Pharmacy Blog: Health & Medical News

Gabapentin Cools Hot Flashes As Well As Estrogen

2006-07-04T05:08:00.000-07:00

University of Rochester researchers, who have been investigating new therapies for hot flashes for several years, report in the July Obstetrics and Gynecology journal that the seizure drug gabapentin is as effective as estrogen, which used to be the gold standard treatment for menopause symptoms.

Estrogen is no longer the preferred therapy because recent, large studies have shown that the hormone increases the risk of heart disease, stroke, breast cancer and Alzheimer's disease for some women. Given that news, millions of women have abandoned hormone replacement therapy (HRT) and are seeking other ways to ease symptoms. So-called natural remedies such as soy, herbal products or acupuncture have not proven safe or effective at this point.

The latest Rochester study is the first to compare gabapentin and estrogen head-to-head against a placebo. Although it showed a substantial placebo effect similar to other menopause studies - women taking the sugar pill reported a 54-percent reduction in hot flashes - the women taking gabapentin and estrogen reported even better results, with a 71 percent to 72 percent decline in symptoms.

"Gabapentin does appear to be as effective as estrogen," said lead author Sireesha Y. Reddy, M.D., assistant professor of Obstetrics and Gynecology at the University of Rochester Medical Center. "Until now its efficacy relative to estrogen was unknown."

Approximately 75 percent of postmenopausal women between the ages of 35 and 60 experience hot flashes. Gabapentin (sold under the trade name Neurontin) was approved by the FDA in 1994 to treat epileptic seizures but has been used off-label for years to treat headaches, shingles pain and other ailments. Scientists hypothesize that gabapentin may reduce hot flashes by regulating the flow of calcium in and out of cells, which is one mechanism for controlling body temperature.

An expert panel on menopause convened by the National Institutes of Health last year cautioned against the tendency to use treatments with scant safety data, and concluded that nothing to date was as effective as estrogen therapy although more research was needed.

In the latest study, Reddy and colleagues enrolled 60 women in a randomized, double-blind, placebo-controlled trial for 12 weeks. Initially the researchers received more than 1,500 calls from women who wanted to participate, but after screening the callers to meet the study's protocol, the number was whittled to 60, with 53 women complying with every step.

They were randomly divided into three groups: 20 women received gabapentin at 2,400 mg per day and a daily placebo or fake estrogen pill; 20 received estrogen in the form of Premarin at 0.625 mg per day and a fake gabapentin pill; 20 received sugar pills resembling gabapentin and estrogen. The women recorded the frequency and severity of their hot flashes in diaries.

Results were tabulated using two statistical methods to compare the women's hot flash reports throughout the 12-week period with their baseline symptoms. Doctors did find that women who took gabapentin complained more often of headaches, dizziness or disorientation. Researchers believe that slowly ramping up the medication and taking it with meals can alleviate the side effects.

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The NIH funded the study. Pfizer Inc. supplied gabapentin but had no role in the research. A co-author on the paper, Thomas Guttuso Jr., M.D., has a patent for the use of gabapentin in the treatment of hot flashes. Guttuso is a former neurologist at the University of Rochester who is now on the faculty at the University of Buffalo.

Contact: Leslie Orr
University of Rochester Medical Center

Effects Of Calcium On Weight Maintenance Among Middle-Aged Adults

2006-07-03T07:05:00.000-07:00

Increased total calcium intake in the form of supplements can help middle-aged adults maintain their weight over a number of years, with particular benefits to women, according to researchers at the Fred Hutchinson Cancer Research Center in Seattle.

The study looked at relationships between calcium and weight change over an eight-to-12-year period among more than 10,000 men and women in their mid-50s. Previous studies have found connections between calcium intake and people's body mass index, but those studies focused on calcium in food, not supplements, according to the researchers.

The study examined people's intakes of dietary calcium, supplemental calcium and total calcium (supplements plus diet) to discover which forms of calcium were associated with weight change. The researchers found "dietary calcium alone had no significant effect on 10-year weight change," but that women who took calcium supplements saw some improvement.

"Although more evidence from randomized clinical trials is needed before calcium supplements can be recommended specifically for weight loss, this study suggests that calcium supplements taken for other reasons (e.g., prevention of osteoporosis) may have a small beneficial influence on reducing weight gain, particularly among women approaching midlife."

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Contact: Julia Dombrowski
American Dietetic Association

Smoking And Obesity May Increase The Risk Of Erectile Dysfunction

2006-07-01T10:59:00.000-07:00

A prospective study by researchers from the Harvard School of Public Health (HSPH) has found that obesity and smoking are strongly associated with a greater risk of erectile dysfunction (ED). Meanwhile, regular physical activity appeared to have a significant impact on lowering the risk of ED. This is the first large-scale prospective study to examine the links between ED and smoking, obesity, alcohol and a sedentary lifestyle. The study will appear in the July 2006 issue of The Journal of Urology.

The researchers, led by Constance Bacon, a former post-doctoral fellow at HSPH, and Eric Rimm, associate professor of epidemiology and nutrition at HSPH, surveyed 22,086 healthy subjects between the ages of 40 and 75 from the Health Professionals Follow-up Study who reported good or very good erectile function and no major chronic disease before 1986. Among the participants, 17.7 percent (3,905) reported new onset of ED between 1986 and 2000. The researchers adjusted the results to take into account those with and without prostate cancer during the follow-up period, since prostate cancer treatments, such as radiation or surgery, may lead to ED.

The results showed that both smoking and obesity were associated with a higher risk of the development of ED among previously healthy men with good erectile function. The researchers also found that regular physical activity showed a strong inverse association with ED risk. "We found a 2.5-fold difference in risk of ED when we compared obese men who did little exercise with men who were not overweight and averaged 30 minutes of vigorous exercise a day. (Obesity was defined as a body mass index of more than 30 kilograms in weight divided by the square of height in meters.) For men younger than 55 there was a 4-fold difference in risk for the same comparison," said Rimm. Alcohol consumption did not increase the risk of ED. In general, men without prostate cancer showed stronger associations with these lifestyle factors than those with prostate cancer.

These results suggest that ED and coronary heart disease may share many of the same risk factors. Rimm said the results should encourage men to follow a more healthy lifestyle. "Many men may choose not to change to a healthier lifestyle, which includes exercise and a prudent diet, because they perceive heart disease as something that may only develop decades in the future. Hopefully, these results will help to motivate men to adopt a more active lifestyle to avoid a problem which may be more immediate," he said.

(The Health Professionals Follow-Up Study was launched in 1986 to examine diet and chronic disease among male health professionals in the U.S.)

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The study was supported by Pfizer, Inc., and by grants from the National Institutes of Health.

Contact: Todd Datz
Harvard School of Public Health

New Insights Into The Impact Of Pregnancy On Inflammatory Arthritis

2006-07-01T03:15:00.000-07:00

During pregnancy, women with inflammatory arthritis usually experience disease improvement or even remission, while a disease flare regularly occurs within 3 to 4 months after delivery. A study featured in the July 2006 issue of Arthritis & Rheumatism (http://www.interscience.wiley.com/journal/arthritis) sheds light on this widely reported yet little understood phenomenon.

Prenatal diagnostic tests have recently established that fetal cells and cell-free DNA routinely flow into the mother's bloodstream during normal pregnancy. On the strength of these findings, researchers in Seattle, Washington, supported in part by a grant from the Washington Women's Foundation and by grants from the National Institutes of Health, set out to investigate whether changes in serum fetal DNA levels correlate with changes in arthritis activity during and after pregnancy. They conducted a study on 25 pregnant women with inflammatory arthritis.

Ranging in age from 23 to 43, 17 of the women were classified as having adult-onset rheumatoid arthritis (RA) and 6 were classified as having juvenile idiopathic arthritis (JIA). Of the subjects, 24 had active disease in the 6 months prior to pregnancy, with one experiencing RA onset in her first trimester. 7 of the women were in their first pregnancy, 7 were in their second pregnancy, and 11 had been pregnant at least twice before. None of the patients took a disease-modifying antirheumatic drug during pregnancy, and patients taking prednisone took no more than 10 milligrams per day, with one exception. All pregnancies resulted in a single live birth.

Samples of peripheral venous blood were taken from all subjects, most 3 times or more during the course of pregnancy, as well as postpartum, within 3 months of delivery. Levels of cell-free fetal DNA were measured using real-time quantitative polymerase chain reaction targeting the fetus-specific genetic markers. Women were evaluated for changes in disease activity in each trimester and 3 to 4 months after giving birth.

During pregnancy, 21 of the 25 women - 79 percent of the RA patients and 100 percent of the JIA patients - experienced improvement or remission of inflammatory arthritis symptoms. Among these women, 62 percent showed signs of disease improvement in the first trimester. Once improvement occurred, it was sustained or progressively increased until delivery. Among these women, levels of serum fetal DNA also progressively rose throughout pregnancy. As fetal DNA quantities doubled, the likelihood of arthritis improvement increased 1.2 fold. By the third or fourth month after delivery, disease recurrence was observed in 90 percent of these patients, coinciding with a drop of serum fetal DNA to very low or undetectable levels.

The remaining 4 women, including the one who had RA onset during the first trimester, did not experience significant reduction of disease symptoms during or after pregnancy. For the women with active disease, serum levels of fetal DNA were dramatically lower - and even undetectable in 2 - throughout pregnancy, especially in the third trimester, compared with those women who experienced arthritis improvement.

