Safety of vaginal oestrogens for genitourinary symptoms in women with breast cancer.

BACKGROUND: Oestrogen deprivation is the mainstay of treatment for women with hormone receptor-positive breast cancer, but unfortunately it causes multiple side effects that can significantly impair quality of life. Genitourinary symptoms are very common and although these symptoms can be effectively managed with vaginal oestrogens, concerns about their safety in women with breast cancer limits their use. OBJECTIVE: The aim of this review is to provide a summary of the data on the safety of vaginal oestrogens in women with breast cancer to help general practitioners advise their patients in this situation. DISCUSSION: Although there are no large randomised prospective studies to assess safety, the current evidence suggests reassurance can be provided to the majority of women with a history of breast cancer considering vaginal oestrogens. Consultation with the oncology team is advised for women taking aromatase inhibitors, where the safety of vaginal oestrogens is less certain.

Different effects of CO2 laser and estrogen treatment on vaginal mucosa microbiota and function in genitourinary syndrome of menopause patients.

AIM: To characterize the effects of CO2 laser treatment and estrogen treatment on vaginal microbiota in patients with genitourinary syndrome of menopause (GSM). METHODS: Sixty-four patients with genitourinary syndrome were divided into the estrogen group, the CO2 laser group, and the control group. The control group did not receive any treatment. Vaginal mucosa was collected after 3 and 12 months of treatment. The former was used for 16S rRNA sequencing, and the latter was used for pathological evaluation. Vaginal health and voiding function were assessed using the vaginal health index (VHI) scale and the UDI-6 scale at 3 and 12 months after treatment. RESULTS: The results showed that both treatments reduced alpha diversity in the vaginal flora. Additionally, the abundance of 65 genera differed significantly between the treatment and control groups, with an increase in potentially beneficial bacteria such as Lactobacillus, IheB3_7, Mycoplasma urealyticum, and Streptococcus. In addition, the VHI and UDI-6 scores improved in both treatment groups compared to the control group after 3 months. Whereas VHI and UDI-6 scores were close to baseline in the estrogen group, and remained significantly improved in the CO2 laser group after 12 months. Pathological results showed that both methods improved the vaginal health status of patients with GSM after 12 months of treatment. However, the CO2 group exhibited a more significant increase in type III collagen. CONCLUSIONS: Both CO2 laser and estrogen therapies can regulate the vaginal flora imbalance of GSM and improve the corresponding symptoms. However, the long-term efficacy of CO2 laser therapy is superior compared to estrogen therapy.

Safety of Vaginal Estrogen Therapy for Genitourinary Syndrome of Menopause in Women With a History of Breast Cancer.

OBJECTIVE: To assess the risk of recurrence of breast cancer associated with vaginal estrogen therapy in women diagnosed with genitourinary syndrome of menopause with a history of breast cancer using a large U.S. claims database. METHODS: A U.S. health research network (TriNetX Diamond Network) was queried from January 2009 to June 2022. Our cohort consisted of women diagnosed with breast cancer within 5 years before the initial genitourinary syndrome of menopause diagnosis. Patients with active disease , defined as those undergoing mastectomy, radiation treatment, or chemotherapy within 3 months before diagnosis of genitourinary syndrome of menopause, were excluded. Recurrence was defined as mastectomy, radiation, chemotherapy, or secondary malignancy within 3 months to 5 years after the initiation of vaginal estrogen therapy for genitourinary syndrome of menopause. The study cohort included those with three or more vaginal estrogen prescriptions. The control cohort included women with breast cancer without any vaginal estrogen prescriptions after genitourinary syndrome of menopause diagnosis. Propensity matching was performed. A subanalysis by positive estrogen receptor status, when available, was performed. RESULTS: We identified 42,113 women with a diagnosis of genitourinary syndrome of menopause after breast cancer diagnosis with any estrogen receptor status, 5.0% of whom received vaginal estrogen. Of the initial cohort, 10,584 patients had a history of positive estrogen receptor breast cancer, and 3.9% of this group received vaginal estrogen. Risk of breast cancer recurrence was comparable between those who received vaginal estrogen and those who did not in both the any estrogen receptor (risk ratio 1.03, 95% CI 0.91-1.18) and positive estrogen receptor (risk ratio 0.94, 95% CI 0.77-1.15) status analyses. CONCLUSION: In a large, claims-based analysis, we did not find an increased risk of breast cancer recurrence within 5 years in women with a personal history of breast cancer who were using vaginal estrogen for genitourinary syndrome of menopause.

