Vaginal Atrophy Research Articles

Microablative and non-ablative laser and radiofrequency treatment of genitourinary syndrome of menopause: A randomised controlled trial with four different energies.

An integrated drug delivery device for the localized treatment of the genitourinary syndrome of menopause.

Platelet-rich plasma in the management of vulvovaginal disorders: a systematic review.

A 51-year-old woman presented with two years of postmenopausal spotting, mainly postcoital. Although vaginal atrophy was considered, prior use of vaginal estrogen at another center had not improved her symptoms. She had a history of persistent human papillomavirus (HPV) 16 infection and abnormal cytology. Initial colposcopy showed CIN 1 but one year later, a biopsy revealed CIN 2, and loop electrosurgical excision procedure (LEEP) was performed with negative margins. At 6-month follow-up, HPV positivity and low-grade squamous intraepithelial lesion persisted, with CIN 2 on colposcopy. Despite being offered repeat LEEP, the patient opted for definitive surgery. Due to a family history of ovarian cancer, she also requested bilateral salpingo-oophorectomy. This case highlights an individualized approach to recurrent cervical dysplasia and postmenopausal bleeding. Despite long-term follow-up, cervical dysplasia persisted, necessitating surgical intervention. The procedure was completed laparoscopically without complications. Cervical stump excision is a rare but important option in patients experiencing persistent symptoms or premalignant lesions after subtotal hysterectomy (SH). This case highlights careful patient selection and thorough counseling regarding potential long-term risks, including bleeding, dysplasia, and cervical malignancy, following SH.

We aimed to evaluate vaginal microbiota distribution before and after laser therapy for gynecologic patients with stress urinary incontinence (SUI) and genitourinary syndrome of menopause (GSM). Fifty patients undergoing CO₂ vaginal laser treatment were enrolled. The primary outcomes included UDI-6, IIQ-7, OABSS, and VSQ-21 scores before and at 1, 2, and 3 months after laser treatment, as well as vaginal microbiota diversity before and 1 month after laser treatment. UDI-6, IIQ-7, OABSS, and VSQ-21 scores for patients who received CO₂ laser therapy all showed significant improvement at 1, 2, and 3 months post-treatment. Vaginal pH showed no significant change after laser treatment. Overall, 91 samples were successfully sequenced. Alpha diversity showed significant differences in the menopause (p = 0.034) and GSM (p = 0.004) groups, but not between pre- and post-laser treatment samples. PERMANOVA revealed differences in microbiota composition associated with menopause (p = 0.009) and SUI (p = 0.026). Beta diversity analysis showed no significant treatment effect due to high inter-individual variability. The six most abundant vaginal bacterial genera included Lactobacillus (40.4%), Gardnerella (8.4%), Prevotella (7.4%), Escherichia-Shigella (6.0%), Streptococcus (5.6%), and Bifidobacterium (3.2%), with changes in Lactobacillus dominance observed in some patients post-treatment. Network analysis revealed that Gardnerella disappeared post-laser treatment, as Lactobacillus increased in abundance. CO₂ laser treatment may improve SUI and GSM, and be associated with shifts in microbiota.

Disclosure: Y.D. Moura: None. J. Panzan: None. C.A. dos Reis: None. S.S. de Afonseca: None. J.M. Ferreira: None. J.A. de Oliveira: None. D.D. Miguel: None. V.A. Pinheiro: None. R.P. Bolzani: None. D. Rodrigues: None. G. Bifulco Soares: None. M.G. Pereira: None. L.H. Graciolli: None.Introduction: The Genitourinary Syndrome of Menopause (GSM) encompasses a set of symptoms resulting from decreased estrogen and other steroid hormones, affecting up to 80% of postmenopausal women. Common symptoms include dyspareunia, dysuria, and vaginal dryness, which significantly impact quality of life. New therapies such as microablative radiofrequency (RFMA) and CO₂ laser have emerged as promising alternatives to traditional hormonal treatments. Methods: A systematic review was conducted using the PubMed, Embase and Cochrane databases, selecting randomized clinical trials from the last five years. Three RCTs were included, analyzing a total of 156 postmenopausal women. Interventions compared RFMA, topical promestriene, and fractional CO₂ laser, with outcomes assessed through the Vaginal Health Index (VHI) and the Female Sexual Function Index (FSFI). All studies adhered to histological safety protocols, including pre- and post-treatment biopsies in some cohorts. Results: All three interventions resulted in significant improvement in GSM symptoms and VHI scores, with no adverse histological findings. RFMA showed the most substantial improvements in sexual function, with one trial reporting a 146.1% increase in FSFI total score after 4 months. Improvements in desire (+1.32), arousal (+2.37), and orgasm (+2.8) domains were significant only in the RFMA group (p < 0.01). In breast cancer survivors under adjuvant endocrine therapy, RFMA and CO₂ laser were as effective as promestriene, with no clinical or histological damage reported. These findings highlight the efficacy and safety of RFMA, especially for women contraindicated for hormonal therapy. Conclusion: RFMA is a safe and effective alternative for managing GSM in postmenopausal women, particularly those with contraindications to hormone therapy. Its superior outcomes in sexual function domains and absence of tissue damage suggest its potential as a first-line non-hormonal therapy. Further long-term studies are warranted to validate these results and assess durability over time.Presentation: Monday, July 14, 2025

