New developments in the management of vulvovaginal atrophy: a comprehensive overview.

INTRODUCTION: Proper recognition and individualized therapy of vulvovaginal atrophy (VVA) is paramount. AREAS COVERED: Assessment of VVA should be performed using several questionnaires in combination with wet mount microscopy to determine Vaginal Cell Maturation Index (VCMI) and infections. PubMed searches were carried out between 1 march 2022 and 15 October 2022.Low dose vaginal estriol seems safe, efficient, and could be used in patients with contraindications for steroid hormones such as women with a history of breast cancer, and should therefore be considered as first choice hormonal treatment, when non-hormonal treatments fail. New estrogens, androgens, and several Selective Estrogen Receptor Modulators (SERMs) are being developed and tested. Intravaginal Hyaluronic Acid (HA) or Vit D can help women who can't or don't want to use hormones. EXPERT OPINION: Proper treatment is not possible without a correct and full diagnosis, including microscopy of the vaginal fluid. Low dose vaginal estrogen treatment, especially with estriol, is very efficient and is preferred in most women with VVA. Oral ospemifene and vaginal dihydroepiandrosterone (DHEA) are now considered efficient and safe alternative therapies for VVA. More safety data are waited for several SERMs and for a newly introduced estrogen: estetrol (E4), although so far no major side effects were seen from these drugs. Indications for laser treatments are questionable.

Vaginal oxygen plus hyaluronic acid on genito-urinary symptoms of breast cancer survivors.

OBJECTIVES: This study aimed to evaluate the efficacy of vaginal oxygen and hyaluronic acid on genito-urinary symptoms of breast cancer survivors. METHODS: Patients were enrolled at the Menopause Outpatient Clinic of a university hospital. Breast cancer patients in a stable relationship, suffering from vaginal atrophy (VA) consequent to hypoestrogenism, were included. Natural oxygen was introduced into the vagina for 15 min, coupled in the last 5 min with a 2% solution of hyaluronic acid. Treatment was repeated five times, every 15 days. RESULTS: Out of the 40 breast cancer patients enrolled, 65% had no sexual intercourse due to pain. During treatment, the Vaginal Health Index Score gradually improved from 9.5 ± 2.2 to 16.8 ± 2.8 (p < 0.001), the visual analog scale score for dyspareunia decreased from 8.9 ± 1.3 to 3.4 ± 2.1 (p < 0.001) and the Female Sexual Function Index increased from 8.6 ± 6.3 to 15.2 ± 8.1 (p < 0.001). At the end of treatment, only 15% women (p = 0.001 vs. pretreatment) had no intercourse due to pain. Benefits remained 30 days after last treatment. CONCLUSION: Vaginal oxygenation coupled with hyaluronic acid every 15 days improves VA, sexuality and urinary symptoms of breast cancer patients. Beside data confirmation, additional studies are needed to determine the best interval between treatments, the optimal length of treatment and the long-term duration of the benefits.

Knowledge of genito-urinary syndrome of menopause among Italian gynecologists: the DIADEM survey.

OBJECTIVE: The objective of this study was to present an updated picture of the knowledge and attitudes of Italian gynecologists with regard to the genitourinary syndrome of menopause (GSM). STUDY DESIGN: An anonymous survey was sent via electronic mail to 3892 gynecologists. The survey consisted of 32 multiple-choice questions divided into four different areas: 1. general demographics of the respondents; 2. knowledge of GSM; 3. most frequently prescribed therapies; and 4. perception of patient compliance and satisfaction with current therapeutic options. MAIN OUTCOME MEASURES: Knowledge of vulvo-vaginal atrophy (VVA) and attitudes of the gynecologists to its management. RESULTS: Three hundred and seventy-four out of 3892 invited Italian gynecologists replied to the survey (response rate 9.7 %). Most (84 %) had a good knowledge of GSM and 74 % reported that they investigated it during clinic visits, but most of them underestimated its prevalence. The most frequently prescribed treatment was topical hormonal therapy (60 %), followed by vaginal moisturizers and lubricants (16 %), ospemifene (12 %) and systemic hormone therapy (12 %). According to the clinical experience of respondents, the most effective therapy is local hormonal therapy (36 %), followed by ospemifene (30 %). According to respondents, less than 50 % of patients continue therapy after 12 months, due to the discomfort in vaginal application, the cost of oral therapies and the fear of possible side-effects. CONCLUSIONS: With the limitation of the low response rate, this study suggests that although Italian gynecologists who answered the survey had some knowledge of GSM, they underestimated its prevalence, did not know its most bothersome symptoms and had inadequate knowledge of the efficacy of treatments, patient compliance and satisfaction.

