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Importance: Safe and effective nonhormonal treatments for menopausal vasomotor symptoms (VMS) are needed. Objective: To evaluate the efficacy and safety of elinzanetant, a selective neurokinin-1,3 receptor antagonist, for the treatment of moderate to severe menopausal vasomotor symptoms. Design, Setting, and Participants: Two randomized double-blind phase 3 trials (OASIS 1 and 2) included postmenopausal participants aged 40 to 65 years experiencing moderate to severe vasomotor symptoms (OASIS 1: 77 sites in the US, Europe, and Israel from August 27, 2021, to November 27, 2023, and OASIS 2: 77 sites in the US, Canada, and Europe from October 29, 2021, to October 10, 2023). Intervention: Once daily oral elinzanetant, 120 mg, for 26 weeks or matching placebo for 12 weeks followed by elinzanetant, 120 mg, for 14 weeks. Main Outcomes and Measures: Primary end points included mean change in frequency and severity of moderate to severe vasomotor symptoms from baseline to weeks 4 and 12, measured by the electronic hot flash daily diary. Secondary end points included Patient-Reported Outcomes Measurement Information System Sleep Disturbance Short Form 8b total T score and Menopause-Specific Quality of Life questionnaire total score from baseline to week 12. Results: Eligible participants (mean [SD] age, OASIS 1: 54.6 [4.9] years; OASIS 2: 54.6 [4.8] years) were randomized to elinzanetant (OASIS 1: n = 199; OASIS 2: n = 200) or placebo (OASIS 1: n = 197; OASIS 2: n = 200). A total of 309 (78.0%) and 324 (81.0%) completed OASIS 1 and 2, respectively. For the elinzanetant and placebo groups, the baseline mean (SD) VMS per 24 hours were 13.4 (6.6) vs 14.3 (13.9) (OASIS 1) and 14.7 (11.1) v 16.2 (11.2) (OASIS 2). Baseline VMS severity was 2.6 (0.2) vs 2.5 (0.2) (OASIS 1) and 2.5 (0.2) vs 2.5 (0.2) (OASIS 2). Elinzanetant significantly reduced VMS frequency at week 4 (OASIS 1: -3.3 [95% CI, -4.5 to -2.1], P < .001; OASIS 2: -3.0 [95% CI, -4.4 to -1.7], P < .001) and at week 12 (OASIS 1: -3.2 [95% CI, -4.8 to -1.6], P < .001; OASIS 2: -3.2 [95% CI, -4.6 to -1.9], P < .001). Elinzanetant also improved VMS severity at week 4 (OASIS 1: -0.3 [95% CI, -0.4 to -0.2], P < .001; OASIS 2: -0.2 [95 CI, -0.3 to -0.1], P < .001) and week 12 (OASIS 1: -0.4 [95% CI, -0.5 to -0.3], P < .001; OASIS 2: -0.3 [95% CI, -0.4 to -0.1], P < .001). Elinzanetant improved sleep disturbances and menopause-related quality of life at week 12, and the safety profile was favorable. Conclusions and Relevance: Elinzanetant was well tolerated and efficacious for moderate to severe menopausal VMS. Trial Registration: ClinicalTrials.gov Identifier: OASIS 1: NCT05042362, OASIS 2: NCT05099159.
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OBJECTIVES: Vasomotor symptoms induced by endocrine therapy are common in breast cancer survivors and a risk factor for therapy discontinuation and lower quality of life. The REALISE study evaluated the real-world treatment landscape in breast cancer survivors with vasomotor symptoms taking endocrine therapy, including pharmaceuticals, lifestyle changes, and over-the-counter products. STUDY DESIGN: Secondary analysis of the Adelphi Vasomotor Disease Specific Programme™, a large cross-sectional point-in-time survey and chart review conducted in the US and five European countries (February-October 2020). Oncologists provided demographic, clinical, and treatment data for adult breast cancer survivors with induced vasomotor symptoms taking endocrine therapy (tamoxifen or aromatase inhibitors); patients voluntarily completed self-report surveys on their symptom severity, concomitant sleep and/or mood symptoms, lifestyle changes, and use of over-the-counter products. MAIN OUTCOME MEASURES: Patient characteristics; vasomotor symptom severity; use of pharmaceuticals, lifestyle changes, and over-the-counter products (from pre-defined lists); lines of treatment. RESULTS: Overall, 77 oncologists reported data for 618 breast cancer survivors, of whom 183 (29.6 %) completed self-report forms. Physicians classified 420 (68.0 %) women as experiencing moderate-severe vasomotor symptoms, of whom 66.9 % were receiving treatment. In total, 15.2 % of all breast cancer survivors were prescribed systemic hormone therapy. Venlafaxine (24.7 %), citalopram (16.5 %), and paroxetine (13.6 %) were the most commonly prescribed nonhormonal medications. Lifestyle changes (77.8 %) and over-the-counter products (61.6 %) were common, especially in patients with concomitant sleep and/or mood symptoms. CONCLUSIONS: Despite contraindications, a relatively large proportion of treatment-seeking breast cancer survivors with vasomotor symptoms were prescribed systemic hormone therapy. This, combined with high patient-reported use of lifestyle changes and over-the-counter products, suggests a need for symptomatic relief and demand for new nonhormonal alternatives with established safety profiles in this population.
