Heidi Splete

A transdermal patch that delivers 20 mcg/hour of the opioid buprenorphine significantly improved pain scores in patients with moderate to severe chronic low back pain, compared with a transdermal dose of 5 mcg/hour or an active control, based on data from 660 patients in a phase III clinical trial.

Transdermal buprenorphine (Butrans) was approved by the Food and Drug Administration in June 2010 for management of chronic pain in adults, said Dr. Deborah Steiner of Purdue Pharma and her colleagues.

In this study, the researchers compared the buprenorphine transdermal system (BTDS), which delivered medication at an average buprenorphine dose of 20 mcg/hour over 7 days, to an average 5-mcg/hour transdermal dose and an active control consisting of 40 mg/day of immediate-release oxycodone capsules. The average age of the patients was 50 years, and the baseline demographics were similar among all three groups.

The findings were published online in the Journal of Pain (doi: 10.1016/j.jpain.2011.06.003).

Patients’ pain was assessed at weeks 4, 8, and 12 using the "average pain over the last 24 hours" scores. In all, 91% of the patients reported musculoskeletal pain as the primary source of their pain at baseline.

At baseline, the mean pain scores in the BTDS 20 group, BTDS 5 group, and oxycodone group were 6.4, 6.5, and 6.5, respectively. After 12 weeks, the mean pain scores in the three groups had dropped to 4.0, 3.3, and 3.3, respectively. The difference of –0.67 between the BTDS 20 and BTDS 5 scores was statistically significant.

"In general, the treatment-emergent adverse effects (TEAEs) observed in this study were similar to those expected with the use of opioid agonists and transdermal patches," the researchers noted. The incidence of TEAEs was 77% in the BTDS 20 group, 59% in the BTDS 5 group, and 73% in the oxycodone group. The most common TEAEs were application-site reactions, nausea, and headaches. The incidence of application-site reactions in the three groups was 29%, 17%, and 22%, respectively; the incidence of nausea was 12%, 8%, and 8%; and the incidence of headache was 11%, 5%, and 10%.

Four separate sensitivity analyses showed that BTDS 20 and oxycodone were significantly more effective for pain control than BTDS 5. In addition, post hoc analyses showed that significantly more patients in the BTDS 20 group than in the BTDS 5 group reported improvements in pain scores of at least 30% from baseline, the researchers said.

The study was sponsored by Purdue Pharma, and most of the study authors are full-time employees of Purdue Pharma.

A transdermal patch that delivers 20 mcg/hour of the opioid buprenorphine significantly improved pain scores in patients with moderate to severe chronic low back pain, compared with a transdermal dose of 5 mcg/hour or an active control, based on data from 660 patients in a phase III clinical trial.

Transdermal buprenorphine (Butrans) was approved by the Food and Drug Administration in June 2010 for management of chronic pain in adults, said Dr. Deborah Steiner of Purdue Pharma and her colleagues.

In this study, the researchers compared the buprenorphine transdermal system (BTDS), which delivered medication at an average buprenorphine dose of 20 mcg/hour over 7 days, to an average 5-mcg/hour transdermal dose and an active control consisting of 40 mg/day of immediate-release oxycodone capsules. The average age of the patients was 50 years, and the baseline demographics were similar among all three groups.

The findings were published online in the Journal of Pain (doi: 10.1016/j.jpain.2011.06.003).

Patients’ pain was assessed at weeks 4, 8, and 12 using the "average pain over the last 24 hours" scores. In all, 91% of the patients reported musculoskeletal pain as the primary source of their pain at baseline.

At baseline, the mean pain scores in the BTDS 20 group, BTDS 5 group, and oxycodone group were 6.4, 6.5, and 6.5, respectively. After 12 weeks, the mean pain scores in the three groups had dropped to 4.0, 3.3, and 3.3, respectively. The difference of –0.67 between the BTDS 20 and BTDS 5 scores was statistically significant.

"In general, the treatment-emergent adverse effects (TEAEs) observed in this study were similar to those expected with the use of opioid agonists and transdermal patches," the researchers noted. The incidence of TEAEs was 77% in the BTDS 20 group, 59% in the BTDS 5 group, and 73% in the oxycodone group. The most common TEAEs were application-site reactions, nausea, and headaches. The incidence of application-site reactions in the three groups was 29%, 17%, and 22%, respectively; the incidence of nausea was 12%, 8%, and 8%; and the incidence of headache was 11%, 5%, and 10%.

Four separate sensitivity analyses showed that BTDS 20 and oxycodone were significantly more effective for pain control than BTDS 5. In addition, post hoc analyses showed that significantly more patients in the BTDS 20 group than in the BTDS 5 group reported improvements in pain scores of at least 30% from baseline, the researchers said.

The study was sponsored by Purdue Pharma, and most of the study authors are full-time employees of Purdue Pharma.

A transdermal patch that delivers 20 mcg/hour of the opioid buprenorphine significantly improved pain scores in patients with moderate to severe chronic low back pain, compared with a transdermal dose of 5 mcg/hour or an active control, based on data from 660 patients in a phase III clinical trial.

Transdermal buprenorphine (Butrans) was approved by the Food and Drug Administration in June 2010 for management of chronic pain in adults, said Dr. Deborah Steiner of Purdue Pharma and her colleagues.

In this study, the researchers compared the buprenorphine transdermal system (BTDS), which delivered medication at an average buprenorphine dose of 20 mcg/hour over 7 days, to an average 5-mcg/hour transdermal dose and an active control consisting of 40 mg/day of immediate-release oxycodone capsules. The average age of the patients was 50 years, and the baseline demographics were similar among all three groups.

The findings were published online in the Journal of Pain (doi: 10.1016/j.jpain.2011.06.003).

Patients’ pain was assessed at weeks 4, 8, and 12 using the "average pain over the last 24 hours" scores. In all, 91% of the patients reported musculoskeletal pain as the primary source of their pain at baseline.

At baseline, the mean pain scores in the BTDS 20 group, BTDS 5 group, and oxycodone group were 6.4, 6.5, and 6.5, respectively. After 12 weeks, the mean pain scores in the three groups had dropped to 4.0, 3.3, and 3.3, respectively. The difference of –0.67 between the BTDS 20 and BTDS 5 scores was statistically significant.

"In general, the treatment-emergent adverse effects (TEAEs) observed in this study were similar to those expected with the use of opioid agonists and transdermal patches," the researchers noted. The incidence of TEAEs was 77% in the BTDS 20 group, 59% in the BTDS 5 group, and 73% in the oxycodone group. The most common TEAEs were application-site reactions, nausea, and headaches. The incidence of application-site reactions in the three groups was 29%, 17%, and 22%, respectively; the incidence of nausea was 12%, 8%, and 8%; and the incidence of headache was 11%, 5%, and 10%.

Four separate sensitivity analyses showed that BTDS 20 and oxycodone were significantly more effective for pain control than BTDS 5. In addition, post hoc analyses showed that significantly more patients in the BTDS 20 group than in the BTDS 5 group reported improvements in pain scores of at least 30% from baseline, the researchers said.

The study was sponsored by Purdue Pharma, and most of the study authors are full-time employees of Purdue Pharma.

The National Heart, Lung, and Blood Institute has halted the triple-drug therapy arm of a treatment trial for idiopathic pulmonary fibrosis because of poor outcomes, according to a statement issued by the National Institutes of Health.

Interim data from the study indicated that patients with idiopathic pulmonary fibrosis (IPF) who received a combined therapy of prednisone, azathioprine, and N-acetylcysteine (NAC) had no improvement in lung function, compared with a placebo group. In addition, compared with the placebo group, the treatment group had significantly higher rates of death (11% vs. 1%), hospitalization (29% vs. 8%), and serious adverse events (31% vs. 9%).

The study, known as PANTHER-IPF (Prednisone, Azathioprine, and N-acetylcysteine: A Study That Evaluates Response in Idiopathic Pulmonary Fibrosis), was designed to evaluate the effectiveness of a triple-therapy regimen in slowing disease progression and improving lung function in patients with moderate to severe IPF. The average age of the study participants at enrollment was 68 years.

"This combination therapy is widely used in patients with IPF but has not previously been studied in direct comparison to a placebo for all three drugs," Dr. Susan B. Shurin, acting director of the NHLBI, noted in a statement.

Patients in the other two treatment arms who are receiving NAC alone or a placebo will continue with their designated treatment protocols, which are scheduled to last up to 60 weeks, according to the NIH statement.

The researchers began enrolling patients in 2009. Completion of the first phase of the study with the two remaining treatment arms is expected by 2013. More details about the trial are available online.

The study was supported by National Institutes of Health and the Cowlin Family Fund at Chicago Community Trust. The NAC and matching placebo treatments were donated by Zambon; study funds were used to purchase the prednisone, azathioprine, and matching placebos.

The National Heart, Lung, and Blood Institute has halted the triple-drug therapy arm of a treatment trial for idiopathic pulmonary fibrosis because of poor outcomes, according to a statement issued by the National Institutes of Health.

Interim data from the study indicated that patients with idiopathic pulmonary fibrosis (IPF) who received a combined therapy of prednisone, azathioprine, and N-acetylcysteine (NAC) had no improvement in lung function, compared with a placebo group. In addition, compared with the placebo group, the treatment group had significantly higher rates of death (11% vs. 1%), hospitalization (29% vs. 8%), and serious adverse events (31% vs. 9%).

The study, known as PANTHER-IPF (Prednisone, Azathioprine, and N-acetylcysteine: A Study That Evaluates Response in Idiopathic Pulmonary Fibrosis), was designed to evaluate the effectiveness of a triple-therapy regimen in slowing disease progression and improving lung function in patients with moderate to severe IPF. The average age of the study participants at enrollment was 68 years.

"This combination therapy is widely used in patients with IPF but has not previously been studied in direct comparison to a placebo for all three drugs," Dr. Susan B. Shurin, acting director of the NHLBI, noted in a statement.

Patients in the other two treatment arms who are receiving NAC alone or a placebo will continue with their designated treatment protocols, which are scheduled to last up to 60 weeks, according to the NIH statement.

The researchers began enrolling patients in 2009. Completion of the first phase of the study with the two remaining treatment arms is expected by 2013. More details about the trial are available online.

