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Am Fam Physician. 2005;72(12):2520-2522

Case Study

In keeping with the 2002 recommendation from the U.S. Preventive Services Task Force (USPSTF) that women 65 years of age and older should be screened for osteoporosis, you have ordered a dual-energy x-ray absorptiometry test for a 66-year-old white woman. The results indicate that she is at increased risk of osteoporotic fractures. She comes to your office to discuss treatment options. She has an intact uterus and took combined estrogen and progestin for five years after menopause. She recalls that while she was taking hormone therapy, you said it would help prevent osteoporosis. She asks if she should start the therapy again.

Case Study Questions

1. Which one of the following statements is accurate and could help guide your discussion with your patient about whether she should begin combined estrogen and progestin therapy?

  • A. Her previous use of combined estrogen and progestin without complications should influence your recommendations about estrogen therapy.

  • B. Estrogen, either unopposed or in combination with progestin, currently is the only effective medication approved by the U.S. Food and Drug Administration (FDA) for the prevention of fractures in women with low bone mineral density.

  • C. Combined estrogen and progestin prevents coronary heart disease in women such as this patient.

  • D. Neither unopposed estrogen nor combined estrogen and progestin is recommended for the prevention of chronic disease in postmenopausal women.

2. Which one of the following statements about the risks and benefits of hormone therapy is correct?

  • A. Unopposed estrogen decreases the risk of stroke.

  • B. Combined estrogen and progestin reduces the incidence of breast cancer mortality.

  • C. Unopposed estrogen and combined estrogen and progestin decrease the risk of ovarian cancer.

  • D. Unopposed estrogen and combined estrogen and progestin increase the risk of dementia.

  • E. Unopposed estrogen decreases the risk of colorectal cancer.

3. Because of the risks you discussed, the patient is worried about having been on hormone therapy in the past. For which of the following conditions does combinbed estrogen and progestin therapy increase risk in the first one to two years of use?

  • A. Breast cancer.

  • B. Coronary heart disease.

  • C. Stroke.

  • D. Venous thromboembolism.


1. The correct answer is D. The USPSTF recommends against the routine use of combined estrogen and progestin for the prevention of chronic conditions in post-menopausal women and makes the same recommendation for unopposed estrogen use in postmenopausal women who have had a hysterectomy. Previous use of either combined therapy or unopposed estrogen without complications is not an indicator that a patient is at reduced risk of the harms of hormone therapy. See Table 1 for the benfits and harms of hormone therapy.

ConditionCombined estrogen and progestinUnopposed estrogen
Reduces riskInsufficient evidenceIncreases riskReduces riskInsufficient evidenceIncreases risk
All-cause mortalityxx
Breast cancerxx
Breast cancer mortalityxx
Colorectal cancerx*x
Coronary heart diseasex
Lower global cognitivexx
Ovarian cancerxx
Venous thromboembolismxx

The probability that a menopausal woman will fracture a hip during her lifetime is estimated at 15 percent. Estrogen alone or in combination with progestin reduces the risk of fractures in women with or without low bone mineral density. However, other effective FDA-approved medications, such as bisphosphonates and calcitonin, are available for preventing fractures in women with low bone density. Their role in preventing fractures in women without low bone mineral density is unclear.

Approximately 46 percent of postmenopausal women will develop coronary heart disease. Combined estrogen and progestin has no beneficial effect on coronary heart disease—the main cause of mortality in postmenopausal women—and may even increase risk. Unopposed estrogen also has no beneficial effect on heart disease.

2. The correct answer is D. Unopposed estrogen and combined estrogen and progestin increase the risk of dementia and lower global cognitive functioning. Some studies have shown a beneficial effect on cognition from combined estrogen and progestin, but those studies have problems with internal and external validity. Currently, overall evidence supports their harmful effects on cognitive function, although the clinical relevance of this is unclear.

Unopposed estrogen and combined estrogen and progestin also increase the risk of venous thromboembolism and stroke. In 1992, when the USPSTF previously made its recommendations on hormone therapy, there was insufficient evidence that unopposed estrogen increases risk of stroke. Since then, a trend to increased stroke risk has been demonstrated in the Women's Health Initiative trial. The unopposed estrogen arm of that trial was terminated in 2004 because of this increased stroke risk in combination with the lack of effect on the risks of heart disease or breast cancer. The combined estrogen and progestin arm was terminated in 2002 because the evidence for cardiovascular disease and breast cancer harm outweighed the evidence of fracture benefits and possible benefit for colon cancer.

There is insufficient evidence to determine the effects of either combined estrogen and progestin or unopposed estrogen on the incidence of ovarian cancer, breast cancer mortality, or all-cause mortality. There is also insufficient evidence to assess the effects of unopposed estrogen on the incidence of colorectal cancer and breast cancer. Combined therapy increases incidence of cholecystitis but decreases the risk of colorectal cancer.

3. The correct answers are B, C, and D. Combined estrogen and progestin increases the risk of coronary heart disease, stroke, and venous thromboembolism. These risks arise within the first one to two years of therapy. Other risks, such as the risk of breast cancer, appear to increase with longer-term use.

Women using hormone therapy for menopausal symptom relief may differ from those who would use hormone therapy for prevention of chronic disease (e.g., age differences). Women and their physicians should discuss the balance of risks and benefits before deciding to initiate or continue hormone therapy for menopausal symptoms. Some expert groups have recommended that women deciding to take hormone therapy for symptomatic relief should use the lowest effective dosage for the shortest possible time.

This series is coordinated by Joanna Drowos, DO, contributing editor.

A collection of Putting Prevention Into Practice published in AFP is available at

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