use of a specially designed vaginal speculum. Once this has been introduced, the laser probe can be inserted inside the speculum. The treatment is delivered, retracting the probe by 5mm each time, until the introitus is reached. The treatment is repeated three times, rotating the speculum by 45 degrees each time, to ensure 360-degree treatment. After the vaginal treatment is complete, some centres also offer a vestibule treatment with a different shaped probe. In total, the procedure lasts around 10 minutes.³⁵

For both CO2 and Erbium:YAG laser, a typical course of treatment involves three sessions at 4–6 week intervals.³⁵

The treatment is outpatient office-based. Most patients report only mild procedural discomfort and the majority do not require topical anaesthesia or analgesia. The majority of women report post-procedural erythema, oedema or discomfort, which resolves within 24–48 hours. No recovery time is usually required, with most patients able to resume regular activities later the same day. Sexual activity should be avoided for 1 week following the procedure.³⁵

Histological changes following vaginal laser treatment have been described in a number of studies relating to CO2 laser including: increase in fibroblast activity, increased collagen and elastin, neoangiogenesis, thickening of the vaginal epithelium, increased glycogen storage, increased epithelial exfoliation, and formation of new dermal papillae.^22,44–49 A return in normal flora following vaginal laser treatment from 30% to 79% lactobacilli and resultant reduction in vaginal PH has also been observed, as may be expected from the epithelial changes.⁵⁰ One study has compared histological samples following vaginal oestrogen treatment vs Erbium:YAG laser.¹⁷ This demonstrated epithelial improvements in both arms but observed angiogenesis in the laser group only.

Evidence to Date for the Use of Lasers in GSM

A number of indications for vaginal laser treatment have been described, including “rejuvenation”, stress urinary incontinence, overactive bladder, vaginal laxity and GSM. The remit of this review is to examine the use of laser in GSM, hence the evidence for other indications will not be discussed further.

Erbium:YAG Laser

The evidence relating to the use of Erbium:YAG laser in GSM treatment, largely originates from a series of publications by Gambacciani with additional studies led by Gaspar, Guerette and Barber.^17,52–56 See Table 1 for a summary of the evidence. Evidence regarding the utility of Erbium:Yag in breast cancer survivors is cited separately in Table 2.

Table 1 Summary of Evidence for Erbium:YAG Laser in GSM Treatment

Table 2 Summary of Evidence for Laser Treatment of GSM in Breast Cancer Survivors

There are six studies in total. All studies are observational, with the number of participants ranging from 24 to 205. The earliest published study was in 2015. Studies reported administering two or three laser treatments, 3–4 weeks apart. Maximum follow-up duration was 24 months. All studies reported a significant improvement in symptoms of GSM including dryness and dyspareunia. Significant improvements in VHIS (vaginal health index), FSFI (female sexual function index) and histology were also reported. Mild and transient adverse effects were reported in up to 4% of 113,174 patients who underwent Erbium:YAG vaginal laser treatment. Studies with 18- and 24-month follow-up duration report a drop-off in benefits after 12 months, suggesting repeat treatments may be required.

Two reviews examining the use of vaginal Erbium:YAG and its indications have been written by Elia and Gambacciani.^1,83 These concluded that Erbium:YAG technology offers a safe and unique treatment, acting by thermal effect and not by tissue ablation. The authors called for randomised studies to compare Erbium:YAG with other laser therapies, as well as to evaluate the duration of therapeutic effects and the safety of repeated applications.^1,83

Fractional Ablative CO2 Laser

Evidence for the use of fractional ablative CO2 laser in GSM treatment is more extensive and encompasses 41 publications.^{45–50,64,84–117} See Table 3 for summary of evidence. Sample sizes range from 12¹¹⁴ to 645⁹⁶ patients. However, evidence is largely observational data with only 8 RCTs, most of which are underpowered (18 to 170 participants) and have limited follow-up data (maximum 6 months).^{100,102–104,106,107,109,117} Number of treatments vary from one to five. Intervals between treatments vary from 2 to 6 weeks. Follow-up duration varies from 1 month to 24 months. There are 2 systematic reviews regarding fractional CO2 laser but the meta-analyses are limited by the quality of data included.^105,118

Table 3 Summary of Evidence for CO2 Laser in GSM Treatment (Non-Cancer Population)

The pioneer of CO2 vaginal laser treatment was Gaspar, who, in 2011, published a study of 40 women with GSM who underwent 3 sessions of fractionated CO2 laser, 2 weeks apart. Significant improvements were observed in dyspareunia and histological analysis in the laser group compared with controls.⁴⁵

Of the 41 publications regarding CO2 laser in GSM treatment, 39 reported significant improvements in subjective symptoms and/or objective signs of GSM.

