Vulvovaginal atrophy in the peri- and post-menopause: relevance and impact on quality of life

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Vulvovaginal atrophy (VVA) in peri- and postmenopause is recognized as a common cause of morbidity in women and a decrease in their quality of life [1]. In 2014, VVA was included in the broader concept of "genitourinary menopausal syndrome" (GUMS), which will combine a broader group of symptoms of urogenital tract lesions that develop during the period of natural extinction of ovarian hormonal activity [2]. However, the use of the term "vulvovaginal atrophy" is still common in the literature (domestic and foreign), and in the everyday vocabulary of doctors.
Genitourinary menopausal syndrome (GUMS) refers to a symptom complex that is associated with a state of hypoestrogenism and a decrease in other sex steroids. This syndrome includes changes in the vulva, vagina, perineum, urethra, and bladder [3].
The development of clinical and physiological signs specific to HUMS is associated with progressive atrophy of the urogenital tract epithelium, changes in subepithelial structures, and/or imbalance of the pelvic floor muscles. The most common symptoms of HUMS are signs of VVA — vaginal dryness, dyspareunia, burning, and itching — and dysuric disorders (urgency to urinate, urinary incontinence, and others) [3].
HUMS dramatically reduces the quality of life in menopause and, unlike vasomotor symptoms that disappear with time, progresses in the absence of treatment, leading to intractable anatomical changes. Despite the pronounced effect of VVA symptoms on social activity, work capacity, mood, and sexual function, women associate their condition with the natural aging process of the body and do not go to the doctor with the corresponding complaints [4–7]. In addition, even when therapy is prescribed, less than half of the patients comply with the prescribed therapy regimen. In this regard, HUMS should be considered as an underestimated condition in practical medicine, the timely diagnosis and treatment of which is difficult [7].
Material and methods
We searched the CochraneLibrary, PubMed, Science Direct, ELibrary databases for the keywords vulvovaginal atrophy, genitourinary syndrome of menopause, quality of life, epidemiology/epidemiology, postmenopausal age 2012–2022.
According to various sources, VVA symptoms are recorded in 15–19% of perimenopausal women and 40–80% (according to some reports, up to 90%) in postmenopausal women [3, 8]. VVA symptoms most frequently include vaginal dryness (27–70%), dyspareunia (33–41%), burning and itching in the vaginal vestibule (18%), and increased susceptibility to genital tract infections [6, 9]. These symptoms significantly reduce health indicators, negatively affect the overall quality of life, labor, social and sexual activity. 41% of women aged 50–79 years have at least one of the symptoms of VVA. The prevalence of dysuric disorders (urgent urge to urinate, urinary incontinence) and their severity depend on the duration of postmenopause, while the frequency increases from 15.5% (with a duration of menopause up to 5 years) to 41.4% (20 years or more) [3].
Nappi RE et al. conducted an epidemiological study (n=2160; postmenopausal women) to determine the prevalence of urogenital atrophy. According to the questionnaire, severe symptoms of vaginal atrophy and vulvar atrophy were experienced by 66% and 30% of respondents, respectively, but physical examination revealed signs of VVA in 90% of participants [8].
Cagnacci A et al analyzed the frequency of complaints and the prevalence of objective signs of HUMS, stratified by years since the onset of menopause (n=913) [10]. At 1 year after menopause, the prevalence of vaginal dryness was 62 to 67%, dyspareunia 67.5%, pruritus 40%, burning 48%, and dysuria 15%. A few years later, the frequency of vaginal dryness and dysuria was higher (85% and 30%, respectively), and itching and burning - 50% and 52%, respectively; dyspareunia - 75% after 6 years, and after a few more years from menopause, this figure decreased to about 41%. With regard to objective signs, the following data were obtained: 1 year after menopause, an increase in pH was confirmed in 78% of the examined; pallor of the mucous membrane, thinning of the folds and objective dryness of the vagina - in 60–62%; fragility of the mucous membrane - in 35%; the presence of petechiae - 15-20%. The prevalence of all objective signs progressively increased every year after menopause, reaching 90% in pH (greater than 5), mucosal pallor, and wrinkle thinning; 80% - by the fragility of the mucous membrane; 51% - by the presence of petechiae. There was no strong association between signs and symptoms other than subjective and objective symptoms of vaginal dryness (sensitivity 0.96; specificity 0.82) [10].
According to Selvi I et al. (n=433; age 43–75 years), the most common symptoms of HUMS were vaginal dryness (66.2%), decreasedlubrication (55.3%), urge to urinate (54.8%), urinary incontinence (39.2%). The study group had a high proportion of moderate to severe forms of all types of urinary incontinence, while the number of patients who had previously visited health care workers about their symptoms was low (52.8%). The authors also noted a decrease in quality of life indicators in psychosocial and sexual aspects [11]. Despite the high medical and socioeconomic significance of issues related to VVA, a critically small part of those who need it receive treatment for this condition [1]. The authors of the Women's EMPOWER study found that only 7% of women 45-90 years old (mean age 58 years, n=1858) are currently using prescribed TVA therapy (topical estrogen therapy or oral selective estrogen receptor modulators). However, it is not only a matter of non-compliance of patients: according to the survey data, only 18% of respondents were previously prescribed VVA treatment, and the majority (81%) did not know about the modern possibilities of VVA therapy or did not consider their condition to be a disease. Never took medication for HUMS or discussed their symptoms with a healthcare professional (72%), one in four (25%) were forced to self-medicate and use over-the-counter drugs, and 50% never used any treatment measures [1]. According to another survey, 56% of respondents discussed the symptoms of HUMS with a doctor, but only 40% used topical treatment (mainly over-the-counter drugs) [5, 12]. As a rule, women do not want to discuss their delicate problem with a doctor, because they are confident in the physiology of their condition, consider signs of VVA to be a natural part of aging that they will have to come to terms with. Respondents reported that discussion of their urogenital problems with a health worker began only after the women themselves actively