Risk of Endometrial Cancer Following Estrogen Replacement With and Without Progestins

Elisabete Weiderpass, Hans-Olov Adami, John A. Baron, et al.
Abramson Cancer Center of the University of Pennsylvania
Ultima Vez Modificado: 1 de noviembre del 2001

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Reviewers: Li Liu, MD
Source: Journal of the National Cancer Institute, Volume 91, No 13 (July):1131-1137, 1999


It has been established that estrogen replacement therapy is effective in preventing osteoporosis in post-menopausal women. Estrogen also raises High-Density Lipoprotein (HDL, good cholesterol), lowers Low-Density Lipoprotein (LDL, bad cholesterol), and therefore reduces the risk of coronary artery disease. However, estrogen replacement is not without cost. The great concern to both physicians and patients is endometrial carcinoma. A number of studies have demonstrated that postmenopausal estrogen therapy is associated with an increase in the incidence of endometrial carcinoma. The addition of progestins is thought to eliminate excess risk of endometrial hyperplasia and carcinoma. This report is of a large population-based study in Sweden to assess the impact of different hormone replacement regimens on the risk of endometrial cancer.


Information was collected on use of hormone replacement from 709 postmenopausal patients with incident endometrial cancer and from 3368 control subjects. Age ranged from 50 to 74 years. Comparison was made with women who never used the respective hormone replacement regimens. Treatment episodes were classified into 4 categories:

  1. Medium-potency estrogens without added progestins.
  2. Medium-potency estrogens combined with cyclical (<16 days per cycle) or continuous (>19 days per cycle) progestin
  3. Low-potency estrogens
  4. Progestins without estrogen


  • Treatment with estrogen alone was associated with a threefold increased relative risk of endometrial cancer.
  • The excess relative risk persisted even 5 or more years after cessation of treatment.
  • Following the use of estrogens plus progestins, the association was remarkably weaker than that for estrogen alone, and the excess relative risk was statistically significant only after 10 or more years of use.
  • The increase in relative risk for endometrial cancer was only confined to women exposed to cyclic addition of progestins, whereas continuous addition of progestins actually reduced the relative risk.


Hormone replacement therapy has become more prevalent throughout the world, especially in the developed countries. Finding the safest way to administer such therapy is of great interest to both physicians and patients. This study demonstrated that the continuous addition of a progestin appears to be the safest regimen for postmanopausal women with a uterus. More studies are needed to further define the duration of adding progestins.


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