Fran Lowry

SAN JUAN, P.R. – Continuous positive airway pressure can be effective for obstructive sleep apnea in children, but parents must be persistent to ensure children's acceptance of the treatment, Dr. Ann C. Halbower said at a meeting sponsored by the American College of Chest Physicians.

Obstructive sleep apnea (OSA) is present in 2%–3% of children, and peaks at 3–6 years of age–which is also the peak age for adenotonsillar hypertrophy. The presentation depends on the age of the child: In the infant, it might present as sudden infant death syndrome (SIDS). Toddlers with OSA will have hyperactivity, school-age children will have failure to thrive and poor school performance, and adolescents may present with obesity and excessive daytime sleepiness.

Adenotonsillectomy is the first-line therapy for children with OSA. When that is not successful, continuous positive airway pressure (CPAP) can promote more ordered breathing during sleep and relieve OSA.

CPAP can be problematic in children, however. “It's very hard to take. Little kids don't like it, but there are things parents and physicians can do to help make CPAP more palatable,” said Dr. Halbower, who serves as medical director of the pediatric sleep disorders program at Johns Hopkins University, Baltimore. Dr. Halbower recommended introducing the device slowly to minimize the fear factor. Put on the mask while the child is awake and doing an activity that is fun and pleasurable, she said.

The worst thing you can do is put the mask on while the child is asleep. “If they wake up and find themselves wearing the mask, they'll panic,” Dr. Halbower said

Another trick that can be used to make CPAP part of the child's normal bedtime routine, along with brushing the teeth and a bedtime story. Other children who use CPAP are wonderful ambassadors for the device and can help relieve anxiety with a show-and-tell. Videos are good for this as well.

Despite these efforts, some children will do everything to resist attempts to put on the mask. Many parents will remove the mask in response to their child's distress.

That is a big mistake, Dr. Halbower said, because it just strengthens the child's escape and avoidance behavior. Eventually, the parent gives up.

Behavioral training can help parents block or prevent their child's avoidance behavior by using brief verbal prompting, redirection to a specific task, and if necessary, physically blocking escape while gently guiding the child to remain in the situation.

The child's attempt to remove the mask must be physically interrupted and the mask replaced immediately every time the child removes it. She said these behavioral techniques are used in her clinic under the guidance of Keith Slifer, Ph.D., a behavioral psychologist. [The techniques] “have proved very successful,” Dr. Halbower said.

Parents should also plan for safety in children who cannot remove the mask during emergencies, Dr. Halbower cautioned.

Use a nasal mask instead of a full-face mask, or have an emergency pull string that can disengage the mask to prevent aspiration or asphyxiation if the child vomits.

It is important for parents to establish a consistent bedtime routine that lasts about 30 minutes, Dr. Halbower explained. Such a routine includes soothing activities, and it always ends with the child putting on the CPAP mask, lying down, and going to sleep.

“Persistence and patience are key,” she said.

When adenotonsillectomy proves unsuccessful for obstructive sleep apnea, continuous positive airway pressure can promote ordered breathing during sleep. Courtesy Dr. Ann C. Halbower

SAN JUAN, P.R. – Continuous positive airway pressure can be effective for obstructive sleep apnea in children, but parents must be persistent to ensure children's acceptance of the treatment, Dr. Ann C. Halbower said at a meeting sponsored by the American College of Chest Physicians.

Obstructive sleep apnea (OSA) is present in 2%–3% of children, and peaks at 3–6 years of age–which is also the peak age for adenotonsillar hypertrophy. The presentation depends on the age of the child: In the infant, it might present as sudden infant death syndrome (SIDS). Toddlers with OSA will have hyperactivity, school-age children will have failure to thrive and poor school performance, and adolescents may present with obesity and excessive daytime sleepiness.

Adenotonsillectomy is the first-line therapy for children with OSA. When that is not successful, continuous positive airway pressure (CPAP) can promote more ordered breathing during sleep and relieve OSA.

CPAP can be problematic in children, however. “It's very hard to take. Little kids don't like it, but there are things parents and physicians can do to help make CPAP more palatable,” said Dr. Halbower, who serves as medical director of the pediatric sleep disorders program at Johns Hopkins University, Baltimore. Dr. Halbower recommended introducing the device slowly to minimize the fear factor. Put on the mask while the child is awake and doing an activity that is fun and pleasurable, she said.