Interestingly, the sham-controlled RCTs have reported conflicting results. A sham-controlled RCT of 88 patients by Ruanphoo reported significant differences in VAS, VHIS and ICIQ-VS in the laser group compared with sham.¹⁰⁰ Similar findings were reported by Salvatore et al in an RCT of 58 patients, in which there were significant improvements in VAS and FSFI in the laser group compared with sham.¹⁰³ This is in contrast to a sham-controlled RCT of 30 patients by Cruff et al, which reported significant improvement in VAS, VHIS and FSFI in both groups with no difference between the treatment group and the sham group, potentially demonstrating a placebo effect.¹⁰⁴ Similar findings were reported in an RCT of 18 patients by Quick et al. This showed no significant difference in VAS scores between the two groups, however there was a significant improvement in FSFI in the laser group compared with sham.¹⁰²

Duration of treatment effect is also unclear. Sokol, Samuels, Li, Alexiades, Athanasiou and Siliquini report that treatment effects (according to VAS, VHIS and FSFI) maintain significance at 12 and 15 months.^{46,89,92,101,108,111} Beyond this time-frame, there is some evidence that treatment benefits decline. Pieralli et al reported a drop-off in patient satisfaction to 25% at 24 months from 95% at 6 weeks, presumably reflecting a recurrence of symptoms.⁹⁰ Eder et al reported that 15/20 patients required an additional treatment between 12 and 15 months, in order to maintain improvements in symptoms, VHIS and FSFI.⁹⁵ In contrast, Behnia-Wilson et al reported that treatment effects were maintained at 24 months.⁹¹ Arroyo et al reported improvements in “vaginal rejuvenation” and satisfaction remained high at 24 months but sexual symptoms had recurred.¹¹⁴

Patient reported satisfaction with CO2 laser treatment for GSM varies from 67.6% (vestibular application)⁸⁶ to 96%,⁸⁸ figures which are largely reflective of short-term evaluation. Satisfaction levels are likely to be dependent on follow-up duration, as they are likely to decrease with increased time post-procedure as benefits subside.

In 2020, Alexiades reported restoration of normal VHI in more patients who were recently postmenopausal (1–3 years) compared with patients who were postmenopausal for >3 years following CO2 laser, suggesting that early intervention is correlated with improved outcomes.¹⁰¹

The first multicentre and largest study to-date was published by Filippini in 2019, involving 645 women with GSM. Significant improvements were found in all parameters (dryness/atrophy, burning, itching, dyspareunia, vaginal orifice pain, pH) at 1 month post 3 or 4 CO2 laser treatments.⁹⁶

In 2022, Filippini also published a systematic review of 25 studies investigating CO2 laser treatment for GSM. This involved 1152 patients. The pooled mean differences for the symptoms were: dryness −5.15 (p < 0.001), dyspareunia −5.27 (p < 0.001), itching −2.75 (p < 0.001), burning −2.66 (p < 0.001) and dysuria −2.14 (p < 0.001). FSFI, VHIS and VMV scores also improved significantly and no major adverse events were reported.¹⁰⁵

Systematic Reviews and Meta-Analysis

There are a number of systematic reviews that incorporate evidence for both CO2 and Erbium:YAG lasers in treatment of GSM.

