Long-term efficacy and safety of subcutaneous pasireotide alone or in combination with cabergoline in Cushing's disease.

Objective: This study evaluated short- and long-term efficacy and safety of the second-generation somatostatin receptor ligand pasireotide alone or in combination with dopamine agonist cabergoline in patients with Cushing's disease (CD). Study design: This is an open-label, multicenter, non-comparative, Phase II study comprising 35-week core phase and an optional extension phase. All patients started with pasireotide, and cabergoline was added if cortisol remained elevated. Eligible patients had active CD, with or without prior surgery, were pasireotide naïve at screening or had discontinued pasireotide for reasons other than safety. Primary endpoint was proportion of patients with a mean urinary free cortisol (mUFC) level not exceeding the upper limit of normal (ULN) at week 35 with missing data imputed using last available post-baseline assessments. Results: Of 68 patients enrolled, 26 (38.2%) received pasireotide monotherapy and 42 (61.8%) received pasireotide plus cabergoline during the core phase. Thirty-four patients (50.0%; 95% CI 37.6-62.4) achieved the primary endpoint, of whom 17 (50.0%) received pasireotide monotherapy and 17 (50.0%) received combination therapy. Proportion of patients with mUFC control remained stable during the extension phase up to week 99. Treatment with either mono or combination therapy provided sustained improvements in clinical symptoms of hypercortisolism up to week 99. Hyperglycemia and nausea (51.5% each), diarrhea (44.1%) and cholelithiasis (33.8%) were the most frequent adverse events. Conclusion: Addition of cabergoline in patients with persistently elevated mUFC on maximum tolerated doses of pasireotide is an effective and well-tolerated long-term strategy for enhancing control of hypercortisolism in some CD patients. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT01915303, identifier NCT01915303.

Real-World Evidence Study on the Long-Term Safety of Everolimus in Patients With Tuberous Sclerosis Complex: Final Analysis Results.

The TuberOus SClerosis registry to increase disease Awareness (TOSCA) Post-Authorization Safety Study (PASS) was a non-interventional, multicenter, safety substudy that assessed the long-term safety of everolimus in patients with tuberous sclerosis complex (TSC) receiving everolimus for its licensed indications in the European Union (EU). This substudy also aimed to address TSC-associated neuropsychiatric disorders (TAND), sexual development, and male infertility. Eligible patients were enrolled from 39 sites across 11 countries in the EU. Outcomes of interest included the incidence of adverse events (AEs), serious adverse events (SAEs), treatment-related AEs (TRAEs), AEs leading to everolimus discontinuation, AEs of special interest (AESIs), the observed relationship between everolimus blood levels and incidence of AESIs, TAND, and reproductive clinical features. Herein, we present the final analysis results from this substudy (data cutoff date: 22 January 2020). At data cutoff, 179 patients were enrolled (female, 59.2%; age ≥18 years, 65.9%), of which the majority completed the study (76%). Overall, 121 patients (67.6%) had AEs regardless of causality. The most frequent TRAEs (≥5%) were stomatitis (7.8%), aphthous ulcer (6.7%), and hypercholesterolemia (6.1%). The most common treatment-related SAEs (>1%) were pneumonia (3.4%), influenza, pyelonephritis, aphthous ulcer, stomatitis, dyslipidemia, and hypercholesterolemia (1.1% each). Ten patients (5.6%) reported AEs leading to everolimus discontinuation. The common psychiatric disorders (N = 179) were autism spectrum disorder (21.8%), anxiety disorder (12.8%), "other" psychiatric disorders (8.9%), attention-deficit hyperactivity disorder, and depressive disorder (7.8% each). Of 179 patients, 88 (49.2%) had ≥1 behavioral problem. Of these (n = 88), the most common (>20%) were sleep difficulties (47.7%), anxiety (43.2%), mood swings (37.5%), depression mood (35.2%), impulsivity (30.7%), severe aggression (23.9%), and overactivity (22.7%). Of 179 patients, four (2.2%) reported abnormal puberty onset, and three (1.7%) reported other reproductive disorders. Of 106 females, 23 (21.7%) reported menstrual cycle disorders and 10 (9.4%) reported amenorrhea. Available data did not show delays in sexual maturation or an association between sexual development and infertility. The results demonstrate that everolimus has a manageable long-term safety profile in the TSC treatment setting. No new safety signals emerged. This substudy also contributed to the mapping of TAND and reproductive clinical features in patients with TSC.