The worst thing you can do is put the mask on while the child is asleep. “If they wake up and find themselves wearing the mask, they'll panic,” Dr. Halbower said

Another trick that can be used to make CPAP part of the child's normal bedtime routine, along with brushing the teeth and a bedtime story. Other children who use CPAP are wonderful ambassadors for the device and can help relieve anxiety with a show-and-tell. Videos are good for this as well.

Despite these efforts, some children will do everything to resist attempts to put on the mask. Many parents will remove the mask in response to their child's distress.

That is a big mistake, Dr. Halbower said, because it just strengthens the child's escape and avoidance behavior. Eventually, the parent gives up.

Behavioral training can help parents block or prevent their child's avoidance behavior by using brief verbal prompting, redirection to a specific task, and if necessary, physically blocking escape while gently guiding the child to remain in the situation.

The child's attempt to remove the mask must be physically interrupted and the mask replaced immediately every time the child removes it. She said these behavioral techniques are used in her clinic under the guidance of Keith Slifer, Ph.D., a behavioral psychologist. [The techniques] “have proved very successful,” Dr. Halbower said.

Parents should also plan for safety in children who cannot remove the mask during emergencies, Dr. Halbower cautioned.

Use a nasal mask instead of a full-face mask, or have an emergency pull string that can disengage the mask to prevent aspiration or asphyxiation if the child vomits.

It is important for parents to establish a consistent bedtime routine that lasts about 30 minutes, Dr. Halbower explained. Such a routine includes soothing activities, and it always ends with the child putting on the CPAP mask, lying down, and going to sleep.

“Persistence and patience are key,” she said.

When adenotonsillectomy proves unsuccessful for obstructive sleep apnea, continuous positive airway pressure can promote ordered breathing during sleep. Courtesy Dr. Ann C. Halbower

SAN JUAN, P.R. – Continuous positive airway pressure can be effective for obstructive sleep apnea in children, but parents must be persistent to ensure children's acceptance of the treatment, Dr. Ann C. Halbower said at a meeting sponsored by the American College of Chest Physicians.

Obstructive sleep apnea (OSA) is present in 2%–3% of children, and peaks at 3–6 years of age–which is also the peak age for adenotonsillar hypertrophy. The presentation depends on the age of the child: In the infant, it might present as sudden infant death syndrome (SIDS). Toddlers with OSA will have hyperactivity, school-age children will have failure to thrive and poor school performance, and adolescents may present with obesity and excessive daytime sleepiness.

Adenotonsillectomy is the first-line therapy for children with OSA. When that is not successful, continuous positive airway pressure (CPAP) can promote more ordered breathing during sleep and relieve OSA.

CPAP can be problematic in children, however. “It's very hard to take. Little kids don't like it, but there are things parents and physicians can do to help make CPAP more palatable,” said Dr. Halbower, who serves as medical director of the pediatric sleep disorders program at Johns Hopkins University, Baltimore. Dr. Halbower recommended introducing the device slowly to minimize the fear factor. Put on the mask while the child is awake and doing an activity that is fun and pleasurable, she said.

The worst thing you can do is put the mask on while the child is asleep. “If they wake up and find themselves wearing the mask, they'll panic,” Dr. Halbower said

Another trick that can be used to make CPAP part of the child's normal bedtime routine, along with brushing the teeth and a bedtime story. Other children who use CPAP are wonderful ambassadors for the device and can help relieve anxiety with a show-and-tell. Videos are good for this as well.

Despite these efforts, some children will do everything to resist attempts to put on the mask. Many parents will remove the mask in response to their child's distress.

That is a big mistake, Dr. Halbower said, because it just strengthens the child's escape and avoidance behavior. Eventually, the parent gives up.

Behavioral training can help parents block or prevent their child's avoidance behavior by using brief verbal prompting, redirection to a specific task, and if necessary, physically blocking escape while gently guiding the child to remain in the situation.

The child's attempt to remove the mask must be physically interrupted and the mask replaced immediately every time the child removes it. She said these behavioral techniques are used in her clinic under the guidance of Keith Slifer, Ph.D., a behavioral psychologist. [The techniques] “have proved very successful,” Dr. Halbower said.

Parents should also plan for safety in children who cannot remove the mask during emergencies, Dr. Halbower cautioned.

Use a nasal mask instead of a full-face mask, or have an emergency pull string that can disengage the mask to prevent aspiration or asphyxiation if the child vomits.