complained or based on the results of a questionnaire before admission (85%) [1]. The authors of the Women's EMPOWER survey concluded that in real clinical practice VVA remains insufficiently recognized, the frequency of prescribing therapy is extremely low, despite numerous clinical guidelines and proposed methods. The gap in communication between healthcare professionals and peri- and postmenopausal patients is still widespread [1]. Thus, according to surveys of doctors, 62% of them discuss VVA symptoms with postmenopausal women, but they themselves initiated the conversation only in 7–10% of cases [6]. It may also be due to the embarrassment of medical professionals or their belief that this is a normal manifestation of aging [4, 5]. Such a catastrophic discrepancy between the high prevalence and rare clinical diagnosis of VVA entails a severe progressive course of VVA and a significant deterioration in the quality of life of patients [13-16]. Over the past decade, many studies have been conducted, mainly surveys, in order to obtain more complete information about the impact VVA on the modern population of postmenopausal women. The results of these studies have shown that VVA symptoms have a global negative impact on sexual health. In a survey of 94,000 women aged 50–79 years, 52% reported having sexual relations during the year [12], but in patients with VVA, libido is reduced, since urogenital symptoms significantly affect the readiness for intimacy (62%) , the ability to enjoy sexual intercourse (72%) and experience libido (66%). Other surveys show that many postmenopausal women "avoid intimacy" (54-77%) and "have lost interest in sex" (71-91%) [6, 7, 9]. In a 2013 survey of more than 3,000 American women up to 85% of respondents noted the negative impact of VVA symptoms on sexual relationships, 47% reported that relationships with a partner suffer, and 27% that VVA negatively affects overall enjoyment of life [5]. Partners of women with VVA also noted the adverse emotional and physical impact of the partner's condition on relationships. In an online survey of 4100 men and 4100 women aged 55–65 years, 52% to 78% of men and 58% to 64% of women reported a negative impact of vulvovaginal symptoms on intimacy, libido, and sexual pain [17].DiBonaventura et al. (2015) analyzed data from the International Women's Health Survey, an online cross-sectional survey of women (n=7068) aged 40-75 in the US and Europe. The analysis included all postmenopausal respondents aged 40–75 years. The severity of VVA symptoms (absent, mild, moderate, severe) was assessed using a menopause rating scale [18]. The prevalence of VVA symptoms ranged from 40% (Germany) to 54.42% (Spain), with every second respondent assessing their symptoms as moderate or severe. The authors found that the decline in quality of life associated with moderate to severe symptoms of VVA is comparable to that of other serious conditions such as arthritis, chronic obstructive pulmonary disease, asthma, and irritable bowel syndrome [18]. VVA does not only affect quality of life , sexual health and couple relationships, but is also associated with an increased risk of depression and anxiety in postmenopausal women [19]. Moyneur E et al. (2020) assessed the relationship between VVA and depression, major depressive disorder and anxiety in their grandiose study [19]. The study included 125,889 women with VVA and 376,057 women without signs of HUMS (age 45 and older, mean 60.7 years). The prevalence of depression, major depressive disorder, and anxiety was 1.26, 1.33, and 1.47 times higher among women with VVA than in controls (23.9% vs. 18.9%, 6.3% vs. 4 .7%, 16.6% versus 11.3%, respectively). Interestingly, the largest difference in performance was at the younger age of the participants. After adjusting for the influence of other signs of menopause (insomnia, vasomotor symptoms, dysuria, and estrogen therapy), VVA remained a significant factor (depression — OR=1.23, major depressive disorder OR=1.22, anxiety OR=1.39; p< 0.0001) [19]. According to the REVIVE study, doctors prescribe hormonal therapy for HUMS — local (23%) and systemic MHT (18% of women). When using topical estrogen therapy, from 33% to 51% of women are satisfied and very satisfied with their effectiveness, but less than half of the patients adhered to the recommended therapy regimen. Women refused local hormone therapy, as a rule, because of the fear of systemic absorption, inconvenience when using creams, the need to reuse the applicator, and unwillingness to stain clothes [6]. According to the questionnaire, for urogenital disorders, the most common methods of treatment/self-treatment were over-the-counter, non-hormonal, topical vaginal preparations; and 32% of postmenopausal women had not previously used any treatment. The main reasons for refusal of prescribed treatment were insufficient severity of symptoms (18%); relief after initiation of therapy (17%). Approximately 45% were satisfied with the treatment. Fear of hormones was common in postmenopausal women using prescription vaginal medications [6]. Thus, the symptoms of HUMS entail a significant deterioration in quality of life, and therefore it is necessary to improve the management of this syndrome in order to mitigate its impact on quality of life of postmenopausal patients [18]. However, when managing patients with HUMS, it is necessary to take into account the lack of compliance of women, their prejudices regarding hormone therapy (even when using topical forms), and low awareness of the possibility of stopping painful symptoms with modern means. Negligence to see a doctor, lack of clear information in women about the available methods of VVA treatment, misconceptions (underestimation of the condition or negative perception of estrogen therapy), threaten the optimization of VVA management and its effective treatment. It is important to note that, despite the proven positive effect of local estrogen therapy in VVA (level of evidence 1A) [3, 20], it is contraindicated in some patients, and therefore it is necessary to search and study the effectiveness and safety of modern alternative non-hormonal and hardware methods. Modern effective and a safe method of HUMS treatment should be minimally invasive with high efficiency, obvious not only for doctors (by anatomical, histological and other signs), but also for the patients themselves. The positive effect of microablative remodeling laser therapy using carbon dioxide in gynecology is described: an improvement tissue regeneration using a CO2 laser, activation of fibroblasts, which promotes the formation of new collagen and elastin fibers, regeneration of the extracellular matrix and vascular proliferation [21, 22]. Evidence of the efficacy and safety of such therapy in high-quality studies is needed.

