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Patients taking active medications frequently experience adverse, nonspecific side effects that are not a direct result of the specific pharmacological action of the drug. Although this phenomenon is common, distressing, and costly, it is rarely studied and poorly understood. The nocebo phenomenon, in which placebos produce adverse side effects, offers some insight into nonspecific side effect reporting. We performed a focused review of the literature, which identified several factors that appear to be associated with the nocebo phenomenon and/or reporting of nonspecific side effects while taking active medication: the patient's expectations of adverse effects at the outset of treatment; a process of conditioning in which the patient learns from prior experiences to associate medication-taking with somatic symptoms; certain psychological characteristics such as anxiety, depression, and the tendency to somatize; and situational and contextual factors. Physicians and other health care personnel can attempt to ameliorate nonspecific side effects to active medications by identifying in advance those patients most at risk for developing them and by using a collaborative relationship with the patient to explain and help the patient to understand and tolerate these bothersome but nonharmful symptoms.

Women report more intense, more numerous, and more frequent bodily symptoms than men. This difference appears in samples of medical patients and in community samples, whether or not gynecologic and reproductive symptoms are excluded, and whether all bodily symptoms or only those which are medically unexplained are examined. More limited, but suggestive, literature on experimental pain, symptom reporting in childhood, and pain thresholds in animals are compatible with these findings in adults. A number of contributory factors have been implicated, supported by varying degrees of evidence. These include innate differences in somatic and visceral perception; differences in symptom labeling, description, and reporting; the socialization process, which leads to differences in the readiness to acknowledge and disclose discomfort; a sex differential in the incidence of abuse and violence; sex differences in the prevalence of anxiety and depressive disorders; and gender bias in research and in clinical practice. General internists need to keep these factors in mind in obtaining the clinical history, understanding the meaning and significance that symptoms hold for each patient, and providing symptom relief. W omen and men experience somatic symptoms, bodily distress, and physical health differently. In this paper, we review the empirical evidence regarding gender differences in symptoms, consider various explanations for these differences, and discuss their implications for clinical practice. Since all physical symptoms contain both somatic and psychological components, the distinction betweeǹ`o rganic'' and``functional'' symptoms is theoretically unsound, arbitrary, and clinically impossible to establish. Accordingly, we will discuss somatic symptom reporting in general, including studies of symptoms which do and do not have a clearly demonstrable pathophysiologic correlate. The term sex is generally used to refer to biological characteristics differentiating males and females, while gender is used to refer to the socially allocated roles and expectations associated with sex, i.e., masculinity and femininity. In this review, however, we will use the terms interchangeably, as it is difficult to distinguish the biological and the social role aspects of somatic symptom reporting. METHODSThe MEDLINE and PsycInfo databases were searched for articles from 1966 through March 1999 that included any of the following MeSH terms: symptoms, somatoform disorders, pain, chronic illness, health behavior, and illness behavior combined with sex, sex differences, gender, gender role, and gender differences. The search was extended by using the bibliographies of selected, recent articles and systematic reviews. Articles were screened for relevance based on title, key words, and abstracts. Only English-language papers were included. The initial search identified approximately 450 articles. Cursory inspection of these led to the elimination of approximately 275 as insufficiently relevant or insufficiently scientific to warrant inclusion. T...