ospemifene and Atrophy

Ospemifene is a novel selective estrogen receptor modulator developed for the treatment of moderate to severe postmenopausal vulvovaginal atrophy (VVA).. The aim of the study is to perform a systematic literature review (SLR) and network meta-analysis (NMA) to assess the efficacy and safety of ospemifene compared with other therapies used in the treatment of VVA in North America and Europe.. Electronic database searches were conducted in November 2021 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Randomized or nonrandomized controlled trials targeting postmenopausal women with moderate to severe dyspareunia and/or vaginal dryness and involving ospemifene or at least one VVA local treatment were considered. Efficacy data included changes from baseline in superficial and parabasal cells, vaginal pH, and the most bothersome symptom of vaginal dryness or dyspareunia, as required for regulatory approval. Endometrial outcomes were endometrial thickness and histologic classifications, including endometrial polyp, hyperplasia, and cancer. For efficacy and safety outcomes, a Bayesian NMA was performed. Endometrial outcomes were compared in descriptive analyses.. A total of 44 controlled trials met the eligibility criteria ( N = 12,637 participants). Network meta-analysis results showed that ospemifene was not statistically different from other active therapies in most efficacy and safety results. For all treatments, including ospemifene, the posttreatment endometrial thickness values (up to 52 wk of treatment) were under the recognized clinical threshold value of 4 mm for significant risk of endometrial pathology. Specifically, for women treated with ospemifene, endometrial thickness ranged between 2.1 and 2.3 mm at baseline and 2.5 and 3.2 mm after treatment. No cases of endometrial carcinoma or hyperplasia were observed in ospemifene trials, nor polyps with atypical hyperplasia or cancer after up to 52 weeks of treatment.. Ospemifene is an efficacious, well-tolerated, and safe therapeutic option for postmenopausal women with moderate to severe symptoms of VVA. Efficacy and safety outcomes with ospemifene are similar to other VVA therapies in North America and Europe.

Topics: Atrophy; Bayes Theorem; Dyspareunia; Endometrial Neoplasms; Female; Humans; Hyperplasia; Network Meta-Analysis; Selective Estrogen Receptor Modulators; Tamoxifen; Vagina; Vaginal Diseases; Vulva

Vulvo-vaginal atrophy (VVA) or genitourinary syndrome of menopause (GSM) is a common condition among breast cancer (BC) patients, especially those undergoing antiestrogen therapy. Despite being an option in refractory cases, the safety of hormonal treatment remains uncertain in this population. The aim of this study was to review the safety and serum estrogen levels of hormonal therapy in patients with BC history presenting with VVA symptoms. Pubmed, Embase, and Cochrane were searched for studies comparing different hormonal treatment options for VVA in breast cancer survivors. Statistical analysis was performed using a random effects model and heterogeneity using Cochran's Q-statistic and the I2 index. We included 17 studies, of which 5 were randomized controlled trials (RCTs). Treatment modalities included in this study were topical vaginal estradiol and estriol preparations, vaginally applied testosterone, DHEA, and ospemifene. We found that, among patients treated with the estriol and estradiol preparations, there was an average increase of 7.67 pg/mL (SMD 7.67 pg/mL; 95% CI -1.00, 16.35; p < .001). Analysis of the testosterone group found temporary peaks of serum estradiol levels, but 1 study showed persistent elevation above normal postmenopausal levels. One study with prasterone revealed no elevation of serum estradiol concentration. One study with ospemifene demonstrated no increase in the risk of BC recurrence. In conclusion, among treatments available for BC survivors, low-dose vaginal estrogen showed the smallest changes in serum estradiol levels and had the most evidence, but safety remains unclear, especially for patients on aromatase inhibitors. Alternative treatments such as ospemifene need more data supporting safety and efficacy. These results suggest that concerns related to cancer recurrence should keep aiming for the lowest possible concentration.

Topics: Atrophy; Breast Neoplasms; Cancer Survivors; Estradiol; Estriol; Estrogens; Female; Humans; Neoplasm Recurrence, Local; Survivors; Testosterone; Vagina; Vaginal Diseases

Vulvovaginal atrophy (VVA) is a frequent, underreported and underdiagnosed condition. Ospemifene is a third-generation Selective Estrogen Receptor Modulator (SERM) that has been shown to be effective in women with VVA and dyspareunia, vaginal dryness and vulvar vestibular symptoms. Some of the possible side effects included by FDA and EMA are hot flushes, headache, muscle spasms, vaginal bleeding and vaginal discharge. Ospemifene does not increase the incidence of endometrial cancer or hyperplasia. While the efficacy is comparable with that of estrogenic treatments, ospemifene is not only well tolerated and safe but also reduces bone turnover in postmenopausal women, and available data indicate no safety concerns for breast tissue.

Topics: Atrophy; Drug-Related Side Effects and Adverse Reactions; Dyspareunia; Female; Humans; Tamoxifen; Treatment Outcome; Vulva; Vulvar Diseases

To evaluate the efficacy of ospemifene in treating dyspareunia associated with postmenopausal vulvo-vaginal atrophy (VVA).. A structured search was carried out in PubMed-Medlin, Embase, Cochrane Controlled Trials Register databases through to 31 July 2018. The search included the following terms: "Ospemifene", "vulvovaginal atrophy", "dyspareunia", "SERM" and "randomized controlled trial" (RCTs). Four outcomes were selected: vaginal pH; proportions of parabasal and superficial vaginal cells; and perception of the most bothersome symptom (vaginal dryness or dyspareunia). A random-effects model was used in the meta-analysis. Study quality and bias risk were assessed with the Cochrane tool.. Six RCTs comparing the efficacy of ospemifene against placebo after 12 and 52 weeks of treatment were included in the meta-analysis. At 12 weeks, changes in vaginal Ph (SMD: -0.96, 95% CI:-1.12 to -0.81; p < 0.0001), parabasal cells (SMD: -36.84 95% CI -46.95 to -26.72; p < 0.0001), superficial cells (SMD: 8.23, 95% CI 3.73-12.74, p < 0.0003), and dyspareunia (SMD= - 2.70, 95% CI - 2.88 to -2.52, p < 0.0001) indicated that ospemifene was more effective than placebo.. The present meta-analysis suggests that ospemifene 60 mg is associated with significant improvement in the morphological and physiological features of the vaginal mucosa that correlate with the symptoms associated with postmenopausal VVA.

Topics: Atrophy; Female; Humans; Randomized Controlled Trials as Topic; Selective Estrogen Receptor Modulators; Tamoxifen; Treatment Outcome; Vagina; Vaginal Diseases; Vulva; Vulvar Diseases

To evaluate the tolerability and safety of ospemifene in treating dyspareunia associated with postmenopausal vulvo- vaginal atrophy (VVA).. The literature was searched through to 31 July 2018 to identify randomized controlled trials comparing ospemifene 60 mg against placebo for the treatment of VVA. Two groups of outcomes were selected: 1) side-effects, including hot flushes, urinary tract infection (UTI), headache, deep venous thrombosis (DVT), coronary heart disease (CHD), cardiovascular event (CVE), discontinuation due to side-effects, serious adverse event (SAE); 2) Safety, in relation to endometrial thickness, vaginal bleeding, breast tenderness, breast and endometrial cancer. A random-effects model was used in the meta-analysis. Study quality and bias risk were assessed with the Cochrane tool.. In the group of patients treated with ospemifene, there was a slightly higher rate of hot flushes (OR:2.36, 95% CI 1.26-4.42; p = 0.007) and UTI (OR:1.97, 95% CI 1.23-3.14, p = 0.005) at 12 weeks of treatment, but no differences were noted after 52 weeks. The incidence of headaches, DVT, CHD, CVE, discontinuation of treatment, and SAEs was not significantly different between groups. Ospemifene treatment was statistically associated with a greater endometrial thickness in women with an intact uterus both at 12 weeks (SMD: 0.40, (95% CI 0.17 to 0.63, p < 0.0005) and at 52 weeks (SMD: 0.62, 95% CI 0.23-1.01, p = 0.002); however, this increase was not clinically relevant. The incidence of vaginal bleeding, endometrial cancer, breast tenderness, breast and endometrial cancer was not significantly different between groups.. This meta-analysis suggests that ospemifene treatment is well tolerated and presents a good safety profile. Long-term safety studies with larger samples, which include patients at high risk, are warranted.

Topics: Atrophy; Female; Humans; Randomized Controlled Trials as Topic; Selective Estrogen Receptor Modulators; Tamoxifen; Vagina; Vaginal Diseases; Vulva; Vulvar Diseases

Topics: Atrophy; Female; Humans; Postmenopause; Tamoxifen; Vagina; Vulva

Ospemifene is a selective estrogen-receptor modulator approved for treating menopause-related moderate to severe dyspareunia and vaginal dryness, symptoms of vulvovaginal atrophy (VVA), in the United States, and for treating menopause-related, symptomatic VVA in women not appropriate for local estrogen therapy in Europe. This review summarizes the effects of ospemifene on bone, including bone biomarker data from a phase 3 vaginal dryness study. Early-phase studies of postmenopausal women showed that ospemifene dose-dependently decreased bone turnover markers versus placebo, similar to raloxifene. A 12-week, phase 3 study of ospemifene 60 mg/day in postmenopausal women showed improvements in all VVA parameters and significantly greater decreases in seven of nine bone biomarkers versus placebo. Lower bone resorption markers with ospemifene were observed regardless of time since menopause (≤5 years or >5 years) or baseline bone mineral density (BMD) (normal [

Topics: Administration, Oral; Atrophy; Bone Density; Female; Humans; Osteoporosis, Postmenopausal; Randomized Controlled Trials as Topic; Selective Estrogen Receptor Modulators; Tamoxifen; Vagina; Vulva

Genitourinary syndrome of menopause (GSM) describes a collection of exam findings and bothersome symptoms associated with estrogen deficiency involving changes to the labia, introitus, clitoris, vagina, urethra, and bladder. Vulvovaginal atrophy is a component of GSM. GSM is a highly prevalent medical condition with adverse effects on the health and quality of life of midlife women. There are many effective treatment options, including nonhormonal lubricants and moisturizers, physical therapy, low-dose vaginal estrogen therapy, vaginal dehydroepiandrosterone, and oral ospemifene. Despite the availability of safe and effective therapies, GSM often remains unrecognized and untreated.