Swiss consensus on the role of DHEA in the management of genitourinary syndrome of menopause.

Genitourinary syndrome of menopause (GSM) has a significantly negative impact on affected women's lives. However, despite the increasing number of GSM treatment options (e.g. non-hormonal vaginal products, vaginal hormones [estrogens], dehydroepiandrosterone [DHEA; prasterone], vaginal laser therapy, oral ospemifene), many women remain untreated. The goal of the Swiss interdisciplinary GSM consensus meeting was to develop tools for GSM management in daily practice: a GSM management algorithm (personalized medicine); a communication tool for vaginal DHEA (drug facts box); and a communication tool for understanding regulatory authorities and the discrepancy between scientific data and package inserts. The acceptance and applicability of such tools will be further investigated.

Treatment of Urogenital Symptoms in Individuals With a History of Estrogen-dependent Breast Cancer: Clinical Consensus.

SUMMARY: With an estimated 3.8 million breast cancer survivors in the United States, obstetrician-gynecologists often are on the front lines of addressing survivorship issues, including the hypoestrogenic-related adverse effects of cancer therapies or early menopause in survivors (1). Although systemic and vaginal estrogen are used widely for symptomatic relief of genitourinary syndrome of menopause in the general population, among individuals with a history of hormone-sensitive cancer, there is uncertainty about the safety of hormone-based therapy, leading many individuals with bothersome symptoms to remain untreated, with potential negative consequences on quality of life (2). An effective management strategy requires familiarity with a range of both hormonal and nonhormonal treatment options, knowledge about the pharmaceutical mechanisms of action, and the ability to tailor treatment based on individual risk factors. This clinical consensus document was developed using an a priori protocol in conjunction with two authors specializing in urogynecology and gynecologic oncology. This document has been updated to review the safety and efficacy of newer hormonal treatment options as well as nonhormonal modalities.

The role of hormone therapy in urogenital health after menopause.

Menopause represents an endocrine challenge to urogenital health, as oestrogens deprivation and androgens decline significantly contributes to age-related involution of vulvovaginal tissues and lower urinary tract. Genitourinary syndrome of menopause (GSM) is a clinical entity including the chronic and progressive condition of vulvovaginal atrophy (VVA) and encompassing both anatomical and functional consequences of menopause. The term GSM describes genital, sexual and urinary symptoms with a detrimental impact on quality of life (QOL). Several treatment options are available, but many barriers are still present to adequately diagnose and treat GSM. This review aims to present current evidences about epidemiology, aetiology, diagnosis and treatment of GSM, with a focus on prescription medications [low-dose local oestrogen therapy (LET), prasterone (DHEA) and the SERM ospemifene] for urogenital symptoms in healthy postmenopausal women and in special populations, including women with premature ovarian insufficiency (POI) and breast cancer survivors (BCS).

A Review on Therapeutic Effects of Labisia pumila on Female Reproductive Diseases.

