Measuring the impact of menopausal symptoms on quality of life: methodological considerations.

U nderstanding the impact of menopause on a woman’s quality of life (QoL) is a critically important question in the clinical management of symptomatic women. Approximately 25 million women in the United States will transition through menopause over the next decade, and most (approximately 70%) will experience some menopausal symptoms. However, the severity of symptoms and the degree to which symptoms interfere with functioning and QoL are highly variable from one woman to another. Although most women experience only mild to moderate symptoms, approximately 20% report severe symptoms, and 10% to 15% of women consult physicians for symptom relief. Once thought to be transient (on the order of 1-2 y), we now know that these symptoms tend to last four years or more for most women. Several treatments are available for symptom relief, but all carry risks, especially when used for more than five years. Menopausal hormone therapy (HT) is the most effective treatment for the vasomotor symptoms (eg, hot flashes and night sweats), but its risks include venous thrombotic events, breast cancer, and cardiovascular disease. Clinical decisions about treating vasomotor symptoms therefore depend on whether the benefits from symptom relief outweigh any associated risks of treatment, which depends on the decrement in QoL associated with vasomotor symptoms. Despite decades of research on menopause and menopausal HT, surprisingly, little is known about how the menopausal transition affects women’s QoL. In this issue of Menopause, Avis et al attempt to understand the change in health-related QoL (HRQL) and the contribution of a variety of symptoms to HRQL during the menopausal transition by examining 3,302 multiethnic women for six years of follow-up (the Study of Women’s Health Across the Nation, or SWAN study). Using data from this landmark study, they sought to answer the following three questions: (1) Does HRQL change during the course of the menopausal transition, after adjusting for chronological age? (2) What is the role of symptoms in predicting changes in HRQL? and (3) Does HRQL change during the menopausal transition, after adjusting for other factors related to HRQL? The authors present compelling data showing the relationship between menopausal symptoms and losses in HRQL, yet come to the conclusion that Bthe menopausal transition showed little impact on HRQL when adjusted for symptoms, medical conditions, and stress. [ Specifically, the authors found that several menopause symptoms were associated with reduced function on each of the five domains of the 36-item Short-Form Health Survey (SF-36) included in their study after adjusting for age. They found that role functioning significantly declined during the menopausal transition. Even after accounting for the effect of symptoms on HRQL, there remained a residual loss in HRQL in the domains of bodily pain, vitality, role-physical, and social functioning. The authors explained this by suggesting that perhaps symptoms do not completely explain the changes in HRQL during the menopausal transition. However, when the 834 women who were present or former HT users (28% of their sample) were removed from the analysis, menopause status was no longer significant for bodily pain. Because HT use is likely a marker for women with more severe menopausal symptoms, this strengthens the likely association between symptoms and losses in HRQL. After additionally adjusting for health conditions, sociodemographics, physical activity, and psychological factors, only role-physical remained significantly related to menopause status (excluding HT use). This study raises an interesting question on the nature of the menopausal transition: once you adjust for age and menopausal symptoms, what residual effect would one expect to see? Is there a Bmenopause effect[ outside symptoms and aging? It is important for the field of menopause research to clarify what is being sought when we look for a persistent menopausal transition effect that is adjusted for symptoms. We know that symptoms are a main driver of reductions in HRQL during menopause; the study by Avis et al supports the finding that HRQL diminishes during the menopausal transition and that this is, in fact, primarily because of symptoms related to estrogen deficiency. Their conclusion that the menopausal transition did not impact HRQL beyond symptoms and other factors is a compelling theoretical finding but may have somewhat limited clinical applicability. If symptoms are on the causal pathway between the menopausal transition and HRQL, adjusting for symptoms to look for a residual effect may not yield practical insights for the clinical setting, although of theoretical interest. Previous work that disentangled symptoms due to estrogen deprivation versus those due to normal aging yielded valuable insights into which of the many symptoms commonly reported among middle-aged women might be expected to respond to estrogen therapy. These analyses found that only vasomotor symptoms and vaginal dryness were definitively associated with the menopausal transition.