The study was supported by National Institutes of Health and the Cowlin Family Fund at Chicago Community Trust. The NAC and matching placebo treatments were donated by Zambon; study funds were used to purchase the prednisone, azathioprine, and matching placebos.

The National Heart, Lung, and Blood Institute has halted the triple-drug therapy arm of a treatment trial for idiopathic pulmonary fibrosis because of poor outcomes, according to a statement issued by the National Institutes of Health.

Interim data from the study indicated that patients with idiopathic pulmonary fibrosis (IPF) who received a combined therapy of prednisone, azathioprine, and N-acetylcysteine (NAC) had no improvement in lung function, compared with a placebo group. In addition, compared with the placebo group, the treatment group had significantly higher rates of death (11% vs. 1%), hospitalization (29% vs. 8%), and serious adverse events (31% vs. 9%).

The study, known as PANTHER-IPF (Prednisone, Azathioprine, and N-acetylcysteine: A Study That Evaluates Response in Idiopathic Pulmonary Fibrosis), was designed to evaluate the effectiveness of a triple-therapy regimen in slowing disease progression and improving lung function in patients with moderate to severe IPF. The average age of the study participants at enrollment was 68 years.

"This combination therapy is widely used in patients with IPF but has not previously been studied in direct comparison to a placebo for all three drugs," Dr. Susan B. Shurin, acting director of the NHLBI, noted in a statement.

Patients in the other two treatment arms who are receiving NAC alone or a placebo will continue with their designated treatment protocols, which are scheduled to last up to 60 weeks, according to the NIH statement.

The researchers began enrolling patients in 2009. Completion of the first phase of the study with the two remaining treatment arms is expected by 2013. More details about the trial are available online.

The study was supported by National Institutes of Health and the Cowlin Family Fund at Chicago Community Trust. The NAC and matching placebo treatments were donated by Zambon; study funds were used to purchase the prednisone, azathioprine, and matching placebos.

TORONTO – More than half of children and teens who reported definite insomnia before being treated for depression experienced significant improvement in both their sleep and depression during their first weeks of treatment with fluoxetine, data from clinical trials involving 234 young patients show.

Previous studies have shown that insomnia is one of the most common residual symptoms in depressed youth, said Dr. Ameena Isa of the University of Texas Southwestern Medical Center, Dallas, and colleagues.

To explore the interaction between depression treatment and insomnia, the researchers reviewed combined data from two open-label clinical trials in which children and teens aged 7-18 years were treated with fluoxetine for the 12 weeks. The patients were seen once a week for 4 weeks and then every other week through 12 weeks. A total of 141 patients (60%) had severe insomnia at baseline, 45 (19%) had mild insomnia, and 48 (21%) had no insomnia. Patients with definite insomnia at baseline were significantly more depressed than other patients based on the Children’s Depression Rating Scale, Revised (CDRS-R). Demographic and clinical characteristics were similar among the treatment groups. The mean age was 13 years; 55% were male, and 73% were white.

Within 2 weeks of starting fluoxetine treatment, 53% of the patients who had reported definite insomnia had improved to reporting mild to moderate insomnia. In addition, 64% of those who had reported mild insomnia at baseline no longer complained of insomnia after 2 weeks of treatment.

The findings were presented at the annual meeting of the American Academy of Child and Adolescent Psychiatry.

Patients whose insomnia improved within the first 2 weeks of treatment also had significantly lower depression severity scores on the CDRS-R, compared to those who showed no improvement in sleep (41 vs. 48, respectively).

The researchers noted that only six of the young people reported a worsening of sleep within 2 weeks of fluoxetine treatment. However, all but one of these patients reported little or no sleep disturbance by the end of the study, they added.

The patients whose insomnia improved after 2 weeks continued to have lower total scores on the CDRS-R at the end of the study, compared to those whose sleep did not improve (27 vs. 34, respectively). This difference remained significant even when sleep was removed from the equation, the researchers noted.

Although the study was limited in part by its open-label design, the findings suggest that children and adolescents with severe and persistent insomnia might gain more from their major depressive disorder treatment if their insomnia is treated when they begin treatment with an antidepressant, the researchers said.

Dr. Isa had no financial conflicts to disclose. Study coauthor Dr. Graham J. Emslie has received research support from numerous companies, including Eli Lilly, Forest, GlaxoSmithKline, and Somerset. This study was funded by a grant from the National Institute of Mental Health.

TORONTO – More than half of children and teens who reported definite insomnia before being treated for depression experienced significant improvement in both their sleep and depression during their first weeks of treatment with fluoxetine, data from clinical trials involving 234 young patients show.

Previous studies have shown that insomnia is one of the most common residual symptoms in depressed youth, said Dr. Ameena Isa of the University of Texas Southwestern Medical Center, Dallas, and colleagues.

To explore the interaction between depression treatment and insomnia, the researchers reviewed combined data from two open-label clinical trials in which children and teens aged 7-18 years were treated with fluoxetine for the 12 weeks. The patients were seen once a week for 4 weeks and then every other week through 12 weeks. A total of 141 patients (60%) had severe insomnia at baseline, 45 (19%) had mild insomnia, and 48 (21%) had no insomnia. Patients with definite insomnia at baseline were significantly more depressed than other patients based on the Children’s Depression Rating Scale, Revised (CDRS-R). Demographic and clinical characteristics were similar among the treatment groups. The mean age was 13 years; 55% were male, and 73% were white.

Within 2 weeks of starting fluoxetine treatment, 53% of the patients who had reported definite insomnia had improved to reporting mild to moderate insomnia. In addition, 64% of those who had reported mild insomnia at baseline no longer complained of insomnia after 2 weeks of treatment.

The findings were presented at the annual meeting of the American Academy of Child and Adolescent Psychiatry.

Patients whose insomnia improved within the first 2 weeks of treatment also had significantly lower depression severity scores on the CDRS-R, compared to those who showed no improvement in sleep (41 vs. 48, respectively).

The researchers noted that only six of the young people reported a worsening of sleep within 2 weeks of fluoxetine treatment. However, all but one of these patients reported little or no sleep disturbance by the end of the study, they added.

The patients whose insomnia improved after 2 weeks continued to have lower total scores on the CDRS-R at the end of the study, compared to those whose sleep did not improve (27 vs. 34, respectively). This difference remained significant even when sleep was removed from the equation, the researchers noted.

Although the study was limited in part by its open-label design, the findings suggest that children and adolescents with severe and persistent insomnia might gain more from their major depressive disorder treatment if their insomnia is treated when they begin treatment with an antidepressant, the researchers said.

Dr. Isa had no financial conflicts to disclose. Study coauthor Dr. Graham J. Emslie has received research support from numerous companies, including Eli Lilly, Forest, GlaxoSmithKline, and Somerset. This study was funded by a grant from the National Institute of Mental Health.

TORONTO – More than half of children and teens who reported definite insomnia before being treated for depression experienced significant improvement in both their sleep and depression during their first weeks of treatment with fluoxetine, data from clinical trials involving 234 young patients show.

Previous studies have shown that insomnia is one of the most common residual symptoms in depressed youth, said Dr. Ameena Isa of the University of Texas Southwestern Medical Center, Dallas, and colleagues.

To explore the interaction between depression treatment and insomnia, the researchers reviewed combined data from two open-label clinical trials in which children and teens aged 7-18 years were treated with fluoxetine for the 12 weeks. The patients were seen once a week for 4 weeks and then every other week through 12 weeks. A total of 141 patients (60%) had severe insomnia at baseline, 45 (19%) had mild insomnia, and 48 (21%) had no insomnia. Patients with definite insomnia at baseline were significantly more depressed than other patients based on the Children’s Depression Rating Scale, Revised (CDRS-R). Demographic and clinical characteristics were similar among the treatment groups. The mean age was 13 years; 55% were male, and 73% were white.

Within 2 weeks of starting fluoxetine treatment, 53% of the patients who had reported definite insomnia had improved to reporting mild to moderate insomnia. In addition, 64% of those who had reported mild insomnia at baseline no longer complained of insomnia after 2 weeks of treatment.

The findings were presented at the annual meeting of the American Academy of Child and Adolescent Psychiatry.

Patients whose insomnia improved within the first 2 weeks of treatment also had significantly lower depression severity scores on the CDRS-R, compared to those who showed no improvement in sleep (41 vs. 48, respectively).

The researchers noted that only six of the young people reported a worsening of sleep within 2 weeks of fluoxetine treatment. However, all but one of these patients reported little or no sleep disturbance by the end of the study, they added.

The patients whose insomnia improved after 2 weeks continued to have lower total scores on the CDRS-R at the end of the study, compared to those whose sleep did not improve (27 vs. 34, respectively). This difference remained significant even when sleep was removed from the equation, the researchers noted.

Although the study was limited in part by its open-label design, the findings suggest that children and adolescents with severe and persistent insomnia might gain more from their major depressive disorder treatment if their insomnia is treated when they begin treatment with an antidepressant, the researchers said.

Dr. Isa had no financial conflicts to disclose. Study coauthor Dr. Graham J. Emslie has received research support from numerous companies, including Eli Lilly, Forest, GlaxoSmithKline, and Somerset. This study was funded by a grant from the National Institute of Mental Health.

TORONTO – Young children who have daily temper tantrums are significantly more likely to have behavioral and emotional problems than are children who have tantrums weekly or less than weekly, a study of 1,478 children has shown.

Previous studies have found that about 70% of young children have temper tantrums. The data also have shown that the number and nature of the tantrums can differ between children with psychopathology and healthy children, said Dr. Heide Hullsiek of the University of Connecticut Health Center, Farmington, and her colleagues.

To determine which characteristics of temper tantrums might be clinically significant, the researchers recruited 751 boys and 727 girls from pediatric primary care settings in Chicago. About one-third of the children were white, one-third were black, and one-third were Hispanic. The children were aged 3-5 years.

Parents completed the Multidimensional Assessment of Preschool Disruptive Behavior (MAP-DB), which includes an assessment of temper loss, aggression, noncompliance, and low concern for others. Anxiety was measured using parents’ responses to the Separation Distress and General Anxiety Subscales of the Infant-Toddler Social and Emotional Assessment.

About 79% of children with daily tantrums related to noncompliance had additional behavioral problems, compared with 20% of children with weekly tantrums, and 1% of children with less than weekly tantrums. In addition, behavioral and emotional problems were significantly associated with a greater frequency of temper tantrums related to aggression, noncompliance, a low concern for others, general anxiety, and separation distress.

