Effect of Early Menopause and Hormone Replacement Therapy on Aortic Stenosis Progression

Background: Early menopause has been associated with several cardiovascular diseases.Its effect on the progression of aortic stenosis (AS) remains unknown.We conducted an analysis to examine the effect of early menopause without hormone replacement therapy (HRT) on the progression of AS in postmenopausal women with AS.Methods: This subanalysis included 33 female patients with at least mild AS (mean age 65 Æ 10 years) who were prospectively enrolled in the Metabolic Determinants of the Progression of Aortic Stenosis (PROGRESSA) study (NCT01679431).Anatomical assessment of AS was performed using multidetector computed tomography, whereas hemodynamic assessment of AS was performed using Doppler echocardiography.Results: Over a median follow-up of 2 (25th-75th percentiles, 1-4) years, early menopausal women without HRT showed faster progression of aortic valve calcification (AVC; median, 100 [25th-75th percentiles, 58-130] vs 23 [25th-75th percentiles, 2-71] arbitrary units per year; P ¼ 0.03); mean pressure gradient (median, 2.37 [25th-75th percentiles, 0.82-3.61]vs 0.33 [25th-75th percentiles, 0.01-1.78]mm Hg per year; P ¼ 0.04) and aortic valve area indexed to body surface area (median, -0.12 [25th-75th percentiles, -0.23 to 0.002] vs -0.004 [25th-75th percentile, -0.07 to 0.08] cm 2 /m 2 /y; P ¼ 0.07).In multivariate analysis adjusted for several clinical, echocardiographic, and anatomic factors, early menopause without HRT remained independently associated with faster AVC progression (P ¼ 0.003).Women who received HRT showed a slower progression of AVC compared with those who never received HRT (median, 62 [25th-75th percentile, 2-100] vs 20 [25th-75th percentile, 10-42] arbitrary units per year; P ¼ R ESUM EContexte : La m enopause pr ecoce est associ ee à un risque accru de maladies cardiovasculaires.Son effet sur la progression de la st enose aortique (SA) demeure inconnu.Nous avons r ealis e une analyse visant à examiner l'effet de la m enopause pr ecoce sans hormonoth erapie substitutive sur la progression de la SA chez des femmes postm enopaus ees atteintes de SA.M ethodologie : Cette sous-analyse a port e sur 33 femmes atteintes de SA au minimum l egère (âge moyen de 65 Æ 10 ans), recrut ees de manière prospective dans l' etude PROGRESSA (NCT01679431).L' evaluation anatomique de la SA a et e r ealis ee par tomographie assist ee par ordinateur à d etecteurs multiples, tandis que l' evaluation h emodynamique de la SA a et e r ealis ee par echocardiographie Doppler.R esultats : Sur une p eriode de suivi m ediane de 2 ans (1 à 4), les femmes qui avaient eu une m enopause pr ecoce sans hormonoth erapie substitutive ont pr esent e une progression plus rapide de la calcification de la valve aortique (CVA) (100 [58 à 130] vs 23 [2 à 71] UA/an, p ¼ 0,03; gradient de pression moyen [GM] : 2,37 [0,82 à 3,61] vs 0,33 [0,01 à 1,78] mmHg/an, p ¼ 0,04; surface valvulaire aortique index ee à la surface corporelle (SVAi) : -0,12 [-0,23 à 0,002] vs -0,004 [-0,07 à 0,08] cm 2 /m 2 /an, p ¼ 0,07).En analyse multivari ee ajust ee pour plusieurs facteurs anatomiques, echocardiographiques et cliniques, la m enopause pr ecoce sans hormonoth erapie substitutive reste ind ependamment associ ee à une progression plus rapide de la CVA (p ¼ 0,003).La progression de la CVA a et e plus lente chez les femmes ayant reçu une hormonoth erapie substitutive comparativement à celles qui n'en ont jamais reçu (62 [2 à 100] vs 20 [10 à 42]Menopause is a natural, physiological process marked by the permanent cessation of the menstrual cycle due to decreased production of the ovarian hormones estrogen and progesterone.Diagnosis of natural menopause occurs when amenorrhea persists for 12 months without any pathological cause. 1 However, menopause can also occur because of iatrogenic factors, such as ovariectomy or hysterectomy, and might be associated with medical therapy, like radiation or