The midlife transition and the risk of cardiovascular disease and cancer Part I: magnitude and mechanisms.

Heart disease and cancer are the leading causes of death in the United States. In women, the clinical appearance of both entities-coronary heart disease and cancer (breast, endometrium, and ovary)-escalate during the decades of the midlife transition encompassing the menopause. In addition to the impact of aging, during the interval between the age of 40 and 65 years, the pathophysiologic components of metabolic syndrome also emerge and accelerate. These include visceral adiposity (measured as waist circumference), hypertension, diabetes, and dyslipidemia. Osteoporosis, osteoarthritis, sarcopenia, depression, and even cognitive decline and dementia appear, and most, if not all, are considered functionally related. Two clinical reports confirm the interaction linking the emergence of disease: endometrial cancer and metabolic syndrome. One describes the discovery of unsuspected endometrial cancer in a large series of elective hysterectomies performed in aged and metabolically susceptible populations. The other is from the Women's Health Initiative Observational Study, which found a positive interaction between endometrial cancer and metabolic syndrome regardless of the presence or absence of visceral adiposity. Both provide additional statistical support for the long-suspected causal interaction among the parallel but variable occurrence of these common entities-visceral obesity, heart disease, diabetes, cancer, and the prevalence of metabolic syndrome. Therefore, 2 critical clinical questions require analysis and answers: 1: Why do chronic diseases of adulthood-metabolic, cardiovascular, endocrine-and, in women, cancers of the breast and endometrium (tissues and tumors replete with estrogen receptors) emerge and their incidence trajectories accelerate during the postmenopausal period when little or no endogenous estradiol is available, and yet the therapeutic application of estrogen stimulates their appearance? 2: To what extent should identification of these etiologic driving forces require modification of the gynecologist's responsibilities in the care of our patients in the postreproductive decades of the female life cycle? Part l of this 2-part set of "expert reviews" defines the dimensions, gravity, and interactive synergy of each clinical challenge gynecologists face while caring for their midlife (primarily postmenopausal) patients. It describes the clinically identifiable, potentially treatable, pathogenic mechanisms driving these threats to quality of life and longevity. Part 2 (accepted, American Journal of Obstetrics & Gynecology) identifies 7 objectives of successful clinical care, offers "triage" prioritization targets, and provides feasible opportunities for insertion of primary preventive care initiatives. To implement these goals, a reprogrammed, repurposed office visit is described.

The midlife transition and the risk of cardiovascular disease and cancer Part II: strategies to maximize quality of life and limit dysfunction and disease.

Chronic dysfunction, disabilities, and complex diseases such as cardiovascular disease, diabetes mellitus type 2, osteoporosis and certain cancers, among other burdens, emerge and accelerate in midlife women. Previously in part l, we described the clinical and laboratory research findings that more readily explain and clarify the underlying pathogenetic mechanisms driving these clinical burdens, including new findings on how in particular visceral obesity and the emergence and acceleration of various components of metabolic syndrome-glucotoxicity and lipotoxicity-and a chronic systemic inflammatory state abetted by the loss of ovarian production of estradiol and the inevitable inroads of aging generate this spectrum of clinical problems. These research insights translate into opportunities for effective care strategies leading to prevention, amelioration, possible correction, and enhanced quality of life. To achieve these goals, updated detailed diagnostic, management, and therapeutic guidelines implemented by a reprogrammed and repurposed "menopause" office visit are described. A triage mechanism-when to refer to other specialists for further care-is emphasized. The previously polarized views of menopausal hormone therapy have narrowed significantly, leading to the construction of a more confident, unified, and wider clinical application. Accordingly, a menopausal hormone therapy program providing maximum benefit and minimum risk, accompanied by an algorithm for enhanced shared decision making, is included.

Impact of hormone therapy for women aged 35 to 65 years, from contraception to hormone replacement.

BACKGROUND: Midlife women (aged 35-65 years) present a complex combination of clinical challenges and health care opportunities. To meet these issues effectively, recognition of the various phases of the entire menopausal transition is necessary, because each possesses unique biological properties underlying phase-specific clinical presentations. OBJECTIVE: The aim of this article is to inform health care decisions by defining the endocrine, metabolic, and clinical consequences of therapeutic inaction or intervention at each stage of the midlife experience. METHODS: Using PubMed, MEDLINE was searched for age- and phase-specific publications about ovarian function and corresponding clinical manifestations in women aged 35 to 65 years. Large, long-term longitudinal prospective, case-control, and observational studies were selected for inclusion. Results of the Framingham Heart Study, Study of Women's Health Across the Nation, Nurses' Health Study (NHS), and Women's Health Initiative (WHI), as well as materials from the World Health Organization and American College of Obstetricians and Gynecologists, were obtained from the relevant groups' Web sites in 2008. RESULTS: Synthesis of the data acquired, particularly the confirmatory and contrasting elements displayed in the WHI and NHS publications, leads to a set of guiding principles whereby individualized phase-specific management strategies may be safely employed. These include the value of weight control and exercise; use of specific nonhormonal therapies for defined indications; definition of strict inclusion/exclusion criteria; and individualization of timing, regimen, dosage, and portal of entry for possible hormone therapy. CONCLUSION: An evidence-based, restrictive inclusion/exclusion strategy can be used to maximize benefits and minimize risks for this large, growing, and health-conscious but increasingly vulnerable population.