OBJECTIVES: Obesity and genetic variation in aromatase and type 1 17-β hydroxysteroid dehydrogenase (HSD) could influence the E2 trajectory of decline during the menopause transition. DESIGN AND PARTICIPANTS: E2 trajectories during the menopause transition (phenotype) were identified using 5934 data points acquired annually from 681 women in Study of Women's Health across the Nation (SWAN), a multiethnic study of the mid-life. E2 trajectories were related to CYP19 and type I 17-βHSD single-nucleotide polymorphisms (SNPs) and obesity. RESULTS: (log) E2 trajectories began to decline precipitously 2 years before the final menstrual period (FMP). The trajectory of the (log) E2 decline varied with genotypes and obesity. (log) E2 rates of decline were greater in nonobese women than in obese women, P < 0·05. Women with the CYP19rs936306 CT variant had (log) E2 rate of decline that was 54% as rapid as the rate of decline of women with the TT variant, P < 0·05. (log) E2 rate of decline in women with the CYP19rs749292 GG variant was two-thirds the rate of (log) E2 decline in women with the AG variant, P < 0·05. (log) Rates of E2 decline with 17-βHSD SNPs (rs2830, rs592389, and rs615942) varied according to genotype within obesity groups. Within each obesity group, (log) E2 rate of decline was greater in heterozygous variants and much less in homozygotes (P < 0·05). Obese women with selected CYP19 and 17-β HSD gene variants had remarkably different E2 trajectories around the FMP, resulting in different postmenopausal E2 levels. The rate of the E2 decline and the subsequent postmenopausal E2 levels may be relevant to oestrogen-sensitive chronic diseases including cancers.
OBJECTIVES:Obesity and genetic variation in aromatase and type 1 17-β hydroxysteroid dehydrogenase (HSD) could influence the E2 trajectory of decline during the menopause transition. DESIGN AND PARTICIPANTS: E2 trajectories during the menopause transition (phenotype) were identified using 5934 data points acquired annually from 681 women in Study of Women's Health across the Nation (SWAN), a multiethnic study of the mid-life. E2 trajectories were related to CYP19 and type I 17-βHSD single-nucleotide polymorphisms (SNPs) and obesity. RESULTS: (log) E2 trajectories began to decline precipitously 2 years before the final menstrual period (FMP). The trajectory of the (log) E2 decline varied with genotypes and obesity. (log) E2 rates of decline were greater in nonobese women than in obesewomen, P < 0·05. Women with the CYP19rs936306 CT variant had (log) E2 rate of decline that was 54% as rapid as the rate of decline of women with the TT variant, P < 0·05. (log) E2 rate of decline in women with the CYP19rs749292 GG variant was two-thirds the rate of (log) E2 decline in women with the AG variant, P < 0·05. (log) Rates of E2 decline with 17-βHSD SNPs (rs2830, rs592389, and rs615942) varied according to genotype within obesity groups. Within each obesity group, (log) E2 rate of decline was greater in heterozygous variants and much less in homozygotes (P < 0·05). Obesewomen with selected CYP19 and 17-β HSD gene variants had remarkably different E2 trajectories around the FMP, resulting in different postmenopausal E2 levels. The rate of the E2 decline and the subsequent postmenopausal E2 levels may be relevant to oestrogen-sensitive chronic diseases including cancers.
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