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Canadian Journal of Cardiology

Parity History and Later Life Sex Hormone Levels in the Multi-Ethnic Study of Atherosclerosis (MESA)

Published:September 07, 2022DOI:https://doi.org/10.1016/j.cjca.2022.09.004

      Abstract

      Background

      Multiparity is a risk factor for cardiovascular disease (CVD). A more androgenic sex hormone profile, with a higher testosterone (T)/estradiol (E2) ratio, is associated with worse CVD outcomes in women and might be one mechanism linking multiparity to increased CVD risk. We investigated the relationship between parity and sex hormones at mid-to-older age.

      Methods

      We performed a cross-sectional analysis of 2979 women with data on parity and endogenous sex hormone levels from the Multi-Ethnic Study of Atherosclerosis (MESA), a community-based cohort. Parity and gravidity (our exposures) were categorized as 0 (reference), 1-2, 3-4, or ≥ 5. Our outcome measures were T, E2, sex hormone binding globulin, dehydroepiandrosterone, and T/E2 ratio. Progressively adjusted linear regression was used to evaluate the association of parity/gravidity with sex hormones.

      Results

      In multivariable adjusted models, there were no significant associations of parity with E2, dehydroepiandrosterone, and sex hormone binding globulin. Compared with nulliparity, after adjustment for CVD risk factors, women with 1-2 and 3-4 live births had higher T, but this was not significant for grand multiparity (≥ 5 live births). However, grand multigravidity (≥ 5 pregnancies) was associated with 10% (95% confidence interval [CI], 1%-20%) higher T and 14% (95% CI, 1%-29%) higher T/E2, compared with null gravidity. Grand multiparity was associated with an 18% (95% CI, 4%-34%) higher T/E2 ratio compared with nulliparity, after adjustment for CVD risk factors.

      Conclusions

      In this multiethnic cohort, women with grand multigravidity and grand multiparity had higher T/E2 levels, reflecting a more androgenic sex hormone profile. Longitudinal studies on sex hormones’ influence on the relationship between multiparity and CVD are warranted.

      Résumé

      Contexte

      La multiparité est un facteur de risque de maladie cardiovasculaire (MCV). Un profil d’hormones sexuelles plus androgène, avec un ratio testostérone/estradiol plus élevé, est associé à des résultats moins favorables relativement à la MCV chez la femme, et pourrait être l’un des mécanismes liant la multiparité à une augmentation du risque de MCV. Nous avons étudié le lien entre la parité et les hormones sexuelles chez des femmes d’âge moyen à avancé.

      Méthodologie

      Nous avons effectué une analyse transversale portant sur 2 979 femmes pour lesquelles on disposait de données concernant la parité et les taux d’hormones sexuelles endogènes, à partir de la cohorte en milieu communautaire de l’étude MESA (Multi-Ethnic Study of Atherosclerosis, ou étude multiethnique de l’athérosclérose). La parité et la gravidité (expositions) ont été catégorisées en différents groupes : 0 (référence), 1-2, 3-4, ou ≥ 5. Les paramètres évalués ont été le taux de testostérone, le taux d’estradiol, le taux de globuline de liaison aux hormones sexuelles, le taux de déhydroépiandrostérone, et le ratio testostérone/estradiol. Un modèle de régression linéaire avec ajustement progressif a été utilisé pour évaluer l’association entre la parité/gravidité et les hormones sexuelles.

      Résultats

      Dans les modèles ajustés à variables multiples, aucune association significative n’a été constatée entre la parité et le taux d’estradiol, le taux de déhydroépiandrostérone, et le taux de globuline de liaison aux hormones sexuelles. Comparativement à la nulliparité, après ajustement en fonction des facteurs de risque de MCV, les femmes avec 1-2 et 3-4 naissances vivantes présentaient des taux accrus de testostérone, mais la différence n’était pas significative chez les femmes présentant une grande multiparité (≥ 5 naissances vivantes). Une grande multigravidité (≥ 5 grossesses) a toutefois été associée à un taux de testostérone 10 % plus élevé (intervalle de confiance [IC] à 95 % : 1 %-20 %) et à un ratio testostérone/estradiol 14 % plus élevé (IC à 95 % : 1 %-29 %), comparativement à une gravidité nulle. Une grande multiparité a été associée à un ratio testostérone/estradiol 18 % plus élevé (IC à 95 % : 4 %-34 %), comparativement à la nulliparité, après l’ajustement en fonction des facteurs de risque de MCV.

      Conclusions

      Dans cette cohorte multiethnique, les femmes présentant une grande multigravidité et une grande multiparité ont présenté des ratios testostérone/estradiol plus élevés, reflétant un profil d’hormones sexuelles plus androgène. Des études longitudinales s’imposent concernant l’influence des hormones sexuelles sur le lien entre la multiparité et la MCV.

      Graphical abstract

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      Linked Article

      • Paring It Down: Parity, Sex Hormones, and Cardiovascular Risk
        Canadian Journal of Cardiology
        • Preview
          Cardiovascular disease (CVD) is the leading cause of death in women,1 prompting examination of female sex–specific factors as potential contributors to cardiovascular risk. Complications of pregnancy, including hypertensive disorders of pregnancy, gestational diabetes, preterm birth, small for gestational age, and pregnancy loss, have been shown to be important markers of future CVD. Studies have suggested that the physiologic stress of pregnancy can unveil existing subclinical CVD,2 while other reports suggest that complications of pregnancy are contributors to increased risk of future CVD.
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