Overall, high levels of behavioral problems were significantly more likely among children with daily tantrums, compared with those with either weekly tantrums or less than weekly tantrums. "Interestingly, although problems were much less prevalent in the weekly tantrum group, they were still significantly more common compared to the less than weekly group," Dr. Hullsiek noted.

The frequency of tantrums decreased with age, but no significant difference was found in the frequency of tantrums per week between boys and girls. In addition, neither poverty status nor maternal education had a significant impact on the frequency of tantrums.

From an early detection perspective, daily temper tantrums warrant further evaluation from providers, the study results indicated. Areas for further investigation include the association between daily temper tantrums and developmental patterns, and signs of emotional dysregulation, Dr. Hullsiek added.

Dr. Hullsiek said she had no relevant financial disclosures. The study was funded by a grant from the National Institute of Mental Health.

TORONTO – Young children who have daily temper tantrums are significantly more likely to have behavioral and emotional problems than are children who have tantrums weekly or less than weekly, a study of 1,478 children has shown.

Previous studies have found that about 70% of young children have temper tantrums. The data also have shown that the number and nature of the tantrums can differ between children with psychopathology and healthy children, said Dr. Heide Hullsiek of the University of Connecticut Health Center, Farmington, and her colleagues.

To determine which characteristics of temper tantrums might be clinically significant, the researchers recruited 751 boys and 727 girls from pediatric primary care settings in Chicago. About one-third of the children were white, one-third were black, and one-third were Hispanic. The children were aged 3-5 years.

Parents completed the Multidimensional Assessment of Preschool Disruptive Behavior (MAP-DB), which includes an assessment of temper loss, aggression, noncompliance, and low concern for others. Anxiety was measured using parents’ responses to the Separation Distress and General Anxiety Subscales of the Infant-Toddler Social and Emotional Assessment.

About 79% of children with daily tantrums related to noncompliance had additional behavioral problems, compared with 20% of children with weekly tantrums, and 1% of children with less than weekly tantrums. In addition, behavioral and emotional problems were significantly associated with a greater frequency of temper tantrums related to aggression, noncompliance, a low concern for others, general anxiety, and separation distress.

Overall, high levels of behavioral problems were significantly more likely among children with daily tantrums, compared with those with either weekly tantrums or less than weekly tantrums. "Interestingly, although problems were much less prevalent in the weekly tantrum group, they were still significantly more common compared to the less than weekly group," Dr. Hullsiek noted.

The frequency of tantrums decreased with age, but no significant difference was found in the frequency of tantrums per week between boys and girls. In addition, neither poverty status nor maternal education had a significant impact on the frequency of tantrums.

From an early detection perspective, daily temper tantrums warrant further evaluation from providers, the study results indicated. Areas for further investigation include the association between daily temper tantrums and developmental patterns, and signs of emotional dysregulation, Dr. Hullsiek added.

Dr. Hullsiek said she had no relevant financial disclosures. The study was funded by a grant from the National Institute of Mental Health.

TORONTO – Young children who have daily temper tantrums are significantly more likely to have behavioral and emotional problems than are children who have tantrums weekly or less than weekly, a study of 1,478 children has shown.

Previous studies have found that about 70% of young children have temper tantrums. The data also have shown that the number and nature of the tantrums can differ between children with psychopathology and healthy children, said Dr. Heide Hullsiek of the University of Connecticut Health Center, Farmington, and her colleagues.

To determine which characteristics of temper tantrums might be clinically significant, the researchers recruited 751 boys and 727 girls from pediatric primary care settings in Chicago. About one-third of the children were white, one-third were black, and one-third were Hispanic. The children were aged 3-5 years.

Parents completed the Multidimensional Assessment of Preschool Disruptive Behavior (MAP-DB), which includes an assessment of temper loss, aggression, noncompliance, and low concern for others. Anxiety was measured using parents’ responses to the Separation Distress and General Anxiety Subscales of the Infant-Toddler Social and Emotional Assessment.

About 79% of children with daily tantrums related to noncompliance had additional behavioral problems, compared with 20% of children with weekly tantrums, and 1% of children with less than weekly tantrums. In addition, behavioral and emotional problems were significantly associated with a greater frequency of temper tantrums related to aggression, noncompliance, a low concern for others, general anxiety, and separation distress.

Overall, high levels of behavioral problems were significantly more likely among children with daily tantrums, compared with those with either weekly tantrums or less than weekly tantrums. "Interestingly, although problems were much less prevalent in the weekly tantrum group, they were still significantly more common compared to the less than weekly group," Dr. Hullsiek noted.

The frequency of tantrums decreased with age, but no significant difference was found in the frequency of tantrums per week between boys and girls. In addition, neither poverty status nor maternal education had a significant impact on the frequency of tantrums.

From an early detection perspective, daily temper tantrums warrant further evaluation from providers, the study results indicated. Areas for further investigation include the association between daily temper tantrums and developmental patterns, and signs of emotional dysregulation, Dr. Hullsiek added.

Dr. Hullsiek said she had no relevant financial disclosures. The study was funded by a grant from the National Institute of Mental Health.

NATIONAL HARBOR, MD. – Extended-release gabapentin at daily doses of either 1,200 mg or 1,800 mg significantly reduced the number and severity of hot flashes and significantly improved sleep problems, compared with a placebo, in postmenopausal women.

Currently, hormone therapy is the only approved treatment for hot flashes in North America and Europe, according to Dr. Mira Baron of Rapid Medical Research Inc., Cleveland, and colleagues.

In previous studies, gabapentin has shown effectiveness in reducing the frequency and severity of hot flashes, but its short half-life may limit its usefulness, the researchers said. However, an extended-release, once-daily dose of gabapentin was approved by the U.S. Food and Drug Administration in February 2011 to treat postherpetic neuralgia, she said at the annual meeting of the North American Menopause Society.

In Breeze 2, a phase III, double-blind, placebo-controlled trial conducted at 45 sites in the United States, Dr. Baron and colleagues compared the effectiveness of 1,200 mg of extended-release gabapentin once daily vs. 1,800 mg twice daily (600 mg in the morning and 1,200 mg at night) on the frequency and severity of hot flashes.

A total of 559 women completed 12 weeks of treatment and were included in the intent-to-treat population; 190 were randomized to once-daily treatment, 186 were randomized to twice-daily treatment, and 183 were randomized to a placebo. Participants used an electronic diary to record the frequency and severity of their hot flashes during the study.

The average age of the patients was 53 years, and the mean age at menopause was 44 years. The eligible participants reported at least seven moderate to severe hot flashes per day during a 1-week baseline period before they started the study.

Overall, the median daily number of hot flashes dropped significantly after 12 weeks of treatment in both treatment groups, compared with the placebo group. The number of daily hot flashes dropped to three in the placebo group and to two in the two treatment groups.

In addition, the severity of the hot flashes decreased significantly from baseline in both treatment groups, compared with the placebo group. The mean change in vasomotor severity score, compared with baseline, was –0.9 in the once-daily group, –0.8 in the twice-daily group, and –0.6 in the placebo group. The reduction in the severity of vasomotor symptoms was significant for both treatment doses, compared with the placebo. "However, the 1,800-mg dosage yielded more significant changes than the 1,200-mg dosage," the researchers noted.

In a second study, Dr. Risa Kagan of the Alta Bates Summit Medical Center in Berkeley, Calif., and colleagues studied the effectiveness of extended-release gabapentin on improving the sleep problems commonly reported by postmenopausal women.

The researchers compared the effects of extended-release gabapentin vs. a placebo on sleep problems in postmenopausal women using data from the Breeze 1 study, which was a phase III, double-blind, placebo-controlled trial conducted at 48 sites in the United States. A total of 531 women made up the intent-to-treat population, and they were randomized to gabapentin 1,200 mg once daily, to 1,800 mg twice daily (600 mg in the morning and 1,200 mg at night), or to a placebo.

Overall, global scores on the PSQI (Pittsburgh Sleep Quality Index) improved significantly with both gabapentin doses, compared with the placebo, at three separate time points.

After 4 weeks, the mean difference in the global PSQI scores was –1.74 in the once-daily group and –1.68 in the twice-daily group. After 12 weeks, the mean differences in the global PSQI scores for the two treatment groups, compared with placebo, were –1.16 and –0.80, respectively. After 24 weeks, the mean differences in the global PSQI scores for the two treatment groups, compared with placebo, were –0.77 and –0.93, respectively.

"The largest differences between the active arms and the placebo arm were observed at week 4," the researchers said. "The decrease in the magnitude of improvement over time likely resulted from the fact that the PSQI instrument requests reporting for the previous 4 weeks." However, the global scores did improve throughout the study, they noted.

No significant difference in daytime dysfunction scores was observed between either of the treatment groups and the placebo group.

Although the drug is not currently approved for this indication, the findings suggest that extended-release gabapentin might have potential as a treatment option for hot flashes and sleep disturbances in postmenopausal women who are reluctant to use hormonal therapies, the researchers said.

The studies were supported by Depomed. Dr. Baron had no personal financial conflicts to disclose. One of the study coauthors on her study is an employee of Depomed. Dr. Kagan disclosed serving as a consultant or advisory board member for multiple companies, including Amgen, Bionovo, Depomed, Merck, Pfizer, and Shionogi. She disclosed receiving research support from Bionovo, BioSante Pharmaceuticals, Boehringer-Ingelheim, Depomed, and Pfizer, and serving on the speakers bureau for Amgen, Novogyne, and Novo Nordisk.

NATIONAL HARBOR, MD. – Extended-release gabapentin at daily doses of either 1,200 mg or 1,800 mg significantly reduced the number and severity of hot flashes and significantly improved sleep problems, compared with a placebo, in postmenopausal women.

Currently, hormone therapy is the only approved treatment for hot flashes in North America and Europe, according to Dr. Mira Baron of Rapid Medical Research Inc., Cleveland, and colleagues.

In previous studies, gabapentin has shown effectiveness in reducing the frequency and severity of hot flashes, but its short half-life may limit its usefulness, the researchers said. However, an extended-release, once-daily dose of gabapentin was approved by the U.S. Food and Drug Administration in February 2011 to treat postherpetic neuralgia, she said at the annual meeting of the North American Menopause Society.

