Using One’s Head to Treat Menopausal Symptoms

The negative effects of estrogen deprivation in young women with a history of breast cancer are broad, potentially involving many areas in which estrogen and its receptors have a role, including the genitourinary, central nervous, skeletal, and neuroendocrine systems. As a consequence, women who have become prematurely menopausal and/or are receiving antiestrogenic endocrine therapy can present with vaginal atrophy causing dyspareunia and itching, urinary incontinence, weight gain, hot flashes, night sweats, irritability, joint pain, and fatigue. Over the past couple of decades, nonhormonal pharmacologic treatments for these hormone-related symptoms have become well established for hot flashes, night sweats, and bone density issues, but not for the other concerns. In addition, there is good evidence that physical activity can improve fatigue and energy balance, though it is a challenge to incorporate it into a busy life, and without simultaneous attention to diet, effects on weight may be suboptimal. Solutions to the complex of symptoms that are common in women deprived of estrogen are clearly needed. The trial by Duijts et al that accompanies this editorial addresses an important complex of symptoms by evaluating three interventions: cognitive behavioral therapy (CBT), physical exercise (PE), and both (CBT/PE), comparing patients receiving them with a control group assigned to a wait list. The authors conclude that CBT and PE, to varying degrees, can decrease estrogen deficiency symptom frequency and/or the perception of symptom severity. The authors rightly note aspects of their trial that make their results less than definitive. These include the lack of patient compliance to the PE and CBT interventions, related, in part, to the time that they take, and the lack of an attention-control placebo trial design. Accepting these limitations, what can be learned from this trial, and how does it fit in with other related publications? Perhaps the most conclusive finding is that PE alone affected neither the perception nor the frequency of hot flashes. This concurs with recently published trial results demonstrating that physical activity consisting of aerobic type exercise alone (devoid of a targeted stress component such as that which is part of yoga) does not significantly reduce hot flashes. Second, CBT, which included relaxation training, did reduce the perceived burden of hot flashes. This finding is consistent with other published studies and the rationale proposed by the authors is quite plausible, as it suggests that stress reduction may affect thermoregulation and that cognitive/emotional interventions may modify the perception of hot flashes. According to both the study’s intent-to-treat and per-protocol analyses, CBT, PE, and CBT/PE each appeared to improve the endocrine subscale of the FACT (FACT-ES) at 12 weeks, an improvement that was maintained at 24 weeks. The change was small, however, and the FACT-ES covers numerous symptoms in 19 questions including gastrointestinal problems, joint pain, mood, weight, sex, vaginal symptoms, hot flashes, and night sweats. It is not clear what areas were actually affected by the interventions and whether the changes in the FACT-ES in the PE arm were different than those in the CBT or CBT/PE arms. This study does demonstrate a proof of concept that is important in helping our patients achieve an optimal health-related quality of life. Psychosocial elements play an important role in the experience of symptoms. Theoretical frameworks posit that there are environmental and psychosocial factors that affect how symptoms are experienced. Well-validated, popular symptom measures such as the Memorial Symptom Assessment Scale include distress or bother content. It is not sufficient to consider only biomedical influences; comprehensive symptom management needs to address the psychosocial context of the symptom, specifically, perception, evaluation, response, and distress. For complete symptom resolution, it may be necessary to address both the physiological expression and psychosocial context of the symptom. In situations where the biology may not be able to be ideally modified and the symptom may not be able to be ameliorated, the perception and response to the symptom can still be positively affected, resulting in better health-related quality of life. The ability to improve symptoms from a psychosocial perspective is exemplified not only by other positive studies using CBT for menopause symptoms, but also in a systematic review evaluating studies that used psychological interventions for physical symptoms. The potential benefit of CBT may seem obvious in behaviorally or cognitively mediated symptoms such as sleep or mood. However, even for more physically mediated symptoms such as pain, nausea, and fatigue, there are pilot level data supporting that CBT can be helpful. The clinical challenge is in delivering the appropriate intervention, in a feasible way, for the right issue. Behavioral interventions should be targeted for specific symptoms with plausible rationale, much the same way as pharmacologic interventions are targeted. The best CBT intervention may be quite different for different symptoms, as opposed to the use of a single CBT program for all women with a plethora of endocrine deficiency symptoms. In addition, the time commitment and degree of benefit need to be taken into account when designing an intervention. In this study by Dijits et al, the combined CBT/PE intervention would have required JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 30 NUMBER 33 NOVEMBER 2