In 2017, reviews were published by Arunkalaivanan, Tadir, Pitsouni and Gambacciani involving 4–20 studies. These yielded promising results for vaginal laser treatment of GSM and called for an urgent need for large, long-term, randomised, placebo-controlled and drug-controlled studies to further evaluate safety and efficacy.^{35,83,120,121}

In 2018 and 2019, further reviews were published by Rabley, Song, Bhide and Franic, again acknowledging promising early data but conclusions remained limited by the weak observational data, small sample sizes and short follow-up duration.^122–125

Focus on: Comparison of Laser with Oestrogen

A number of studies have compared the effect of vaginal laser and vaginal oestrogen on GSM,^{17,54,106–109,117} 5 of which relate to CO2 laser^{106–109,117} and 2 of which relate to Erbium:YAG laser.^17,54

The first comparison of laser and topical oestrogen for GSM was reported by Gambacciani in 2015. This study compared 3 × monthly Erbium:YAG laser treatments (n = 45) vs 3 months vaginal oestrogen twice weekly (n = 25). Both groups showed a significant improvement in vaginal dryness and dyspareunia but after 24 weeks the improvement had diminished in the oestrogen group following cessation of treatment.^1,54

Gaspar 2017 reported a study comparing the treatment of 25 women receiving estriol for 8 weeks with 25 women receiving 2 weeks of estriol followed by 3 sessions of Erbium:YAG laser. There was a statistically significant reduction in all symptoms in both groups up to the 6-month follow-up (p < 0.05); however, the relief of symptoms was more pronounced in the laser group. Furthermore, the effect of the laser treatment remained statistically significant at 12 and 18-months, while the effect of estriol diminished. Side effects were minimal and of transient nature in both groups, affecting 4% of patients in the laser group and 12% of patients in the estriol group.^1,17

Also, in 2017, a double-blinded RCT was published by Cruz comparing CO2 laser vs topical oestrogen vs combination treatment with 15 women in each arm. The VHIS was significantly higher in all groups, but the greatest improvement was seen in the combined treatment group (p = 0.01). Laser and combination therapy groups showed a significant improvement in vaginal dryness, burning and dyspareunia, whereas the oestrogen arm demonstrated improvement in the symptom of dryness only (p < 0.001). Only the combination therapy group showed an improvement in FSFI scores, overall suggesting that combination therapy may be superior if oestrogen is not contraindicated, though this was underpowered for some of the outcomes.¹¹⁷

In 2019, the multicentre “VeLVET” RCT was published comparing CO2 laser with topical oestrogen for GSM. There was no significant difference between the groups in terms of symptom improvement, FSFI scores and adverse events at 6-month follow-up, although vaginal maturation index (VMI) remained higher in the oestrogen group.¹⁰⁶ Similarly, in 2020, a multicentre cohort study comparing CO2 laser with 3 months of topical oestrogen was published. This showed that at 6 months there was symptomatic improvement in both groups with no significant difference between the two groups.¹⁰⁸ These findings were supported by an RCT by Dutra in 2021, which compared CO2 laser with topical oestrogen. Histological analysis at 30 days reported a significant increase in vaginal epithelium thickness in both groups, with a tendency for a higher maturation index in the oestrogen group. The authors also reported a significant improvement in sexual function in both groups.¹⁰⁹

However, in 2019, an RCT by Politano comparing CO2 laser vs topical oestrogen vs vaginal lubricant reported that at 14-week follow-up, the VHIS was higher in the CO2 laser group (mean score 18.68) than in the oestrogen (15.11) and lubricant (10.44) groups (p < 0.001).¹⁰⁷

A systematic review was published by Li in 2021 including data from 3 RCTs, 16 prospective, and 7 retrospective observational studies, representing 2678 participants overall. Pooled data failed to demonstrate a difference in terms of vaginal or sexual symptoms between vaginal laser and vaginal oestrogen treatments.¹²⁶

The jury is still out on whether laser or oestrogen is the superior treatment for GSM. Current evidence suggests their effects are comparable. Symptom recurrence may be quicker following cessation of oestrogen treatment then after a course of laser; however, most evidence suggests that symptoms do eventually recur following laser treatment also, in the region of 12–24 months later. With little between the apparent treatment effects, the primary utility of vaginal laser may be for breast cancer survivors, as topical oestrogen use is controversial in this patient group.

Evidence for Vaginal Laser Treatment of GSM in Breast Cancer Survivors

There are currently 28 studies published regarding the use of vaginal laser treatment for GSM in breast cancer survivors, of which 19 relate to CO2 laser^{44,51,65–81}, 8 relate to Erbium:YAG laser^57–64 and one relates to solid-state vaginal laser.⁸² See Table 2 for a summary of the evidence.

