Hormone replacement therapy-estrogens progestogens

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. 

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. 

Rozenberg S, Caubel P, Lim PC. Constant estrogen, intermittent progestogen vs. continuous combined hormone replacement therapy tolerability and effect on vasomotor symptoms. Int J Gynaecol Obstet 2001 72(3) 235-43. 

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. 

As far as hormone replacement therapy is concerned (Table 2) one must provisionally conclude, with the authors of a major Canadian study published in 1992, that long-term past use of estrogens is not related to risk, but that current estrogen use increases the risk of breast cancer to a modest degree, and that the addition of progestogens probably does not remove the increased risk resulting from the use of unopposed estrogen (150). 

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