The Labisia pumila (LP) is a traditional plant that is locally known as Kacip Fatimah, Selusuh Fatimah, or Pokok Ringgang by the Malaysian indigenous people. It is believed to facilitate their childbirth, treating their postchild birth and menstrual irregularities. The water extract of LP has shown to contain bioactive compounds such as flavonoids, ascorbic acid, ß-carotene, anthocyanin, and phenolic acid, which contribute extensive antioxidant, anti-inflammatory, antimicrobial, and antifungal. The LP ethanolic extract exhibits significant estrogenic effects on human endomentrial adenocarcinoma cell in estrogen-free basal medium and promoting an increase in secretion of alkaline phosphate. Water based has been used for many generations, and studies had reported that it could displace in binding the antibodies and increase the estradiol production making it similar to esterone and estradiol hormone. LP extract poses a potential and beneficial aspect in medical and cosmeceutical applications. This is mainly due to its phytoestrogen properties of the LP. However, there is a specific functionality in the application of LP extract, due to specific functional group in phytoconstituent of LP. Apart from that, the extraction solvent is important in preparing the LP extract as it poses some significant and mild side effects towards consuming the LP extracts. The current situation of women reproductive disease such as postmenopausal syndrome and polycystic ovary syndrome is increasing. Thus, it is important to find ways in alternative treatment for women reproductive disease that is less costly and low side effects. In conclusion, these studies proven that LP has the potential to be an alternative way in treating female reproductive related diseases such as in postmenopausal and polysystic ovarian syndrome women.

Triticum vulgare para el tratamiento del síndrome genitourinario de la menopausia, Armenia, Colombia / Triticum vulgare for the treatment of genitourinary syndrome of menopause, Armenia, Colombia

OBJETIVO: Evaluar la eficacia y la seguridad de Triticum vulgare en el tratamiento del síndrome genitourinario de la menopausia (SGUM). MÉTODO: Estudio cuasiexperimental (antes-después, con grupo control) en mujeres posmenopáusicas (amenorrea ≥ 36 meses, hormona estimulante del folículo > 40 U/l y estradiol < 25 pg/ml), sexualmente activas, con un índice de maduración vaginal (IMV) < 50 y pH ≥ 5, citología cervical negativa (Papanicolaou) y diagnóstico de SGUM, atendidas en el programa de climaterio y menopausia de una clínica privada de mediana complejidad, en Armenia, Quindío (Colombia). Se seleccionaron 207 mujeres con edad promedio de 55,19 ± 7,28 años. Se realizó un muestreo consecutivo. Se asignaron dos grupos: A (n = 105), que recibió T. vulgare, y B (n = 102), que recibió placebo. Se hizo seguimiento al inicio (basal) y 4, 8 y 12 semanas después, utilizando el IMV y el Índice de Función Sexual Femenina (IFSF). Los síntomas del SGUM se evaluaron con una escala visual analógica (EVA). Se aplicó estadística descriptiva. RESULTADOS: La puntuación media del IMV fue mayor en las semanas 4, 8 y 12 en todas las mujeres del grupo A (p = 0,01). Se observó una diferencia significativa en el promedio final de la puntuación del IMV de T. vulgare frente al placebo (p < 0,05). Al final del estudio, el grupo A mostró una mejoría significativa en la puntuación promedio del IFSF, en comparación con el grupo B (p < 0,001). Las puntuaciones de la EVA presentaron una disminución progresiva a lo largo del estudio, pero fueron comparables entre los dos grupos (p = 0,813). CONCLUSIONES: T. vulgare es una efectiva, segura e innovadora alternativa, no hormonal, para el tratamiento del SGUM. No se registraron eventos adversos, por lo que se demostró su seguridad.

OBJECTIVE: To evaluate the efficacy and safety of Triticum vulgare in the treatment of genitourinary syndrome of menopause. METHOD: Quasi-experimental study (before-after, with control group) in postmenopausal women (amenorrhea ≥ 36 months, FSH > 40 U/L and estradiol < 25 pg/ml), sexually active, with a vaginal maturation index (VMI) < 50 and pH ≥ 5, negative cervical cytology (Papanicolaou) and with a diagnosis of genitourinary syndrome of menopause (SGUM); who were treated in the climacteric and menopause program of a private clinic of medium complexity, in Armenia, Quindío (Colombia). 207 participants were selected, with a mean age of 55.19 ± 7.28 years. A consecutive sampling was carried out. Two groups were assigned: A (n = 105) with T. vulgare and B (n = 102) with placebo. Follow-up was done at baseline (baseline), four, eight and twelve weeks later, using the VMI and the female sexual function index (IFSF). Symptoms of SGUM were evaluated using a visual analog scale (VAS). Descriptive statistics were applied. RESULTS: The mean score of the IMV was higher in weeks 4, 8 and 12 in all the participants of group A (p = 0.01). A significant difference was observed in the final mean MVI score of T. vulgare versus placebo (p < 0.05). At the end of the study, group A showed a significant improvement in the mean IFSF score, compared to placebo (p < 0.001). The VAS scores showed a progressive decrease throughout the study but were comparable between the two groups (p = 0.813). CONCLUSIONS: T. vulgare is an effective, safe and innovative non-hormonal alternative for the treatment of SGUM. No adverse events were recorded, guaranteeing their safety.