Three studies are RCTs and the remainder are observational studies. Number of participants vary from 16 to 256. Number of laser treatments vary from one to five. Follow-up duration varies from 30 days to 2 years. All studies report a significant improvement in objective signs and/or subjective symptoms of GSM except one, the only sham-controlled RCT by Mension et al. In contrast to all other studies, this reported that after five treatments there was no significant difference in VHIS, VMV, FSFI, pH, dyspareunia, body image or quality of life compared with the sham group at follow-up up to 6 months.⁸¹

Studies with a duration follow-up of 2 years reported conflicting results in terms of long-term treatment effect. Gambacciani et al reported a significant improvement in VAS scores for dryness, dyspareunia and VHIS for up to 12 months, following 3 treatments with Erbium:YAG laser. However, by 18 months, these improvements were no longer significant.⁵⁹ Whereas Quick et al reported significant improvements in VAS, VHIS and FSFI following three CO2 laser treatments, which were maintained at 24 months, with a drop off in urinary symptom relief only (urogenital distress index).⁵¹ Similar findings were reported by Veron et al, with significant improvements in FSFI and pH maintained at 18 months, but the significant improvement seen in urinary quality of life (Ditrovie score) at 6 months had returned to baseline at 18 months.⁷⁷ Pieralli et al reported a step-wise decline in patient satisfaction with time post-procedure from 95.4% at 4 weeks, to 92% at 6 months, 72% at 12 months, 63% at 18 months, and 25% at 24 months, suggesting repeat treatments are likely to be required and perhaps with a shorter time interval than in non-oncological patients.⁶⁸

Last year, Lopez et al published a study, which utilised a different medium for vaginal laser treatment in breast cancer survivors, solid-state vaginal laser (SSVL). They reported on 27 patients who received three laser treatments, 15–20 days apart. At 6 months, there was significant improvement in dyspareunia, VHIS, vulval health index, VMV, FSFI and quality of life.⁸²

Six systematic reviews evaluating vaginal laser for GSM treatment in breast cancer patients have been produced.^22,127–131 Four were published in 2019, although conclusions were limited by the small observational studies included. About 6–10 studies were pooled and significant improvements were demonstrated in GSM symptoms (VAS), FSFI scores and VHIS. Whilst the authors acknowledged the promising results, they called for further research to establish long-term follow-up data and clarify the optimum medium for laser therapy, device settings, how many treatments are required and how often treatment needs to be repeated.^22,129–131 Two further systematic reviews were published in 2023, which analysed 12 and 20 studies, respectively, including over 700 breast cancer survivors though only two randomised trials. Both made similar conclusions to the earlier reviews; further studies are required to establish long-term efficacy and safety.^127,128

Whilst conclusive evidence and powered multicentre RCTs are still awaited, findings thus far suggest vaginal laser may be an efficacious treatment for GSM in the breast cancer population but improvements may not be as marked, more treatments may be required to alleviate symptoms, and results may not be as long-lasting as the natural menopause population. Despite those caveats, this patient group are set to gain the most if vaginal laser is to be deemed safe and efficacious, due to the lack of hormonal alternatives available.

Number of Sessions

The majority of studies reviewed utilise 3 treatments at intervals of 4 weeks (range 2–6 weeks). Few studies report outcomes following 1 or 2 treatments. One study in breast cancer survivors reported outcomes following 5 treatments, based on the presumption that GSM is more severe in this population.⁷⁸

Only one study by Athanasiou compares alternative regimes of 3, 4 or 5 CO2 treatments (monthly intervals).¹¹⁰ In this study, 55 women received three sessions, 53 received 4 sessions and 22 received 5 sessions. Following the third, fourth and fifth laser sessions, vaginal dryness resolved in 36%, 66% and 86%, respectively; dyspareunia resolved in 27%, 58%, and 81%, respectively; sexual function improved in 41%, 69% and 84%, respectively; and VHIS improved in 80%, 96%, and 100% of participants. The authors concluded that CO2-laser therapy appears to treat signs and symptoms of GSM in a dose-responsive manner and an additional fourth or fifth session may add value in terms of further reduction in symptoms.¹¹⁰ This paper was followed by the publication of 12-month outcomes for this same cohort a year later. The positive laser effect was sustained at 12-months in all groups regardless of the number of laser sessions, but there was a significant difference between 3 and 5 sessions, in favour of the 5-session group. No differences were detected between 4 and 5 session groups.¹¹¹