Safety and Efficacy of Subcutaneous Pasireotide in Patients With Cushing's Disease: Results From an Open-Label, Multicenter, Single-Arm, Multinational, Expanded-Access Study.

Introduction: The efficacy and safety of subcutaneous (sc) pasireotide have been evaluated in a Phase III trial. Here, we report safety and efficacy results from a multinational, expanded-access study of pasireotide sc in patients with Cushing's disease (CD) in a real-world setting (clinicaltrials.gov, identifier: NCT01582061). Methods: Adults with active CD previously untreated with pasireotide were enrolled; pasireotide sc was initiated at 600 µg twice daily (bid; EU countries) or 900 µg bid (non-EU countries; 600 µg bid in patients with impaired glucose metabolism). Pasireotide dose could be adjusted in 300 µg increments/decrements to a maximum of 900 µg bid or minimum of 300 µg bid for sustained urinary free cortisol (UFC) normalization/tolerability issues. Primary objective: document the safety of pasireotide sc in patients with CD. Key secondary objectives: assess the proportion of patients with mean UFC (mUFC) not exceeding the upper limit of normal (ULN) and changes from baseline in clinical signs/symptoms and quality of life (QoL) to weeks 12, 24, and 48. Results: One hundred and four patients received pasireotide: female, n = 84 (80.8%); median duration of pasireotide exposure, 25.1 weeks; median (range) baseline mUFC, 321.2 nmol/24 h (142-10,920; 2.3 × ULN [1.0-79.2]). Forty (38.5%) patients completed the study. The most common reasons for premature discontinuation of pasireotide were unsatisfactory therapeutic effect (n = 26, 25.0%) and adverse events (AEs; n = 20, 19.2%). Drug-related grade 3/4 AEs or drug-related serious AEs (primary endpoint) were documented in 42 (40.4%) patients, most commonly diabetes mellitus (n = 12, 11.5%) and hyperglycemia (n = 8, 7.7%). All patients experienced ≥1 AE and most (n = 102; 98.1%) reported ≥1 drug-related AE; six (5.8%) patients discontinued treatment because of hyperglycemia-related AEs. At weeks 12, 24, and 48, respectively, 36/66 (54.5%), 22/46 (47.8%), and 9/21 (42.9%) evaluable patients had normalized mUFC levels. Clinical signs/symptoms and QoL were also improved. Conclusions: In an international, real-world, clinical-practice setting, pasireotide sc was generally well-tolerated (no new safety signals were identified), effectively reduced UFC (normalization in ~50% of evaluable patients) and improved clinical signs and QoL in patients with CD. While hyperglycemia-related AEs were common, consistent with previous studies, most were manageable, with <6% of patients discontinuing treatment because of these events.

Long-term safety and efficacy of subcutaneous pasireotide in patients with Cushing's disease: interim results from a long-term real-world evidence study.

PURPOSE: Clinical trials have demonstrated the favorable efficacy/safety profile of pasireotide in patients with Cushing's disease (CD). We report interim long-term results of an ongoing real-world evidence study of subcutaneous pasireotide in patients with CD. METHODS: Adults with CD receiving pasireotide, initiated before (prior-use) or at study entry (new-use), were monitored for ≤ 3 years during a multicenter observational study ( http://clinicaltrials.gov identifier NCT02310269). Primary objective was to assess long-term safety of pasireotide alone or with other CD therapies. RESULTS: At the time of this interim analysis, 127 patients had received pasireotide (new-use, n = 31; prior-use, n = 96). Eight patients had completed the 3-year observation period, 53 were ongoing, and 66 had discontinued. Among 31 new-use and 92 prior-use patients with ≥ 1 safety assessment, respectively: 24 (77%) and 37 (40%) had drug-related adverse events (AEs); 7 (23%) and 10 (11%) had serious drug-related AEs. Most common drug-related AEs were nausea (14%), hyperglycemia (11%) and diarrhea (11%); these were more frequently reported in new users and mostly of mild-to-moderate severity. 14 (45%) new-use and 15 (16%) prior-use patients experienced hyperglycemia-related AEs. Mean urinary free cortisol (mUFC) was within normal range at baseline and months 1, 12 and 24, respectively, in: 1/16 (6%), 9/18 (50%), 1/3 (33%) and 0/0 new users; 28/43 (65%), 15/27 (56%), 27/33 (82%) and 12/19 (63%) prior users. CONCLUSIONS: Pasireotide is well tolerated and provides sustained reductions in mUFC during real-world treatment of CD. The lower rate of hyperglycemia-related AEs in prior users suggests that hyperglycemia tends not to deteriorate if effectively managed soon after onset. CLINICAL TRIAL REGISTRATION NUMBER: NCT02310269.

