Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Jul 13:14:1131995.
doi: 10.3389/fendo.2023.1131995. eCollection 2023.

Hormonal contraceptive exposure relates to changes in resting state functional connectivity of anterior cingulate cortex and amygdala

Esmeralda Hidalgo-Lopez  1   2 , Isabel Noachtar  1   2 , Belinda Pletzer  1   2
Affiliations

Hormonal contraceptive exposure relates to changes in resting state functional connectivity of anterior cingulate cortex and amygdala

Esmeralda Hidalgo-Lopez et al. Front Endocrinol (Lausanne). .

Abstract

Introduction: Hormonal contraceptives (HCs), nowadays one of the most used contraceptive methods, downregulate endogenous ovarian hormones, which have multiple plastic effects in the adult brain. HCs usually contain a synthetic estrogen, ethinyl-estradiol, and a synthetic progestin, which can be classified as androgenic or anti-androgenic, depending on their interaction with androgen receptors. Both the anterior cingulate cortex (ACC) and the amygdala express steroid receptors and have shown differential functionality depending on the hormonal status of the participant and the use of HC. In this work, we investigated for the first time the relationship between ACC and amygdala resting state functional connectivity (rs-FC) and HC use duration, while controlling for progestin androgenicity.

Methods: A total of 231 healthy young women participated in five different magnetic resonance imaging studies and were included in the final analysis. The relation between HC use duration and (i) gray matter volume, (ii) fractional amplitude of low-frequency fluctuations, and (iii) seed-based connectivity during resting state in the amygdalae and ACC was investigated in this large sample of women.

Results: In general, rs-FC of the amygdalae with frontal areas, and between the ACC and temporoparietal areas, decreased the longer the HC exposure and independently of the progestin's androgenicity. The type of HC's progestin did show a differential effect in the gray matter volume of left ACC and the connectivity between bilateral ACC and the right inferior frontal gyrus.

Keywords: amygdala; anterior cingulate cortex; brain connectivity; hormonal contraceptives; progestins; resting state fMRI.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Main effect of current HC use duration on ACC and amygdala connectivity. (A) Current HC users showed lower connectivity between the right ACC and right insula/bilateral post-central gyrus, the longer the use of HC, irrespective of the androgenicity (in green). (B) Independently of the androgenicity of the HC, current users showed lower connectivity between left (in blue) and right (in purple) amygdala with left prefrontal cortex the longer the use of the HC. ACC, anterior cingulate cortex; PoCG, post-central gyrus; PI, posterior insula; amyg, amygdala; MFG, middle frontal gyrus; SFG, superior frontal gyrus; HC, hormonal contraceptive; A, androgenic; AA, anti-androgenic.
Figure 2
Figure 2
Interactive effect of current HC use duration and androgenicity on the connectivity between left (in red) and right ACC (in orange) with right inferior frontal gyrus (IFG). Current users of an androgenic HC (A-HC) showed lower connectivity between bilateral ACC and the right IFG the longer the HC use. In contrast, current users of an anti-androgenic HC (AA-HC) showed stronger connectivity between bilateral ACC and the right IFG the longer the HC use. ACC, anterior cingulate cortex; IFG, inferior frontal gyrus HC, hormonal contraceptive; A, androgenic; AA, anti-androgenic.
See this image and copyright information in PMC

References

    1. McEwen B. Estrogen actions throughout the brain. Recent Prog Hormone Res (2002) 57(FEBRUARY 2002):357–84. doi: 10.1210/rp.57.1.357 - DOI - PubMed
    1. Wendler A, Albrecht C, Wehling M. Nongenomic actions of aldosterone and progesterone revisited. Steroids (2012) 77(10):1002–6. doi: 10.1016/j.steroids.2011.12.023 - DOI - PubMed
    1. Brinton RD, Thompson RF, Foy MR, Baudry M, Wang JM, Finch CE, et al. . Progesterone receptors: form and function in brain. Front Neuroendocrinol (2008) 29(2):313–39. doi: 10.1016/j.yfrne.2008.02.001 - DOI - PMC - PubMed
    1. Pritschet L, Santander T, Taylor CM, Layher E, Yu S, Miller MB, et al. . Functional reorganization of brain networks across the human menstrual cycle. NeuroImage (2020) 220:117091. doi: 10.1016/j.neuroimage.2020.117091 - DOI - PubMed
    1. United Nations . (2022). United Nations, Department of Economic and Social Affairs, Population Division. Available at: https://www.un.org/development/desa/pd/sites/www.un.org.development.desa....

Publication types

Substances