Greater lifetime exposure to ovarian hormones was associated with brain structure measures generally consistent with preserved morphology in aging.
Researchers analyzed baseline data from 459 cognitively unimpaired women aged 65 to 80 years enrolled in the Investigating Gains in Neurocognition in an Intervention Trial of Exercise (IGNITE) study. Participants underwent structural magnetic resonance imaging and completed questionnaires on reproductive history, including hormonal contraceptive use, menopausal hormone therapy (MHT), and age at menopause. Researchers used whole-brain voxel-based morphometry and surface-based morphometry to evaluate associations between hormone exposure and measures of gray matter volume and cortical thickness.
The primary outcomes were regional gray matter volume and cortical thickness. Researchers examined associations with hormonal contraceptive use, MHT use, duration and timing of hormone exposure, and age at menopause.
More than three-quarters of participants reported a history of hormonal contraceptive use, and 40% reported prior MHT use. Researchers found that women with a history of hormonal contraceptive use had larger gray matter volumes in several temporal, frontal, and occipital regions compared with women who had never used hormonal contraceptives. Regions associated with contraceptive exposure included the inferior temporal gyrus, middle occipital gyrus, inferior frontal gyrus, parahippocampal gyrus, and superior temporal gyrus.
Longer duration of hormonal contraceptive use was also associated with greater volume in the right fusiform gyrus.
Researchers observed additional associations with menopausal hormone therapy. Women with a history of MHT had larger volumes in the cuneus, precuneus, inferior temporal cortex, and inferior parietal cortex, as well as greater cortical thickness in the left middle temporal cortex compared with women who had never used MHT.
Among measures of endogenous hormone exposure, later menopause was associated with greater cortical thickness in the precuneus, middle occipital gyrus, superior temporal gyrus, and superior parietal lobe.
Several secondary analyses yielded more limited findings. Women who reported both hormonal contraceptive use and MHT use had greater cortical thickness in the posterior cingulate gyrus compared with women who had used neither therapy. However, researchers found no association between brain morphology and age at initiation of hormonal contraceptives, age at initiation of MHT, duration of MHT use, or the interval between menopause and MHT initiation.
The findings should be interpreted in the context of several limitations. Hormone exposure history was based on retrospective self-report, introducing the possibility of recall bias. Information on specific hormone formulations, doses, routes of administration, and treatment schedules was unavailable. In addition, the cross-sectional design precludes conclusions about causality, and unmeasured reproductive, cardiometabolic, and lifestyle factors may have contributed to the observed associations.
Overall, the findings suggest that both endogenous and exogenous ovarian hormone exposure may be associated with differences in brain structure later in life.
Disclosures: The authors reported no conflicts of interest related to the study. Several investigators disclosed consulting relationships or industry-sponsored research outside the reported work, including Kirk I. Erickson and Jeffrey M. Burns. The study was funded by the National Institute on Aging and other National Institutes of Health programs.
Source: NeuroImage
