NAMS Statement on Hormone Therapy

The 2003 Hormone Therapy Advisory Panel of the North American Menopause Society (NAMS) has released its position statement on estrogen and progestogen use in peri- and postmenopausal women. The statement is available online at:http://www.menopause.org.

Because of the influx of new clinical trial data regarding postmenopausal hormone therapy (HT), the NAMS convened an advisory panel to present clinical recommendations for use of HT in peri- and postmenopausal women. Among the various recommendations are the following:

• Treatment of moderate and severe menopause symptoms (i.e., vasomotor symptoms, sleep disruption from vasomotor symptoms) remains the primary indication for systemic estrogen therapy (ET) and combined estrogen-progestogen therapy (EPT). Every systemic ET/EPT product is approved by the U.S. Food and Drug Administration (FDA) for this indication.

• Every systemic and local ET/EPT product is FDA-approved for treating moderate to severe symptoms of vulvar and vaginal atrophy, such as vaginal dryness, dyspareunia, and atrophic vaginitis. When hormones are considered solely for this indication, local ET generally is recommended.

• The primary menopause-related indication for progestogen use is endometrial protection from unopposed ET. For all women with an intact uterus who are using ET, physicians are advised to prescribe adequate progestogen, in either a continuous-combined EPT or a continuous-sequential EPT regimen. Women without a uterus should not be prescribed a progestogen.

• Some women with an intact uterus who choose EPT may experience undesirable side effects from the progestogen component. However, there is insufficient evidence regarding long-term endometrial safety to recommend use of long-cycle progestogen (i.e., progestogen every three to six months for 12 to 14 days), a progestin-containing intrauterine device, or low-dose estrogen without progestogen as an alternative to standard EPT regimens. If using any of these approaches, closer surveillance of the endometrium is recommended, pending more definitive research.

• No EPT regimen should be used for primary or secondary prevention of coronary heart disease (CHD) or stroke.

• The effect of ET on CHD and stroke is not yet clear. ET does not have a significant effect on stroke risk in postmenopausal women with known ischemic cerebrovascular disease, but for healthy older women, effects of ET on stroke risk are not clear. However, unless confirming data become available, ET should not be used for primary or secondary prevention of these conditions.

• Breast cancer risk is increased with ET use and, to a greater extent, EPT use beyond five years. Progestogen appears to contribute substantially to that adverse effect. EPT and, to a lesser extent, ET increase breast cell proliferation, breast pain, and mammographic density. HT may impede the diagnostic interpretation of mammograms.

• HT may be associated with increased breast cancer mortality, but insufficient data are available to determine whether ET or EPT, or duration of use of ET or EPT, is associated with any increase in mortality.

• There is definitive evidence of EPT efficacy in reducing risk for post-menopausal osteoporosis fracture. There is, to date, no comparable evidence for ET. Many EPT and ET products are FDA-approved for prevention of postmenopausal osteoporosis through long-term treatment. Because of the potential risks associated with HT, for women who require drug therapy for osteoporosis risk reduction (including women at high risk of fracture in the next five to 10 years), alternatives to HT should be considered, weighing the risks and benefits of each.

• Premature menopause and premature ovarian failure are conditions associated with earlier onset of osteoporosis and CHD, but there are no clear data as to whether ET or EPT will reduce morbidity or mortality from these conditions. The benefit-risk ratio may be more favorable for younger women.

The report also includes information on areas where insufficient or conflicting evidence precludes consensus, and needs for future research.

editor’s note: Since the publication of this guideline, the Women’s Health Initiative announced termination of the estrogen-only arm of this study. The researchers found no cardiovascular benefit and a small but significant increase in the risk of stroke in postmenopausal women without a uterus assigned to estrogen only instead of placebo (eight additional strokes per 10,000 women). However, they found no increase in the risk of breast cancer in women taking estrogen only.—MARK H. EBELL, M.D., M.S.

Registration Deadlines for AAFP Scientific Assembly

The 2004 Scientific Assembly of the American Academy of Family Physicians (AAFP) will take place October 13 through 17 in Orlando, Fla. The Assembly will be held in conjunction with the 17th World Conference of Family Doctors (WONCA).

A course registration form and a brochure about continuing medical education (CME) events will be mailed to all AAFP members and posted on the AAFP Web site in May. In addition to registering for courses online, you also can fax or mail the form to the AAFP.

To qualify for the Early Bird Discount, preregistration must be received (not postmarked) by July 14. The final preregistration deadline is September 1, after which onsite fees will apply to the registration charges.

More information about the Scientific Assembly is available online at:https://www.aafp.org/x24594.xml.

Anti-Infective Agents for Intra-Abdominal Infections

The Infectious Diseases Society of America, the Surgical Infection Society, the American Society for Microbiology, and the Society of Infectious Disease Pharmacists have released guidelines for the selection of antimicrobial therapy for adults with complicated intra-abdominal infections. The recommendations were published in the Oct. 15, 2003, issue of Clinical Infectious Diseases and are available online at:http://www.journals.uchicago.edu/CID/journal/issues/v37n8/31800/31800.html.