This study, the first to focus on fetal DNA in women with RA during pregnancy, found a significant inverse correlation between arthritis activity and serum fetal DNA concentration over the course of pregnancy and postpartum. Yet, researchers acknowledge the study's limitations, including its small size, and inability to determine whether serum fetal DNA has any direct biologic effect on inflammatory arthritis or therapeutic value.

"Whether the dynamic changes in fetal DNA reflect the potential for immune modulation of maternal arthritis, are a result of disease activity changes, or are not causally related cannot be determined from these studies," notes researcher J. Lee Nelson, M.D. "If the former, further studies could generate new therapeutic strategies for RA."

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Contact: Amy Molnar
John Wiley & Sons, Inc.

Dietary Supplements Do Not Reverse The Chemistry Of Emotional Stress

2006-06-30T07:54:00.000-07:00

Eating extra amounts of certain fats linked to numerous health benefits does not reverse the underlying metabolic changes that occur in emotional stress, an international group of researchers report. Their study is scheduled for the July 7 issue of the ACS Journal of Proteome Research.

The fats, termed long-chain polyunsaturated fatty acids (LC-PUFAs), are used to make infant formulas more like breast milk. Research has suggested that LC-PUFA supplements may help control inflammatory bowel disease, a condition in which stress plays a role. There also are hints that LC-PUFAs may help to prevent or delay the effects of cancer, diabetes, clinical depression, Alzheimer's disease, multiple sclerosis and other chronic diseases.

Jeremy K. Nicholson, of Imperial College London, and colleagues used a powerful metabolic research tool in the study. The approach is called metabonomics, and can reveal the biochemical consequences of dietary changes and disease. The researchers studied metabolic changes in stressed laboratory rats fed standard diets and diets enriched in LC-PUFAs. Contrary to expectation and widely held beliefs, dietary enrichment with LC-PUFAs did not reverse any of the stress-induced biochemical changes.

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Contact: Michael Woods
m_woods@acs.org
American Chemical Society

Estrogen Plays Different Role During Stress In Black And White Teens

2006-06-27T23:44:00.000-07:00

Estrogen seems to play a different role during stress in black and white girls, a difference that may help explain higher cardiovascular disease rates in blacks, researchers have found.

Using a model that mimics common life stressors, researchers found estrogen levels drop during stress in healthy black girls but remain consistent in whites, said Dr. Gregory Harshfield, director of the Medical College of Georgia's Georgia Prevention Institute.

"Estrogen, which helps blood vessels dilate, is good for your blood vessels and if you lose that protection during periods of stress in the day it may contribute to the early development of heart disease we typically see in black women," says Dr. Harshfield.

Research being presented during the 21st Annual International Interdisciplinary Conference on Hypertension and Related Cardiovascular Risk Factors in Ethnic Populations in Atlanta June 23-26 looked at 48 mostly female teens with normal blood pressure.

Researchers found the greatest changes in blood pressure response to stress in black girls and blood samples taken before, during and one hour after playing a competitive video game showed their estrogen levels dropped during stress and went back up afterward.

"Conventional thinking tells us estrogen is not normally a major player in regulating blood pressure during stress," says Dr. Harshfield. "This tells us sex hormones do play a role in regulating blood pressure but, unfortunately, it's a bad one in black females."

Estrogen influences blood pressure by releasing nitric oxide, a vasodilator, and by blunting the response of the sympathetic nervous system - the fight or flight response - as well as angiotensin II, a vasodilator. Estrogen is believed to be one of the main reasons women have lower rates of heart disease than men until after menopause, says Martha Castles, research manager, who is presenting the research.

"We are now thinking that when black girls are under stress, they are losing all the protective effects of estrogen," Dr. Harshfield says. "In whites under stress, their estrogen levels are consistent so they are secreting vasodilators, they are blocking angiotensin and the sympathetic nervous system so the stress is not affecting them as much." In fact, black girls in the study also showed the greatest change in angiotensin levels in response to stress.

The prevalence of hypertension is increasing in females, he says, particularly in black females whose prevalence is greater than black males and overall death rate from hypertension is more than twice that of white females.

Dr. Harshfield notes that little is known about mechanisms underlying racial differences in blood pressure. His previous work has shown that, compared to their white peers, healthy black girls and boys also have reduced ability to secrete sodium following stress, which leaves their blood pressure elevated for longer periods and may help explain why blood pressures don't decrease as much during sleep. "Estrogen is probably another mechanism through which the blood pressure is staying elevated," he says.

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Contact: Toni Baker
Medical College of Georgia

Viagra Improves High Altitude Exercise Performance Up To 45% For Some

2006-06-25T04:13:00.000-07:00

Sildenafil (Viagra) significantly improved the cardiovascular and exercise performance measures of trained cyclists at high altitude, mostly because the drug helped some participants improve a lot -- up to 45% -- while others showed little change. Sildenafil provided no benefit at sea level.

Ten cyclists who took sildenafil at altitude collectively lowered the time it took to cover six kilometers by 15% compared to placebo trials at altitude. The cyclists also significantly improved stroke volume (the volume of blood moved out of one ventricle of the heart per beat) and cardiac output (stroke volume times heart rate) compared to the placebo trial. Sildenafil also minimized the decline of arterial oxygen saturation of the arteries when the cyclists were at simulated altitude of 12,700 feet.

But the researchers discovered that these improvements occurred largely because some people achieve major gains with sildenafil at altitude while others improve much less or not at all. The responders improved 39% in the time trial performance at altitude compared to their performance at altitude with a placebo. Some in the responder group improved as much as 45%, according to a study in the Journal of Applied Physiology published by The American Physiological Society. Non-responders improved an insignificant 1%.

The study, "Sildenafil improves cardiac output and exercise performance during acute hypoxia but not normoxia," by Andrew R. Hsu, Kimberly E. Barnholt, and Nicolas K. Grundmann, Veterans Affairs Palo Alto Health Care System; Joseph H. Lin and Stewart W. McCallum, Stanford University Medical Center; and Anne L. Friedlander, Veterans Affairs Palo Alto Health Care System and Stanford University appears in the June issue of the Journal of Applied Physiology.

Drug expands the blood vessels
Sildenafil citrate is best known as Viagra, a drug used to treat erectile dysfunction. The drug was originally developed to relieve high blood pressure. It causes blood vessels in certain tissues, such as the lungs, to relax. This improves blood flow from the heart and increases oxygen transport to working muscles. Because the high altitude atmosphere contains less oxygen, it is more difficult to get enough oxygen to support strenuous physical activity than it is at sea level.

Sildenafil works by inhibiting phosphodiestrase-5, an enzyme which degrades cyclic guanosine monophosphate (cGMP) a cell messenger that causes the blood vessels to relax, Friedlander explained. By inhibiting the enzyme, the drug allows greater vasodilation and greater blood flow. Although the drug works in different target sites, this study focused on the lungs.

The researchers hypothesized that the drug would allow the study's participants to improve their performance at altitude because it would reduce the constriction of vessels in the lungs that sometimes occurs at altitude. In turn, that would allow greater blood flow through the heart, better transfer of oxygen from the lungs to the blood and improved oxygen delivery to working muscles.

The participants, all trained cyclists, performed a total of 10 cycling trials, with and without sildenafil at sea level and at simulated altitude of 3,874 meters. Neither the participants nor the researchers knew whether the trial included a placebo or one of the two sildenafil doses, 50 mg or 100 mg.

The high altitude simulation was achieved by changing the mix of air. The cyclists began breathing the high altitude mix starting one hour before the exercise session and continuing through the session. The simulation did not include the lower air pressure that would occur at altitude, Friedlander said.

Researchers analyzed the changes in each individual's performance under various exercise conditions and also compared the group's performance under different drug conditions.

Responders versus non-responders
Four of the 10 participants responded to sildenafil while the remaining six did not, Friedlander said. The responders showed the greatest drops in stroke volume, cardiac output, and cycling performance between the sea level and high altitude trials without the drug.

"Without sildenafil, their performance went down more than others," Friedlander said. "With it, it brought them back up to the levels of the non-responders." The results suggest that the responders experienced a greater degree of constriction of the vessels in the lungs at altitude and therefore benefited more from the vessel relaxation effects of sildenafil.

"One of the messages of the paper is that not everybody benefits," Friedlander said. Sildenafil (Viagra) could be considered as a treatment for those who suffer most at altitude but, because of side effects that can include severe headaches and the apparent inability to help some people, it should not be taken as an exercise aid by everyone, she said.

The bigger picture

This study adds to the scientific knowledge of what physiological factors limit performance at altitude, including the role that cardiac output plays, Friedlander said. For instance, physiologists don't know why some people have trouble at altitude and may develop illnesses such as acute mountain sickness or high altitude pulmonary edema while others adapt quickly. Studies like this may help identify some of the underlying differences between people and lead to better treatments.

In future studies, Friedlander wants to identify:

* what steps individuals could take to acclimatize before they go to altitude
* who is likely to acclimatize quickly at altitude and who may need additional help
* how to minimize performance declines at altitude

Friedlander and her team are working on issues that could apply to those who have to rapidly acclimatize to high altitude. For instance, when soldiers deploy to Afghanistan, they must quickly undertake physically taxing work at 12,000-14,000 feet, conditions that can severely affect performance under potentially life-threatening conditions.

