A new hydrogel applied directly to vaginal tissues may help alleviate the negative impacts of menopause, according to a new study from scientists at the University of California San Diego. The results, published in Advanced Materials , could pave the way for a hormone-free treatment that alleviates vaginal dryness and pain caused by genitourinary syndrome of menopause (GSM), which negatively impacts quality of life for millions of women.
"We have developed a new material, which was designed specifically for the vagina," said Karen Christman, a professor in the Shu Chien-Gene Lay Department of Bioengineering and the Sanford Stem Cell Institute at UC San Diego and one of the senior authors on the paper.
Genitourinary syndrome of menopause, or GSM, affects up to 85% of women over 40 years of age, with 30% to 60% suffering from vaginal dryness and pain. Women suffering from the condition report that it interferes with their sleep, sex life and ability to travel, work out and socialize. Importantly, 65% of women suffering from GSM report that they are not satisfied with the currently available prescription and over-the-counter treatments.
"An estimated 47 million women in the U.S. become menopausal every year, thus GSM represents a major public health issue that urgently needs investment," said one of the senior authors of the paper, Dr. Marianna Alperin, a professor and vice chair for Translational Research in the Department of Obstetrics, Gynecology, and Reproductive Sciences and a co-director of the Center for Women's Health Innovations through Scientific Discoveries, Engineering, and Medicine (WHISDEM) in the UC San Diego Institute of Engineering in Medicine.
The hormonal changes after menopause have a wide range of impacts on women's health, including vaginal and lower urinary tract tissues. Vaginal tissues thin out. Blood vessels shrink, as do the connective tissue and smooth muscle layers that help the vagina expand during sexual activity and provide support for pelvic organs, such as the bladder, uterus and rectum. In addition, immune cells in the female reproductive tract change and start producing inflammatory proteins.
The current gold-standard treatment for GSM is low-dose vaginal estrogen therapy, which has been shown to be highly effective at thickening the lining of the vagina, which will thin in menopause. But this treatment doesn't affect the deeper smooth muscle tissue in the vaginal wall that is responsible for the organ's structure and function. In addition, a number of patients and even some clinicians still reject this treatment because of concerns that it might increase the risk of hormone-sensitive cancers–a concern that studies have shown is not warranted. The treatment is also costly and not always covered by insurance.
Bioengineers in Christman's laboratory make hydrogels from the natural scaffolding of tissue, also known as the extracellular matrix. They have shown that these types of biomaterials help heal cardiac muscle tissue after a heart attack, among several other applications. These hydrogels for cardiac applications also have successfully been tested during a Phase 1 FDA-approved clinical trial.
Christman and colleagues partnered with the Alperin research group to see if hydrogels would constitute a good treatment for GSM, running a study in small animal models as a first step.
"We are not looking to replace estrogen treatments," said Emma Zelus, the first author of the Advanced Materials study, who is currently working as a preclinical research manager at the Sanford Stem Cell Institute. "We want to provide an alternative for patients and physicians who either do not want to use hormone-based therapy or for women for whom vaginal estrogen alone is insufficient."
How the study was conducted
Researchers randomly assigned 24 menopausal rats to receive as a topical intravaginal application a daily dose of a solution containing either hydrogel at two different concentrations–6 or 8 milligrams per milliliter–or collagen or saline. After 14 days of treatment, researchers took samples of vaginal tissues and analyzed them.
They found that in rats that had received the hydrogel treatment, vaginal tissues appeared closer to those of pre-menopausal animals. In addition, treatment with the hydrogel led to an increase in smooth muscle thickness. Researchers also found that the 8 milligram dose seemed to be more effective, likely due to a higher concentration of extracellular matrix proteins.
Researchers sampled tissues from the animals in the first three days of treatment and found that the hydrogel was present not only in the surface layer but also in the muscular layer of the vaginal wall. They found that macrophages, which are part of the immune system, in particular responded to the hydrogel with increases in the kind of macrophage that helps with tissue repair.
Researchers also didn't find any safety concerns or adverse effects on the rats during the study.
Next steps
Next steps include testing various concentrations of the hydrogel in a larger preclinical study over a longer period of time. The researchers also need to test whether the hydrogel can be administered less frequently–twice or three times a week rather than daily.
"We need a multidisciplinary approach to solving women's health issues," said Dr. Alperin, urogynecology and reconstructive pelvic surgery specialist at UC San Diego Health.
The research was supported in that part by the NIH National Institute on Aging and the NIH National Institute of Child Health and Human Development.
Christman is a cofounder of Ventrix Bio. Inc., which is commercializing a similar hydrogel technology for treating heart disease.
Emma I. Zelus and Karen L Christman, Shu-Chien Gene Lay Department of Bioengineering, Sanford Consortium for Regenerative Medicine and Sanford Stem Cell Institute
Marianna Alperin, Sanford Consortium for Regenerative Medicine and UC San Diego Department of Obstetrics, Gynecology and Reproductive Sciences
Jacqueline Grime, UC San Diego Division of Biological Sciences
Anthony Saviola, Maxwell McCabe and Kirk C. Hansen, Department of Biochemistry and Molecular Genetics, University of Colorado
Alperin and Christman are co-corresponding authors
