Local Estrogen Therapy Research Articles

The effect of serotonin reuptake inhibitors on the vaginal epithelium in postmenopausal women

Purpose: Selective serotonin reuptake inhibitors (SSRIs) and serotonin–norepinephrine reuptake inhibitors (SNRIs) are used as alternative treatments for the vasomotor symptoms of menopause in women who are unwilling or unable to receive hormone therapy. These agents have been associated with sexual dysfunction and xerostomia (dry mouth), but the effect on the vagina has not been studied. The objective of this study was to determine the effect of SSRIs and SNRIs on the vaginal epithelium and sexual function in postmenopausal women, using both subjective and objective measures.Materials and methods: A cross-sectional study of postmenopausal women not using any local or systemic estrogen therapy was conducted. The main outcomes included the Female Sexual Function Index (FSFI), vaginal epithelial maturation index (MI), and pH.Results: Sixty-six women were recruited, 30 using SSRIs/SNRIs and 36 who were not (control). Both the proportion of superficial vaginal epithelial cells and the total MI were higher in the SSRI/SNRI group (p = 0.006 and p = 0.047, respectively). There were no significant differences in FSFI scores, vaginal pH, or total MI values.Conclusion: The use of serotonin reuptake inhibiting drugs does not appear to have a negative influence on the vaginal epithelium and associated vaginal atrophy.

Management of ASC-US/HPV positive post-menopausal woman

BackgroundThe aim of our study was to determine which diagnostic course is best to identify women at risk of CIN2+ among post-menopausal women with cytological diagnosis of ASCUSMethodsWe selected women who had been post-menopausal for at least one year , and who had completed the entire diagnostic-therapeutic course that they had undertaken. The sample was divided into two arms: in the first arm, we considered 146 ASCUS positive women who had undergone the HPV test, colposcopy and then underwent more detailed diagnostics by means of LEEP or a scraping of the cervical canal. The second arm was made up of 124 ASCUS positive women who had undergone a vaginal administration of estriolo, the HPV test and colposcopy. Estriol was administered for 5 weeks: the first week one vaginal suppository every evening, the other four weeks the administration was twice a week. Then, the patients underwent colposcopy. In cases of positivity a biopsy was carried out, the patients positive for CIN2+ at the biopsy underwent excisional therapy using LEEP and were followed up. The patients, who were negative at colposcopy or with histological diagnosis of CIN1, were examined again at 1 year.ResultsIn the first arm the HPV test had an SE of 94%, an SP of 68%, NPV of 99%, and PPV of 28%. The PPV is very low because of the elevated percentage of false positives that the HPV test gave (71%). In the second arm the HPV test maintained its high SE (100%), an SP of 74%, a NPV of 100%, and a PPV of 43%. The use of estrogen increased the specificity of the test.ConclusionIt is important to say that the second arm indicates the use of local estrogen therapy only for ASCUS/HPV positive postmenopausal women. Therefore, the HPV test should be used as the first diagnostic possibility in cases of ASCUS in post-menopausal women, associating local estrogen therapy only with HPV positive women.

Local oestrogen therapy modulates extracellular matrix and immune response in the vaginal tissue of post‐menopausal women with severe pelvic organ prolapse

This study investigates the effect of local oestrogen therapy (LET) on the expression of proteins participating in collagen/elastin biogenesis and immune markers in vaginal tissues of post‐menopausal women with severe pelvic organ prolapse (POP). Vaginal biopsies were collected from the anterior vaginal wall of informed and consented 52 post‐menopausal women with severe POP undergoing total hysterectomy. Twenty‐nine of the 52 women were treated with LET (in the form of vaginal oestrogen cream or tablet), while the remaining 23 untreated patients served as the controls. This study was approved by Sinai Health System REB. Vaginal tissue specimens were analysed for gene and protein expression using real‐time RT‐PCR and Luminex assays, protein localization and immune cell infiltration were assessed by immunohistochemistry. Forty‐four cytokines were detected. We found that LET application: (a) significantly increased (P < 0.05) gene and protein expression levels of extracellular matrix (ECM) structural proteins, collagen and elastin, as well as the expression of ECM maturation enzyme BMP1; (b) decreased protein expression level of ECM degradation enzymes MMP1, MMP2 and MMP3 accompanied by an increase in their tissue inhibitors, TIMP1 and TIMP4; (c) significantly increased (P < 0.05) the gene and protein expression levels of 14 vaginal cytokines involved in leucocyte infiltration, which was confirmed by immunohistochemistry. Our results indicate that LET plays an important role in the activation of immune system within the local vaginal environment, limiting the undesirable ECM degradation, which supports the strengthening of vaginal ECM in post‐menopausal women, therefore resisting menopause/age‐related changes and inducing urogenital tract tissue regeneration.

