Menopause and Hormone Replacement Therapy

Over the last decade, we have witnessed key discrepancies between observational and randomized clinical trials concerning the beneficial and adverse effects of menopausal hormone therapy (MHT), especially regarding coronary heart disease (CHD) and Alzheimer's disease (AD) (Rossouw et al. 2002). Earlier cohort studies and small-scale trials appeared to demonstrate consistent benefit of MHT on almost every organ system, for example, decreased risk of CHD, AD, depression, colorectal cancer; improvement in hot flashes, sleep, and cognitive function; prevention of osteoporosis; and prevention/reversal of genital atrophy and associated symptoms (Lindsay et al. 1996). These findings led to an all-time high in the marketing and use of MHT (Parente et al. 2008). The publication of the results of Women's Health Initiative (WHI) estrogen plus progestin trial, a placebo-controlled, randomized clinical trial, resulted in a dramatic reduction in the prescribing of MHT by medical doctors and its request by patients, since an increased risk of CHD, stroke, pulmonary embolism, and breast cancer was observed in estrogen plus progestin users (Rossouw et al. 2002). The administration of conjugated equine estrogen (CEE) alone in women who had previously undergone hysterectomy was subsequently shown to increase the risk of stroke without affecting CHD risk (Anderson et al. 2004). Although a nonstatistically significant decrease in the incidence of breast cancer and a significant decrease in hip fractures were observed in the CEE-alone trial, there was no overall benefit. Thus, at this time the routine use of MHT in any form for the purpose of chronic disease prevention is not recommended (American College of Obstetricians and Gynecologists Women's Health Care Physicians 2004; North American Menopause Society 2007a). The discrepant findings against the benefit of MHT for cardiovascular disease (CVD) and AD prevention are currently areas of intense interest and investigation. There are several hypotheses that have been preferred to explain the discrepancy - the leading one being that early initiation of estrogen, prior to its complete withdrawal at menopause, may be associated with improved outcomes for both of these disorders (Grodstein et al. 2006; Hsia et al. 2006). There is also interest in the fact that breast cancer risk was lower in women who had a hysterectomy and took estrogen alone; this finding - although not statistically significant - suggests that progestin combined with estrogen has an adverse effect on breast proliferation but estrogen alone may be a more neutral treatment. At the present time, however, given the lack of any major clinical trial favoring hormone use in any subgroup of at-risk women for any indication other than symptoms, the current therapeutic options for menopausal therapies only favor hormone for symptom control. This chapter will review the treatment options for menopausal symptoms, the potential prevention of medical conditions associated with menopause, and the beneficial and adverse effects of MHT.