A multi-institutional, randomized trial comparing fractionated CO2 laser therapy with vaginal estrogen therapy for the treatment of vaginal dryness and genitourinary syndrome of menopause (GSM) found the treatments to be similarly effective at six months. Moreover, 70% to 80% of participants were satisfied with either treatment, and no serious adverse events were reported.
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“There are women who won’t take estrogen therapy because they can’t afford it, are afraid of it or because it is contraindicated due to a history of estrogen-dependent tumors. This gives us an option,” says Marie Fidela Paraiso, MD, a gynecologist in Cleveland Clinic’s Women’s Health Institute and Professor of Obstetrics, Gynecology and Reproduction Biology at the Cleveland Clinic Lerner College of Medicine. Dr. Paraiso was principal investigator of the study, which was published ahead of print on Sept. 30, 2019, in Menopause.
Fractional CO2 lasers have demonstrated safety and efficacy in the remodeling of tissue and production of new collagen, elastic fibers and angiogenesis in various body areas. The regenerative effects of intravaginal fractional CO2 laser therapy in postmenopausal GSM at 12-week followup had been previously reported. The laser had been shown to decrease the severity of dyspareunia related to vaginal dryness and was associated with improvement in sexual function and satisfaction.
“The objective of our study was to compare improvement in symptoms of GSM at six months between participants who underwent laser therapy and those treated with vaginal estrogen alone,” says Dr. Paraiso.
Study design and outcomes
Participants randomized to estrogen therapy applied conjugated estrogen cream 0.5 grams daily for 14 days, followed by twice weekly for 24 weeks.
Participants randomized to laser therapy underwent three vaginal treatments a minimum of six weeks apart.
The primary outcome was determined by comparing subjective improvement in vaginal dryness using the visual analog scale (VAS) between the two groups at six months. Secondary outcomes included comparisons of the vaginal health index (VHI) and vaginal maturation index (VMI), effect of GSM on quality of life, effect of treatment on sexual function and urinary symptoms, and patient satisfaction.
Laser therapy and estrogen therapy were found to be similarly effective, except in VMI, which favored estrogen. On patient global impression, 85.8% of laser participants rated their improvement as “better or much better,” and 78.5% reported being “satisfied or very satisfied,” compared to 70% and 73.3% in the estrogen group. This difference was not statistically significant.
A fly in the ointment
It was determined that 196 participants were needed for this noninferiority trial. However, after only 38% had been enrolled, the U.S. Food & Drug Administration (FDA) decided to require an investigational device exemption for the laser and inclusion of a sham treatment arm. Since this would have required a prolonged hiatus, total trial redesign, reconsent of all participants and a substantial increase in costs, the study was closed. Instead of 169 patients, the analysis was performed on the 62 patients who completed the study. Dr. Paraiso calls this development “deflating.”
“We were disappointed we couldn’t meet the power of the trial. You want people to have confidence in your data,” she says.
Alternative to estrogen needed
Vaginal estrogen remains the gold standard treatment for GSM. However, the total cost of $100-$200 per month is not always fully covered. Furthermore, some women find the messy cream a turn-off. Those who are intolerant of the base product find it causes irritation. Other women don’t respond to the treatment. In addition, estrogen is contraindicated in women with a history of estrogen-dependent gynecologic or breast cancer.
“I entered the trial with hopes that it would lead to greater acceptance of the laser, and we would have another option for these women,” says Dr. Paraiso. “However, as the laser is still not FDA-approved for GSM, most women have to pay out of pocket for three treatments at $500 each.”
Dr. Paraiso remains hopeful there will be additional trials that will lead to FDA approval of laser therapy for GSM.
“It would be wise to embark on a well-designed trial that is sufficiently powered and includes FDA-recommended indications, so we can proceed to make laser treatment affordable through insurance,” she says.
The Foundation of Female Health Awareness, which provided unrestricted grant to cover this trial, has expressed interest in moving forward.
Until laser therapy is approved, Dr. Paraiso and her colleagues continue to prescribe estrogen therapy or treat the symptoms of GSM individually.
“If a woman is not willing to use vaginal estrogen, we recommend vaginal lubricants or lidocaine for pain with intercourse. If urinary symptoms are bothersome, we can offer decreasing bladder irritants, behavioral modification, physical therapy and overactive bladder medication, if indicated,” she says.
“But if the woman’s symptoms are primarily dryness or dyspareunia, and she wants or needs a different option, we will offer her the laser.”