NIH-funded study finds dietary supplement does not alleviate BPH

Are These Berries the Cure for Prostate Problems?

Saw palmetto, a widely used herbal dietary supplement, does not reduce urinary problems associated with prostate enlargement any better than a placebo, according to research funded by the National Institutes of Health. The study was published Sept. 28 in the Journal of the American Medical Association.

Prostate enlargement, also called benign prostatic hyperplasia (BPH), can cause frequent urination, a weak or intermittent urine stream and an inability to empty the bladder completely. More than half of men in their 60s, and up to 90 percent in their 70s and 80s, have symptoms of BPH.

The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the National Center for Complementary and Alternative Medicine (NCCAM) and the Office of Dietary Supplements (ODS) supported the study. All are part of the NIH.

According to Robert A. Star, M.D., director of the NIDDK’s Division of Kidney, Urologic and Hematologic Diseases, the current study met an important need for rigorous evaluation of standard and higher doses of saw palmetto. The trial also confirmed results of the earlier NIDDK- and NCCAM-sponsored Saw Palmetto Trial for Enlarged Prostates (STEP), which found that a standard daily dose of 320 milligrams provided no greater symptom relief than placebo.

“Investigators designed the current trial to determine whether daily doses of up to 960 milligrams — three times the standard daily dose — would prove better than a placebo at improving lower urinary tract symptoms in men due to BPH,” said Star. “We were disappointed to find that higher doses of saw palmetto did not improve symptoms more than placebo.”

Josephine P. Briggs, M.D., director of NCCAM, added that this study further illustrates the importance of conducting research on botanical products that are used extensively by the general public.

“This was a well-designed study that addressed limitations of earlier, smaller trials — it was a multicenter study with a larger sample size and tested different doses of a carefully analyzed saw palmetto product,” Briggs said. “The NIH is committed to bringing rigorous science to the study of natural products and to building the evidence base that can guide consumer decisions.”

The study was a double-blind randomized placebo-controlled clinical trial conducted at 11 North American clinical sites from June 2008 to October 2010. A cohort of 369 men aged 45 years or older participated, each with a peak urine flow rate of at least four milliliters per second at the beginning of the study — which is less than normal. Also, all had an American Urological Association Symptom Index (AUASI) score of between eight and 24 — a lower score is better. The AUASI score ranges from zero to 35. Escalating doses of saw palmetto or placebo were given, starting at one, then two, and then three pills of 320 milligrams per day, with dose increases at 24 and 48 weeks.

The study measured the differences between the AUASI score at the start of the trial and after 72 weeks of treatment. Secondary measures included improvements in frequency, nocturia (nighttime urination), peak urine flow, prostate-specific antigen (PSA) level, sexual function, incontinence and sleep quality.

Between baseline and 72 weeks, mean AUASI scores decreased from 14.4 to 12.2 points with saw palmetto extract and from 14.7 to 11.7 points with placebo. The group average change in AUASI score from baseline to 72 weeks between the saw palmetto and placebo groups was 0.79 points, favoring placebo. Saw palmetto was not more effective than placebo in reducing urinary symptoms for any of the secondary outcomes.

According to Joseph M. Betz, Ph.D., director of the Analytical Methods and Reference Materials program at ODS and a study co-author, the study used a very well-characterized saw palmetto product. Through batch testing, study investigators took extreme care to ensure that the composition of the supplement was consistent over the whole study.

“Saw palmetto and other herbs are often manufactured in different ways, so no two brands are likely to have the same composition,” Betz said.

Rottapharm/Madaus, Cologne, Germany, donated the saw palmetto extract and matching placebo used in the study.

New Understanding Into the Causes of ALS and Dementia

National Institutes of Health scientists and worldwide teams of researchers have identified the most common genetic cause known to date for two neurological diseases, amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The discovery offers clues to underlying mechanisms of these diseases, and may eventually contribute to the design and testing of possible therapies. The research results appeared online in Neuron on Sept. 21, 2011.

