Hormone-replacement therapy risks

Cardiovascular disease (CVD) is one of the leading causes of death worldwide. There are a number of established risk factors including serum cholesterol levels, smoking and family history, which are responsible for between 50 and 75% of the CVD cases, with the remainder due to factors that cause atherosclerosis. Estrogen treatment such as hormone replacement therapy is known to protect against CVD by decreasing the levels of low-density... 

There is much interest in the possible hormonal effects of phytoestrogens in both men and women. The majority of studies conducted in women have examined the ability of phytoestrogens to alleviate menopausal symptoms. Whilst hormone replacement therapy is recommended for women experiencing menopausal symptoms, there remains some uncertainty as to whether HRT can increase the risk of breast cancer. As a result of these concerns, investigations into natural alternatives such as phytoestrogens have received considerable attention. 

Explain the risks and benefits associated with hormone-replacement therapy. 

Long-term use of hormone-replacement therapy and concurrent use of progestins appear to contribute to breast cancer risk.7 The use of postmenopausal estrogen-replacement therapy in women with a history of breast cancer generally is considered contraindicated. However, most experts believe that the safety and benefits of low-dose oral contraceptives currently outweigh the potential risks and that changes in the prescribing practice for the use of oral contraceptives are not warranted. Oral contraceptives are known to reduce the risk of ovarian cancer by about 40% and the risk of endometrial cancer by about 60%. 

In a reanalysis of 51 studies, less than 5 years of therapy with combined estrogen and progestogen was associated with a 15% increase in risk for breast cancer, and the risk increased with greater duration of treatment. Five years after discontinuation of hormone replacement therapy, the risk of breast cancer was no longer increased. 

Cano A, Van Baal WM (2001) The mechanisms of thrombotic risk induced by hormone replacement therapy. Maturitas 40 17-38... 

Chen FPL, Lee N, Wang CH, Soong YK (1998) Effects of hormone replacement therapy on cardiovascular risk factors in postmenopausal women. Fertil Steril 69 267-273... 

Daly E, Vessey MP, Hawkins MM, Carson JL, Gough P, Marsh S (1996) Risk of venous thromboembolism in users of hormone replacement therapy. Lancet 348 977-980... 

Perez-Gutthan S, Garcfa-Rodriguez LA, Castellsague J, Duque-Oliart A (1997) Hormone replacement therapy and risk of venous thromboembolism population based case-control study. Br Med J 314 796-800... 

Santen RJ, Pinkerton J, McCartney C (2001) Clinical review 121 Risk of breast cancer with progestins in combination with estrogen as hormone replacement therapy. J Clin Endocrinol Metab 86(l) 16-23... 

Hormone therapy has proven highly effective in controlling the menopausal syndrome, especially severe hot flushes (MacLennan et al. 2004), even at doses significantly lower than those used until now (Speroff et al. 2000 Utian et al. 2001). Women s Health Initiative studies found that hormone replacement therapy, when administered as a primary prevention intervention for CVD in older women, increases the risk of heart disease and breast cancer. Even if a protective effect on fracture and colon cancer was observed, the risk-benefit ratio led to a recommendation of this treatment only for the short-term relief of menopausal symptoms (Rossouw et al. 2002 Anderson et al. 2004). The role of early administration of ovarian hormones to young postmenopausal women in the prevention of cardiovascular disease or late dementia remains... 

The statins have been demonstrated to markedly lower plasma LDL levels (and triglyceride levels to a lesser extent). In fact, statins were approved by the US FDA on the basis of a surrogate endpoint reduction in plasma cholesterol levels. Since we know that increased plasma cholesterol levels are correlated with increased risk of coronary artery disease, it seems logical that reducing plasma cholesterol levels would lead to reduced risk. That turns out to be true in this case. However, see the case of hormone replacement therapy (HRT) for women for a more complex example, discussed below. 

The clinical problems that arise in the menopause are hot flushes, sweating, depression, decreased libido, increased risk of cardiovascular disease and osteoporosis. The latter results in increased incidence of hip, radial and vertebral fractures. Oestrogen is one factor controlling synthesis of active vitamin D and osteoporosis is in part due to a deficiency of vitamin D. Not surprisingly, to reduce these problems, administration of oestrogen is recommended (known as hormone replacement therapy or HRT). HRT reduces some of the risk factors for coronary artery disease since it reduces blood pressure and decreases the blood level of LDL-cholesterol and increases that of HDL-cholesterol. However, there is considerable debate about whether HRT increases the risk of breast or endometrial cancer. 

Hormone replacement therapy provides relief from vasomotor symptoms, decreases the risk of osteoporosis and decreases the risk of cardiovascular disease in post-menopausal women. 

This combination product is on example of a combined hormone replacement therapy that increases the risk of stroke slightly and, with long-term use, increases the risk of ovarian cancer slightly. Hormone replacement therapy alleviates symptoms of menopause and can be used as a prophylaxis of osteoporosis. 

Estrogens are most commonly used as a component of combination contraceptives or as hormone replacement therapy in postmenopausal women. Benefits in postmenopausal women include relief of moderate to severe vasomotor symptoms and decreased risk of osteoporosis. Hormone replacement therapy also may be used in vaginal and vulvar atrophy and in hypoestrogenism caused by hypogonadism, castration, or primary ovarian failure. Less commonly, select breast or prostate cancer... 

Ross RK, Paganini-Hill A, Wan PC, Pike MC. Effect of hormone replacement therapy on breast cancer risk estrogen versus estrogen plus progestin. J Natl Cancer Inst 2000 92(4) 328-32. 

Currently recommended that use of hormone replacement therapy be limited to treating symptomatic women, preferably for 5 yr or less. Risk felt to outweigh benefit in asymptomatic women using only for prophylaxis of other conditions... 

Psaty, B.M., N.L. Smith, R.N. Lemaitre, H.L. Vos, S.R. Heckbert, A.Z. LaCroix, and F.R. Rosendaal, Hormone replacement therapy, prothrombotic mutations, and the risk of incident nonfatal myocardial infarction in postmenopausal women. Jama, 2001.285(7) 906-13. 

Gomes MPV, Deitcher SR Risk of venous thromboembolic disease associated with hormonal contraceptives and hormone replacement therapy A clinical review. Arch Intern Med 2004 164 1965. [PMID 15477430]... 

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