It is important for parents to establish a consistent bedtime routine that lasts about 30 minutes, Dr. Halbower explained. Such a routine includes soothing activities, and it always ends with the child putting on the CPAP mask, lying down, and going to sleep.

“Persistence and patience are key,” she said.

When adenotonsillectomy proves unsuccessful for obstructive sleep apnea, continuous positive airway pressure can promote ordered breathing during sleep. Courtesy Dr. Ann C. Halbower

ATLANTA — A single prostate-specific antigen screening measurement of 3 ng/mL or higher is sufficient to justify a biopsy of the prostate without a repeat measurement of the PSA, researchers reported at the annual meeting of the American Urological Association.

Traditional wisdom has been that the serum PSA, if elevated, should be measured again before biopsy, on the theory that PSA levels could normalize before the second test. This premise is not valid, said Dr. Freddie C. Hamdy, head of urology at Sheffield (England) University.

He reported data from the ongoing Prostate Testing for Cancer and Treatment (Protect) study, a large randomized controlled trial in the United Kingdom. The study is scheduled to complete recruitment in 2008.

He and his associates analyzed the value of a repeat PSA test in 7,383 asymptomatic men aged 50–69 years during the feasibility phase of the Protect study. PSA testing was done between 1999 and 2001. Of the men, 723 (10%) had a PSA level of at least 3 ng/mL. All of these men were biopsied after the first PSA test, and 224 (31%) were found to have cancer. Repeat PSA measures were performed, but it was the first measure that triggered the biopsies.

If the criterion of PSA normalization had led to deferred biopsy, prostate cancer would have been missed in 8.1% of men biopsied after a PSA level of 3 ng/mL or higher and in 11.1% of men biopsied after a PSA level of 4 ng/mL or higher.

Cancer could be missed in 8.1% of men biopsied after a PSA level of 3 ng/mL or higher that later normalized. DR. HAMDY

ATLANTA — A single prostate-specific antigen screening measurement of 3 ng/mL or higher is sufficient to justify a biopsy of the prostate without a repeat measurement of the PSA, researchers reported at the annual meeting of the American Urological Association.

Traditional wisdom has been that the serum PSA, if elevated, should be measured again before biopsy, on the theory that PSA levels could normalize before the second test. This premise is not valid, said Dr. Freddie C. Hamdy, head of urology at Sheffield (England) University.

He reported data from the ongoing Prostate Testing for Cancer and Treatment (Protect) study, a large randomized controlled trial in the United Kingdom. The study is scheduled to complete recruitment in 2008.

He and his associates analyzed the value of a repeat PSA test in 7,383 asymptomatic men aged 50–69 years during the feasibility phase of the Protect study. PSA testing was done between 1999 and 2001. Of the men, 723 (10%) had a PSA level of at least 3 ng/mL. All of these men were biopsied after the first PSA test, and 224 (31%) were found to have cancer. Repeat PSA measures were performed, but it was the first measure that triggered the biopsies.

If the criterion of PSA normalization had led to deferred biopsy, prostate cancer would have been missed in 8.1% of men biopsied after a PSA level of 3 ng/mL or higher and in 11.1% of men biopsied after a PSA level of 4 ng/mL or higher.

Cancer could be missed in 8.1% of men biopsied after a PSA level of 3 ng/mL or higher that later normalized. DR. HAMDY

ATLANTA — A single prostate-specific antigen screening measurement of 3 ng/mL or higher is sufficient to justify a biopsy of the prostate without a repeat measurement of the PSA, researchers reported at the annual meeting of the American Urological Association.

Traditional wisdom has been that the serum PSA, if elevated, should be measured again before biopsy, on the theory that PSA levels could normalize before the second test. This premise is not valid, said Dr. Freddie C. Hamdy, head of urology at Sheffield (England) University.

He reported data from the ongoing Prostate Testing for Cancer and Treatment (Protect) study, a large randomized controlled trial in the United Kingdom. The study is scheduled to complete recruitment in 2008.

He and his associates analyzed the value of a repeat PSA test in 7,383 asymptomatic men aged 50–69 years during the feasibility phase of the Protect study. PSA testing was done between 1999 and 2001. Of the men, 723 (10%) had a PSA level of at least 3 ng/mL. All of these men were biopsied after the first PSA test, and 224 (31%) were found to have cancer. Repeat PSA measures were performed, but it was the first measure that triggered the biopsies.