In Breeze 2, a phase III, double-blind, placebo-controlled trial conducted at 45 sites in the United States, Dr. Baron and colleagues compared the effectiveness of 1,200 mg of extended-release gabapentin once daily vs. 1,800 mg twice daily (600 mg in the morning and 1,200 mg at night) on the frequency and severity of hot flashes.

A total of 559 women completed 12 weeks of treatment and were included in the intent-to-treat population; 190 were randomized to once-daily treatment, 186 were randomized to twice-daily treatment, and 183 were randomized to a placebo. Participants used an electronic diary to record the frequency and severity of their hot flashes during the study.

The average age of the patients was 53 years, and the mean age at menopause was 44 years. The eligible participants reported at least seven moderate to severe hot flashes per day during a 1-week baseline period before they started the study.

Overall, the median daily number of hot flashes dropped significantly after 12 weeks of treatment in both treatment groups, compared with the placebo group. The number of daily hot flashes dropped to three in the placebo group and to two in the two treatment groups.

In addition, the severity of the hot flashes decreased significantly from baseline in both treatment groups, compared with the placebo group. The mean change in vasomotor severity score, compared with baseline, was –0.9 in the once-daily group, –0.8 in the twice-daily group, and –0.6 in the placebo group. The reduction in the severity of vasomotor symptoms was significant for both treatment doses, compared with the placebo. "However, the 1,800-mg dosage yielded more significant changes than the 1,200-mg dosage," the researchers noted.

In a second study, Dr. Risa Kagan of the Alta Bates Summit Medical Center in Berkeley, Calif., and colleagues studied the effectiveness of extended-release gabapentin on improving the sleep problems commonly reported by postmenopausal women.

The researchers compared the effects of extended-release gabapentin vs. a placebo on sleep problems in postmenopausal women using data from the Breeze 1 study, which was a phase III, double-blind, placebo-controlled trial conducted at 48 sites in the United States. A total of 531 women made up the intent-to-treat population, and they were randomized to gabapentin 1,200 mg once daily, to 1,800 mg twice daily (600 mg in the morning and 1,200 mg at night), or to a placebo.

Overall, global scores on the PSQI (Pittsburgh Sleep Quality Index) improved significantly with both gabapentin doses, compared with the placebo, at three separate time points.

After 4 weeks, the mean difference in the global PSQI scores was –1.74 in the once-daily group and –1.68 in the twice-daily group. After 12 weeks, the mean differences in the global PSQI scores for the two treatment groups, compared with placebo, were –1.16 and –0.80, respectively. After 24 weeks, the mean differences in the global PSQI scores for the two treatment groups, compared with placebo, were –0.77 and –0.93, respectively.

"The largest differences between the active arms and the placebo arm were observed at week 4," the researchers said. "The decrease in the magnitude of improvement over time likely resulted from the fact that the PSQI instrument requests reporting for the previous 4 weeks." However, the global scores did improve throughout the study, they noted.

No significant difference in daytime dysfunction scores was observed between either of the treatment groups and the placebo group.

Although the drug is not currently approved for this indication, the findings suggest that extended-release gabapentin might have potential as a treatment option for hot flashes and sleep disturbances in postmenopausal women who are reluctant to use hormonal therapies, the researchers said.

The studies were supported by Depomed. Dr. Baron had no personal financial conflicts to disclose. One of the study coauthors on her study is an employee of Depomed. Dr. Kagan disclosed serving as a consultant or advisory board member for multiple companies, including Amgen, Bionovo, Depomed, Merck, Pfizer, and Shionogi. She disclosed receiving research support from Bionovo, BioSante Pharmaceuticals, Boehringer-Ingelheim, Depomed, and Pfizer, and serving on the speakers bureau for Amgen, Novogyne, and Novo Nordisk.

NATIONAL HARBOR, MD. – Extended-release gabapentin at daily doses of either 1,200 mg or 1,800 mg significantly reduced the number and severity of hot flashes and significantly improved sleep problems, compared with a placebo, in postmenopausal women.

Currently, hormone therapy is the only approved treatment for hot flashes in North America and Europe, according to Dr. Mira Baron of Rapid Medical Research Inc., Cleveland, and colleagues.

In previous studies, gabapentin has shown effectiveness in reducing the frequency and severity of hot flashes, but its short half-life may limit its usefulness, the researchers said. However, an extended-release, once-daily dose of gabapentin was approved by the U.S. Food and Drug Administration in February 2011 to treat postherpetic neuralgia, she said at the annual meeting of the North American Menopause Society.

In Breeze 2, a phase III, double-blind, placebo-controlled trial conducted at 45 sites in the United States, Dr. Baron and colleagues compared the effectiveness of 1,200 mg of extended-release gabapentin once daily vs. 1,800 mg twice daily (600 mg in the morning and 1,200 mg at night) on the frequency and severity of hot flashes.

A total of 559 women completed 12 weeks of treatment and were included in the intent-to-treat population; 190 were randomized to once-daily treatment, 186 were randomized to twice-daily treatment, and 183 were randomized to a placebo. Participants used an electronic diary to record the frequency and severity of their hot flashes during the study.

The average age of the patients was 53 years, and the mean age at menopause was 44 years. The eligible participants reported at least seven moderate to severe hot flashes per day during a 1-week baseline period before they started the study.

Overall, the median daily number of hot flashes dropped significantly after 12 weeks of treatment in both treatment groups, compared with the placebo group. The number of daily hot flashes dropped to three in the placebo group and to two in the two treatment groups.

In addition, the severity of the hot flashes decreased significantly from baseline in both treatment groups, compared with the placebo group. The mean change in vasomotor severity score, compared with baseline, was –0.9 in the once-daily group, –0.8 in the twice-daily group, and –0.6 in the placebo group. The reduction in the severity of vasomotor symptoms was significant for both treatment doses, compared with the placebo. "However, the 1,800-mg dosage yielded more significant changes than the 1,200-mg dosage," the researchers noted.

In a second study, Dr. Risa Kagan of the Alta Bates Summit Medical Center in Berkeley, Calif., and colleagues studied the effectiveness of extended-release gabapentin on improving the sleep problems commonly reported by postmenopausal women.

The researchers compared the effects of extended-release gabapentin vs. a placebo on sleep problems in postmenopausal women using data from the Breeze 1 study, which was a phase III, double-blind, placebo-controlled trial conducted at 48 sites in the United States. A total of 531 women made up the intent-to-treat population, and they were randomized to gabapentin 1,200 mg once daily, to 1,800 mg twice daily (600 mg in the morning and 1,200 mg at night), or to a placebo.

Overall, global scores on the PSQI (Pittsburgh Sleep Quality Index) improved significantly with both gabapentin doses, compared with the placebo, at three separate time points.

After 4 weeks, the mean difference in the global PSQI scores was –1.74 in the once-daily group and –1.68 in the twice-daily group. After 12 weeks, the mean differences in the global PSQI scores for the two treatment groups, compared with placebo, were –1.16 and –0.80, respectively. After 24 weeks, the mean differences in the global PSQI scores for the two treatment groups, compared with placebo, were –0.77 and –0.93, respectively.

"The largest differences between the active arms and the placebo arm were observed at week 4," the researchers said. "The decrease in the magnitude of improvement over time likely resulted from the fact that the PSQI instrument requests reporting for the previous 4 weeks." However, the global scores did improve throughout the study, they noted.

No significant difference in daytime dysfunction scores was observed between either of the treatment groups and the placebo group.

Although the drug is not currently approved for this indication, the findings suggest that extended-release gabapentin might have potential as a treatment option for hot flashes and sleep disturbances in postmenopausal women who are reluctant to use hormonal therapies, the researchers said.

The studies were supported by Depomed. Dr. Baron had no personal financial conflicts to disclose. One of the study coauthors on her study is an employee of Depomed. Dr. Kagan disclosed serving as a consultant or advisory board member for multiple companies, including Amgen, Bionovo, Depomed, Merck, Pfizer, and Shionogi. She disclosed receiving research support from Bionovo, BioSante Pharmaceuticals, Boehringer-Ingelheim, Depomed, and Pfizer, and serving on the speakers bureau for Amgen, Novogyne, and Novo Nordisk.

NATIONAL HARBOR, MD.  – A novel selective estrogen–receptor modulator called ospemifene was significantly more effective than placebo for reducing symptoms of vaginal dryness and dyspareunia in a study of 919 postmenopausal women.

"Despite its negative impact on sexual function, psychosocial well-being, and partner relationships, vulvovaginal atrophy (VVA) frequently goes untreated," said Dr. David Portman of the Columbus (Ohio) Center for Women’s Health Research.

Only estrogen-based treatments have been approved in the United States to treat VVA in postmenopausal women, but concerns about the effects of estrogen on breast and endometrial tissue have prompted doctors and patients to seek alternatives, Dr. Portman said at the annual meeting of the North American Menopause Society.

"Despite its negative impact on sexual function, psychosocial well-being, and partner relationships, vulvovaginal atrophy (VVA) frequently goes untreated."

"We do need to find alternatives because many of our patients still have concerns even with local estrogen," he emphasized.

Ospemifene (OSP), a selective estrogen–receptor modulator (SERM) – also referred to as a nonsteroidal estrogen–receptor agonist/antagonist – is distinct from other SERMs because its estrogenic activity occurs on the vaginal epithelium, "but not on the endometrium," said Dr. Portman.

Previous studies have shown that ospemifene is well tolerated, with a favorable pharmacologic profile in postmenopausal women with VVA, he added.

In a 12-week randomized, double-blind, placebo-controlled, phase III parallel group study, Dr. Portman and his colleagues assessed the efficacy, safety, and tolerability of ospemifene for women with moderate to severe vaginal dryness or moderate to severe dyspareunia. VVA and dyspareunia symptoms and severity were self-reported, and use of a nonhormonal vaginal lubricant was permitted as needed. Demographic characteristics were similar between the two groups.

The women ranged from 40 to 80 years of age at baseline. Those with a body mass index of 37 kg/m² or greater were excluded, as were those with clinically significant abnormal gynecologic findings other than vaginal atrophy and those using hormonal medications or other products with possible estrogenic or antiestrogenic effects within a timeframe too close to the study screening.

A total of 314 postmenopausal women who reported vaginal dryness as their primary symptom were randomized to 60 mg of OSP orally each morning or a placebo.