Topics: Administration, Intravaginal; Administration, Oral; Atrophy; Dehydroepiandrosterone; Dyspareunia; Estrogens; Female; Humans; Laser Therapy; Lower Urinary Tract Symptoms; Lubricants; Menopause; Physical Therapy Modalities; Selective Estrogen Receptor Modulators; Tamoxifen; Vagina; Vulva

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.

Topics: Atrophy; Dyspareunia; Estrogens; Female; Humans; Medication Adherence; Postmenopause; Selective Estrogen Receptor Modulators; Tamoxifen; Vaginal Diseases; Vulva

Topics: Administration, Cutaneous; Atrophy; Dyspareunia; Estradiol; Female; Humans; Menopause; Selective Estrogen Receptor Modulators; Tamoxifen; Treatment Outcome; Vagina; Vulva

The results of large clinical trials have led physicians and patients to question the safety of hormone therapy for menopause. In the past, physicians prescribed hormone therapy to improve overall health and prevent cardiac disease, as well as for symptoms of menopause. Combined estrogen/progestogen therapy, but not estrogen alone, increases the risk of breast cancer when used for more than three to five years. Therefore, in women with a uterus, it is recommended that physicians prescribe combination therapy only to treat menopausal symptoms such as vasomotor symptoms (hot flashes) and vaginal atrophy, using the smallest effective dosage for the shortest possible duration. Although estrogen is the most effective treatment for hot flashes, nonhormonal alternatives such as low-dose paroxetine, venlafaxine, and gabapentin are effective alternatives. Women with a uterus who are using estrogen should also take a progestogen to reduce the risk of endometrial cancer. Women who cannot tolerate adverse effects of progestogens may benefit from a combined formulation of estrogen and the selective estrogen receptor modulator bazedoxifene. There is no highquality, consistent evidence that yoga, paced respiration, acupuncture, exercise, stress reduction, relaxation therapy, and alternative therapies such as black cohosh, botanical products, omega-3 fatty acid supplements, and dietary Chinese herbs benefit patients more than placebo. One systematic review suggests modest improvement in hot flashes and vaginal dryness with soy products, and small studies suggest that clinical hypnosis significantly reduces hot flashes. Patients with genitourinary syndrome of menopause may benefit from vaginal estrogen, nonhormonal vaginal moisturizers, or ospemifene (the only nonhormonal treatment approved by the U.S. Food and Drug Administration for dyspareunia due to menopausal atrophy). The decision to use hormone therapy depends on clinical presentation, a thorough evaluation of the risks and benefits, and an informed discussion with the patient.

Topics: Acupuncture Therapy; Administration, Intravaginal; Amines; Antidepressive Agents; Atrophy; Cyclohexanecarboxylic Acids; Dietary Supplements; Drug Therapy, Combination; Dyspareunia; Estrogen Replacement Therapy; Estrogens; Exercise Therapy; Female; Gabapentin; gamma-Aminobutyric Acid; Hot Flashes; Humans; Hypnosis; Indoles; Menopause; Paroxetine; Progestins; Selective Estrogen Receptor Modulators; Tamoxifen; Vagina; Vaginal Diseases; Vasomotor System; Venlafaxine Hydrochloride

The term genitourinary syndrome of menopause (GSM) emerged following a consensus conference held in May 2013. GSM is a more descriptive term than vulvovaginal atrophy (VVA) and does not imply pathology. However there are concerns that GSM is all encompassing and includes not only symptoms resulting from estrogen deficiency, but also those arising from the effects of ageing and other processes on the bladder and pelvic floor. Focusing on symptoms related to estrogen deficiency, the update provides a practical guide for health and allied health professionals on the impact of GSM on women and their partners, assessment, management and areas for future research. As GSM is a chronic condition, long term therapy is required. Hormonal, nonhormonal, laser and alternative and complementary therapies are described.

Topics: Atrophy; Complementary Therapies; Estrogen Replacement Therapy; Estrogens; Female; Humans; Laser Therapy; Menopause; Norpregnenes; Quality of Life; Selective Estrogen Receptor Modulators; Sexuality; Syndrome; Tamoxifen; Vagina; Vulva

The vagina, vulva, vestibule, labia majora/minora, and bladder trigone have a high concentration of estrogen receptors; therefore, they are a sensitive biological indicator of serum levels of these hormones in women. The estrogen loss in postmenopausal women produces a dysfunction called genitourinary syndrome of menopause. The principal therapeutic goal in the genitourinary syndrome of menopause is to relieve symptoms. Treatment options, as well as local and systemic hormonal treatment are changes in lifestyle and non-hormonal treatments mainly based on the use of moisturizers and lubricants. New treatments that have recently appeared are ospemifeme, the first selective hormone receptor modulator for dyspareunia and vulvovaginal atrophy treatment, and the use of vaginal laser. This review has been written with the intention of giving recommendations on the prevention and treatment of genitourinary syndrome of menopause.

Topics: Androgens; Atrophy; Dyspareunia; Estrogen Replacement Therapy; Estrogens; Female; Female Urogenital Diseases; Humans; Laser Therapy; Life Style; Lubricants; Menopause; Postmenopause; Selective Estrogen Receptor Modulators; Syndrome; Tamoxifen; Vagina; Vulva; Women's Health

Vulvar vaginal atrophy (VVA), a component of genitourinary syndrome of menopause, is a chronic, progressive medical condition that results from estrogen deficiency at menopause. Ospemifene is a nonhormonal, estrogen receptor agonist/antagonist (ERAA) FDA-approved for the treatment of moderate to severe dyspareunia, a symptom of VVA, due to menopause.. PubMed was searched from inception to March 2015 with keywords ospemifene and vulvar vaginal atrophy; no other similar clinical reviews were found. This is a comprehensive review describing the clinical safety and efficacy of ospemifene for the treatment of dyspareunia and VVA. Preclinical and clinical data suggesting further potential use or benefits of ospemifene for women's health will also be reviewed.. Ospemifene is an approved oral option for postmenopausal women seeking treatment for VVA with bothersome dyspareunia, particularly for those who have tried and failed over-the-counter options or do not want vaginal therapies. Further clinical studies are needed to evaluate the preclinical and early clinical findings of antagonistic to neutral effect on breast tissue and positive effect on bone, which, in the future, may support the use of ospemifene to prevent bone loss or treat VVA in women at high risk or with breast cancer.

Topics: Atrophy; Clinical Trials, Phase III as Topic; Dyspareunia; Female; Humans; Postmenopause; Randomized Controlled Trials as Topic; Selective Estrogen Receptor Modulators; Tamoxifen; Vagina; Vulva

Vaginal estrogen therapy at the lowest effective dose is generally recommended for the treatment of vulvar and vaginal atrophy (VVA), but not all women are candidates. Selective estrogen receptor modulators (SERMs) aim to elicit specific positive effects on targeted tissues with neutral or minimal negative effects on other tissues. This review compares the vaginal effects of currently available and investigational SERMs.. Relevant English-language articles published between 1980 and 2012 were identified through the PubMed database (search string "[Selective Estrogen Receptor Modulator OR SERM] AND [Vulvar OR Vaginal] AND Atrophy"), article reference lists, and EMBASE searches for individual SERMs. Both authors reviewed all articles, which formed the basis of this narrative literature review.. Activity profiles of SERMs in various tissues are distinct. Tamoxifen and arzoxifene have no specific positive vaginal effects but have reported variable or adverse gynecologic effects. Raloxifene does not improve VVA but can be used safely in combination with vaginal estrogen. Bazedoxifene has no demonstrated efficacy for VVA but, in combination with oral conjugated equine estrogens, improves the signs and symptoms of VVA. SERMs with positive vaginal effects (such as improvement in the vaginal maturation index, reduced vaginal pH, and improvement in the signs and symptoms of VVA) on postmenopausal symptomatic women include lasofoxifene (clinical development on hold) and ospemifene, which was recently approved for the treatment of VVA-related dyspareunia, with a class effect warning of potential venous thrombosis risk.. SERMs that specifically target the pathophysiology underlying VVA may provide an alternative to vaginal or systemic estrogen therapy.

Topics: Atrophy; Estrogens; Estrogens, Conjugated (USP); Female; Humans; Indoles; Pelvic Organ Prolapse; Postmenopause; Pyrrolidines; Raloxifene Hydrochloride; Selective Estrogen Receptor Modulators; Tamoxifen; Tetrahydronaphthalenes; Treatment Outcome; Vagina; Vaginal Diseases; Vulva; Vulvar Diseases

Ospemifene, a novel selective estrogen receptor modulator, has been developed for the treatment of vulvovaginal atrophy and dyspareunia in postmenopausal women.. We carried out a systematic review and meta-analysis to assess the efficacy and safety of the drug for treating dyspareunia associated with postmenopausal vulvar and vaginal atrophy.. A literature review was performed to identify all published randomized double-blind, placebo-controlled trials of ospemifene for the treatment of vulvovaginal atrophy and dyspareunia. The search included the following databases: MEDLINE, EMBASE, and the Cochrane Controlled Trials Register. The reference lists of the retrieved studies were also investigated. A systematic review and meta-analysis was conducted.. Six publications involving a total of 1,772 patients were used in the analysis, including three randomized controlled trials (RCTs) that were short-term (12 weeks) comparisons of ospemifene with placebo and three RCTs that were long-term (1 year) comparisons of ospemifene with placebo.. For the comparison of short-term ospemifene with placebo, parabasal cells (the standardized mean difference [SMD] = -37.5, 95% confidence interval [CI] = -41.83 to -33.17, P < 0.00001), superficial cells (SMD = 9.24, 95% CI = 7.70 to 10.79, P < 0.00001), vaginal PH (SMD = -0.89, 95% CI = -0.98 to -0.80, P = 0.00001), and dyspareunia (SMD = -0.37, 95% CI = -0.43 to -0.30, P = 0.00001) indicated that ospemifene was more effective than the placebo. For the comparison of long-term ospemifene with placebo, endometrial thickness (SMD = 0.90, 95% CI = 0.58 to 1.23, P = 0.00001), treatment emergent adverse event, discontinuations due to adverse event, and serious adverse event indicated that ospemifene was generally safe.. This meta-analysis indicates that ospemifene to be an effective and safe treatment for dyspareunia associated with postmenopausal vulvar and vaginal atrophy.

