What are the difficulties for a gynecologist associated with the treatment of urogenital syndrome?
The first thing worth noting is that this symptom complex or syndrome has a very complex pathogenesis. Today, many molecular genetic aspects are being studied, but for practical medicine, the results of these studies do not change much and the range of drugs with which we treat is very limited. Unfortunately, all therapy is symptomatic, there is no pathogenetic therapy for OAB yet, and our main task is to make the patient tolerate the treatment as best as possible. We cannot cure an overactive bladder, it is clear that this treatment is practically lifelong. it is necessary to find some middle ground so that there are fewer complications, remissions are longer, and so on.
How much has this problem been studied and how long has it been the subject of close study?
Urogenital atrophy, I think, has existed since a woman’s life span began to exceed the age of menopause. This was not always the case, nature acted as follows: the woman stopped giving birth, somewhere close to menopause, and nature removed this woman from the population. And when life expectancy increased, symptoms appeared that we today call menopausal, including urogenital atrophy. keen interest in this problem appeared only in the late 70s – early 80s. This is due to the fact that urinary incontinence has been associated with aging and estrogen deficiency. in addition, it was in the early 80s that estriol appeared, that is, that hormonal drug that turned the ideas of gynecologists about urogenital atrophy. although gynecologists began to seriously deal with this issue only at the very end of the 80s – early 90s. the terminology has changed over the years: most often they talked about senile colpitis, although there is usually no inflammation in this situation. they said and say “atrophic colpitis”, “senile” and “atrophic” urethritis, “trigonitis”, “urethral syndrome”. for today the most capacious terms are “urogenital atrophy” and “urogenital disorders”. in MCB10 there is only one position that reflects the situation: N95.2, “postmenopausal atrophic vaginitis”.
What is the reason for such terminological discrepancies?
Today the terminology is changing, and gynecologists know about it. I would not say that it has changed dramatically, this is just an attempt to change the terminology by our and international associations. The experts considered that the term “vulvovaginal atrophy”, which is very often used in the West, absolutely does not consider urinary disorders (they have been considered in our country for a very long time), and suggested moving to the term “genitourinary syndrome.” why is the terminology changing? the term “atrophy” refers to the ultimate loss of functionality. in addition, the word “vagina” is hardly accepted in the media. and “vulvovaginal atrophy,” as I said, does not cover urinary disorders: urgency or urgency, dysuria, recurrent infections. gynecological symptoms appear first, but I always say that they just feel faster: a woman first of all pays attention to gynecological symptoms.
Whatever the name of this disorder, let’s see what it is, in the first place, dangerous.
Let’s start with what urogenital disorders are. it is a complex of vaginal and urinary symptoms, the development of which is a complication of atrophic processes in estrogen-dependent tissues and structures of the lower third of the urinary tract. at the same time, atrophic changes in the urogenital tract are one of the main “markers” of estrogen deficiency. according to our own data, in almost 20% of patients, they appear simultaneously with vivid manifestations of climacteric syndrome. a woman pays attention to hot flashes and sweating more quickly, they interfere with her very much, and this is noticeable to others. But urogenital atrophy develops stealthily, does not immediately begin to interfere, and attention is paid to this symptom, mainly after 5 years or more, when it no longer passes in a mild, but in a severe form and greatly reduces the quality of life.
How high is the prevalence of the problem in the general population and are there any groups of patients requiring special treatment?
The incidence of urogenital syndrome ranges from 13% in perimenopause to 60% in postmenopausal women lasting more than 5 years. the highest frequency and severity are observed in women who smoke and in patients receiving treatment for breast cancer. this is a special group of patients, here we are bound hand and foot. even local estrogens are not always allowed to be prescribed by oncologists, but this point is now being revised in the international community, and it is believed that local drugs should not have the same contraindications as systemic ones. thus, oncological diseases, including breast cancer, should not be considered a contraindication in any way, because local estrogens do not have a systemic effect.
What manifestations of the syndrome do gynecologists most often face?
To begin with, these are vaginal symptoms, including dryness and itching in the vagina, dyspareunia (painful sensations during intercourse), recurrent vaginal discharge (but not of an infectious nature), prolapse of the vaginal walls, bleeding of the vaginal mucosa (this is due to the fact that with estrogen deficiency, blood flow begins to suffer) and sexual dysfunctions. the other side of the coin is the symptoms of cystourethral atrophy or urinary symptoms. here it is undesirable to use, for example, the concept of “atrophic cystitis”, there is no inflammation, these are symptoms associated with atrophy of the urothelium, which becomes extremely sensitive to the ingress of even a small amount of urine into the bladder. the following symptoms are important here: frequent day and night urination, dysuria, recurrent urinary tract infections, cystalgia, urge to urinate, urgent, stressful and mixed urinary incontinence. if these symptoms appear along with the last menstruation, that is, when a woman enters menopause or a few years after, then we attribute them to urinary manifestations of urogenital atrophy, and if in younger women (most often after childbirth), we do not talk about it , but it is known that the severity of symptoms is significantly aggravated in postmenopausal women, if the patient has not previously thought about treatment.