In the intent-to-treat population, the change in the vaginal dryness severity score improved in the OSP group vs. the placebo group (–1.3 vs. –1.1). In addition, the percentages of superficial and parabasal cells were significantly different in the OSP group vs. the placebo group (12% vs. 3% and –32% vs. –4%, respectively). Measuring these types of cells indicates changes in the vaginal microflora, which have been shown to affect vaginal dryness and pain.

The mean change in vaginal pH was –1.01 in the OSP group, compared with –0.25 in the placebo group, respectively.

An additional 605 women who reported dyspareunia as their primary symptom were randomized to 60 mg OSP orally each morning or a placebo.

In the intent-to-treat population, the change in the dyspareunia severity score improved in the OSP group vs. the placebo group (–1.5 vs. –1.2, P = .0001), a significant difference. In addition, the percentages of superficial cells and parabasal cells were significantly different in the OSP vs. the placebo groups (12% vs. 2% and –40% vs. 0%, respectively). The mean change in vaginal pH also differed significantly between the OSP and placebo groups (–1.0 vs. –0.06, respectively).

Overall, ospemifene had "a very clean safety profile," Dr. Portman said. The total number of treatment-emergent adverse events was not significantly different between the OSP and placebo groups (290 vs. 232). A total of 122 treatment-related adverse events occurred in the OSP group, compared with 62 in the placebo group, but the number of serious adverse events and severe adverse events were similar between the groups (6 vs. 7 and 28 vs. 29, respectively). The most common treatment-emergent adverse events in the OSP group were urinary tract infection, (8%), hot flashes (7%), and vaginal discharge (5%).

No deaths, myocardial infarctions, and or breast cancer cases were reported in any of the patients during the study period.

While not yet approved for VVA, "this investigational SERM has the potential to be an efficacious, nonestrogen oral prescription therapy for this prevalent, bothersome, and undertreated condition," Dr. Portman said.

The study was sponsored in part by Shionogi, which develops and markets ospemifene, and several coinvestigators were Shionogi employees. Dr. Portman has received consulting fees, honoraria, and/or grant support from multiple companies including Shionogi, Bayer, Boehringer Ingelheim, Teva, Warner Chilcott, and Watson Pharmaceuticals.

NATIONAL HARBOR, MD.  – A novel selective estrogen–receptor modulator called ospemifene was significantly more effective than placebo for reducing symptoms of vaginal dryness and dyspareunia in a study of 919 postmenopausal women.

"Despite its negative impact on sexual function, psychosocial well-being, and partner relationships, vulvovaginal atrophy (VVA) frequently goes untreated," said Dr. David Portman of the Columbus (Ohio) Center for Women’s Health Research.

Only estrogen-based treatments have been approved in the United States to treat VVA in postmenopausal women, but concerns about the effects of estrogen on breast and endometrial tissue have prompted doctors and patients to seek alternatives, Dr. Portman said at the annual meeting of the North American Menopause Society.

"Despite its negative impact on sexual function, psychosocial well-being, and partner relationships, vulvovaginal atrophy (VVA) frequently goes untreated."

"We do need to find alternatives because many of our patients still have concerns even with local estrogen," he emphasized.

Ospemifene (OSP), a selective estrogen–receptor modulator (SERM) – also referred to as a nonsteroidal estrogen–receptor agonist/antagonist – is distinct from other SERMs because its estrogenic activity occurs on the vaginal epithelium, "but not on the endometrium," said Dr. Portman.

Previous studies have shown that ospemifene is well tolerated, with a favorable pharmacologic profile in postmenopausal women with VVA, he added.

In a 12-week randomized, double-blind, placebo-controlled, phase III parallel group study, Dr. Portman and his colleagues assessed the efficacy, safety, and tolerability of ospemifene for women with moderate to severe vaginal dryness or moderate to severe dyspareunia. VVA and dyspareunia symptoms and severity were self-reported, and use of a nonhormonal vaginal lubricant was permitted as needed. Demographic characteristics were similar between the two groups.

The women ranged from 40 to 80 years of age at baseline. Those with a body mass index of 37 kg/m² or greater were excluded, as were those with clinically significant abnormal gynecologic findings other than vaginal atrophy and those using hormonal medications or other products with possible estrogenic or antiestrogenic effects within a timeframe too close to the study screening.

A total of 314 postmenopausal women who reported vaginal dryness as their primary symptom were randomized to 60 mg of OSP orally each morning or a placebo.

In the intent-to-treat population, the change in the vaginal dryness severity score improved in the OSP group vs. the placebo group (–1.3 vs. –1.1). In addition, the percentages of superficial and parabasal cells were significantly different in the OSP group vs. the placebo group (12% vs. 3% and –32% vs. –4%, respectively). Measuring these types of cells indicates changes in the vaginal microflora, which have been shown to affect vaginal dryness and pain.

The mean change in vaginal pH was –1.01 in the OSP group, compared with –0.25 in the placebo group, respectively.

An additional 605 women who reported dyspareunia as their primary symptom were randomized to 60 mg OSP orally each morning or a placebo.

In the intent-to-treat population, the change in the dyspareunia severity score improved in the OSP group vs. the placebo group (–1.5 vs. –1.2, P = .0001), a significant difference. In addition, the percentages of superficial cells and parabasal cells were significantly different in the OSP vs. the placebo groups (12% vs. 2% and –40% vs. 0%, respectively). The mean change in vaginal pH also differed significantly between the OSP and placebo groups (–1.0 vs. –0.06, respectively).

Overall, ospemifene had "a very clean safety profile," Dr. Portman said. The total number of treatment-emergent adverse events was not significantly different between the OSP and placebo groups (290 vs. 232). A total of 122 treatment-related adverse events occurred in the OSP group, compared with 62 in the placebo group, but the number of serious adverse events and severe adverse events were similar between the groups (6 vs. 7 and 28 vs. 29, respectively). The most common treatment-emergent adverse events in the OSP group were urinary tract infection, (8%), hot flashes (7%), and vaginal discharge (5%).

No deaths, myocardial infarctions, and or breast cancer cases were reported in any of the patients during the study period.

While not yet approved for VVA, "this investigational SERM has the potential to be an efficacious, nonestrogen oral prescription therapy for this prevalent, bothersome, and undertreated condition," Dr. Portman said.

The study was sponsored in part by Shionogi, which develops and markets ospemifene, and several coinvestigators were Shionogi employees. Dr. Portman has received consulting fees, honoraria, and/or grant support from multiple companies including Shionogi, Bayer, Boehringer Ingelheim, Teva, Warner Chilcott, and Watson Pharmaceuticals.

NATIONAL HARBOR, MD.  – A novel selective estrogen–receptor modulator called ospemifene was significantly more effective than placebo for reducing symptoms of vaginal dryness and dyspareunia in a study of 919 postmenopausal women.

"Despite its negative impact on sexual function, psychosocial well-being, and partner relationships, vulvovaginal atrophy (VVA) frequently goes untreated," said Dr. David Portman of the Columbus (Ohio) Center for Women’s Health Research.

Only estrogen-based treatments have been approved in the United States to treat VVA in postmenopausal women, but concerns about the effects of estrogen on breast and endometrial tissue have prompted doctors and patients to seek alternatives, Dr. Portman said at the annual meeting of the North American Menopause Society.

"Despite its negative impact on sexual function, psychosocial well-being, and partner relationships, vulvovaginal atrophy (VVA) frequently goes untreated."

"We do need to find alternatives because many of our patients still have concerns even with local estrogen," he emphasized.

Ospemifene (OSP), a selective estrogen–receptor modulator (SERM) – also referred to as a nonsteroidal estrogen–receptor agonist/antagonist – is distinct from other SERMs because its estrogenic activity occurs on the vaginal epithelium, "but not on the endometrium," said Dr. Portman.

Previous studies have shown that ospemifene is well tolerated, with a favorable pharmacologic profile in postmenopausal women with VVA, he added.

In a 12-week randomized, double-blind, placebo-controlled, phase III parallel group study, Dr. Portman and his colleagues assessed the efficacy, safety, and tolerability of ospemifene for women with moderate to severe vaginal dryness or moderate to severe dyspareunia. VVA and dyspareunia symptoms and severity were self-reported, and use of a nonhormonal vaginal lubricant was permitted as needed. Demographic characteristics were similar between the two groups.

The women ranged from 40 to 80 years of age at baseline. Those with a body mass index of 37 kg/m² or greater were excluded, as were those with clinically significant abnormal gynecologic findings other than vaginal atrophy and those using hormonal medications or other products with possible estrogenic or antiestrogenic effects within a timeframe too close to the study screening.

A total of 314 postmenopausal women who reported vaginal dryness as their primary symptom were randomized to 60 mg of OSP orally each morning or a placebo.

In the intent-to-treat population, the change in the vaginal dryness severity score improved in the OSP group vs. the placebo group (–1.3 vs. –1.1). In addition, the percentages of superficial and parabasal cells were significantly different in the OSP group vs. the placebo group (12% vs. 3% and –32% vs. –4%, respectively). Measuring these types of cells indicates changes in the vaginal microflora, which have been shown to affect vaginal dryness and pain.

The mean change in vaginal pH was –1.01 in the OSP group, compared with –0.25 in the placebo group, respectively.

An additional 605 women who reported dyspareunia as their primary symptom were randomized to 60 mg OSP orally each morning or a placebo.

In the intent-to-treat population, the change in the dyspareunia severity score improved in the OSP group vs. the placebo group (–1.5 vs. –1.2, P = .0001), a significant difference. In addition, the percentages of superficial cells and parabasal cells were significantly different in the OSP vs. the placebo groups (12% vs. 2% and –40% vs. 0%, respectively). The mean change in vaginal pH also differed significantly between the OSP and placebo groups (–1.0 vs. –0.06, respectively).

Overall, ospemifene had "a very clean safety profile," Dr. Portman said. The total number of treatment-emergent adverse events was not significantly different between the OSP and placebo groups (290 vs. 232). A total of 122 treatment-related adverse events occurred in the OSP group, compared with 62 in the placebo group, but the number of serious adverse events and severe adverse events were similar between the groups (6 vs. 7 and 28 vs. 29, respectively). The most common treatment-emergent adverse events in the OSP group were urinary tract infection, (8%), hot flashes (7%), and vaginal discharge (5%).

No deaths, myocardial infarctions, and or breast cancer cases were reported in any of the patients during the study period.

