Introduction
In humans and animals, mechanisms have developed during evolution that allow the individual to maximize their chances of survival when confronted with a stressor. A stressor in this context is any situation which represents a threat to the homeostasis, or balance of the organism, or which is perceived as such. A coordinated behavioral stress response including the subjective emotional feeling of fear is believed to be at the core of a wide variety of real threats, including attacks by enemies, assaults and natural disasters. However, similar responses can also be observed in situations which do not represent live threatening situations, but are nevertheless perceived as a stressor, such as public speaking, relationship problems and financial worries. The associated subjective emotion associated with such non-life threatening stressors is referred to as anxiety. In the specific case of patients with functional GI disorders, such situations include the worry of not being close enough to a bathroom or about developing abdominal pain when eating a meal.

Why most research on stress comes from studies in males
The characteristic active response of an individual to a threat is the fight and flight response. In the case of an overwhelming threat which the individual perceives as out of his or her control, a different pattern of stress response may occur, the so-called defeat response. Since the original seminal observations by Cannon in 1932, a vast number of studies has been reported to characterize both the behavioral as well as the biological response associated with different stressors. The problem with this research (at least if you are a woman) is the fact that the preponderance of such research has been conducted in males, especially male rats.

Prior to 1995, women constituted only about 17% of participants in laboratory studies of physiological and neuroendocrine responses to stress, while in recent years, the gender bias has somewhat decreased. (By the way, a similar gender bias has existed in the evaluation of novel drugs by FDA and NIH. Until recent federal guidelines were introducted which assure equal representation of gender in such studies, the majority of new drugs were evaluated in men and recommended doses for clinical use in both men and women were based on those determined in male samples. The higher prevalence of side effects for certain drugs observed in women was generally explained with the greater tendency of women to report physical symptoms or, even worse, with the greater prevalence of neuroticism and illness behavior!).

Men vs women – fight and flight vs tend and befriend
Could it be that the majority of research studies on the stress response apply only to men, but not to women? In a recent article, reviewed in May by the New York Times, a prominent psychologist from UCLA, Shelley Taylor and coworkers, summarized published scientific evidence from behavioral and biological studies and made a strong argument for differences in the way male and female animals, and men and women respond to stressful, threatening situation. The authors made the following theoretical assumptions about the evolution of gender-specific stress response patterns:

a Traditionally and throughout evolutions, males have been selected which mount a successful behavioral response to a threat which maximizes the survival of self, by either defeating the enemy or overcoming the threat in a fight situation. A similar evolutionary advantage exists for males which are able to flee from a superior enemy. However, the same fight and flight response which is advantageous for the survival of the male individual, puts defenseless and unprotected offspring at significantly greater risk of being harmed.
aThe fight and flight response should result in the selection of males which maximizes biological mechanisms to assure superior fight or flight responses, such as cardiovascular performance, motor planning and necessary neuroendocrine responses, such as activation of the sympathetic nervous system and the HPA axis.
Different considerations apply to females:
a Compared to males, females make a greater investment initially in pregnancy and nursing, and typically play the primary role in bringing offspring to maturity. Therefore, behavioral responses to threat that were successfully passed on, would have been those that protected offspring as well as self.
aThis maternal investment should result in selection of female stress responses that do not jeopardize the health of the female and her offspring, and maximize the likelihood that they will survive.
aThis response pattern should favor the development of biological mechanisms which inhibit the fight and flight response, but rather shift the individuals attention to caring and tending to the young (attachment behavior) and form networks of females for the defense of the group.

Men and women: Biological differences in the stress responses.
Based on these considerations, the authors make a convincing argument that high sympathetic nervous system activation (targeted primarily at the cardiovascular system, thereby optimizing physical performance), effective activation of pain inhibition systems (to prevent distraction of fight and flight performance from injury related pain), and high cortisol responses are characteristic biological components of the male stress response. These responses are related to higher male sex hormone levels.

In contrast, greater activation of vagal mechanisms, and greater release of oxytocin and endorphins within the brain will inhibit the underlying fight and flight response, and promote attachment behavior both to the offspring as well as to other females.
Do these differences also apply to the non-life threatening stressors of daily life, and could the differences in biological mechanisms play a role in the well known fact that men are more likely to die of chronic diseases of the cardiovascular system (hypertension, coronary artery disease), while women are more likely to suffer from a wide range of functional disorders, such as IBS, fibromyalgia and interstitial cystitis?

What does all this have to do with IBS?
Recent studies performed by investigators of the Neuroenteric Disease Program have confirmed some of these hypotheses. In studies where distension of the rectum or sigmoid colon with a balloon was used as a stressor, male IBS patients showed consistently greater sympathetic nervous system responses compared to female patients. Most interesting, these differences were reflected in associated differences in brain activation, measured by positron emission tomography.

What studies are performed at UCLA to study gender-related differences in the response to stress?
We are currently enrolling patients into several studies which address the question of how mild stressors activate the brain and how this activation differs between men and women. We are also looking at gender differences in the release of various stress hormones. If you are interested in learning more about any of these studies, or would like to participate, please call (310) 312-9381.