RESUMO
The 20th annual Santa Fe Bone Symposium was held August 9-10, 2019, in Santa Fe, New Mexico, USA. This is an annual meeting devoted to clinical applications of recent advances in skeletal research that impact the care of patients with osteoporosis, metabolic bone diseases, and inherited bone diseases. Participants included practicing and academic physicians, fellows, advanced practice providers, fracture liaison service (FLS) coordinators, clinical researchers, and bone density technologists. The symposium consisted of lectures, case presentations, and panel discussions, with an emphasis on learning through interaction of all attendees. Topics included new approaches in the use of anabolic agents for the treatment osteoporosis, a review of important events in skeletal health over the past year, new and emerging treatments for rare bone diseases, the use of genetic testing for bone diseases in clinical practice, medication-associated causes of osteoporosis, new concepts in the use of estrogen therapy for osteoporosis, new Official Positions of the International Society for Clinical Densitometry, skeletal consequences of bariatric surgery, and update on the progress and potential of Bone Health TeleECHO, a virtual community of practice using videoconferencing technology to link healthcare professionals for advancing the care of osteoporosis worldwide. Sessions on rare bone diseases were developed in collaboration with the Rare Bone Disease Alliance. Symposium premeetings included an FLS workshop by the National Osteoporosis Foundation and others devoted to the use of new therapeutic agents for the care of osteoporosis and related disorders.
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Doenças Ósseas/terapia , Osteoporose/terapia , Animais , Densidade Óssea , Doenças Ósseas/genética , Doenças Ósseas/metabolismo , Humanos , Doenças Raras/terapiaRESUMO
BACKGROUND: We performed a post hoc, subgroup analysis of a phase 3, randomized, double-blind, placebo-controlled study of erenumab for prevention of episodic migraine (STRIVE) to determine the efficacy and safety of erenumab in women with self-reported menstrual migraine. METHODS: Patients received placebo, erenumab 70 mg, or erenumab 140 mg subcutaneously once monthly during the 6-month double-blind treatment phase of STRIVE. Women who reported history of menstrual migraine and who were ≤ 50 years old were included in the analysis. Endpoints were change from baseline in monthly migraine days (MMD) and monthly acute migraine-specific medication days (MSMD; among patients who took acute migraine-specific medications at baseline), proportion of patients achieving ≥ 50% reduction from baseline in MMD, and incidence of adverse events. RESULTS: Among 814 women enrolled in STRIVE, 232 (28.5%) reported a history of menstrual migraine and were ≤ 50 years old. Of the 232 patients, 214 (92%) had a baseline MMD > 5, suggesting a high proportion of women with attacks outside of the 5-day perimenstrual window (2 days before and 3 days after the start of menstruation). Information on "migraine days" includes (and does not discriminate between) perimenstrual and intermenstrual migraine attacks. Between-group differences from placebo over months 4-6 for erenumab 70 mg and 140 mg were - 1.8 (P = 0.001) and - 2.1 (P < 0.001) days for MMD and - 1.6 (P = 0.002) and - 2.4 (P < 0.001) days for acute MSMD, respectively. The odds of having a ≥ 50% reduction from baseline in MMD over months 4-6 were 2.2 (P = 0.024) and 2.8 (P = 0.002) times greater for erenumab 70 mg and 140 mg, respectively, than for placebo. Erenumab had an overall safety profile comparable to placebo. CONCLUSION: Data from this subgroup analysis of women with menstrual migraine are consistent with data from the overall STRIVE episodic migraine population, supporting the efficacy and safety of erenumab in women who experience menstrual migraine. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02456740. Registered 28 May 2015.
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antagonistas do Receptor do Peptídeo Relacionado ao Gene de Calcitonina/uso terapêutico , Ciclo Menstrual/efeitos dos fármacos , Transtornos de Enxaqueca/tratamento farmacológico , Adulto , Anticorpos Monoclonais Humanizados/farmacologia , Antagonistas do Receptor do Peptídeo Relacionado ao Gene de Calcitonina/farmacologia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Ciclo Menstrual/fisiologia , Pessoa de Meia-Idade , Transtornos de Enxaqueca/fisiopatologia , Autorrelato , Resultado do Tratamento , Adulto JovemRESUMO
