Frontiers in Neuroendocrinology最新文献

In the last decade, there has been a remarkable surge in research on the neural and behavioral correlates of hormonal contraceptive use, particularly oral contraceptive use. Questions have evolved swiftly and notably, with studies no longer revealing if hormonal contraceptives matter for the brain and behavior, but rather how, when, and for whom they matter most. Paralleling this shift, the goal of this review is to move beyond an average synthesis of hormonal contraceptive influences on human cognition and psychopathology (and their neural substrates) in order to consider the nature and specificity of effects. Accompanied by an evaluation of study methods and informed by findings from animal models, this consideration uncovers promising areas of research in the next ten years, including potential activational and organizational effects of hormonal contraceptive use, individual differences in effects that matter for the wellbeing of unique individuals, and correlates of intrauterine device use.

Incidents of strokes are increased in young women relative to young men, suggesting that oral contraceptive (OC) use is one of the causes of stroke among young women. Long-term exposures to the varying combinations of estrogen and progestogen found in OCs affect blood clotting, lipid and lipoprotein metabolism, endothelial function, and de novo synthesis of neurosteroids, especially brain-derived 17β-estradiol. The latter is essential for neuroprotection, memory, sexual differentiation, synaptic transmission, and behavior. Deleterious effects of OCs may be exacerbated due to comorbidities like polycystic ovary syndrome, sickle cell anemia, COVID-19, exposures to endocrine disrupting chemicals, and conventional or electronic cigarette smoking. The goal of the current review is to revisit the available literature regarding the impact of OC use on stroke, to explain possible underlying mechanisms, and to identify gaps in our understanding to promote future research to reduce and cure stroke in OC users.

Men and women partially differ in how they respond to stress and how stress in return affects their cognition and emotion. The influence of hormonal contraceptives (HCs) on this interaction has received little attention, which is surprising given the prevalence of HC usage. This selective review illustrates how HC usage modulates the effects of stress hormones on cognition and emotion. As three examples, we discuss stress hormone effects on episodic memory, fear conditioning and cognitive emotion regulation. The identified studies revealed that stress effects on cognitive-emotional processes in women using HCs were at times reduced or even absent when compared to men or naturally cycling women. Especially striking were the few examples of reversed effects in HC women. As underlying neuroendocrine mechanisms, we discuss influences of HCs on the neuroendocrine stress response and effects of HCs on central glucocorticoid sensitivity. The summarized findings emphasize the need for additional translational research.

Progestins are an important component of hormonal contraceptives (HCs) and hormone replacement therapies (HRTs). Despite an increasing number of studies elucidating the effects of HCs and HRTs, little is known about the effects of different types of progestins included in these medications on the brain. Animal studies suggest that various progestins interact differently with sex steroid, mineralocorticoid and glucocorticoid receptors and have specific modulatory effects on neurotransmitter systems and on the expression of neuropeptides, suggesting differential impacts on cognition and behavior. This review focuses on the currently available knowledge from human behavioral and neuroimaging studies pooled with evidence from animal research regarding the effects of progestins on the brain. The reviewed information is highly relevant for improving women’s mental health and making informed choices regarding specific types of contraception or treatment.

Polycystic-ovary syndrome (PCOS) is the most common endocrine disorder affecting women of reproductive age, and many features associated with PCOS – such as elevated androgens, insulin resistance and inflammation – are known to affect cognition. However, effects of PCOS on cognition are not well-understood. Here we review the current literature on PCOS and cognition, note the extent of PCOS symptomatology studied in relation to cognitive outcomes, and identify key research gaps and common methodological concerns. Findings indicate a pattern of worse performance across cognitive domains and brain measures in women with PCOS relative to non-PCOS controls, as well as a lack of evidence for the common assumption that women with PCOS will have higher performance on tasks with a demonstrated male-advantage due to high testosterone levels. We suggest strategies for moving beyond the focus on elevated androgens, in favor of research practices that account for the nuances and heterogeneity of PCOS symptoms.

