Diseases Update — The Family Health Guide

Estrogen Replacement Therapy Found Not Effective for Mild to Moderate Alzheimer's Disease
Several small, short-term clinical trials have indicated that estrogen may slow or halt the progression of Alzheimer's disease in women, and many animal studies have suggested mechanisms by which the hormone may accomplish this.

However, in the largest and longest clinical trial of its kind to date, researchers found that estrogen did not slow or stop cognitive decline, or improve mood, in women with Alzheimer's disease.

In the randomized, double-blind study, published in the February 23, 2000 Journal of the American Medical Association, researchers assigned study participants to receive either a placebo, or a daily dose of either 0.625 mg or 1.25 mg of estrogen. All 120 participants were women with an average age of 75 years who had mild to moderate Alzheimer's. After one year of treatment, women receiving high- or low-dose estrogen replacement therapy did not have any cognitive or functional improvements compared to the women who took a placebo. The researchers concluded that estrogen should not be used to treat women with established Alzheimer's disease.

Though the results of this study are disappointing, the potential for estrogen to prevent or delay the onset of Alzheimer's disease still exists and is being investigated in several large-scale studies including the Women's Health Initiative Memory Study and the Women's International Study of Long Duration Oestrogen After Menopause.

For more information on Alzheimer's disease, see page 363 of the Harvard Medical School Family Health Guide. To learn more about estrogen replacement therapy, see page 1049 of the Harvard Medical School Family Health Guide.

Physical Therapy and Exercise Helpful for People with Arthritis of the Knee
Osteoarthritis of the knee, a condition that can make it difficult to walk, climb stairs, or rise from a chair, affects one out of every three people between the ages of 63 and 94. It is commonly treated with nonsteroidal anti-inflammatory drugs (NSAIDs) such as naproxen (Aleve) or ibuprofen (Motrin), physical therapy and exercise, cortisone injections, or joint replacement surgery. A recent study in the journal Annals of Internal Medicine confirms the effectiveness of physical therapy and exercise in relieving the discomfort of osteoarthritis of the knee, and suggests that a combination of these two treatments may delay or prevent the need for knee replacement surgery.

At the beginning of the study, patients with osteoarthritis of the knee described the level of pain and discomfort they experienced. Researchers then measured the distance that the patients were able to walk in six minutes. About half of the patients were then assigned to receive manual physical therapy and to participate in an exercise program that included stretching, strengthening, and range-of-motion exercises. The treatment lasted four weeks. The other patients, assigned to a placebo group, did not receive manual physical therapy or perform any exercises.

At the end of four weeks and eight weeks, patients in the treatment group reported significantly less pain and stiffness than before they started treatment. Patients in the placebo group did not show notable improvement. Patients who had undergone treatment were also able to walk a greater distance in six minutes than they could before the start of the study, unlike patients in the placebo group.

At the end of one year, patients who had received treatment continued to feel better and perform better than the placebo group, reflecting the long-term benefits of physical therapy and exercise. Treatment also reduced the likelihood of needing joint replacement surgery. At the end of one year, only 5% of patients in the treatment group had undergone knee replacement surgery, compared to 20% of patients in the placebo group.

For more information about osteoarthritis, see page 604 of the Harvard Medical School Family Health Guide.

ACE Inhibitor Protects High-Risk Patients from Cardiovascular Complications
Results from an international study suggest patients at high-risk for cardiovascular events may benefit from taking 10 mg of ramipril (Altace) daily. Canadian researchers involved in the HOPE (Heart Outcomes Prevention Evaluation) study determined ramipril, a type of ACE inhibitor, significantly reduces the death rate of people with cardiovascular disease but without congestive heart failure. The results were so clear early on, in fact, that the trial ended ahead of schedule so that all participants could benefit.

The HOPE study began in 1994 and includes 267 health centers in 19 countries around the world. The participants, nearly 10,000 men and women, are all at high risk for cardiovascular events. The researchers randomly assigned 9,297 patients age 55 or older to take either 10 mg of ramipril once per day or a placebo. After nearly five years, they found treatment with ramipril reduced the rate of death from cardiovascular causes, as well as the rate of heart attack, heart failure, and stroke. The number of new diabetes cases, as well as the risk of complications related to diabetes, also declined. The effects were present regardless of age, gender, or the presence of coronary artery disease.

Whether other ACE inhibitors have the same beneficial effects is unknown. Ramipril is used to treat high blood pressure and received FDA approval in 1991. It enhances blood flow and prevents angiotensin from converting into a more potent substance that increases salt and water retention. Its side effects include cough, headache, and dizziness.

St. John's Wort as Effective as Low-Dose Tricyclic Antidepressants
Hypericum extract, the active ingredient in St. John's wort, is as effective as a low dosage of a tricyclic antidepressant, according to a study in the Dec. 11, 1999, British Medical Journal. Researchers gave 263 patients with moderate depression hypericum extract, imipramine (a popular tricyclic antidepressant), or a placebo. After eight weeks, the researchers compared the participants' depression rating scores and quality of life scores. They found hypericum extract was just as effective in treating depression as imipramine, and more effective than placebo. In addition, participants taking hypericum extract suffered fewer adverse side effects. St. John's wort products vary considerably in composition, the researchers note, so these results cannot be generalized. They also point out that the dosage of hypericum extract that they tested was higher than recommended.

In 1998, the National Institutes of Health began a three-year study to compare the effectiveness of hypericum extract versus a selective serotonin reuptake inhibitor, another commonly prescribed drug to treat depression. Results from this trial will be reported when they are released.

About 19 million American adults suffer from depression in any given year. Unfortunately, many of them do not seek professional help and may turn instead to over-the-counter remedies. It is essential that you tell your doctor if you take St. John's wort. The herb has been found to interact adversely with many prescription drugs, including oral contraceptives, antivirals (in particular, a drug prescribed to treat HIV infection), and antidepressants. A research team in Switzerland also found the herb can interfere with cyclosporine, a drug used to prevent patients from rejecting organ transplants. Two heart transplant patients were hospitalized after taking St. John's wort because they suffered acute rejection of their hearts.

Depression is a treatable disorder. If you or someone you love shows signs of depression, such as decreased appetite, insomnia, loss of energy, and feelings of hopelessness and guilt, contact your physician immediately. For more information about depression, including a depression questionnaire, see page 395 of the Family Health Guide.