Topics: Atrophy; Double-Blind Method; Dyspareunia; Female; Humans; Postmenopause; Selective Estrogen Receptor Modulators; Tamoxifen; Treatment Outcome; Vagina; Vulva

To review the pharmacology, efficacy, and safety of ospemifene in the management of dyspareunia.. Literature was sought using PubMed (1966-January 2014) and EMBASE (1973-January 2014). Search terms included ospemifene, FC-1271a, dyspareunia, vulvovaginal atrophy, and vaginal atrophy.. All studies, including studies on humans, published in English with data assessing the efficacy and safety of ospemifene in the management of dyspareunia were evaluated.. Ospemifene is a new oral estrogen receptor agonist/antagonist indicated for moderate to severe dyspareunia. Clinical trials evaluating efficacy have shown a significant improvement in superficial cells, parabasal cells, vaginal pH, vaginal dryness, and dyspareunia. The most frequently reported adverse drug reactions in the clinical trials included hot flashes, vaginal discharge, muscle spasms, and hyperhidrosis. Similar to systemic estrogen, boxed warnings with ospemifene include risk for thromboembolism and cerebrovascular disease. Additionally, patients with a uterus still need to use a progestogen with ospemifene to reduce the risk of hyperplasia.. Ospemifene has been effective in improving symptoms of vulvovaginal atrophy when compared with placebo; however, no studies comparing ospemifene with estrogen products exist. Additional clinical trials are needed to evaluate the efficacy and safety in specialty populations, and long-term safety data are needed to assess the potential for serious adverse events. With the risks being similar to that for systemic estrogen therapy, ospemifene appears to be an alternative agent to estrogen therapy but does not have any advantages over estrogen.

Topics: Atrophy; Dyspareunia; Female; Humans; Selective Estrogen Receptor Modulators; Tamoxifen; Vagina; Vulva

Vulvovaginal atrophy (VVA) and dyspareunia are common problems experienced by postmenopausal women, although few seek treatment. Symptom-based therapies include nonhormonal vaginal lubricants, vaginal moisturizers, low-dose vaginal estrogen, and systemic estrogen. The 2013 United States Food and Drug Administration approval of ospemifene, an estrogen agonist/antagonist for the treatment of moderate-to-severe dyspareunia associated with VVA, increased options available to women. Several studies have evaluated the effects of ospemifene on VVA and dyspareunia and indicate an improvement in subjective findings. Objective findings such as a decrease in pH and recovery of a premenopausal vaginal maturation index have been reported. Beneficial effects have also been demonstrated in bone. Evaluations of breast health support the safety of ospemifene, although data are limited to 1 year. Short-term risks appear to be limited and include the development of hot flushes. Until additional comparative studies of ospemifene and estrogens have been performed, ospemifene should be recommended for women with symptoms of VVA and dyspareunia who are unable to tolerate or unwilling to take local or systemic estrogens. In this review, current evidence for the safety and efficacy of ospemifene in the treatment of moderate-to-severe VVA and dyspareunia are evaluated.

Topics: Atrophy; Clinical Trials as Topic; Dyspareunia; Female; Humans; Postmenopause; Tamoxifen; Treatment Outcome; Vagina; Vulva

Ospemifene is a selective estrogen receptor modulator (SERM) approved for the treatment of dyspareunia associated with vulvar and vaginal atrophy (VVA) due to menopause. As the first non-hormonal treatment for this indication, the approval of ospemifene represents a significant milestone in postmenopausal women's health. Ospemifene is a triphenylethylene similar in chemical structure to tamoxifen and toremifene. Consistent with other SERMs such as tamoxifen, toremifene, and raloxifene, ospemifene possesses a distinctive mix of estrogenic and antiestrogenic tissue-specific effects in bone, breast tissue, serum lipids, and the vagina. Among the approved SERMs, ospemifene is the only agent with a nearly full estrogen agonist effect on the vaginal epithelium while having neutral to slight estrogenic effects in the endometrium, making ospemifene uniquely suited for the treatment of dyspareunia associated with VVA, also known as atrophic vaginitis, which affects up to 50% of postmenopausal women. This review begins with a brief history of the discovery of ospemifene, its mechanism of action, and its preclinical development, with an emphasis on its tissue-specific effects on bone, breast, uterus and endometrium, serum lipids and vagina. A brief discussion on the genotoxicity of ospemifene compared to tamoxifen and toremifene is included. The focus then shifts to the clinical development of ospemifene from Phase I through Phase III. We will close with the FDA approval of ospemifene and a justification of the future clinical evaluation of ospemifene as a potential breast cancer chemopreventive agent, where several preclinical studies in different rodent breast cancer models strongly suggest ospemifene is as effective as tamoxifen.

Topics: Atrophy; Dyspareunia; Female; Humans; Selective Estrogen Receptor Modulators; Tamoxifen; Vagina; Vaginal Diseases; Vulva

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 or other factors. After 20+ years in development, ospemifene (Osphena™) was approved by the US Food and Drug Administration in 2013 for treatment of moderate-to-severe dyspareunia associated with VVA due to menopause. 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), from the same chemical class as the breast cancer drugs tamoxifen and toremifene. Unlike other selective estrogen receptor modulators, ospemifene exerts a strong, nearly full estrogen agonist effect in the vaginal epithelium, making it well suited for the treatment of dyspareunia in postmenopausal women. Results of Phase III clinical trials showed that ospemifene significantly improved the vaginal maturation index (decreased parabasal cells and increased superficial cells), decreased vaginal pH, and decreased severity of the self-identified most bothersome symptom (dyspareunia or vaginal dryness) compared to placebo. Long-term safety studies revealed that 60 mg ospemifene given daily for 52 weeks was well tolerated and was not associated with any endometrium or breast-related safety concerns. This review discusses the preclinical and clinical data supporting the use of ospemifene for the treatment of dyspareunia associated with VVA due to menopause and provides an overview of its clinical safety.

Topics: Animals; Atrophy; Dyspareunia; Female; Humans; Postmenopause; Randomized Controlled Trials as Topic; Rats; Selective Estrogen Receptor Modulators; Tamoxifen; Vagina; Vulva

Ospemifene (Osphena™) is an oral selective estrogen receptor modulator (SERM), with tissue-specific estrogenic agonist/antagonist effects. QuatRx Pharmaceuticals conducted the global development of the agent before licensing it to Shionogi for regulatory filing and commercialization worldwide. Ospemifene is the first non-estrogen treatment approved for moderate to severe dyspareunia in women with menopause-related vulvar and vaginal atrophy. The drug is approved in the USA, and application for EU regulatory approval is underway. This article summarizes the milestones in the development of ospemifene leading to this first approval for moderate to severe dyspareunia, a symptom of postmenopausal vulvar and vaginal atrophy.

Topics: Animals; Atrophy; Clinical Trials as Topic; Drug Approval; Drug Industry; Dyspareunia; Female; Humans; Postmenopause; Selective Estrogen Receptor Modulators; Tamoxifen; Vaginal Diseases; Vulva

The incidence and severity of vulvovaginal atrophy (VVA) in postmenopausal breast cancer patients has a significant impact on quality of life. While the etiology of VVA is primarily related to low estrogen levels seen in menopause, women with breast cancer have an added risk of VVA induced by a combination of chemotherapy, hormonal therapy, and menopause. Ospemifene is a new, non-hormonal selective estrogen receptor modulator (SERM) triphenylethylene derivative that is effective in treating VVA in postmenopausal women. Although other SERMs have antagonistic effects on the vagina, ospemifene exerts an estrogen-like effect on the vaginal epithelium. This review will focus on data demonstrating the antiestrogenic activity of ospemifene in several unique breast cancer animal models, and the implications for utilizing ospemifene in patients with breast cancer suffering from VVA. Additional research addressing the expanded use of ospemifene in breast cancer patients is also warranted.

Topics: Animals; Antineoplastic Agents, Hormonal; Atrophy; Breast Neoplasms; Disease Models, Animal; Female; Humans; Menopause; Postmenopause; Quality of Life; Selective Estrogen Receptor Modulators; Tamoxifen; Vagina; Vulva

Millions of women worldwide suffer from vulvovaginal atrophy (VVA) associated with menopause, and many women report that this adversely affects their quality of life. Ospemifene is a non-hormonal estrogen receptor agonist/antagonist effective in the treatment of VVA. Although similar in structure to other estrogen receptor agonists/antagonists that have antagonistic effects on the vagina, ospemifene has an estrogen-like effect on vaginal epithelium. This review focuses on ospemifene including its pharmacologic properties, clinical efficacy and safety.. The paper provides information on the phamacodynamic and pharmacokinetic properties of ospemifene. It also contains an overview of its preclinical and clinical efficacy as well as its clinical safety.. From this paper, the reader will gain an appreciation for a new non-hormonal estrogen receptor agonist/antagonist, ospemifene.. The pharmacologic properties of ospemifene make it a logical candidate for the treatment of women with moderate to severe symptoms of VVA associated with menopause. Clinical trials have confirmed that daily doses are well-tolerated and that it is effective in normalizing vaginal maturation index and pH as well as improving the symptoms associated with VVA including dyspareunia.

