Hormones, the Brain, and Me

Canadian Psychology, Feb 2008 by Sherwin, Barbara B

CPA Donald O. Hebb Award For Distinguished Contributions to Psychology as a Science - 2007

Prix Donald O. Hebb pour contributions remarquables à la psychologie en tant que science - 2007

Abstract

My research program in psychoneuroendocrinology, a subdiscipline of psychology, has focused on the investigation of three areas of women's health. First, the authors have studied the role of androgen in female sexuality; second, the authors have investigated the effects of estrogen on mood in women, and more recently, the authors have demonstrated the conditions under which estrogen treatment would be neuroprotective with regard to cognitive functioning in aging women. The results of our own and of other researchers' studies in all three areas of psychoneuroendocrinology are discussed.

Keywords: estrogen, testosterone, menopause, cognition, mood

Although I never anticipated participating in such an exercise, recalling the history of the research ideas that inspired me throughout my career and the manner in which I chose to pursue them has been instructive to me and, I hope, may be of some interest or use to others. When I entered graduate school in clinical psychology at Concordia University in 1975, I had the vague but compelling idea that I wanted to build a research program that would focus on how endocrine changes affected behaviour. The endocrine system had always held a great deal of appeal to me because of its unique system of checks and balances that ensured the organism would maintain a constant internal milieu in the face of environmental changes. But the fact that I was entering a graduate program in clinical psychology was clear evidence that I was also very interested in human behaviour. My challenge concerned finding a way to marry these two interests. Although I did not know it at the time, I was about to enter the subdiscipline of psychology called human psychoneuroendocrinology. The fact that neither my research advisor, nor anyone else in my department or, for that matter, anyone in Montreal was an expert in psychneuroendocrinology did not deter my naïve self at the time; the area aroused my passion, and I decided to pursue my ideas and seek guidance wherever I might find it.

First, I searched for an experimental model for the questions I hoped to investigate. Women experience radical changes in hormone levels during various reproductive events that occur universally during their lives such as the menstrual cycle, pregnancy and postpartum, and menopause. Although all of these reproductive events are associated with changes in behaviour in some women, there was a dearth of empirical evidence from controlled studies that the hormonal fluctuations were the cause of the behavioural changes that occurred coincidentally in vulnerable women. Not surprisingly, in the absence of such evidence, physical and psychological symptoms frequently associated with these reproductive events were generally not accorded serious consideration by physicians. As I read the mostly anecdotal literature available at the time, I became convinced that rigorous studies were required to determine whether cause and effect hormone-behaviour relationships were actually evident in women before we could conceptualise possible interventions to treat them. Over the years, my research program has focused on three major areas of human psychoneuroendocrinology, namely, testosterone (T) and sexual behaviour, estrogen (E) and mood, and E and cognition in women. A short description of the findings from my laboratory in each of these three areas over the years follows.

Hormones and Sexual Behaviour in Women

The ovaries produce over 90% of estrogen in a women's body, and when I was a graduate student in the late 1970s and early 1980s, women were frequently treated with estrogen following a spontaneous or a surgical menopause. However, the ovarian stroma also produces about one third of all the T in a woman's body. Although the ovarian stroma continues to secrete T for several years following a natural menopause, women whose ovaries are surgically removed are deprived of this source of T production, and their T levels decrease significantly following surgery. Despite this knowledge, women were not treated with T following surgical removal of the ovaries, a surgical procedure carried out considerably more frequently 25 years ago than it is today. Although studies in female rats and monkeys suggested that T was important for the motivational aspects of sexual behaviours, at the time, no empirical information was available concerning the possible role of T on behaviour in women. In the first prospective, randomised controlled trial (RCT) I carried out, premenopausal women who had normal ovarian function and who needed to undergo a total abdominal hysterectomy (TAH) along with the removal of both ovaries (BSO) for benign disease were administered questionnaires to characterise and to quantify aspects of their sexual behaviour before surgery. Postoperatively, the women were randomly assigned to treatment with either estrogen (E)-alone, T-alone, a combined E T drug or with a placebo for 3 months. They were tested again and were then crossed-over to a drug treatment they had not received during the first 3-month treatment phase for an additional 3 months. Women who received either of the T-containing drugs reported ratings of sexual desire and sexual arousal that did not differ from their own preoperative scores and were significantly higher than the postoperative scores of women who had randomly received treatment with E-alone or placebo (Sherwin, Gelfand, & Brender, 1985). These findings were subsequently confirmed in another study of surgically menopausal women who had been treated with the E T combined drug long term compared with matched groups of surgically menopausal women who had been treated long term with E-alone and a third group that remained untreated following their TAH and BSO at least 2 years earlier (Sherwin & Gelfand, 1987b). These were the first findings from controlled studies to demonstrate that T is important for sexual desire and interest in women, just as it is for men.