Genito Urinary Syndrome of Menopause (GSM) or Vulvo-vaginal Atrophy (VVA) an Unspoken Sorrow

GSM includes wide spectrum of vulvovaginal Symptoms and urinary troubles replacing the term vulvovaginal atrophy (VVA). It is a silent epidemic condition affecting 50-60% postmenopausal women. Estrogen withdrawal causes thinning, narrowing, tissue loss & reduced blood supply in vulvo-vaginal area, which results GSM. GSM causes burning in vagina, dyspareunia, urinary urgency, repeated UTI. Dyspareunia affects all the domain of sexual function and deteriorates the quality of life. Irony is, women are oblivious to share and doctors are reluctant to discuss. So women keep continue suffering without knowing the restorative treatment. Repercussion of GSM/VVA intensifies the sorrows, distress and sufferings. It has profound effect on relationship and psychology and quality of life of women. Good history taking and clinical examination do diagnosis. Investigations are done to exclude other causes. Treatment is challenging. Maintenance of optimum body weight, exercise, regular coitus, quitting smoking & excessive alcohol intake are the key factors. Vaginal moisturizers are recommended as 1st line therapy for mild to moderate VVA or women who can’t take estrogen. Ideal moisturizers should have similarity with vaginal secretion of osmolality, pH and composition. Meta analysis shows local estrogen therapy is effective. It restores vaginal pH and maturation index. Systemic absorption is minimal so progesterone needs not to be added. Testosterone improves dyspareunia, sexual desire, lubrication and satisfaction. DHEA (Prasterone) penetrates vaginal wall better. It increases elasticity and vascularity of vagina. RCTs have not shown benefits of it’s systemic therapy. But local daily administration of DHEA reduces dyspareunia and GSM so improves the quality of life. Ospemifene is well tolerated. It’s agonist effect on vaginal mucosa and antagonist effect on endometrium and breast, makes it promising. Lasofoxifene, third generation SERM, is also very effective but it needs FDA approval. Laser is widely being used and very effective. It is simple, faster, painless procedure. It activates dominant fibroblasts, proteoglycans, hyaluronic acid, thereby improves GSM & sexuality. Black cohosh, Botox, G-shot, probiotics, gabapentin are not yet evidence based. Still there is significant unmet need for medical treatment. Women reports GSM but that is only tip of iceberg. Good communication and optimum treatment only can break the sorrows GSM/VVA.

Vaginal estrogen and mammogram results: case series and review of literature on treatment of genitourinary syndrome of menopause (GSM) in breast cancer survivors.

To examine mammographic density before and after at least 1 year of vaginal estrogen use in a small cohort of healthy postmenopausal women and women with a personal history of breast cancer. We extracted data via chart review of patients from a single practitioner's menopause specialty clinic in Baltimore, MD. Mammographic change was primarily determined via the Bi-RADS scoring system, including the Bi-RADS density score. In addition, we conduct a narrative review of the current literature on the usage of local estrogen therapy, and systemic and local alternatives in the treatment of genitourinary syndrome of menopause (GSM) in breast cancer survivors. Twenty healthy postmenopausal women and three breast cancer survivors fit our inclusion criteria. Amongst these two groups, we did not find an increase in mammographic density after at least 1 year and up to 18 years of local vaginal estrogen. Ospemifene use in one patient did not appear to be associated with any change in Bi-RADS score. Our narrative review found little data on the effects of vaginal estrogen therapy or newer alternative systemic therapies such as ospemifene on mammographic density. Low-dose vaginal estrogen use for 1 or more years in a small cohort of women with GSM did not appear to be associated with any changes in breast density or Bi-RADS breast cancer risk scores in the majority of study participants, including three breast cancer survivors. Larger long-term controlled clinical trials should be conducted to examine the effects of low-dose vaginal estrogen on mammographic density in women with and without a personal history of breast cancer. Furthermore, relative efficacy and risk of vaginal estrogen compared with other forms of treatment for GSM should also be studied in long-term trials.

