An understanding of the implications of that finding needs some background. This common disorder, affecting roughly 50%-60% of postmenopausal women is described also as vaginal atrophy or genitourinary syndrome of menopause. The terms encompass symptoms that can range from annoying to depleting and accepted origins of the problem has been estrogen loss with age. With so many affected by this phenomenon, and most healthcare providers believe the estimates are lower than the actual incidence, the problem is not well understood clinically and moreover is even taboo.
Quite simply, many women are too embarrassed to discuss this issue with their doctors or even between themselves. Results of the REVEAL (Revealing Vaginal Effect At mid-Life)1 study found that about half of postmenopausal women surveyed agreed that it is still taboo to acknowledge symptoms such as atrophic vaginitis, and less than half had ever initiated a conversation with their healthcare provider about their symptoms. As such, it is estimated that only 20-25% of symptomatic women seek medical help for atrophic vaginitis (“AV”). Unfortunately, AV is often progressive and either doesn’t resolve or worsens without intervention.
So exactly what is it? AV presents as a complex mixture of sexual and nonsexual/urological complications due in large part to the response in female genitourinary tissue to the reduction in the levels of the sex hormone estrogen, which accompanies menopause. The most common symptoms are vaginal and vulvar pain, vaginal dryness due to lower estrogen levels, external and internal irritation, itching, burning and dyspareunia (pain during intercourse). Frequently women also report urogenital problems and urinary complaints that may include multiple irritative urinary tract infections, dysuria (pain or discomfort during urination), nocturia (frequent urination at night), vaginal discharge, increased urinary frequency and incontinence, and discomfort originating from the urethral opening. Such urogenital changes, coupled with changes in sexual function, can significantly affect overall quality of life for post-menopausal women.
While the dramatic reduction in estrogen during menopause is attributed to be the most common cause of AV, any condition that lowers estrogen production or inhibits the availability of estrogen can lead to its development, it is commonly held. This view includes the use of anti-estrogenic therapies such as selective estrogen receptor degraders (SERDs), selective estrogen receptor modulators (SERMs), and aromatase inhibitors, which are commonly used to treat estrogen receptor positive breast cancers and other estrogen-mediated disorders, such as uterine fibroids and endometriosis.2 Upon the onset of AV, it is likely to persist and become worse without treatment.
Because the widely accepted source of the problem is naturally decreasing levels of estrogen, most physicians recommend the use of topical low-dose estrogen products applied directly to the vaginal tissue. Vaginal application of low-dose estrogen involves less exposure of breast and endometrial tissues, where estrogen can increase the risk of cancer by stimulating the growth of cells. Low-dose estrogen products recommended specifically for the treatment of AV include vaginal creams (Estrace®, Estrone®, and Premarin®), the vaginal tablet Vagifem®, and vaginal rings (Estring® and Femring®, which are estradiol-infused silicone rings that sit around the cervix and releases a very low, steady dose of estrogen).
The use of topical low-dose estrogen products is, however, not without risk. For example, postmenopausal women using topically applied low-dose estrogen are at an increased risk, albeit low, of developing endometrial hyperplasia and thickening. In addition, a small increased risk of stroke, development of blood clots, and the development of uterine cancer is associated with the use of topically applied low-dose estrogen. Moreover not all women with AV may be appropriate candidates for this treatment due to the risks associated with estrogen replacement therapy, including women with—or a past history of—estrogen receptor (ER+) positive breast or ovarian cancer and women significantly post-menopause. Other contraindications include genital bleeding, history of deep vein thrombosis and/or pulmonary embolism, arterial thromboembolic disease (e.g., stroke, myocardial infarction), liver dysfunction or disease, and known or suspected pregnancy. As such, many women and their primary practitioners select against estrogen therapy, including local estrogen therapy, because of the real or perceived risks of the treatment.
With all that, recent clinical evidence would seem to point to an even more fundamental cause for AV than estrogen depletion. The discovery especially brightens the prospects for women “at risk.”
“A pathway to recovery independent of estrogen opens a lot of doors,” says Dr. Allan Wu whose medical research in Southern California has focussed in large part on gynecologic disorders.
“We’ve been looking at a unique molecule whose precursor is in avocado that renormalizes a key phenotype. It has demonstrated zero estrogen activity in our clinical study but the results have been simply outstanding and patient satisfaction overwhelmingly positive. Our study was small but established several significant findings for future development.”
Any number of natural products and compounds have been tried for AV. Coconut oil, aloe vera and avocado oil for example are helpful for a short period of time but none of these or others has demonstrated continuing relief. More technical formulas containing vitamin E, vitamin A, hyaluronic acid are also used and well known brands like Replens® and Vagisil® that use carbophilic polymers that adhere to the vaginal walls provide some relief, as well as the hormone DHEA.
“I haven’t found any of these satisfactory which is why Dr. Wu’s findings are very exciting for my patients whose quality of life has deteriorated.” says Dr. Catheryn Yashar a gynecologist and Professor of Radiation Medicine and Applied Sciences at the Moores Cancer Center, La Jolla, California. Her patients are “at risk” and most suffer extensively from AV especially following therapeutic treatments for their cancer.