If the criterion of PSA normalization had led to deferred biopsy, prostate cancer would have been missed in 8.1% of men biopsied after a PSA level of 3 ng/mL or higher and in 11.1% of men biopsied after a PSA level of 4 ng/mL or higher.

Cancer could be missed in 8.1% of men biopsied after a PSA level of 3 ng/mL or higher that later normalized. DR. HAMDY

ATLANTA — A prostate-specific antigen velocity threshold of approximately 0.4 ng/mL a year is a useful predictor of prostate cancer risk in men under the age of 60 years who have lower median PSA levels, according to research presented at the annual meeting of the American Urological Association.

“A decade ago, it was thought that a PSA velocity threshold of 0.75 ng/mL per year was useful to distinguish between prostate cancer and benign conditions and that total PSA levels between 4 and 10 warranted a biopsy. However, in the modern era, many men present with lower total PSA levels, particularly younger men,” said the lead author, Dr. Stacy Loeb of Georgetown University, Washington.

Dr. Loeb and her colleagues have previously shown in a large screening study that the median PSA level is 0.7 ng/mL for men in their 40s and 0.9 ng/mL for men in their 50s. “Thus, we felt that the traditional PSA velocity threshold of 0.75 ng/mL a year might be too high in these young men,” she said.

The researchers examined this issue in 6,488 men aged 60 or younger (mean age, 54 years). The median PSA velocity and performance characteristics of various PSA velocity thresholds were compared between men with prostate cancer and those with benign conditions.

Overall, 346 (5%) of the men under the age of 60 were diagnosed with prostate cancer during the study period, which was from 1991 to 2001. The median total PSA level was 2.8 ng/mL in men with prostate cancer, compared with 1.0 ng/mL in men who did not develop prostate cancer. In addition, a significantly greater number of men with prostate cancer presented with a PSA level greater than 4 ng/mL, Dr. Loeb said.

The median PSA velocity was 0.8 ng/mL a year in men with prostate cancer, versus 0.1 ng/mL a year in men with benign conditions. This difference was statistically significant.

The PSA velocity was useful in detecting prostate cancer. Cancer detection rates increased continuously as the PSA velocity increased from 0.4 ng/mL to 2 ng/mL a year.

A PSA velocity of 0.4 ng/mL a year had the optimal sensitivity and specificity for prostate cancer detection in men under the age of 60 years, Dr. Loeb reported. This threshold was associated with 57% sensitivity and 81% specificity for prostate cancer detection.

A PSA velocity greater than 0.4 ng/mL a year is a significant independent predictor of prostate cancer in young men, along with total PSA level and race, Dr. Loeb added.

“This means that a young man with a PSA velocity greater than 0.4 ng/mL a year has a 6.7-fold increased risk of prostate cancer over a young man with a PSA velocity less than 0.4. Furthermore, these results indicate that PSA velocity is a stronger predictor of prostate cancer in young men than race, total PSA, age, or family history,” she said.

The PSA velocity is also a highly significant independent predictor in the subgroup of men with total PSA levels less than 4 ng/mL. In these men, there was a 4.3-fold increased risk of prostate cancer if the PSA velocity was greater than 0.4 ng/mL a year, compared with men whose PSA velocity was less than 0.4 ng/mL a year.

Dr. Loeb noted that “4 ng/mL is a very high total PSA threshold, especially for young men, but this is what many people in the community still use. … In fact, part of what we are trying to disseminate through this paper is that the median PSA levels are much lower in young men, so lower total PSA and PSA velocity thresholds should be used in these men.”

In addition, there is controversy over the management of men with total PSA levels less than 4 ng/mL, so “this is another reason we chose to do a separate multivariate model for them, to show the message that even in this controversial group, PSA velocity is useful,” Dr. Loeb said in an interview.

ATLANTA — A prostate-specific antigen velocity threshold of approximately 0.4 ng/mL a year is a useful predictor of prostate cancer risk in men under the age of 60 years who have lower median PSA levels, according to research presented at the annual meeting of the American Urological Association.

“A decade ago, it was thought that a PSA velocity threshold of 0.75 ng/mL per year was useful to distinguish between prostate cancer and benign conditions and that total PSA levels between 4 and 10 warranted a biopsy. However, in the modern era, many men present with lower total PSA levels, particularly younger men,” said the lead author, Dr. Stacy Loeb of Georgetown University, Washington.