IMPORTANCE: The neurokinin 3 receptor antagonist fezolinetant 45 mg/d significantly reduced frequency/severity of moderate to severe vasomotor symptoms (VMS) of menopause compared with placebo in two phase 3 randomized controlled trials. Its efficacy relative to available therapies is unknown. OBJECTIVE: We conducted a systematic review and Bayesian network meta-analysis to compare efficacy with fezolinetant 45 mg and hormone therapy (HT) and non-HT for VMS in postmenopausal women. EVIDENCE REVIEW: Using OvidSP, we systematically searched multiple databases for phase 3 or 4 randomized controlled trials in postmenopausal women with ≥7 moderate to severe VMS per day or ≥50 VMS per week published/presented in English through June 25, 2021. Mean change in frequency and severity of moderate to severe VMS from baseline to week 12 and proportion of women with ≥75% reduction in VMS frequency at week 12 were assessed using fixed-effect models. FINDINGS: The network meta-analysis included data from the pooled phase 3 fezolinetant trials plus 23 comparator publications across the outcomes analyzed (frequency, 19 [34 regimens]; severity, 6 [7 regimens]; ≥75% response, 9 [15 regimens]). Changes in VMS frequency did not differ significantly between fezolinetant 45 mg and any of the 27 HT regimens studied. Fezolinetant 45 mg reduced the frequency of moderate to severe VMS events per day significantly more than all non-HTs evaluated: paroxetine 7.5 mg (mean difference [95% credible interval {CrI}], 1.66 [0.63-2.71]), desvenlafaxine 50 to 200 mg (mean differences [95% CrI], 1.12 [0.10-2.13] to 2.16 [0.90-3.40]), and gabapentin ER 1800 mg (mean difference [95% CrI], 1.63 [0.48-2.81]), and significantly more than placebo (mean difference, 2.78 [95% CrI], 1.93-3.62]). Tibolone 2.5 mg (the only HT regimen evaluable for severity) significantly reduced VMS severity compared with fezolinetant 45 mg. Fezolinetant 45 mg significantly reduced VMS severity compared with desvenlafaxine 50 mg and placebo and did not differ significantly from higher desvenlafaxine doses or gabapentin ER 1800 mg. For ≥75% responder rates, fezolinetant 45 mg was less effective than tibolone 2.5 mg (not available in the United States) and conjugated estrogens 0.625 mg/bazedoxifene 20 mg (available only as 0.45 mg/20 mg in the United States), did not differ significantly from other non-HT regimens studied and was superior to desvenlafaxine 50 mg and placebo. CONCLUSIONS: The only HT regimens that showed significantly greater efficacy than fezolinetant 45 mg on any of the outcomes analyzed are not available in the United States. Fezolinetant 45 mg once daily was statistically significantly more effective than other non-HTs in reducing the frequency of moderate to severe VMS. RELEVANCE: These findings may inform decision making with regard to the individualized management of bothersome VMS due to menopause.
Assuntos
Fogachos , Menopausa , Feminino , Humanos , Fogachos/tratamento farmacológico , Succinato de Desvenlafaxina/farmacologia , Succinato de Desvenlafaxina/uso terapêutico , Metanálise em Rede , Gabapentina , Teorema de Bayes , Menopausa/fisiologia , Estrogênios Conjugados (USP)/uso terapêuticoRESUMO
OBJECTIVE: The aim of this study was to demonstrate whether lasofoxifene improves vaginal signs/symptoms of genitourinary syndrome of menopause. METHODS: Two identical, phase 3 trials randomized postmenopausal women with moderate to severe vaginal symptoms to oral lasofoxifene 0.25 or 0.5 mg/d, or placebo, for 12 week. Changes from baseline to week 12 in most bothersome symptom, vaginal pH, and percentages of vaginal parabasal and superficial cells were evaluated. These coprimary endpoints were analyzed using analysis of covariance, except superficial cells, which were analyzed by the nonparametric, rank-based Kruskal-Wallis test. RESULTS: The two studies enrolled 444 and 445 women (mean age, ~60 y), respectively. Coprimary endpoints at week 12 improved with lasofoxifene 0.25 and 0.5 mg/d greater than with placebo ( P < 0.0125 for all). Study 1: most bothersome symptom (least square mean difference from placebo: -0.4 and -0.5 for 0.25 and 0.5 mg/d, respectively), vaginal pH (-0.65, -0.58), and vaginal superficial (5.2%, 5.4%), and parabasal (-39.9%, -34.9%) cells; study 2: most bothersome symptom (-0.4, -0.5), vaginal pH (-0.57, -0.67), and vaginal superficial (3.5%, 2.2%) and parabasal (-34.1%, -33.5%) cells. Some improvements occurred as early as week 2. Most treatment-emergent adverse events were mild or moderate and hot flushes were most frequently reported (lasofoxifene vs placebo: 13%-23% vs 9%-11%). Serious adverse events were infrequent and no deaths occurred. CONCLUSIONS: In two phase 3 trials, oral lasofoxifene 0.25 and 0.5 mg/d provided significant and clinically meaningful improvements in vaginal signs/symptoms with a favorable safety profile, suggesting beneficial effects of lasofoxifene on genitourinary syndrome of menopause.
