The Effects of Estrogen on Brain Function, edited by Natalie L. Rasgon, is a collection of chapters about estrogen written by experts from different scientific disciplines. The research and controversies surrounding cognitive and neurophysiological changes related to hormone replacement therapy, especially within the context of Alzheimer's disease, are a primary focus. Apparent discrepancies arising from animal models suggesting beneficial effects of estrogen on cognitive performance paired with increased risk of Alzheimer's disease in postmenopausal women are addressed, and relevant literature from basic science research on estrogen neuroprotective and neurodegenerative effects at the cellular level to epidemiological studies in humans are discussed. Related research in neuroimaging and psychiatry are also included. However, one does not need an in-depth understanding of these diverse disciplines in order to come away from the book with a comprehensive understanding of the science and theoretical models involved. Although little time is spent on neuropsychological issues, the book should be of interest to anyone who does clinical assessment or research involving women. The effects of estrogen on cognitive performance are complex, as this book makes clear, and the information contained within this volume is relevant to the field of neuropsychology.
Chapter 1, “Preclinical Data Relating to Estrogen's Effects on Cognitive Performance” by Robert B. Gibbs, nicely summarizes preclinical data relating to estrogen and progesterone effects in the brain and on cognitive performance. Estrogen-mediated effects in the hippocampus and on cholinergic and serotonergic systems are described and well-summarized. Research using rodent models, in which ovariectomized animals were given estrogen replacement, resulted in improved cognitive performance compared to untreated ovariectomized animals; these studies are well described and create a basis for discussions in later chapters of the cognitive effects of estrogen in humans. Dose-dependent and time-dependent effects are also revealed, and the potential relevance to human hormone replacement studies is explained.
In Chapter 2, “Short-lived Effects of Hormone Therapy on Cognitive Function,” Eva Hogervorst discusses human epidemiological studies, especially the Women's Health Initiative Memory Study (WHIMS), which investigated hormone replacement therapy and cognitive decline in elderly women. As the WHIMS data failed to support previous findings of improved cognitive performance following hormone therapy, Hogervorst lays out various potential reasons for the discrepant findings. Much time is spent discussing potential confounds in prior studies, a discussion that is interesting from an experimental design point of view. Various alternative treatment regimens also are described, such as selective estrogen receptor modulators and phytoestrogens.
Structural and functional brain imaging data related to the effects of estrogen are addressed in Chapter 3, “Clinical Data From Structural and Functional Brain Imaging on Estrogen's Effects in The Central Nervous System,” by Daniel G.S. Silverman, Cheri L. Geist, and Natalie L. Rasgon. This chapter begins with brief, clear descriptions of various PET and MRI procedures, and then outlines findings from glucose metabolism (FDG), cerebral blood flow (O-15 water), volumetric, and functional MRI studies in healthy premenopausal women, healthy elderly women, and women with Alzheimer's disease. Unfortunately, very little research has been done in this area, and the chapter's brevity is a reflection of this lack of research. Research into differences in brain activation during the different phases of the menstrual cycle are also described, as these differences are possibly due to differences in hormone levels.
Psychiatric issues related to estrogen and hormone replacement therapy are included and discussed in Chapter 4, “Clinical Data on Estrogen's Effects on Mood,” by Natalie L. Rasgon, Laurel N. Zappert, and Katherine E. Williams. Estrogen affects serotonin receptor expression, and therefore mood, and can be used in conjunction with serotonin reuptake inhibitors in the treatment of mood disorders. As women who have a history of major depressive disorder may experience clinical mood symptoms, adjunctive treatment with hormones like estradiol are helpful.
Chapter 5, “Preclinical Efforts to Develop Effective Neuroserms for the Brain,” by Roberta Diaz Brinton and Liquin Zhao, and Chapter 6, Basic and Clinical Data on the Effects of Serms on Cognition by Kristine Yaffe, Pauline M. Maki and Peter J Schmidt, discuss research on the development and effects of NeuroSERMs (selective estrogen receptor modulators). NeuroSERMs are alternatives for estrogen therapy that are currently being developed. As estrogen appears to have protective effects on healthy neurons and deleterious effects on damaged neurons, some research groups are investigating estrogen alternatives that may have desired advantageous effects on the aging female brain without the deleterious effects outside the brain.
The Effects of Estrogen on Brain Function is well-written and well-edited. For anyone interested in understanding the complexities of estrogen actions in the brain or the potential risks and benefits of estrogen therapy, this book is a good place to start. The book is not long—only six chapters—and is a relatively fast read. A basic understanding of biology and neuroscience are necessary; beyond that, the authors explain the intricacies well.
