Oral contraceptive use is associated with smaller hypothalamic and pituitary gland volumes in healthy women: A structural MRI study

Abstract

The effects of hormonal contraceptives on structural features of the hypothalamus and pituitary are incompletely understood. One prior study reported microstructural changes in the hypothalamus with oral contraceptive pill (OCP) use. However, effects on hypothalamic volume have not been reported. One prior study reported volumetric changes in the pituitary. However, this study was limited by including participants evaluated for neurological symptoms. We sought to determine if OCP use is associated with alteration of hypothalamic or pituitary volume. High-resolution 3T MRI was performed for a prospective cohort of 50 healthy women from 2016 to 2018, which comprised 21 OCP users (age, 19–29) and 29 naturally cycling women (age, 18–36). Participants were excluded if they were pregnant or had significant medical conditions including neurological, psychiatric, and endocrine disorders. After confirming reliability of the image analysis techniques, 5 raters independently performed manual segmentation of the hypothalamus and semi-automated intensity threshold-based segmentation of the pituitary using ITK-SNAP. Total intracranial volume was estimated using FreeSurfer. A general linear model tested the association of OCP use with hypothalamic and pituitary volumes. Hypothalamic (B = -81.2 ± 24.9, p = 0.002) and pituitary (B = -81.2 ± 38.7, p = 0.04) volumes in OCP users were smaller than in naturally cycling women. These findings may be related to interference with known trophic effects of sex hormones and suggest a structural correlate of central OCP effects.

Ovarian steroid hormones: A long overlooked but critical contributor to brain aging and Alzheimer’s disease

“…In a recent MRI study of midlife women at risk for AD, OC users exhibited greater GM volume in medial temporal lobe, precuneus, fusiform gyrus, parietal and frontal cortex as compared to never-users (Schelbaum et al, 2021), which is in line with findings in younger women . However, other studies reported reduced GM volume of amygdala, parahippocampal gyrus, hypothalamus, pituitary gland, posterior cingulate cortex and orbitofrontal cortex of OC users compared to non-users (Petersen et al, 2015;Lisofsky et al, 2016;Chen et al, 2021). When comparing the follicular phase of naturally cycling women with the inactive phase of androgenic progestins or antiandrogenic pills, OC users had lower GM volume in cingulate gyrus and bilateral culmen, although these effects did not survive correction for multiple 10.3389/fnagi.2022.948219 comparisons (De Bondt et al, 2016).…”

Changes to hypothalamic volume and associated subfields during gender-affirming hormone treatment in gender dysphoria

“…These naturally occurring variations of hormone concentrations in the human body could affect brain morphometry as well. In fact, an exploratory analysis of naturally cycling women revealed volumetric differences of the total hypothalamus during different menstrual cycle phases (Chen et al, 2021). Also other studies showed variations of volumetric findings of the human brain in different menstrual cycle phases of naturally cycling women (De Bondt et al, 2013; Protopopescu et al, 2008).…”

“…A study exploring the effects of OCPs on human brain structure, reported smaller hypothalamic volume in healthy CW with OCP intake compared to naturally cycling CW (Chen et al, 2021). OCP mostly consists of estrogens and progestogens (Dragoman, 2014).…”

“…This is supported by an earlier study, which revealed larger hypothalamus volumes in cisgender men and linked these findings to higher amounts of estrogen and androgen receptor densities in this structure (Goldstein et al, 2001). Interestingly, when analyzing central effects of oral contraceptives (OCP), mainly consisting of estrogens and progestogens (Dragoman, 2014), a reduction of hypothalamic grey matter volume in OCP users compared to naturally cycling women was revealed (Chen et al, 2021). Therefore, an influence of sex steroid hormones on hypothalamic structure could be assumed.…”

Hypothalamic microstructure and function are related to body mass, but not mental or cognitive abilities across the adult lifespan

“…Finally, it remains unclear how influences of age and physical health in the hypothalamus are temporally related, how one affects the other, and which other participant characteristics could further explain hypothalamic microstructure. For example, potential effects of sleep and hormonal medication (e.g., oral contraceptive use) need to be considered [ 57 , 58 ]. Longitudinal investigations could shed light onto these mechanisms to better understand their individual and shared contributions to better target interventions aiming at healthy aging.…”