Modern possibilities of optimization of local hormonotherapy of urogenital disorders in women on the basis of combined use of vaginal forms of estriol and progesterone

In the review article, the problem of optimization of local hormone therapy of urogenital disorders in women from the perspective of evidence based medicine on the basis of the modern multifactorial concept of genito-urinary menopausal syndrome (GUMS), which implies an important pathogenetic role of not only the age-related estrogen deficiency, but also the deficiency of other sex hormones in the pathogenesis of disorders urogenital tract in women in peri- and postmenopausal women. The important role of bioidentical progesterone as a metabolically active hormone possessing not only classical (reproductive) physiological effects in the body of a woman but also a whole spectrum of nonclassical (nonproductive) effects that demonstrate the pathogenetic justification of the expediency of topical administration of preparations containing a bioidentical analog of natural progesterone within the framework of a complex and personalized treatment of various clinical manifestations of GUMS, especially in women with sop favoring endogenous progesterone deficiency, which can occur chronologically after the 35 years preceding the age of estrogen deficiency. The comparative characteristics of the available dosage forms of progesterone delivery are demonstrated, and the pathogenetic expediency and effectiveness of the additional prescription of topical progesterone to local estrogen therapy in the most common clinical variants of the GUMS is demonstrated using the latest research.

Randomized, double-blind, placebo-controlled clinical trial for evaluating the efficacy of fractional CO2 laser compared with topical estriol in the treatment of vaginal atrophy in postmenopausal women.

The aim of the study was to evaluate efficacy of fractional CO2 vaginal laser treatment (Laser, L) and compare it to local estrogen therapy (Estriol, E) and the combination of both treatments (Laser + Estriol, LE) in the treatment of vulvovaginal atrophy (VVA). A total of 45 postmenopausal women meeting inclusion criteria were randomized in L, E, or LE groups. Assessments at baseline, 8 and 20 weeks, were conducted using Vaginal Health Index (VHI), Visual Analog Scale for VVA symptoms (dyspareunia, dryness, and burning), Female Sexual Function Index, and maturation value (MV) of Meisels. Forty-five women were included and 3 women were lost to follow-up. VHI average score was significantly higher at weeks 8 and 20 in all study arms. At week 20, the LE arm also showed incremental improvement of VHI score (P = 0.01). L and LE groups showed a significant improvement of dyspareunia, burning, and dryness, and the E arm only of dryness (P < 0.001). LE group presented significant improvement of total Female Sex Function Index (FSFI) score (P = 0.02) and individual domains of pain, desire, and lubrication. In contrast, the L group showed significant worsening of pain domain in FSFI (P = 0.04), but FSFI total scores were comparable in all treatment arms at week 20. CO2 vaginal laser alone or in combination with topical estriol is a good treatment option for VVA symptoms. Sexual-related pain with vaginal laser treatment might be of concern.

What if you are not a candidate for (local) estrogens?

Vulvovaginal atrophy (VVA) or atrophic vaginitis is a clinical challenge because it is underreported by women and underrecognised by healthcare providers (HCPs), and is therefore undertreated. Women are often poorly aware that VVA is a progressive chronic condition with a significant impact on sexual health and quality of life (QoL), but that effective treatments are available. HCPs should be proactive in encouraging women to discuss symptoms related to VVA and to seek treatment. In the REal women's VIews of treatment options for Vaginal changEs (REVIVE) European survey, women who had discussed VVA with an HCP were twice as likely to be current medication users than those who had not (59.7% vs 22.7%, respectively). Local estrogen therapy and over-the-counter products for symptomatic relief have been viewed as the mainstay of treatment for VVA. All types of local estrogen preparations are effective. However, not all women with VVA are candidates for local vaginal estrogen therapy, for example those with contraindications or who are unsuitable for medical or personal reasons (e.g. breast cancer survivors, women with physical inability/impairment or uterine prolapse and those who do not want to use hormones). For these women, it is up to the HCP and the woman to make an appropriate decision regarding treatment. Patient preference is a key factor influencing the choice of treatment for VVA. This may be influenced by the woman's personality type, her personal beliefs, fears and past experiences, and the experiences of family members and friends. It is essential that women are provided with adequate information by well-trained HCPs, and are actively involved in the decision-making process.