Association between postmenopausal vulvovaginal discomfort, vaginal microbiota, and mucosal inflammation.

BACKGROUND: Half of all postmenopausal women report symptoms of vulvar, vaginal, or urinary discomfort with substantial impact on sexual function and quality of life; underlying mechanisms leading to symptoms are poorly understood. OBJECTIVE: To examine the possibility that the vaginal microbiota and/or mucosal immune response contributes to the severity of bothersome vaginal symptoms, we conducted a substudy of samples from a randomized trial of vaginal treatment for genitourinary syndrome of menopause to compare these features between women whose symptoms improved and women whose symptoms did not improve. STUDY DESIGN: This is a secondary analysis of samples collected in a 12-week randomized trial of treatment with vaginal estradiol or moisturizer vs placebo for moderate-severe postmenopausal symptoms of vaginal discomfort. We randomly selected 20 women in each arm with ≥2-point decrease in most bothersome symptom severity (responders) and 20 matched controls with ≤1-point decrease (nonresponders). At 0, 4, and 12 weeks, we characterized vaginal microbiota (16S ribosomal RNA gene sequencing), vaginal fluid metabolites (broad-based metabolomic profiling), vaginal fluid-soluble immune markers (Meso Scale Discovery), pH, and vaginal maturation index. We compared responders with nonresponders at baseline and across all visits using linear mixed models to evaluate associations with microbiota, metabolites, and immune markers, incorporating visit and participant-specific random effects while controlling for treatment arm. RESULTS: Here, the mean age of women was 61 years (n=120), and most women (92%) were White. At enrollment, no significant differences were observed between responders and nonresponders in age, most bothersome symptom type or severity, microbiota composition or diversity, Lactobacillus dominance, metabolome, or immune markers. There was a significant decrease in diversity of the vaginal microbiota in both responders and nonresponders (P<.001) over 12 weeks. Although this change did not differ by responder status, diversity was associated with treatment arm: more women in the estradiol arm (63%) had Lactobacillus-dominant, lower diversity bacterial communities than women in the moisturizer (35%) or dual placebo (23%) arms (P=.001) at 12 weeks. The metabolome, vaginal maturation index, and measured immune markers were not associated with responder status over the 12 weeks but varied by treatment arm. CONCLUSION: Postmenopausal vaginal symptom severity was not significantly associated with vaginal microbiota or mucosal inflammatory markers in this small study. Women receiving vaginal estradiol experienced greater abundance of lactobacilli and lower vaginal pH at end of treatment.

Vaginal Estrogen-What a Urologist Should Know.

The implications of estrogen depletion on the lower urinary tract and vagina are relevant to the urologist treating women with genitourinary symptoms. The main symptoms of vaginal estrogen depletion that affect women are dyspareunia and vaginal dryness, recurrent urinary tract infection, and lower urinary tract symptoms. Vaginal estrogen can be used to effectively treat these conditions. Vaginal estrogen is available in a variety of formulations. Each formulation has different considerations regarding its use and patients should be actively involved in choosing the right product for them. Contrary to concerns over the risks of oral estrogen, vaginal estrogen has a low-risk profile. In terms of contra-indications for use, there are relatively few absolute contraindications for vaginal estrogen. A thorough understanding of vaginal estrogen's safety, efficacy and correct use is essential to the urologist treating the post-menopausal female.

