Hormone Replacement Therapy

Menopause and HT

Menopause is the permanent cessation of menstruation due to the loss of ovarian follicular function. The perimenopause refers to the time period immediately preceding menopause when fertility wanes and menstrual cycle irregularity increases. This period continues until 12 months after cessation of menses, at which time the woman is considered menopausal. The mean duration of the perimenopause is 4 years, while signs consistent with the perimenopause may precede the final menses by 2 to 8 years.

There is strong evidence that the transition to menopause is associated with vasomotor symptoms (hot flashes and night sweats). For instance, in one U.S. study, nearly 60% of women reported hot flashes in the 2 years before their final menses. There is also reasonable evidence that this period can cause sleep disturbances in some women. However, there is inconclusive or insufficient evidence that a decrease in ovarian mass is the major cause of mood swings, depression, impaired memory and the ability to concentrate, somatic symptoms, urinary incontinence, or sexual dysfunction. Notably, symptom intensity, duration, frequency, and effects on quality of life are highly variable.

The decision to use postmenopausal HT for the treatment of the symptoms and conditions listed above is complicated. Although many women rely on their health care providers for a definitive answer to the question of whether to use postmenopausal [Page 504]hormones, balancing the benefits and risks for an individual patient is challenging, especially when the individual risk for HT-associated morbidity cannot be precisely quantitated. Despite this context and until the earlier years after the turn of the 20th century, many were prescribed HT as a means of alleviating vasomotor symptoms, for which its effectiveness has been well demonstrated. However, HT was increasingly promoted as a potential preventive strategy against disorders that accelerate after menopause, such as osteoporosis and atherosclerotic CVD.

These positions were based on results primarily from observational cohort studies. Although previous observational studies suggest that HT prevents cardiovascular and other chronic diseases, some of the apparent benefits may have resulted from differences between women who opt to take postmenopausal hormones and women who do not. Specifically, in these observational studies, those using HT tended to be healthier, have greater access to medical care, were more compliant with prescribed treatments, and maintained a more health-promoting lifestyle. On the other hand, randomized trials, which eliminate these confounding factors, have not consistently confirmed the benefits found in observational studies. For example, by enrolling more than 27,000 women from 50 to 70 years of age (mean age: 63 years), the Women's Health Initiative (WHI) was the largest randomized clinical trial of both estrogen-progestin and estrogenalone postmenopausal hormone therapies. After a follow-up period of 5 to 7 years, both WHI hormone trials were stopped early because of an overall unfavorable risk-benefit ratio in the estrogen-progestin arm and an excess risk of stroke that was not offset by a reduced risk of coronary heart disease in the estrogen-only arm. Thus, recent clinical trials have raised doubts about the use of HT for prevention of chronic diseases, especially when initiated more than a decade past menopause.

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