Successful Therapy of Overactive Bladder Syndrome with Percutaneous Tibial Nerve Stimulation: A Case Report

Introduction: Overactive bladder syndrome is defined as urgency with or without incontinence, often with frequency and nocturia but without infection or other pathology. For the patient, overactive bladder syndrome means an essential loss of quality of life. The therapeutic concept follows a graduated, stepwise scheme. The first step consists of behavioral treatment with bladder training and pelvic floor education as well as local estrogen therapy. Following inadequate response to these measures, it is often necessary to add anti-muscarinic drugs or beta-3 agonists. In case of medical contraindication or insufficient response to pharmacologic treatment, neuromodulation, i.e. percutaneous posterior tibial nerve stimulation, should be routinely offered to overactive bladder syndrome patients. Case Report: We present the case of an 81-year-old woman with long-lasting overactive bladder syndrome without incontinence. Behavioural treatment, local estrogen and anti-muscarinic therapy were unsatisfactory, therefore, an additional treatment employing percutaneous posterior tibial nerve stimulation was implemented. Under this regimen, the symptoms dramatically improved. Conclusion: The reported overall success rate of percutaneous posterior tibial nerve stimulation in the literature ranges from 33 - 71%, with success being defined as more than a 50% decrease in urgency and a 25% reduction of frequency and nocturia, respectively. There is no other therapeutic option for overactive bladder syndrome patients, that reaches similar success rates. Percutaneous posterior tibial nerve stimulation should be routinely offered to overactive bladder syndrome patients and employed as an early step in the treatment of overactive bladder syndrome, sometimes in combination with or even before the introduction of medications.

Aerobic vaginitis: no longer a stranger

Aerobic vaginitis (AV) is the name given in 2002 to a vaginal infectious entity which was not recognized as such before. It is characterized by abnormal (dysbiotic) vaginal microflora containing aerobic, enteric bacteria, variable levels of vaginal inflammation and deficient epithelial maturation. Although AV and bacterial vaginosis (BV) share some characteristics, such as a diminished number or absence of lactobacilli, increased discharge (fishy smelling in BV, while in severe forms of AV, a foul, rather rotten smell may be present) and increased pH (often more pronounced in AV), there are also striking differences between the two. There is no inflammation in women with BV, whereas the vagina of women with AV often appears red and edematous, and may even display small erosions or ulcerations. The color of the discharge in BV is usually whitish or gray and of a watery consistency, whereas in AV it is yellow to green and rather thick and mucoid. Women with BV do not have dyspareunia, while some women with severe AV do. Finally, the microscopic appearance differs in various aspects, such as the presence of leucocytes and parabasal or immature epithelial cells in AV and the absence of the granular aspect of the microflora, typical of BV. Despite all these differences, the distinction between AV and BV was not recognized in many former studies, leading to incomplete and imprecise diagnostic workouts and erroneous management of patients in both clinical and research settings.The prevalence of AV ranges between 7 and 12%, and is therefore less prevalent than BV. Although still largely undiagnosed, many researchers and clinicians increasingly take it into account as a cause of symptomatic vaginitis. AV can co-occur with other entities, such as BV and candidiasis. It can be associated with dyspareunia, sexually transmitted infections (such as human papilloma virus, human immunodeficiency virus, Trichomonas vaginalis and Chlamydia trachomatis), chorioamnionitis, fetal infection, preterm birth and cervical dysplasia. Many other possible pathological associations are currently under investigation.The diagnosis of AV is made using wet mount microscopy, ideally using phase contrast. An AV score is calculated, according to: lactobacillary grade, presence of inflammation, proportion of toxic leucocytes, characteristics of the microflora and presence of immature epithelial cells. To circumvent the hurdle of microscopic investigation, some groups have begun to develop nucleic-acid-based and enzymatic diagnostic tests, but the detailed information obtained with phase contrast microscopy is irreplaceable.The best treatment is not yet fully determined, but it must be tailored according to the microscopic findings and the patient's needs. There is a role for local estrogen therapy, corticosteroids, antimicrobials and probiotics. Further research will reveal more precise data on diagnosis, pathogenesis, management and prevention.