Are these two groups of symptoms more likely to appear separately or together?
A third of postmenopausal patients may have isolated manifestations of genitourinary syndrome, but according to recent data, 65-100% of women have symptoms of vaginal and cystourethral atrophy combined. isolated symptoms, we can, of course, treat without systemic menopausal hormone therapy, but unfortunately, two thirds of patients and more combine urogenital atrophy and menopausal syndrome with osteoporosis and a high risk of cardiovascular disease. then we have to think about systemic therapy or its combination with local drugs.
Please tell us a little about the diagnosis of the disorder.
First, you need to ask the patient simple questions: how many times a day does she urinate? if the patient answers “10–12”, the corresponding signal is triggered in our head. the next question is: how many times do you get up at night? next to him: if you want to go to the toilet, can you finish what you were doing: for example, cook soup or finish typing some text? if a woman says “no, I have to give up everything and run to the toilet,” it means that this patient probably has an GMF, and we must further examine her. urination diaries help well, but often our patients do not like to write down a lot. then you have to ask additional questions in order to get a clear quantitative assessment of this symptom complex.
We have already found out that the problem itself has existed for a long time and, possibly, is evolutionarily determined. And how long have there been drugs that can alleviate its manifestations?
The similarity of the vaginal epithelium and the urothelium, as well as the ability of the urothelium to synthesize glycogen, was described as early as 1947. in the next year, 1948, the sensitivity of the urothelium to estrogen was described, and in 1957 the reaction of the urothelium to the introduction of estrogens in postmenopausal women was shown. that is, probably even earlier it was necessary to combine the views of urologists and gynecologists on the problem. in those days, unfortunately, there were no drugs that could be used for a very long time to treat any problems in the urogenital tract associated with atrophic changes. pathogenesis is associated with estrogen deficiency, ischemia develops first in all structures of the urogenital tract, only after a few years the proliferation of urothelium and vaginal epithelium decreases. collagen structures of the urogenital tract and muscle structures of the urethral tract suffer, symptoms of vaginal and cystourethral atrophy, stress, urgent and mixed urinary incontinence develop. Professor Peter Smith in 1990 for the discovery of receptors in the urogenital tract in women received the Nobel Prize, he showed quantitatively how many receptors are in various structures of the urogenital tract. if we compare with the uterus, where there are 100% of them, then 60% are localized in the vagina, and 40% in the urethra and bladder. in the muscles of the pelvic floor and collagen structures – only 25%, so the muscles need not only drugs and menopausal hormone therapy, but also mandatory training of the pelvic floor muscles, behavioral therapy.
It is also worth mentioning the localization of sex hormone receptors in the urogenital tract. if there are both a and estrogen receptors in the vagina, androgen receptors dominate in the perineum and the lower third of the vagina, in the bladder and urethra – in estrogen receptors, so these structures may respond a little later to the effects of estrogens than, for example, the walls of the vagina. in order to completely restore the structures of the urogenital tract, hormone therapy should be used at the first stage for at least three months. Today, new forms of estrogen receptors have been studied and found in vaginal biopsies and, accordingly, other drugs are being considered, in addition to estrogen replacement hormone therapy, this is also very interesting. There is a lot of talk about selective estrogen receptor modulators.
For example, the first course was completed, the patient was regularly treated for three months. what happened during this time?
After three months, under the influence of estrogens, blood flow is restored, and this is probably the main result of therapy. the processes of proliferation in the urothelium and vaginal epithelium are resumed, and the population of lactobacilli is restored, the PH level normalizes the contractile activity of the myofibrils of the vaginal wall, detrusor and urethra, improves the innervation of the urogenital tract. in addition, the synthesis of a and b-adrenergic receptors, as well as muscarinic receptors, increases, sensitivity to norepinephrine and acetylcholine is restored. the elasticity of collagen is also improved due to the destruction of the old and the synthesis of the new. in addition, there is a significant effect on local immunity, which protects the woman from ascending infection and is completely estrogen-dependent.