Evaluation of the Efficacy and Safety of Switching to Pasireotide in Patients With Acromegaly Inadequately Controlled With First-Generation Somatostatin Analogs.

Introduction: Acromegaly is a rare, serious endocrine disorder characterized by excess growth hormone (GH) secretion by a pituitary adenoma and overproduction of insulin-like growth factor I (IGF-I). Transsphenoidal surgery is the treatment of choice, although many patients require additional interventions. First-generation somatostatin analogs (SSAs) are the current standard of medical therapy; however, not all patients achieve control of GH and IGF-I. Outcomes from a Phase IIIb open-label study of patients with uncontrolled acromegaly on first-generation SSAs switching to pasireotide are reported. Methods: Adults with uncontrolled acromegaly (mean GH [mGH] ≥1 µg/L from a five-point profile over 2 h, and IGF-I >1.3× upper limit of normal [ULN]) despite ≥3 months' treatment with maximal approved doses of long-acting octreotide/lanreotide received open-label long-acting pasireotide 40 mg/28 days. Pasireotide dose could be increased (maximum: 60 mg/28 days) after week 12 if biochemical control was not achieved, or decreased (minimum: 10 mg/28 days) for tolerability. Patients who completed 36 weeks' treatment could continue receiving pasireotide during an extension (weeks 36-72) when concomitant medication for acromegaly was permitted. Primary endpoint was proportion of patients with mGH <1 µg/L and IGF-I 2.5 µg/L. For patients who entered the extension, 14.8% (95% CI: 8.1-23.9), 12.5% (95% CI: 6.4-21.3), 14.8% (95% CI: 8.1-23.9) and 11.4% (95% CI: 5.6-19.9) had mGH <1 µg/L and IGF-I

Prevalence of postmenopausal symptoms in North America and Europe.

OBJECTIVE: This study aims to evaluate differences and similarities in the prevalence of postmenopausal symptoms and their impact on postmenopausal women and male partners of postmenopausal women in North America and Europe. METHODS: The Internet-based survey Clarifying Vaginal Atrophy's Impact on Sex and Relationships (CLOSER) was conducted in North America and Europe. The questionnaire included questions on symptoms experienced by women after menopause and the impact of these symptoms overall and specifically on emotional and physical relationships. This study included 8,200 respondents: 4,100 were postmenopausal women who had experienced vaginal discomfort and 4,100 were male partners of postmenopausal women with this symptom. Differences were significant at the 95% level of confidence. RESULTS: The survey identified vaginal dryness, hot flashes, night sweats, disrupted sleep, and weight gain as the top five symptoms experienced by postmenopausal women in North America and Europe. Overall, symptoms were found to be more prevalent in women from the United States, United Kingdom, and Canada (P < 0.05), and less prevalent in women from Sweden and Italy compared with other countries. In regards to the impact of symptoms overall and on emotional and physical relationships, the greatest number of women from the United States, United Kingdom, and Canada found the impact to be "worse than expected." CONCLUSIONS: The impact of postmenopausal symptoms on relationships is greater in women from countries where symptoms are more prevalent. Postmenopausal women and male partners of postmenopausal women may benefit from greater education about menopause and open discussions with their healthcare provider.

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

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: Low-dose LET tablets, compared with cream formulations, are associated with greater persistence in the treatment of VA.

Postmenopausal vaginal atrophy: evaluation of treatment with local estrogen therapy.

Postmenopausal vaginal atrophy, resulting from decreased estrogen production, frequently requires treatment. Estrogen preparations provide the most effective treatment; local application is preferred to systemic drugs when treating only vaginal symptoms. As local estrogen therapies have comparable efficacy, this study aimed to understand treatment practices, assess experiences with different forms of local estrogen-delivering applicators, and evaluate satisfaction. Women who were US residents aged ≥18 years, menopausal (no spontaneous menstrual period for ≥1 year or with a double oophorectomy), and receiving local estrogen therapy for 1-6 months (vaginal cream [supplied with a reusable applicator] or vaginal tablets [supplied with a single-use/disposable applicator]), completed an online questionnaire. Data from 200 women (100 cream users and 100 tablet users; mean therapy duration 3.48 months) showed that most stored medication in the room in which it was applied (88%) and applied it at bedtime (71%), a procedure for which cream users required, on average, more than twice the time of tablet users (5.08 minutes versus 2.48 minutes). Many cream users applied larger-than-prescribed amounts of cream, attempting to achieve greater efficacy (42%), or lower-than-recommended doses (45%), most frequently to avoid messiness (33%) or leakage (30%). More tablet users (69%) than cream users (14%) were "extremely satisfied" with their applicator. Postmenopausal women using local estrogen therapy were generally more satisfied with the application of vaginal tablets than cream. Patient satisfaction may help to facilitate accurate dosing. Positive perceptions of medication will help to optimize treatment, which, although not assessed in this study, is likely, in turn, to improve vaginal health.