A Dermatologist's Approach to Genitourinary Syndrome of Menopause.

Genitourinary syndrome of menopause (GSM) is a debilitating condition caused by hypoestrogenism that presents with vaginal dryness and dyspareunia as well as other genital, sexual, and urinary symptoms. Previously known as atrophic vaginitis, the term GSM is now used. To help familiarise dermatologists with diagnosing and managing GSM. In total, 218 articles were identified and reviewed by 2 independent authors using PubMed. Articles included were from December 2005 to December 2015. Sixty-seven articles met our inclusion criteria. GSM is a clinical diagnosis, requiring the presence of symptoms that should be bothersome and not accounted for by another condition. A pH test may help with diagnosis as vaginal pH will be increased from acidic to neutral. The Papanicolaou test is not recommended because of poor clinical correlation. First-line treatment is low-dose local vaginal estrogen therapy, which has proven efficacy and safety. Serum estrogen levels are not significantly affected with the exception of creams containing high-dose conjugated equine estrogens. Other options have yet to be approved for use in Canada but show promise. GSM is a debilitating and common condition that suffers from barriers to diagnosis and treatment. Current treatments are well tolerated, rewarding, and effective with rapid onset.

Clinical profile of women with vulvar and vaginal atrophy who are not candidates for local vaginal estrogen therapy.

Vulvar and vaginal atrophy (VVA) is a chronic medical condition in postmenopausal women, which is predominantly due to a permanent cessation of ovarian estrogen production. Current available treatment options for VVA are over-the-counter (OTC) symptomatic relief products or local estrogen therapy (LET) aiming to treat this underlying atrophic condition. Recent surveys indicated that these products decrease sexual spontaneity, are messy and indiscrete. Ospemifene is an oral daily drug, which has proven to treat vaginal dryness and dyspareunia effectively. However, despite the comparable efficacy of ospemifene versus placebo to estrogen versus placebo, ospemifene is currently indicated for women, who are not candidates for LET. It is up to the gynecologist to make an appropriate therapeutic decision. There are potential candidates who have not been considered for ospemifene and yet would benefit from this treatment, such as breast cancer survivors, or patients unable to perform or that have problems performing vaginal insertion/application of estrogen based treatments, such as women that suffer from prolapse. Likewise, a patient's concern for hormone treatment safety, treatment regimens complexity or cross contamination with their partner are potential issues to consider when prescribing treatment for VVA in order to provide the best therapeutic option for patients who are generally not compliant with their current therapy.

Sindrome genitourinario de la menopausia: clinica y manejo

El síndrome genitourinario de la menopausia clínicamente se evidencia 4 a 5 años después de la menopausia, y los cambiosobjetivos, están presentes en un 25–57% de todas las mujeres postmenopáusicas. Los síntomas más frecuentes sonsequedad vaginal (75%), dispareunia (38%), y prurito vaginal, flujo vaginal y dolor (15%); y el diagnóstico se basa en criteriosclínicos. Los principios terapéuticos están basados en la restauración de la fisiología urogenital y alivio de los síntomas;contando para ello, las opciones terapéuticas no-hormonales/lubricantes, terapia hormonal sistémica, terapia estrogénicalocal y otras alternativas. El síndrome genitourinario de la menopausia es uno de los determinantes más importantes de lafunción sexual y de la salud urogenital, con un impacto significativo en la calidad de vida relacionada con la salud femenina.