Researchers found that a mutation on a single gene, C9ORF72 on the short arm of chromosome 9, accounts for nearly 50 percent of the directly inherited, familial ALS and FTD in the Finnish population, and more than a third of familial ALS in other groups of European ancestry. The mutation, called a hexanucleotide repeat expansion, is an unusual one that involves repeating a DNA sequence over and over again. The researchers also found these mutations in Finnish people with the more common, sporadic form of ALS.

Bryan Traynor, M.D., of the Laboratory of Neurosciences at the NIH’s National Institute on Aging (NIA), led the NIH work with support from NIH’s National Institute of Neurological Disorders and Stroke (NINDS). NIA and NINDS also funded work by a team from the Mayo Clinic in Florida, reported by Mayo investigator Rosa Rademakers, Ph.D., and colleagues, which independently identified the same repeat DNA sequence as a genetic cause of FTD/ALS.

“Identifying this defective gene common to both the inherited forms of ALS and FTD and the sporadic form of ALS provides important new insights into the development of these neurodegenerative diseases,” said NIA Director Richard J. Hodes, M.D. “We still have much to learn about the complex interplay between genetic risk for a disorder and the other factors that determine disease onset and progression. But finding these types of mutations is critically important to a better understanding of disease mechanisms so that we can ultimately target disease biology to develop therapeutics.”

“This finding highlights the importance of studying isolated populations with high rates of a specific disease. Finland has the highest rates of ALS in the world. By collecting virtually every case within the Finnish population, Traynor and colleagues were able to definitively show that this particular gene mutation plays a role in ALS development—a discovery relevant not just to that population, but critical to our basic understanding of the disorder,” said NINDS Director Story Landis, Ph.D.

Both ALS, often referred to as Lou Gehrig’s disease, and FTD are rapidly progressive, fatal neurological disorders that attack and kill brain cells, or neurons. People with ALS lose strength and the ability to move their arms, legs, and body, and eventually, the ability to breathe without support. About 5 percent of people with ALS have the directly inherited form of the disease. People with FTD develop erratic behavior, emotional problems, trouble communicating, or difficulty with walking and other basic movements. About 20 to 40 percent of those with FTD have a family history of the disorder. ALS and FTD can sometimes occur together in the same individual, but they also occur independently of each other.

There is growing scientific evidence that the pathologies of ALS and FTD somehow overlap. To date, a number of mutated genes have been identified as playing a role in the development of familial FTD and ALS, but not to the level of significance as the discovery of the 9p21 gene mutation. The five major genes previously identified for ALS account for approximately 25 percent of familial cases. The new discovery increases this figure to around 65 percent.

“Until now, the gene alteration responsible for the chromosome 9p-linked inherited forms of these diseases remained elusive,” said Traynor. “Investigators around the world worked together to identify a common genetic cause of these fatal disorders. At NIH, our state of the art DNA sequencing facilities enabled us to rapidly generate the data needed to identify this repeat expansion.”

The findings reported by Traynor and the team resulted from an international collaboration involving scientists in the United States, Canada and Europe. In the United States, participating institutions included the University of Washington School of Medicine, Seattle; Johns Hopkins University, Baltimore; Georgetown University, Washington, D.C.; and the Miller School of Medicine, University of Miami. The European collaborators included Cardiff University School of Medicine, Wales; VU University Medical Centre, Amsterdam, and Erasmus MC – University Medical Center, Rotterdam, The Netherlands; University of Manchester and University College London, England; University of Oulu and University of Helsinki, Finland; the University of Toronto; University of Würzburg, Germany; and the University of Turin, Catholic University Rome, and the University of Modena Cagliari, Italy.

Research project will focus on doctors, communities and families to help children make healthy choices

The Centers for Disease Control and Prevention (CDC) today launched a new effort to address childhood obesity using successful elements of both primary care and public health. Funding made available through the Affordable Care Act will support a four year Childhood Obesity Demonstration Project.  Supported by $25 million in funding awards, the project will build on existing community efforts and will work to identify effective health care and community strategies to support children’s healthy eating and active living and help combat childhood obesity.