Assuntos
Atrofia , Pós-Menopausa , Pirrolidinas , Moduladores Seletivos de Receptor Estrogênico , Tetra-Hidronaftalenos , Vagina , Humanos , Feminino , Pessoa de Meia-Idade , Vagina/patologia , Vagina/efeitos dos fármacos , Pós-Menopausa/efeitos dos fármacos , Tetra-Hidronaftalenos/uso terapêutico , Tetra-Hidronaftalenos/administração & dosagem , Tetra-Hidronaftalenos/efeitos adversos , Atrofia/tratamento farmacológico , Pirrolidinas/efeitos adversos , Pirrolidinas/administração & dosagem , Pirrolidinas/uso terapêutico , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Moduladores Seletivos de Receptor Estrogênico/administração & dosagem , Método Duplo-Cego , Administração Oral , Idoso , Resultado do Tratamento , Doenças Vaginais/tratamento farmacológicoRESUMO
OBJECTIVES: The Women's Health Initiative study reported an increased risk of venous thromboembolism among menopausal women treated with conjugated equine estrogens/medroxyprogesterone acetate (CEE/MPA) versus placebo. Newer hormone therapies may have a lower venous thromboembolism risk. The study compared the risk of venous thromboembolism between women treated with the combined oral product 17ß-estradiol/micronized progesterone (E2/P4) and those treated with oral CEE/MPA regimens. STUDY DESIGN: In a retrospective longitudinal study using real-world claims data from April 2019 to June 2021, women aged 40 years or more treated with oral E2/P4 or oral CEE/MPA who did not have a venous thromboembolism diagnosis before first dispensing claim of CEE/MPA or E2/P4 identified on or after May 1st 2019 (index date) were observed for 6 months or more after the index date. Oral E2/P4 and oral CEE/MPA had been prescribed by the treating physician in real-world practice and were observed through pharmacy dispensing records. MAIN OUTCOME MEASURES: Venous thromboembolism risk was compared between women receiving oral E2/P4 versus oral CEE/MPA. RESULTS: The study included 36,061 women treated with oral E2/P4 or oral CEE/MPA. In the analyses weighted by the inverse probability of treatment for control of potential confounding factors, the incidence of venous thromboembolism was significantly lower for oral E2/P4 compared with oral CEE/MPA (37/10,000 women-years for oral E2/P4 vs 53/10,000 women-years for oral CEE/MPA; incidence rate ratio 0.70, 95 % confidence interval: 0.53-0.92). CONCLUSIONS: Real-world evidence suggests that the risk of venous thromboembolism is significantly lower among women treated with oral E2/P4 compared with oral CEE/MPA.
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Estrogênios Conjugados (USP) , Tromboembolia Venosa , Feminino , Humanos , Estrogênios Conjugados (USP)/efeitos adversos , Progesterona/efeitos adversos , Acetato de Medroxiprogesterona/efeitos adversos , Estradiol , Tromboembolia Venosa/induzido quimicamente , Tromboembolia Venosa/epidemiologia , Estudos Longitudinais , Estudos Retrospectivos , Terapia de Reposição de Estrogênios/efeitos adversosRESUMO
OBJECTIVE: To evaluate bone turnover markers (BTM) in the REPLENISH trial (NCT01942668). METHODS: REPLENISH evaluated oral estradiol/progesterone (E2/P4) for the treatment of moderate to severe vasomotor symptoms (VMS) in postmenopausal women with a uterus. Eligible women for this analysis had ≥50 moderate to severe VMS/wk, were <5âyears since last menstrual period, and had BTM measurements at baseline, and months 6 and 12. Percent changes for three BTM (bone-specific alkaline phosphatase [BSAP], C-terminal telopeptide of type I collagen [CTX-1], and N-terminal propeptide of type I procollagen [P1NP]) assessed by immunoassay methods were evaluated from baseline to months 6 and 12 for the 1âmg E2/100âmg P4, 0.5âmg E2/100âmg P4, and placebo groups. RESULTS: A total of 157 women (40-61ây, 69% White) were analyzed. Mean baseline values ranged from 14.0 to 14.3âU/L for BSAP, 0.34 to 0.39âng/mL for CTX-1, and 76.9 to 79.3âng/mL for PINP. Mean differences in percent change from baseline for both E2/P4 doses versus placebo significantly decreased at months 6 and 12 and ranged from -8% to -16% for BSAP (all, Pâ<â0.05), -30% to -41% for CTX-1 (all, P ≤ 0.001), and -14% to -29% for PINP (all, Pâ<â0.01). CONCLUSIONS: REPLENISH data provide support for a potential skeletal benefit of E2/P4 when it is used for the treatment of moderate to severe VMS. Further studies are warranted.
Video Summary : http://links.lww.com/MENO/A894 .
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Fogachos , Progesterona , Adulto , Biomarcadores , Remodelação Óssea , Cápsulas , Colágeno Tipo I , Feminino , Fogachos/tratamento farmacológico , Humanos , Pessoa de Meia-Idade , Fragmentos de Peptídeos , Pós-MenopausaRESUMO
OBJECTIVE: Menopause is associated with an increased prevalence of sleep difficulties. We evaluated the economic burden of sleep disturbances among working midlife women. METHODS: This retrospective, longitudinal cohort study collected data from the US Study of Women's Health Across the Nation (SWAN) database of women age 42-52âyears at enrollment. We assessed the association between sleep disturbances (trouble falling asleep, waking early, or nocturnal awakenings) and workplace productivity (employment [yes/no] and work hours/wk) for women who were employed at the baseline visit and had ≥1 follow-up visit. We estimated overall economic burden by multiplying changes in productivity by median age-specific hourly US wages. Each woman's data were compared from visit to visit and were excluded after the first observed unemployment. Regression analysis was used to estimate associations between changes in sleep and changes in workplace productivity while controlling for relevant characteristics that varied over time. RESULTS: The analysis included 2,489 working women (19,707 visits); 31% became unemployed during follow-up. Risk of unemployment was 31% higher for women with versus without new-onset sleep disturbances (Pâ =â0.0474). Onset of sleep disturbances was associated with a 0.44-0.57âhours/wk reduction in work time (not significant). Using the more conservative reduction (0.44âh), sleep problems were associated with an annual loss of $517 to $524 per woman and $2.2âbillion/yr in lost productivity among women age 42-64 nationwide. CONCLUSIONS: New-onset sleep problems in midlife women are associated with significant increases in risk of unemployment and â¼$2âbillion/yr in lost productivity nationwide.