Disclosure: C. Dos Santos: None. A. Dominguez-Bali: None. C. Dominguez-Bali: None. A. Perera: None. A. Zarrinidarban: None. S. Verma: None. S. Escobar: None.An increased incidence of abnormal Papanicolaou (PAP) smears has been observed in women over 40 years of age who have no prior history of cervical abnormalities. Many of these women are in long-term monogamous relationships or report fewer than three lifetime sexual partners. Pathological studies have shown that cervical and vaginal atrophy due to hypoestrogenism can produce cellular changes that mimic dysplasia, suggesting that many of these abnormal findings may be misclassified. Despite undergoing multiple gynecologic interventions—including cryotherapy, loop electrosurgical excision procedures (LEEP), cone biopsies, and even hysterectomies—persistent abnormalities often remained unexplained. Given the potential role of declining estrogen in altering cervical and vaginal cytology, we investigated whether local vaginal estrogen therapy administered over a 4–6-month period could reverse these abnormalities and reduce false positive diagnoses associated with genitourinary syndrome of menopause (GSM).To evaluate this hypothesis, we analyzed clinical data collected over a 12-year period from more than 800 women aged 40 and older who presented with abnormal PAP smears. All participants received local vaginal estrogen therapy, and cytologic outcomes were followed longitudinally. The primary endpoint was the resolution of atypical or dysplastic PAP findings after treatment. Over 90% of participants experienced resolution of abnormal cytology within 4–6 months of initiating local estrogen therapy. These improvements were sustained only while treatment continued. Retrospective analysis revealed that more than 80% of abnormal smears in this population were ultimately linked to early manifestations of GSM rather than true cervical dysplasia.These findings suggest that in perimenopausal and postmenopausal women, many abnormal PAP smear results reflect hypoestrogenic epithelial changes rather than true dysplastic lesions. Local vaginal estrogen therapy appears to be a highly effective intervention, with the potential to prevent misdiagnosis and avoid unnecessary procedures such as colposcopies, biopsies, and hysterectomies. Incorporating this approach into clinical practice could lead to substantial cost savings and improved patient outcomes. Recognizing genitourinary syndrome of menopause as a frequent cause of false positive cervical dysplasia may enhance diagnostic accuracy and inform more appropriate management strategies.Presentation: Sunday, July 13, 2025

The perimenopausal period and menopause are often accompanied by symptoms of depression, since a decrease in estrogen levels causes the decline of reproductive function, emotional disorders, vasomotor symptoms, and genitourinary menopausal syndrome. Since the occurrence of disorders in the psycho-emotional sphere is due to the direct genomic effect of hypoestrogenism, hormone replacement therapy remains the most effective treatment method for vasomotor manifestations. The appointment of antidepressants, neuroleptics, antiepileptic drugs, and anxiolytics allows for a sustained effect in the emotional sphere, improving both the general condition and mental status of women during menopausal transition and menopause.