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OBJECTIVE: This study aimed to examine physicians' and patients' perceptions regarding symptom burden and impact in women experiencing natural vasomotor symptoms (nVMS) or vasomotor symptoms induced by endocrine therapy for breast cancer (iVMS). METHODS: The cross-sectional survey based on real-world clinical consultations was conducted in the USA and five European countries. Obstetrician-gynecologists, primary-care physicians and oncologists provided demographic and symptom data for patients experiencing VMS; patients optionally self-reported their experiences via questionnaires, including their symptom profile and work/activity burden through the Menopause Quality of Life (MENQOL) and Work Productivity and Activity Impairment (WPAI) tools. RESULTS: Physicians completed survey forms on 2451 consulting patients; patients completed 1029 questionnaires. nVMS and iVMS severity was significantly associated with the severity of mood symptoms and sleep disturbances (p < 0.0001). However, around half of the patients with mild nVMS/iVMS also experienced moderate-severe mood changes (55.4%/43.7%) or sleep disturbances (42.4%/40.4%). Presence of mood/sleep disturbances alongside nVMS increased MENQOL vasomotor scores (p = 0.004/p < 0.001). Presence of sleep disturbances increased WPAI activity impairment (p < 0.001) but mood changes did not. Similar findings were reported for iVMS patients. CONCLUSION: Significant burden from the triad of natural or induced menopausal symptoms, sleep disturbances and mood changes affected women's daily activities, work and quality of life more than vasomotor symptoms alone.
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Neoplasias de la Mama , Sofocos , Menopausia , Calidad de Vida , Humanos , Femenino , Europa (Continente) , Persona de Mediana Edad , Estudios Transversales , Estados Unidos/epidemiología , Encuestas y Cuestionarios , Menopausia/fisiología , Trastornos del Sueño-Vigilia , Adulto , Anciano , Índice de Severidad de la Enfermedad , Sistema Vasomotor/fisiopatologíaRESUMEN
OBJECTIVE: Elinzanetant is a selective neurokinin-1,3 receptor antagonist in development for the treatment of vasomotor symptoms (VMS) associated with menopause. The pivotal, double-blind, randomized, placebo-controlled phase 3 studies Overall Assessment of efficacy and Safety of elinzanetant In patients with vasomotor Symptoms (OASIS) 1 and 2 will assess the efficacy and safety of elinzanetant in women with VMS. METHODS: The OASIS 1 and 2 pivotal studies are designed in accordance with regulatory guidance. Postmenopausal women with moderate/severe VMS are randomized to receive 120 mg elinzanetant or placebo once daily for 12 weeks, followed by a 14-week active treatment extension. Primary endpoints are the mean change in frequency and severity of moderate/severe VMS from baseline to weeks 4 and 12. Key secondary endpoints will assess the onset of action and effects on sleep disturbance and menopause-related quality of life. Primary and key secondary endpoints will be analyzed using a mixed model with repeated measures. Feedback from postmenopausal women with VMS was used during protocol development. RESULTS: Women confirmed the relevance of endpoints that assess the impact of VMS, sleep disturbance, and mood changes, and the need for new nonhormone treatments. Educational materials around study design, conduct and expected assessments and procedures were developed based on questions and concerns raised by women. CONCLUSIONS: The OASIS 1 and 2 pivotal phase 3 studies will enable assessment of the efficacy and safety of elinzanetant as a treatment for VMS, together with its effect on sleep disturbances, depressive symptoms, and menopause-related quality of life. Feedback from postmenopausal women with VMS was used to maximize patient centricity in the trials.
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Sofocos , Menopausia , Calidad de Vida , Adulto , Femenino , Humanos , Persona de Mediana Edad , Método Doble Ciego , Sofocos/tratamiento farmacológico , Menopausia/efectos de los fármacos , Posmenopausia , Resultado del TratamientoRESUMEN
The Heavy menstrual bleeding: Evidence-based Learning for best Practice (HELP) Group developed an educational website about heavy menstrual bleeding (HMB). The "HMB improving Outcomes with Patient counseling and Education" (HOPE) project examined the website's impact on women's knowledge, confidence, and consultations with healthcare providers (HCPs). HOPE was a quantitative online survey of gynecologists and women with HMB in Brazil. After an initial consultation, patients had unlimited access to the website and completed a survey. HCPs also completed a survey about the sconsultation. After a second consultation, HCPs and patients completed another survey. HCP surveys assessed their perception of patients' awareness, understanding, and willingness to discuss HMB. Patient surveys assessed their knowledge, experience, and confidence in discussing HMB. Forty HCPs recruited 400 women with HMB. Based on HCP perceptions at the first consultation, 18 percent of patients had "good knowledge" or "very good knowledge" of HMB, increasing to 69 percent after patients had visited the website. Before and after visiting the website, 34 percent and 69 percent of patients, respectively, regarded their HMB knowledge as "goo.d" Additionally, 17 percent of women reported their anxiety as "highest" during the first consultation; this decreased to 7 percent during the second consultation. After visiting the HELP website, patients' knowledge of HMB improved and they were less anxious.
