Long-term effects of vaginal erbium laser in the treatment of genitourinary syndrome of menopause

Abstract

Objectives: To evaluate the long-term efficacy of a second generation of vaginal laser treatment, the vaginal erbium laser, as a non-ablative photothermal therapy for the management of genitourinary syndrome of menopause.

Methods: The study was performed using an erbium laser crystal yttrium-aluminum-garnet (XS Fotona Smooth™, Fotona, Ljubljana, Slovenia) with a wavelength of 2940 nm. Postmenopausal women (n = 205) were treated with three laser applications at 30-day intervals. Symptoms were assessed before and after treatment throughout 24 months, using the subjective visual analog scale (VAS) and the objective vaginal health index score (VHIS). In addition, postmenopausal women suffering from stress urinary incontinence were evaluated with the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF).

Results: Vaginal erbium laser treatment induced a significant (p < 0.01) decrease in VAS for both vaginal dryness and dyspareunia, as well an increase in VHIS (p < 0.01) up to the 12th month after the last laser treatment. The values returned to levels similar to the baseline after 18 and 24 months. In addition, vaginal erbium laser treatment improved mild-moderate stress urinary incontinence in 114 postmenopausal women. Less than 3% of patients discontinued treatment due to adverse events.

Conclusions: These results suggest that vaginal erbium laser may be effective and safe for the treatment of genitourinary syndrome of menopause.

Keywords:

• Erbium laser
• menopause
• genitourinary syndrome of menopause
• vaginal atrophy
• dyspareunia
• stress urinary incontinence

Introduction

The genitourinary syndrome of menopause (GSM) is a new definition for the variety of menopausal symptoms associated with physical changes of the vulva and vagina, as well as urinary symptoms related to estrogen deficiency¹. GSM also includes sexual symptoms of lack of lubrication, discomfort or pain, and impaired function¹. GSM is chronic and generally progressive over time, jeopardizing the quality of life and sexual relationships of postmenopausal women¹. Several therapeutic options are available to alleviate GSM symptoms, including hormonal and non-hormonal products as well as selective estrogen receptor modulators, either for local or systemic administration^2–5. Recently, several papers have reported interesting results on the use of laser for the treatment of GSM^6–32. A growing body of evidence world-wide has accumulated on the application of a non-invasive vaginal erbium laser (VEL) using the non-ablative 2940-nm Er : YAG laser^11–17. In addition, the effects of laser thermotherapy on collagen remodeling and synthesis have been proposed as a treatment for stress urinary incontinence (SUI)^18–32. Previous papers have reported that VEL might induce a clinical improvement in SUI patients^18–32. However, no data on the duration of laser effects after 6–12 months are currently available. The aim of the present study was to evaluate the long-term effectiveness and acceptability of VEL in postmenopausal women suffering from GSM.

Materials and methods

This was a prospective, longitudinal study performed in postmenopausal women suffering from GSM and attending the outpatient Menopause Clinic of Pisa University Hospital. The protocol was revised by a National Independent Advisory Board and approved by the Ethics Committee of the Department of Obstetrics and Gynecology. The procedures were in accordance with the ethical standards of the Committee on Institutional Human Experimentation, and with the Helsinki Declaration of 1975, as revised in 1983. Inclusion criteria were the presence of GSM in women with plasma levels of gonadotropin and estradiol in the postmenopausal range (follicle stimulating hormone >40 U/l; estradiol <25 pg/ml) and negative Pap smear. Exclusion criteria were: use of lubricants, local preparations, hormones or other medications to relieve menopausal symptoms in the previous 3 months prior to inclusion in the study; lesions, scars or infection, active or recent (30 days) of the genitourinary tract; abnormal uterine bleeding; history of photosensitivity disorder or use of photosensitizing drugs; genital prolapse (grade II–III classification POP-Q); and serious or chronic illness that could interfere with the study. All patients gave written informed consent to the study. All patients (n = 235) were treated with VEL (XS Fotona Smooth™, Fotona, Ljubljana, Slovenia) with a wavelength of 2940 nm. Patients were treated with three VEL applications (L1, L2, L3) every 30 days, with a screening visit 2–4 weeks prior to the first laser treatment (baseline). Follow-up evaluations were performed after 1 (T1), 3 (T3), 6 (T6), 12 (T12), 18 (T18) and 24 (T24) months from the last laser application. The VEL procedures were performed in an outpatient clinical setting, without any preparation, anesthesia, or post-treatment medications. Before the procedure, the vagina was cleaned with disinfectant solution and dried with a swab.