Dr. Loeb and her colleagues have previously shown in a large screening study that the median PSA level is 0.7 ng/mL for men in their 40s and 0.9 ng/mL for men in their 50s. “Thus, we felt that the traditional PSA velocity threshold of 0.75 ng/mL a year might be too high in these young men,” she said.

The researchers examined this issue in 6,488 men aged 60 or younger (mean age, 54 years). The median PSA velocity and performance characteristics of various PSA velocity thresholds were compared between men with prostate cancer and those with benign conditions.

Overall, 346 (5%) of the men under the age of 60 were diagnosed with prostate cancer during the study period, which was from 1991 to 2001. The median total PSA level was 2.8 ng/mL in men with prostate cancer, compared with 1.0 ng/mL in men who did not develop prostate cancer. In addition, a significantly greater number of men with prostate cancer presented with a PSA level greater than 4 ng/mL, Dr. Loeb said.

The median PSA velocity was 0.8 ng/mL a year in men with prostate cancer, versus 0.1 ng/mL a year in men with benign conditions. This difference was statistically significant.

The PSA velocity was useful in detecting prostate cancer. Cancer detection rates increased continuously as the PSA velocity increased from 0.4 ng/mL to 2 ng/mL a year.

A PSA velocity of 0.4 ng/mL a year had the optimal sensitivity and specificity for prostate cancer detection in men under the age of 60 years, Dr. Loeb reported. This threshold was associated with 57% sensitivity and 81% specificity for prostate cancer detection.

A PSA velocity greater than 0.4 ng/mL a year is a significant independent predictor of prostate cancer in young men, along with total PSA level and race, Dr. Loeb added.

“This means that a young man with a PSA velocity greater than 0.4 ng/mL a year has a 6.7-fold increased risk of prostate cancer over a young man with a PSA velocity less than 0.4. Furthermore, these results indicate that PSA velocity is a stronger predictor of prostate cancer in young men than race, total PSA, age, or family history,” she said.

The PSA velocity is also a highly significant independent predictor in the subgroup of men with total PSA levels less than 4 ng/mL. In these men, there was a 4.3-fold increased risk of prostate cancer if the PSA velocity was greater than 0.4 ng/mL a year, compared with men whose PSA velocity was less than 0.4 ng/mL a year.

Dr. Loeb noted that “4 ng/mL is a very high total PSA threshold, especially for young men, but this is what many people in the community still use. … In fact, part of what we are trying to disseminate through this paper is that the median PSA levels are much lower in young men, so lower total PSA and PSA velocity thresholds should be used in these men.”

In addition, there is controversy over the management of men with total PSA levels less than 4 ng/mL, so “this is another reason we chose to do a separate multivariate model for them, to show the message that even in this controversial group, PSA velocity is useful,” Dr. Loeb said in an interview.

ATLANTA — A prostate-specific antigen velocity threshold of approximately 0.4 ng/mL a year is a useful predictor of prostate cancer risk in men under the age of 60 years who have lower median PSA levels, according to research presented at the annual meeting of the American Urological Association.

“A decade ago, it was thought that a PSA velocity threshold of 0.75 ng/mL per year was useful to distinguish between prostate cancer and benign conditions and that total PSA levels between 4 and 10 warranted a biopsy. However, in the modern era, many men present with lower total PSA levels, particularly younger men,” said the lead author, Dr. Stacy Loeb of Georgetown University, Washington.

Dr. Loeb and her colleagues have previously shown in a large screening study that the median PSA level is 0.7 ng/mL for men in their 40s and 0.9 ng/mL for men in their 50s. “Thus, we felt that the traditional PSA velocity threshold of 0.75 ng/mL a year might be too high in these young men,” she said.

The researchers examined this issue in 6,488 men aged 60 or younger (mean age, 54 years). The median PSA velocity and performance characteristics of various PSA velocity thresholds were compared between men with prostate cancer and those with benign conditions.

Overall, 346 (5%) of the men under the age of 60 were diagnosed with prostate cancer during the study period, which was from 1991 to 2001. The median total PSA level was 2.8 ng/mL in men with prostate cancer, compared with 1.0 ng/mL in men who did not develop prostate cancer. In addition, a significantly greater number of men with prostate cancer presented with a PSA level greater than 4 ng/mL, Dr. Loeb said.