Neurocognitive and psychiatric symptoms are non-negligible in Cushing’s disease and are accompanied by structural and functional alterations of the brain. In this review, we have summarized multimodal neuroimaging and neurophysiological studies to highlight the current and historical understandings of the structural and functional brain alterations in Cushing’s disease. Specifically, structural studies showed atrophy of the gray matter, loss of white matter integrity, and demyelination in widespread brain regions. Functional imaging studies have identified three major functional brain connectome networks influenced by hypercortisolemia: the limbic network, the default mode network, and the executive control network. After endocrinological remission, atrophy of gray matter regions and the compromised functional network activities were partially reversible, and the widespread white matter integrity alterations cannot recover in years. In conclusion, Cushing’s disease patients display structural and functional brain connectomic alterations, which provides insights into the neurocognitive and psychiatric symptoms observed in this disease.

Oral contraceptives (OCs) are widely used yet understudied given their potential for public health consequences. Emerging investigations scaling from single-subject, dense-sampling neuroimaging studies to population-level metrics have linked OCs to altered brain structure and function. Modeling the hypogonadal, hypergonadal, or mixed state effects of OCs in terms of their impact on hormone action in the brain is a valuable approach to synthesizing results across neuroimaging studies and comparing OC effects to companion findings from research on menstrual cycle phase effects on brain anatomy and function. Resting-state functional connectivity studies provide a powerful tool to evaluate the role of OCs on the intrinsic network connectivity that underlies multiple behavioral domains. The preponderance (but not consensus) of the current literature indicates that (1) as the menstrual cycle proceeds from a low to high progesterone state, prefrontal connectivity increases and parietal connectivity decreases; (2) OCs tend to mimic this connectivity pattern; therefore (3) OCs may produce a hyperprogestogenic state in the brain, in spite of overall reductions in endogenous steroid hormone levels. Alternative models are also considered.

Hormonal contraceptives are among the most important health and economic developments in the 20th Century, providing unprecedented reproductive control and a range of health benefits including decreased premenstrual symptoms and protections against various cancers. Hormonal contraceptives modulate neural function and stress responsivity. These changes are usually innocuous or even beneficial, including their effects on mood. However, in approximately 4–10% of users, or up to 30 million people at any given time, hormonal contraceptives trigger depression or anxiety symptoms. How hormonal contraceptives contribute to these responses and who is at risk for adverse outcomes remain unknown. In this paper, we discuss studies of hormonal contraceptive use in humans and describe the ways in which laboratory animal models of contraceptive hormone exposure will be an essential tool for expanding findings to understand the precise mechanisms by which hormonal contraceptives influence the brain, stress responses, and depression risk.

Exposure therapy is a central component of the first-line treatment for anxiety disorders, a common mental health condition that is twice as prevalent in women relative to men. A key underlying mechanism of exposure therapy is fear extinction, which is an active learning process supported by a neural circuitry that is highly regulated by ovarian hormones. This review synthesises research examining the impact of hormonal contraceptives on laboratory fear extinction tasks in female rats and women, and on exposure therapy in women with anxiety disorders. The evidence indicates that hormonal contraceptives have a detrimental impact on fear extinction and exposure therapy that is consistent across species, and from laboratory to clinical settings. Candidate pathways by which hormonal contraceptives impede fear extinction and exposure therapy include suppression of endogenous ovarian hormones and glucocorticoids, and downregulation of signalling pathways that support extinction learning. Key areas of focus for future research are discussed.

Worldwide over 150 million women use oral contraceptives (OCs), which are the most prescribed form of contraception in both the United States and in European countries. Sex hormones, such as estradiol and progesterone, are important endogenous hormones known for shaping the brain across the life span. Synthetic hormones, which are present in OCs, interfere with the natural hormonal balance by reducing the endogenous hormone levels. Little is known how this affects the brain, especially during the most vulnerable times of brain maturation. Here, we review studies that investigate differences in brain gray and white matter in women using OCs in comparison to naturally cycling women. We focus on two neuroimaging methods used to quantify structural gray and white matter changes, namely structural MRI and diffusion MRI. Finally, we discuss the potential of these imaging techniques to advance knowledge about the effects of OCs on the brain and wellbeing in women.