Topics: Atrophy; Female; Humans; Selective Estrogen Receptor Modulators; Tamoxifen; Vagina; Vulva

Selective estrogen receptor modulators (SERMs) are structurally different compounds that interact with intracellular estrogen receptors in target organs as estrogen agonists and antagonists. These drugs have been intensively studied over the past decades and have proven to be a highly versatile group for the treatment of different conditions associated with menopause, including hormone-responsive cancer and osteoporosis. However, currently available SERMS are also responsible for side effects such as thromboembolic disorders, or gynecological symptoms (especially vaginal dryness and hot flushes).. The purpose of this article is to review the clinical trials of ospemifene, a new SERM in Phase III development for the treatment of vulvar and vaginal atrophy. The medical literature was reviewed for appropriate articles containing the terms 'ospemifene' and 'SERMs'.. The recently released results from a pivotal Phase III study in postmenopausal women demonstrated statistically significant improvements of ospemifene 60 mg/day in symptoms of vulvar and vaginal atrophy over the use of non-hormonal vaginal lubricant. Ospemifene also appeared to be well tolerated, with few patients experiencing side effects. The additional positive results on bone and the breast observed in preclinical studies need to be clinically confirmed to extend the therapeutic potential of this new SERM.

Topics: Atrophy; Clinical Trials as Topic; Drug Evaluation, Preclinical; Drugs, Investigational; Female; Humans; Molecular Structure; Patents as Topic; Postmenopause; Selective Estrogen Receptor Modulators; Tamoxifen; Vagina; Vulva

To prospectively evaluate the effects of ospemifene on the vulva and vagina in postmenopausal women using vulvar-vestibular photography and direct visual assessments.. Postmenopausal women (aged 40-80 years) with moderate to severe vaginal dryness as their most bothersome symptom (MBS) were randomized to daily ospemifene 60 mg or placebo in this 12-week, multicenter, double-blind, phase 3 study. Vulvar-vestibular photographic images were captured at baseline and week 12 and were independently assessed with the Vulvar Imaging Assessment Scale (VIAS). Changes from baseline in Vaginal and Vulvar Health Indices (VHI and VuHI) with ospemifene versus placebo were analyzed at weeks 4, 8, and 12. Correlations between VIAS, VHI, and VuHI, with vaginal dryness severity and the Female Sexual Function Index (FSFI) scores were also assessed.. In all, 631 eligible participants were randomized (ospemifene 316, placebo 315) and included in the intention-to-treat population. Compared with placebo, ospemifene significantly improved total scores for VIAS (P = 0.0154), VHI (P < 0.0001), and VuHI (P < 0.0001) from baseline to week 12; significant VHI (P < 0.0001) and VuHI (P = 0.002) improvements were observed at week 4. Most VHI and VuHI individual items were significantly better with ospemifene versus placebo at week 12 (P < 0.05). Most correlations between the vulvovaginal assessment total scores versus vaginal dryness severity and FSFI scores were significant (P < 0.05).. Improvements observed in vulvovaginal health with ospemifene assessed by prospective vulvar-vestibular photography and other direct visual assessments support its efficacy in addition to the treatment of moderate to severe vaginal dryness due to menopause and the use of photographic and direct visual evaluations in future clinical trials.. Supplemental Digital Content 1, http://links.lww.com/MENO/A415.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Atrophy; Cross-Sectional Studies; Double-Blind Method; Female; Humans; Middle Aged; Photography; Prospective Studies; Selective Estrogen Receptor Modulators; Tamoxifen; Treatment Outcome; United States; Vagina; Vaginal Diseases; Vulva

To evaluate the safety and efficacy of ospemifene for the treatment of moderate to severe vaginal dryness in postmenopausal women with vulvovaginal atrophy (VVA).. This 12-week, multicenter, double-blind phase 3 study randomized postmenopausal women (aged 40-80 years) with VVA and moderate to severe vaginal dryness as their most bothersome symptom to daily oral ospemifene 60 mg or placebo. Coprimary efficacy endpoints included changes from baseline to week 12 in percentages of vaginal parabasal and superficial cells, vaginal pH, and vaginal dryness severity with ospemifene versus placebo; other secondary endpoints were evaluated (weeks 4, 8, and 12). Safety was assessed by treatment-emergent adverse events (TEAEs) and endometrial biopsies.. Women (n = 631; ospemifene [n = 316], placebo [n = 315]) had a mean age of 59.8 years, a mean body mass index of 27.2 kg/m, and most were white. Ospemifene significantly improved (P < 0.0001) the percentages of parabasal and superficial cells, vaginal pH, and severity of vaginal dryness severity compared with placebo at week 12; significant between-group differences were noted by week 4. Secondary endpoints of dyspareunia (P < 0.001), maturation value (P < 0.0001), and the Female Sexual Function Index (P < 0.05) also significantly improved with ospemifene versus placebo at week 12. Significantly more women responded (31.5% vs 6.0%; P < 0.0001) or were satisfied (49.2% vs 33.8%; P = 0.0007) with ospemifene versus placebo at week 12. No unexpected TEAEs, treatment-related serious TEAEs, thrombotic events, or endometrial hyperplasia or carcinoma were observed.. Ospemifene was effective and well tolerated for the treatment of moderate-to-severe vaginal dryness in postmenopausal women with VVA.

Topics: Adult; Aged; Aged, 80 and over; Atrophy; Double-Blind Method; Dyspareunia; Female; Hot Flashes; Humans; Middle Aged; Patient Satisfaction; Postmenopause; Selective Estrogen Receptor Modulators; Severity of Illness Index; Tamoxifen; Treatment Outcome; Vagina; Vaginal Diseases; Vulva

To evaluate the safety of daily oral ospemifene 60 mg, estrogen agonist/antagonist, used to treat moderate-to-severe dyspareunia due to postmenopausal vulvovaginal atrophy, which is part of genitourinary syndrome of menopause.. Post hoc analysis of safety data (treatment-emergent adverse events [TEAEs]) pooled from six phase 2 and 3 randomized, double-blind, multicenter placebo-controlled studies, evaluating the effects of ospemifene 60 mg on the breast, cardiovascular system, and bone in postmenopausal women.. At least one TEAE was reported by 67.6% (840/1242) and 54.1% (518/958) of women taking ospemifene 60 mg and placebo, respectively. Most TEAEs were mild or moderate and occurred within 4 to 12 weeks. The most commonly reported TEAEs with ospemifene were hot flush (8.5% vs. 3.3% for placebo) and urinary tract infection (6.5% vs. 4.8%). Discontinuation due to TEAEs was 7.6% with ospemifene and 3.8% with placebo. Most women discontinued treatment due to adverse events (AEs): hot flushes, muscle spasms, headache, and vaginal discharge. Serious AEs occurred infrequently (ospemifene, 2.6%; placebo, 1.8%); most were not considered related to treatment. Breast cancer and other breast-related TEAE incidences were comparable between ospemifene (2.5%) and placebo (2.2%), and cardiovascular TEAE incidence, including deep vein thrombosis, was low with ospemifene (0.3%) and placebo (0.1%).. No unexpected safety signals were reported, and discontinuation due to TEAEs was low, with use of ospemifene 60 mg versus placebo in six phase 2 and 3 trials, suggesting a lack of detrimental effects on the breast, bone, and cardiovascular health of postmenopausal women when ospemifene is used to effectively treat moderate-to-severe postmenopausal dyspareunia.

Topics: Adult; Aged; Atrophy; Bone and Bones; Breast; Cardiovascular System; Double-Blind Method; Dyspareunia; Estrogen Antagonists; Female; Hot Flashes; Humans; Middle Aged; Placebos; Postmenopause; Tamoxifen; Treatment Outcome; Vagina; Vulva

To determine whether assessment of all moderate-to-severe symptoms at baseline gives a more accurate evaluation of the treatment effect of ospemifene in vulvovaginal atrophy (VVA) than the most bothersome symptom (MBS) approach.. Data were pooled from two pivotal phase-III clinical trials evaluating the efficacy and safety of oral ospemifene 60 mg/day for the treatment of symptoms of VVA (n = 1463 subjects). Symptoms of vaginal dryness, dyspareunia, and vaginal and/or vulvar irritation/itching reported as moderate or severe at baseline were evaluated. Clinically relevant differences between ospemifene and placebo were analyzed using a four-point severity scoring system and presented as improvement, substantial improvement, or relief.. Subjects in these studies reported statistically significant improvement, substantial improvement, and relief for vaginal dryness (p < 0.00001), dyspareunia (p < 0.001) and statistically significant improvement and relief for vaginal and/or vulvar irritation/itching (p < 0.01) from baseline to week 12 with ospemifene compared with placebo. A similar trend was observed for women who reported substantial improvement of vaginal and/or vulvar irritation/itching.. For drug registration purposes, the use of the MBS model is appealing because of its simplicity and ease of scientific validation. However, the MBS model may underestimate the total magnitude of the clinical benefit of ospemifene treatment for symptomatic women suffering from VVA.

Topics: Adult; Aged; Aged, 80 and over; Atrophy; Double-Blind Method; Dyspareunia; Female; Humans; Middle Aged; Postmenopause; Pruritus; Selective Estrogen Receptor Modulators; Tamoxifen; Treatment Outcome; Vagina; Vaginal Diseases; Vulva

This study aims to assess the endometrial safety of ospemifene based on phase 2/3 clinical trials of postmenopausal women with up to 52 weeks of exposure to ospemifene 60 mg/day versus placebo.. Endometrial safety was evaluated in a development program of six randomized, double-blind, placebo-controlled, parallel-group studies of postmenopausal women aged between 40 and 80 years who had vulvar and vaginal atrophy. Participants were randomized 1:1 to ospemifene 60 mg/day or placebo in one 6-week trial and three 12-week trials; one of the 12-week trials had a 40-week extension study. In a separate 52-week trial, women were randomized 6:1 to ospemifene 60 mg/day or placebo. Endometrial safety was assessed by endometrial histology (biopsy), transvaginal ultrasound, and gynecologic examination.. In these trials, 1,242 women who received ospemifene 60 mg/day and 924 women who received placebo were evaluable for safety. Endometrial hyperplasia occurred in less than 1% of women treated with ospemifene; no endometrial cancer was reported. The mean (SD) increase in endometrial thickness among women treated with ospemifene was 0.51 (1.54) mm at 12 weeks, 0.56 (1.61) mm at 6 months, and 0.81 (1.54) mm at 12 months. Women who received placebo had a mean (SD) increase of 0.07 (1.23) mm at 12 months.. These clinical trial data indicate that up to 52 weeks of treatment with oral ospemifene 60 mg/day was safe for the endometrium. There was no increase in the incidence of endometrial cancer or hyperplasia among postmenopausal women treated with ospemifene compared with placebo.