CLarifying vaginal atrophy’s impact On SEx and Relationships (CLOSER) survey in South Africa

Objective: With a paucity of information from sub-Saharan Africa, the impact of postmenopausal vaginal atrophy on women and male partners in South Africa was investigated.Methods: Four hundred individuals in South Africa (200 postmenopausal women who had experienced symptoms of vaginal atrophy, and 200 male partners) completed a structured questionnaire.Results: Sixty-eight percent of women had avoided intimacy because of vaginal discomfort; 62% of men described observing this behavior in their partners. Consequently, 52% of women and 51% of men reported decreased sexual activity – 20% of women and 18% of men believed vaginal discomfort had ‘caused a big problem’. Significantly higher proportions of women than men (p < 0.05) described being ‘put off’ having sex (27% vs. 14%) and feeling emotionally distant from their partners (21% vs. 11%). Twenty-one percent of women had used local estrogen therapy, reporting benefits including feeling ‘happy’ that their body was ‘working again’ (76%) and increased confidence as sexual partners (71%).Conclusion: For many postmenopausal women and their partners, symptoms of vaginal atrophy adversely affected sex and relationships, physically and emotionally. Substantial improvements were reported by women who received local estrogen therapy, supporting greater efforts to improve awareness and accessibility of such treatment in South Africa.

Efficacy of an orally administered combination of hyaluronic acid, chondroitin sulfate, curcumin and quercetin for the prevention of recurrent urinary tract infections in postmenopausal women

ObjectiveTo assess whether the orally administered combination of hyaluronic acid (HA), chondroitin sulfate (CS), curcumin and quercetin could be effective in preventing recurrent cystitis in postmenopausal women and whether its efficacy was conditioned by the concurrent use of local estrogen therapy. Study designThis was a prospective evaluation of 145 postmenopausal women consecutively recruited from the database of three different investigators. All women should have mild-to-moderate urogenital atrophy and a history of recurrent urinary tract infections (≥2 episodes within 6 months or ≥3 episodes within 12 months documented by positive urine cultures) during the last year. Patients were assigned to three different therapeutic regimens: the first group was treated only with vaginal estrogens, the second group only with HA, CS, curcumin and quercetin per os, and the third group was treated with HA, CS, curcumin and quercetin associated with local estrogens. We evaluated the number of patients with <2 infective episodes in the 6-month follow-up and <3 episodes in the 12-month follow-up (main aim definition) and the reduction of related symptoms through a Visual Analog Scale (VAS) and the Pelvic Pain and Urgency/Frequency (PUF) patient symptom scale. Student's t-test and chi-squared test were used for data analysis as appropriate. ResultsAt 6-month follow up, the main aim rate was 8%, 11.1% and 25% in the three groups, respectively (p<0.05 compared to baseline only in group 3). Although the reduction in the number of recurrent episodes became significant in all groups at 1 year follow-up, the main aim rate was almost double in women receiving both local estrogens and oral therapy (group 3) compared to those receiving single treatments. The improvement of related symptoms was significant in all groups at 12-month follow-up. ConclusionsIn postmenopausal women, the combination of HA, CS, curcumin and quercetin per os was effective in preventing recurrent urinary tract infections, especially if administered with vaginal estrogen therapy.

Impact of new systemic oral and local, hormonal and non-hormonal treatments on genitourinary syndrome and Vulvo-Vaginal-Atrophy (VVA) through the menopausal transition: the right therapy in patients at risk