The median PSA velocity was 0.8 ng/mL a year in men with prostate cancer, versus 0.1 ng/mL a year in men with benign conditions. This difference was statistically significant.

The PSA velocity was useful in detecting prostate cancer. Cancer detection rates increased continuously as the PSA velocity increased from 0.4 ng/mL to 2 ng/mL a year.

A PSA velocity of 0.4 ng/mL a year had the optimal sensitivity and specificity for prostate cancer detection in men under the age of 60 years, Dr. Loeb reported. This threshold was associated with 57% sensitivity and 81% specificity for prostate cancer detection.

A PSA velocity greater than 0.4 ng/mL a year is a significant independent predictor of prostate cancer in young men, along with total PSA level and race, Dr. Loeb added.

“This means that a young man with a PSA velocity greater than 0.4 ng/mL a year has a 6.7-fold increased risk of prostate cancer over a young man with a PSA velocity less than 0.4. Furthermore, these results indicate that PSA velocity is a stronger predictor of prostate cancer in young men than race, total PSA, age, or family history,” she said.

The PSA velocity is also a highly significant independent predictor in the subgroup of men with total PSA levels less than 4 ng/mL. In these men, there was a 4.3-fold increased risk of prostate cancer if the PSA velocity was greater than 0.4 ng/mL a year, compared with men whose PSA velocity was less than 0.4 ng/mL a year.

Dr. Loeb noted that “4 ng/mL is a very high total PSA threshold, especially for young men, but this is what many people in the community still use. … In fact, part of what we are trying to disseminate through this paper is that the median PSA levels are much lower in young men, so lower total PSA and PSA velocity thresholds should be used in these men.”

In addition, there is controversy over the management of men with total PSA levels less than 4 ng/mL, so “this is another reason we chose to do a separate multivariate model for them, to show the message that even in this controversial group, PSA velocity is useful,” Dr. Loeb said in an interview.

ATLANTA — Adding gabapentin to venlafaxine does not augment the effectiveness of the antidepressant to control hot flashes, according to a study presented at the annual meeting of the American Society of Clinical Oncology.

Separate, previously reported, randomized, controlled trials have shown that both gabapentin and newer antidepressants, such as venlafaxine, are each significantly more effective than placebo in preventing hot flashes. However, in this study, which combined the two, no potentiation of relief was noted, said Dr. Charles Loprinzi, codirector of the Mayo Clinic Cancer Center's research program in cancer prevention and control in Rochester, Minn.

Vasomotor symptoms tend to be severe in breast cancer survivors because their estrogen supply is suddenly interrupted, and they may also be taking agents, such as tamoxifen, that are known to cause hot flashes. In addition, chemotherapy can cause abrupt menopause in a premenopausal woman, Dr. Loprinzi said in an interview.

The anticonvulsant gabapentin has been shown to reduce hot flashes when taken at 900 mg/day, compared with placebo. Similarly, venlafaxine (75 mg/day) has been shown to decrease hot flash episodes significantly more than placebo.

Dr. Loprinzi and his colleagues reasoned that it might be beneficial to add gabapentin to the regimen of women who continued to experience hot flashes despite receiving venlafaxine therapy.

In a randomized 4-week study involving 113 women, one group of 57 patients continued on the antidepressant and added gabapentin to their regimen; the second group of 56 patients stopped taking venlafaxine when they started on gabapentin.

The majority of the women had a history of breast cancer and had been treated with tamoxifen, raloxifene, or an aromatase inhibitor within 4 weeks of entry into the study. A minority of the study population did not have breast cancer, but did not wish to take hormonal therapy. Women in the gabapentin group had an average age of 55 years (ranging from 39 to 72); those in the combination therapy group had an average age of 58 years (ranging from 41 to 81). At baseline, the women were suffering from a mean of 14 bothersome hot flashes a week. The investigators found that when gabapentin was added to venlafaxine, “there was about a 50% reduction in hot flashes, but the reduction was the same whether the women were on gabapentin alone, or on gabapentin and an antidepressant,” Dr. Loprinzi said.

There was a 50% reduction in hot flashes whether gabapentin was used alone or in combination with an antidepressant. DR. LOPRINZI

ATLANTA — Adding gabapentin to venlafaxine does not augment the effectiveness of the antidepressant to control hot flashes, according to a study presented at the annual meeting of the American Society of Clinical Oncology.