While not yet approved for VVA, "this investigational SERM has the potential to be an efficacious, nonestrogen oral prescription therapy for this prevalent, bothersome, and undertreated condition," Dr. Portman said.

The study was sponsored in part by Shionogi, which develops and markets ospemifene, and several coinvestigators were Shionogi employees. Dr. Portman has received consulting fees, honoraria, and/or grant support from multiple companies including Shionogi, Bayer, Boehringer Ingelheim, Teva, Warner Chilcott, and Watson Pharmaceuticals.

NATIONAL HARBOR, MD. – Women who had a longer exposure to estradiol before menopause had a significantly lower risk of developing depression during the menopausal transition, based on data from 1,282 women.

"It is unclear why some women are at increased risk of depression while undergoing the menopausal transition," said Dr. Wendy Marsh of the University of Massachusetts, Worcester.

Data from previous studies have suggested that endocrine factors in general, and estrogen levels in particular, may contribute to a woman’s susceptibility to depression during menopause, she noted.

Dr. Marsh and her colleagues reviewed data from 1,282 women participating in the Study of Women's Health Across the Nation (SWAN), a multisite, long-term epidemiologic study of women during midlife and through the menopausal transition. The women were premenopausal when they entered the study.

"It is unclear why some women are at increased risk of depression while undergoing the menopausal transition."

Each additional year of premenopausal estradiol exposure conveyed a 15% reduction in risk of experiencing depression during menopause (hazard ratio, 0.85) after confounding factors including premenopausal depression, baseline age, smoking status, education, antidepressant use, ethnicity, and length of time in the study were controlled for.

The average duration of estradiol exposure was 36 years. Longer exposure was significantly associated with a lower risk of having a score of 16 or higher on the Center for Epidemiologic Studies Depression (CES-D) scale.

Estradiol has been shown to affect mood regulation, Dr. Marsh noted, but "it is unknown how such a modulatory effect during premenopausal years would lead to a protective effect against depression during the menopausal transition," she said.

Although the data are preliminary, they may provide a foundation for further research that may help clinicians identify and manage women at increased risk for depression during menopause.

"Additional analyses will further qualify and quantify other variables related to estrogen exposure, including use of oral contraceptives, pregnancies, and lactation," Dr. Marsh said at the annual meeting of the North American Menopause Society.

The Study of Women’s Health Across the Nation is supported by grants from the National Institutes of Health, the U.S. Department of Health and Human Services, the National Institute of Nursing Research, and the NIH Office of Research on Women’s Health. Dr. Marsh reported having no relevant financial disclosures.

NATIONAL HARBOR, MD. – Women who had a longer exposure to estradiol before menopause had a significantly lower risk of developing depression during the menopausal transition, based on data from 1,282 women.

"It is unclear why some women are at increased risk of depression while undergoing the menopausal transition," said Dr. Wendy Marsh of the University of Massachusetts, Worcester.

Data from previous studies have suggested that endocrine factors in general, and estrogen levels in particular, may contribute to a woman’s susceptibility to depression during menopause, she noted.

Dr. Marsh and her colleagues reviewed data from 1,282 women participating in the Study of Women's Health Across the Nation (SWAN), a multisite, long-term epidemiologic study of women during midlife and through the menopausal transition. The women were premenopausal when they entered the study.

"It is unclear why some women are at increased risk of depression while undergoing the menopausal transition."

Each additional year of premenopausal estradiol exposure conveyed a 15% reduction in risk of experiencing depression during menopause (hazard ratio, 0.85) after confounding factors including premenopausal depression, baseline age, smoking status, education, antidepressant use, ethnicity, and length of time in the study were controlled for.

The average duration of estradiol exposure was 36 years. Longer exposure was significantly associated with a lower risk of having a score of 16 or higher on the Center for Epidemiologic Studies Depression (CES-D) scale.

Estradiol has been shown to affect mood regulation, Dr. Marsh noted, but "it is unknown how such a modulatory effect during premenopausal years would lead to a protective effect against depression during the menopausal transition," she said.

Although the data are preliminary, they may provide a foundation for further research that may help clinicians identify and manage women at increased risk for depression during menopause.

"Additional analyses will further qualify and quantify other variables related to estrogen exposure, including use of oral contraceptives, pregnancies, and lactation," Dr. Marsh said at the annual meeting of the North American Menopause Society.

The Study of Women’s Health Across the Nation is supported by grants from the National Institutes of Health, the U.S. Department of Health and Human Services, the National Institute of Nursing Research, and the NIH Office of Research on Women’s Health. Dr. Marsh reported having no relevant financial disclosures.

NATIONAL HARBOR, MD. – Women who had a longer exposure to estradiol before menopause had a significantly lower risk of developing depression during the menopausal transition, based on data from 1,282 women.

"It is unclear why some women are at increased risk of depression while undergoing the menopausal transition," said Dr. Wendy Marsh of the University of Massachusetts, Worcester.

Data from previous studies have suggested that endocrine factors in general, and estrogen levels in particular, may contribute to a woman’s susceptibility to depression during menopause, she noted.

Dr. Marsh and her colleagues reviewed data from 1,282 women participating in the Study of Women's Health Across the Nation (SWAN), a multisite, long-term epidemiologic study of women during midlife and through the menopausal transition. The women were premenopausal when they entered the study.

"It is unclear why some women are at increased risk of depression while undergoing the menopausal transition."

Each additional year of premenopausal estradiol exposure conveyed a 15% reduction in risk of experiencing depression during menopause (hazard ratio, 0.85) after confounding factors including premenopausal depression, baseline age, smoking status, education, antidepressant use, ethnicity, and length of time in the study were controlled for.

The average duration of estradiol exposure was 36 years. Longer exposure was significantly associated with a lower risk of having a score of 16 or higher on the Center for Epidemiologic Studies Depression (CES-D) scale.

Estradiol has been shown to affect mood regulation, Dr. Marsh noted, but "it is unknown how such a modulatory effect during premenopausal years would lead to a protective effect against depression during the menopausal transition," she said.

Although the data are preliminary, they may provide a foundation for further research that may help clinicians identify and manage women at increased risk for depression during menopause.

"Additional analyses will further qualify and quantify other variables related to estrogen exposure, including use of oral contraceptives, pregnancies, and lactation," Dr. Marsh said at the annual meeting of the North American Menopause Society.

The Study of Women’s Health Across the Nation is supported by grants from the National Institutes of Health, the U.S. Department of Health and Human Services, the National Institute of Nursing Research, and the NIH Office of Research on Women’s Health. Dr. Marsh reported having no relevant financial disclosures.

Children with Down syndrome can be diagnosed with autism via the autism spectrum disorder criteria from the Diagnostic and Statistical Manual of Mental Disorders, based on results of a cluster analysis of 293 children with Down syndrome.

Previous studies have suggested that autism spectrum disorders (ASD) can’t be effectively diagnosed in children with Down syndrome (DS) because of the cognitive impairment already associated with DS, said Dr. N.Y. Ji of Johns Hopkins University, Baltimore.

In this study, Dr. Ji and colleagues used the Aberrant Behavior Checklist to show that children with both DS and ASD match the DSM criteria for autism diagnoses (J. Intellect. Disabil. Res. 2011 Aug. 30 [doi:10.1111/j.1365-2788.2011.0465.x]).

The researchers assessed more than 1,000 children aged 0-21 years who visited the Down syndrome clinic of the Kennedy Krieger Institute in Baltimore during 1992-2008. They identified 293 children for cluster analysis and used the Aberrant Behavior Checklist–Community (ABC-C) and the Autism Behavior Checklist to identify autism features. For comparison, the researchers also identified children with DS and two other common DS comorbidities: disruptive behavior disorder (DBS) and stereotypic movement disorder (SMD).

Overall, 114 children (39%) met criteria for ASD, 104 (36%) met criteria for DBS, and 43 (15%) had SMD. Another 32 children (11%) did not meet criteria for any coexisting major psychiatric condition in addition to DS.

The findings add to the field of Down syndrome research because they confirm the DSM diagnostic criteria of autism spectrum disorder in children with Down syndrome.

The researchers divided the children into four clusters based on the ABC-C and Autism Behavior Checklist.

Participants in clusters 1 and 4 had lower levels of intellectual functioning than did those in clusters 2 and 3, although there was no significant difference in the median age among the groups, the researchers noted.

In addition, children in cluster 1 had a broad range of behavioral problems, including self-injury and highly disruptive behavior.

Children in cluster 2 had the lowest ABC-C scores and the mildest levels of maladaptive behavior.

Children in cluster 3 had high disruptive behavior scores similar to those seen in cluster 1, but significantly less severe autistic behaviors.

Children in cluster 4 had the most severe autistic behaviors, compared with the other clusters.

Children in clusters 1 and 4 underwent additional analysis to confirm that they resembled the original DS plus ASD diagnostic group. This additional analysis confirmed that children with DS and ASD with "more irritable and hyperactive behaviors as well as high levels of self-injury" were more likely to fall into cluster 1, whereas children with more severe autistic behavior fell into cluster 4. In addition, significantly more children in cluster 4 had a history of late onset ASD, compared with those in cluster 1.

"These data also support the existence of ASD subtypes in DS, in line with the heterogeneity of the behavioral disorder in the general population," the researchers noted.

The study was limited by the relatively small number of children in each category and by the use of only the ABC-C data for the primary analysis, the researchers said.

However, the findings add to the field of DS research because they confirm the DSM diagnostic criteria of ASD in children with DS. Additional longitudinal studies could examine whether the DSM diagnoses remain stable over time. Better behavioral instruments are needed to help clinicians recognize comorbidities and suggest targeted interventions, they added.

"We have known for some time that Down syndrome is associated with a range of neurodevelopmental and behavioral outcomes," said Dr. George T. Capone, a study coauthor. "We hypothesized that the association between developmental function and behavior was not random; rather, the two are related in such a manner that distinct behavioral clusters can be identified."

The study underscores the point that children with Down syndrome are not all alike, he explained, which has "direct implications for our understanding of brain organization and possibly the relationship between genotype and phenotype in young children with the diagnosis."

He and his colleagues were not particularly surprised by the findings, he added, because "it has long been our observation that children with Down syndrome and maladaptive behavior differ from their typical peers with the diagnosis." These differences are obvious and measurable both to parents who respond to validated behavioral questionnaires and to neurodevelopmental pediatricians who use a DSM classification to identify behavior and mental health disorders.