Postmenopausal Hormone Therapy-Local and Systemic: A Pharmacologic Perspective.

Every woman, if she lives long enough, will transition into menopause, and as the US population ages, women will be spending more time in a postmenopausal state than before. For postmenopausal women, the decision to initiate menopausal hormone therapy should be individualized. A thorough evaluation of the patient's cardiovascular, venous thromboembolic, cancer, and fracture risk should be considered along with the woman's quality of life. Hormone therapy exerts its therapeutic effects on vasomotor symptoms, the skeleton, and the genitourinary system independent of age since menopause and these benefits are lost once hormone therapy is stopped. Here we review the pharmacologic properties dose, formulation, mode of administration, timing of initiation, and duration of hormonal therapies in regard to optimizing benefit and minimizing risk to the patient. This discussion will focus on the effects of common hormonal therapies including estrogen (local and systemic), progesterone, estrogen receptor agonist/antagonist, and local dehydroepiandrosterone and include a brief review of compounded bioidentical hormone therapy.

Comparison of the effects of Pueraria mirifica gel and of placebo gel on the vaginal microenvironment of postmenopausal women with Genitourinary Syndrome of Menopause (GSM).

OBJECTIVE: To compare the effects of a 12-week course of 5%Pueraria mirifica gel and placebo gel on the prevalence of bacterial vaginosis, vaginal fungi, vaginal pH, vaginal health index (VHI), and genitourinary symptoms in postmenopausal women. STUDY DESIGN: In a randomized, double-blinded, placebo-controlled study (TCTR20160517002), 60 postmenopausal women were randomly assigned to a 12-week course of eitherP. mirifica gel or identical placebo gel. MAIN OUTCOME MEASURE: Vaginal Nugent score, fungal culture, pH, VHI, and genitourinary symptoms were evaluated at baseline and after 12 weeks of treatment. RESULTS: After 12 weeks of treatment, the proportion of participants with an abnormal Nugent score in the P. mirifica and the placebo groups were 6.7 % (2/30) and 23.3 % (7/30), respectively (p =  0.006). The mean changes in Nugent scores and VHI were significantly higher in the P. mirifica group (p <  0.05). There were no significant decreases in the prevalence of symptoms between the two groups after treatment (p > 0.05). CONCLUSION: A 12-week course of treatment with 5 % P. mirifica vaginal gel in postmenopausal women with GSM has been proved to be effective in reducing indicators of bacterial vaginosis compared with placebo gel. Nevertheless, the effect on alleviating genital symptoms was not demonstrated.

Effects of vaginal administration of conjugated estrogens tablet on sexual function in postmenopausal women with sexual dysfunction: a double-blind, randomized, placebo-controlled trial.

BACKGROUND: Female sexual dysfunction (FSD) is prevalent in women with genitourinary syndrome of menopause (GSM). Vaginal estrogen is effective GSM treatment. This study was primarily aimed to evaluate the effects of vaginal administration of conjugated estrogens tablet on postmenopausal FSD using the Female Sexual Function Index (FSFI). Secondary aims were to evaluate vaginal pH, Vaginal Maturation Value (VMV), Normal Flora Index (NFI) and Most Bothersome Symptoms (MBS) changes. METHODS: A double-blind trial was conducted in postmenopausal women with FSD (FSFI ≤26.55). Sixty-seven participants were randomized into two arms; vaginally administered conjugated estrogens tablet (0.625 mg, daily for 3 weeks then twice weekly for 9 weeks, n = 33), or placebo (n = 34). RESULTS: There was no significant improvement of FSFI observed in estrogens arm compared to placebo in each domain and overall index (p = 0.182). The estrogens significantly improved vaginal pH and VMV, toward more acidity (p = < 0.001), higher VMV (p = < 0.001) and more superficial cells (p = < 0.001). We observed no significant difference in NFI and MBS between arms (p = 0.282, 0.182). CONCLUSION: We found no significant changes in FSFI, NFI, and MBS, but significant improvement in vaginal pH and VMV in postmenopausal women with FSD treated with vaginally administered conjugated estrogens tablet. Few side-effects were reported. TRIAL REGISTRATION: Thai Clinical Trial Registry identification number TCTR20180219001 , prospectively registered since 2018-02-19 11:33:21.