In a study Friedlander and colleagues conducted at 14,000 feet on Pike's Peak, Colorado, participants showed marked hormonal changes at altitude. These changes facilitate oxygen delivery. However, this benefit is suppressed when individuals don't eat enough and the body shifts focus to store more energy, Friedlander explained. That study appears in the June issue of the American Journal of Physiology-Endocrinology and Metabolism, also published by APS.

Next steps

One next step is to do a study with women, to see if they react the same way to sildenafil and altitude. The researchers also want to take a closer look at sildenafil responders to see if they can identify ahead of time who will benefit from treatment. In addition, a question still outstanding is whether non-responders would benefit from sildenafil at a higher elevation.

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Contact: Christine Guilfoy
American Physiological Society

Animal Studies Suggest Vegetables May Reduce Hardening Of Arteries

2006-06-22T09:10:00.000-07:00

New research suggests one reason vegetables may be so good for us - a study in mice found that a mixture of five common vegetables reduced hardening of the arteries by 38 percent compared to animals eating a non-vegetable diet. Conducted by Wake Forest University School of Medicine, the research is reported in the current issue of the Journal of Nutrition.

"While everyone knows that eating more vegetables is supposed to be good for you, no one had shown before that it can actually inhibit the development of atherosclerosis," said Michael Adams, D.V.M., lead researcher. "This suggests how a diet high in vegetables may help prevent heart attacks and strokes."

The study used specially bred mice that rapidly develop atherosclerosis, the formation on blood vessel walls of fatty plaques that eventually protrude into the vessel's opening and can reduce blood flow. The mice have elevated low-density lipoprotein ( LDL), or "bad" cholesterol, which is also a risk factor for atherosclerosis in humans.

Half of the mice in the study were fed a vegetable-free diet and half got 30 percent of their calories from a mixture of freeze-dried broccoli, green beans, corn, peas and carrots. These five vegetables are among the top-10 vegetables in the United States based on frequency of consumption.

After 16 weeks, the researchers measured two forms of cholesterol to estimate the extent of atherosclerosis. In mice that were fed the vegetable diet, researchers found that plaques in the vessel were 38 percent smaller than those in the mice fed vegetable-free diets. There were also modest improvements in body weight and cholesterol levels in the blood.

The estimates of atherosclerosis extent involved measuring free and ester cholesterol, two forms that accumulate in plaques as they develop. The rate of this accumulation has been found to be highly predictive of the actual amount of plaque present in the vessels.

Adams said it is not clear exactly how the high-vegetable diet influenced the development of plaques in the artery walls.

"Although the pathways involved remain uncertain, the results indicate that a diet rich in green and yellow vegetables inhibits the development of hardening of the arteries and may reduce the risk of heart disease," said Adams.

He said that a 37 percent reduction in a certain marker of inflammation in mice suggests that vegetable consumption may inhibit inflammatory activity.

"It is well known that atherosclerosis progression is intimately linked with inflammation in the arteries," Adams said. "Our results, combined with other studies, support the idea that increased vegetable consumption inhibits atherosclerosis progression through antioxidant and anti-inflammatory pathways."

Numerous studies in humans have shown that a high-vegetable diet is associated with a reduced risk of cardiovascular disease, as well as with reductions in blood pressure and increases in "good" cholesterol. This is believed to be the first study to address the effect of increased vegetable consumption on the development or progression of atherosclerosis.

Despite compelling evidence supporting the health benefits of increased vegetable consumption, intake remains low, Adams said. The mean consumption is 3.2 servings per days, with about 40 percent coming from starchy vegetables such as potatoes.

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Contact: Karen Richardson
or Shannon Koontz mailto:shkoontz@wfubmc.edu
Wake Forest University Baptist Medical Center

Coping Strategies For Relief From Summer Allergens Offered By UT Southwestern Allergist

2006-06-20T06:57:00.000-07:00

The good news for allergy sufferers is that springtime mountain cedars and tree pollens have generally subsided.

The bad news: It's summertime.

"For summer, it will be grass pollen along with high ozone levels combining for a one-two punch," said Dr. David Khan, associate professor of internal medicine at UT Southwestern Medical Center. "In July, cedar elm will appear."

While heat doesn't influence the amount of pollen in the air, it does aid in the formation of ground-level ozone, which, in turn, can exacerbate allergy symptoms.

To cope, Dr. Khan, who also directs the asthma clinic at Parkland Memorial Hospital, offers these tips:

* Limit outdoor exposure during peak times � from mid-morning to midday.
* Air-conditioning filters out some allergens. Keeping windows closed lessens the amount of allergens that travel into the home.
* If you're out for long periods during the day, take a shower before bedtime to wash off some of the allergens and prevent them from being transferred to pillows. "Your hair can be like a pollen magnet," warns Dr. Khan.
* Wear a mask while mowing the lawn or doing yard work.
* Take allergy medications before you go outside, so they have time to work into your system.

Choosing the right medications to help control symptoms is important, Dr. Khan said. Antihistamines are the most common medications used for allergies. They can help relieve itching, sneezing and runny noses, but don't generally help with stuffiness. Oral decongestants like pseudoephedrine generally work for stuffy noses.

Topical decongestants and nose sprays aren't a good long-term solution because you can become addicted to them, causing nasal passages to swell even more and possibly resulting in other nasal problems as well.

If symptoms aren't subdued or allergies are interfering with your lifestyle or work, it's probably a good time to find an allergy specialist and see if other treatments may help.

"It's reasonable to try some of the over-the-counter drugs first, and if you're not satisfied with those results, then you need to see a doctor," Dr. Khan said.

At UT Southwestern, patients can be evaluated by UT Southwestern allergists in clinics at the James W. Aston Ambulatory Care Center, Parkland Memorial Hospital and Children's Medical Center Dallas, where doctors treat airborne and environmental allergies or asthma, food and drug allergies, and conditions like hives and allergic reactions.

Prescription antihistamines can offer more potency and be less sedating than over-the-counter measures, Dr. Khan said.

Corticosteroid anti-inflammatory nasal sprays can be used regularly, often once a day, and are generally safe and effective. These are not the same as anabolic steroids that athletes sometimes abuse and for which some school systems now test.

Antihistamines, decongestants and corticosteroids, however, do no more than depress symptoms. "Although you'll be reducing the effect of the allergic reaction, you'll still be just as allergic at the end of the day," Dr. Khan said.

Shots are the most effective medical treatment, he said, actually making allergy sufferers less allergic.

There's also a novel clinical approach, called rush immunotherapy, which simply means taking more shots over a shorter period of time. Doctors think this may help expedite results.

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Contact: Russell Rian
UT Southwestern Medical Center

Menopausal Women Don't Get Enough Guidance On Treatment Options, Stanford Survey Shows

2006-06-18T05:25:00.000-07:00

Few women are consulting their doctors before opting to use herbal therapies and soy products to treat their menopausal symptoms, researchers at the Stanford University School of Medicine have found.

The trend is of particular note because growing numbers of women are turning to alternative therapies to relieve such symptoms as hot flashes, headaches, mood swings and sleep disruptions because of concerns about health risks associated with hormone therapy, which is still considered the most effective way of treating such difficulties. The researchers recommend that physicians learn more about these products so that they can help their patients choose safe, effective methods of treating their symptoms.

"We're not promoting the use of these alternative therapies," said lead author Jun Ma, MD, PhD, research associate at the Stanford Prevention Research Center. "We're just saying that the demand for these therapies is growing and that physicians should be prepared to talk to their patients about it."

The study appears in the May/June issue of The Journal of the North American Menopause Society. The study was funded by GlaxoSmithKline Consumer Healthcare, which had no role in the study design, data collection or preparation of the manuscript for publication. The pharmaceutical company manufactures the herbal product RemiFemin Menopause.

The study was based on a 2004 online survey of a random sample of 781 U.S. women between the ages of 40 and 60. Because the sample size was small, Ma cautioned that the findings may not accurately represent all women, but said the data provide useful insights into women's attitudes toward menopause treatments and how much physician guidance they have received in deciding which therapies to use.

Among the women surveyed, nine out of 10 reported having experienced at least one menopausal symptom at some point. When it came to treating their symptoms, 37 percent reported using hormone therapy while slightly less than that - 31 percent - used herbal products. Soy supplements were used by 13 percent.

What interested Ma and her colleagues was that three-quarters of the women who had formerly taken hormone therapy said they stopped primarily because of concern about potential risks. "A majority of the women who had discontinued their hormone therapy were not on any therapy - not because of lack of need or desire to continue, but because they didn't know which therapy would best suit their clinical needs," Ma said.

The concerns about hormone therapy stem largely from the federally funded Women's Health Initiative, a long-term study that turned the conventional wisdom about hormone therapy on its head. For many years, observational studies indicated that in addition to relieving menopausal symptoms, hormone therapy helped protect women against heart disease. However, the WHI found that neither estrogen nor the combination of estrogen and progestin helped prevent heart disease. Instead, although both forms of hormone therapy offered some benefits in easing menopausal symptoms, they both posed substantial health risks.

Despite these risks, hormone therapy is still considered the most effective approach for treating menopausal symptoms. Women are advised to use the lowest possible dose of hormones and to limit the duration of the treatment in order to minimize the risks.

But the new study shows that many women are instead turning to herbal and soy products to ease their menopausal symptoms. The most commonly used herbal products reported by survey participants were ginkgo biloba, ginseng, St. John's wort, black cohosh or a combination product.

"The reduced use of menopausal hormone therapy, while an appropriate response to the WHI findings, has left both patients and their physicians in a difficult position," said Randall S. Stafford, MD, PhD, associate professor of medicine and senior author of the study. "While other pharmaceuticals and alternative therapies are available, many physicians are not fully prepared to discuss these options, particularly given the limited data available about the effectiveness of these options."

