Maturitas 57 (2007) 23–26 Estrogen, estrogen treatment and the post-reproductive woman’s brain Frederick Naftolin a,* , Dolores Malaspina b a Department of Obstetrics and Gynecology New York University, New York 10016, USA b Department of Psychiatry New York University, New York 10016, USA Abstract From early embryonic life to death, estrogen is a primary regulator of brain neurogenesis and cell number, synaptogenesis and synaptolysis, multiple cognitive and autonomic functions, vascular function, immune responses and defense measures against brain lesions and dystrophy. Although recent attention has focused on the roles of estrogen during the climacteric, knowing estrogen’s role in brain development and reproductive function is necessary to understand what happens when this powerful influence is removed during the climacteric. This review will therefore address the full picture, with stress on the later-life role of estrogen in the brain. © 2007 Elsevier Ireland Ltd. All rights reserved. Keywords: Estrogen; Woman’s brain; Estrogen receptors 1. The expression of aromatase and estrogen receptors (ER) in the brain, and the concept of selective estrogen receptor modulators (SERM’s) The early and widespread presence of the enzyme, estrogen synthatase (aromatase) in the brain indicates the intimate relationship of estrogen to the brain [1]. Estrogens are among the oldest regulatory substances in biology. They act via receptors (ER)- and non- receptor mechanisms. Usually, these actions can be separated by the speed of action; hours versus minutes, respectively [2–4]. The distribution of both ER and * Corresponding author. E-mail address: frederick.naftolin@med.nyu.edu (F. Naftolin). ER in the brain is very widespread [5] and includes cells of the vascular and immune systems, indicating that estrogens are versatile players in the brain [4,6]. Estrogens have been defined according to their rela- tionship to ER. Many more natural (steroidal and plant estrogens) and synthetic, clinically available, compounds interact with the ER than was previously appreciated. They range from estradiol which is a non- selective SERM to phenatoin and genistein, which are, respectively, ER and ER-selective. 2. The effects of removal of the ovary as the main source of estrogen during the climacteric The chief estrogen in women is estradiol. The major source of estradiol during the reproductive period is 0378-5122/$ – see front matter © 2007 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.maturitas.2007.02.005