Topics: Adult; Aged; Aged, 80 and over; Atrophy; Double-Blind Method; Dyspareunia; Endometrial Hyperplasia; Endometrial Neoplasms; Endometrium; Female; Humans; Middle Aged; Placebos; Postmenopause; Selective Estrogen Receptor Modulators; Tamoxifen; Vagina; Vaginal Diseases; Vulva

Ospemifene is a non-estrogen, tissue selective estrogen receptor agonist/antagonist, or selective estrogen receptor modulator, recently approved for the treatment of dyspareunia, a symptom of vulvar and vaginal atrophy (VVA), due to menopause. Postmenopausal dyspareunia is often associated with female sexual dysfunction (FSD). In this report, we present data that demonstrate the effect of ospemifene 60 mg/day on FSD assessed by the Female Sexual Function Index (FSFI), a widely used tool with six domains (Arousal, Desire, Orgasm, Lubrication, Satisfaction, and Pain).. A phase-3, randomized, double-blind, 12-week trial (n = 919) compared the efficacy and safety of oral ospemifene 60 mg/day vs. placebo in postmenopausal women with VVA in two strata based on self-reported, most bothersome symptom of either dyspareunia or dryness. Primary data were published previously. We report herein pre-specified secondary efficacy endpoints analyses, including changes from baseline to Weeks 4 and 12 for FSFI total and domain scores as well as serum hormone levels.. Ospemifene 60 mg/day demonstrated a significantly greater FSFI total score improvement vs. placebo at Week 4 (p < 0.001). Improvement in FSFI scores continued to Week 12 (p < 0.001). At Week 4, the FSFI domains of Sexual Pain, Arousal, and Desire were significantly improved with ospemifene vs. placebo; at Week 12, improvements in all domains were significant (p < 0.05). Changes in serum hormones were minor and uncorrelated with changes in sexual functioning.. In a large, randomized, double-blind, placebo-controlled trial, ospemifene 60 mg/day significantly improved FSD in women with VVA. Consistent effects across FSFI domains were observed.

Topics: Aged; Atrophy; Double-Blind Method; Dyspareunia; Female; Hormones; Humans; Middle Aged; Placebos; Selective Estrogen Receptor Modulators; Sexual Dysfunction, Physiological; Surveys and Questionnaires; Tamoxifen; Treatment Outcome; Vagina; Vulva

To explore clinically relevant differences in severity of vulvar and vaginal atrophy (VVA) in postmenopausal women treated with ospemifene compared with placebo.. Analysis of two multicenter, randomized, double-blind, 12-week phase-III studies in postmenopausal women (40-80 years, with VVA, treated with ospemifene 60 mg/day or placebo (Study 310 and Study 821)). Severity of vaginal dryness and dyspareunia were evaluated using a four-point scoring system and clinically relevant differences between ospemifene and placebo were analyzed and are presented as improvement (reduction in ≥ 1 unit on four-point scoring system), substantial improvement (reduction in 2-3 units on four-point scoring system) and relief (severity score of mild/none after 12 weeks).. In Study 310, significantly more women with a most bothersome symptom of dyspareunia had improvement (68.3% vs. 54.1%; p = 0.0255) or relief (57.5% vs. 41.8%; p = 0.0205) in the severity of dyspareunia from baseline to week 12 with ospemifene compared with placebo. For those with a most bothersome symptom of vaginal dryness, significantly more experienced improvement (74.6% vs. 57.7%; p = 0.0101), substantial improvement (42.4% vs. 26.9%; p = 0.0172) and relief (66.1% vs. 49.0%; p = 0.0140) of vaginal dryness from baseline to week 12 with ospemifene compared with placebo. Proportions of women with improvement/substantial improvement/relief of symptoms of vaginal dryness or dyspareunia were similar in Study 821. Clinically relevant differences were noticeable by week 4.. Treatment with ospemifene was consistently associated with greater improvement, substantial improvement or relief in the severity of the most bothersome symptoms of vaginal dryness or dyspareunia compared with placebo.

Topics: Adult; Aged; Aged, 80 and over; Atrophy; Double-Blind Method; Dyspareunia; Female; Humans; Middle Aged; Placebos; Selective Estrogen Receptor Modulators; Tamoxifen; Treatment Outcome; Vagina; Vaginal Diseases; Vulva

Assessment of 12-month safety of ospemifene 60 mg/day for treatment of postmenopausal women with vulvar and vaginal atrophy (VVA).. In this 52-week, randomized, double-blind, placebo-controlled, parallel-group study, women 40-80 years with VVA and an intact uterus were randomized 6 : 1 to ospemifene 60 mg/day or placebo. The primary objective was 12-month safety, particularly endometrial; 12-week efficacy was assessed. Safety assessments included endometrial histology and thickness, and breast and gynecological examinations. Efficacy evaluations included changes from baseline to week 12 in percentage of superficial and parabasal cells and vaginal pH.. Of 426 randomized subjects, 81.9% (n = 349) completed the study with adverse events the most common reason for discontinuation (ospemifene 9.5%; placebo 3.9%). Most (88%) treatment-emergent adverse events with ospemifene were considered mild or moderate. Three cases (1.0%) of active proliferation were observed in the ospemifene group. For one, active proliferation was seen at end of study week 52, and diagnosed as simple hyperplasia without atypia on follow-up biopsy 3 months after the last dose. This subsequently resolved with progestogen treatment and dilatation and curettage. In six subjects (five ospemifene (1.4%), one placebo (1.6%)) endometrial polyps were found (histopathology); however, only one (ospemifene) was confirmed as a true polyp during additional expert review. Endometrial histology showed no evidence of carcinoma. Statistically significant improvements were seen for all primary and secondary efficacy measures and were sustained through week 52 with ospemifene vs. placebo.. The findings of this 52-week study confirm the tolerance and efficacy of oral ospemifene previously reported in short- and long-term studies.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Atrophy; Double-Blind Method; Female; Humans; Middle Aged; Postmenopause; Tamoxifen; Treatment Outcome; Vagina; Vaginal Diseases; Vulva

To examine the long-term safety of oral ospemifene, a non-estrogen tissue-selective estrogen agonist/antagonist, for the treatment of moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy (VVA) due to menopause.. This multicenter, long-term, open-label, safety extension study was conducted in women without a uterus aged 40-80 years (N=301) who received oral ospemifene 60 mg/day for 52 weeks. Participants either continued their 60-mg/day ospemifene dose from the initial 12-week pivotal efficacy study or switched from blinded placebo or ospemifene 30 mg/day to open-label ospemifene 60 mg/day. The 52-week open-label extension period plus initial 12-week treatment period totaled up to 64 weeks of ospemifene exposure. A 4-week posttreatment follow-up ensued (68 weeks total).. Safety assessments included adverse events, laboratory studies, physical and gynecologic examination, vital signs, breast palpation, and mammography.. Most treatment-emergent adverse events (TEAEs) during the extension study were mild or moderate in severity. The most common TEAE related to study drug was hot flushes (10%; leading to discontinuation for 2% of patients). One serious TEAE, a non-ST-elevation myocardial infarction in a patient with pre-existing cardiac disease, was considered possibly related to study medication. One mild breast-related TEAE, considered unrelated to study drug, was ongoing at study completion. There were no instances of pelvic organ prolapse, incontinence, venous thromboembolism, fractures, breast cancers or death. No clinically significant adverse changes were observed in other safety parameters.. Ospemifene is clinically safe and generally well tolerated in postmenopausal patients with dyspareunia, a symptom of VVA.

Topics: Aged; Atrophy; Dyspareunia; Female; Humans; Hysterectomy; Middle Aged; Postmenopause; Postoperative Complications; Selective Estrogen Receptor Modulators; Tamoxifen; Vagina; Vulva

Ospemifene is a new oral estrogen receptor agonist/antagonist with tissue-selective effects approved for the treatment of moderate to severe dyspareunia, a symptom of postmenopausal vulvar and vaginal atrophy (VVA).. The aim of the study is to assess ospemifene or lubricant use on the clinical signs of VVA.. Subjects in three double-blind, placebo-controlled clinical trials were randomized to ospemifene or placebo. In two of the trials, women were provided nonhormonal lubricants for use as needed, and a preplanned evaluation of the frequency of lubricant use was performed. Additionally, a post hoc placebo group analysis for impact of lubricant use or nonuse on physiologic effects of the percentage of superficial and parabasal cells (maturation index) and vaginal pH was conducted. A secondary preplanned end point included visual examination of the vagina (clinical signs of vaginal dryness, petechiae, pallor, friability, and redness of the mucosa) comparing change from baseline to end of treatment for the ospemifene 60-mg/day group and vs. placebo.. The primary end points in the phase 3 clinical trials included the percentage of superficial cells, parabasal cells, vaginal pH, and most bothersome symptoms compared with placebo.. There was no significant difference in physiologic effects between placebo lubricant users vs. nonusers in either 12-week study. Compared with baseline, substantially more subjects receiving ospemifene 60 mg/day than placebo showed complete resolution of clinical signs of VVA after 12 and 52 weeks of treatment.. Ospemifene substantially improved clinical signs of VVA. Within the placebo group, there was no difference in physiologic effects in lubricant users vs. nonusers. Based on gynecologic evaluation of the vagina, benefits were apparent at 12 weeks and sustained for 52 weeks in the ospemifene-treated subjects with significant improvement over placebo. In these three clinical trials, in contrast to ospemifene-treated women, placebo subjects who utilized lubricants had no improvement in their underlying vaginal physiology.

