Ultra-low-dose estradiol and dydrogesterone for treatment of vasomotor symptoms in Europe and China.

OBJECTIVE: Among postmenopausal women, oral, ultra-low-dose continuous combined estradiol (E0.5 mg) plus dydrogesterone (D2.5 mg) reduces vasomotor symptoms (VMS). METHODS: This study was a post hoc analysis of data from two phase 3, double-blind studies. Postmenopausal women were randomized 2:1:2 to receive E0.5 mg/D2.5 mg, E1 mg/D5 mg (not included in this analysis) or placebo for 13 weeks (European study), or randomized 1:1 to receive E0.5 mg/D2.5 mg or placebo for 12 weeks (Chinese study). Endpoints assessed in ethnicity subgroups (European and Chinese) included changes from baseline in number of hot flushes, number of moderate-to-severe hot flushes and Menopause Rating Scale (MRS) score. RESULTS: Overall, 579 women were included in the analysis (E0.5 mg/D2.5 mg, n = 288; placebo, n = 291). European and Chinese women receiving E0.5 mg/D2.5 mg experienced greater reductions from baseline in mean daily number of hot flushes and mean daily number of moderate-to-severe hot flushes at week 4, week 8 and end of treatment versus those receiving placebo. Significant improvements in the 'hot flushes, sweating' MRS item score were reported in both European and Chinese women. CONCLUSION: Oral, ultra-low-dose continuous combined 0.5 mg 17ß-estradiol and 2.5 mg dydrogesterone improved VMS compared with placebo in European and Chinese postmenopausal women, with a positive impact on health-related quality of life.

Ultra-low-dose continuous combined estradiol and dydrogesterone in postmenopausal women: A pooled safety and tolerability analysis.

Objective: To assess the safety and tolerability of ultra-low dose estradiol and dydrogesterone (E0.5 mg/D2.5 mg) among postmenopausal women. Methods: This pooled analysis of data from three clinical studies assessed the effects of continuous combined ultra-low-dose estradiol and dydrogesterone among postmenopausal women. Participants received E0.5 mg/D2.5 mg or placebo for 13 weeks (double-blind, randomized, European study), E0.5 mg/D2.5 mg or placebo for 12 weeks (double-blind, randomized, Chinese study), or E0.5 mg/D2.5 mg for 52 weeks (open-label, European study). Safety outcomes included treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (TESAEs), treatment discontinuation due to a TEAE, and adverse events of special interest (AESIs). Results: Overall, 1027 women were included in the pooled analysis (E0.5 mg/D2.5 mg, n = 736; placebo, n = 291). Mean treatment exposure was 288.9 days in the E0.5 mg/D2.5 mg group and 86.6 days in the placebo group. The proportion of women experiencing ≥1 TEAE was similar in the E0.5 mg/D2.5 mg and placebo groups (50.1% vs 49.5%, respectively). TESAEs occurred in 12 (1.6%) women receiving E0.5 mg/D2.5 mg and 9 (3.1%) women receiving placebo. Discontinuation of study treatment was infrequent in both groups (E0.5 mg/D2.5 mg: 1.5%; placebo: 2.4%). The occurrence of breast pain was more common in the E0.5 mg/D2.5 mg group than in the placebo group (2.0% vs 0.3%) as was uterine hemorrhage (6.5% vs 2.4%). The incidence of acne, hypertrichoses and weight increased was similar between groups. Conclusions: Across three studies, ultra-low-dose estradiol plus dydrogesterone was well tolerated among postmenopausal women, with no increase in TEAEs or TESAEs compared with placebo.

Riesgos y beneficios de la THR despues de WHI / Risk and benefit of HRT after WHI

En el presente artículo se hace una revisión sobre los riesgos y beneficios que tiene la terapia de reemplazo hormonal. Los síntomas aparecen al poco tiempo del cese de la función ovárica, mientras que con el tiempo aparecen las molestias genitourinarias y a largo plazo hay complicaciones como son la osteoporosis, la enfermedad cardiovascular y la demencia de Alzheimer. Con respecto a la prevención de osteoporosis; hay evidencia suficiente que respalda el uso de la terapia hormonal. Se revisan los resultados de estudios observacionales, del estudio HERS y del estudio de Iniciativa de Salud de las Mujeres (WHI) con respecto a prevención primaria y secundaria de enfermedad cardiovascular. Cuando la terapia se utiliza en dosis adecuadas y en mujeres apropiadas puede conferir protección cardiovascular. Con respecto a la enfermedad de Alzheimer, los estudios observacionales sugieren disminución en el riesgo, más no mejoría de síntomas en aquellas mujeres con la demencia manifiesta.En cuanto a riesgos, estos son pequeños y están representados especialmente por el incremento en el cáncer de seno con el uso prolongado, así como el de eventos trombóticos. Se concluye que con una adecuada selección de la paciente, utilizando el compuesto adecuado, en las dosis mínimas necesarias y la vía adecuada, los beneficios superan los riesgos de una terapia hormonal