Energy Power Setting

The majority of studies referenced in this review reported power settings of 20–40w. Only one study by Pitsouni has compared 30 vs 40w CO2 laser treatment of GSM, with 25 women in each group. This demonstrated no significant difference between the 30w and the 40w groups.¹¹²

Preparation of Vaginal Mucosa

The majority of studies in this review did not utilise preparatory topical vaginal treatments prior to vaginal laser treatment. Bojanini reported two studies that compared pre-treatment topical oestrogen 3 × per week for 2 weeks vs platelet-rich plasma (PRP) intravaginal injection 2 weeks prior to Erbium:YAG laser. The authors hypothesised that efficacy of laser treatment would be improved if mucosa is hydrated as this will potentiate the warming effects. The aim of platelet-rich plasma (PRP) is bio-stimulation, involving an increase in growth factors and the secretion of proteins that are able to maximize the healing of the tissue, as well as being a safe alternative for breast cancer survivors. There was significant improvement in GSM symptoms in both groups, with no significant difference between the groups. Unfortunately, these studies did not have a control group with patients who had not had vaginal preparation prior to laser treatment.^57,58

The majority of studies included in this review did not routinely offer topical local anaesthetic prior to vaginal laser treatment.

Safety

A number of small observational studies have reported on adverse outcomes following vaginal laser treatment, with reassuring results that these are infrequent, transient and mild in nature.

In 2015, Gambacciani reported a review of the Italian vaginal Erbium:YAG laser Academy results, evaluating 622 procedures performed in a number of centres. 20 patients reported the treatment was a “bad experience”, one patient described it an “unacceptable experience”, 36 patients felt the treatment was “acceptable” and the remaining 565 patients reported the treatment was a “good to excellent experience”.⁴⁰

However, the FDA issued a statement in July 2018 declaring “the safety and effectiveness of vaginal energy-based devices has not yet been established”, that they “can lead to serious side effects, including burns, vaginal discharge, scarring, pain during intercourse and recurrent/chronic pain” and calling for “high vigilance and robust data to validate claims they are both safe and effective”.^11,132

This was followed by a publication by Gambacciani in 2020 focussing on the safety of Erbium:YAG laser. This study involved responses from 188 clinicians, who provided information regarding adverse outcomes for 62,727 patients. The collated data revealed a mean frequency of the following transient effects; vaginal discharge 6.5%, oedema 3.7%, pain during procedure 1.9%, post-operative pain 0.5%, burns 0.1%, irritation 0.5%, itch 0.06%, infection 0.03%, abnormal bleeding 0.04%, and dyspareunia 0.004%. All adverse outcomes were classified as mild or moderate and no permanent complications were reported.⁵³ This is in contrast to a study by Samuels, who reported erythema in 54% and oedema in 55% with CO2 laser treatment, although this did involve vestibular treatment as well as vaginal.⁴⁶ Similarly, a study by Marin reported itch in 95%, and leukorrhoea in 70% post CO2 laser, as well as intra-operative symptoms of “warmth” in 70% and irritation in 18%.⁹⁸

A case series of adverse events following vaginal laser treatment was published by Gordon in 2019. The first case was a 65-year-old lady with vaginal stenosis who suffered vaginal lacerations related to intercourse. Two cases were of persistent dyspareunia post laser, and the final case was the formation of vaginal adhesion resulting in dyspareunia.¹³³

A study investigating the safety of vaginal CO2 laser for 53 GSM patients was published in 2020 by Di Donato. One patient reported post-procedure transient dizziness, one patient reported a minor bleed related to probe introduction, and two patients reported transient post-procedure dysuria. In one case, the laser treatment was abandoned due to discomfort; however, this patient later completed the treatment 2 weeks later. The mean pain score at first treatment was 3.57 ± 1.50. This significantly decreased between the first and third treatment. There were no severe complications reported within the 6-month follow-up period, leading the authors to conclude that vaginal CO2 laser seems a safe therapeutic option for GSM.¹¹³

There is a high degree of variability regarding the prevalence of post-procedure side effects reported in the literature yet, with the exception of the FDA warning and case series by Gordon, no serious complications have been reported. However, evaluation of the safety of repeated applications is certainly lacking in the literature to date.¹

Currently, this is not a standardised or centralised mechanism for reporting complications associated with vaginal laser treatment. If we are to learn from the mistakes of the vaginal mesh scandal, we must surely establish a national/international registry for reporting outcomes for this relatively novel medical device in order to allow early recognition of any emerging patterns of complications and prompt intervention in an effort to reduce incidence.

