Recommendations on Combined Hormone Therapy

The U.S. Preventive Services Task Force (USPSTF) has issued new recommendations against the use of combined estrogen and progestin therapy for preventing cardiovascular disease and other chronic conditions in postmenopausal women. The recommendations are available online atwww.ahrq.gov.

In 1996, the USPSTF found insufficient evidence to recommend for or against taking hormone therapy to prevent chronic conditions. Now, after reviewing additional studies, including recent clinical trial data that showed the risks of hormone therapy, the USPSTF recommends against taking estrogen and progestin to prevent long-term health problems (a “D” recommendation), and found insufficient evidence to recommend for or against the use of estrogen alone in women who have had a hysterectomy (an “I” recommendation).

The USPSTF found evidence for both benefits and harms of combined estrogen and progestin therapy, one of the most commonly prescribed hormone regimens. However, the USPSTF concluded that harmful effects of the combined therapy are likely to exceed the chronic disease prevention benefits for most women.

Evidence is insufficient to recommend for or against the use of estrogen alone for prevention of chronic conditions in postmenopausal women who have had a hysterectomy. A studyof estrogen therapy in women who have had hysterectomies is continuing as part of the National Institutes of Health (NIH) Women's Health Initiative because it has not yet found clear benefit or harm.

The USPSTF examined hundreds of studies, including the recently terminated trial within the NIH's Women's Health Initiative, which reported the effects of taking combined estrogen and progestin therapy on a variety of chronic diseases. The USPSTF concluded that combined hormone therapy could increase bone mineral density, reduce the risk of fractures, and may reduce the risk of colorectal cancer. The USPSTF found equally strong evidence, however, that combined hormone therapy increases the risk for breast cancer, blood clots, stroke, and gallbladder disease. In addition, evidence suggests that hormone therapy does not reduce the risk of heart disease, and that estrogen and progestin combined actually increase the risk of heart attacks. The effects of hormone therapy on dementia, cognitive function, and ovarian cancer are uncertain.

An estimated 14 million American women take hormone therapy to help relieve hot flushes and other menopausal symptoms, as well as to prevent chronic conditions such as heart disease. The use of hormone therapy to treat hot flushes or other symptoms of menopause was not evaluated by the USPSTF.

The USPSTF recommends that women who are considering starting or continuing hormone therapy to relieve menopausal symptoms discuss their individual risks for specific chronic conditions and personal preferences with their physician.

AAP Recommendations on Reporting Child Abuse

The American Academy of Pediatrics (AAP) has issued a policy statement on determining when inflicted skin injuries in children constitute physical abuse. The report is available online atwww.aap.org/policy/0105.html.

For more than 50 years, recognition of child abuse has been increasing. However, new social legislation, judicial decisions, and administrative policies can pose a problem for physicians in deciding when to report injuries as child abuse. According to the AAP, possible indicators that an injury is the result of child abuse include the following:

• The injury is not only inflicted, but also nonaccidental (compared with, for example, a parent accidentally stepping on the child's toes, causing bruising).

• The pattern of injuries fits a biomechanical model of trauma that is considered abusive (e.g., a handprint bruise on the face).

• The pattern of injuries may correspond to infliction with an instrument in a manner that would not occur through play or natural environmental interactions (e.g., loop cord injuries).

• The provided history of injury is not in keeping with the child's development (e.g., a one-month-old child rolling off the bed).

• The history does not explain the injury (e.g., bruising versus temporary red marks from spanking).

The AAP recommends that physicians consider child abuse the most likely explanation for inflicted skin injuries if they are nonaccidental and there is any injury beyond temporary reddening of the skin. The AAP also calls on physicians to counsel or provide appropriate referral to caregivers to help with behavioral management of children.

NIH Statement on Management of Cancer Symptoms

The National Institutes of Health (NIH) has issued a consensus statement on symptom management in cancer patients. The report is available online at consensus.nih.gov.

Nearly 9 million Americans have had some form of cancer, and the number of cancer survivors continues to grow. Approximately 1.3 million people will be diagnosed with cancer in 2002, and approximately 60 percent will survive at least five years. Although research is producing new insights into the causes and cures of cancer, efforts to manage the symptoms of the disease and its treatments have not kept pace. As patients live longer with cancer, concern is growing about the quality of care patients receive and their quality of life.

Among the most common symptoms of cancer and its treatment are pain, depression, and fatigue, which may persist even after treatment ends. The NIH panel determined that physicians need to be able to identify who is at risk for cancer-related pain, depression, and fatigue; which treatments work best to address these symptoms when they occur; and how best to intervene.

Physicians should routinely use brief assessment tools to ask patients about severity of pain, pain-related impairment, depression, and fatigue, and to initiate evidence-based treatments.

Research is needed on the definition, occurrence, assessment, and treatment of pain, depression, and fatigue alone and together through adequately funded prospective studies. Evidence is also needed to support the concept of cancer-symptom clusters.

According to the consensus statement, the fear of cancer and its consequences must be ameliorated. All patients with cancer should have optimal symptom control from diagnosis throughout the course of illness, irrespective of personal and cultural characteristics.

FDA Advisories

• Mefloquine. The U.S. Food and Drug Administration (FDA) announced that it and Roche have strengthened the contraindications, warnings, precautions, and adverse reactions sections of the product label for mefloquine hydrochloride (Lariam). Mefloquine is indicated for the treatment of mild to moderate acute malaria caused by mefloquine-susceptible strains of Plasmodium falciparum (both chloroquine-susceptible and resistant strains) or by Plasmodium vivax.