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Menorragia , Médicos , Humanos , Femenino , Menorragia/psicología , Encuestas y Cuestionarios , BrasilRESUMEN
OBJECTIVE: Neurokinin (NK)-3 and NK-1 receptors have been implicated in the etiology of vasomotor symptoms (VMS) and sleep disturbances associated with menopause. This phase 2b, adaptive, dose-range finding study aimed to assess the efficacy and safety of multiple doses of elinzanetant (NT-814), a selective NK-1,3 receptor antagonist, in women experiencing VMS associated with menopause, and investigate the impact of elinzanetant on sleep and quality of life. METHODS: Postmenopausal women aged 40 to 65 years who experienced seven or more moderate-to-severe VMS per day were randomized to receive elinzanetant 40, 80, 120, or 160 mg or placebo once daily using an adaptive design algorithm. Coprimary endpoints were reduction in mean frequency and severity of moderate-to-severe VMS at weeks 4 and 12. Secondary endpoints included patient-reported assessments of sleep and quality of life. RESULTS: Elinzanetant 120 mg and 160 mg achieved reductions in VMS frequency versus placebo from week 1 throughout 12 weeks of treatment. Least square mean reductions were statistically significant versus placebo at both primary endpoint time points for elinzanetant 120 mg (week 4: -3.93 [SE, 1.02], P < 0.001; week 12: -2.95 [1.15], P = 0.01) and at week 4 for elinzanetant 160 mg (-2.63 [1.03]; P = 0.01). Both doses also led to clinically meaningful improvements in measures of sleep and quality of life. All doses of elinzanetant were well tolerated. CONCLUSIONS: Elinzanetant is an effective and well-tolerated nonhormone treatment option for postmenopausal women with VMS and associated sleep disturbance. Elinzanetant also improves quality of life in women with VMS.
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Sofocos , Calidad de Vida , Femenino , Humanos , Sofocos/tratamiento farmacológico , Resultado del Tratamiento , Menopausia , Sueño , Método Doble CiegoRESUMEN
Since its introduction in 1990, the levonorgestrel-releasing intrauterine system (LNG-IUS) has played a key role in shaping the healthcare landscape of women. Here we explore the development of the first LNG-IUS (Mirena®) and the early clinical trials that demonstrated its potential. We highlight the contraceptive and therapeutic benefits of Mirena®, and discuss how clinical practice has been changed since the introduction of LNG-IUS and other long-acting reversible contraceptive methods. The history of Mirena® is rich in innovation and has also paved the way to the development of smaller intrauterine systems with lower hormone doses. Along with Mirena®, these newer LNG-IUS contribute to improving contraceptive choices for women, allowing them to select the option that is right for them and that meets their needs no matter their age, parity or circumstances.
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Levonorgestrel/historia , Salud de la Mujer/historia , Adulto , Difusión de Innovaciones , Femenino , Historia del Siglo XX , Historia del Siglo XXI , Humanos , EmbarazoRESUMEN
Universal access to sexual and reproductive health services is essential to facilitate the empowerment of women and achievement of gender equality. Increasing access to modern methods of contraception can reduce the incidence of unplanned pregnancy and decrease maternal mortality. Long-acting reversible contraceptives (LARCs) offer high contraceptive efficacy as well as cost-efficacy, providing benefits for both women and healthcare systems. The levonorgestrel-releasing intrauterine system (LNG-IUS) first became available in 1990 with the introduction of Mirena (LNG-IUS 20), a highly effective contraceptive which can reduce menstrual blood loss and provide other therapeutic benefits. The impact of the LNG-IUS on society has been wide ranging, including decreasing the need for abortion, reducing the number of surgical sterilisation procedures performed, as well as reducing the number of hysterectomies carried out for issues such as heavy menstrual bleeding (HMB). In the context of the COVID-19 pandemic, Mirena can provide a treatment option for women with gynaecological issues such as HMB without organic pathology, minimising exposure to the hospital environment and reducing waiting times for surgical appointments. Looking to the future, research and development in the field of the LNG-IUS continues to expand our understanding of these contraceptives in clinical practice and offers the potential to further expand the choices available to women, allowing them to select the option that best meets their needs.