Video Summary : http://links.lww.com/MENO/A798 .
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Transtornos do Sono-Vigília , Adulto , Feminino , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Estudos Retrospectivos , Sono , Transtornos do Sono-Vigília/epidemiologia , DesempregoRESUMO
Genitourinary syndrome of menopause is a condition comprising the atrophic symptoms and signs women may experience in the vulvovaginal and bladder-urethral areas as a result of the loss of sex steroids that occurs with menopause. It is a progressive condition that does not resolve without treatment and can adversely affect a woman's quality of life. For a variety of reasons, many symptomatic women do not seek treatment and, of those who do, many are unhappy with their options. Additionally, many healthcare providers do not actively screen their menopausal patients for the symptoms of genitourinary syndrome of menopause. In this review, we discuss the clinical presentation of genitourinary syndrome of menopause as well as the treatment guidelines recommended by the major societies engaged in women's health. This is followed by a review of available treatment options that includes both hormonal and non-hormonal therapies. We discuss both the systemic and vaginal estrogen products that have been available for decades and remain important treatment options for patients; however, a major intent of the review is to provide information on the newer, non-estrogen pharmacologic treatment options, in particular oral ospemifene and vaginal prasterone. A discussion of adjunctive therapies such as moisturizers, lubricants, physical therapy/dilators, hyaluronic acid, and laser therapy is included. We also address some of the available data on both the patient and healthcare providers perspectives on treatment, including cost, and touch briefly on the topic of treating women with a history of, or at high risk for, breast cancer.
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Doenças Urogenitais Femininas/diagnóstico , Doenças Urogenitais Femininas/tratamento farmacológico , Menopausa/fisiologia , Terapia de Reposição de Estrogênios , Feminino , Doenças Urogenitais Femininas/fisiopatologia , Humanos , Menopausa/efeitos dos fármacos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Síndrome , Saúde da MulherRESUMO
OBJECTIVE: The aim of this study was to determine the clinical meaningfulness of TX-001HR in reducing moderate to severe vasomotor symptoms (VMS) in menopausal women with a uterus. METHODS: In the REPLENISH study (NCT01942668), women with moderate to severe hot flushes (≥7/d or ≥50/wk) were enrolled in a VMS substudy and randomized to four doses of daily TX-001HR (17ß-estradiol/progesterone) or placebo. Participants assessed improvement of their VMS by the Clinical Global Impression and the Menopause-Specific Quality of Life (MENQOL) questionnaire, which were used to define clinical responders, clinically important differences (CIDs) or minimal CID (MCID) in VMS frequency. Response thresholds were determined by nonparametric discriminant analyses utilizing bootstrapping methods. RESULTS: In the modified intent-to-treat VMS substudy population (n = 726), statistically significantly more Clinical Global Impression-based clinical responders were observed with TX-001HR than placebo for MCID (weekly reduction of ≥25 moderate to severe VMS: 82-88% vs 69%; all, Pâ<â0.05) and CID (weekly reduction of ≥39 VMS: 68%-73% vs 52%; all, Pâ<â0.05) at week 12. Week 4 results were similar. For Menopause Quality of Life-based analysis, significantly more clinical responders were observed with TX-001HR than placebo for MCID (weekly reduction of ≥34 VMS: 74%-81% vs 55%; all, Pâ<â0.01) and CID (weekly reduction of ≥44 VMS: 61%-69% vs 42%; all, Pâ<â0.01) at week 12. CONCLUSIONS: TX-001HR provided clinically meaningful improvements (as measured by 2 different methods), in addition to statistically significant reductions, in menopausal VMS frequency. TX-001HR may provide a new option, as a single oral capsule of estradiol and progesterone (identical to the hormones naturally occurring in women) for the treatment of moderate to severe VMS in menopausal women with a uterus.
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Estradiol/uso terapêutico , Terapia de Reposição de Estrogênios/métodos , Estrogênios/uso terapêutico , Fogachos/tratamento farmacológico , Progesterona/uso terapêutico , Progestinas/uso terapêutico , Adulto , Idoso , Método Duplo-Cego , Combinação de Medicamentos , Estradiol/administração & dosagem , Estrogênios/administração & dosagem , Feminino , Humanos , Menopausa , Pessoa de Meia-Idade , Progesterona/administração & dosagem , Progestinas/administração & dosagem , Qualidade de Vida , Inquéritos e Questionários , Resultado do Tratamento , ÚteroRESUMO
OBJECTIVE: To explore the bone turnover marker profile during the menstrual cycle of premenopausal women. DESIGN: This was a noninterventional study. Levels of bone turnover markers, including serum C-terminal telopeptide of type I collagen (sCTX), bone-specific alkaline phosphatase, osteocalcin, procollagen type 1 N propeptide, and urinary N-terminal telopeptide of type I collagen, were measured in blood and urine samples during one menstrual cycle. Levels were expressed as raw test results and percent change from serum luteinizing hormone peak. Differences in mean levels of bone turnover markers between menstrual phases and subphases were examined. RESULTS: Fifty-five women comprised the per-protocol population. Mean sCTX values were 0.48 ng/mL during the follicular phase (FP), 0.47 ng/mL at serum luteinizing hormone peak, and 0.43 ng/mL during the luteal phase (LP). Additionally, the mean percent change from luteinizing hormone peak varied from +4.35% during the FP to -5.11% during the LP (P = 0.0014). Mean sCTX levels during the early and through mid FP were significantly higher than levels during the mid and late LP. The pattern for urinary N-terminal telopeptide of type I collagen was similar to that of sCTX but not statistically significant. There was a statistically significant tendency for procollagen type I N propeptide levels to be lower during the FP relative to the LP. Levels of osteocalcin and bone-specific alkaline phosphatase did not vary significantly during the menstrual cycle. CONCLUSIONS: Levels of some bone turnover markers varied during the menstrual cycle. A statistically significant change in sCTX (9.46%) occurred between the FP and LP of the menstrual cycle.