Laser parameters (phase I Renovalase™ mode) were set as previously reported¹¹. The diameter of the laser spot size was 7 mm, with a pulse according to the SMOOTH™ mode at a frequency of 1.6 Hz, and fluence (laser energy emitted per unit area) of 6.0 J/cm², in order to achieve a controlled deep thermal effect, without ablation and carbonization of the tissues, so avoiding the risk of perforation with accidental lesions of the urethra, bladder or rectum. After inserting the specifically designed vaginal speculum, the probe (R11) is inserted into the speculum, without direct contact with the vaginal mucosa. Subsequently, circular treatment of the vaginal wall is performed, with four pulses given every 5 mm, up to the vaginal vestibule. The procedure is repeated three times. Finally, after removing the speculum, the vestibule and the introitus are treated¹¹. In addition, in 114 postmenopausal women suffering also from stress urinary incontinence (SUI), the degree of incontinence was assessed with the International Consultation on Incontinence Questionnaire - Urinary Incontinence Short Form (ICIQ-UI SF). None of these patients presented a pelvic organ prolapse greater than stage II, according to the Pelvic Organ Prolapse Quantification (POP-Q) system classification. During the VEL procedures, these patients received additional laser treatment of the anterior vaginal wall (Incontilase ™ Phase 1 procedure) specifically designed for urinary incontinence. After treatment, all patients are advised to practice sexual abstinence for 1 week.

An active control group of postmenopausal women were treated with local treatments (LT), either hormonal (estriol gel 50 mg twice weekly) or non-hormonal established therapies such hyaluronic acid-based preparations or different moisturizers and lubricants for 3 months.

At the first visit, the eligibility of the patient was verified, written informed consent was obtained and sociodemographic and clinical characteristics were collected. Subjective symptoms (vaginal dryness and dyspareunia) were evaluated by a visual-analog scale (VAS) at every visit (range 0–10, 0 = total absence of the symptom and 10 = the worse possible symptom). In addition, at each visit during the gynecologic examination, the Vaginal Health Index Score (VHIS) was evaluated. VHIS evaluates the appearance of vaginal mucosa (elasticity, pH, vaginal discharge, mucosal integrity and moisture). Each parameter is graded from 1 to 5, with a total score ≤15 defining an atrophic condition^13–15. Women were asked to assess the general acceptability and efficacy of the VEL therapy as excellent, good, acceptable, bad, or unacceptable. All the results were reported as the means ± standard errors of absolute values. Baseline values were compared by Student’s t-test. Two-way analysis of variance for repeated measures and factorial analysis of variance were used to test the differences within and between the groups, respectively. The post-hoc comparison was made by the Scheffe F-test, using Sigma Stat View software (SPSS Science, Chicago, IL, USA).

Results

There were no significant differences in age, age at menopause, years since menopause, and body mass index (BMI) in the two treatment groups before the study (Table 1). In the VEL group, 205 women completed the study; 11 patients left the study for personal reasons, 13 due to other pharmacological or surgical interventions, and one who complained of discomfort after the first application.

Table 1. Baseline characteristics of participants. Data are expressed as a mean ± standard deviation.

	Vaginal erbium laser group (n = 205)	Local treatment group (n = 49)
Age (years)	61.2 ± 7.2	62.0 ± 7.5
Age at menopause (years)	47.9 ± 5.7	50.5 ± 4.3
Years since menopause	13.4 ± 7.2	12.8 ± 3.8
Body mass index (kg/m^2)	27.1 ± 5.3	25 ± 5.4

The basal VAS scores were similar in the two groups (Table 2, Figure 1). In both groups, the VAS scores for vaginal dryness and dyspareunia showed a significant (p < 0.01) decrease 4 weeks after the first VEL treatment or 4 weeks of LT (L1). In the LT group, no major differences were found among different treatments and, thus, all the patients were grouped together. In the follow-up period, the dryness and dyspareunia values were significantly (p < 0.01) different from baseline values after the second and third laser applications, as well as during the first 12 months of observation (Table 1, Figure 1). Conversely, the values measured after 18 and 24 months from the last VEL application were significantly (p < 0.05) higher than the values at the 6th month and not significantly different from corresponding basal values (Table 2, Figure 1). VHIS values showed a significant increase after VEL treatments (Table 2).