Disclosure: I. Murta: None. J. Bicca: None. N. Cardoso: None.Background: Endometriosis is an estrogen-dependent clinical syndrome traditionally regarded as a premenopausal condition that tends to regress after menopause. Contrary to this assumption, it can affect up to 4% of postmenopausal women. Hormone replacement therapy (HRT) in this population is challenging due to the potential reactivation of endometriotic lesions, reported in 16-22% of women aged 49-55 and a 1% risk of malignant transformation in those receiving combined HRT. Estrogen deprivation is often preferred out of concern for these complications, raising issues related to bone, cardiovascular, and metabolic health. The efficacy of HRT in this context depends on the dose, route of estrogen administration, and the type, metabolism, and progestogenic potency of the progestin used for symptom control. Clinical Case: A 54-year-old woman, SF, with no prior diagnosis of endometriosis but a long-standing history of deep dyspareunia, started presenting with hot flashes at age 47, followed by persistent pelvic pain and menorrhagia. Bone densitometry revealed osteopenia. Pelvic MRI with bowel preparation identified deep infiltrating endometriosis. Initial treatment with conventional oral progestin therapy failed to alleviate pelvic pain. She underwent surgical intervention, followed by oral progestin therapy, again with no clinical improvement. She started GnRH analog therapy with Goserelin (Zoladex), but experienced worsening vasomotor symptoms and vaginal atrophy, making the treatment poorly tolerated. After multiple failed approaches, the patient began treatment with a novel progestin (R2323) combined with low-dose transdermal estradiol (50 mcg, three times per week), which led to complete resolution of clinical symptoms and improved bone mineral density after two years of HRT. Conclusion: Although oral progestins are considered first-line therapy for endometriosis, they have a reported failure rate of 33%. GnRH agonists serve as an alternative but often induce hypoestrogenic side effects such as vasomotor symptoms and concerns regarding bone loss, particularly in menopausal patients. In this case, the progestin demonstrated antiestrogenic and antiprogestogenic activity with mild androgenic potential. Its therapeutic use led to a modest increase in bone mineral density, possibly due to this androgenic effect. Some evidence suggests that bone receptors may respond differently to this progestin's antiestrogenic action. The addition of low-dose estrogen supported metabolic and cardiovascular health. Combined HRT in patients with endometriosis should be assessed individually, considering dose, route, and type of progestin. Clinical guidelines and further clinical evidence are still needed to support decision-making regarding HRT in this population.Presentation: Monday, July 14, 2025

Disclosure: C. Dominguez-Bali: None. W.K. Massah: None. M.A. Bencomo: None. E. Johnson: None. K. McCoy: None. E.S. Tsehaye: None. H.A. Goraya: None. M.A. Syed: None. R. Polam: None. L. Yousif: None. A. Dominguez-Bali: None.Vulvo-vaginal obliteration is a rare condition, with fewer than 25 cases reported in the literature. This study presents 11 cases of vulvovaginal obliteration, with 3 cases of complete and 8 cases of partial obliteration. A shared characteristic among these patients was a prolonged period (10-35 years) without sexual activity and the absence of hormone therapy.This study aims to examine the presentation, treatment, and outcomes in patients with vulvovaginal obliteration, with a focus on the role of dilator and hormone therapy in post-operative management and potential enhancements in sexual function and prevention of the genitourinary syndrome of menopause consequences.This retrospective analysis included 11 cases of vulvovaginal obliteration. In the two most severe cases, patients presented with symptoms including total urinary retention, urocolpos, bladder distention, bilateral megaloureters, and hydronephrosis with abnormal renal function tests. Emergency procedures were performed to open the inter-labial fusion for urine drainage, followed by treatment with vaginal estradiol and gradual introduction of vaginal dilators.Immediate relief of symptoms was achieved upon opening the inter-labial fusion, with continuous urine drainage lasting up to 45 minutes. While vaginal estradiol alone was insufficient for maintaining the vaginal opening, the introduction of vaginal dilators proved effective. Over time, the required frequency of dilator use decreased. Notably, one patient (92 years old) reported experiencing orgasm for the first time following the use of dilators as a pelvic physical therapy.Early recognition and intervention are essential for managing vulvovaginal obliteration, with vaginal dilators playing a crucial role in post-operative care. But we would like to emphasize the importance of sexual activity (with or without a partner, and in this case, with the use of dilators) and local hormone replacement therapy in the prevention of this kind of severe manifestations of the genitourinary syndrome of menopause. The findings suggest that dilator use may offer therapeutic benefits beyond maintaining patency, potentially enhancing sexual function. Further research is needed to evaluate management options for vulvovaginal obliteration and similar conditions, including those resulting from Stevens-Johnson syndrome, radiation, and chemotherapy.Presentation: Saturday, July 12, 2025