About the authors

Mekan R. Orazov

People’s Friendship University of Russia (RUDN University)

Author for correspondence.
Email: omekan@mail.ru
ORCID iD: 0000-0002-1767-5536

D. Sci. (Med.), Prof.

Russian Federation, Moscow

Elena S. Silantyeva

Clinical Hospital “Lapino-1” “Mother and Child”

Email: essdoktor@yandex.ru
ORCID iD: 0000-0002-7667-3231

D. Sci. (Med.)

Russian Federation, Moscow

Viktor E. Radzinsky

People’s Friendship University of Russia (RUDN University)

Email: radzinsky@mail.ru
ORCID iD: 0000-0003-4956-0466

D. Sci. (Med.), Prof., Corr. Memb. RAS

Russian Federation, Moscow

Liudmila M. Mikhaleva

Avtsyn Research Institute of Human Morphology of Petrovsky National Research Centre of Surgery

Email: mikhalevalm@yandex.ru
ORCID iD: 0000-0003-2052-914X

D. Sci. (Med.), Prof., Corr. Memb. RAS

Russian Federation, Moscow

Elizaveta A. Khripach

Multidisciplinary Medical Center “DEKA Medical”

Email: elizaveta.ark@mail.ru
ORCID iD: 0000-0003-2895-1193

obstetrician-gynecologist

Russian Federation, Moscow

Evgeny D. Dolgov

People’s Friendship University of Russia (RUDN University)

Email: 1586dolgde@gmail.com
ORCID iD: 0000-0001-6709-5209

Clinical Resident

Russian Federation, Moscow

References

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