The project will target children ages 2–12 years covered by the Children’s Health Insurance Program (CHIP), which provides low cost health insurance to over 7 million children from working families.  Rates of childhood obesity are high overall, but for minority and low–income communities in particular, they are even higher. Using innovative approaches to reach low–income and minority families to tackle childhood obesity prevents the onset of many diseases associated with childhood obesity, including type 2 diabetes, asthma, and heart disease.

These innovative approaches include combining changes in preventive care at doctor visits with supportive changes in schools, child care centers, and community venues such as retail food stores and parks. Community health workers will provide a bridge between families and resources in their communities in order to inform and educate hard–to–reach, limited English proficiency, and minority communities about disease prevention (including obesity), health insurance enrollment opportunities, and disease management.  Overall, the grantees’ work will focus on strategies that improve children’s health behaviors by involving the children themselves, their parents and other family members and the communities in which they live.

“Over the last three decades, obesity rates among children and adolescents have nearly tripled,” said CDC Director Thomas R. Frieden, MD, MPH.  “Obese children are more likely to have asthma, depression, diabetes, and other serious and costly health problems.  This project will help figure out ways our children can grow up to lead long, healthy and productive lives.”

The project grantees include three research facilities, each of which will receive approximately $6.2 million over four years, to identify effective childhood obesity prevention strategies. The evaluation center will receive about $4.2 million over four years and will determine successful strategies and share lessons and successes.

Research Facilities:

• University of Texas Health Science Center at Houston
• San Diego State University
• Massachusetts State Department of Public Health

Evaluation Center:

• The University of Houston

At the end of the project in September 2015, CDC will disseminate the findings and provide recommendations for successful strategies to prevent obesity among underserved children throughout the United States.

From Britain’s National Health Services

Scientists have discovered how to switch off the pain of migraines, The Daily Telegraph reported. The newspaper said that new drugs may soon be able to counteract the debilitating headaches.

The study behind the news analysed the DNA of over 1,200 people to look for mutations within a gene known to play a role in the working of nerve cells. The analysis found a particular mutation in a woman who had migraines with “aura” (visual disturbances that accompany a migraine). When the mutation was traced back through the woman’s family, it was found that all those who carried the mutation also had migraines with aura. Further testing of the mutation showed that it affects the way cells in the spinal cord and brain chemically transfer signals to each other.

As yet, we do not know how commonly people with migraine and aura are affected by the mutation, or whether mutations in the gene might play a role in migraine without aura. Also, there is likely to be a variety of genetic and environmental factors that increase the risk of getting migraines. While this genetic discovery may eventually help migraine sufferers, the media have been overly optimistic in interpreting this research as it is too soon to anticipate it leading directly to a treatment.

Where did the story come from?

The study was carried out by researchers from Université de Montréal in Canada and other research organisations across the world. It was funded by Genome Canada, Genome Quebec, Emerillon Therapeutics, the Wellcome Trust and the Pfizer pharmaceutical company. It was published in the peer-reviewed medical journal Nature Medicine.

This genetic study is an important but early step in the investigation of potential genetic causes of typical migraines with aura. It is unclear whether it will have an application for migraine treatments and it is too soon to claim that scientists have discovered how to “switch off” the pain of migraines. This study did not investigate a treatment.

What kind of research was this?

This was a type of genetic study called a “candidate gene study”. This is where researchers investigate a particular gene for mutations that may be linked with a condition, in this case migraines. It is a form of case-control study, in which the DNA sequences found in that particular gene are compared between people with the condition (cases) and a group of people without the condition (controls).

When communicating with each other, nerve and brain cells use ions (atoms or a group of atoms with an electrical charge) to transfer tiny electrical impulses from cell to cell. As part of this process, ions pass through “channel proteins”, which are complex proteins that act as gates and will only let specific substances through. Problems with channelling ions across cells have previously been linked to other types of migraine, although not to migraines with aura. Here, researchers were interested in a gene called KCNK18. This gene contains the code for producing a protein called TRESK K2P, which channels potassium ions in the spinal cord. TRESK K2P is known to have a role in the “excitability” of nerve cells, i.e. their ability to generate nerve impulses. The protein is also thought to play a role in pain.