Among the women who used herbal therapies, 55 percent chose the products because of concerns about hormone therapy while 45 percent said they wanted to use a natural remedy. But Ma said many women mistakenly equate the term "natural" with "safe," and falsely believe that herbal products won't interact with other medications. "That misperception really needs to be corrected," she said.

In fact, herbal products may have side effects. For instance, some studies have shown that St. John's wort interacts with selective serotonin-reuptake inhibitors, which are the most commonly prescribed class of antidepressants, and it is recommended that the two not be combined.

Additionally, Ma said there is little in the way of high-quality data on the efficacy of many of the alternative therapies, adding that most of the data are limited to short-term use of the products.

The women in the study regarded physicians as their most-trusted source of information about alternative therapies, yet many said they didn't get enough guidance in choosing a remedy for their menopausal symptoms. Nearly 75 percent of the women said that they - not their doctors - initiated discussions about possible treatments for their symptoms. And when it came to alternative therapies, 20 percent of the women weren't confident in their doctors' ability to discuss the treatments knowledgeably.

"Hormone therapy is unique in that patient preference is important in deciding what therapy to use," Ma said. "A balanced dialogue is essential because it's a treatment decision that a physician should make with a patient, not for a patient."

Ma suggested that physicians know enough about alternative menopause therapies to put them in four categories: those that have data suggesting some effectiveness, those that have data demonstrating concerns about side effects, those with neutral data and those lacking any data.

"It's OK to tell patients that little is known about a product, despite any anecdotal stories they may have heard. Anecdotal stories should not be taken as a substitute for rigorous clinical evidence," Ma said.

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Contact: Susan Ipaktchian
Stanford University School of Medicine

Target Women's Depression To Reduce Disability From Chronic Conditions, Suggests Study

2006-06-17T03:48:00.000-07:00

Women with higher levels of depression when suffering with long-term pain report greater disability than men in the same situation, according to new research published in the latest edition of the European Journal of Pain.

This suggests that by targeting their depression, doctors could help reduce disability in female patients with chronic conditions such as arthritis and back pain.

The study, which involved 260 chronic pain patients from Royal National Hospital for Rheumatic Diseases (RNHRD), builds on growing evidence that "psychosocial" factors can have an effect on a person's health and behavior.

"It is now accepted that pain is more than just a sensory experience, and that factors like a person's gender, their emotional condition or their interactions with others, can contribute to their pain experiences," said Dr. Ed Keogh from the Pain Management Unit at the University of Bath and RNHRD.

"This research shows that pain-related emotions are associated with pain-related behaviour, such as the number of visits to the GP, the number of medications taken, the amount of sleep lost, and disability, but it also highlights a significant discrepancy between the behaviours of men and women.

"For women in particular, targeting depression may help reduce disability associated with chronic pain."

Women are already known to report higher levels of depression than men, and are generally found to report greater levels of pain, with greater frequency and greater intensity when compared to men.

Evidence is emerging that suggests men and women also respond differently to the drugs and other treatments, such as psychology-based interventions, used to treat pain.

"We found that within men with chronic pain, higher levels of depression were related to a greater of number of medications being used than women," said Dr. Keogh.

"Why this should be is not clear, but the social gender roles we adopt throughout our lives may have some important part to play.

"Alongside drugs, other therapies that focus on the behaviours and tendencies associated with depression, such as avoidance and withdrawal, may also be effective in these situations for some people."

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Contact: Andrew McLaughlin
University of Bath

New Study Suggests Antidepressants Save Lives

2006-06-15T08:27:00.000-07:00

A just published UCLA study suggests that the use of antidepressants to treat depression has saved thousands of lives, despite the concern about a possible link between suicide risk and the class of drugs called selective serotonin reuptake inhibitors (SSRI). The lead author of the study is Dr. Julio Licinio, the new chairman of the Department of Psychiatry and Behavioral Sciences at the University of Miami Leonard M. Miller School of Medicine. Licinio conducted the study at UCLA while he was the director of the Center for Pharmacogenomics and Clinical Pharmacology at the Semel Institute for Neuroscience and Human Behavior.
Published in the June 2006 edition of the peer-reviewed journal PLoS Medicine, the study analyzes federal data on overall suicide rates since the early 1960s and sales of the SSRI fluoxetine, or Prozac, in the United States since the antidepressant's introduction in 1988 through 2002.

The data show the U.S. suicide rate held fairly steady for 15 years prior to the introduction of fluoxetine, then dropped steadily over 14 years as sales of the antidepressant rose. The research team found the strongest effect among women.

Mathematical modeling of probable suicide rates from 1988 to 2002, based on pre-1988 data, suggests a cumulative decrease in expected suicide mortality of 33,600 people since the introduction of the antidepressant.

"Our findings certainly suggest that the introduction of SSRIs has contributed to reduction of suicide rates in the United States," Licinio said. "However, the findings do not preclude the possibility of increased risk of suicide among small populations of individuals."

The Food and Drug Administration introduced "black box warnings" on the most popular SSRIs in 2004 amid rising concerns in the United States and United Kingdom concerning the relationship between suicide and antidepressant use in children and adults.

A key unanswered question involves whether antidepressants increase suicide over and above the underlying disorder, such as major depression.

"Much of the psychiatric community fears that the absence of treatment may prove more harmful to depressed individuals than the effects of the drugs themselves," Licinio said. "Most people who commit suicide suffer from untreated depression. Our goal is to explore a possible SSRI suicide link while ensuring that effective treatment and drug development for depression is not halted without cause."

The study examined age-adjusted suicide rate data from the Centers for Disease Control and the U.S. Census Bureau from the early 1960s until 2002. Data show suicide rates fluctuated between 12.2 and 13.7 per 100,000 people for the entire U.S. population until 1988. Since then, suicide rates have gradually declined, with the lowest rate at 10.4 per 100,000 in 2000. The decline is significantly associated with increased numbers of fluoxetine prescriptions dispensed, from 2.47 million in 1988 to 33.32 million in 2002.

Major depressive disorder affects approximately 10 percent of American men and 20 percent of women over their lifetimes. Because the prevalence is so high and treatment lasts several months or years, antidepressant medications are the most common form of treatment. Fluoxetine is the most widely prescribed antidepressant medication in the world and the only antidepressant that is FDA-approved for treatment of depression in children.

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Contact: Dan Page
University of California - Los Angeles

First High-Flex Knee Replacement Implant Shaped Specifically To Fit Woman's Anatomy

2006-06-14T01:38:00.000-07:00

The first knee replacement shaped to fit a woman's anatomy has received clearance from the U.S. Food and Drug Administration, and will be distributed to orthopedic surgeons to use next week. Dr. Aaron G. Rosenberg and Dr. Richard A. Berger, orthopedic surgeons at Rush University Medical Center, were two of the 10 developer surgeons who sought to address shape-related differences of a woman's knee.

The Gender Solutions High-Flex Knee, made by Zimmer, Inc, is designed based on three distinct and scientifically documented shape differences between women's and men's knees. The implant addresses the shape-related differences typical of a woman's knee: a narrower shape; thinner shape, and the need for more natural motion for the knee when walking.

"Knee implants have been functioning very well for men and women, but we want to meet women's unique needs by making knee replacements that feel, fit and function even better," says Rosenberg. "The implant is the best of both worlds. It's based on the current implant we use, a highly successful implant with great mechanics and 10 years of clinical success. Only the shape of this new implant is different, to make it feel more natural."

The clearance allows Zimmer to begin distributing the implant to U.S. orthopedic surgeons and hospitals as part of Zimmer's NexGen Complete Knee System. The Gender Solutions Knee will be implanted using existing, clinically successful surgical techniques, including Zimmer's minimally invasive approaches. Rosenberg and other surgeons who helped with development will be using the implant in patients next week. The implant is expected to be globally available this fall.

The Need for a Woman's Knee Implant

"Mounting research indicates that a woman's knee is not simply a smaller version of a man's knee. The differences involve the bones, ligaments and tendons in the joints," says Rosenberg. "Women can wear men's clothing and shoes, but most prefer clothing and shoes made for them. It's the same with knees, and it makes perfect sense to design knee implants with women in mind, particularly considering that women are by far the majority of the knee replacement patient population."

Nearly two-thirds of the more than 400,000 annual knee replacement patients are women, according to the National Center for Health Statistics, and the numbers continue to increase each year. Research shows that while both women and men vastly under use knee replacement, women are three times less likely than men to undergo the procedure, although they suffer from more knee pain and resulting disability.

"Less invasive procedures are helping patients get back to enjoying their lives faster than ever before. Now that we have a knee shaped to fit women's anatomy, we expect far more women will want to consider knee replacement."

Knee replacements have long been available in many sizes, but merely using a different size for women doesn't resolve anatomical differences. Various studies show that women's knees significantly differ in shape from men's knees. Pioneering research conducted for Zimmer precisely maps out those differences and is the foundation for the design and development of the female implant.

The female implant can be placed using minimally invasive techniques which typically offer smaller scars, shorter hospitalization and quicker rehabilitation and recovery; and safely accommodates high flexion (up to 155 degrees), which is necessary for many activities, such as climbing stairs, sitting in a chair, gardening and golfing.