Clarifying Vaginal Atrophy's Impact on Sex and Relationships (CLOSER) survey: emotional and physical impact of vaginal discomfort on North American postmenopausal women and their partners.

OBJECTIVE: This study aims to determine the emotional and physical impact of vaginal atrophy on North American postmenopausal women and their male partners. METHODS: A weighted sample of 1,000 married or cohabiting North American postmenopausal women aged 55 to 65 years with vaginal discomfort and 1,000 male partners of postmenopausal women aged 55 to 65 years who experienced vaginal discomfort participated in the Clarifying Vaginal Atrophy's Impact on Sex and Relationships (CLOSER) online survey to determine the impact of vaginal discomfort and local estrogen therapy on intimacy, relationships, and women's self-esteem. RESULTS: Vaginal discomfort caused most surveyed North American women to avoid intimacy (58%), experience loss of libido (64%), and experience pain associated with sex (64%). Most surveyed North American men also believed that vaginal discomfort caused their partners to avoid intimacy (78%), experience loss of libido (52%), and find sex painful (59%). Approximately 30% of North American women and men cited vaginal discomfort as the reason they ceased having sex altogether. North American women who used local estrogen therapy to treat their vaginal discomfort reported less painful sex (56%), more satisfying sex (41%), and improved sex life (29%). Most men reported looking forward to having sex (57%) because of their partner's use of local estrogen therapy. CONCLUSIONS: Local estrogen therapy ameliorates the negative impact of vaginal atrophy on the intimate relationships of North American postmenopausal women and their male partners. Additional education and awareness efforts about the symptoms of and available treatments for vaginal atrophy may be of further benefit to North American partners.

The CLOSER (CLarifying Vaginal Atrophy's Impact On SEx and Relationships) survey: implications of vaginal discomfort in postmenopausal women and in male partners.

INTRODUCTION: Postmenopausal vaginal atrophy (VA) is a chronic condition with symptoms that include vaginal dryness, soreness, itching, burning, and dyspareunia. AIM: The CLarifying Vaginal Atrophy's Impact On SEx and Relationships survey evaluated the impact of VA on the physical and emotional aspects of sexual relationships between postmenopausal women and their male partners. METHODS: Four thousand one hundred females and 4,100 males representing the United Kingdom, Finland, Norway, Sweden, Denmark, Italy, France, Canada, and the United States were surveyed. Assessments included: (i) talking about VA and its symptoms; (ii) the impact of VA on intimacy, relationships, and women's self-esteem; (iii) talking about VA and erectile dysfunction (ED); and (iv) the impact of local estrogen therapy (LET) on intimacy and relationships. MAIN OUTCOME MEASURES: Descriptive data on the impact of VA. RESULTS: Twenty-eight percent of women did not tell their partners when they first encountered vaginal discomfort, mainly because they felt "it was just a natural part of growing older" (52%) or because of "embarrassment" (21%). Eighty-two percent of males wanted their partner to share their experiences with VA; males were also more comfortable discussing VA than females (68% vs. 58%, respectively). Having sex less often (women: 58%, men: 61%), less satisfying sex (women: 49%, men: 28%), and putting off having sex (women: 35%, men: 14%) were the main effects of VA. Intimacy avoidance was attributed to painful sex (women: 55%, men: 61%) and women's reduced sexual desire (women: 46%, men: 43%). Discussions about vaginal discomfort and ED were generally limited to partners and healthcare providers (HCPs). LET use resulted in less painful sex (women: 62%, men: 59%) and more satisfying sex (women: 47%, men: 49%). CONCLUSIONS: VA has an adverse emotional and physical impact on postmenopausal women and their partners. These findings may encourage more open communication about VA between couples and their HCPs.

