RESUMEN
OBJECTIVE: Phase 3 studies of postmenopausal women with or at risk for osteoporosis reported that, compared with placebo, bazedoxifene increased the incidence of hot flushes. The current study evaluated the vasomotor effects of bazedoxifene in healthy nonflushing postmenopausal women. METHODS: In this phase 2 study, nonflushing postmenopausal women (n = 494) were randomized to daily treatment with bazedoxifene 5, 10, or 20 mg; raloxifene 60 mg; or placebo for 12 weeks. The primary endpoint was the percentage of women reporting hot flushes at any time during the study; secondary endpoints included the mean number and severity of hot flushes and the mean number of days with hot flushes. Effects on bone turnover markers and lipid parameters were also evaluated. RESULTS: Over the 12-week study, 25.5% of placebo-treated women reported hot flushes. The incidence of hot flushes with bazedoxifene 5, 10, and 20 mg and raloxifene 60 mg was 26.0%, 33.7%, 27.6%, and 21.4%, respectively, with no significant differences from that with placebo. The active treatment groups showed no significant differences from placebo in the mean number or severity of hot flushes during week 12 or any 4-week period. Bazedoxifene and raloxifene showed beneficial effects on lipid parameters and markers of bone turnover. All doses of bazedoxifene were generally well tolerated and did not increase endometrial thickness, vaginal bleeding, or breast pain compared with placebo over 12 weeks of therapy. CONCLUSIONS: Data from this phase 2 clinical trial suggest that bazedoxifene does not increase the incidence of hot flushes relative to placebo in nonflushing postmenopausal women.
Asunto(s)
Sofocos/inducido químicamente , Indoles/uso terapéutico , Posmenopausia/efectos de los fármacos , Moduladores Selectivos de los Receptores de Estrógeno/uso terapéutico , Conservadores de la Densidad Ósea/efectos adversos , Conservadores de la Densidad Ósea/farmacología , Huesos/efectos de los fármacos , Huesos/metabolismo , Femenino , Humanos , Indoles/efectos adversos , Lípidos/sangre , Persona de Mediana Edad , Osteoporosis Posmenopáusica/tratamiento farmacológico , Clorhidrato de Raloxifeno/efectos adversos , Clorhidrato de Raloxifeno/uso terapéutico , Moduladores Selectivos de los Receptores de Estrógeno/efectos adversosRESUMEN
OBJECTIVE: To evaluate the effects of a tissue-selective estrogen complex (TSEC) composed of bazedoxifene/conjugated estrogens (BZA/CE) on menopausal symptoms, metabolic parameters, and overall safety. DESIGN: Multicenter, double-blind, placebo- and active-controlled phase 3 trial (Selective estrogens, Menopause, And Response to Therapy [SMART]-1). SETTING: Outpatient clinical. PATIENT(S): Healthy, postmenopausal women (n = 3,397) age 40 to 75 with an intact uterus. INTERVENTION(S): Single tablets of BZA (10, 20, or 40 mg), each with CE (0.625 or 0.45 mg); raloxifene 60 mg; or placebo taken daily for 2 years. MAIN OUTCOME MEASURE(S): Hot flushes, breast pain, vaginal atrophy, metabolic parameters, and adverse events. RESULT(S): BZA (20 mg)/CE (0.625 or 0.45 mg) significantly reduced the frequency and severity of hot flushes and improved measures of vaginal atrophy compared with placebo. At week 12, the daily number of hot flushes decreased by 51.7% to 85.7% with all BZA/CE doses vs. 17.1% for placebo. BZA/CE improved lipid parameters and homocysteine levels, did not significantly change carbohydrate metabolism, and had only minor effects on some coagulation parameters. The incidences of breast pain and adverse events were similar between BZA/CE and placebo. CONCLUSION: The TSEC composed of BZA (20 mg)/CE (0.625 or 0.45 mg) is an effective and safe treatment for menopausal symptoms.
Asunto(s)
Estrógenos Conjugados (USP)/uso terapéutico , Estrógenos/uso terapéutico , Sofocos/tratamiento farmacológico , Indoles/uso terapéutico , Menopausia/metabolismo , Moduladores Selectivos de los Receptores de Estrógeno/uso terapéutico , Vagina/patología , Adulto , Anciano , Atrofia/tratamiento farmacológico , Atrofia/patología , Metabolismo de los Hidratos de Carbono/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Quimioterapia Combinada , Estrógenos/efectos adversos , Estrógenos/farmacología , Estrógenos Conjugados (USP)/efectos adversos , Estrógenos Conjugados (USP)/farmacología , Femenino , Homocisteína/metabolismo , Humanos , Indoles/efectos adversos , Indoles/farmacología , Metabolismo de los Lípidos/efectos de los fármacos , Menopausia/efectos de los fármacos , Persona de Mediana Edad , Pacientes Ambulatorios , Moduladores Selectivos de los Receptores de Estrógeno/efectos adversos , Moduladores Selectivos de los Receptores de Estrógeno/farmacología , Resultado del Tratamiento , Vagina/efectos de los fármacosRESUMEN
OBJECTIVE: To assess the endometrial effects of bazedoxifene acetate in healthy postmenopausal women. METHODS: The endometrial effects of bazedoxifene 2.5, 5.0, 10, 20, 30, and 40 mg/d were evaluated in a 2-part, 6-month, double-blind, randomized, active- and placebo-controlled study among a total of 497 healthy postmenopausal women. Conjugated estrogens (0.625 mg)/medroxyprogesterone acetate (2.5 mg) served as the active control. Patients underwent transvaginal ultrasonography to measure double-wall endometrial thickness and endometrial biopsy at baseline and at 6 months of treatment. The incidence of amenorrhea was assessed from self-reported daily diaries. RESULTS: Bazedoxifene treatment at 2.5-20 mg/d resulted in mean changes from baseline in endometrial thickness that were no different than those seen with placebo treatment. Changes in endometrial thickness for the bazedoxifene 30 and 40 mg groups were significantly smaller than for placebo. The change from baseline in endometrial thickness was significantly and inversely related to dose (P < or = .001). None of the endometrial biopsy specimens demonstrated endometrial hyperplasia. Subjects in the 2.5-20 mg bazedoxifene groups experienced amenorrhea rates of 57-74%, comparable with the 59% seen in placebo. Over 90% of subjects treated with bazedoxifene 30 or 40 mg/d were amenorrheic at 6 months. CONCLUSION: Bazedoxifene at dosages up to 40 mg/d was well tolerated and did not stimulate the endometrium. The significant decreases in endometrial thickness and decreased uterine bleeding observed with doses of 30 and 40 mg/d as compared with placebo suggest endometrial antagonism, representing a novel characteristic not previously associated with any selective estrogen receptor modulator.