Figure 1. Effect of second-generation laser thermotherapy on vaginal dryness (upper panel) and dyspareunia (lower panel) (visual analog score, VAS: 10-point scale). VEL, vaginal erbium laser group; LT, local treatment group. *p < 0.01 vs. corresponding basal values in both groups; †, p < 0.05 vs. LT basal values and corresponding VEL group values; see text for details.

Table 2. Effect of second-generation laser thermotherapy on vaginal dryness and dyspareunia (visual analog score, VAS: 10-point scale).

	Atrophy		Dyspareunia		Vaginal Health Index Score		Vaginal erbium laser
	VEL	LT	VEL	LT	VEL	LT	Group (n)	Effective (months)	Repeat (n)
Basal	8.3 ± 1.5	8.0 ± 2.7	8.5 ± 1.3	8.0 ± 2.7	10.6 ± 2.7	10.8 ± 1.7	205
L1	5.2 ± 1.7^a	3.1 ± 1.5	5.1 ± 1.8^a	4.5 ± 1.5^a	16.2 ± 1.5^a	18 ± 2.5^a	205
L2	4.3 ± 20^a	3.0 ± 2.0^a	4.0 ± 1.9^a	4.2 ± 2.0^a	18.1 ± 2.0^a	19 ± 2.4^a	205
L3	3.0 ± 1.3^a	4.0 ± 2.1^a	4.1 ± 1.9^a	3.8 ± 2.1^a	19.5 ± 1.2^a	18 ± 2.6^a	205
T1	3.0 ± 1.1^a	3.0 ± 1.5^a	3.5 ± 1.0^a	4.0 ± 1.5^a	20.1 ± 1.3^a	18 ± 2.8^a	204
T3	3.0 ± 0.9^a^,b	5.0 ± 2.9	3.8 ± 1.5^a	6.8 ± 1.5^b	19.5 ± 1.5^a	16 ± 2.7^a	203	23	2
T6	3.5 ± 1.2^a	6.0 ± 3.2^b	4.2 ± 2.0^a	7.7 ± 2.7^b	18.7 ± 1.5^a	12 ± 2.9^a	163	18	20
T12	5.6 ± 1.5^a	–	5.3 ± 2.2^a	–	16.5 ± 2.0^a	–	152	103	62
T18	6.2 ± 1.3	–	7.5 ± 2.3	–	15.3 ± 2.0^a	–	119	49	55
T24	7.0 ± 1.0	–	8.2 ± 2.4	–	12.7 ± 2.7	–	66	5	34

^a p < 0.01 vs. corresponding basal values in both groups; p < 0.05 vs. corresponding laser group values.

VEL, vaginal erbium laser group; LT, local treatment group.

The VAS values in the LT group showed a similar decrease during the treatment period, with a comparable pattern. No significant difference was evident between VEL and LT during the treatment period. Conversely, the VAS scores for both vaginal dryness and dyspareunia in the LT group showed a progressive increase after the end of the treatment period, and the values after 6 months were significantly (p < 0.05) different from corresponding values measured in the VEL group (Table 2, Figure 1). In the LT group, the follow-up period ended after 6 months, since almost all patients started a new local or systemic treatment for the GSM symptoms.

In the VEL group, eight patients (3.9%) affirmed that the treatment was not effective in reducing GSM symptoms. Treatment was defined as effective up to 3 months by 23 patients (11.2%), up to 6 months by 18 patients (8.8%), while 73.6% of them (n = 151) reported that the VEL treatment was effective for 12–18 months (Table 2). Only five patients (2.4%) were still satisfied after 24 months from the last VEL application. A total of 174 (84.9%) patients decided to repeat the complete VEL procedure at different time points of our follow-up period, and were excluded thereafter in the data analysis (Table 2).

