The most common type of MHT (previously referred to as hormone replacement therapy, or HRT) consists of the administration of estrogens together with a progestogen. Because of the risk of uterine cancer, estrogen therapy alone is used only in hysterectomized women. Initially used to counteract “hot flashes” and other symptoms of menopause, early clinical studies suggested that MHT use in postmenopausal women could prevent or slow the progression of osteoporosis (Chapter 21) and reduce the likelihood of myocardial infarction. However, subsequent randomized clinical trials have produced decidedly mixed results. According to these, although MHT did reduce the number of fractures in women on treatment, it was also reported that after 5 years of treatment, combination MHT increased the risk of breast cancer (Chapter 19), stroke, and venous thromboembolism and had no effect on the incidence of coronary heart disease. But during the past few years there has been a reappraisal of the risks and benefits of MHT. These newer analyses showed that MHT effects depend on the type of hormone therapy regimen used (combination estrogen-progestin versus estrogen alone), the age and risk factor status of the woman at the start of treatment, the duration of the treatment, and possibly the hormone dose, formulation, and route of administration. The current risk:benefit consensus can be summarized as follows:
Combination estrogen-progestin increases the risk of breast cancer after a median time of 5 to 6 years. In contrast, estrogen alone in women with hysterectomy is associated with a borderline reduction in the risk of breast cancer.
MHT may have a protective effect on the development of atherosclerosis and coronary disease in women younger than 60 years of age, but there is no protection in women who started MHT at an older age. These data support the notion that there may be a critical therapeutic window for MHT effects on the cardiovascular system. Protective effects in younger women depend in part on the response of estrogen receptors in healthy vascular endothelium. However, MHT should not be used for the http://ebooksmedicine.net prevention of cardiovascular disease or other chronic diseases.
• MHT increases the risk of stroke and venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism. The increase in VTE is more pronounced during the first 2 years of treatment and in women who have other risk factors, such as immobilization and hypercoagulable states caused by prothrombin or factor V Leiden mutations (Chapter 4). Whether risks of VTE and stroke are lower with transdermal than oral routes of estrogen administration warrants further study.
As can be appreciated from these associations, assessment of risks and benefits when considering the use of MHT in women is complex. The current feeling is that these agents have a role in the management of menopausal symptoms in early menopause but should not be used long term for chronic disease prevention.
Although OCs have been used for several decades, disagreement continues about their safety and adverse effects. They nearly always contain a synthetic estradiol and a variable amount of a progestin (“combination OCs”), but a few preparations contain only progestins. Currently prescribed OCs contain a smaller amount of estrogens (less than 50 µg/day) and clearly have fewer side effects than those reported for earlier formulations. Hence, the results of epidemiologic studies must be interpreted in the context of the dosage. Nevertheless, there is reasonable evidence to support the following conclusions:
Breast carcinoma: The prevailing opinion is that OCs do not cause an increase in breast cancer risk.
Endometrial cancer and ovarian cancers: OCs have a protective effect against these tumors.
Cervical cancer: OCs may increase the risk of cervical carcinomas in women infected with human papillomavirus.