Researchers assessed whether mutations in this particular gene were linked with migraine with aura. Some people experience aura before the onset of migraine, which often involves visual disturbances. For example, some people see black spots or flashing shapes before a migraine.

What did the research involve?

The study enrolled 110 people who experienced typical migraine with aura and determined the DNA sequence of their KCNK18 genes. This was then compared to the KCNK18 sequence in a group of 80 people who did not have migraines.

To verify their findings from the initial phase of the study, the researchers replicated their analysis in a group of 511 Australians with migraine and a group of 505 people, matched for ethnicity, who did not have migraines. The researchers investigated the genetics of one mutation, which they identified further by assessing DNA samples of family members of an individual with the mutation.

As well as looking at mutations of the KCNK18 gene, the researchers investigated where the TRESK protein it coded for was concentrated. Tissue from mice and humans was used to determine whether the TRESK protein was produced in regions of the brain that were relevant to migraine. The researchers also used frog cells to investigate how the mutations they identified might cause functional changes within the TRESK potassium channel.

What were the basic results?

The candidate gene analysis identified four variants in the KCNK18 gene that were present in migraine sufferers but not in people without migraines. Of the four variants, one would not have caused any change in the TRESK protein and one was already known to be common in African populations. These were unlikely to be involved in migraines. Another variant was identified in only one migraine sufferer, but no DNA samples were available from the family members of this individual, so the researchers did not study this variation further.

The final variant, called F139WfsX24, involved the deletion of two “letters” in the code of the DNA. This meant that the full-length TRESK protein could not be made. This was likely to have an impact on the protein’s function, and could possibly lead to migraines. When this mutation was subject to further study in a detailed family analysis, it was found to be present only in the eight family members who were migraine sufferers. This fitted with the idea that this mutation could cause migraine with aura in this family.

By tracing the family’s history, the researchers found that this mutation acted in a dominant way (i.e. people carrying just a single copy of the mutation were affected by migraine with aura). The mutation was also found to have “full penetrance”, which means that all people in the family with the mutation suffered from migraines.

The phase of the study which looked at mouse and human tissue found that the TRESK protein was present in mouse spinal cord and brain regions and in the trigeminal ganglion neurons (a group of nerve cells outside the central nervous system) of humans. As expected, during functional studies in frog cells, the mutation completely suppressed the appropriate functioning of TRESK potassium channels.

How did the researchers interpret the results?

The researchers say that they have identified a mutation in TRESK that is associated with typical migraine with aura in a large multigenerational family. They say that the results support the possibility that TRESK is involved in typical migraines with aura and that these channels may be a target for treatments.

Conclusion

The study was well conducted and well described, but the media’s interpretation of the results was overly optimistic. The study did not investigate a treatment for migraine or a method to “switch off” the pain of migraines. Several important details are still unknown, including the number of people whose migraines may be caused by this faulty gene. It appears that the key mutation identified (F139WfsX24) was found in only one person out of the 600 or so who had migraines in this study (although it was also found in their family members). Further research will be needed to see whether these findings can be generalised to a larger population. Even if they can be, treatments based on these findings will be a long way off. The findings also only apply to people who have auras with their migraines, while most sufferers do not.

Such research can be a first step in the development of drugs. The researchers have not only identified genetic variations associated with migraine, but they have also gone some way to investigating the functional consequences of the mutation in rat, human and frog cells. Additionally, they have attempted to clarify the complex biochemical pathways behind it.

It will now take further research to determine whether these findings will have a direct application to most migraine sufferers. Drug development is a long process, and few drugs make it all the way through to being a successful human treatment.

NIH Scientists Consider Fate of Pandemic H1N1 Flu Virus

From the National Institutes of Health

Whither pandemic H1N1 virus? In a new commentary, scientists from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, review the fates of previous pandemic influenza viruses in the years following a pandemic and speculate on possible future courses for the 2009 pandemic H1N1 (pH1N1) virus during the upcoming flu season and beyond.