What is the advantage of prescribing local estrogens today?
According to the results of a large-scale study undertaken, hormone therapy drugs with systemic effects in 20–45% of cases do not have a systemic effect on the symptoms of urogenital atrophy. non-drug therapy, in turn, is close to placebo in terms of effectiveness, but local forms of estrogens have minimal systemic effects and lead to regression of atrophic changes in the urogenital tract.
Can you single out the most effective of them?
A meta-analysis of 15 randomized trials involving 3,000 women shows that estriol remains the most effective and safest drug, since it has practically no systemic absorption, and this is very important for our breast cancer patients. an example of a formulation containing estriol may be ovestin or its analogue ovipol in the form of suppositories or cream.
Have there been comparative studies of the effectiveness of combined and mono-therapy of GMP?
Our latest 2016 data indicate that both combination therapy and monotherapy with M-anticholinergics are effective against the symptoms of OAB. after 3 months of treatment, the frequency of pollakiuria decreases 8 times, nocturia – 4.5 times, urgency – 4.4 times, and urgent urinary incontinence – 3 times. At the same time, an important advantage of combined therapy is a more pronounced decrease in the main symptom of OAB – urgency (by 1.7 times) and a decrease in the frequency of relapses by 2.5 times. that is, a woman has the opportunity, without M-anticholinergic therapy, but only with local estrogens, to hold out until the next course two and a half times longer than with monotherapy.
Is it possible to identify risk factors for this disorder and somehow influence them?
According to Professor Yevgeny Leonidovich Vishnevsky, an overactive bladder is a chronic recurrent disease, which is based on ischemia and vascular stress. accordingly, the main risk factors here are inflammatory diseases (for example, recurrent cystitis), pregnancy, neurological diseases and, in fact, the climacteric period. if we take population data, we see that 20% of urinary disorders occur in women of reproductive age, although we are used to associating this problem with aging. we have conducted a large study on urinary disorders in pregnant women. it turned out that during pregnancy only 20% of patients do not have urinary disorders. most often, the symptoms are associated with the growth of the uterus, hormonal disorders, – there can be many reasons. Having studied the structure of disorders, we saw that the overactive bladder dominates. until recently, this was considered practically the norm. then we looked at what happens after childbirth. comparing the picture during pregnancy and 4 months after delivery, we saw that pregnancy is indeed a very high risk factor for urinary disorders. in most women, they do go away, but in 15.7% they remain. in most cases, these are symptoms of an OAB. thus, abnormalities caused by pregnancy can persist for the rest of your life. then they can pass for some time or worsen, but after menopause, persistent forms of urination disorders are already developing.
What difficulties, in addition to the symptoms themselves, can patients face?
Unfortunately, not all drugs used in the treatment of OAB and urogenital syndrome are subsidized by the state. if in the west a woman, as a rule, pays only for hygiene products, and then only partially, then in our country the cost of medicines can be half of the average pension. when choosing a treatment, it should be borne in mind that drugs are not always well tolerated, are expensive, and it is necessary to find a doctor who will select the right therapy and will be able to select the Mholinolytic individually. some drugs allow you to manipulate the dosage, others do not, but the minimum effective dose is always chosen so that the woman can receive therapy for as long as possible. For example, the appearance on our market of “urotol” of the generic tolterodine has become very important. “Urotol” is one of the most affordable drugs for our women. despite the large number of side effects of all drugs in this series, there is only one absolute contraindication – glaucoma.
How does such a medicine work?
In the mechanism of action, only one thing is important: while we are giving the drug, it blocks the action of acetylcholine on muscarinic receptors and prevents detrusor contraction. if you stop taking, all symptoms return. Until a drug has been developed that can cure an overactive bladder, “urotol” significantly reduces the amount of urination and episodes of urgent urinary incontinence. Another very important point: according to the recommendations of the International Menopause Association, the symptoms of vaginal atrophy are easily controlled by estrogens, and anti-muscarinic drugs in combination with local estrogens are the first-line therapy for women with OAB in menopause. however, neither systemic nor local hormonal therapy is prevention of stress urinary incontinence.
From your point of view, is the treatment of this disorder a task, first of all, for a gynecologist or urologist?
An overactive bladder is an absolutely interdisciplinary problem; it makes no sense to divide it between gynecologists and urologists. to whom the woman has come, from that she will be treated. in addition, the role of neurologists, traumatologists and general practitioners is important. the main point of treatment is the appointment of anticholinergics and menopausal hormone therapy. what it will be depends on the woman, but local estrogen therapy must be present here. as of today, this is not even disputed.