Vaginal Energy-based Devices: Characterization of Adverse Events Based on the Last Decade of MAUDE Safety Reports

Shannon L. Wallace, MD; Eric R. Sokol, MD; Ekene A. Enemchukwu, MD, MPH

Disclosures

Menopause. 2021;28(2):135-141. 

In This Article

Discussion

The present study characterizes the safety events of vaginal energy-based devices by analysis of surveillance data from the FDA Manufacturer and User Facility Device Experience (MAUDE) database and specifically looks at those events that occurred prior to the July 30, 2018 warning. Overall, the MAUDE-reported data suggests that patients with complaints who receive treatment with energy-based vaginal devices most commonly report vaginal pain, bladder pain, and urinary symptoms. The majority of complaints are not severe, and some may be related to progression of the disease.

Our review of the MAUDE database supports the data from previous studies that vaginal pain is the most commonly reported patient complaint after vaginal energy-based treatment. Although dyspareunia was the second most commonly reported complaint in the MAUDE database, few published studies report dyspareunia as an adverse event. This discrepancy is likely because most studies are assessing dyspareunia for efficacy of vaginal energy-based therapy and not for posttreatment complications. When analyzing MAUDE data, it is important to keep in mind that adverse events are often reported by patients who may not have been formally diagnosed by a physician. Therefore, a patient may perceive continued dyspareunia and vaginal pain as an adverse event, although it is possible that her diagnosis is insufficient treatment of her symptoms.

Bladder pain and urinary frequency were also commonly reported as adverse events in the MAUDE database. Surprisingly, urinary symptoms are rarely reported as adverse events in the current literature. Again, a possible explanation is that urinary symptoms may be included in the evaluation of vaginal energy-device treatment efficacy or, alternatively, patients may not associate a vaginal procedure with triggering urinary symptoms.

In analyzing our data, almost two-thirds of MDR complaints (68.2%) were pain related. In fact, the majority (89%) of the MDR complaints made prior to the July 30, 2018 FDA warning were pain-related. Although they include a small percentage (3.5%) of all MDR complaints, all three patients suffering third-degree burns reported them prior to the FDA warning. The severity of these initial complaints may have prompted the FDA to release their warning statement to those companies marketing vaginal energy-based devices.

The timing of MDR submissions suggests a strong recall bias in patients who reported their events after the FDA warning. Patients may have experienced adverse events from vaginal energy-based device treatments previously, but only submitted reports of these adverse events after the FDA highlighted possible violations of the FD&C Act. Additionally, the violation notice may have prompted some patients to pursue litigation against these companies for adverse events that occurred prior to the FDA warning. The MAUDE database allows patients and providers an additional method of documentation of these adverse events, which may be used to strengthen a plaintiff's case.

Data showing the long-term efficacy, safety, and complications of energy-based devices for the treatment of PFDs is limited and lacking. Outcomes data are often extracted from small, prospective case series which are underpowered to accurately report the risk of adverse events and complications. Although many of the initial 12-week observational studies on energy-based devices reported no adverse events, long-term outcomes of complication rates are necessary to characterize their safety profiles.[22–26]

One-year observational studies seem to highlight the mild and transient nature of most adverse events. Sokol and Karram followed 30 women for 12 months who underwent fractional CO2 laser treatment for GSM. Adverse events resolved in 2 to 3 days and included two patients who reported mild-to-moderate pain posttreatment and two patients who reported mild vaginal bleeding.[26,27] Similarly, Samuels and Garcia performed a 12-month observational prospective study of 43 patients who underwent fractional CO2 vaginal laser treatment for GSM. The authors reported common immediate treatment responses including mild to moderate erythema (54%), edema (55%), and mild bleeding (4.7%) which all resolved within 24 hours. Seven treatment-related adverse events including vaginal burning, itching, bleeding, and swelling resolved within 1 week.[28]

Gasper et al published an 18-month prospective study comparing patients who received Erbium:YAG vaginal laser therapy with vaginal estrogen cream to those patients who received vaginal estrogen cream alone. In the vaginal laser group, 4% of patients experienced side effects including mild-to-moderate pain, transient edema, and vaginal spotting. This was less than the side effects of the vaginal estrogen group, 8% of whom experienced vaginal spotting, 4% mastodynia, and 12% abdominal pain.[29] Although the authors compared outcomes to a control group, this study was observational and nonrandomized. Recently, two randomized controlled trials of fractional CO2 laser therapy for the treatment of GSM have been published. Cruz et al randomized 45 patients to either vaginal laser therapy or vaginal estrogen cream and found that vaginal laser treatment significantly improved burning, dyspareunia, and dryness, similar to treatment with vaginal estrogen cream. The authors noted that no adverse events were observed during the study duration of 20 weeks.[30] Paraiso et al also randomized 30 women with GSM to vaginal laser therapy and 32 women with GSM to vaginal estrogen cream and followed these patients for 6 months. Adverse events were similar between the groups and five patients in the vaginal laser group reported adverse events including two patients with vaginal bleeding (6.7%), one patient with vaginal pain (3.3%), one patient with vaginal discharge (3.3%), and one patient with a urinary tract infection (3.3%).[31]