Isoflavones, natural bioactive compounds with estrogen-like properties, are increasingly used by postmenopausal women to manage menopausal symptoms. However, research on their efficacy has produced inconsistent results, necessitating a comprehensive review to guide clinical practice. To evaluate the effects of isoflavone interventions on vaginal atrophy, skin health, and sex-related hormone levels in postmenopausal women through a systematic review and meta-analysis of randomized controlled trials. A systematic literature search was conducted in PubMed, Embase, Scopus, and the Cochrane Library databases from inception to January 2025. Eligible studies were randomized controlled trials investigating isoflavone interventions in postmenopausal women. Effect sizes were summarized as standardized mean differences (SMDs) with 95% CIs using a random-effects model. The risk of bias was assessed using the Risk of Bias 2 tool. The analysis included 47 studies comprising 2,657 participants. Isoflavone interventions significantly reduced vaginal dryness (SMD=-1.147; 95% CI, -2.077 to -0.216; P=0.016; I2=95.4%) and increased the vaginal maturation value (SMD=0.605; 95% CI, 0.087 to 1.123; P=0.022; I2​​​​​​=88.7%). Improvements in skin health were observed, including reduced skin roughness measure R2 (SMD=-0.209; 95% CI, -0.389 to -0.029; P=0.028; I²=0.0%) and wrinkle surface (SMD=-0.342; 95% CI, -0.560 to -0.124; P=0.002; I2=0.0%). Isoflavones also significantly increased estradiol levels (SMD=0.247; 95% CI, 0.059 to 0.435; P=0.010; I2=60.5%). Isoflavone interventions effectively manage vaginal atrophy in postmenopausal women and show potential for improving skin health and sex-related hormone levels. These findings underscore the therapeutic value of isoflavones while emphasizing the need for further research, particularly regarding their effects on skin health.

This randomized crossover study evaluated the 12week efficacy of a 10µg estradiol hemihydrate vaginal tablet versus a vaginal gel (available at Siriraj Hospital, Thailand) in postmenopausal women with vaginal atrophy. Secondary endpoints included the most bothersome symptom, vaginal health index (VHI), vaginal pH, female sexual function index, serum estradiol, endometrial thickness, ease of use, comfort, and satisfaction. Ninety participants were randomized to receive either the 10µg estradiol tablet or the gel daily for 2weeks, followed by twice-weekly application for 10weeks. Afterward, they switched to the alternate treatment for another 12weeks using the same dosing regimen. Assessments of VHI, pH, vaginal maturation value (VMV), female sexual function index, endometrial thickness, and estradiol levels were conducted at baseline, 12weeks, and 24weeks. Eighty-five participants completed the study. At 12weeks (intention-to-treat analysis), the gel significantly increased VMV compared with the tablet (60.16 ± 12.00 vs 51.62 ± 23.77; P = 0.035; 95% CI 0.54 to 16.46), although the 95% CI included the noninferiority margin of 15. Per-protocol analysis showed no significant difference between groups. VHI improved, and pH decreased more markedly with the gel at 12weeks. By 24weeks, there were no significant between-group differences in VMV, pH, or most bothersome symptom. Acceptability was high for both treatments, although 55.3% of participants indicated a preference for continued gel use. Noninferiority of the 10µg estradiol hemihydrate tablet relative to the gel could not be established. However, both treatments exhibited clinical benefits and high patient satisfaction, providing valuable insights for therapeutic decision-making in postmenopausal vaginal atrophy.

While vaginal estrogen (VE) is a common treatment option for women with genitourinary syndrome of menopause, VE can be cost-prohibitive, causing medication nonadherence. The objective of this study was to compare trends in VE pricing through retail pharmacies, Medicare Part D, the Mark Cuban Cost Plus Drug Company (CPD), and with the application of GoodRx coupons. For this economic study, data from CPD and GoodRx were reviewed to obtain listed prices for various VE types and formulations, including conjugated estrogen cream (Premarin), estradiol 0.01% cream (Estrace), and estradiol 10mcg tablets (Vagifem). GoodRx prices were obtained from 4 retail pharmacies within the most populous zip code from each U.S. state. Prices were adjusted to account for dosage and prescribed quantity to estimate an average cost per dosage unit ($/adu). Within zip codes, the mean $/adu of Premarin, Estrace, and Vagifem were $9.03, $3.45, and $9.86, with a standard deviation of 0.45 $/adu, 0.48 $/adu, and 0.56 $/adu. Comparing GoodRx to retail pricing, cost reductions were seen for all 3 medications, with an average saving of $7.45, $1.34, and $6.00 per dosing unit. Reduced prices for all medications were available through CPD versus GoodRx, with cost reduction of $0.35, $0.89, and $2.31 for each unit of Premarin, Estrace, and Vagifem. While significant price variations for prescriptions were seen on a regional level within zip codes and between pharmacies, notable price savings were consistently seen with CPD and GoodRx, offering a solution to the financial strain that these prescriptions may impose.