The authors estimate that at least 183 million Americans (about 59 percent of the total U.S. population) have some immunity to pH1N1 because they were exposed to related viruses or vaccines prior to 2009, were immunized against pH1N1 or developed immunity following infection with the pandemic virus.

To stay in circulation in the face of such high levels of population immunity, the pH1N1 virus must adapt either through abrupt or gradual changes. The authors briefly examine a number of earlier pandemics and trace paths taken by the causative viruses. Some—for reasons not well understood—died out, while others, like those of 1889 and 1918, returned in an explosive fashion. Such an explosive return of pH1N1 virus is unlikely, note the authors, because global levels of immunity are already high and will increase further through immunization with 2010-2011 seasonal influenza vaccines, which contain the pH1N1 strain.

In light of what is known about pH1N1, the NIAID authors express a cautious optimism that unless it disappears entirely the virus will follow a route like that of 1968 pandemic virus, that is, it will persist in a form that causes relatively few deaths.

Nevertheless, the authors caution against complacency. As they acknowledge, many gaps remain in understanding how a given pandemic influenza virus adapts to increased immunity in humans. For that reason, influenza vaccination for everyone older than six months is a wise public health measure to maintain high levels of population-wide immunity. Immunization with 2010-2011 seasonal flu vaccine is particularly urged for babies older than six months, children, teens and young adults as the best way to protect individuals in those potentially more susceptible age groups from illness.

Approximately one in five (19 percent) men who have sex with men (MSM) in a study of 21 major U.S. cities is infected with HIV, and nearly half (44 percent) of those men are unaware of their infection, according to a new analysis from the Centers for Disease Control and Prevention.  In the study, young MSM and MSM of color were least likely to know their HIV status.  The findings were published today in CDC’s Morbidity and Mortality Weekly Report.

“This study’s message is clear:  HIV exacts a devastating toll on men who have sex with men in America’s major cities, and yet far too many of those who are infected don’t know it,”  said Kevin Fenton, M.D., director of CDC’s National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention.  “We need to increase access to HIV testing so that more MSM know their status, and we all must bring new energy, new approaches, and new champions to the fight against HIV among men who have sex with men.”

The study’s results bolster key themes in the President’s National HIV/AIDS Strategy for the United States.  The recently released strategy states that “the United States cannot reduce the number of HIV infections nationally without better addressing HIV among gay and bisexual men,” and MSM are listed among a few priority populations to focus HIV prevention efforts.  The President’s strategy also sets targets for reducing the number of individuals living with HIV who are unaware of their HIV status.

The CDC study tested 8,153 MSM in 21 cities participating in the 2008 National HIV Behavioral Surveillance System (NHBS), and examined HIV prevalence and awareness of HIV status among this group.  NHBS monitors HIV testing, risk behaviors, and access to prevention services among at-risk populations in cities with high numbers of persons living with AIDS.

While MSM of all races and ethnicities were severely affected, black MSM were particularly impacted:  28 percent of black MSM were HIV-infected, compared to 18 percent of Hispanic and 16 percent of white MSM.

The study also found a strong link between socioeconomic status and HIV among MSM: prevalence increased as education and income decreased, and awareness of HIV status was higher among MSM with greater education and income.  These findings echo similar disparities found in recent NHBS research among heterosexuals.

Low awareness of HIV infection a major concern, particularly for younger men

The study provided additional insight into the populations of MSM most in need of HIV testing and prevention:

• Among racial/ethnic groups, black MSM with HIV were least likely to be aware of their infection (59 percent unaware, vs. 46 percent for Hispanic MSM and 26 percent for white MSM).
• While young MSM (under age 30) had lower HIV prevalence than older men, they were far more likely to be unaware of their HIV infection.  Among MSM aged 18-29 who had HIV, nearly two-thirds (63 percent) were unaware, versus 37 percent for men age 30 and older.
• Among young MSM, young MSM of color were less likely than whites to know they were HIV-infected.  Among HIV-infected black MSM under age 30, 71 percent were unaware of their infection; among HIV-infected Hispanic MSM under age 30, 63 percent were unaware.  This compares to 40 percent of HIV-infected white MSM under age 30.