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Remodelação Óssea , Colágeno Tipo I/metabolismo , Ciclo Menstrual , Peptídeos/metabolismo , Pré-Menopausa , Adolescente , Adulto , Fosfatase Alcalina/metabolismo , Biomarcadores/análise , Feminino , Fase Folicular/metabolismo , Humanos , Fase Luteal/metabolismo , Osteocalcina/metabolismo , Fragmentos de Peptídeos/metabolismo , Pró-Colágeno/metabolismoAssuntos
Conservadores da Densidade Óssea/uso terapêutico , Osteoporose Pós-Menopausa/prevenção & controle , Fraturas por Osteoporose/prevenção & controle , Doenças Ósseas Metabólicas/tratamento farmacológico , Doenças Ósseas Metabólicas/fisiopatologia , Técnicas de Apoio para a Decisão , Feminino , Humanos , Fraturas por Osteoporose/etiologia , Medição de RiscoRESUMO
Menopause practitioners are often asked to help postmenopausal women restore vaginal health and function. A common scenario is the postmenopausal woman who has been without a sexual partner for many years and is now about to resume or has already unsuccessfully attempted penetrative sexual activity. This Practice Pearl addresses the pathophysiology and effect of atrophic genital changes and offers advice on how vaginal health and comfortable sexual activity can be restored.
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Dispareunia/terapia , Menopausa , Doenças Vaginais/terapia , Terapia de Reposição de Estrogênios , Feminino , Humanos , Modalidades de Fisioterapia , SíndromeRESUMO
OBJECTIVE: In the 1-year phase 3 Selective estrogens, Menopause, And Response to Therapy-5 trial, cumulative amenorrhea rates with conjugated estrogens/bazedoxifene (CE/BZA) were similar to placebo and higher than with conjugated estrogens/medroxyprogesterone acetate (CE/MPA). This post hoc analysis reports bleeding/spotting rates in 4-week intervals (cycles) and 3-month intervals (quarters) with these therapies and the percentage of cases attributable to spotting only. METHODS: Generally healthy postmenopausal women with menopausal symptoms recorded vaginal bleeding/spotting in daily diaries while receiving CE 0.45 mg/BZA 20 mg, CE 0.625 mg/BZA 20 mg, CE 0.45 mg/MPA 1.5 mg, or placebo. RESULTS: A total of 1596 women in the modified intent-to-treat population contributed data. Incidence of bleeding/spotting was significantly (p < 0.001) lower with CE 0.45 mg/BZA 20 mg (0.54â4.44%), CE 0.625 mg/BZA 20 mg (1.26â5.02%), and placebo (1.55â4.82%) compared with CE 0.45 mg/MPA 1.5 mg (8.81â25.63%) in all 4-week cycles. Each quarter, <10% of women taking CE/BZA doses or placebo had bleeding/spotting, significantly (p < 0.001) less than the 21-36% with CE 0.45 mg/MPA 1.5 mg. Odds ratio for bleeding/spotting with CE 0.45 mg/BZA 20 mg vs CE 0.45 mg/MPA 1.5 mg was 0.1 in each quarter (95% CI, Q1-Q3: 0.1-0.2; Q4: 0.1-0.3). Across all treatments, most (88-100%) bleeding/spotting cases were spotting only. Mean days of bleeding/spotting were <1 per quarter with CE/BZA doses and placebo, which was significantly (p < 0.01) less than the 3-5 days per quarter with CE/MPA. CONCLUSIONS: Bleeding/spotting with CE/BZA treatment was similar to placebo and significantly less frequent than with CE/MPA treatment. Most cases were spotting only across all treatments.