The CLOSER survey: impact of postmenopausal vaginal discomfort on relationships between women and their partners in Northern and Southern Europe.

OBJECTIVES: CLOSER investigated how postmenopausal vaginal atrophy ('vaginal discomfort') affects relationships between women and their partners. STUDY DESIGN: CLOSER involved postmenopausal women (55-65 years) with vaginal discomfort, and male partners of women with the condition. MAIN OUTCOME MEASURES: Structured questionnaire collecting information on impact of vaginal discomfort and local oestrogen treatment on intimacy and relationships, and symptoms and impact of menopause. RESULTS: 1600 women and 1600 men from Northern Europe and 1000 women and 1000 men from Southern Europe were included. Worry that vaginal discomfort would never go away was expressed by 28% and 38% of women in Northern and Southern Europe, respectively (p<0.05), while 21% and 27% worried that vaginal discomfort would ruin their future sex life (p<0.05). Half of women who avoided intimacy worried about painful sex. Among men, 86% wanted their partner to talk about symptoms; two-thirds felt comfortable with this. In Northern and Southern Europe, 15% and 11% of men, respectively, feared that discussing vaginal discomfort would ruin intimacy, while 29% and 19% believed that vaginal discomfort was a big problem in their sex life. Men with partners who avoided intimacy recognised that worry about painful sex was the main reason. Vaginal discomfort impaired self-esteem and emotional wellbeing among women, while local oestrogen treatment improved relationships, particularly in Southern Europe. CONCLUSIONS: Vaginal discomfort impairs quality of life in postmenopausal women and their partners. Southern European women were generally more worried about long-term effects on their relationship, and were more likely to report benefits after treatment.

The CLOSER survey: impact of postmenopausal vaginal discomfort on women and male partners in the UK.

OBJECTIVE: To understand the physical and emotional impact of postmenopausal vaginal discomfort on relationships between women and their male partners. STUDY DESIGN: In a quantitative, Internet-based survey, 8200 individuals from the UK, Denmark, Sweden, Norway, Finland, France, Italy, US and Canada (postmenopausal, married/cohabiting women, aged 55-65 years, who had experienced vaginal discomfort, and male partners of such women) completed a structured questionnaire. MAIN OUTCOME MEASURES: Results for respondents from the UK (500 men, 500 women), expressed as percentages of women/men describing particular answers, are reported. RESULTS: Avoiding physical intimacy because of vaginal discomfort was reported by 69% of women and 76% of male partners, mainly due to concern about sex being painful (women 63%; men 61%); 18% of women considered vaginal discomfort had created emotional distance between them and their partners. Local estrogen treatment was used by 21% of women, among whom 58% subsequently reported less painful sex. Following such treatment, 33% of women and 30% of male partners reported an improved sex life, while 33% of women and 34% of male partners described becoming emotionally closer. Although 73% of women did not consider enough information about vaginal discomfort to be available, 60% would consult a physician to obtain this. CONCLUSIONS: Although vaginal discomfort has a substantial impact on postmenopausal women and their partners, improvements in sexual and emotional relationships can follow use of local estrogen therapy. Not all women may be aware of therapeutic options; healthcare providers can improve outcomes by more openly communicating and initiating discussion with patients.

Improved compliance and patient satisfaction with estradiol vaginal tablets in postmenopausal women previously treated with another local estrogen therapy.

Up to half of all postmenopausal women will experience changes in the genitourinary tract induced by the hypoestrogenic state, collectively known as vaginal atrophy. Vaginally administered local estrogen therapy (LET) is the standard of care for symptoms of vaginal atrophy that do not respond to nonhormonal interventions. Several LET formulations are available, and choice of therapy is based largely on patient needs and preferences. This online survey of postmenopausal LET users was conducted to investigate reasons for switching to vaginal estradiol tablets from other formulations and to evaluate factors associated with patient preference for and compliance with use of LET. Data was analyzed from 73 respondents currently using estradiol vaginal tablets who have previously used the estradiol vaginal ring, estradiol vaginal cream, and/or conjugated estrogen vaginal cream. Patients in this survey rated vaginal symptoms of vaginal atrophy as being more bothersome than urinary symptoms. Respondents preferred their current treatment with the vaginal tablet to their previous treatment with a cream or ring. The preference for tablets over creams was mainly related to formulation and application rather than to any perceived safety issues. Tablets were perceived as efficacious, convenient, and neat to apply. The study participants also reported a longer duration of tablet use compared with creams or rings, and greater compliance with vaginal tablets than with vaginal cream. This study provides new insights into reasons for patient noncompliance with estrogen cream or ring therapy that can be used to maximize patient adherence with LET.

