Menopause, hormone-replacement therapy risks

Lacey JV, Mink PJ, Lubin JH, et al. Menopausal hormone replacement therapy and risk of ovarian cancer. JAMA 2002 288 3343-3341. 

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. 

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 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. 

In untreated women, the main risk factors for endometrial carcinoma are age, obesity, nulliparity, late menopause (and possibly early menarche), the Stein-Leventhal syndrome, exposure to exogenous estrogens, radiation, and certain systemic diseases, including diabetes mellitus, hypertension, hypothyroidism, and arthritis (SED-14, 1451) (88). Certain of these risk factors indicate that an altered endocrine state with increased estrogen stimulation is a predisposing cause, and one might thus in theory expect estrogen treatment (and notably hormonal replacement therapy) to increase the risk (SEDA-22, 466). 

Options for treatment include hormone replacement therapy (HRT), bisphosphonates, calcitriol, calcitonin, raloxifene, strontium ranelate, and teriparatide. Hormone replacement therapy is generally indicated for women who are under 50 years and are experiencing a premature menopause. Symptomatic menopausal women may opt to use HRT also, as the benefits outweigh the risks for up to 5 years treatment. They may choose an alternative treatment for osteoporosis if preferred. Hormone replacement therapy is not recommended for first line treatment for long-term prevention of osteoporosis in women over 50 years of age. 

The last women s mental health issue discussed here is menopause. Only a few years ago, women thought that taking hormone replacement therapy (HRT) was necessary to prevent every aspect of aging, and the belief that HRT warded off depression in the fifth decade and beyond was just one more element in its assumed panacea. More recent studies have suggested that HRT does not protect against heart disease and dementia, and it does increase the risk for stroke and for certain cancers... 

Feigin VL, Wiebers DO, Nikitin YP et al. (1998). Risk factors for ischemic stroke in a Russian community a population-based case-control study. Stroke 29 34-39 Fine-Edelstein JS, Wolf PA, O Leary et al. (1994). Precursors of extracranial carotid atherosclerosis in the Framingham Study. Neurology 44 1046-1050 Gabriel SR, Carmona L, Roque M et al. (2005). Hormone replacement therapy for preventing cardiovascular disease in post-menopausal women. Cochrane Database Systems Review 2 CD002229... 

MAGNESIUM HORMONE REPLACEMENT THERAPY May cause magnesium depletion Mg levels tend to l during menopause. Risk-benefit ratios need to be considered on an individual basis as there are suggestions that magnesium can counteract the alleged T risk of heart attacks and strokes in patients on hormone replacement therapy Be aware... 

Alendronate is currently the drug of choice to prevent osteoporosis in patients who must be maintained on steroids for their antiinflammatory and immunosuppressive effects. The drug also decreases bone resorption during menopause and is sometimes favored in patients who are at risk for neoplasias if treated with sex hormones. Care must be taken with alendronate to avoid esophageal ulceration. Estrogen hormone replacement therapy +/- vitamin D also has proven value for slowing bone resorption in menopause, and increases in bone mass have been reported for combinations of estrogens with alendronate. 

Hormone replacement therapy (HRT) with oestrogen and progesterone is no longer recommended and should not be used as first line treatment in post-menopausal women for osteoporosis. This is because of the increased risk of breast, endometrial and ovarian cancer with HRT. Its use should be reserved for patients in whom other drugs are contraindicated, not tolerated or ineffective. HRT is most effective if started early in the menopause and continued for up to five years (after which osteoporosis will return, possibly at an accelerated rate). 

---