According to our study, most patients with adverse events list their indication for vaginal energy-based device therapy as "vaginal rejuvenation." Vaginal rejuvenation is a much-contested umbrella term that describes both surgical and nonsurgical approaches for treating vaginal symptoms. Vaginal rejuvenation covers cosmetic procedures for treatment of vaginal laxity to corrective therapies targeting atrophy, dyspareunia, and urinary incontinence. When analyzing data to determine which patients are at risk for adverse events, vague terminology for the indications for vaginal energy-based device therapy confound this analysis and make characterizing a risk profile challenging. The IHCTOA Letters from the FDA specifically asked the manufacturers of energy-based devices to provide evidence of FDA clearance or approval for umbrella terms like "vaginal rejuvenation" and "vaginal health restoration," potentially as a way to rein in this "off-label" usage.

Another barrier to characterizing the safety profile of vaginal energy-based devices is the variation in technique and administration. The optimal interval between vaginal treatments for both duration of sessions and maintenance regimens has not been standardized, which can make outcomes research difficult to interpret. Additionally, as Gordon et al recently discussed, providers in different fields use energy-based devices for the treatment of vaginal conditions. Dermatologists, plastic surgeons, gynecologists, and urologists all use energy-based therapies which can lead to nonstandardized regimens and wide variation in indications for treatment.[32]

Early investigations of energy-based devices show good promise for the treatment of PFDs, but there is insufficient evidence of long-term efficacy and side effects. Recognizing that most laser and energy-based device literature pertaining to PFDs is observational, we need to conduct large, long-term, RCTs to understand the risk profile and complication rates of energy-based therapies prior to widespread adoption. On clinicaltrials.gov, there are 40 registered trials that are studying the use of vaginal energy-based devices in different populations, including breast cancer patients. We are responsible for ensuring that there is important emphasis on documentation of adverse events. The therapeutic advantages of nonsurgical energy-based devices can only be recommended after robust clinical trials have demonstrated their long-term complication profile, safety, and efficacy. The recent FDA order to remove transvaginal mesh from the market is a warning that we need to avoid past pitfalls by demonstrating the safety and effectiveness of energy-based devices, so that we can confidently recommend this therapy to our patients.

We are also responsible for counseling our patients on the risks, benefits, and alternatives of all treatment options including vaginal lubricants and vaginal moisturizers, topical estrogen therapies, oral selective-estrogen receptor modulators and vaginal energy-based devices. Patient education on the available data or lack of data will allow them to make informed decisions.

The MAUDE database is a unique tool to identify both common and rare complications of medical devices. Clinical trials of new devices take many years to publish peer-reviewed data and the MAUDE database allows an assessment of adverse events in real time. Additionally, infrequent complications might only occur after large numbers of procedures have been performed and may not occur in larger clinical trials. Clinicians, patients, and researchers can use the MAUDE database as a tool to allow specific instances of these rare complications to be made known.

A major limitation of using the MAUDE database to assess the risk profile of vaginal energy-based devices is that the absolute number of procedures is not available. We can characterize the types of adverse events associated with each device but cannot provide a risk percentage. As device manufacturers release limited data on the number of devices sold, it is difficult to estimate how many devices are operational and, therefore, how many patients have undergone vaginal energy-based therapy. Additionally, the MAUDE database can also skew the results toward the most commonly used device. Adverse events were most commonly reported for the fractional CO2 Mona Lisa Touch vaginal laser system, possibly because this device is the most commonly used vaginal energy-based device. There is also the potential for underreporting of complications, variability in detail and accuracy, and an inability to prove that patient injury is directly causal to device malfunction. For example, all three adverse events reports regarding "third degree burns" were reported by patients, but neither the diagnoses nor malfunction or improper use of the device could not be verified. Additionally, adverse events are reported by device manufacturers, physician, and patients, and thus duplicate reports may occur and can be difficult to discriminate in the database.

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