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Terapia de Reposição de Estrogênios/efeitos adversos , Estrogênios Conjugados (USP)/efeitos adversos , Indóis/efeitos adversos , Acetato de Medroxiprogesterona/efeitos adversos , Moduladores Seletivos de Receptor Estrogênico/efeitos adversos , Hemorragia Uterina/induzido quimicamente , Adulto , Idoso , Relação Dose-Resposta a Droga , Método Duplo-Cego , Terapia de Reposição de Estrogênios/métodos , Estrogênios Conjugados (USP)/administração & dosagem , Feminino , Humanos , Indóis/administração & dosagem , Acetato de Medroxiprogesterona/administração & dosagem , Pessoa de Meia-Idade , Pós-Menopausa , Moduladores Seletivos de Receptor Estrogênico/administração & dosagemRESUMO
OBJECTIVE: The aim of the study was to evaluate the effects of TX-001HR, a single-capsule 17ß-estradiol-progesterone on sleep parameters in postmenopausal women with vasomotor symptoms (VMS) using the Medical Outcomes Study (MOS)-Sleep scale questionnaire in the REPLENISH trial. METHODS: In the REPLENISH trial (NCT01942668), women were randomized to one of four doses of TX-001HR or placebo, and the 12-item MOS-Sleep questionnaire (secondary endpoint) was self-administered at baseline, week 12, and months 6 and 12. Changes from baseline in the MOS-Sleep total score and 7 subscale scores were analyzed for treatment groups versus placebo at all time points. Somnolence was also collected as an adverse event. RESULTS: Women (mean age 55 y) were randomized to TX-001HR (estradiol/ progesterone [E2/P4] [mg/mg]) doses: 1/100 (nâ=â415), 0.5/100 (nâ=â424), 0.5/50 (nâ=â421), 0.25/50 (nâ=â424), or placebo (nâ=â151). TX-001HR significantly improved MOS-Sleep total score, Sleep Problems Index II subscale, and sleep disturbance subscale versus placebo at all time points, except with 0.25âmg E2/50âmg P4 at week 12. Differences in LS mean changes between TX-001HR and placebo for MOS-Sleep total scores ranged from -6.5 to -7.6 at 12 months (all; P ≤ 0.001). All doses of TX-001HR significantly improved the Sleep Problems Index I subscale at all time points. The sleep somnolence subscale significantly improved from baseline with 0.5âmg E2/100âmg P4 and 0.5âmg E2/50âmg P4 at month 12. The incidence of somnolence as a treatment-emergent adverse event ranged from 0.2% to 1.2% versus 0% with placebo. CONCLUSION: TX-001HR significantly improved MOS-Sleep parameters from baseline to week 12, which was sustained for up to 12 months, and was associated with a very low incidence of somnolence.
Assuntos
Estradiol/uso terapêutico , Pós-Menopausa , Progesterona/uso terapêutico , Transtornos do Sono-Vigília/tratamento farmacológico , Administração Oral , Relação Dose-Resposta a Droga , Estradiol/administração & dosagem , Terapia de Reposição de Estrogênios , Feminino , Humanos , Pessoa de Meia-Idade , Progesterona/administração & dosagem , Inquéritos e Questionários , Resultado do Tratamento , Estados UnidosRESUMO
OBJECTIVE: To evaluate efficacy, endometrial safety, and overall safety of a single-capsule 17ß-estradiol-progesterone (TX-001HR) for treating menopausal moderate-to-severe vasomotor symptoms. METHODS: REPLENISH was a phase 3, 12-month, randomized, double-blind, placebo-controlled, multicenter trial. Women (aged 40-65 years) with vasomotor symptoms and a uterus were randomized to daily estradiol (mg)-progesterone (mg) (1/100, 0.5/100, 0.5/50, or 0.25/50), and women in the vasomotor symptoms substudy (women with moderate-to-severe hot flushes [seven or greater per day or 50 or greater per week]) to those estradiol-progesterone doses or placebo. The primary safety endpoint was endometrial hyperplasia incidence at 12 months in all women (the total population), and the primary efficacy endpoints were frequency and severity changes (from daily diaries) in moderate-to-severe vasomotor symptoms with estradiol-progesterone compared with placebo at weeks 4 and 12 in the vasomotor symptoms substudy. A sample size of 250 women in each active treatment arm with two or less endometrial hyperplasia cases would result in 1% or less annual incidence (upper bound 2.5% or less, one-sided 95% CI). RESULTS: One thousand eight hundred forty-five women were enrolled and randomized from August 2013 to October 2015; 1,835 received medication (safety population); 1,255 were eligible for the endometrial safety population; 726 comprised the vasomotor symptoms substudy; their mean age and body mass index were 55 years and 27, respectively; one third were African American. No endometrial hyperplasia was found. Frequency and severity of vasomotor symptoms significantly decreased from baseline with 1 mg estradiol and 100 mg progesterone and 0.5 mg estradiol and 100 mg progesterone compared with placebo at week 4 (frequency: by 40.6 and 35.1 points [1 mg and 100 mg and 0.5 mg and 100 mg, respectively] vs 26.4 points [placebo]; severity: by 0.48 and 0.51 vs 0.34 points) and week 12 (by 55.1 and 53.7 vs 40.2; severity: by 1.12 and 0.90 vs 0.56); 0.5 mg estradiol and 50 mg progesterone improved (P<.05) frequency and severity at week 12, and 0.25 mg estradiol and 50 mg progesterone frequency but not severity at weeks 4 and 12. CONCLUSION: No endometrial hyperplasia was observed while single-capsule estradiol-progesterone provided clinically meaningfully improvements in moderate-to-severe vasomotor symptoms. This estradiol-progesterone formulation may represent a new option, using naturally occurring hormones, for the estimated millions of women using nonregulatory-approved, compounded hormone therapy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT01942668.