Separate, previously reported, randomized, controlled trials have shown that both gabapentin and newer antidepressants, such as venlafaxine, are each significantly more effective than placebo in preventing hot flashes. However, in this study, which combined the two, no potentiation of relief was noted, said Dr. Charles Loprinzi, codirector of the Mayo Clinic Cancer Center's research program in cancer prevention and control in Rochester, Minn.

Vasomotor symptoms tend to be severe in breast cancer survivors because their estrogen supply is suddenly interrupted, and they may also be taking agents, such as tamoxifen, that are known to cause hot flashes. In addition, chemotherapy can cause abrupt menopause in a premenopausal woman, Dr. Loprinzi said in an interview.

The anticonvulsant gabapentin has been shown to reduce hot flashes when taken at 900 mg/day, compared with placebo. Similarly, venlafaxine (75 mg/day) has been shown to decrease hot flash episodes significantly more than placebo.

Dr. Loprinzi and his colleagues reasoned that it might be beneficial to add gabapentin to the regimen of women who continued to experience hot flashes despite receiving venlafaxine therapy.

In a randomized 4-week study involving 113 women, one group of 57 patients continued on the antidepressant and added gabapentin to their regimen; the second group of 56 patients stopped taking venlafaxine when they started on gabapentin.

The majority of the women had a history of breast cancer and had been treated with tamoxifen, raloxifene, or an aromatase inhibitor within 4 weeks of entry into the study. A minority of the study population did not have breast cancer, but did not wish to take hormonal therapy. Women in the gabapentin group had an average age of 55 years (ranging from 39 to 72); those in the combination therapy group had an average age of 58 years (ranging from 41 to 81). At baseline, the women were suffering from a mean of 14 bothersome hot flashes a week. The investigators found that when gabapentin was added to venlafaxine, “there was about a 50% reduction in hot flashes, but the reduction was the same whether the women were on gabapentin alone, or on gabapentin and an antidepressant,” Dr. Loprinzi said.

There was a 50% reduction in hot flashes whether gabapentin was used alone or in combination with an antidepressant. DR. LOPRINZI

ATLANTA — Adding gabapentin to venlafaxine does not augment the effectiveness of the antidepressant to control hot flashes, according to a study presented at the annual meeting of the American Society of Clinical Oncology.

Separate, previously reported, randomized, controlled trials have shown that both gabapentin and newer antidepressants, such as venlafaxine, are each significantly more effective than placebo in preventing hot flashes. However, in this study, which combined the two, no potentiation of relief was noted, said Dr. Charles Loprinzi, codirector of the Mayo Clinic Cancer Center's research program in cancer prevention and control in Rochester, Minn.

Vasomotor symptoms tend to be severe in breast cancer survivors because their estrogen supply is suddenly interrupted, and they may also be taking agents, such as tamoxifen, that are known to cause hot flashes. In addition, chemotherapy can cause abrupt menopause in a premenopausal woman, Dr. Loprinzi said in an interview.

The anticonvulsant gabapentin has been shown to reduce hot flashes when taken at 900 mg/day, compared with placebo. Similarly, venlafaxine (75 mg/day) has been shown to decrease hot flash episodes significantly more than placebo.

Dr. Loprinzi and his colleagues reasoned that it might be beneficial to add gabapentin to the regimen of women who continued to experience hot flashes despite receiving venlafaxine therapy.

In a randomized 4-week study involving 113 women, one group of 57 patients continued on the antidepressant and added gabapentin to their regimen; the second group of 56 patients stopped taking venlafaxine when they started on gabapentin.

The majority of the women had a history of breast cancer and had been treated with tamoxifen, raloxifene, or an aromatase inhibitor within 4 weeks of entry into the study. A minority of the study population did not have breast cancer, but did not wish to take hormonal therapy. Women in the gabapentin group had an average age of 55 years (ranging from 39 to 72); those in the combination therapy group had an average age of 58 years (ranging from 41 to 81). At baseline, the women were suffering from a mean of 14 bothersome hot flashes a week. The investigators found that when gabapentin was added to venlafaxine, “there was about a 50% reduction in hot flashes, but the reduction was the same whether the women were on gabapentin alone, or on gabapentin and an antidepressant,” Dr. Loprinzi said.

