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Research Roundup
April 3, 2007, Volume 53, No. 28

Increasing Fertility in Women with PCOS

Researchers from Penn’s School of Medicine and the National Institutes of Health Reproductive Medicine research network have found that metformin, a drug used to treat diabetes and once thought to have great promise in overcoming the infertility associated with polycystic ovary syndrome (PCOS), is less effective than the standard fertility drug treatment, clomiphene. This is the largest, most comprehensive effort yet to compare the two drugs in helping PCOS patients achieve successful pregnancy.

“With this study, my colleagues and I recommend and support the use of clomiphene alone and not in combination with metformin as a first-line therapy for infertility in women with PCOS,” said Dr. Christos Coutifaris, director of the Division of Reproductive Endocrinology and Infertility and the principal investigator.

PCOS affects seven to eight percent of women in the U.S. and may be the most common cause of female infertility. With PCOS, an excess of male hormones interfere with ovulation and cause the ovaries to enlarge and fill with cysts. Women with PCOS frequently experience insulin resistance, a pre-diabetic condition in which higher-than-normal amounts of insulin are required to allow glucose to enter tissues. Earlier studies had shown that drugs such as metformin—which make the body more sensitive to insulin—could increase ovulation in PCOS patients. Similarly, several smaller studies had suggested that metformin, alone or when taken together with the drug clomiphene, could result in greater fertility rates for PCOS patients than could clomiphene alone.

According to the study authors, women who took metformin ovulated more than the women who were given the standard treatment. Similarly, women in the combination therapy group ovulated more frequently than did the women in either the clomiphene-alone or the metformin-alone groups. However, as the current study revealed, an increase in ovulation did not result in more successful pregnancies and deliveries for either the metformin alone, or combination group. The researchers theorize that although the combination of the two drugs might stimulate more cycles of ovulation than clomiphene alone, these extra cycles might result in a higher number of eggs that are not capable of fertilization or development.

“The bottom line here is that ovulation does not necessarily result in a successful pregnancy,” said Dr. Coutifaris. “The results suggest that an ovulation due to clomiphene is two times as likely to result in pregnancy compared to an ovulation caused by metformin.”

Veterans Highly Tolerant of Detainee Abuse

  In a study that appears in Military Medicine, Dr. William C. Holmes, assistant professor of medicine and epidemiology in Penn’s School of Medicine, assesses veterans’ tolerance for detainee abuse and variables associated with it.

In the study, three scenarios of detainee abuse, taken directly from Abu Ghraib prison in Iraq, were presented to veterans. After each scenario, zero tolerance—or the belief that abuse is “completely unacceptable” regardless of who the detainee is—was assessed for the described abuse. Dr. Holmes found that 16% of veterans indicated zero tolerance for detainee exposure and deprivation, 31% indicated zero tolerance for detainee exposure and sexualized humiliation, and 48% indicated zero tolerance for detainee rape.

“The level of tolerance exhibited by these findings is surprising, but may not be true for all veterans and certainly cannot be said to be representative of active-duty military,” says Dr. Holmes. “These findings do indicate, however, the value of assessing tolerance for abuse, and for using scenario-based assessment to do that; it provides an argument for similar work being done in active-duty military, particularly those who are heading to Iraq to become involved in sensitive, oversight positions.”

The study was completed by administering paper questionnaires to 351 veteran volunteers at the Philadelphia VA Medical Center’s Mental Health Clinic, Primary Care Clinic, and Women’s Health Center. In general, veterans’ tolerance for abuse was least when soldier-initiated, and greatest when superior-ordered. Tolerance for abuse also was high when a whistleblower was involved. The strongest, most consistently significant variable related to tolerance was depression and comorbid depression/posttraumatic stress disorder (PTSD). Those with depression alone and those with comorbid depression/PTSD exhibited odds that were approximately two and three times more tolerant of abuse than those with neither depression nor PTSD. Gender of the respondent also was related to tolerance. Men exhibited odds that were 4 to 20 times more tolerant of abuse than women.