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Anticonceptivos Femeninos/uso terapéutico , Dispositivos Intrauterinos Medicados/tendencias , Levonorgestrel/uso terapéutico , Salud de la Mujer/tendencias , COVID-19 , Preparaciones de Acción Retardada/uso terapéutico , Femenino , Humanos , Salud Pública/tendenciasRESUMEN
OBJECTIVE: The PULSE survey investigated contraceptive decision making, focusing on the use of long-acting reversible contraceptives (LARCs) to determine reasons for their low adoption rates. METHODS: An online questionnaire was sent to women aged 18-49 years in 14 European countries who were considering starting or changing contraceptive method and asked questions based on four stages of contraceptive decision making: awareness, consideration, consultation, and adoption. RESULTS: Overall, 7221 women responded. LARC awareness was high (~73%) but current usage was low (11.3%). Only 24% of LARC-aware women would consider switching to them. Factors associated with decision making differed depending on the stage: e.g. at the awareness phase, women were concerned with suitability, reversibility, and whether the method is hormonal; and at the consideration phase, the efficacy, convenience, and adverse-effect profile were important. Healthcare professionals (HCPs) were the most trusted information source for women's contraceptive decision making. LARCs were discussed less frequently during consultations than other contraceptives and HCPs may be perceived to hold negative opinions on LARCs. CONCLUSION: A lack of knowledge about the features and benefits of LARCs can contribute to misconceptions and low adoption rates. HCPs play an important role in addressing this, as information conveyed during consultations influences women's contraceptive choices.
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Conducta Anticonceptiva/psicología , Toma de Decisiones , Conocimientos, Actitudes y Práctica en Salud , Anticoncepción Reversible de Larga Duración/psicología , Adolescente , Adulto , Conducta Anticonceptiva/estadística & datos numéricos , Europa (Continente) , Femenino , Humanos , Anticoncepción Reversible de Larga Duración/estadística & datos numéricos , Persona de Mediana Edad , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Purpose: Evidence from real-world settings is important to provide an accurate picture of health care delivery. We investigated use of long-acting reversible contraception (LARC) in women aged 15-49 years.Materials and methods: Two surveys, one of women and one of health care professionals (HCPs), were conducted in parallel across seven countries. Participating women completed an online survey to assess contraceptive awareness, current method of contraception, age, and experience with current contraceptive method. HCPs participated in an online survey to provide practice-level information and three anonymous charts of hormonal LARC users.Results: Of 6903 women who completed the survey, 3225 provided information about their current primary contraception method. Overall, 16% used LARC methods, while 52% used oral contraceptives (OCs). Of hormonal intrauterine system users, 72% described their experience as 'very favourable', compared with only 53% of women using OCs. Anonymous patient records (n = 1605) were provided by 550 HCPs who completed the online survey. Most women (64%) had used short-acting reversible contraception before switching to LARC. Physicians perceived 56-84% of LARC users to be highly satisfied with their current form of contraception.Conclusions: Although usage of LARC was low, most women using LARC were highly satisfied with their method of contraception.
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Actitud del Personal de Salud , Anticoncepción Reversible de Larga Duración/psicología , Satisfacción del Paciente , Adolescente , Adulto , Factores de Edad , Concienciación , Dispositivos Anticonceptivos Femeninos , Anticonceptivos Orales/administración & dosificación , Europa (Continente) , Femenino , Humanos , Persona de Mediana Edad , América del Norte , Prioridad del Paciente , Adulto JovenRESUMEN
BACKGROUND: Rates of unintended pregnancies are particularly high in young women, a finding that may be associated with their tendency not to use contraceptives correctly and/or consistently. For millennial women, busy lifestyles and associated stress may impact on daily activities including taking an oral contraceptive pill. METHODS: Contraceptive pill users aged 21-29 years ('millennial' women; N = 4500) from nine countries in Europe and North and South America completed an online questionnaire on their daily habits and activities, disruptions to their routine and associated stress levels. RESULTS: Thirty-nine percent of surveyed participants had forgotten to take their contraceptive pill at least once in the past month; 39% also admitted not taking it at the same time each day. On average, participants had experienced two major disruptions to their daily lives in the past year, with three quarters (74%) believing these disruptions increased their stress levels. Of those who had missed at least one pill in the past year, 40% attributed it to a busy schedule and 21% to stress, among other reasons. Over half of respondents (55%) reported they were more likely to forget their pill when preoccupied. CONCLUSIONS: Times of stress may make it more likely for millennial women to forget to take their pill. Health care providers should be aware of typical contraceptive adherence rates among young women and ensure that contraceptive counselling sessions include discussion of lifestyle issues and potential barriers to adherence. Every woman should be counselled on all available methods, so that she can make an informed choice on what best suits her.