Prescribing Trends for Vaginal Estrogen: What Role Do Urogynecology and Reconstructive Pelvic Surgery Urologists Play?

To compare the efficacy and safety of fractional microablative radiofrequency (RF) and topical estriol in the treatment of genitourinary syndrome of menopause (GSM). This pilot randomized controlled trial included 30 healthy postmenopausal women with GSM. Participants were randomly assigned to receive either fractional microablative RF plus placebo cream (RF group) or topical estriol plus sham RF (estriol group). Both treatments were administered over 3 months. Primary outcomes included vaginal health (Vaginal Health Index Score-VHIS), sexual function (Female Sexual Function Index-FSFI), and urinary symptoms (International Consultation on Incontinence Questionnaire-Short Form-ICIQ-SF). Safety was assessed through reports of adverse effects. Both RF and estriol significantly improved VHIS, FSFI, and ICIQ-SF scores (p < 0.05). Estriol provided greater improvement in sexual desire, while RF demonstrated superior results in satisfaction, dyspareunia reduction, and epithelial elasticity. No severe adverse effects occurred; mild discomfort was reported in the RF group. Fractional microablative RF and topical estriol are both effective and safe for relieving GSM symptoms. RF offers a promising non-hormonal alternative, especially for women who cannot or choose not to use estrogen therapy.

This contemporary review paper analyzes the impact of fluid reduction in overactive bladder and associated factors related to nephrolithiasis. Historically, overactive bladder and nephrolithiasis have been considered separate urologic pathologies. However, patients with OAB symptoms often restrict fluid intake to prevent episodes of urinary incontinence with resultant supersaturated urine, which precipitates nephrolithiasis formation. Coexistent pathologies promote the relationship between overactive bladder and nephrolithiasis, including urinary tract infection-related urolithiasis, bladder stones secondary to voiding dysfunction, and genitourinary syndrome of menopause. Overactive bladder and nephrolithiasis are profoundly impacted by fluid intake. The approach to overactive bladder should aim to optimize quality of life primarily by managing symptoms to avoid patient-imposed fluid intake restriction. By promoting patient confidence to consume the recommended daily fluid intake, nephrolithiasis formation risk is reduced. Eradication of other coexistent pathologies will further reduce overactive bladder symptoms and decrease stone formation.

Biostimulation with polynucleotide cream during adjuvant therapy for breast cancer.

Hyaluronic acid injection to treat symptoms of vulvovaginal atrophy and improve sexual function in postmenopausal women: A 52-week long-term follow-up.

Genitourinary syndrome of menopause

Objectives: Local estrogen therapy (LET) has many benefits, but little is known regarding adherence and reasons for discontinuation. We aimed to evaluate fill/continuation rates of LET and assess factors associated with not filling/discontinuation. Materials and Methods: Prospective observational study of adult women newly prescribed LET. Participants completed Pelvic Floor Distress Inventory 20 (PFDI-20) and the Day-to-Day Impact of Vaginal Aging (DIVA) at baseline, 3-, 6-, and 12-months from initial prescription. Participants who discontinued LET were queried regarding reason for discontinuation. Results: A total of 155 participants were included. Mean age was 65 (+/-10) and 57% had private insurance. The most common indications for prescription with LET were atrophic vaginitis 61 (39%) and recurrent urinary tract infection 34 (22%). At baseline, 94% filled initial prescription. Continuation rates were 78%, 90%, and 79% at 3-, 6-, and 12-months, respectively, but 93 (60%) were lost to follow-up over the study period. Common reasons for not starting LET included cost (33%) and concern for side effects (22%). Common reasons for discontinuing were mess of using therapy (19%) and concern for side effects (16%). PFDI-20 and DIVA domain scores except self-concept decreased across all timepoints for all participants with no difference between women who continued versus discontinued LET. Univariate analysis did not find any factors associated with LET discontinuation. Conclusions: LET use is associated with improved pelvic floor and vaginal symptoms up to 12 months following initiation. Prospective evaluation was challenging due to high loss to follow-up. A total of 26% discontinued LET over 1 year. Barriers to initiation and discontinuation such as cost, mess, and concern for side effects are potentially modifiable factors that physicians can address to improve adherence.