The knee joint is composed of three bones: the end of the femur (thighbone), the top of the tibia (shinbone) and the patella (kneecap), which are all held together by tendons and ligaments and cushioned by cartilage. Knees can become painful, due to arthritis, injury and infection, which cause deterioration of the cartilage. When the cartilage is gone, the bones of the knee grind against each other, wearing away and typically causing severe pain. Total knee replacement involves removing the portion of bone that is damaged and resurfacing the knee with metal and plastic implants.

Historically, implants used for knee replacement have been designed based upon an average between the size of women's and men's knees. Total knee replacement is a highly successful surgery, strongly supported by more than 20 years of follow-up data, according to the National Institutes of Health (NIH) consensus statement on total knee replacement released in February 2004. The NIH consensus panel concluded that total knee replacement provides substantial improvement in patients' pain, functional status, and overall health-related quality of life in about nine out of 10 patients.

Three Distinct Differences

The Gender Solutions implant addresses the following research-documented, shape-related differences of a woman's knee:

-- Narrower Shape, Proportioned to Female Anatomy: When determining the appropriate-sized implant, surgeons measure the end of the femur from front to back and from side to side. Women's knees typically are narrower from side to side, and are more trapezoid-shaped, whereas men's knees are more rectangle-shaped. Surgeons typically choose the implant size based on the front-to-back measurement, which is key in allowing the knee to move and flex properly. However, an implant that fits a woman's knee from front to back often will be too wide from side to side, leading to the implant overhanging the bone and potentially pressing on, or damaging, surrounding ligaments and tendons, possibly causing pain. The Gender Solutions knee is proportionally contoured to the entire bone to provide a more precise fit.

-- Thinner Shape: The bone in the front of a woman's knee is typically less prominent than in a man's knee. Therefore, when a traditional implant is used to replace the damaged bone, the joint may end up feeling and functioning better than before surgery but still feel "bulky," which may result in pain and decrease optimal function. This implant is thinner in shape in the front so the knee replacement more appropriately matches the natural female anatomy.

-- More Natural Tracking: The angle between the pelvis and the knee affects how the kneecap tracks over the end of the femur as the knee moves through a range of motion. Women tend to have a different angle than men due to their specific shape and contour. The Gender Solutions Knee Implant was designed to accommodate the different tracking angle and function more like a woman's natural knee.

http://www.rush.edu

Organon Starts Phase III Development Of Unique Combined Oral Contraceptive

2006-06-12T05:50:00.000-07:00

Organon, the human healthcare business unit of Akzo Nobel, announced today that it has started the phase III development program for NOMAC/E2, its novel combined oral contraceptive.

NOMAC/E2 is viewed as the first major innovation in hormone content since the introduction of "The Pill" in the nineteen sixties. NOMAC/E2 is the first natural estrogen containing combined oral contraceptive; it contains exactly the same estrogen - estradiol - that is produced in women's bodies. All currently available combined oral contraceptives contain synthetic ethinyl estradiol (EE). The new combined pill also contains NOMAC , a hormone new in contraception that resembles the progesterone a women's body produces at certain times in her menstrual cycle.

"NOMAC/E2 represents a novel approach for oral contraception and one that has been pursued by many in this field for a considerable time," said Herm Cukier, Executive Vice President, Global Marketing and Global Venture Teams. "NOMAC/E2, when approved, will complement our already innovative contraceptive portfolio. The development of NOMAC/E2 also reflects our continued commitment to using novel technologies in order to address important unmet needs for women seeking an efficacious, safe and convenient method of contraception, be it oral or otherwise. Bringing this new contraceptive into phase III adds value to Organon's strong late stage development pipeline."

The phase III program includes two large, randomized open-label multi-centre 13-cycle comparative trials that will enrol more than 4200 women and generate more than 30,000 cycles of exposure to NOMAC/E2. In total more than 200 centres in 24 countries including the USA are taking part.

Organon was granted development and marketing rights of NOMAC/E2 by Merck KgaA affiliate Laboratoire Theramex in 2005. Theramex successfully completed a phase II program suggesting that NOMAC/E2 will be the first E2-containing pill able to combine good contraceptive efficacy with an expected cyclic bleeding pattern and an acceptable safety profile.

NOMAC is the acronym given to the progestogen, nomegestrol acetate.

Avoid Air Pollution While Exercising In The City

2006-06-11T03:53:00.000-07:00

As environmentalists have pointed out, it can be as dangerous to be outdoors behind a city bus -- walking or bicycling -- as it is to be in front of one. All the exhaust and smoke -- even when they have been reduced by clean air technology -- can damage a person's health. The dangers of urban air pollution are of special concern to those who exercise by running, bicycling, or skating. These individuals, while trying to help their bodies through exercise, should take care that they do not harm themselves through exposure to air pollution.

Dr. Joseph T. Cooke, Associate Professor of Clinical Medicine and Patient Safety Officer at NewYork-Presbyterian Hospital/Weill Cornell Medical Center, says that air pollution is definitely a problem for those who work out in the city. The main culprits are ozone, fine particulate matter, and carbon monoxide, he says. These pollutants irritate the lungs and respiratory system, and can exacerbate the problems of persons with underlying disease -- such as asthma, bronchitis, emphysema, or cardiopulmonary maladies.

If you have heart or lung disease, Dr. Cooke says, in summer, you should, if possible, exercise indoors, preferably in an air-conditioned room. If you must go outdoors, the early morning or evening is best. It will be cooler, the sun is not at its peak, and the ozone levels will be at their lowest.

Dr. Cooke says that epidemiologic studies have linked air pollutants to harmful effects on the heart and lungs, to emergency hospital admissions, and to deaths. The pollutants affect the lungs by causing inflammation or irritation of the airway lining. More mucus and phlegm is produced, he says, and small muscles surrounding the airway respond by squeezing down. The work of breathing increases and it becomes more difficult to get oxygen into the body.

In addition to fine particulates -- which are emitted by the diesel engines of trucks and buses -- the two most significant environmental culprits are carbon monoxide and ozone, Dr. Cooke says. Carbon monoxide arises from cigarette smoke and automobile exhaust. It has a tremendous ability to force oxygen out of our circulatory system -- it combines with hemoglobin 200 times faster than oxygen. Overexposure may lead to headache, dizziness, confusion, and dangerous increases in body temperature.

Ozone, which is a large component of the smog found in cities like Los Angeles and New York, results from the interaction of sunlight and chemicals found in car exhaust. Ozone adversely affects a person's breathing pattern and causes the airways in the lungs to become smaller and more resistant to oxygen exchange. Because of ozone, a person working out has difficulty taking deep breaths, and has to breathe faster. As a result, the exercise becomes more stressful and difficult.

Dr. Cooke offers these simple tips

-Do not run on or near roads where there is heavy truck or bus traffic.

-Work out in the early morning or later in the evening.

-Exercise indoors if possible.

-If you experience any difficulty breathing, stop your exercise immediately and see your doctor.

By taking a few simple precautions, Dr. Cooke says, you can make your exercise a wholly good thing, and keep air pollution out of your body.

NewYork-Presbyterian Hospital
425 East 61st St., Fl. 7
New York, NY 10021
United States

New Study Re-evaluates Cardiovascular Risks Of Non-steroidal Anti-inflammatory Drugs (NSAIDS)

2006-06-07T05:59:00.000-07:00

High doses of some traditional non-steroidal anti-inflammatory drugs (NSAIDS) are associated with similar cardiovascular risks as the new generation of anti-inflammatory drugs known as COX 2 inhibitors (like Vioxx ®), finds a study in this week's BMJ.

Researchers from the UK and Italy performed a combined analysis (known as a "meta-analysis") of all the available randomised trials that compared a COX 2 inhibitor with placebo, or a COX 2 inhibitor with a traditional NSAID, and had recorded serious cardiovascular events. By including data from 138 trials among 140,000 patients, this meta-analysis provides a much more reliable estimate of the cardiovascular risks of these drugs, since individual trials were too small to study this question.

The study showed, as expected, that, COX 2 inhibitors were associated with an increased risk of vascular events, mainly heart attack. Unfortunately, there were insufficient data to reliably assess whether these risks were dose dependent, or whether the risks might differ among aspirin and non-aspirin users.

But the study also showed that high doses of two of the NSAIDs studied, diclofenac and ibuprofen, were associated with a similar increase in the risk of vascular events to COX 2 inhibitors, although the risks of high doses of another NSAID, naproxen, were smaller.

However, the average increased risk of vascular events was modest among the people studied in the trials: For every 1,000 people taking an NSAID or COX 2 inhibitor, around three extra people per year would have a vascular event, most likely a heart attack.

The authors conclude that very large randomised trials are needed to identify which anti-inflammatory drug regimens minimise serious cardiovascular and gastrointestinal problems.

An accompanying editorial discusses other options for treating chronic pain and suggests that doctors work with their patients to choose the best solutions for them.

Do cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials; BMJ Volume 332, pp 1302-5

Emma Dickinson
edickinson@bmj.com
BMJ-British Medical Journal

Can A High-Fiber Diet Prevent Obesity?

2006-06-05T05:58:00.000-07:00

While diets low in carbohydrates and high in protein continue to attract the public's attention, researchers at the University of Texas - Austin report that "normal-weight" adults tend to eat more fiber and fruit than people who are overweight or obese.

The researchers looked at dietary intakes of more than 100 people of generally the same age and height, half of whom were considered normal weight based on their body mass index and other measurements, and half of whom were overweight or obese.

