Estrogen replacement therapy, bone loss

The beneficial role of estrogen replacement therapy (ERT) to prevent bone loss has been largely demonstrated (Nelson et al. 2002 Wells et al. 2002). Re-... 

Estrogen replacement therapy can prevent bone loss and actually increase bone density in postmenopausal women. Estrogen treatment is the most effective therapy for osteoporosis and significantly reduces the incidence of bone fractures in postmenopausal women. The usual dose of estrogen prescribed is 0.625 mg/day of conjugated equine estrogens (Premarin). Alternatively, a transdermal estrogen patch can be used. 

With increasing concern over the long-term safety of hormone replacement therapy, the benefit to harm balance has to be continually reassessed, and conclusions as to its prophylactic or therapeutic value need to be adjusted as experience accumulates. Not all the promises held out for the benefits of this therapy have been confirmed. For example, while estrogens prevent peripheral bone loss they do not prevent vertebral fractures (6) and in a 2-year placebo-controlled, crossover study in 34 healthy postmenopausal women, treatment with transder-mal estrogen alone (Menorest 50 micrograms/day) did not improve lipid profiles or any indices of arterial function (7). 

Although estrogen replacement therapy at menopause can prevent bone loss and cardiovascular disease, there is evidence that estrogens are associated with an increased risk of breast cancer as well as endometrial cancer(Gambrell, 1994), which thus seriously limits the use of estrogen replacement therapy. The ideal compound for women s health should be one able to decrease the risk of the most important causes of morbidity and mortality in women, namely breast cancer, uterine cancer, osteoporosis, bone fractures, and cardiovascular disease. Heart disease is, in fact, the leading cause of death in postmenopausal women (Lerner and Kannel, 1986). This ideal compound should also have an excellent safety profile to ensure compliance over 20 to 40 years of a woman s life. 

Because of the absence of protective effects of raloxifene on vasomotor symptoms or hot flashes, many authors suggest that conventional estrogen replacement therapy is likely to remain the intervention of choice for the prevention of bone loss in symptomatic postmenopausal women (Baynes and Compston, 1998). In fact, since the majority of women seek medical attention because of vasomotor symptoms (Gam-brell, 1996) and the compounds of the SERM class, such as raloxifene (Draper et al., 1996), can lead to exacerbation (Draper et al., 1996) or have no influence (Delmas et al., 1997) on these symptoms, compliance is likely to be a problem. In fact, even tamoxifen has been shown to increase hot flashes (Love etal, 1991a). 

Correct answer = D. Estrogens decrease but do not restore the age-related loss of bone. Vasomotor symptoms of menopause, such as hot flashes, are decreased with estrogen replacement therapy. Symptoms of menopause, such as atrophic vaginitis, are decreased with estrogen replacement therapy. Oral contraceptives contain higher doses of estrogen than those used with estrogen replacement therapy. 

Lukert BP, Johnson BE, Robinson RG. Estrogen and progesterone replacement therapy reduces glucocorticoid-induced bone loss. J Bone Miner Res 1992 7(9) 1063-9. 

Tibolone is an agonist at estrogen and progestogen receptors, with weak androgenic activity. It is given as an alternative to hormone replacement therapy, without added progestogen, and has been in use for some 30 years to treat bone loss in post-menopausal women. Some long-term studies (for example over 10 years) appear to have confirmed its safety and relative freedom from adverse effects (1). In particular there is little or no increase in thrombotic events and the incidence of breast tenderness is low. 

Estrogen replacement (see p. 264) is the most effective therapy for the prevention of postmenopausal bone loss. When initiated in the immediate postmenopausal period, estrogen prevents osteoporosis and reduces the risk of hip fracture. Raloxifene, a second-generation selective estrogen receptor modulator (see p. xxx), increases women s bone density without increasing the risk for endometrial cancer. In addition, raloxifene has recently been reported to decrease the risk of estrogen receptor-positive breast cancer. 

Estrogens, etidronate, and parathyroid hormone have been used with partial success to prevent gonadorelin-induced bone loss. In a prospective study of 49 women treated with goserelin and randomized to estradiol plus norethisterone or placebo, bone loss persisted 6 years after stopping therapy, and the hormone replacement therapy had only a minor protective effect (44). 

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