The likely infectious agent(s), and therefore the drugs used to treat the infection, are determined by whether the infection is community acquired or health care associated. Health care-associated intra-abdominal infections are acquired most commonly as complications of previous elective or emergent intra-abdominal operations and are caused by nosocomial isolates particular to the site of the operation and the specific hospital and unit. For community-acquired infections, the location of the gastrointestinal perforation defines the infecting flora. Established infection beyond the proximal small bowel is caused by facultative and aerobic gram-negative organisms; infections beyond the proximal ileum also can be caused by a variety of anaerobic microorganisms.

Given the activity of common regimens against the anaerobic organisms identified in community-acquired infections, microbiologic work-up for specimens from such infections should be limited to identification and susceptibility testing of facultative and gram-negative bacilli. Susceptibility profiles for Bacteroides fragilis group isolates show substantial resistance to clindamycin, cefotetan, and quinolones, and these agents should not be used alone empirically in contexts in which B. fragilis is likely to be encountered.

Infections may be managed with a variety of single- and multiple-agent regimens (see accompanying table). No regimen has been shown consistently to be superior. Although many regimens have been studied in prospective trials, many of the studies have had serious methodologic flaws. Therefore, recommendations are based on in vitro activities.

For patients with community-acquired infections of mild to moderate severity, agents that have a narrower spectrum of activity and that are not commonly used for nosocomial infections are preferable to agents with broader coverage against gram-negative organisms or a greater risk of toxicity. Patients with more severe infections or those thought to be immunosuppressed may benefit from regimens with a broader spectrum of activity against facultative and aerobic gram-negative organisms.

Postoperative infections are likely to be caused by more resistant flora, such as Pseudomonas aeruginosa, Enterobacter species, Proteus species, methicillin-resistant Staphylococcus aureus, enterococci, and Candida species. For these infections, complex, multidrug regimens are recommended because adequate empiric therapy appears to decrease mortality. Local nosocomial resistance patterns should dictate treatment, and treatment should be altered on the basis of results of a thorough microbiologic work-up of infected fluid.

Cancer Statistics, 2004

The American Cancer Society has released its annual report on cancer incidence, mortality, and survival rates. “Cancer Statistics, 2004” was published in the January/February 2004 issue of CA: A Cancer Journal for Clinicians and is available online at:http://caonline.amcancersoc.org/cgi/content/full/54/1/8.

Approximately 1.37 million new cancer cases and 564,000 cancer-related deaths are expected in the United States in 2004. Incidence rates in men stabilized from 1995 through 2000, but rates in women continue to increase by 0.4 percent per year. Mortality rates in men have decreased by 1.5 percent per year since 1992, but rates in women have stabilized.

Cancer mortality rates continue to decrease from the three major cancer sites in men (i.e., lung and bronchus, colon and rectum, and prostate), and from breast and colorectal cancers in women.

Compared with white men and women, black men and women have 40 percent and 20 percent higher mortality rates, respectively, from all cancers combined. Cancer incidence and mortality rates are lower in other racial and ethnic groups than in whites and blacks for all sites combined. However, minority populations are more likely to be diagnosed with advanced-stage disease.

IDSA Guideline for Candida Infections

The Infectious Diseases Society of America (IDSA) has released a clinical guideline for the treatment of patients with candidiasis. The guideline was published in the January 15, 2004, issue of Clinical Infectious Diseases and is available online at:http://www.journals.uchicago.edu/CID/journal/issues/v38n2/32301/32301.html.

Although treatment of candidiasis now can be guided by in vitro susceptibility testing, it is not considered a routine procedure in many laboratories, is not always promptly available, and is not universally considered as the standard of care. However, knowledge of the infecting species is highly predictive of likely susceptibility and can be used to guide therapy.

The guideline reviews the information supporting current testing procedures and interpretive breakpoints and puts these data into clinical context. Susceptibility testing is most helpful in dealing with deep infection by species other than Candida albicans. In this setting, especially if the patient has been treated previously with an azole antifungal agent, the possibility of microbiologic resistance must be considered.

In addition to acute hematogenous candidiasis, the guideline reviews strategies for treatment of 15 other forms of invasive candidiasis. Extensive data from randomized trials are available only for therapy of acute hematogenous candidiasis in the non-neutropenic adult. Choice of therapy for other forms of candidiasis is based on case series and anecdotal reports.

In general, amphotericin B-based preparations, azole antifungal agents, and echinocandin antifungal agents have a role in treatment. Choice of therapy is guided by weighing the greater activity of amphotericin B–based preparations and the echinocandin antifungal agents for some nonalbicans species (e.g., Candida krusei) against the availability of oral and parenteral formulations of azole antifungal agents. Flucytosine has activity against many isolates of Candida but is not frequently used.

Therapy for mucosal infections is dominated by the azole antifungal agents. These drugs may be used topically or systemically and are safe and efficacious. A small proportion of patients with mucosal disease will have repeated relapses. In some situations, the explanation for such a relapse is obvious (e.g., recurrent oropharyngeal candidiasis in a patient with advanced and uncontrolled human immunodeficiency virus infection), but in other cases, the cause is not as clear (e.g., relapsing vaginitis in a healthy woman). Strategies for these situations are discussed in the IDSA guideline.

Prophylactic strategies are useful if the risk of a target disease is sharply elevated in a readily identified patient group. Selected patient groups undergoing therapy that produces prolonged neutropenia (e.g., some bone marrow transplant recipients) or who receive a solid organ transplant (e.g., some liver transplant recipients) have sufficient risk of invasive candidiasis to warrant prophylaxis.