IMPORTANCE Postmenopausal vaginal symptoms are common and frequently detrimental to a woman's quality of life. Fractional carbon dioxide vaginal laser is increasingly offered as a treatment, but the efficacy remains unproven.OBJECTIVE To determine the efficacy of fractional carbon dioxide laser for treatment of vaginal symptoms associated with menopause. DESIGN, SETTING, AND PARTICIPANTSA double-blind, randomized, sham-controlled trial with 12-month follow-up was undertaken at a single tertiary referral hospital in Sydney, Australia. Enrollment commenced on September 19, 2016, with final follow-up on June 30, 2020. Participants were postmenopausal women with vaginal symptoms substantive enough to seek medical treatment. Of 232 participants approached, 85 were randomized.INTERVENTIONS Three treatments using a fractional microablative carbon dioxide laser system performed 4 to 8 weeks apart, with 43 women randomized to the laser group and 42 to the sham group. MAIN OUTCOMES AND MEASURESThe co-primary outcomes were symptom severity assessed using a visual analog scale (VAS; range, 0-100; 0 indicates no symptoms and 100 indicates the most severe symptoms) and the Vulvovaginal Symptom Questionnaire (VSQ; range, 0-20; 0 indicates no symptoms and 20 indicates the most severe symptoms) at 12 months. The minimal clinically important difference was specified as a 50% decrease in both VAS and VSQ severity scores. There were 5 prespecified secondary outcomes, including quality of life (range, 0-100; higher scores indicate better quality of life), the Vaginal Health Index Score (range, 5-25; higher scores indicate better health), and vaginal histology (premenopausal or postmenopausal status). RESULTSOf 85 randomized participants (mean [SD] age, 57 [8] years), 78 (91.7%) completed the 12-month follow-up. From baseline to 12 months, there was no significant difference between the carbon dioxide laser group and the sham group in change in symptom severity (VAS score for overall vaginal symptoms: -17.2 vs -26.6; difference, 9.4 [95% CI, -28.6 to 47.5]; VAS score for the most severe symptom: -24.5 vs -20.4; difference -4.1 [95% CI, -32.5 to 24.3]; VSQ score: -3.1 vs -1.6; difference, -1.5 [95% CI, -5.9 to 3.0]). There were no significant differences between the laser and sham group in the mean quality of life score (6.3 vs 1.4; difference, 4.8 [95% CI, -3.9 to 13.5]) and Vaginal Health Index Score (0.9 vs 1.3; difference, -0.4 [95% CI, -4.3 to 3.6]) or in histological comparisons between laser and sham treatment groups. There were 16 adverse events in the laser group and 17 in the sham group, including vaginal pain/discomfort (44% vs 68%), spotting, discharge, and lower urinary tract symptoms. No severe adverse events were reported in either group.CONCLUSIONS AND RELEVANCE Among women with postmenopausal vaginal symptoms, treatment with fractional carbon dioxide laser vs sham treatment did not significantly improve vaginal symptoms after 12 months.

Cobrotoxin produces intense analgesia but it has an onset of response of 1-3 h which hampers its clinical use in cancer pain. Recently, a compound analgesic formulation combining cobrotoxin, tramadol hydrochloride and ibuprofen (Compound Keluoqu, CKLQ) has become available in China. The aim of this study was to evaluate the clinical efficacy of CKLQ for moderate to severe cancer pain. A consecutive series of patients with chronic moderate to severe cancer pain was enrolled into two multicenter trials. Of the 230 eligible patients, 119 were assigned to a randomized, double-blind, cross-over study, while 111 entered an open-label study. They were all of Han-China nationality and had a mean age of 52.0 and 55.4 years and a mean body weight of 55.6 and 52.9 kg, respectively. A total of 11 patients discontinued the study, 6 (54.5%) because of insufficient pain relief and 5 due to the occurrence of adverse events. In the cross-over study, 59 patients were randomized to receive a CKLQ package with 2 CKLQ tablets (each containing 0.16 mg cobrotoxin, 25 mg tramadol hydrochloride and 50 mg ibuprofen) and 2 placebo capsules, a placebo package with 2 placebo tablets and 2 placebo capsules, and an active control package with 2 tramadol hydrochloride capsules (each containing 50 mg tramadol hydrochloride) and 2 placebo tablets (arm A), and 60 to receive a tramadol hydrochloride package, a placebo package and a CKLQ package (arm B), sequentially and only once. Patients in the open-label study only received CKLQ and were given the option to continue for up to 7 days as long as they had satisfactory pain relief. Pain response was classified as CR, PR and NC. CR was defined as 100% pain relief, with a pain score of 0 on a 0-10 VAS. PR was defined as decreased to mild pain, with a pain score of no more than 4 on a 0-10 VAS. NC was defined as pain that either remained unchanged or that was reduced from severe to moderate at baseline, with a VAS pain score of more than 4 after treatment. One hundred and eight patients completed the cross-over study with all the three drug units. The overall rate of pain relief was 93/ 111 (83.7%) for CKLQ, 75/110 (68.2%) for tramadol hydrochloride (P=0.011) and 39/111 (35.1%) for placebo (P<0.001). The mean duration of pain relief with CKLQ was significantly longer than that of the other two agents (P<0.001). Of the 35 patients who did not respond to tramadol hydrochloride, 27 (77.1%) responded to CKLQ, while of the 18 who did not respond to CKLQ, 8 (55.6%) achieved satisfactory pain control with tramadol hydrochloride. In the open-label study, the overall relief rate of a single-dose of CKLQ was 99/111 (89.2%). A reduction in the percentage of complete relief, an increase in that of PR and a significant decrease in duration of relief were observed after continuous treatment with at least 10 doses of CKLQ. The frequency of adverse events for CKLQ was similar to that of tramadol hydrochloride. The results of the randomized, double-blind, cross-over study and the open-label study of CKLQ in cancer pati...

Following menopause, up to 49% of women will experience genitourinary symptoms such as vaginal itching, dryness, dyspareunia and incontinence as a result of oestrogen deficiency. Treatments such as vaginal lubricants and moisturisers only temporarily relieve symptoms, while local oestrogen treatments are often unacceptable or unsafe for many women. Recently, a novel laser treatment has been proposed as a non-invasive, long-term solution to vulvo-vaginal and urinary symptoms. While preliminary histological results have been promising, its therapeutic, clinical effect has yet to be determined. However, despite the scarcity of evidence for its safety and long-term benefit, laser treatments are widely marketed for a range of genitourinary symptoms, with high uptake by both clinicians and women alike. This review aims to examine the evidence for laser treatments to the vulvo-vagina and to evaluate its safety and efficacy. Our results include 17 studies investigating the effect of laser therapy for vulvo-vaginal symptoms, seven for its effects on urinary incontinence and four for histology. These are limited to non-randomised, observational data with small sample sizes between 15 to 175 women and follow-up duration from none to two years. As such, strong evidence for laser efficacy and safety is limited and warrants more robust, placebo-controlled, randomised trials before widespread implementation.

(Abstracted from Aust N Z J Obstet Gynaecol 2017; doi: 10.1111/ajo.12735) As a result of estrogen deficiency, up to 49% of postmenopausal women will experience vulvovaginal symptoms (VVSs) such as vaginal itching, dryness, dyspareunia, and incontinence. Treatment of VVS may be nonhormonal or hormonal.