CDC officials note that low awareness of HIV status among young MSM likely reflects several factors:  they may have been infected more recently, may underestimate their personal risk, may have had fewer opportunities to get tested, or may believe that advances in HIV treatment minimize the threat of HIV.  For young MSM of color, discrimination and socioeconomic factors – such as poverty, homophobia, stigma, and limited health-care access – may be especially acute and pose particular challenges.

“For young men who have sex with men – including young men of color who are least likely to know they may be infected – the future is truly on the line,” said Jonathan Mermin, M.D., director of CDC’s Division of HIV/AIDS Prevention.  “It is critical that we reach these young men early in their lives with HIV prevention and testing services and continue to make these vital services available as they become older.”

CDC estimates that the majority of new sexually transmitted infections are transmitted by individuals who are unaware of their infection, and studies show that once people learn they are HIV-infected, most take steps to protect their partners.  Therefore, because undiagnosed infection likely plays a major role in HIV transmission, reaching younger MSM with regular HIV testing is critical.

CDC recommends that MSM of all ages get tested for HIV at least annually, or more often (every three to six months) if they are at increased risk (e.g., those with multiple or anonymous sex partners, or who use drugs during sex).  Notably, only 45 percent of HIV-infected MSM who were unaware of their infection had been tested in the past year, underscoring the importance of more frequent testing among those at highest risk.

While HIV prevention for MSM remains a top CDC priority, agency officials note that a renewed national commitment to HIV prevention is needed to reduce the toll of HIV on MSM and increase access to prevention.

Researchers at the National Institutes of Health and other institutions have found that exposure to lead in childhood may delay the onset of puberty in young girls, with higher doses increasing the chance for later maturation.

The researchers analyzed data on blood drawn from more than 700 girls ages 6 to 11. They found that girls with elevated levels of lead (at or above five micrograms of lead per deciliter of blood) were 75 percent less likely than girls with low levels of lead to have key adolescent hormones at levels that are associated with the beginning of puberty. In girls with elevated levels of both lead and cadmium, this pattern was even more pronounced.

The researchers speculate that lead, alone or in concert with cadmium, might suppress the ovary’s production of hormones that prepare a young girl’s body to ovulate, or release an egg, for the first time.

Previous studies have shown that exposure to such heavy metals can disrupt normal hormone patterns or, in some cases, reproductive development. The Centers for Disease Control and Prevention advise treatment for lead exposure at levels exceeding 10 micrograms of lead per deciliter of blood (http://ephtracking.cdc.gov/showChildhoodLeadPoisoning.action), but the study authors believe their findings suggest that lead exposure may have harmful effects at even lower levels.

“Our findings suggest childhood exposure to lead has worrisome effects as children age and reach adolescence,” said lead first author Audra L. Gollenberg, Ph.D., a fellow at the NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), where the research was conducted. “These issues are of concern in some parts of the United States as well as in countries where children are exposed to leaded gasoline, paint or industrial pollutants.”

According to the U.S. Environmental Protection Agency, the most common sources of lead exposure are deteriorating lead-based paint, lead contaminated dust, and lead contaminated residential soil (http://www.epa.gov/lead/).

Gollenberg worked with NICHD colleagues Mary L. Hediger, Ph.D., and Germaine M. Buck Louis, Ph.D., Peter A. Lee, M.D., of Penn State College of Medicine, Hershey, Pa. and John H. Himes, Ph.D., M.P.H., of the University of Minnesota School of Public Health, Minneapolis.

Their findings appear in Environmental Health Perspectives, published by the National Institute of Environmental Health Sciences.

The researchers worked with data on blood and urine samples taken as part of the Third National Health and Nutrition Examination Survey between 1988 and 1994. They compared levels of lead and cadmium to levels of the reproductive hormone inhibin B, an indicator of the development of previously dormant egg cells in the ovaries. Inhibin B is known to increase steadily before the start of puberty.