Assuntos
Estradiol/administração & dosagem , Terapia de Reposição de Estrogênios/métodos , Pós-Menopausa/efeitos dos fármacos , Progesterona/administração & dosagem , Administração Oral , Adulto , Idoso , Cápsulas , Método Duplo-Cego , Feminino , Fogachos/tratamento farmacológico , Humanos , Pessoa de Meia-Idade , Resultado do Tratamento , Sistema Vasomotor/efeitos dos fármacosRESUMO
The objective of The North American Menopause Society (NAMS) and The International Society for the Study of Women's Sexual Health (ISSWSH) Expert Consensus Panel was to create a point of care algorithm for treating genitourinary syndrome of menopause (GSM) in women with or at high risk for breast cancer. The consensus recommendations will assist healthcare providers in managing GSM with a goal of improving the care and quality of life for these women. The Expert Consensus Panel is comprised of a diverse group of 16 multidisciplinary experts well respected in their fields. The panelists individually conducted an evidence-based review of the literature in their respective areas of expertise. They then met to discuss the latest treatment options for genitourinary syndrome of menopause (GSM) in survivors of breast cancer and review management strategies for GSM in women with or at high risk for breast cancer, using a modified Delphi method. This iterative process involved presentations summarizing the current literature, debate, and discussion of divergent opinions concerning GSM assessment and management, leading to the development of consensus recommendations for the clinician.Genitourinary syndrome of menopause is more prevalent in survivors of breast cancer, is commonly undiagnosed and untreated, and may have early onset because of cancer treatments or risk-reducing strategies. The paucity of evidence regarding the safety of vaginal hormone therapies in women with or at high risk for breast cancer has resulted in avoidance of treatment, potentially adversely affecting quality of life and intimate relationships. Factors influencing decision-making regarding treatment for GSM include breast cancer recurrence risk, severity of symptoms, response to prior therapies, and personal preference.We review current evidence for various pharmacologic and nonpharmacologic therapeutic modalities in women with a history of or at high risk for breast cancer and highlight the substantial gaps in the evidence for safe and effective therapies and the need for future research. Treatment of GSM is individualized, with nonhormone treatments generally being first line in this population. The use of local hormone therapies may be an option for some women who fail nonpharmacologic and nonhormone treatments after a discussion of risks and benefits and review with a woman's oncologist. We provide consensus recommendations for an approach to the management of GSM in specific patient populations, including women at high risk for breast cancer, women with estrogen-receptor positive breast cancers, women with triple-negative breast cancers, and women with metastatic disease.
Assuntos
Neoplasias da Mama , Terapia de Reposição de Estrogênios , Doenças Urogenitais Femininas/tratamento farmacológico , Menopausa , Atrofia , Feminino , Saúde Global , Humanos , América do Norte , Guias de Prática Clínica como Assunto , Sociedades Médicas , Sobreviventes , Síndrome , Vagina/patologia , Vulva/patologiaRESUMO
BACKGROUND: Biochemical markers of bone turnover (BTMs) provide useful information in the diagnosis and management of metabolic bone diseases. Currently, there exist few published reference ranges for bone markers in healthy premenopausal women using the newer, automated assays of bone turnover. This cross-sectional study of healthy premenopausal women was performed to determine reference ranges for four different markers of bone turnover and to compare reference ranges in users and non-users of oral contraceptives (OCs). METHODS: Urinary N-telopeptide of type 1 collagen (NTX) was determined from fasting second morning-void urine of healthy premenopausal women. In addition, fasting serum was collected for determination of C-telopeptide of type I collagen (CTX), bone-specific alkaline phosphatase (bone ALP), and N-terminal propeptide of type 1 procollagen (PINP). Subjects underwent central dual energy X-ray absorptiometry and completed a questionnaire regarding medical history and activities known to affect bone health. RESULTS: Serum and urine samples were collected from 237 healthy premenopausal women (119 OC users and 118 non-users) between the ages of 28 and 45 years. The mean age of subjects was 37 years, with a mean bone mineral density T-score of -0.1 at the lumbar spine and 0.0 at the total hip. Logarithmic transformation produced normal distributions for all markers but NTX. Mid-95% ranges for each marker were generally consistent with those reported by manufacturers. For each BTM examined, values were skewed toward the lower end of the range. Median NTX levels for OC users and non-users were 16.0 and 29.0 nmol/mmol creatinine, respectively. The mid-95% ranges for NTX in OC users and non-users were 3-60 and 4-64 nmol/mmol creatinine, respectively. Median levels of CTX, bone ALP, and PINP were also lower in OC users than non-users. The mean level of each BTM was significantly lower in OC users than non-users (P<0.01), whereas reference ranges (geometric mean+/-2 SD) were somewhat similar for the two groups. CONCLUSION: Values obtained from this well-characterized population provide reference ranges for BTMs in healthy premenopausal women. Median and mean BTM levels for OC users were consistently lower compared with non-users; thus, separate reference ranges are required for these two groups of premenopausal women. The relevance of premenopausal reference ranges for postmenopausal women remains uncertain.