During the menopausal transition, women experience a number of symptoms due to declining estrogen levels, including vasomotor symptoms and vulvar and vaginal atrophy (VVA). Unlike vasomotor symptoms, vaginal dryness and dyspareunia, the main symptoms of VVA, typically worsen without treatment and can significantly impact the quality of life. Up to 60% of postmenopausal women may be affected by VVA, but many women unfortunately do not seek treatment due to embarrassment, cardiovascular and oncologic risk factor, or other factors. Therefore, local estrogen treatment is still controversial due to the systemic absorption of estradiol and its potential effects on the breast and endometrium.The fact that up to 26% of women using systemic hormonal therapy continue to experience symptoms of urogenital atrophy is sufficient reason to justify not recommending systemic hormonal therapy in women with vaginal symptoms only; many women initially require a combination of systemic and local estrogen therapy, especially when it is used at low doses.Intravaginal application of DHEA as an alternative treatment compared to local estrogen therapy. Intravaginal DHEA does not increase serum E2 levels and may be a better option for long term treatment of VVA as there is no increase in serum E2 levels with DHEA. Previous data have shown that intravaginal dehydroepiandrosterone (DHEA, prasterone) improved all the domains of sexual function, an effect most likely related to the local formation of androgens from DHEA.As the first non-hormonal alternative to estrogen-based products for this indication, the approval of ospemifene represents a significant milestone in postmenopausal women's health. Ospemifene is a non-steroidal estrogen receptor agonist/antagonist, also known as a selective estrogen receptor modulator (SERM), which seems to be effective in genitourinary symptoms.There is now a new alternative to systemic hormone therapy with estrogen/gestagens. The tissue-selective estrogen complex (TSEC) which combines a SERM (bazedoxifene, BZA) with conjugated equine estrogens (CEE) is designed not only to improve menopausal symptoms but to prevent osteoporosis, while maintaining the benefits of estrogen therapy on vasomotor symptoms and vulvovaginal atrophy, but antagonizing stimulatory effects on the endometrium and mammary gland. The two studied doses of BZA/CEE (20 mg BZA + 0.425 mg CEE and 20 mg BZA + 0.625 mg CEE) have been shown to improve the percentage of superficial cells, reducing the percentage of basal cells. Thus, 20 mg BZA + 0.625 mg CEE reduces the severity of symptoms caused by atrophic vulvovaginitis by 56% and normalizes vaginal histology and pH. This efficacy persists for 2 years.Here we aim to evaluate current experimental and actual clinical strategies to achieve the main therapeutic goal for genitourinary syndrome and VVA in menopause which is the relief of symptoms, a better quality of life and women’ s health in menopausal women not eligible for Hormonal Replacement Therapy (HRT).

Vaginal estrogen products in hormone receptor-positive breast cancer patients on aromatase inhibitor therapy.

Atrophic vaginitis represents a major barrier to compliance with aromatase inhibitor (AI) therapy in breast cancer (BC) survivors. While local estrogen therapy is effective for postmenopausal vaginal dryness, the efficacy of such therapies has not been evaluated systematically in hormone receptor-positive (HR+) BC patients on AI therapy. Furthermore, the potential risk of breast cancer recurrence with vaginal estrogen therapy represents a long-term safety concern for the patients with HR+BC. Unfortunately, there is no standardized assay to measure very low concentrations of estradiol (E2) in these women being treated with AI therapy. This makes it difficult to evaluate even indirectly the potential risk of BC recurrence with vaginal estrogen therapy in HR+BC patients on AI therapy. In this review, we describe available assays to measure very low concentrations of E2, discuss the Food and Drug Administration-approved vaginal estrogen products on the market, and summarize published and ongoing clinical trials evaluating the safety and efficacy of vaginal estrogen in HR+BC patients on AI therapy. In the absence of any randomized controlled clinical trials, this review serves as a summary of available clinical data and ongoing studies to aid clinicians in selecting the best available option for their patients.

One-year treatment persistence with local estrogen therapy in postmenopausal women diagnosed as having vaginal atrophy.