Designating a specific threshold level for inhibin B, which indicated puberty, the researchers calculated the likelihood that girls with low, medium, or high levels of exposure to lead would reach that threshold. For all age groups, the researchers found that girls with higher blood levels of lead had reduced levels of inhibin B, and so were less likely to reach the threshold. High levels of lead and cadmium together were even more likely to be associated with low levels of inhibin B. (Cadmium levels of .27-3.7 nanograms per milliliter of urine were considered to be high.) According to the Centers for Disease Control and Prevention, cadmium damages the kidneys, lungs and bones and increases the risk for cancer. Breathing cigarette smoke is a principal source of cadmium exposure (http://www.atsdr.cdc.gov/tfacts5.html).

In addition, the findings suggested the pubertal delay associated with lead was more prevalent in girls with iron deficiencies. Girls with even moderate levels of lead and low iron levels were much less likely to have reached the inhibin B threshold levels indicating puberty than their counterparts with low lead exposure and normal iron levels.

“Iron deficiency appears to be a critical factor in the context of lead exposure,” Dr. Gollenberg said. “Health care providers may wish to pay particular attention to the importance of screening for iron deficiency among girls at high risk for exposure to lead.”

A study by researchers at the National Institutes of Health and the University of Oxford supports the widespread belief that stress may reduce a woman’s chance of becoming pregnant. The study is the first of its kind to document, among women without a history of fertility problems, an association between high levels of a substance indicative of stress and a reduced chance of becoming pregnant.

This line graph shows the saliva levels of alpha-amylase for women in the study, and categorizes the data into the highest 25 percent, the lowest 25 percent, and the medium group. For each of the five days before ovulation, the day of ovulation, and the day after ovulation, the 25 percent of women with the highest alpha-amylase levels had a 12 percent overall reduction in fertility, when compared to the 25 percent of women with the lowest levels.

The researchers showed that women who had higher levels of a substance called alpha-amylase were less likely to get pregnant than were women with lower levels of the substance. Alpha-amylase is secreted into saliva by the parotid gland, the largest of the salivary glands. Although alpha-amylase digests starch, in recent years many researchers have used it as a barometer of the body’s response to physical or psychological stress. The substance is secreted when the nervous system produces catecholamines, compounds that initiate a type of stress response.

In addition to researchers at the NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the University of Oxford, England, the study also includes an author from The Ohio State University College of Medicine, Columbus.

“The study results suggest that finding safe ways to alleviate stress may play a role in helping couples become pregnant,” said Alan E. Guttmacher, M.D., director of the NICHD.

The study was published online in Fertility and Sterility.

To conduct the study, the researchers charted the ovulation cycles of 274 English women aged 18-40 years who were trying to conceive, and who participated in the Oxford Conception Study led by Cecilia Pyper, MB.BS. This clinical study sought to determine whether daily information from a fertility-monitoring device would increase the conception rate in women wishing to achieve pregnancy. The women were given at-home fertility test kits to track the phases of their monthly cycles.

“This is the first study to show an association between a biomarker of stress and a reduction in women’s chances of conceiving throughout the fertile window — underscoring the importance of considering stress when attempting to identify the determinants of conception,” Dr. Pyper said.

On the sixth day of her cycle, each woman collected a sample of her saliva, which was subsequently tested for alpha-amylase. The women’s saliva samples were also analyzed for cortisol, another hormone produced by the adrenal glands in response to stress. Each woman took part in the study until she became pregnant, or at the end of six menstrual cycles.

The researchers found that, all other factors being equal, women with high alpha-amylase levels were less likely to conceive than were women with low levels, during the fertile window — the six days when conception is most likely to occur. The researchers did not find a correlation between cortisol levels and the chances of conception.

“Overall, the 25 percent of women in the study who had the highest alpha-amylase levels had roughly an estimated 12 percent reduction in getting pregnant each cycle in comparison to women with the lowest concentrations,” said the study’s first author, Germaine Buck Louis, Ph.D., M.S., director of the NICHD’s Division of Epidemiology, Statistics, and Prevention Research.

Dr. Buck Louis added that she and her colleagues are currently conducting a study with a larger group of women to confirm the findings. Similarly, they also hope to learn whether stress is associated with infertility.