In the 114 patients suffering from SUI (mean age 64.6 ± 4.4 years; age at menopause 49.6 ± 3.6 years), the VEL treatment induced a significant (p < 0.05) decrease in the ICIQ-SF scores from basal values of 12.2 ± 2.5 to 8.0 ± 1.4 at L1, to 4.7 ± 1.8 at L2, and 5.1 ± 2.0 at L3 (Figure 2). The ICIQ-SF scores remained significantly (p < 0.01) lower than basal values after 1 (4.8 ± 1.8), 3 (6.2 ± 1.9), 6 (7.0 ± 2.3) and 12 (8.0 ± 1.8) months after the last VEL application (Figure 2). The values measured after 18 (9.3 ± 2.7) and 24 (9.9 ± 2.8) months from the last VEL application were, however, not significantly different from the basal values (Figure 2). In this group, a total of 96 patients asked for repetition of the VEL procedure: 51 patients after the 12th, 30 after the 18th and 15 patients after the 24th month. A total of nine patients were still satisfied after 24 months from the last VAL application. Only ten patients (7.2%) underwent surgery, while 23 patients (16.6%) were lost at follow-up. No adverse events related to the procedure were recorded throughout the study period.

Figure 2. Effect of second-generation laser thermotherapy on International Consultation on Incontinence Questionnaire (ICIQ- SF) score in 114 postmenopausal women suffering from stress urinary incontinence. *p < 0.01 vs. corresponding basal values; see text for details.

Discussion

The results of our longitudinal study indicate that the VEL effects on GSM symptoms are rapid and long lasting. This study shows for the first time that VEL treatment significantly improves GSM symptoms for 12 months after the last laser application, while the effects seem to vanish afterwards. This study confirms that VEL is effective in the treatment of GSM, with clinical effects similar to those exerted by established local therapies^12–17. The effect of VEL is evident on subjective symptoms as well as on objective evaluation of vaginal conditions, appearance and trophism. An important question arising from this study is at what time should a new VEL procedure(s) be offered. The beneficial action of thermotherapy may last at least 1 year and the large majority of our patients were satisfied, as demonstrated by the high percentage of patients that choose to repeat the treatment. These data further suggest VEL is safe and well accepted, with no major side-effects or adverse events reported. Present data reinforce the contention that VEL is appropriate for women who cannot or do not want to be treated with hormones, as well as in women who do not accept long-term use of moisturizers and lubricants.

This study also shows that VEL treatment may induce a significant decrease in clinical symptoms in women suffering from SUI^15,18–30. The effects on SUI are ascribed to the effects of VEL on collagen remodeling^31,32. Collagen is an important component of the pelvic floor, making up more than 80% of protein content of the endopelvic fascia. Besides possible childbirth injuries, aging is associated with a decrease in collagen content and functional damage to the pelvic floor, and SUI is more frequent in women with reduced collagen content in their anterior vaginal walls and the pubocervical fasciae^33–35. Since the Er : YAG laser is strongly absorbed in water, VEL increases the tissue temperature in the range of 60–70 °C, leading to the initiation of neocollagenesis without ablation or irreversible tissue damage^31,32. VEL treatment has been consistently associated with a reduction of four to six points in the ICIQ-UI¹⁵. The effectiveness of VEL has also been confirmed in a randomized clinical trial vs. sham treatment¹⁹. Our results indicate that the results are maintained up to 12 months after VEL treatment.

Different aspects of vaginal laser treatment need further investigations. Further studies are required to explore the use of VEL in GSM patients in association with different therapeutic options, in order to offer the procedures in alternative and/or in sequence with established therapies. The possible difference in the outcomes of VEL treatment with or without estrogen pretreatment or the current use of estrogenic or non-hormonal therapies is a matter of future randomized studies. VEL treatment of SUI needs to be tested not only in women who are not suited for surgery, but also in those who are candidates for surgery in order to evaluate the possible avoidance of surgical procedures. Further properly sized, long-duration, randomized studies are required to evaluate the effects of VEL treatments in comparison with other therapies.

In conclusion, VEL for vaginal functional restoration is an effective ambulatory procedure for the treatment of GSM and mild-moderate SUI. VEL may add to our armamentarium of available options for the treatment of GSM, allowing postmenopausal women to choose, considering the limits and the balance between benefits and risks associated with each therapeutic approach.

Conflict of interest

The authors report no direct conflict of interest.

Additional information

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.