Topics: Administration, Intravaginal; Administration, Oral; Adult; Aged; Aged, 80 and over; Atrophy; Double-Blind Method; Dyspareunia; Female; Humans; Lubricants; Middle Aged; Selective Estrogen Receptor Modulators; Tamoxifen; Treatment Outcome; Vagina; Vulva

To evaluate the efficacy and safety of ospemifene, a novel selective oestrogen receptor modulator, in the treatment of vaginal dryness in postmenopausal women with vulvovaginal atrophy (VVA).. A 12 week, multicentre, randomised, double-blind, parallel-group phase III study of women (40-80 years) with VVA and self-reported vaginal dryness as their most bothersome symptom.. The co-primary efficacy endpoints were the change from baseline to Week 12 in (1) percentage of parabasal cells in the maturation index (MI), (2) percentage of superficial cells in the MI, (3) vaginal pH, and (4) severity of vaginal dryness. Safety assessments included physical examination, cervical Papanicolaou test and clinical laboratory analyses. Endometrial thickness and histology was also assessed.. A total of 314 women were randomised to once-daily ospemifene 60 mg/day (n=160) or placebo (n=154). Significant improvements in the percentages of parabasal and superficial cells in the MI and vaginal pH were observed with ospemifene compared with placebo (p<0.001 for all parameters). The mean change from baseline in severity score of vaginal dryness reported by women receiving ospemifene compared with those receiving placebo approached statistical significance (p=0.080). Improvements in each of the four co-primary endpoints with ospemifene were statistically significant compared to placebo in the per protocol population. The majority of treatment-emergent adverse events were considered mild to moderate in severity.. Once-daily oral ospemifene 60 mg was effective for the treatment of VVA in postmenopausal women with vaginal dryness.

Topics: Aged; Atrophy; Double-Blind Method; Dyspareunia; Female; Humans; Hydrogen-Ion Concentration; Middle Aged; Postmenopause; Selective Estrogen Receptor Modulators; Tamoxifen; Vagina; Vaginal Diseases; Vulva

The aim of this study was to assess the safety of ospemifene, a novel selective estrogen receptor modulator, for the treatment of vulvar and vaginal atrophy in postmenopausal women with a uterus.. In this multicenter, randomized, double-blind, placebo-controlled, long-term safety extension study, nonhysterectomized women aged 40 to 80 years (n = 180) received daily oral doses of placebo, ospemifene 30 mg/day, or ospemifene 60 mg/day for 40 weeks (continued as blinded treatments from the initial 12-week pivotal efficacy study of ospemifene). The total treatment period was 52 weeks. Safety assessments included adverse events, cervical Papanicolaou tests, endometrial histology, endometrial thickness, gynecological examination, breast palpation, mammography, physical examination, and clinical safety laboratory assessments.. No clinically significant adverse changes in safety assessments were observed in any treatment group. Most treatment-emergent adverse events were mild or moderate in severity. Hot flushes, the most frequently occurring treatment-emergent adverse event related to the study drug, had a low discontinuation rate (1.6%). No study participants discontinued because of endometrial or cervical pathology; no endometrial findings were clinically meaningful. On week 52, more than 95% of endometrial biopsy samples either were classified as atrophic or inactive or had insufficient tissue for diagnosis. There were no treatment-emergent adverse events of pelvic organ prolapse or venous thromboembolism. No cases of endometrial hyperplasia or carcinoma were observed. Only three participants (1.7%) taking ospemifene experienced vaginal bleeding or spotting, which was self-limiting.. Daily doses of ospemifene 30 mg and ospemifene 60 mg yielded few treatment-emergent adverse events and demonstrated no significant endometrial changes during the 1-year treatment of vulvar and vaginal atrophy in postmenopausal women with a uterus.

Topics: Adult; Aged; Aged, 80 and over; Atrophy; Biopsy; Double-Blind Method; Endometrial Hyperplasia; Endometrium; Female; Humans; Middle Aged; Placebos; Postmenopause; Selective Estrogen Receptor Modulators; Tamoxifen; Vagina; Vaginal Smears; Vulva

The aim of this work was to study the role of ospemifene, a novel selective estrogen receptor modulator, in the treatment of vulvar and vaginal atrophy in postmenopausal women with moderate to severe dyspareunia and physiological vaginal changes.. This multicenter phase 3 study used a randomized, double-blind, parallel-group design to compare the efficacy, safety, and tolerability of oral ospemifene 60 mg/day versus placebo. A total of 605 women aged 40 to 80 years who self-reported a most bothersome symptom of dyspareunia and had a diagnosis of vulvar and vaginal atrophy were randomized to take a once-daily dose of ospemifene (n = 303) or placebo (n = 302) for 12 weeks.. Analysis of the intent-to-treat (n = 605) population found the efficacy of ospemifene to be significantly greater than that of placebo for each of the following coprimary endpoints: percentages of parabasal and superficial cells, vaginal pH, and severity of dyspareunia. With ospemifene, the percentage of parabasal cells and vaginal pH significantly decreased; the percentage of superficial cells significantly increased; and dyspareunia was significantly reduced versus placebo (all P < 0.0001, except for dyspareunia: P = 0.0001). Among the randomized women, 186 (61.4%) in the ospemifene group and 154 (51.0%) in the placebo group reported at least one treatment-emergent adverse event. Hot flushes were the most frequently reported treatment-related adverse event (ospemifene 6.6% vs placebo 3.6%); only one participant discontinued in each group. As determined by the investigators, no serious adverse events related to the study drug were reported.. In this study, once-daily oral ospemifene 60 mg was effective for the treatment of vulvar and vaginal atrophy in postmenopausal women with dyspareunia.

Topics: Adult; Aged; Aged, 80 and over; Atrophy; Double-Blind Method; Dyspareunia; Female; Humans; Middle Aged; Placebos; Postmenopause; Selective Estrogen Receptor Modulators; Tamoxifen; Treatment Outcome; Vagina; Vulva

This study aimed (i) to compare the vaginal microbiome profiles of women suffering from vulvovaginal atrophy with that of healthy postmenopausal women and to (ii) assess the effect of ospemifene and systemic hormone treatment on the composition of the vaginal microbiome.. Sixty-seven postmenopausal women attending the Gynecology Clinic of Azienda Ospedaliero-Universitaria of Bologna (Italy) were enrolled. Of them, 39 received a diagnosis of atrophy and 28 were considered healthy controls. In the group of atrophic women, 20 were prescribed ospemifene and 19 received hormone treatment. The vaginal health index was calculated, and a vaginal swab was collected for the assessment of vaginal maturation index and the analysis of vaginal microbiome through 16S rRNA gene sequencing. Clinical/microbiological analyses were repeated after 3 months of treatment.. The vaginal microbiome of atrophic women was characterized by a significant reduction of Lactobacillus ( P = 0.002) and an increase of Streptococcus ( P = 0.008) and Sneathia ( P = 0.02). A positive correlation between vaginal health index/vaginal maturation index and Lactobacillus abundance was found ( P = 0.002 and P = 0.035, respectively). Both therapeutic approaches effectively improved vaginal indices. Systemic hormone treatment induced changes in minority bacterial groups of the vaginal microbiome, whereas ospemifene was able to eliminate specific bacterial taxa, such as Staphylococcus ( P = 0.04) and Clostridium ( P = 0.01). Both treatments induced a trend in the increase of bifidobacteria.. The vaginal microbiome of atrophic women differs significantly from that of healthy postmenopausal women. Ospemifene may lead to a condition of vaginal health, likely characterized by the reduction of "potentially harmful" bacteria.

Topics: Atrophy; Double-Blind Method; Dyspareunia; Female; Hormones; Humans; Postmenopause; RNA, Ribosomal, 16S; Selective Estrogen Receptor Modulators; Tamoxifen; Vagina; Vulva

Overactive bladder (OAB) is a complex and multifactorial syndrome associated with urinary frequency, urgency and incontinence. The menopause-associated hormonal changes play a role in the development of this condition. Vaginal estrogens are effective in improving OAB in postmenopausal women (PMW) with vulvovaginal atrophy (VVA). Ospemifene is a selective estrogen receptor modulator licensed for the treatment of VVA. This study aimed to evaluate the effects of ospemifene on OAB symptoms in PMW with VVA.. Forty PMW suffering from OAB and VVA received oral ospemifene (60 mg/day) for 12 weeks. All patients were assessed with a urodynamic study, a 3-day bladder diary and validated questionnaires (International Consultation on Incontinence Questionnaire - Urinary Incontinence Short Form [ICIQ-UI SF] and International Consultation on Incontinence Questionnaire - Overactive Bladder [ICIQ-OAB]) at enrollment and at the end of the study.. Cytometric capacity, bladder compliance and verbal sensory threshold responses during bladder filling were improved after treatment. The voiding diary showed a significant reduction of daily voids, urge urinary incontinence episodes and nocturnal events. The median overall scores of the ICIQ-UI and ICIQ-OAB were also significantly improved.. Our study suggest that treatment with ospemifene in PMW suffering from OAB is associated with a reduction of OAB symptoms due to a decreased bladder sensitivity and with an improvement in quality of life.

Topics: Atrophy; Female; Humans; Postmenopause; Quality of Life; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence

This study aimed to evaluate the self-reported satisfaction of Spanish postmenopausal women currently treated for vulvovaginal atrophy (VVA) symptoms.. The CRETA (CRoss sectional European sTudy on Adherence) is a multicenter cross-sectional study conducted in 29 public and private hospitals in Spain, which enrolled postmenopausal women receiving treatment with ospemifene, local hormone therapy (HT) or vaginal moisturizers for VVA. After the prior informed consent of the patients, sociodemographic and treatment perception data were collected using a structured questionnaire.. Among 752 women who completed the survey, the satisfaction score was significantly higher for the group treated with ospemifene (mean 8.3 ± 1.4) compared with the local HT group (7.2 ± 1.7) and the vaginal moisturizer group (6.5 ± 2.1) according to a 10-point Likert scale (. Among postmenopausal women with VVA, treatment with ospemifene has the most positive perceptions and the highest overall satisfaction level and could be an optimal therapeutic approach, maximizing patient adherence.