First Use of Thermal Stabilized Hyaluronic Acid Injection in One-Year Follow-Up Patients with Genitourinary Syndrome.

OBJECTIVE: Evaluation of the impact of hyaluronan hybrid cooperative complex (HCC) injections in premenopausal and postmenopausal Italian women affected by vulvar-vaginal atrophy (VVA), one of the symptoms of genitourinary syndrome (GS), on self-reported quality-of-life, vaginal symptoms, and sexual activity, as well as treatment side-effects. METHODS: We surveyed a sample of 26 women affected by VVA with follow-up at 6 and 12 months. Deep intradermal injections of HCC were delivered at 1-month intervals. Evaluation of the treatment impacting the VVA patients was assessed by three international validated questionnaires (Visual Analogic Scale, VAS; health-related quality-of-life test, SF12; Female Sexual Function Index, FSFI). The statistically significant differences between pre- and after-treatment responses have been assessed by Wilcoxon signed-rank test and repeated measures ANOVA test. RESULTS: At 6-12-month follow-up, general quality-of-life (SF12) did not show any significant improvement. On the contrary, VVA patients showed significant improvements of genital symptoms (VAS) and sexual function (FSFI). Global FSFI score increased by 58% and evidenced important satisfaction (P≤0.05). CONCLUSION: Vestibular HCC injection is an office, safe, fast, not expensive, and reproducible procedure effective in vulvar-vaginal atrophy. This study can be used as a pilot for future trials.

Lower urinary tract symptoms and their relation to vaginal atrophy in women across the menopausal age span. Results from the ANGEL multicentre observational study.

OBJECTIVES: To evaluate the relation between lower urinary tract symptoms (LUTS) and vaginal atrophy (VA) in 518 women across the menopausal age span (40-55 years of age). STUDY DESIGN: Multicentre, cross-sectional study. MAIN OUTCOME MEASURES: VA was evaluated by the contemporaneous presence of a pH > 5, vaginal dryness and at least one objective sign of VA (mucosal pallor, dryness, thinning, fragility or with petechiae)., LUTS were evaluated by the Urogenital Distress Inventory (UDI-6). Sexuality was evaluated by the Female Sexual Function Index (FSFI). RESULTS: Women were categorized by age: group 1, 40-45 years; group 2, 46-48 years; group 3, 49-51 years; and group 4, 52-55 years. Similar rates of recurrent urinary infection (RUI) were present in different age groups. RUI rate was related to VA (OR 1.703, 95 %CI 1.037, 2.799) and dyspareunia (OR 2.060, 95 %CI 1.199, 3.539). The rates of LUTS were also similar in the different age groups or in the presence of VA. The LUTS rate was related to dyspareunia (OR 1.971, 95 %CI 1.020, 3.808). Distress from LUTS was similar among different age groups and in the presence of VA. It was related to RUI (CR 7.187, 95 %CI 3.532, 10.841; p < 0.0001) and being an ex-smoker (CR 5.189, 95 %CI 1.425. 6.952; p < 0.007), and was inversely related to FSFI score (CR -0.314, 95 %CI -0.478, -0.149; p < 0.0002), CONCLUSIONS: In women across the menopausal age span, RUI, but not LUTS, is related to VA. The presence of LUTS is related to dyspareunia, and distress from LUTS is inversely related to sexuality. These results obtained in women across the menopausal age span are not applicable to older postmenopausal women.

The results of new low dose fractional CO2 Laser - A prospective clinical study in France.

OBJECTIVES: The aim of this research was to assess the efficacy of the new generation micro-fractional CO2 laser low dose energy (Aphrodite, BH LASER, France) in the treatment of genitourinary syndrome. MATERIALS AND METHODS: This prospective interventional clinical study, included a total of 25 menopausal symptomatic patients and 25 non-menopausal symptomatic patients having symptoms of vulvovaginal atrophy. There were only two laser sessions spaced at 6 weeks. It was evaluated the Female Sexual Function Index (FSFI) and the QoL at baseline, 3 and 6 months. RESULTS: The study showed a significant improvement in both groups when assessing FSFI scores at 3- and 6-months follow-up compared to baseline (p<0.05) and secondary it was observed a significant initial improvement of QoL score at 3 and 6 months (p<0.05), compared to baseline. There were no important adverse events registered during the study period. CONCLUSIONS: The new micro-fractionated laser device with low dose energy - 18W, demonstrated significant improvement of genitourinary syndrome in both non-menopausal and post-menopausal women with no important adverse event.

