Postmenopausal Carcinoma as a Result of Estrogen Treatment: Survey of Evidence

Recent studies concerning the relationship of exogenous estrogens and endometrial cancer have been reviewed and the objections to their conclusions discussed. Even considering the most serious of these reservations, it is difficult to avoid the tentative conclusion that estrogens are causally linked to endometrial cancer and that the attributable risk is numerically sizable. Whether the medical costs will be ultimately shown to outweigh the benefits of estrogen replacement therapy will depend largely on whether or not a relationship to breast cancer is shown and on the magnitude of the effect of estrogens in preventing serious complications of ovarian failure. For the time being, treatment of menopausal symptoms with estrogens should be as brief as possible, should use the lowest dose possible, and should probably be given in cyclic fashion, particularly to women with intact uteruses. Every attempt should be made to give patients a quantitative understanding of both potential risks and benefits before they decide in favor of or against estrogen therapy.

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Invited Review: Pharmacogenetics of estrogen replacement therapy

Journal of Applied Physiology ◽

10.1152/jappl.2001.91.6.2776 ◽

2001 ◽

Vol 91 (6) ◽

pp. 2776-2784 ◽

Cited By ~ 28

Author(s):

David M. Herrington ◽

Karen Potvin Klein

Keyword(s):

Estrogen Replacement Therapy ◽

Genetic Factors ◽

Estrogen Receptor Α ◽

Estrogen Replacement ◽

Risk Gene ◽

Thrombosis Risk ◽

Venous Thromboembolic Events ◽

Venous Thromboembolic ◽

Relationship Of ◽

The Relationship

There are a number of genetic factors that likely modulate both the beneficial and adverse effects of estrogen. An important domain of consideration is the relationship of estrogen and thrombosis risk. Gene polymorphisms among the key elements of the coagulation and fibrinolytic cascade appear to influence the effects of estrogen on risk for venous thromboembolic events and possibly arterial thrombosis as well. Emerging data also suggest that allelic variants in the estrogen receptor-α may modulate estrogen's effects, especially with respect to bone and lipid metabolism.

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Randomized Double-Blind Trial of Estrogen Replacement Therapy Versus Placebo in Stage I or II Endometrial Cancer: A Gynecologic Oncology Group Study

Journal of Clinical Oncology ◽

10.1200/jco.2005.02.8464 ◽

2006 ◽

Vol 24 (4) ◽

pp. 587-592 ◽

Cited By ~ 133

Author(s):

Richard R. Barakat ◽

Brian N. Bundy ◽

Nick M. Spirtos ◽

Jeffrey Bell ◽

Robert S. Mannel

Keyword(s):

Endometrial Cancer ◽

Placebo Group ◽

Replacement Therapy ◽

Recurrence Rate ◽

Estrogen Replacement Therapy ◽

Disease Recurrence ◽

Stage I ◽

Age At Diagnosis ◽

Estrogen Replacement

Purpose To determine the effect of estrogen replacement therapy (ERT) on recurrence rate and survival in women who have undergone surgery for stage I or II endometrial cancer. Patients and Methods After surgery, eligible patients were allocated to therapy with ERT or placebo after undergoing hysterectomy with or without pelvic and aortic nodal sampling. Planned duration of hormonal versus placebo treatment was 3 years, with an additional 2 years of follow-up. Results The median follow-up time for all 1,236 eligible and assessable patients was 35.7 months. Stage, grade, histologic subtype, and percentage of patients receiving adjuvant therapy were similarly distributed between the groups. The median age at diagnosis for the 618 patients randomly assigned to ERT was 57 years (range, 26 to 91 years). Two hundred fifty-one patients (41.1%) were compliant with ERT for the entire treatment period. Disease recurrence was experienced in 14 patients (2.3%). Eight patients (1.3%) developed a new malignancy. There were 26 deaths (4.2%), and five deaths (0.8%) were a result of endometrial cancer. The median age at diagnosis for the 618 patients in the placebo group was 57 years (range, 30 to 88 years). Twelve patients (1.9%) experienced disease recurrence. Ten patients (1.6%) developed a new malignancy. There were 9 deaths (3.1%) in the placebo group, and four deaths (0.6%) were a result of endometrial cancer. Conclusion Although this incomplete study cannot conclusively refute or support the safety of exogenous estrogen with regard to risk of endometrial recurrence, it is noteworthy that the absolute recurrence rate (2.1%) and the incidence of new malignancy were low.

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