Topics: Atrophy; Cross-Sectional Studies; Dyspareunia; Female; Hormones; Humans; Medication Adherence; Personal Satisfaction; Tamoxifen; Vagina; Vaginal Diseases; Vulva

Vulvovaginal atrophy (VVA) is an underdiagnosed and undertreated chronic condition resulting in physiological and histological changes in the genitourinary tract of postmenopausal women. Treatment of moderate to severe VVA includes local estrogens, dehydroepiandrosterone (DHEA) and oral ospemifene, a third-generation selective estrogen receptor modulator (SERM). Due to venous thromboembolism (VTE) safety concerns classically associated with the SERM class, and as part of its original marketing authorization approval (MAA), the European Medicines Agency (EMA) requested the performance of a 5-year post-authorization safety study (PASS) to study the incidence rate of VTE among women receiving ospemifene. The results have led to important regulatory changes to ospemifene's labeling, extending its indication and eliminating concerted risk management measures. A panel of experts discussed and reached consensus on the impact of these regulatory changes on clinical practice, reflecting on the reassurance of ospemifene's benefit-risk balance and recommending its positioning as a first-line pharmacological treatment option for moderate to severe VVA together with local therapies. In a scenario where different treatments present similar efficacy and safety profiles, a shared decision between clinician and patient, according to her needs and preferences over time, is fundamental to improve adherence and persistence with sequential treatment, contributing to the achievement of health outcomes.

Topics: Atrophy; Dyspareunia; Expert Testimony; Female; Humans; Postmenopause; Selective Estrogen Receptor Modulators; Tamoxifen; Vagina; Venous Thromboembolism; Vulva

To assess the correlation of different vulvovaginal atrophy therapeutic options with the quality of life of postmenopausal women.. The CRETA study is a descriptive, observational, cross-sectional, multicenter study designed to measure, besides treatment satisfaction and adherence, the quality of life of postmenopausal women diagnosed with vulvovaginal atrophy in 29 hospitals and centers across Spain.. The study enrolled postmenopausal women currently receiving treatment with vaginal moisturizers, local estrogen therapy or ospemifene. Clinical features and treatment perceptions were collected by self-report questionnaire and quality of life was evaluated using the Cervantes scale.. Among the 752 women included, the ospemifene cohort showed a statistically significant lower global score (44.9 ± 21.7) on the Cervantes scale (and therefore, a better quality of life) than the cohorts treated with moisturizers (52.5 ± 21.6, p = 0.003) or local estrogen therapy (49.2 ± 23.8, p = 0.0473). In the analysis by domains, ospemifene-treated women showed statistically significant better scores in menopause & health and psychological status than moisturizers-treated women (p < 0.05). In the domains of sexuality and couple relations, the score for the quality of life of the ospemifene cohort was statistically significantly better than the scores in either of the cohorts treated with moisturizers (p < 0.001) or local estrogen therapy (p < 0.05).. Postmenopausal women diagnosed with vulvovaginal atrophy and treated with ospemifene have better quality of life than women treated with vaginal moisturizers or local estrogen therapy. The improvement observed with ospemifene is more remarkable in those aspects related to sex life and couple relations. CLINCIALTRIALS.. NCT04607707.

Topics: Atrophy; Cross-Sectional Studies; Dyspareunia; Estrogens; Female; Humans; Postmenopause; Quality of Life; Selective Estrogen Receptor Modulators; Tamoxifen; Vagina; Vulva

Topics: Atrophy; Endometrium; Female; Humans; Selective Estrogen Receptor Modulators; Tamoxifen; Vagina; Vulva

The objective is to assess the perception of gynecologists regarding patients' adherence to vulvovaginal atrophy (VVA) treatments, to evaluate the gynecologists' opinions on what their patients think about treatment adherence, and to compare the gynecologists' opinions with the patients' own perceptions within the CRETA study.. Spanish gynecologists who participated in the CRETA study were asked to fill out an online 41-item questionnaire to evaluate their views on VVA management.. From 29 centers across Spain, 44 gynecologists completed the survey. Their mean age was 47.2 years old, two-thirds of them were women, and the average professional experience was over 20 years. According to the gynecologists, the therapy most frequently used by VVA-diagnosed women was vaginal moisturizers (45.5%), followed by local estrogen therapy (36.4%) and ospemifene (18.2%). Nevertheless, ospemifene was viewed as the therapeutic option with the most efficacy, easiest route of administration, shorter time to symptom improvement, lower percentage of dropouts, and higher treatment adherence.. Spanish gynecologists are in general agreement with their patients regarding VVA treatment preferences and the main issues for adherence and effectiveness. However, there is an opportunity for doctor-patient communication improvement. Among the three therapeutic options evaluated, ospemifene is regarded as offering some competitive advantages.

Topics: Atrophy; Delivery of Health Care; Female; Gynecologists; Humans; Male; Middle Aged; Perception; Postmenopause; Tamoxifen; Treatment Adherence and Compliance; Vagina; Vaginal Diseases; Vulva

To assess the improvement in vulvovaginal atrophy (VVA) of postmenopausal women treated with oral ospemifene 60 mg/day under conditions of routine clinical practice after 12 months of follow-up.. The AYSEX study is a Spanish observational, prospective, and unicentric study in which five gynecologists recruited postmenopausal women with VVA in routine clinical practice treated with oral ospemifene 60 mg/day as an appropriate therapeutic option. Vaginal health, the most bothersome symptoms, sexual health, endometrial safety, bone resorption markers, bone densitometry, mammography, treatment satisfaction, and quality of life were assessed at baseline and after 12 months using appropriate scales.. A total of 100 postmenopausal women cytologically and clinically diagnosed with VVA were included in the study. After 3 months of treatment with ospemifene, a significant improvement was observed in all domains of Vaginal Health Index. This improvement was maintained at month 12 and only one patient remained with vaginal atrophy. In addition, a significant improvement was observed in the most bothersome symptoms, sexual function, and quality of life. There was no significant change in endometrial thickness, mammography, and bone health during the 12 months of treatment.. This study in routine clinical practice conditions confirms the results previously reported by randomized controlled trials, including a significant improvement in VVA, sexual function, quality of life, endometrial safety, and satisfaction with the treatment.

Topics: Atrophy; Dyspareunia; Female; Follow-Up Studies; Humans; Prospective Studies; Quality of Life; Selective Estrogen Receptor Modulators; Tamoxifen; Treatment Outcome; Vagina; Vaginal Diseases; Vulva

Local oestrogens, the current treatment for vulvar and vaginal atrophy (VVA), are not suitable for all women. Standard of care (SoC) consists of over-the-counter lubricants and moisturisers. Senshio. The aim of this study was to estimate the cost-effectiveness of ospemifene, a selective oestrogen receptor modulator, for the treatment of moderate to severe symptomatic VVA in postmenopausal women who are not candidates for local vaginal oestrogen therapy.. The Scottish Medicines Consortium (SMC) recently evaluated the clinical and cost-effectiveness evidence of ospemifene plus SoC compared with SoC alone. A cost-effectiveness study, from a National Health Service (NHS) Scotland perspective over a lifetime time horizon, was submitted to the SMC. The cohort-based Markov model used robust clinical evidence from two large pivotal phase III randomised controlled studies and included four health states classified by dyspareunia symptom severity: none, mild, moderate and severe. The movement of women between health states was dependent on the effectiveness of treatment in reducing dyspareunia. Extensive sensitivity analyses were undertaken to assess the level of confidence associated with the base-case results.. Treatment with ospemifene was associated with an additional cost of £847 per patient and an increase in quality-adjusted life-years (QALY) of 0.06 per patient. Ospemifene had an incremental cost-effectiveness ratio of £14,138 per QALY. In the probabilistic sensitivity analysis, there was a probability of 89% that ospemifene was cost-effective at a threshold of £20,000 per QALY gained. Ospemifene remained cost-effective under all scenario analyses. The SMC reviewed the clinical and economic evidence and judged that the evidence demonstrated a robust case to support prescribing ospemifene in NHS Scotland.. Ospemifene is a cost-effective intervention that has recently been accepted by the SMC for the treatment of postmenopausal women with moderate to severe VVA who are not candidates for local oestrogen.

Topics: Atrophy; Cost-Benefit Analysis; Female; Humans; Postmenopause; Scotland; State Medicine; Tamoxifen; Vagina

To assess the effect of ospemifene 60 mg/day in vulvovaginal atrophy (VVA) in postmenopausal women under conditions of routine clinical practice after 3 months of follow-up.. The AYSEX study is a Spanish observational, prospective, and unicentric study in which 5 gynecologists recruited postmenopausal women with VVA in routine clinical practice treated with ospemifene 60 mg/day as an appropriate therapeutic option. Vaginal health, sexual health, dryness, dyspareunia, quality of life, and satisfaction with treatment were assessed at baseline and after three months using validated scales.. A total of 100 postmenopausal women cytologically and clinically diagnosed with VVA were included in the study. After 3 months of treatment with ospemifene, vaginal health index increased and vaginal pH, dryness, and dyspareunia decreased significantly (. This study in routine clinical practice conditions confirms the results previously reported by randomized controlled trials, including a significant improvement in VVA, sexual function, quality of life, and satisfaction with the treatment.

Topics: Adult; Aged; Atrophy; Dyspareunia; Female; Follow-Up Studies; Humans; Middle Aged; Personal Satisfaction; Postmenopause; Prospective Studies; Quality of Life; Spain; Tamoxifen; Treatment Outcome; Vagina; Vaginal Diseases; Vulva; Vulvar Diseases

Vulvovaginal atrophy (VVA) resulting from estrogen deprivation at menopause often results in distressing vaginal dryness and dyspareunia. Fewer than 25% of affected women seek help for this condition citing embarrassment, cultural values, an aging or unavailable partner and concerns about use of estrogens following the Women's Health Initiative. Available non-hormonal treatments, such as moisturizers, while affording some relief can be messy to apply and do not prevent disease progression. A new oral selective estrogen receptor modulator, ospemifene, has been found to have strong estrogenic activity in vaginal tissues without adverse estrogenic effects at other sites.