The researchers found the diets of the two groups were similar in many ways, including intakes of sugar, bread, dairy products and vegetables. The main difference between the groups was the amount of fiber consumed by the normal-weight adults - 33 percent more dietary fiber and 43 percent more complex carbohydrates each day (per 1,000 calories).

"Obviously, no magic formula exists for weight loss," the researchers write, "but our results indicated that a diet containing more than average amounts of fiber, complex carbohydrate and fruit was associated with normal body fat stores and standard weight for height."

Additional research articles in the June Journal of the American Dietetic Association include:

-- "The Effects of Dieting on Food and Nutrient Intake of Lactating Women"

-- "Relationship of Ghrelin and Leptin Hormones with Body Mass Index and Waist Circumference in a Random Sample of Adults"

-- "Psychosocial Correlates of Fruit, Vegetable and Dietary Fat Intake among Adolescent Boys and Girls."

The Journal of the American Dietetic Association is the official research publication of the American Dietetic Association and is the premier peer-reviewed journal in the field of nutrition and dietetics.

With approximately 65,000 members, the American Dietetic Association is the nation's largest organization of food and nutrition professionals. ADA serves the public by promoting optimal nutrition, health and well-being. To locate a registered dietitian in your area, visit the American Dietetic Association at http://www.eatright.org.

Calorie Restriction Appears Better Than Exercise At Slowing Primary Aging

2006-06-01T09:55:00.000-07:00

Investigators at Washington University School of Medicine in St. Louis have found that eating a low-calorie yet nutritionally balanced diet lowers concentrations of a thyroid hormone called triiodothyronine (T3), which controls the body's energy balance and cellular metabolism.

The researchers also found that calorie restriction (CR) decreases the circulating concentration of a powerful inflammatory molecule called tumor necrosis factor alpha (TNF). They say the combination of lower T3 levels and reduced inflammation may slow the aging process by reducing the body's metabolic rate as well as oxidative damage to cells and tissues.

Previous research on mice and rats has shown that both calorie restriction and endurance exercise protect them against many chronic diseases including obesity, diabetes, cardiovascular disease and some types of cancer. However, the research has shown that only CR increases the animals' maximum lifespan by up to 50 percent. These animal studies suggest that leanness is a key factor in the prevention of age-associated disease, but reducing caloric intake is needed to slow down aging.

For the new study, researchers examined 28 members of the Calorie Restriction Society who had been eating a CR diet for an average of six years. Although the CR group consumed fewer calories -- averaging only about 1,800 per day -- they consumed at least 100 percent of the recommended daily amounts of protein and micronutrients. A second group of 28 study subjects was sedentary, and they ate a standard Western diet. A third group in the study ate a standard Western diet -- approximately 2,700 calories per day -- but also did endurance training. The researchers found reduced T3 levels -- similar to those seen in animals whose rate of aging is reduced by CR -- only in the people on CR diets.

But their serum concentrations of two other hormones -- thyroxin (T4) and thyroid stimulating hormone (TSH) -- were normal, indicating that those on CR were not suffering from the thyroid disease of clinical hypothyroidism. The findings are published online in the Journal of Clinical Endocrinology and Metabolism.

Interestingly, body fat levels did not affect serum T3 concentrations. The people in the CR group and the endurance athletes had similar amounts and composition of body fat. But although the CR group had lower T3 levels, the exercise group had T3 levels closer to those seen in the sedentary people who ate a standard Western diet.

"The difference in T3 levels between the CR group and the exercise group is exciting because it suggests that CR has some specific anti-aging effects that are due to lower energy intake, rather than to leanness," says first author Luigi Fontana, M.D., Ph.D., assistant professor of medicine at Washington University in St. Louis and an investigator at the Istituto Superiore di Sanita, Rome, Italy. "These findings suggest that although exercise helps prevent problems that can cut life short -- such as obesity, diabetes and cardiovascular disease -- only CR appears also to have an impact on primary aging."

Primary aging determines maximal length of life. Secondary aging, on the other hand, refers to diseases that can keep a person or an animal from reaching that expected lifespan. Eliminating factors related to secondary aging allows more people to reach their projected length of life. By slowing primary aging, CR may increase maximal lifespan.

In a related study in 1997, co-investigator John O. Holloszy, M.D., professor of medicine at Washington University School of Medicine, reported in the Journal of Applied Physiology that in rats, CR extended life longer than exercise.

"Sedentary rats who ate a standard diet had the shortest average life-spans," Holloszy says. "Those who exercised by running on a wheel lived longer, but animals on calorie restriction lived even longer."

Earlier this year, Fontana's group reported that CR seemed to prevent or delay primary aging in the heart. Ultrasound examinations showed that the hearts of people on calorie restriction were more elastic than those of age- and gender-matched control subjects. Their hearts were able to relax between beats in a way similar to the hearts of younger people.

This latest study targeted another marker of primary aging. The thyroid gland produces critical hormones that play an indispensable role in cell growth and development as well as in lipid and carbohydrate metabolism. T4 is the main product secreted by the cells of the thyroid gland, but most actions of thyroid hormone are initiated by T3. Fontana says T3 controls body temperature, cellular metabolism and to some extent, it also appears to be involved with production of free radicals, unstable molecules that can damage cells. All are important aspects of aging and longevity. In fact, a 2002 study in Science magazine from researchers at the National Institute on Aging observed that men with lower body temperatures tended to live longer those with higher body temperatures.

Fontana says lower levels of T3, cholesterol and the inflammatory molecules TNF and C-reactive protein, combined with evidence of "younger" hearts in people on calorie restriction, suggest that humans on CR have the same adaptive responses as did animals whose rates of aging were slowed by CR.

Holloszy and Fontana are getting ready to launch a 2-year study to look at the effects of calorie restriction. Later this year, they will begin recruiting volunteers between the ages of 25 and 45 who are willing to go on a CR diet for 24 months.

Called the Comprehensive Assessment of the Long Term effects of Reducing Intake of Energy (CALERIE) study, the goal is to get some clues about whether putting a normal weight person on calorie restriction will lower their levels of inflammation and their serum concentrations of T3, improve their heart function and change other markers of aging, as Fontana and Holloszy have observed in members of the Calorie Restriction Society.

"We want to learn whether calorie restriction can reverse some of these markers of aging in healthy people," Holloszy says. "It's going to be many years before we know whether calorie restriction really lengthens life, but if we can demonstrate that it changes these markers of aging, such as oxidative damage and inflammation, we'll have a pretty good idea that it's influencing aging in the same way that CR slows aging in experimental animals."

Contact: Jim Dryden
jdryden@wustl.edu
Washington University School of Medicine

FDA Approves Duramed's SEASONIQUE(TM) Extended-Cycle Oral Contraceptive

2006-05-27T04:48:00.000-07:00

Barr Pharmaceuticals, Inc. (NYSE: BRL) today announced that the U.S. Food and Drug Administration (FDA) has approved its Duramed Pharmaceuticals, Inc.'s New Drug Application (NDA) for SEASONIQUE(TM) (levonorgestrel/ethinyl estradiol tablets 0.15 mg/0.03 mg and ethinyl estradiol tablets 0.01 mg) extended-cycle oral contraceptive for the prevention of pregnancy. SEASONIQUE represents the next generation of extended-cycle oral contraceptives in a category the Company created with the launch of the SEASONALE(R) extended-cycle oral contraceptive in 2003.

SEASONIQUE will be shipped to trade customers and will be available by prescription to women in July 2006. The Company intends to immediately initiate multiple marketing programs aimed at healthcare providers and patients. The Company will initiate full scale detailing for SEASONIQUE to healthcare providers in August using its Duramed Sales Forces. Information about SEASONIQUE will be available at http://www.SEASONIQUE.com.

"SEASONIQUE joins SEASONALE in offering American women a new option in extended-cycle oral contraception," said Bruce L. Downey, Chairman and CEO of Barr Pharmaceuticals, Inc. "The science involving extended-cycle oral contraceptives continues to evolve and SEASONIQUE represents an exciting and unique development in this category. SEASONIQUE provides continuous hormonal support in the form of a low-dose of estrogen in place of the seven placebo pills. There is no other product like SEASONIQUE on the market today."

Downey continued, "We believe that our SEASONIQUE product line, including our Lo SEASONIQUE(TM) product that is currently in Phase III clinical studies, as well as other extended-cycle oral contraceptive products also in development, expands our commitment and leadership to a franchise that provides women with the option of four periods per year and low dose estrogen instead of a hormonal free interval."

The Company's application for SEASONIQUE had received an Approvable Letter in August 2005. In March 2006, the FDA notified the Company that it had determined that additional clinical studies would not be required to support the approval of SEASONIQUE. Following this notification, the Company submitted product labeling that has now gained approval.

SEASONIQUE

Under the SEASONIQUE extended-cycle regimen, women take active tablets of 0.15 mg of levonorgestrel/0.03 mg of ethinyl estradiol for 84 consecutive days, followed by seven days of 0.01 mg of ethinyl estradiol. The regimen is designed to reduce the number of withdrawal bleeding periods from monthly to four per year. The clinical data supporting the SEASONIQUE NDA resulted from one large pivotal randomized, open-label, multi-center trial and one supportive randomized, open-label, multi-center trial, both of which ended in April 2004. The trials involved approximately 2,500 female patients between the ages of 18-40 at 43 sites in the United States. Patients were enrolled in the pivotal trial for the duration of 12 months (four (4) 91-day cycles).