Addressing Vulvovaginal Atrophy (VVA)/Genitourinary Syndrome of Menopause (GSM) for Healthy Aging in Women.

Vaginal health is an essential component of active and healthy aging in women at midlife and beyond. As a consequence of hormonal deprivation and senescence, the anatomy and function of urogenital tissues are significantly affected and vulvovaginal atrophy (VVA) may occur. In a high proportion of postmenopausal women, progressive and chronic VVA symptoms have a strong impact on sexual function and quality of life. The new definition of genitourinary syndrome of menopause (GSM) comprises genital symptoms (dryness, burning, itching, irritation, bleeding), sexual symptoms (dyspareunia and other sexual dysfunctions) and urinary symptoms (dysuria, frequency, urgency, recurrent urinary infections). Many variables (age, sexual activity and partnership status) influence the clinical impact VVA/GSM symptoms and attitudes of elderly women to consult for receiving effective treatments. Psychosocial factors play a critical role in sexual functioning, but the integrity of the urogenital system is as well important affecting many domains of postmenopausal women's health, including sexual function. Several international surveys have extensively documented the need to improve VVA/GSM management because of the strong impact on women's daily life and on couple's intimacy. Health care providers (HCPs) need to be proactive in the early recognition of VVA/GSM in order to preserve urogenital and sexual longevity, by using hormonal and non-hormonal strategies. The clinical diagnosis is based on genital examination to identify objective signs and on the use of subjective scales to rate most bothersome symptoms (MBS), especially vaginal dryness. Recent studies point to the importance of addressing VVA/GSM as a potential early marker of poor general health in analogy with vasomotor symptoms. Therefore, a standard of VVA/GSM care in elderly women is desirable to enhance physical, emotional and mental well-being.

Pharmacotherapy for the treatment of vaginal atrophy.

INTRODUCTION: Despite its frequency, recognition and therapy of vulvovaginal atrophy (VVA) remain suboptimal. Wet mount microscopy, or vaginal pH as a proxy, allows VVA diagnosis in menopause, but also in young contraception users, after breast cancer, or postpartum. Intravaginal low dose estrogen product is the main therapy. Ultra-low-dose vaginal estriol is safe and sufficient in most cases, even in breast cancer patients, while hyaluronic acid can help women who cannot or do not want to use hormones. AREAS COVERED: The authors provide an overview of the current pharmaceutical treatment for vulvovaginal atrophy and provide their expert opinions on its future treatment. EXPERT OPINION: The basis of good treatment is a correct and complete diagnosis, using a microscope to study the maturity index of the vaginal fluid. Minimal dose of estriol intravaginally with or without lactobacilli is elegant, cheap and can safely be used after breast cancer and history of thromboembolic disease. Laser therapy requires validation and safety data, as is can potentially cause vaginal fibrosis and stenosis, and safer and cheaper alternatives are available.

BMS - Consensus statement.

Urogenital atrophy is more common than it would first appear and women do not always seek advice and guidance. Confusion still exists between systemic hormone replacement therapy (HRT) and local estrogen preparations but new treatment modalities have emerged that extend the range of options beyond lubricants, moisturisers and vaginal estrogen preparations.

Why are there no FDA-approved treatments for female sexual dysfunction?

After many years of research, female sexual dysfunction (FSD) is still an unmet clinical need because no FDA-approved treatments are available for women. The bio-psychosocial model is essential to understand whether a candidate drug induces a meaningful effect over placebo on sexual symptoms with a significant impact on women's quality of life and partnership. Vasoactive agents, hormone therapy and psychoactive drugs have been investigated. Randomized placebo-controlled trials showing efficacy and safety, however, did not convince the FDA to approve either transdermal testosterone patch in postmenopausal women or the serotoninergic agent flibanserin in premenopausal women, for the treatment of hypoactive sexual desire disorder. The process of balancing efficacy and safety of a chronic treatment for a non-life threatening condition, such as FSD, is very difficult in women of any age, but there is some hope that the gender gap in sexual medicine will soon come to an end. Insightful research centered on women's needs and expectations and the availability of novel compounds, tested according to the new DSM-5 diagnostic criteria, will finally lead medical regulatory agencies to approve an effective and safe pharmacotherapy for FSD.