Topics: Aged; Atrophy; COVID-19 Drug Treatment; Dyspareunia; Female; Humans; Menopause; Middle Aged; Postmenopause; Selective Estrogen Receptor Modulators; Tamoxifen; Vagina; Vulva

Ospemifene is a nonsteroidal selective estrogen receptor modulator (SERM) for the treatment of moderate symptomatic vulvar and vaginal atrophy (VVA) due to menopause. A postauthorization safety study is currently examining the incidence of venous thromboembolism (VTE) among postmenopausal women receiving ospemifene or other SERM (raloxifene, bazedoxifene, or tamoxifen, for noncancer indications), or with untreated VVA.. This interim analysis used the US MarketScan Commercial and Medicare Supplemental claims database from 2013 to 2017 to identify incident VTE. The incidence rate and 95% confidence interval of VTE during the first continuous course of treatment (or continuous untreated time for the untreated cohort) were calculated for each cohort overall and by age group, with sensitivity analyses examining incidence in the short term (up to 90 days) and long term (all available follow-up, regardless of treatment changes).. Analyses included 8,188 ospemifene users, 11,777 other SERM users, and 220,242 women with untreated VVA. The incidence per 1,000 person-years and 95% confidence interval of VTE were 3.7 (1.7-7.1) for ospemifene, 11.5 (8.9-14.6) for other SERM, and 11.3 (10.8-11.7) for untreated VVA. Stratification by age and altering the time frame for analysis produced results with similar patterns to the primary analysis.. This interim analysis of an ongoing study suggests a favorable safety profile for ospemifene with respect to VTE. Comparative analyses with covariate adjustment will be performed when data accrual is complete.

Topics: Aged; Atrophy; Female; Humans; Incidence; Medicare; Postmenopause; Selective Estrogen Receptor Modulators; Tamoxifen; United States; Vagina; Venous Thromboembolism; Vulva

Topics: Atrophy; Female; Humans; Incidence; Postmenopause; Selective Estrogen Receptor Modulators; Tamoxifen; Venous Thromboembolism; Venous Thrombosis; Vulva

To report the effects on the urinary function of ospemifene prescribed for vulvovaginal atrophy (VVA) in patients with overactive bladder (OAB) symptoms refractory to the first line of pharmacologic treatment with antimuscarinic or β3-agonists drugs. We also try to identify any predictors of response to the ospemifene treatment.. Twenty-five patients with OAB confirmed by detrusor overactivity at urodynamics, refractory to first-line therapy for OAB, were enrolled for the study. All of them received ospemifene 60 mg for 12 weeks because of concomitant VVA. We performed a clinical examination, a 3-day voiding diary, ultrasound examination of bladder wall thickness (BWT), and evaluation by Visual Analogic Scale (VAS) of vaginal dryness at baseline and at 12 weeks. We evaluated urinary symptoms and their impact on the quality of life with UDI-6 SF and OAB-Q (Qol, sf) questionnaires.. After 12 weeks of treatment, we observed a significant reduction in the daily (24 h) numbers of episodes of micturition, of nocturia, of urgency and of incontinence. We also found a significant reduction in BWT and vaginal dryness, together with an improvement of OAB-Q and UDI6 SF scores. Among patients who subjectively benefited from the treatment, we found a baseline lower prevalence of constipation and a higher degree of vaginal dryness.. Ospemifene might be a useful option for postmenopausal women with VVA and OAB symptoms, refractory to the first line of treatment with β3-agonists or antimuscarinic drugs, before considering invasive options.

Topics: Aged; Atrophy; Female; Humans; Middle Aged; Tamoxifen; Treatment Outcome; Urinary Bladder, Overactive; Urodynamics; Vagina; Vaginal Diseases

To estimate the incidence and recurrence of breast cancer (BC) in patients with vulvovaginal atrophy (VVA) treated with ospemifene and matched untreated VVA patients using real-world data.. Retrospective matched cohort study.. VVA patients were identified from the 2011-2018 US MarketScan® insurance claims database. For incidence, ospemifene-treated VVA patients without evidence of BC prior to index treatment were matched to two untreated VVA controls similarly without history of BC on age, index VVA year, geographic region, Charlson Comorbidity categories, and follow-up time. BC after the index treatment was identified by BC diagnosis codes, mastectomy, chemotherapy, or radiation procedure. Incidence rate, rate ratio (RR) and their 95 % confidence intervals (CI) were calculated. The process was repeated to estimate BC recurrence in patients with a history of BC in 1:1, 1:2 and 1:3 matches.. 1728 ospemifene users and 3456 untreated patients met the inclusion and matching criteria for assessing incidence. The average number of days for which ospemifene was supplied was 314 (standard deviation [SD] = 340). Average follow-up time from index treatment was 937 days (SD = 392) for treated patients and 915 days (SD = 396) for controls. BC incidence rates per 1000 person-years was 2.03 (95 % CI: 1.06-3.91) for treated patients and 3.53 (95 % CI: 2.49-4.99) for controls (RR = 0.58, 95 % CI: 0.28-1.21). No difference in recurrence was observed between ospemifene-treated and matched untreated patients. Ten (32.3 %) treated vs. 25 (40.3 %) controls in the 1:2 matched analysis had a recurrence.. No differences were observed in the BC incidence and recurrence rates in ospemifene users compared with matched controls.

Topics: Atrophy; Breast Neoplasms; Female; Humans; Incidence; Middle Aged; Neoplasm Recurrence, Local; Retrospective Studies; Risk Factors; Selective Estrogen Receptor Modulators; Tamoxifen; Vulva

Topics: Adjuvants, Immunologic; Administration, Intravaginal; Atrophy; Dehydroepiandrosterone; Estrogens; Female; Female Urogenital Diseases; Humans; Lubricants; Menopause; Tamoxifen; Vagina; Vulva

The aim of this study was to assess the effectiveness of ospemifene in the improvement of sexual function in postmenopausal women with vulvovaginal atrophy (VVA) affected by overactive bladder syndrome (OAB) or urge urinary incontinence (UUI). One hundred five postmenopausal patients with VVA affected by OAB and/or UUI were enrolled for the study. All patients received ospemifene 60 mg for 12 weeks. Clinical examination, 3-d voiding diary and the vaginal health index (VHI) were performed at baseline and at 12 weeks. Patients completed the OAB-Q SF, FSFI, FSDS, and SF-36 questionnaires. The patient's satisfaction was also calculated. After 12 weeks, the reduction of urinary symptoms was observed. The OAB-Q symptoms, OAB-Q (HRQL) score were (55.34 ± 13.54 vs. 23.22 ± 9.76; p < .0001) and (22.45 ± 9.78 vs. 70.56 ± 15.49; p < .0001), before and after treatment. SF-36 questionnaire showed a significant improvement (p < .0001). VHI score increased and the women who regularly practice sexual activity increased after treatment. The total FSFI score increased significantly and the FSDS score changed after 12 weeks (p < .0001). The PGI-I after 12 weeks showed a total success rate of 90.5%. Ospemifene is an effective potential therapy for postmenopausal women with VVA affected by OAB or UUI improving sexual function and quality of life.

Topics: Aged; Atrophy; Female; Humans; Middle Aged; Postmenopause; Selective Estrogen Receptor Modulators; Sexuality; Tamoxifen; Urinary Bladder, Overactive; Vagina; Vaginal Diseases

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.

Topics: Atrophy; Consensus; Estrogen Replacement Therapy; Female; Humans; Laser Therapy; Lubricants; Selective Estrogen Receptor Modulators; Sexuality; Tamoxifen; Vagina; Vulva

Vulvo-vaginal atrophy affects the daily lives of most post-menopausal women. We know that ospemifene intake can induce vaginal epithelial improvements within a few weeks; however, direct evidence of the effects of ospemifene on the human vulva and on connective tissue of both the vagina and vulva are lacking.. To evaluate the changes induced by ospemifene on epithelium thickness, glycogen content proliferation index, collagen content, and type I/III collagen ratio in vulvar and vaginal tissue of post-menopausal women.. 20 women who attended our gynecologic clinic for planned surgery were recruited for the study. 11 subjects were taking ospemifene at the time of inclusion, and 9 subjects who were not taking ospemifene were selected as control group. Vaginal and vulvar biopsies were taken during surgery. Histological features and glycogen content were evaluated by standard hematoxylin-eosin and periodic acid-Schiff staining, total collagen and collagen type I/III ratio were evaluated by hydroxyproline assay and Sirius red staining, while the expression of Ki67 was evaluated by immunohistochemistry.. We analyzed histological features of the epithelial and stromal layer of the vaginal and vulvar vestibule mucosa.. Vaginal and vulvar biopsies from women taking ospemifene showed an increased epithelium thickness, glycogen content, and proliferation index compared with the control group. Collagen content was also higher in women taking ospemifene, while an increased ratio between type I and III collagen fibers was found only at vaginal level.. Our study shows that the effectiveness of ospemifene on vaginal tissue also extends to the vulvar vestibule.. This study provides direct evidence of the impact of ospemifene on vaginal and vulvar tissue. A specifically designed longitudinal study may further support our findings.. Ospemifene intake is associated with a marked improvement of various morphological and physiological features of both vaginal and vulvar vestibule epithelium, including the collagen content of the tissues. Alvisi S, Baldassarre M, Gava G, et al. Structure of Epithelial and Stromal Compartments of Vulvar and Vaginal Tissue From Women With Vulvo-Vaginal Atrophy Taking Ospemifene. J Sex Med 2018;15:1776-1784.

Topics: Atrophy; Connective Tissue; Epithelium; Female; Humans; Longitudinal Studies; Middle Aged; Selective Estrogen Receptor Modulators; Tamoxifen; Treatment Outcome; Vaginal Diseases; Vulva; Vulvar Diseases

Two new products recently approved for the treatment of menopausal symptoms contain estrogen receptor agonists/antagonists, which have varying effects on bone, breast, endometrial, and vaginal tissues. Ospemifene improves symptoms of dyspareunia associated with vulvovaginal atrophy. Bazedoxifene combined with conjugated estrogens improves vasomotor symptoms and bone mineral density in postmenopausal women. Clinicians must consider the increased risk for venous and arterial thromboembolic disease posed by these drugs. Clinical trials are ongoing to fully evaluate the drugs' efficacy and safety compared with traditional estrogen-based regimens.

Topics: Atrophy; Bone Density; Female; Hot Flashes; Humans; Indoles; Middle Aged; Postmenopause; Selective Estrogen Receptor Modulators; Tamoxifen; Vaginal Diseases; Vulvar Diseases