Important Information About Oral Contraceptives

It is estimated that more than 16 million women currently take oral contraceptives in the United States. Oral contraceptives are not for every woman. Serious as well as minor side effects have been reported with the use of hormonal contraceptives. Serious risks include blood clots, stroke, and heart attack. Cigarette smoking increases the risk of serious cardiovascular side effects, especially in women over 35 years. Oral contraceptives do not protect against HIV infection (AIDS) and other sexually transmitted diseases.

Barr Pharmaceuticals, Inc.

New Book Looks At Menstrual Disorders In Primary Care

2006-05-25T07:58:00.000-07:00

Many menstrual irregularities can be traced to medical problems that, if left unresolved, can profoundly affect women's health. Moreover, many menstrual disorders can and should be managed by primary care physicians. To help internists and other primary care providers treat the medical causes and implications of menstrual disorders, ACP this spring released the latest title in its acclaimed Women's Health book series, "Menstrual Disorders."

The book provides a detailed discussion of the range of menstrual disorders that patients may experience from menarche through menopause and the relationship between menstrual disorders and other medical illnesses.

"It is the first book on menstrual disorders that my co-editors and I are aware of that blends the fields of gynecology, adolescent medicine, internal medicine and other medical subspecialties into one comprehensive, integrated volume," said Deborah B. Ehrenthal, MD, FACP, assistant residency program director for the obstetrics and gynecology program at Christiana Care Health System in Wilmington, Del.

Dr. Ehrenthal co-edited the book with Matthew K. Hoffman, MD, MPH, FACOG, of the Department of Obstetrics and Gynecology at Christiana Care Health System and Paula J. Adams Hilliard, MD, of the University of Cincinnati College of Medicine.

"Menstrual Disorders" covers menstrual, contraceptive and reproductive issues for women with chronic medical problems. These issues affect a growing number of patients being cared for by internists.

The book includes chapters on caring for women with polycystic ovary syndrome and on the complex menstrual and contraceptive management of women with disabilities. One chapter guides clinicians through the evaluation and management of bleeding disorders, including von Willebrand's Disease. The book also provides an overview of procedures used in managing abnormal uterine bleeding, with old and new treatment modalities including endometrial ablation and uterine artery embolization.

The ACP Women's Health Series provides in-depth coverage of diseases, disorders, and health and wellness issues unique to female patients. The series gives physicians the knowledge they need to optimize patient care, from the initial approach to the patient through diagnosis, treatment and long-term management. Other titles include, "Breast Health and Common Breast Problems: A Practical Approach," "Coronary Artery Disease in Women," and "Medical Care of the Pregnant Patient."

ACP (Doctors of Internal Medicine. Doctors for Adults.(R)) is the largest medical-specialty organization and second-largest physician group in the United States. Membership includes more than 119,000 internists, related subspecialists, medical students, residents and fellows. Internists specialize in the prevention, detection and treatment of illnesses in adults.

The American College of Physicians was founded in 1915 to promote the science and practice of medicine. In 1998 it merged with the American Society of Internal Medicine, which was established in 1956 to study economic aspects of medicine. ACP works to enhance the quality and effectiveness of health care by fostering excellence and professionalism in the practice of medicine. Its publishing program includes the journal Annals of Internal Medicine, electronic products, and books for the medical community and general reader. For more information, visit http://www.acponline.org

Lynda Teer
lteer@acponline.org
American College of Physicians

New Alternative To Hip Replacement Designed For Patients With Active Lifestyles

2006-05-22T04:02:00.000-07:00

There is a new option for patients suffering from hip pain who do not want to give up their active lifestyle. NewYork-Presbyterian/Columbia University Medical Center is one of the first hospitals in the U.S. to offer a new alternative for total hip replacement-hip resurfacing. The technique allows the orthopedic surgeon to shave and cap several centimeters of bone within the hip joint, helping to preserve bone and joint stability for young or active patients.

The Innovative Birmingham Hip Resurfacing™ System preserves more of the patient's natural bone structures and stability, covering the joint's surfaces with an all-metal implant that more closely resembles a tooth cap than a hip implant. This approach reduces post-operative risks of dislocation and inaccurate leg length, and because the all-metal implant is made from durable, smooth cobalt chrome, it has the potential to last longer than traditional hip implants.

"Hip resurfacing is ideal for many of my young, active patients who suffer from hip pain. As we've seen greater numbers of younger patients and older patients that are physically active, there's been an increased need for an alternative to total hip replacement that accommodates their age and lifestyle," says Dr. William B. Macaulay, director of the Center for Hip and Knee Replacement at NewYork-Presbyterian Hospital/Columbia, and associate professor of orthopaedic surgery and advisory dean at Columbia University College of Physicians and Surgeons.

The FDA-approved procedure is indicated for patients under that age of 60 who live non-sedentary lifestyles and suffer from hip pain due to a variety of diseases which affect the hip joint.

Total hip replacement involves the removal of the entire femoral head and neck. The hip resurfacing technique, however, leaves the head and neck untouched. It is this neck length and angle that determines the natural length of a patient's leg after surgery, and since it is not removed and replaced with an artificial device during the resurfacing procedure, there is a greater likelihood of maintaining accurate leg length.

While the implant closely matches the size of a patient's natural femoral head (hip ball), it is substantially larger than the femoral head of a traditional total hip replacement implant. This increased size translates to greater stability in the new joint, and it decreases the chance of dislocation of the implant after surgery. Dislocation is a leading cause of implant failure after total hip replacement.

The Birmingham Hip implant is an all-metal ball and socket joint. Traditional hip replacements use a metal ball and a plastic socket. This plastic socket wears down over time, and may need to be replaced surgically. In fact, it is a leading cause of follow-up surgeries.

The Innovative Birmingham Hip Resurfacing™ System is manufactured by Smith & Nephew Inc. of Memphis.

NewYork-Presbyterian Hospital/Columbia University Medical Center

NewYork-Presbyterian Hospital/Columbia University Medical Center, located in New York City, is one of the leading academic medical centers in the world, comprising the teaching hospital NewYork-Presbyterian and its academic partner, Columbia University College of Physicians and Surgeons. NewYork-Presbyterian/Columbia provides state-of-the-art inpatient, ambulatory and preventive care in all areas of medicine, and is committed to excellence in patient care, research, education and community service. NewYork-Presbyterian, which is among U.S. News & World Report's top 10 hospitals nationally, also comprises NewYork-Presbyterian Hospital/Weill Cornell Medical Center and its academic affiliate, Weill Medical College of Cornell University.

NewYork-Presbyterian Hospital/Columbia University Medical Center
627 West 165th Street
New York, NY 10032
http://www.nyp.org

Cutting Calories Slightly Can Reduce Aging Damage

2006-05-19T08:06:00.000-07:00

A lifelong habit of trimming just a few calories from the daily diet can do more than slim the waistline - a new study shows it may help lessen the effects of aging.

Scientists from the University of Florida's Institute on Aging have found that eating a little less food and exercising a little more over a lifespan can reduce or even reverse aging-related cell and organ damage in rats.

The discovery, described this month in the journal Antioxidants and Redox Signaling, builds on recent research in animals and humans that has shown a more drastic 20 percent to 40 percent cut in calories slows aging damage. The UF findings indicate even small reductions in calories could have big effects on health and shed light on the molecular process responsible for the phenomenon, which until now has been poorly understood.

"This finding suggests that even slight moderation in intake of calories and a moderate exercise program is beneficial to a key organ such as the liver, which shows significant signs of dysfunction in the aging process," said Christiaan Leeuwenburgh, Ph.D., an associate professor of aging and geriatric research at the UF College of Medicine and the paper's senior author.

UF scientists found that feeding rats just 8 percent fewer calories a day and moderately increasing the animals' activity extended their average lifespan and significantly overturned the negative effects of cellular aging on liver function and overall health.

An 8 percent reduction is the equivalent of a few hundred calories in an average human diet and moderate exercise is equivalent to taking a short walk.

To reveal the workings of the body's chemical climate when aging-related damage happens, UF researchers tracked levels of biomarkers - chemicals and molecules present in the liver - in groups of rats. The liver, a crucial organ for maintaining good health during aging, cleans the blood and helps regulate the body's immune system. The researchers also plan to assess the same biomarkers in a study of rats' hearts, muscle and brains.

The research team was surprised to find one of the biomarkers, RNA, which is important for coding DNA and for protein synthesis, is more quickly damaged by aging than the more frequently studied DNA. RNA damage, therefore, could be an excellent early signal to indicate the onset of aging, researchers say.

"Because it is more sensitive to oxidative stress, RNA can be useful as an early marker of oxidative damage and even aging," said Arnold Y. Seo, a doctoral student in UF's Institute on Aging.

Seo authored the report along with Tim Hofer, Ph.D., an Institute on Aging research associate.

"To avoid disease, we can increase our defense and look for aging biomarkers and then test interventions," Hofer said. "It is better to protect what is there to improve the quality of life than to have to resort to invasive procedures."

In the study, which followed the rats over their lifespan, one group of animals ate as much food as they wanted and did not exercise, another group of animals exercised lightly and were fed slightly less than they would have eaten if allowed to have their fill. Liver samples from these groups were compared with samples taken from young rats.

The old sedentary rats that ate until they were full had increased levels of harmful oxidizing and inflammatory molecules in the liver that were associated with cell damage caused by aging. Meanwhile, aging rats that exercised and consumed a calorie-restricted diet, had the reverse outcome - they showed a decrease in these molecules in the liver.