“It has been suggested that stress may increase with the disappointment of several failed attempts at getting pregnant, setting off a cycle in which pregnancy becomes even more difficult to achieve,” she said.

The current findings also suggest the need for finding appropriate ways to help women alleviate stress while trying to conceive.

“The question is, ‘what do you do to help women to relax?’ People often turn to alcohol or tobacco to relieve stress, but these substances also reduce the likelihood of pregnancy,” Dr. Buck Louis said. She added that additional research may be needed to determine whether relaxation techniques such as meditation, biofeedback, yoga, or increasing social support can assist women having difficulty conceiving.

Treating High Cholesterol

By Carolyn M. Clancy, M.D.

August 3, 2010

If you’re older than 45, there’s a good chance that you or someone you know has high cholesterol. It’s so common that treating high cholesterol led to 44 million doctor visits in 2006.

High cholesterol may be widespread, but understanding how to treat it can be confusing. However, lowering high cholesterol can prevent heart attacks and strokes. It could even save your life.

That’s why my agency, the Agency for Healthcare Research and Quality (AHRQ), offers a guide called Treating High Cholesterol. The guide explains in plain English how this common medical condition is treated and the pros and cons of different cholesterol medicines.

Cholesterol is vital to your body. Your liver makes cholesterol, which is found in your blood. We all need some cholesterol, but too much is harmful. Your diet and family history affect your cholesterol levels.

There are two main types of cholesterol—good (HDL) and bad (LDL) cholesterol. When your cholesterol is too high, that refers to your bad cholesterol, or your LDL level. When bad cholesterol builds up and leaves deposits (called plaque) in the walls of your arteries, it can limit blood flow and cause a heart attack or stroke.

A simple blood test can determine your cholesterol level and your risk for heart disease. The more risk factors you have, the higher the chance you have high cholesterol. Risk factors include:

• Age (being 45 or older for men or 55 or older for women).
• Family history of early heart disease.
• Smoking.
• High blood pressure.
• Low levels of good (HDL) cholesterol.
• Diabetes or certain other conditions.

Your doctor can help you determine your level of risk. The first step in controlling your cholesterol is a balanced diet and more exercise. Your doctor or nurse may recommend a diet that includes fresh fruits, vegetables, and whole grains, while limiting foods that are high in fat. However, even with a good diet and exercise habits, you may need medicine to lower your cholesterol.

Different kinds of medicines work in different ways to improve cholesterol levels. Some block the liver from making cholesterol, while others decrease the amount of fat absorbed from food.

Most people start with a medicine called a statin, which works to lower bad (LDL) cholesterol. If your bad cholesterol remains high, your doctor or nurse may increase your statin dose or add a different kind of medicine to help you reach healthy levels.

Our guide Treating High Cholesterol, based on a review of more than 100 research studies of cholesterol medicines, shows that all such medicines can cause minor side effects. These side effects include heartburn, upset stomach, and diarrhea. These problems often go away and are not usually serious. But you should tell your doctor if any symptoms do not disappear.

It’s important to talk with your doctor or nurse about your high cholesterol. Good topics include:

• Diet and exercise. Everyone with high cholesterol should be on a cholesterol-lowering diet. Exercise helps, too. Ask if diet and exercise alone can help meet your cholesterol goals.
• Medicines. Talk to your doctor about how and when to take cholesterol medicines. Once you start taking medicine to lower cholesterol levels, you will probably need to continue.
• Cost. Some medicines are available as generics, which cost less than brand-name drugs. Check with your health insurance plan about the cost. Our guide offers resources if you need help paying for your medicines or have other questions.
• Other steps for a healthy heart. Lowering high cholesterol is vital. But it’s also important to control other health problems, like diabetes and high blood pressure. Stopping smoking will also help.

AHRQ’s guides can help make complex decisions—including how to treat high cholesterol—easier to understand. By understanding the benefits and risks of treatments, you can work with your doctor to make decisions that are right for you.

I’m Dr. Carolyn Clancy, and that’s my advice on how to navigate the health care system.