What has them excited is Avogen302 from avocado that is the active ingredient in Avogen Medical’s Intimate Capsules, used as a vaginal suppository for dryness.
“The chemistry is unique,” according to Richard Huber, a chemist who established the intellectual property and discovery development for Avogen Medical. “Nature has few singularities and the 17 carbon lipid furan of 302 molecular weight from avocado is one of them. Avocados have, so far, avoided the genetic erosion of cross breeding so there are many interesting natural metabolites found nowhere else. Avogen302 is by far the most significant of these.”
The origins of the discovery go back decades to a coffee plantation in the Central Highlands of Guatemala where a chance meeting set the odyssey of discovery in motion. Here was an obscure varietal of avocado fruit that shaded the coffee plants and also provided a large dietary component for the workers. Their overall health was immediately apparent in an area of the world where the life expectancy was not more than 50 years. Within several years from that meeting a body of safety studies developed at Eli Lilly that focused on the Avogen302 molecule from that fruit. The Lilly work demonstrated safety and posited a variety of mechanisms with tantalizing potentials. During that time interest centered on topical usage. In a twist of fate, the division to develop that was sold off by Lilly and any development lay dormant for a decade.
The advent of 302 Professional Skincare in 2003 came about with the capacity to process avocados on large scale and to extract and purify Avogen302. The goal was to pick up where Eli Lilly had left off. The boutique skincare company efforts helped to understand the significance of the molecule and its practical utility.
“It became clear early on that Avogen302 had the ability to reverse the visible effects of chronologic aging. But it did this without risky exfoliation and in a much more profound way,” Huber explained. “We coined a term internally to describe it: renormalization. We explained to ourselves that the molecule must be guiding cells back to normative behavior and for that reason we expected it keyed on networks of cell signaling processes. Phenotype workups confirmed this.
“One of the most compelling aspects of this molecule is its safety. Nature does not put molecules out there to benefit us for the most part. There are disadvantages to natural products. They are often ineffective, short lived in results or cumulatively harmful and dosing is all over the map. With Avogen302 this is not so and the day to day results and over the long haul speak for themselves.”
The follow-on was to encapsulate the Avogen302 extract as a dietary supplement beginning in 2017. “We had safety data and long history and the product we decided should be like a dose of avocado daily,” as Charlie Edwards operations and marketing lead at Avogen Medical described the genesis.
“We put it out there to get feedback and we heard back that visible effects were first. Sun damage eruptions and scars cleared and the thin papery skin look was gone. Avogen302 is the first orally dosed skincare product to make visible change. Anti-aging is an over-worked and under delivering category out there, but what we see and hear from our supplement users confirms all of our previous data.
“Then came the feedback on deep seated scars, adhesions, capsular contractures and a lot more internal benefits. This was with low doses, too,” said Edwards who grew up around avocados. “I began to think: is there anything it can’t do?’
The epigenetic nature of Avogen302 would explain the broad reach of the products with it. As Huber puts it, “re-normalizing is more about what you’re not doing wrong anymore. In biochemical terms there is both up regulating and down regulating going on to reach your happy medium – the way you hope any natural secondary metabolite would contribute. Re-normalizing is the essential factor to reverse visible aging. The skin first changes texture, it grows softer and yet with more turgor. We know that better skin begins in the epidermis and that is where Avogen302 does its work.”
It is synergistic with vitamin A and its analogs.
“They do different things, that complement each other. You can easily overdo it with topical or oral retinoids, though. But not Avogen302. Big difference there,” said Jane Mann a practicing skin esthetics guru in Las Vegas.
“Everything coming out of that company (Avoscience) works for my clients. The Avogen Intimate Capsules, the Avogen Dietary Supplement, the 302 Professional Skincare products. There is not a me-too product in their line-up. These are real tools that get results.”
Dermatologist Douglas Hamilton, associate professor at UCLA and in private practice sees Avogen302 as the future. “It’s doing things nothing else has been able to do without serious inflammation going along with it. That is very significant. It may take awhile in some applications for it to exert itself which can be frustrating in our right now today culture but for me it’s a plus to know it is working with the natural metabolism and not forcing a functional change in three days that won’t last.”
The Avogen Intimate Capsules exemplifies that. The home care instructions are to insert one capsule in the evening, every evening for about six weeks – or 40 capsules. At some point along the way in those first six weeks the consumer will note a moisturizing change and at that point, may reduce frequency of application to once or twice per week for most.
“Avogen Intimate Capsules are an outstanding, exceptional value,” says Shonda Chase, R.N. of Revive Wellness Centers in Palm Springs and Torrance, California. “After the first reset phase you have resolved a huge quality of life issue, for a few dollars a month.”
Dr. Wu concurs. “When we concluded the clinical study we had the test subjects ask to buy the product and that tells me as much as anything about its worth. So, it is really refreshing to hear that cost to the consumer for a valuable product will not be the limiting factor for a change.”