Leeuwenburgh said the study results support the theory that cell death and aging-related organ damage are caused by unstable molecules known as free radicals and by cellular oxidation and inflammation.

"In a calorie-restricted environment, you reduce the inflammatory response and prevent cell death," Leeuwenburgh said.

John O. Holloszy, a professor of medicine in the division of geriatrics and nutritional sciences at Washington University School of Medicine in St. Louis, said the study is of major importance because it shows a mild degree of caloric restriction - just enough to prevent weight gain with advancing age - can have beneficial effects against aging. From a scientific perspective, he added, it is important to learn that RNA is a very good marker of aging damage.

"I'd never really thought about RNA before," Holloszy said. "Research has always looked at DNA. Because RNA is the template for the information on the genes on the DNA, RNA damage is a major problem because it results in mutations in the transcription of proteins."

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Contact: Denise Trunk
University of Florida

Study Identifies Substances In Grapefruit Juice That Interact Dangerously With Some Drugs

2006-05-17T09:41:00.000-07:00

New research from the University of North Carolina at Chapel Hill has identified and established the substance in grapefruit juice that causes potentially dangerous interactions with certain medications.

For almost a decade, people have been told by their doctors and pharmacists to avoid grapefruit juice if they are being treated with certain medications, including some drugs that control blood pressure or lower cholesterol. Studies have shown that grapefruit juice can cause more of these drugs to enter the blood stream, resulting in undesirable and even dangerous side effects.

The drugs affected by grapefruit juice usually have some difficulty entering the body after they are consumed because an intestinal enzyme, CYP3A, partially destroys them as they are absorbed. Grapefruit juice, but not other commonly consumed fruit juices, inhibits this enzyme, allowing more of these drugs to enter the body.

It was originally assumed that the ingredients responsible for drug interactions were the flavonoids that give grapefruit juice its bitter taste.

The new study shows that a group of chemicals called furanocoumarins are the likely culprit.

"This is the best evidence to date that furanocoumarins are the active ingredients in grapefruit juice that cause the interaction with medications," said Dr. Paul Watkins, the Dr. Verne S. Caviness distinguished professor of medicine and director of UNC's General Clinical Research Center (GCRC). Watkins led the study team.

A report of the new findings appears in the May issue of the American Journal of Clinical Nutrition.

To determine whether furanocoumarins are responsible for grapefruit juice-drug interactions, Watkins worked with scientists at the Florida Department of Citrus to selectively remove only the furanocoumarins from the juice. He and his collaborators then studied the effect of the whole juice versus furanocoumarin-free juice on the ability to affect absorption of felodipine, an anti-hypertension drug known to interact with grapefruit juice "And we found that removing the furanocoumarins from grapefruit juice entirely got rid of this interaction," Watkins said.

In this randomized study, 18 healthy volunteers took 10 milligrams of felodipine with each of three juices: orange juice, regular grapefruit juice, and grapefruit juice devoid of furanocoumarins. Blood was collected over 24 hours to measure felodipine blood levels. One week elapsed between each felodipine-juice "treatment."

The study found that in contrast to whole grapefruit juice, the furanocoumarin-free grapefruit juice behaved like orange juice and did not cause an interaction with felodipine.

Watkins notes that there are several implications of this work.

"First, it should now be possible to market the furanocoumarin-free grapefruit juice to patients who would otherwise need to avoid grapefruit. In addition, it should be possible to screen new foods for the potential for drug interactions by determining whether they contain furanocoumarins.

"Finally, it may be possible to add furanocoumarins to formulations of certain drugs that tend to be poorly or erratically absorbed to improve their oral delivery."

Contact: Leslie H. Lang
University of North Carolina School of Medicine

Rapid Return To Menses Once Oral Contraception Stopped, Study Shows

2006-05-13T09:12:00.000-07:00

A study by a Columbia University Medical Center researcher shows that 99 percent of participants experienced either a return to menstruation or became pregnant within 90 days after stopping an investigational, low-dose oral contraceptive taken every day without placebo. Findings from the first large clinical examination were presented this week at the American College of Obstetricians and Gynecologists (ACOG) Annual Clinical Meeting in Washington, D.C.

Anne R. Davis, M.D., assistant professor of clinical obstetrics and gynecology at Columbia University Medical Center, presented the findings abstract relating to a non-cyclic oral contraceptive, [90 Âµg levonorgestrel/20 Âµg ethinyl estradiol tablets], that would be taken every day of the year without a placebo interval. In contrast to a 28-day cyclic regimen, this regimen would be taken every day of the year, without a placebo (or sugar pill) interval, resulting in a temporary interruption of menses.

The follow-up study after a Phase 3, multicenter, open-label study of the safety and contraceptive efficacy of a non-cyclic oral contraceptive investigated return to menstruation after study participants stopped taking the contraceptive. Results showed that 185 of the 187 women in the study experienced either a return to menses or became pregnant within 90 days once they stopped the study drug after taking it for a median of 364 days. Four women became pregnant before returning to menses and two women reported a return to menses more than 90 days after the completion of the study.

"Patients want to know if, after taking an oral contraceptive every day without placebo pills, their menses will return," said Dr. Davis. "By evaluating this, we were able to learn that women who followed this daily regimen experienced a return to menses without a considerable delay."

The most widely used method of contraception in 1995 was oral contraceptives, used by 10.4 million women, according to National Survey of Family Growth (NSFG).

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Columbia University Medical Center provides international leadership in pre-clinical and clinical research, in medical and health sciences education, and in patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, nurses, dentists, and public health professionals at the College of Physicians & Surgeons, the College of Dental Medicine, the School of Nursing, the Mailman School of Public Health, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. http://www.cumc.columbia.edu/

Contact: Elizabeth Streich
Columbia University Medical Center

Report Shows Popular Birth Control Pill, Ortho Tri-Cyclen(R) LO, Not Associated With Increased Pregnancy Risk In Heavier Women

2006-05-12T09:15:00.000-07:00

The popular birth control pill, ORTHO TRI-CYCLEN(R) LO (norgestimate/ethinyl estradiol) Tablets, is not associated with an increased risk of pregnancy in heavier women, according to findings(1) presented today at the 54th Annual Clinical Meeting of the American College of Obstetricians and Gynecologists (ACOG).

Previous research suggested that higher weight or body mass index (BMI) may compromise the efficacy of birth control pills leading to a greater number of unintended pregnancies.(2,3) This analysis evaluates the risk of pregnancy in heavier women using ORTHO TRI-CYCLEN LO.

"A significant number of women with a wide range of weights and BMIs were included in this analysis, creating a rich source of data to evaluate the association between body weight and efficacy," said Dr. Katherine LaGuardia, director, medical affairs, Ortho Women's Health & Urology. "These results reinforce ORTHO TRI-CYCLEN LO as an effective birth control option for women in a broad range of body weights."

Study Details

The report is based on a retrospective analysis of ORTHO TRI-CYCLEN LO Phase III efficacy data to determine the association of pregnancies with body weight and BMI, a standard measure of weight-for-height. The data were from 1,673 ORTHO TRI-CYCLEN LO users, weighing from 90 to 240 pounds, for 11,003 use cycles.

Investigators found that a total of 20 pregnancies occurred - 14 likely due to "method failure" (eg, the Pill did not work) and six due to failure on the part of the individual (eg, forgetting to take the Pill). This translated into a total pregnancy probability of 1.9 percent and a probability of failure of the Pill of 1.5 percent.

The probability of total and method-failure pregnancies was the same across different body weights. ORTHO TRI-CYCLEN LO users weighing 155 lbs. or more (n=435) did not experience significantly higher pregnancy risk than those less than 155 lbs. with either method-failure pregnancies (relative risk 1.03, p=0.95) or total pregnancies (relative risk 1.42, p=0.46). The results were the same when other weight criteria (median weight of 139 lbs. and over vs. less than 139 lbs., over 175 lbs. vs. less than or equal to 175 lbs., and 198 lbs. and over vs. less than 198 lbs.) and BMI criteria (25 and over vs. less than 25) were applied. The study was conducted and funded by Ortho Women's Health & Urology, a division of Ortho-McNeil Pharmaceutical, Inc.

About ORTHO TRI-CYCLEN LO (norgestimate/ethinyl estradiol) ORTHO TRI-CYCLEN LO is indicated for the prevention of pregnancy in women who elect to use oral contraceptives as their method of contraception.

Important Safety Information

Serious as well as minor side effects have been reported with the use of oral contraceptives. Serious risks include blood clots, stroke and heart attacks. Cigarette smoking increases the risk of serious cardiovascular side effects, especially in women over 35. Women who use oral contraceptives are strongly advised not to smoke. The Pill does not protect against HIV or sexually transmitted diseases.

For more information about ORTHO TRI-CYCLEN LO, please visit http://www.thepill.com.

About Ortho Women's Health & Urology

Ortho Women's Health & Urology, a division of Ortho-McNeil Pharmaceutical, Inc., is a leader in the fields of women's health and urology and is committed to providing patients with products that help them to live healthier lives. Ortho Women's Health & Urology, a trusted partner of healthcare professionals, is committed to meeting the needs of providers and patients with products such as ORTHO EVRA(R) (norelgestromin/ethinyl estradiol transdermal system), ORTHO TRI-CYCLEN(R) LO (norgestimate/ethinyl estradiol), DITROPAN XL(R) (oxybutynin chloride), and ELMIRON(R) (pentosan polysulfate sodium).

Ortho Women's Health & Urology
http://www.thepill.com