[Urogenital Myiasis Caused by Psychoda spp. in Female Patient with No Risk Factor for Myiasis]. / Miyaz Için Risk Faktörü Bulundurmayan Bir Kadin Hastada Psychoda spp. Kaynakli Ürogenital Miyaz Olgusu.

Myiasis is defined as follows; some flies lay their eggs and larvae on live organs and tissues or on cavities of nose, eye, ear and etc of humans or animals and the larvae develop there and cause pathological disorders. One of the rare types of myiasis is the urogenital myiasis. This condition has been associated with covering urogenital area with clothes in almost all populations and therefore, less chance for flies to reach this site and lay their eggs. Low socio-cultural level and poor hygiene conditions are stated as the most important risk factors of myiasis. On the other hand, toilets within the human living spaces are ideal environments for fly larvae that are fed on bacteria as they contain moisture and a microbial environment. It is stated that especially in case of the presence of an underlying infection, flies are more prone to lay their eggs or larvae on this area due to the bad smell. In this case report, a patient with a moderate sociocultural level with no underlying chronic disease, no open wound in the genital area and no urinary tract infection was presented. A 53-year-old female patient living with her family in an apartment flat in the city center of Konya admitted to the outpatient clinic of infectious diseases with the complaint of moving worms in her urine. The patient stated that she had seen maggots while urinating for two weeks and that she passed her urine into a container to be sure that the maggots were coming from her urine, upon seeing the maggots there she has admitted to the hospital. The Larvae were defined as the fourth stage larvae of Psychoda spp. No open lesions or wounds were seen in genitourinary area of the patient who had no complaints other than mild urinary burning. Complete blood count test results of the patient were normal and there was no growth in her urine culture. It was stated that other family members whom she lived with did not have similar complaints. The patient was diagnosed as genitourinary myiasis caused byPsychoda spp. and informed about the relationship between hygiene and the disease. And urinary antiseptics were initiated as the treatment for the patient. After the treatment, no larvae were seen in the urine of the patient. In conclusion, many regions are suitable for Psychoda type of adult flies to live in our country due to the climate conditions. It is considered that infestation may develop in patients with less risk factors in terms of urogenital myiasis, that larvae may increase in number of patients who are not treated or followed up and that the infestation may become chronic and results in more serious clinical conditions. The necessary treatment and follow-up must be performed in such cases and the patients should be educated about the relationship between infestation and hygiene.

An overview of dehydroepiandrosterone (EM-760) as a treatment option for genitourinary syndrome of menopause.

Introduction: Dyspareunia caused by vulvovaginal atrophy is a primary symptom of genitourinary syndrome of menopause (GSM), a chronic, progressive medical condition that results from estrogen and androgen deficiency at menopause. Dehydroepiandrosterone (DHEA, prasterone) is an endogenous precursor steroid hormone that is metabolized into both androgens and estrogens that has been recently been approved by the FDA for the treatment of moderate to severe dyspareunia caused by vulvovaginal atrophy secondary to menopause.Areas covered: This is a comprehensive drug evaluation describing the chemical composition, pharmacokinetics, metabolism, clinical efficacy and safety of dehydroepiandrosterone (prasterone) in the treatment of dyspareunia and VVA secondary to menopause. Preclinical and clinical data suggesting further potential uses, benefits, and contraindications in the genitourinary health of postmenopausal women are also considered.Expert opinion: Intravaginal dehydroepiandrosterone (prasterone) is effective for the management of dyspareunia secondary to menopause and may be effective in the treatment of other types of sexual dysfunction that are secondary to menopause. Further studies should explore additional dosing regimens and different indications.