Mefloquine is also indicated for the prophylaxis of P. falciparum and P. vivax malaria infections, including prophylaxis of chloroquine-resistant strains of P. falciparum.

Mefloquine is contraindicated for prophylaxis in patients with active depression, a recent history of depression, generalized anxiety disorder, psychosis, schizophrenia, or other major psychiatric disorders, or with a history of convulsions. During pro-phylactic use, if psychiatric symptoms such as acute anxiety, depression, restlessness, or confusion occur, these may be considered prodromal to a more serious event. In these cases, the drug must be discontinued and an alternative medication should be substituted.

The MedWatch 2002 safety summary is available online atwww.fda.gov. The text of a letter sent by Roche to physicians, and the full, revised label are also available.

• Lunelle. The FDA announced in October that Pharmacia is voluntarily recalling all Lunelle (medroxyproges-terone acetate and estradiol cypionate injectable suspension) prefilled syringe lots distributed in the United States, Puerto Rico, and the U.S. Virgin Islands during 2002, because of a lack of assurance of full potency and possible risk of contraceptive failure. A sub-potent dose of Lunelle may not be effective in preventing pregnancy. Lunelle packaged in vials is not affected by this recall, nor is any other Pharmacia contraceptive product.

Women who have been using Lunelle as their contraceptive are advised to seek the advice of their physician regarding alternative methods of birth control and to use an additional barrier method of birth control (such as male or female condoms, diaphragm, or spermicide) until beginning a new form of hormonal contraception.

Physicians may call the Pharmacia medical information service at 800-323-4204 for more information. Patients may call the Pharmacia patient information service at 888-691-6813.

FDA Approvals

• Dutasteride. The U.S. Food and Drug Administration (FDA) approved dutasteride (Avodart) for the treatment of symptomatic benign prostatic hyperplasia (BPH) in men with an enlarged prostate to improve urinary symptoms, reduce risk of acute urinary retention, and reduce the need for BPH-related surgery.

According to the manufacturer, dutasteride inhibits type 1 and type 2 enzymes responsible for the conversion of testosterone to dihydrotestosterone, the primary cause of prostate growth. Side effects may include impotence, decreased libido, breast tenderness, gynecomastia, and ejaculation disorders.

Women and children should not use dutasteride. Women who are pregnant or may become pregnant should not handle dutasteride because of the risk of absorbing duta-steride and the subsequent potential risk to a male fetus. Men treated with dutasteride should not donate blood until at least six months after their final dose to prevent giving the drug to a pregnant woman through a blood transfusion. Dutasteride is contraindicated in men with an allergic reaction to the drug or its ingredients.

• Buprenorphine. Buprenorphine hydrochloride (Subutex) and the combination buprenorphine hydrochloride and naloxone hydrochloride (Suboxone) have been approved for the treatment of opiate dependence. The agents treat opiate addiction by preventing symptoms of withdrawal from heroin and other opiates.

Buprenorphine only is intended for use at the beginning of treatment for drug abuse. Buprenorphine combined with the opiate antagonist naloxone is intended to be the formulation used in maintenance treatment of opiate addiction. Naloxone is added to buprenorphine to guard against intravenous abuse of bupre-norphine by persons physically dependent on opiates.

The U.S. Drug Enforcement Administration (DEA) placed bupre-norphine in Schedule III under the Controlled Substances Act. Bupre-norphine is considered to have less risk for causing psychologic and physical dependence than the drugs in Schedule II (such as morphine, oxycodone, fentanyl, or methadone).

Buprenorphine can be prescribed in an office setting under the Drug Addiction Treatment Act (DATA) of 2000. Until recently, opiate dependence treatments in Schedule II, like methadone, could be dispensed in a very limited number of clinics that specialized in addiction treatment. As a consequence, there have not been enough addiction treatment centers to accommodate all patients desiring therapy. Under this new law, medications for the treatment of opiate dependence that are subject to less restrictive controls than those of Schedule II can be prescribed in a physician's office by specially trained physicians. This change is expected to provide patients greater access to needed treatment.

Side effects most commonly seen with the use of both drugs include cold or influenza-like symptoms, headaches, sweating, sleeping difficulties, nausea, and mood swings. Clinical data indicate that the risk of serious diminished breathing may be less with buprenorphine than other opioids when used in high doses or in overdose situations. Buprenorphine has been associated with deaths related to diminished breathing, especially when used in combination with alcohol or other central nervous system depressant drugs, according to reports from France, where it has been available for several years.

A risk-management program has been designed to deter abuse and diversion from legitimate use by training physicians regarding proper use of these drugs, close monitoring of drug distribution channels, and child-resistant packaging.

DATA provisions include limits on the number of patients individual physicians are allowed to treat and special DEA registration for the use of this drug, thus providing additional safeguards as buprenorphine enters the office-based treatment setting.

The risk-management program also provides for active and passive surveillance to identify if and when the drugs are being abused. The surveillance will include interviews with substance abusers, monitoring local drug markets, data collection, and the monitoring of adverse event reports. Reports of the results of these surveillance efforts will enable the FDA to identify untoward effects from the availability of buprenorphine and, if indicated, to take appropriate actions to protect the public health. ▪