Increased vigilance, screening, and evaluation for atypical development and behavior problems have recently received greater emphasis in the American Academy of Pediatrics’ updated "Health Supervision for Children with Down Syndrome" guidelines (Pediatrics 2011 128:393-406).

"Our study findings support the existence of well-delineated behavior clusters in children with DS, and in our clinic we have witnessed educational success when these issues are recognized and addressed. Pediatricians can do families a great service by recognizing that a coexisting neurobehavioral condition may be present," said Dr. Capone of the department of pediatrics at Johns Hopkins University, who is also director of the Down syndrome clinic at the Kennedy Krieger Institute, both in Baltimore. With proper evaluation and treatment, he noted, children with DS and disruptive behaviors or ASD can benefit from a combination of medication and behavior management, in addition to an educational program emphasizing functional communication and social skills development.

The study was supported in part by grants from Autism Speaks, a nonprofit association. The researchers had no relevant financial conflicts disclosures.

Children with Down syndrome can be diagnosed with autism via the autism spectrum disorder criteria from the Diagnostic and Statistical Manual of Mental Disorders, based on results of a cluster analysis of 293 children with Down syndrome.

Previous studies have suggested that autism spectrum disorders (ASD) can’t be effectively diagnosed in children with Down syndrome (DS) because of the cognitive impairment already associated with DS, said Dr. N.Y. Ji of Johns Hopkins University, Baltimore.

In this study, Dr. Ji and colleagues used the Aberrant Behavior Checklist to show that children with both DS and ASD match the DSM criteria for autism diagnoses (J. Intellect. Disabil. Res. 2011 Aug. 30 [doi:10.1111/j.1365-2788.2011.0465.x]).

The researchers assessed more than 1,000 children aged 0-21 years who visited the Down syndrome clinic of the Kennedy Krieger Institute in Baltimore during 1992-2008. They identified 293 children for cluster analysis and used the Aberrant Behavior Checklist–Community (ABC-C) and the Autism Behavior Checklist to identify autism features. For comparison, the researchers also identified children with DS and two other common DS comorbidities: disruptive behavior disorder (DBS) and stereotypic movement disorder (SMD).

Overall, 114 children (39%) met criteria for ASD, 104 (36%) met criteria for DBS, and 43 (15%) had SMD. Another 32 children (11%) did not meet criteria for any coexisting major psychiatric condition in addition to DS.

The findings add to the field of Down syndrome research because they confirm the DSM diagnostic criteria of autism spectrum disorder in children with Down syndrome.

The researchers divided the children into four clusters based on the ABC-C and Autism Behavior Checklist.

Participants in clusters 1 and 4 had lower levels of intellectual functioning than did those in clusters 2 and 3, although there was no significant difference in the median age among the groups, the researchers noted.

In addition, children in cluster 1 had a broad range of behavioral problems, including self-injury and highly disruptive behavior.

Children in cluster 2 had the lowest ABC-C scores and the mildest levels of maladaptive behavior.

Children in cluster 3 had high disruptive behavior scores similar to those seen in cluster 1, but significantly less severe autistic behaviors.

Children in cluster 4 had the most severe autistic behaviors, compared with the other clusters.

Children in clusters 1 and 4 underwent additional analysis to confirm that they resembled the original DS plus ASD diagnostic group. This additional analysis confirmed that children with DS and ASD with "more irritable and hyperactive behaviors as well as high levels of self-injury" were more likely to fall into cluster 1, whereas children with more severe autistic behavior fell into cluster 4. In addition, significantly more children in cluster 4 had a history of late onset ASD, compared with those in cluster 1.

"These data also support the existence of ASD subtypes in DS, in line with the heterogeneity of the behavioral disorder in the general population," the researchers noted.

The study was limited by the relatively small number of children in each category and by the use of only the ABC-C data for the primary analysis, the researchers said.

However, the findings add to the field of DS research because they confirm the DSM diagnostic criteria of ASD in children with DS. Additional longitudinal studies could examine whether the DSM diagnoses remain stable over time. Better behavioral instruments are needed to help clinicians recognize comorbidities and suggest targeted interventions, they added.

"We have known for some time that Down syndrome is associated with a range of neurodevelopmental and behavioral outcomes," said Dr. George T. Capone, a study coauthor. "We hypothesized that the association between developmental function and behavior was not random; rather, the two are related in such a manner that distinct behavioral clusters can be identified."

The study underscores the point that children with Down syndrome are not all alike, he explained, which has "direct implications for our understanding of brain organization and possibly the relationship between genotype and phenotype in young children with the diagnosis."

He and his colleagues were not particularly surprised by the findings, he added, because "it has long been our observation that children with Down syndrome and maladaptive behavior differ from their typical peers with the diagnosis." These differences are obvious and measurable both to parents who respond to validated behavioral questionnaires and to neurodevelopmental pediatricians who use a DSM classification to identify behavior and mental health disorders.

Increased vigilance, screening, and evaluation for atypical development and behavior problems have recently received greater emphasis in the American Academy of Pediatrics’ updated "Health Supervision for Children with Down Syndrome" guidelines (Pediatrics 2011 128:393-406).

"Our study findings support the existence of well-delineated behavior clusters in children with DS, and in our clinic we have witnessed educational success when these issues are recognized and addressed. Pediatricians can do families a great service by recognizing that a coexisting neurobehavioral condition may be present," said Dr. Capone of the department of pediatrics at Johns Hopkins University, who is also director of the Down syndrome clinic at the Kennedy Krieger Institute, both in Baltimore. With proper evaluation and treatment, he noted, children with DS and disruptive behaviors or ASD can benefit from a combination of medication and behavior management, in addition to an educational program emphasizing functional communication and social skills development.

The study was supported in part by grants from Autism Speaks, a nonprofit association. The researchers had no relevant financial conflicts disclosures.

Children with Down syndrome can be diagnosed with autism via the autism spectrum disorder criteria from the Diagnostic and Statistical Manual of Mental Disorders, based on results of a cluster analysis of 293 children with Down syndrome.

Previous studies have suggested that autism spectrum disorders (ASD) can’t be effectively diagnosed in children with Down syndrome (DS) because of the cognitive impairment already associated with DS, said Dr. N.Y. Ji of Johns Hopkins University, Baltimore.

In this study, Dr. Ji and colleagues used the Aberrant Behavior Checklist to show that children with both DS and ASD match the DSM criteria for autism diagnoses (J. Intellect. Disabil. Res. 2011 Aug. 30 [doi:10.1111/j.1365-2788.2011.0465.x]).

The researchers assessed more than 1,000 children aged 0-21 years who visited the Down syndrome clinic of the Kennedy Krieger Institute in Baltimore during 1992-2008. They identified 293 children for cluster analysis and used the Aberrant Behavior Checklist–Community (ABC-C) and the Autism Behavior Checklist to identify autism features. For comparison, the researchers also identified children with DS and two other common DS comorbidities: disruptive behavior disorder (DBS) and stereotypic movement disorder (SMD).

Overall, 114 children (39%) met criteria for ASD, 104 (36%) met criteria for DBS, and 43 (15%) had SMD. Another 32 children (11%) did not meet criteria for any coexisting major psychiatric condition in addition to DS.

The findings add to the field of Down syndrome research because they confirm the DSM diagnostic criteria of autism spectrum disorder in children with Down syndrome.

The researchers divided the children into four clusters based on the ABC-C and Autism Behavior Checklist.

Participants in clusters 1 and 4 had lower levels of intellectual functioning than did those in clusters 2 and 3, although there was no significant difference in the median age among the groups, the researchers noted.

In addition, children in cluster 1 had a broad range of behavioral problems, including self-injury and highly disruptive behavior.

Children in cluster 2 had the lowest ABC-C scores and the mildest levels of maladaptive behavior.

Children in cluster 3 had high disruptive behavior scores similar to those seen in cluster 1, but significantly less severe autistic behaviors.

Children in cluster 4 had the most severe autistic behaviors, compared with the other clusters.

Children in clusters 1 and 4 underwent additional analysis to confirm that they resembled the original DS plus ASD diagnostic group. This additional analysis confirmed that children with DS and ASD with "more irritable and hyperactive behaviors as well as high levels of self-injury" were more likely to fall into cluster 1, whereas children with more severe autistic behavior fell into cluster 4. In addition, significantly more children in cluster 4 had a history of late onset ASD, compared with those in cluster 1.

"These data also support the existence of ASD subtypes in DS, in line with the heterogeneity of the behavioral disorder in the general population," the researchers noted.

The study was limited by the relatively small number of children in each category and by the use of only the ABC-C data for the primary analysis, the researchers said.

However, the findings add to the field of DS research because they confirm the DSM diagnostic criteria of ASD in children with DS. Additional longitudinal studies could examine whether the DSM diagnoses remain stable over time. Better behavioral instruments are needed to help clinicians recognize comorbidities and suggest targeted interventions, they added.

"We have known for some time that Down syndrome is associated with a range of neurodevelopmental and behavioral outcomes," said Dr. George T. Capone, a study coauthor. "We hypothesized that the association between developmental function and behavior was not random; rather, the two are related in such a manner that distinct behavioral clusters can be identified."

The study underscores the point that children with Down syndrome are not all alike, he explained, which has "direct implications for our understanding of brain organization and possibly the relationship between genotype and phenotype in young children with the diagnosis."

He and his colleagues were not particularly surprised by the findings, he added, because "it has long been our observation that children with Down syndrome and maladaptive behavior differ from their typical peers with the diagnosis." These differences are obvious and measurable both to parents who respond to validated behavioral questionnaires and to neurodevelopmental pediatricians who use a DSM classification to identify behavior and mental health disorders.

Increased vigilance, screening, and evaluation for atypical development and behavior problems have recently received greater emphasis in the American Academy of Pediatrics’ updated "Health Supervision for Children with Down Syndrome" guidelines (Pediatrics 2011 128:393-406).

"Our study findings support the existence of well-delineated behavior clusters in children with DS, and in our clinic we have witnessed educational success when these issues are recognized and addressed. Pediatricians can do families a great service by recognizing that a coexisting neurobehavioral condition may be present," said Dr. Capone of the department of pediatrics at Johns Hopkins University, who is also director of the Down syndrome clinic at the Kennedy Krieger Institute, both in Baltimore. With proper evaluation and treatment, he noted, children with DS and disruptive behaviors or ASD can benefit from a combination of medication and behavior management, in addition to an educational program emphasizing functional communication and social skills development.