Women's preferences toward attributes of local estrogen therapy for the treatment of vaginal atrophy.

OBJECTIVES: Decreased estrogen production due to menopause is often associated with vaginal atrophy, and estrogen therapy is the most effective treatment for the management of this condition. This study investigated women's preferences relating to various aspects of local estrogen therapy (LET) for the treatment of postmenopausal vaginal atrophy. STUDY DESIGN: The study involved 423 women aged >50 years who were resident in Sweden, had experienced menopausal changes in and around the vagina, and had used LET for these changes. The women completed an online questionnaire. MAIN OUTCOME MEASURES: The questionnaire involved a discrete choice experiment to determine women's willingness to pay for different characteristics of therapy. Time of LET appliance, use of disposable applicators with small tablets compared with both dosing syringes with vaginal cream and vagitories, and therapy that did/did not cause smudges/leakage were all considered. RESULTS: The women had no significant preference as to the time of day LET should be used. However, quantifying other preferences suggested that respondents were willing to pay € 66.58 or € 60.32 per month extra for using disposable applicators with small tablets rather than dosing syringes with vaginal cream or vagitories, respectively, and to avoid smudges/leakage. CONCLUSIONS: This survey suggests that women may prefer using disposable applicators with small tablets to deliver LET and value therapy that does not cause smudges/leakage. It is possible that if women are able to use their preferred form of LET, improved uptake or adherence of such medication may enhance the management of postmenopausal vaginal atrophy.

Vaginal Health: Insights, Views & Attitudes (VIVA) survey - Canadian cohort.

OBJECTIVE: To evaluate knowledge of vaginal atrophy among postmenopausal women (aged 55-65 years), using the Vaginal Health: Insights, Views & Attitudes (VIVA) survey. METHODS: An independent research organization conducted a quantitative Internet-based survey, to obtain information from 3520 women who were living in the UK, the USA, Canada, Sweden, Denmark, Finland or Norway. Findings from Canada are presented (n = 500). RESULTS: Almost half of Canadian respondents had experienced vaginal discomfort since they had stopped menstruating, most commonly (88%) vaginal dryness; over half (56%) reported having experienced symptoms for three years or longer. Seven percent would have attributed vaginal symptoms to vaginal atrophy. Eighty-two percent of women felt that vaginal discomfort would have a negative impact on various aspects of their lives, most notably sexual intimacy (72%), 'having a loving relationship with a partner' (39%) and 'overall quality of life' (30%). While the majority of women (66%) who had experienced vaginal atrophy eventually sought the assistance of a health-care professional, a considerable proportion (34%) did not. Most women (58%) had tried lubricating gels and creams to treat their symptoms, but many were less aware of specific means of treating the underlying cause. However, compared with systemic hormone replacement therapy, more women indicated that they would consider local estrogen therapy (e.g. vaginal tablets or creams). CONCLUSIONS: These data indicate that many postmenopausal women in Canada have a low understanding of vaginal atrophy. Medical practitioners should proactively initiate dialogue about this chronic condition with their patients, and discuss appropriate treatment options.

Treatment of postmenopausal vaginal atrophy with 10-µg estradiol vaginal tablets.

Postmenopausal estrogen deficiency can lead to symptoms of urogenital atrophy. Individuals with urogenital atrophy have symptoms that include vaginal dryness, vaginal and vulval irritation, vaginal soreness, pain and burning during urination (dysuria), increased vaginal discharge, vaginal odour, vaginal infections, recurrent urinary tract infections, pain associated with sexual activity (dyspareunia) and vaginal bleeding associated with sexual activity. Despite the frequency and effects of vaginal atrophy symptoms, they are often under-reported and, consequently, under-treated. Therefore, care of a menopausal woman should include a physical assessment of vaginal atrophy and a dialogue between the physician and the patient that explores existing symptoms and their effect on vulvovaginal health, sexuality and quality-of-life issues. The development of the ultra-low-dose 10-µg estradiol vaginal tablets is in line with the requirements of regulatory agencies and women's health societies regarding the use of the lowest effective hormonal dose. Because of its effectiveness and safety profiles, in addition to its minimal systemic absorption, the 10-µg estradiol vaginal tablet can offer greater reassurance to health-care providers and postmenopausal women with an annual estradiol administration of only 1.14 mg.