Limitations of Evidence

Despite a wealth of observational data, there are a number of limitations regarding the evidence-base for vaginal laser treatment of GSM. There is a paucity of adequately powered RCTs and existing systematic reviews are limited by the quality of data included.

To date, there is no evidence regarding safety or efficacy of vaginal laser treatment beyond 24 months.

The majority of studies report VAS and VHI scores. VHI is assessed and graded by a clinician and is subject to interobserver variation and bias.²² Quality of life outcomes are only reported in a handful of studies, and there is a lack of studies utilising validated patient reported outcome measures (PROMs).^{66,69,78,85,98,116} The DIVA (Day-to-Day Impact of Vaginal Aging) questionnaire, is a recently developed multidimensional self-reported tool for the assessment of GSM, validated to measure the impact of vaginal symptoms including dryness, irritation, soreness, itching, and dyspareunia on quality of life.¹³⁴

There remain a number of unanswered questions with regard to laser machine settings (dwell time, spacing, depth, mode), number of sessions, interval between sessions, energy power settings and pre-treatment vaginal preparation, all of which warrant more rigorous investigation.²²

There are no studies directly comparing CO2 with Erbium:YAG in the context of GSM treatment, although a protocol for a large multicentre RCT to investigate the effectiveness of CO2 vs Erbium:YAG in GSM treatment has been published.¹¹

Recommendations of Official Bodies

The UK National Institute for Health and Care Excellence (NICE) published interventional procedure guidance for “Transvaginal laser therapy for urogenital atrophy” in 2021. This advised laser treatment be restricted to research settings until robust data are available.¹³⁵ This was echoed in the RCOG Scientific Impact Paper “Laser Treatment for Genito-urinary syndrome of the menopause” in July 2022.¹³⁴

This stance is also consistent with the International Urogynaecological Association (IUGA) committee opinion on vaginal laser devices published in 2018, which stated;

The therapeutic advantages of nonsurgical laser-based devices in urogynaecology can only be recommended after robust clinical trials have demonstrated their long-term complication profile, safety and efficacy.¹³⁶

Similar statements have also been issued by the American College of Obstetricians and Gynaecologists, the North American Menopause Society, the International Society for the Study of Vulvovaginal Disease (ISSVD), and the International Continence Society (ICS); all recommending against use of vaginal laser therapy pending the availability of rigorous evidence to verify long-term effectiveness and safety.^127–140

Future Research

There is an urgent need for adequately powered randomised sham-controlled trials with long-term follow-up to validate findings seen in observational data before widespread implementation of vaginal laser. Evidence to date suggests that effects diminish with time and repeat treatments are likely to be necessary. As such, the efficacy and safety of repeated treatments must also be established.

Further comparison trials with vaginal oestrogen (in patients not affected by breast cancer) and CO2 vs Erbium:YAG would also be of value. By virtue of its ablative nature, CO2 laser may theoretically be associated with more transient symptoms or complications than Erbium:YAG but results may potentially be more dramatic – these are questions worthy of further investigation.

A cost–benefit analysis comparing vaginal oestrogen with vaginal laser for GSM in non-breast cancer patients, as well as a study of patient views and preferences regarding the two options, would be essential before laser treatment in this patient group could be considered.

Further clarification is required regarding the necessity of vaginal preparation as well as optimum machine settings.

Conclusion

While evidence remains in its infancy and national/international bodies cannot currently recommend it outside of a research context, this review suggests that vaginal laser is likely to be a safe and effective treatment for GSM, with breast cancer patients set to benefit most. However, these findings must be validated in robust randomised sham-controlled trials of adequate power. There remain a number of unanswered questions in terms of which laser medium to opt for, optimal device settings, ideal interval between treatments, vaginal preparation prior to treatment, as well as efficacy and safety of repeated treatments in the long-term. These issues could be addressed most efficiently with a mandatory registry of all vaginal laser procedures. The development of registries is paramount for the safety monitoring and governance of any new medical device, and surely a lesson we must heed from the vaginal mesh scandal.