Gonadotropinhormonereleasing Hormone Analogues In Combination

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Use of GnRH analogues in premenopausal women is predictably associated with hypo-

estrogenic symptoms, including hot flushes, vaginal dryness, and sleep disturbances. In the majority of studies with protracted GnRH analogue treatment, loss of bone mineral density (BMD) has been evident. As oophorectomy at a young age is associated with an increased risk of cardiovascular disease, long-term use of GnRH analogues is of concern. While the side effects and risks associated with hypoestrogenemia are acceptable in the setting of metastatic breast cancer and in the adjuvant treatment of early breast cancer, such effects may not be acceptable to women only at risk for the development of the disease. While a GnRH analogue should achieve major reduction in a woman's lifetime breast cancer risk, the benefit will occur only if the agent were to be continued for prolonged periods of time. To permit such protracted use, methods for reducing the side effects and morbidity must be considered.

The effect of protracted GnRH analogue treatment on BMD has prompted consideration of several strategies to combat the loss of bone density. A logical choice is addition of a SERM such as tamoxifen, which is known to have protective effects on BMD.23 The use of tamoxifen combined with a GnRH analogue is also of interest because of the known chemopreventive effects of tamoxifen.24 Bisphosphonates are important agents in the management of osteopenia in postmenopausal women. A study testing the combination of a GnRH analogue and a bispho-sphonate has also been proposed. While either approach may ultimately prove useful in reducing the loss of BMD, the tolerance of women to hypoestrogenic symptoms, which will not be alleviated by these approaches, remains to be evaluated. Analogues of GnRH are associated with greater symptoms than tamoxifen alone in the adjuvant setting,25 and control of these symptoms may significantly impact on use in the preventive setting.

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Natural Cures For Menopause

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