Illnesses May Cause Chronic Subjective Dizziness

It’s estimated that 9-15 million people in the U.S. suffer from recurring episodes of dizziness and 3 million experience daily symptoms of dizziness. According to a paper that appears in the February issue of Archives of Otolaryngology—Head & Neck Surgery, researchers at the Penn School of Medicine found that chronic subjective dizziness (CSD) may have several common causes, including anxiety disorders, migraine, mild traumatic brain injuries, and neurally mediated dysautonomias—disorders in the autonomic nervous system, which controls involuntary actions. Among the various forms of dizziness, clinicians have found CSD to be particularly vexing. “Patients with CSD experience persistent dizziness not related to vertigo, imbalance, and hypersensitivity to motion, which is heightened in highly visual settings, such as walking in a busy store or driving in the rain,” said Dr. Jeffrey P. Staab, assistant professor in the departments of psychiatry and otorhinolaryngology, and coauthor of the paper.

Dr. Staab and coauthor, Dr. Michael J. Ruckenstein, associate professor in the department of otorhinolaryngology, studied 345 men and women age 15 to 89 (average age 43.5) who had dizziness for three months or longer due to unknown causes. “All but six patients were diagnosed as having psychiatric or neurologic conditions…” said Dr. Ruckenstein. Most patients (59.7%) had CSD with anxiety, 38.6% had CSD and illnesses of the central nervous system (migraine, traumatic brain injuries, or dysautonomias), and 1.7% had CSD and irregular heartbeats. Two-thirds of patients had medical conditions associated with the onset of dizziness, whereas one-third had anxiety disorders as the initial cause. Therefore, CSD may be triggered by either neurologic or psychiatric conditions.

Key diagnostic features were identified in the clinical history for each illness. For example, those with migraines often had nausea or vomiting, anxiety disorders were associated with fear and worry, and those with dysautonomias tended to become dizzy when they exerted themselves. “Careful inquiry about these key features during exams may lead to better diagnoses and more specific treatment recommendations for the many patients with chronic dizziness who have not found a cause for their symptoms and those who have been given diagnoses that have not brought them relief,” said Dr. Staab.

Effects of Meditation on Early Cognitive Impairment

Researchers at Penn’s School of Medicine are examining the effectiveness of meditation on early cognitive impairment. Once this new study is completed, the results could help answer lingering questions over whether or not stress-reducing techniques and mind exercises can lessen or even prevent cognitive decline. This is the first study at Penn’s new “Center for Spirituality and the Mind,” which evolved from work initiated in Penn’s Department of Radiology, to embrace and encourage researchers from the fields of medicine, pastoral care, religious studies, social work, nursing, and bioethics to expand knowledge of how spirituality may affect the human brain. “We’ll be looking at patients with mild cognitive impairment or symptoms of early Alzheimer’s disease,” explains Dr. Andrew Newberg, associate professor of radiology, psychiatry, and religious studies, who also directs the Center’s investigations and is principal investigator of this pilot study. “We’ll combine their meditation with brain imaging over a period of time to see if meditation improves cognitive function and is associated with actual change in the brain’s activity levels. Specifically, we’ll be looking for decreased activity in specific areas of the brain.”

The dementia process causes a decreased function of neurons in the brain and can result in problems with memory, visual-spatial tasks, and handling emotional issues. As it worsens in a patient, it can also eventually lead to the need for round-the-clock care. In this study, investigators want to look at the early symptoms of dementia. Study participants will learn a particular kind of meditation, called Kirtan Kriya, identified as one of the most fundamental types of meditation practice. It is a repeated chanting of sounds and finger movements designed to help the mind focus and become sharper. Study participants will perform this meditation program every day for eight weeks to see if this relaxation technique can change the brain’s response to different tasks. “This is a form of exercise for the brain which enables the brain to strengthen itself and battle the unknown processes working to weaken it. We want to keep the mind sharp and work that muscle,” Dr. Newberg adds. “We might see improvements in baseline activity levels in the brain and these patients might be able to activate their brain in a more robust way in particular. So if this kind of meditation is successful in helping patients with neurological problems, it could then someday become a low-cost additional treatment to current therapy.”


Almanac - April 3, 2007, Volume 53, No. 28