Estrogen therapy is considered to be the most effective treatment of vaginal atrophy (VA) symptoms. This retrospective study compares rates of pharmacy refill-based treatment persistence in women treated for VA with local estrogen therapy (LET) creams versus low-dose vaginally administered tablets. Study cohort included treatment-naive women aged 45 years or older within the IMS PharMetrics Plus claims database who filled one or more prescriptions for a LET cream or tablet between January 1, 2010 and September 30, 2012. Index LET was the first observed LET claim in pharmacy records. Persistence was defined as the number of consecutive days of treatment available of the index LET during the 12-month follow-up period. In adjusted analyses, we compared the risks of discontinuation of index therapy. Of 30,197 women eligible for analysis, 12,187 (40.4%) initiated treatment with conjugated estrogens vaginal cream, 11,574 (38.3%) initiated treatment with estradiol vaginal cream, and 6,436 (21.3%) initiated treatment with 10-μg vaginal estradiol tablets (formulation introduced in 2010). Cohorts were comparable on age, geography, and baseline comorbidities. During the 12-month follow-up period, 86.2% to 89.4% of cream users discontinued LET after the first prescription compared with 57.8% of tablet users (P < 0.0001). A greater proportion of tablet initiators than cream users were fully (100%) persistent during the 12-month follow-up period. Mean treatment duration was 103.4 days for tablets versus 44.6 to 48.1 days for creams (P < 0.0001). After adjustment for baseline characteristics, tablet initiators had a lower risk of discontinuation compared with cream users (P < 0.0001). Low-dose LET tablets, compared with cream formulations, are associated with greater persistence in the treatment of VA.

Local Oestrogen for Pelvic Floor Disorders: A Systematic Review.

ObjectiveThe decline in available oestrogen after menopause is a possible etiological factor in pelvic floor disorders like vaginal atrophy (VA), urinary incontinence (UI), overactive bladder (OAB) and pelvic organ prolapse (POP). This systematic review will examine the evidence for local oestrogen therapy in the treatment of these pelvic floor disorders.Evidence AcquisitionWe performed a systematic search in MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials and the non-MEDLINE subset of PubMed from inception to May 2014. We searched for local oestrogens and VA (I), UI/OAB (II) and POP (III). Part I was combined with broad methodological filters for randomized controlled trials (RCTs) and secondary evidence. For part I and II two reviewers independently selected RCTs evaluating the effect of topical oestrogens on symptoms and signs of VA and UI/OAB. In part III all studies of topical oestrogen therapy in the treatment of POP were selected. Data extraction and the assessment of risk of bias using the Cochrane Risk of Bias Tool was undertaken independently by two reviewers.Evidence SynthesisThe included studies varied in ways of topical application, types of oestrogen, dosage and treatment durations. Objective and subjective outcomes were assessed by a variety of measures. Overall, subjective and urodynamic outcomes, vaginal maturation and vaginal pH changed in favor of vaginal oestrogens compared to placebo. No obvious differences between different application methods were revealed. Low doses already seemed to have a beneficial effect. Studies evaluating the effect of topical oestrogen in women with POP are scarce and mainly assessed symptoms and signs associated with VA instead of POP symptoms.ConclusionTopical oestrogen administration is effective for the treatment of VA and seems to decrease complaints of OAB and UI. The potential for local oestrogens in the prevention as well as treatment of POP needs further research.

Effect of local estrogen therapy (LET) on urinary and sexual symptoms in premenopausal women with interstitial cystitis/bladder pain syndrome (IC/BPS)

The association between vulvodynia and interstitial cystitis/bladder pain syndrome (IC/BPS), a chronic, debilitating disease of unknown etiology, may involve sex hormone-dependent mechanisms regulating vulvo-vaginal health. We aimed to prospectively investigate the effects of 12 weeks of local estrogen therapy (LET) on urinary/bladder and sexual symptoms in premenopausal women with IC/BPS. Thirty-four women (mean age: 36.1 ± 8.4) diagnosed with IC/BPS were treated vulvo-vaginally three-times/week with estriol 0.5 mg cream and tested by validated questionnaires (ICSI/ICPI, pain urgency frequency [PUF], female sexual function index [FSFI]) and by cotton swab testing, vaginal health index (VHI) and maturation index (MI) before and after treatment. Vulvodynia was present in 94.1% of IC/BPS women. A significant positive effect of LET was evident on urinary and sexual function (p < 0.001, for both) following 12 weeks, as well as an improvement of the VHI (p < 0.001) and the MI (p < 0.04). The results of this open study indicate that 12 weeks of local estriol cream at vaginal and vestibular level may ameliorate urinary/bladder pain symptoms, as well as may improve domains of sexual function. The association between vulvar pain and bladder pain could, therefore, be related to a vaginal environment carrying signs of hypoestrogenism, but further studies are needed to clarify this issue.