Assuntos
Osso e Ossos/metabolismo , Saúde , Pré-Menopausa , Adulto , Distribuição por Idade , Fosfatase Alcalina/sangue , Biomarcadores/sangue , Biomarcadores/urina , Colágeno Tipo I/sangue , Colágeno Tipo I/urina , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Pró-Colágeno/sangue , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: The aim of the study was to examine whether physicians who are better informed about large, published hormone therapy (HT) trials (eg, the Women's Health Initiative) are more likely to prescribe HT for menopausal symptoms. METHODS: US obstetricians/gynecologists and primary care physicians completed a 15- to 20-minute Internet-based survey. Knowledge was assessed via nine true-false statements about HT trials (range: 0-9). Prescribing practices were assessed via six case studies with a seven-point response scale of "extremely unlikely" to "extremely likely" in relation to treatment options (range: 6-42). The primary analysis examined the correlation between HT trial knowledge and likelihood of prescribing HT. Secondary analyses gauged knowledge and prescribing practices based on practice type, sex, and years in practice. RESULTS: Among 501 physicians who completed the survey (representing 10.7% of those invited; median age: 51.0 y; female: 26.9%; obstetricians/gynecologists: 49.9%; median 19.0 y in practice), HT knowledge (mean [SD] 3.8 [2.3]), and prescribing (mean [SD] 24.5 [5.6]) exhibited a statistically significant, moderate positive correlation (0.30; 95% CI, 0.21-0.37; Pâ<â0.0001). Obstetricians/gynecologists were significantly (Pâ<â0.0001) more knowledgeable and more likely to prescribe HT than primary care physicians. Male physicians were more likely (Pâ<â0.05) to prescribe HT but not more knowledgeable about it than female physicians. Knowledge (but not likelihood of prescribing) significantly increased as a function of years in practice. CONCLUSIONS: Physicians who are more knowledgeable about large, published HT trials are more likely to prescribe HT for menopausal symptoms.
Assuntos
Terapia de Reposição de Estrogênios/estatística & dados numéricos , Conhecimentos, Atitudes e Prática em Saúde , Menopausa , Padrões de Prática Médica/estatística & dados numéricos , Adulto , Idoso , Feminino , Fogachos/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Estados Unidos , Saúde da MulherRESUMO
INTRODUCTION: While benefits and risks of hormone therapy (HT) have been shown in rigorous randomized, controlled trials, clinical use and further study have discovered effects of age, time of HT initiation, and differential effects of various regimens and administration routes on its safety profile. Areas covered: The safety of HT with regard to cardiovascular disease, thrombosis, the endometrium, the breast, and cognition was reviewed. Differential safety effects of estradiol versus conjugated equine estrogens, and progesterone versus synthetic progestins are reported. Expert opinion: Perceived safety of HT has evolved based on data from observational studies, the Women's Health Initiative and its subsequent analyses, more recent randomized, controlled trials, and studies examining the differences between different estrogens and between different progestogens. Unexpected safety concerns with HT became apparent with release of the first results from WHI. Differences between estrogen-alone versus estrogen-progestogen therapies, estradiol versus conjugated equine estrogens, and progesterone versus progestins were found in subsequent WHI analyses and studies examining components of various regimens. The decision to use HT depends on balancing risks and benefits for each individual and determining the most appropriate choice of therapy, dosing, and route of administration, while also considering the safety evidence of different estrogens and progestogens.
Assuntos
Terapia de Reposição de Estrogênios/métodos , Menopausa , Estradiol/administração & dosagem , Estradiol/efeitos adversos , Terapia de Reposição de Estrogênios/efeitos adversos , Estrogênios/administração & dosagem , Estrogênios/efeitos adversos , Estrogênios Conjugados (USP)/administração & dosagem , Estrogênios Conjugados (USP)/efeitos adversos , Humanos , Progestinas/administração & dosagem , Progestinas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
OBJECTIVE: To evaluate the response of the vaginal mucosa with TX-004HR and its correlation with vulvar and vaginal atrophy (VVA) symptoms, and whether visual examination is a useful measure for assessing VVA. METHODS: REJOICE was a 12-week, phase 3, multicenter, randomized, double-blind, placebo-controlled study of a vaginal, muco-adhesive, 17ß-estradiol softgel capsule (TX-004HR 4, 10, and 25âµg) in postmenopausal women with VVA and moderate-to-severe dyspareunia. Treatments were self-administered vaginally once per day for 2 weeks, then twice per week for 10 weeks. The vagina was visually examined at baseline and at weeks 2, 6, 8, and 12; changes were evaluated using a 4-item scale for vaginal color, vaginal epithelial integrity, vaginal epithelial surface thickness, and vaginal secretions. RESULTS: Significant improvements were observed with all three TX-004HR doses versus placebo in vaginal color (least square mean score changes of -0.96 to -1.06 for TX-004HR doses vs -0.60 for placebo at week 12), epithelial integrity (-0.97 to -1.07 vs -0.60), epithelial surface thickness (-0.94 to -1.03 vs -0.61), and secretions (-1.01 to -1.06 vs -0.64) (Pâ<â0.001 for all comparisons at all time points). Both Pearson's correlations and logistic regression receiver-operating characteristic curve analyses significantly correlated the sum of the individual visual assessment scores with dyspareunia (Pâ<â0.0001) and vaginal dryness (Pâ<â0.0001) at 12 weeks. CONCLUSIONS: Greater improvements in the vaginal mucosa of postmenopausal women with VVA and moderate-to-severe dyspareunia were observed with TX-004HR versus placebo, and vaginal mucosa assessment scores correlated with vaginal symptoms of dyspareunia and dryness. Visual vaginal assessment by healthcare professionals is a useful measure for diagnosing VVA and assessing response to treatment.