Hormones & Menopause

Determining if Estrogen is Protective Against Degenerative Changes in Blood Vessel Walls

Aydin Arici, M.D.

Aydin Arici, M.D., Professor of Obstetrics and Gynecology

Coronary artery disease (CAD) is a major contributor to making cardiovascular disease the leading cause of death among women. The decline of estrogen in women is associated with increased CAD, yet the underlying mechanisms through which estrogen may be a protective factor against CAD is unknown. Dr. Arici’s study examined whether estrogen has a protective effect against degenerative changes in blood vessel walls by inhibiting a protein that recruits damage to artery walls.

Highlighted Study Findings

One way in which estrogen seems to have a protective effect against degenerative changes in blood vessel walls is by inhibiting a protein that recruits damage to the walls of arteries. Among the earliest recognizable events in atherosclerosis (hardening of the arteries) are a build-up of plaque in the arterial wall and an increased influx of macrophages (which initially serve a disease-fighting positive role). Recent data indicate that a specific protein, known as monocyte chemotactic protein-1 (MCP-1), may act to recruit macrophages to the artery wall in numbers that begin to play an adverse role. Dr. Arici studied the impact of estrogen on MCP-1 using a mouse model. The results of this study suggest that one way in which estrogen seems to have a protective effect against degenerative changes in blood vessel walls is by inhibiting MCP-1. This finding provides specific insights into the mechanisms of estrogen’s action. Better understanding of the selective molecular mechanisms of estrogen’s action is necessary for the development of improved estrogenic substances which preferentially affect certain tissues, such as heart, rather than others, such as breast. These new agents are necessary provide more targeted interventions for women and thus provide a major benefit to their health.

Understanding the Brain's Response to Ovarian Hormones

Ronald S. Duman, Ph.D.

Ronald S. Duman, Ph.D.,   Professor of Psychiatry and Pharmacology

Mood disorders such as depression are more prevalent in women than in men, and often precipitated by stress. Studies have suggested that mood disorders may result in part from the effects of stress on the growth and survival of brain cells. Dr. Duman has studied how estrogen may play a role in mood disorders by influencing a major mechanism that sustains brain cells, including those important for mood.

Highlighted Study Findings

In this Ethel F. Donaghue Women’s Health Investigator Program-funded study, Dr. Duman examined the impact of estrogen on the expression of BDNF (Brain-derived neurotrophic factor) - a growth factor that helps support the survival of existing nerve cells, or neurons, and the growth of new nerve cells. His results demonstrated that estrogen influences the expression of BDNF, suggesting a route by which fluctuations of hormones could contribute to neurobiological dysfunction. Moreover, interactions between fluctuating hormones and stress could further compromise the functioning of neurons. These findings represented the beginnings of a foundation for developing strategies to counteract the effects of stress and hormone fluctuations on BDNF expression and neuronal functioning. Continued research and progress in this area will eventually lead to a more complete understanding of the cellular basis of the effects of hormones on mood.

Determining the Effects of Hormone Therapy on Memory

Karyn Frick, Ph.D.

Karyn Frick, Ph.D.,   Assistant Professor of Psychology

One of the key studies within the NIH-funded Women's Health Initiative suggested that treatment with estrogen and progestin significantly increases the risk of cognitive decline and dementia in postmenopausal women. Those data sharply contrast with studies in women and rodents that have demonstrated a clear ability of estrogen to alleviate age- and hormone-related memory loss. Dr. Frick’s study was designed to determine the effects of estrogen and progesterone on memory.

Highlighted Study Findings

Dr. Frick found in using a mouse model that, to preserve memory, estrogen likely needs to be administered during a critical window – for example, when women are just entering menopause. Such therapy would appear to be of little benefit to women who are well past menopause, and could increase health risks. Building on earlier pilot research, Dr. Frick investigated estrogen relative to a cell-signaling pathway in the hippocampus – an area of the brain critical to learning and memory. Dr. Frick’s lab previously identified this area as crucial to estrogen’s ability to enhance memory. She found that estrogen activated this signaling pathway in the hippocampus and improved the ability of middle-aged female mice to recall objects. However, estrogen had no effect on memory or cell signaling in older female mice. The data support the notion of a window of opportunity early in menopause in which hormone treatment can benefit cognition, and suggest that the failure of estrogen to improve memory in older females may result from dysfunction of specific molecular pathways in the brain.

Pilot Project Study was funded in 2005, Dr. Frick is now at the University of Wisconsin