The study was supported in part by grants from Autism Speaks, a nonprofit association. The researchers had no relevant financial conflicts disclosures.

NATIONAL HARBOR, MD. –Women who used transdermal ­estrogen had a 30% lower risk of ­venous thromboembolism than did patients who used oral estrogen, based on data collected from more than 50,000 women, said Eric
Beresford, Pharm.D., of Novartis.

The observation is limited, how­ever, by the lack of data on specific estrogen doses in the oral estrogen users. Further, the data were not adjusted for the participants’ weights or BMIs.

Transdermal estrogen has the ­potential to reduce VTE risk by ­delivering unmetabolized estradiol ­directly to the bloodstream, he said.

Women who used transdermal estrogen had a 30% lower risk of venous thromboembolism than did patients who used oral estrogen, based on data from more than 50,000 women.

"Women treated with oral estrogen–containing hormone therapy have an increased risk of developing venous thromboembolism," according to data from previous studies, said Eric Beresford, Pharm.D., of Novartis. Dr. Beresford presented the findings at the annual meeting of the North American Menopause Society.

Transdermal estrogen has the potential to reduce VTE risk by delivering unmetabolized estradiol directly to the bloodstream, he explained.

In retrospective, matched-cohort study, Dr. Beresford and colleagues compared VTE incidence for up to 90 days in 27,018 women who began taking oral estrogen only, and in 27,018 who began using a high-dose estradiol transdermal system (ETS) between January 2002 and October 2009. The data were collected from the Thomson Reuters MarketScan database of health insurance claims.

The mean age of the women was 49 years, and 22% of them had menopausal or postmenopausal disorders.

Overall, 115 women (0.40 events per 100 person-years) in the ETS group developed VTE, compared with 164 women (0.56 events per 100 person-years) in the oral estrogen group; this difference was statistically significant (P = .006).

The incidence of hospitalization-related VTE events was significantly lower in the ETS group, compared with the oral estrogen group (24 vs. 44, respectively). The number of events per 100 person-years was 0.08 and 0.15, respectively.

VTE was defined as at least one diagnosis code for deep vein thrombosis or pulmonary embolism. Women with a prior VTE diagnosis were excluded from the study.

When shown on a Kaplan-Meier curve, the rates of VTE in the ETS group at 6, 12, and 24 months after the start of therapy were 0.24%, 0.42%, and 0.68%, respectively. The rates of VTE in the oral estrogen group were 0.31%, 0.59%, and 1.13%, respectively. The differences between the two groups were statistically significant (P = .006).

The differences in VTE rates between the two groups were significant with EST doses of either 0.075 mg/day or 0.1 mg/day, Dr. Beresford noted. The women in the oral estrogen hormone therapy group were taking a variety of brands of oral estrogen replacements in various dosages; the study was not designed to compare ETS with specific oral estrogen doses, he added.

The most common concomitant medications were antihypertensives, which were taken by 11% of the women in each group. The most common risk factor for VTE was surgical resection of abdominal or pelvic cancer (24%) and other major surgery (17%).

The findings were limited by the lack of information about the participants’ weight or body mass index, which can affect the risk of thrombotic events, and by the observational nature of the study, Dr. Beresford said.

However, the results suggest that "women receiving ETS have a significantly lower incidence of VTE and hospitalization-related VTE than [do] women receiving oral estrogen–only hormone therapy," he said. More research is needed to assess transdermal estrogen as an option for women at increased risk for VTE.

The study was sponsored by Novartis and several of the coinvestigators are employed by Novartis.

NATIONAL HARBOR, MD. –Women who used transdermal ­estrogen had a 30% lower risk of ­venous thromboembolism than did patients who used oral estrogen, based on data collected from more than 50,000 women, said Eric
Beresford, Pharm.D., of Novartis.

The observation is limited, how­ever, by the lack of data on specific estrogen doses in the oral estrogen users. Further, the data were not adjusted for the participants’ weights or BMIs.

Transdermal estrogen has the ­potential to reduce VTE risk by ­delivering unmetabolized estradiol ­directly to the bloodstream, he said.

Women who used transdermal estrogen had a 30% lower risk of venous thromboembolism than did patients who used oral estrogen, based on data from more than 50,000 women.

"Women treated with oral estrogen–containing hormone therapy have an increased risk of developing venous thromboembolism," according to data from previous studies, said Eric Beresford, Pharm.D., of Novartis. Dr. Beresford presented the findings at the annual meeting of the North American Menopause Society.

Transdermal estrogen has the potential to reduce VTE risk by delivering unmetabolized estradiol directly to the bloodstream, he explained.

In retrospective, matched-cohort study, Dr. Beresford and colleagues compared VTE incidence for up to 90 days in 27,018 women who began taking oral estrogen only, and in 27,018 who began using a high-dose estradiol transdermal system (ETS) between January 2002 and October 2009. The data were collected from the Thomson Reuters MarketScan database of health insurance claims.

The mean age of the women was 49 years, and 22% of them had menopausal or postmenopausal disorders.

Overall, 115 women (0.40 events per 100 person-years) in the ETS group developed VTE, compared with 164 women (0.56 events per 100 person-years) in the oral estrogen group; this difference was statistically significant (P = .006).

The incidence of hospitalization-related VTE events was significantly lower in the ETS group, compared with the oral estrogen group (24 vs. 44, respectively). The number of events per 100 person-years was 0.08 and 0.15, respectively.

VTE was defined as at least one diagnosis code for deep vein thrombosis or pulmonary embolism. Women with a prior VTE diagnosis were excluded from the study.

When shown on a Kaplan-Meier curve, the rates of VTE in the ETS group at 6, 12, and 24 months after the start of therapy were 0.24%, 0.42%, and 0.68%, respectively. The rates of VTE in the oral estrogen group were 0.31%, 0.59%, and 1.13%, respectively. The differences between the two groups were statistically significant (P = .006).

The differences in VTE rates between the two groups were significant with EST doses of either 0.075 mg/day or 0.1 mg/day, Dr. Beresford noted. The women in the oral estrogen hormone therapy group were taking a variety of brands of oral estrogen replacements in various dosages; the study was not designed to compare ETS with specific oral estrogen doses, he added.

The most common concomitant medications were antihypertensives, which were taken by 11% of the women in each group. The most common risk factor for VTE was surgical resection of abdominal or pelvic cancer (24%) and other major surgery (17%).

The findings were limited by the lack of information about the participants’ weight or body mass index, which can affect the risk of thrombotic events, and by the observational nature of the study, Dr. Beresford said.

However, the results suggest that "women receiving ETS have a significantly lower incidence of VTE and hospitalization-related VTE than [do] women receiving oral estrogen–only hormone therapy," he said. More research is needed to assess transdermal estrogen as an option for women at increased risk for VTE.

The study was sponsored by Novartis and several of the coinvestigators are employed by Novartis.

NATIONAL HARBOR, MD. –Women who used transdermal ­estrogen had a 30% lower risk of ­venous thromboembolism than did patients who used oral estrogen, based on data collected from more than 50,000 women, said Eric
Beresford, Pharm.D., of Novartis.

The observation is limited, how­ever, by the lack of data on specific estrogen doses in the oral estrogen users. Further, the data were not adjusted for the participants’ weights or BMIs.

Transdermal estrogen has the ­potential to reduce VTE risk by ­delivering unmetabolized estradiol ­directly to the bloodstream, he said.

Women who used transdermal estrogen had a 30% lower risk of venous thromboembolism than did patients who used oral estrogen, based on data from more than 50,000 women.

"Women treated with oral estrogen–containing hormone therapy have an increased risk of developing venous thromboembolism," according to data from previous studies, said Eric Beresford, Pharm.D., of Novartis. Dr. Beresford presented the findings at the annual meeting of the North American Menopause Society.

Transdermal estrogen has the potential to reduce VTE risk by delivering unmetabolized estradiol directly to the bloodstream, he explained.

In retrospective, matched-cohort study, Dr. Beresford and colleagues compared VTE incidence for up to 90 days in 27,018 women who began taking oral estrogen only, and in 27,018 who began using a high-dose estradiol transdermal system (ETS) between January 2002 and October 2009. The data were collected from the Thomson Reuters MarketScan database of health insurance claims.

The mean age of the women was 49 years, and 22% of them had menopausal or postmenopausal disorders.

Overall, 115 women (0.40 events per 100 person-years) in the ETS group developed VTE, compared with 164 women (0.56 events per 100 person-years) in the oral estrogen group; this difference was statistically significant (P = .006).

The incidence of hospitalization-related VTE events was significantly lower in the ETS group, compared with the oral estrogen group (24 vs. 44, respectively). The number of events per 100 person-years was 0.08 and 0.15, respectively.

VTE was defined as at least one diagnosis code for deep vein thrombosis or pulmonary embolism. Women with a prior VTE diagnosis were excluded from the study.

When shown on a Kaplan-Meier curve, the rates of VTE in the ETS group at 6, 12, and 24 months after the start of therapy were 0.24%, 0.42%, and 0.68%, respectively. The rates of VTE in the oral estrogen group were 0.31%, 0.59%, and 1.13%, respectively. The differences between the two groups were statistically significant (P = .006).

The differences in VTE rates between the two groups were significant with EST doses of either 0.075 mg/day or 0.1 mg/day, Dr. Beresford noted. The women in the oral estrogen hormone therapy group were taking a variety of brands of oral estrogen replacements in various dosages; the study was not designed to compare ETS with specific oral estrogen doses, he added.

The most common concomitant medications were antihypertensives, which were taken by 11% of the women in each group. The most common risk factor for VTE was surgical resection of abdominal or pelvic cancer (24%) and other major surgery (17%).

The findings were limited by the lack of information about the participants’ weight or body mass index, which can affect the risk of thrombotic events, and by the observational nature of the study, Dr. Beresford said.

However, the results suggest that "women receiving ETS have a significantly lower incidence of VTE and hospitalization-related VTE than [do] women receiving oral estrogen–only hormone therapy," he said. More research is needed to assess transdermal estrogen as an option for women at increased risk for VTE.

The study was sponsored by Novartis and several of the coinvestigators are employed by Novartis.