Hormone replacement therapy endometrial cancer

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%. 

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. 

The chief therapeutic uses of estrogens and progestins are as oral contraceptives and hormone replacement therapy. Progestins and SERMs are also important agents in the treatment of osteoporosis, breast cancer, endometrial cancer, and infertility. 

Suggestive case histories raised at an early phase the notion of a possible correlation of oral contraceptives with endometrial cancer. Among cases of endometrial cancer there seemed to be an excess of users of oral contraceptives, particularly of the early high-dose estrogen type. With the virtual demise of these early products, the situation seems to have reversed a 1983 study from the Centers for Disease Control (CDC) in Atlanta showed that women who had used fixed combinations for oral contraception at some time in their lives had a relative risk of endometrial cancer of only 0.5 compared with never-users (112). The protective effect occurred only in women who had used oral contraception for at least 12 months, and lasted for at least 10 years after withdrawal. The WHO adopted the same view in 1988 in the light of multinational data (113). As in the case of hormonal replacement therapy, the protective effect seems to be due to the progestogen component. 

While the risk that hormone replacement therapy may cause endometrial tumors has been widely discussed, less attention has been given to the possibility that it could increase the risk of epithelial ovarian cancer. Since cancer of the ovary has some risk factors in common with endometrial cancer (notably low parity and obesity), this possible risk needs to be considered, especially in view of the fact that the endometrioid epithelial type of ovarian tumor is histologically so similar to adenocarcinoma of the endometrium. 

Sulak PJ. Endometrial cancer and hormone replacement therapy. Appropriate use of progestins to oppose endogenous and exogenous estrogen. Endocrinol Metab Clin North Am 1997 26(2) 399 U2. 

The associations between hormone replacement therapy and breast, endometrial, and ovarian cancers are discussed in the monograph on estrogens. 

Hill DA, Weiss NS, Beresford SA, Voigt LF, Daling JR, Stanford JL, Self S. Continuous combined hormone replacement therapy and risk of endometrial cancer. Am J Obstet Gynecol 2000 183(6) 1456-61. 

Jain MG, Rohan TE, Howe GR. Hormone replacement therapy and endometrial cancer in Ontario, Canada. J Clin Epidemiol 2000 53(4) 385-91. 

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). 

However, estrogen has been demonstrated to be associated with the increased incidence of breast and endometrial cancer after prolonged treatment. In addition, during HRT, venous thrombo-embolic complications are encountered more frequently than in women not undergoing HRT [71]. Therefore, there is a growing interest in using isoflavones as a potential alternative to the estrogens in hormone replacement therapy. 

Hormone replacement therapy (HRT)— with estrogens to i endometrial cancer... 

This study has again confirmed that endometrial problems can be induced by tamoxifen early in the course of treatment and that these problems do not arise with aromatase inhibitors, which may actually reduce the endometrial changes induced by tamoxifen. The idea that the new oral aromatase inhibitors might well replace tamoxifen in breast cancer was tentatively advanced in SEDA-26 (p. 445) and has now been supported by some of the material cited above, as well as by a panel consensus (25). Citing efficacy and safety data on anastrozole, exemestane, and letrozole, the authors concluded that third-generation aromatase inhibitors may be considered first-line therapy of hormone-receptor-positive advanced breast cancer in postmenopausal women and may also be used for preoperative therapy of breast cancer. 

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