There was a 50% reduction in hot flashes whether gabapentin was used alone or in combination with an antidepressant. DR. LOPRINZI

WASHINGTON — Oral medroxyprogesterone acetate and oral contraceptives are equally effective in stopping nongestational acute uterine bleeding, according to a small randomized controlled trial presented at the annual meeting of the American College of Obstetricians and Gynecologists.

Cessation of bleeding occurred in 88% of the women randomized to oral contraceptives and in 76% of the women randomized to medroxyprogesterone. The mean time to cessation in the oral contraceptive group was 3.2 days vs. 3.8 days in the medroxyprogesterone group, reported Dr. Malcolm G. Munro, professor of obstetrics and gynecology at the University of California, Los Angeles, and chairman of the abnormal uterine bleeding working group for Kaiser Permanente, Southern California.

Women with nongestational acute uterine bleeding are seen frequently, and yet there has been a paucity of research on how best to treat them. Oral contraceptives are the most commonly used treatment in North America, but their efficacy for this indication has not been scientifically tested, Dr. Munro said. “There's never been a case report, a series, or a comparative trial. To my knowledge, the use of some type of combination oral contraceptives is based on a textbook that espouses this as being a treatment, and probably because it seems to work reasonably well, people perceive that a lot of research has been done in the area, but that is not the case.”

Currently, treatment options have been surgical therapy (D&C) or medical therapy with gonadal steroids, estrogen alone, progestins alone, or a combination estrogen-progestin formulation, Dr. Munro said.

He noted that only two studies of acute uterine bleeding have been reported in the literature. The first, a study of unopposed estrogen given intravenously in 32 women, was published in the early 1980s, and the second, a study of medroxyprogesterone acetate in 24 women, was published in 1997. “This is the sum total of the research, so clinicians need to know there's hardly any research in this area.”

In an open-label trial, Dr. Munro and his colleagues at Kaiser Permanente randomized 40 women with acute uterine bleeding, defined as excessively heavy or prolonged bleeding that was not related to pregnancy, to receive either medroxyprogesterone acetate, 20 mg three times a day for 7 days, and then 20 mg a day for 3 weeks, or combination oral contraceptive treatment with norethindrone (1 mg) and ethinyl estradiol (35 mcg) in one tablet three times a day for 7 days, followed by one tablet a day for 3 weeks.

At the end of the study, 33 of the original 40 patients remained, and in these patients both treatments were “roughly equivalent” with respect to efficacy, time to bleeding cessation, and nausea. Patient satisfaction in both groups was high, Dr. Munro reported.

“The degree of nausea was statistically even between the two but there was a trend toward more nausea in the oral contraceptive group, and this trend may have been significant if we had a larger sample size,” commented Dr. Munro.

One patient in the oral contraceptive group required an emergency procedure, compared with none in the medroxyprogesterone acetate group. “All of the women in the study had been bleeding for more than 10 days. They were the type of patient who is often taken to the operating room. At the very least, they needed emergent intervention, and only one required an emergent intervention in this study,” he added.

This study, although small, provides some support for clinicians who have been using oral contraceptives in some type of multidose format, feeling that it is the right thing to do, Dr. Munro noted. “And for those clinicians who are wedded to the notion of inpatient therapy, our results let them know that there are a couple of medical alternatives that may be effective.”

'People perceive that a lot of research has been done in the [OC] area, but that is not the case.' DR. MUNRO

WASHINGTON — Oral medroxyprogesterone acetate and oral contraceptives are equally effective in stopping nongestational acute uterine bleeding, according to a small randomized controlled trial presented at the annual meeting of the American College of Obstetricians and Gynecologists.

Cessation of bleeding occurred in 88% of the women randomized to oral contraceptives and in 76% of the women randomized to medroxyprogesterone. The mean time to cessation in the oral contraceptive group was 3.2 days vs. 3.8 days in the medroxyprogesterone group, reported Dr. Malcolm G. Munro, professor of obstetrics and gynecology at the University of California, Los Angeles, and chairman of the abnormal uterine bleeding working group for Kaiser Permanente, Southern California.

Women with nongestational acute uterine bleeding are seen frequently, and yet there has been a paucity of research on how best to treat them. Oral contraceptives are the most commonly used treatment in North America, but their efficacy for this indication has not been scientifically tested, Dr. Munro said. “There's never been a case report, a series, or a comparative trial. To my knowledge, the use of some type of combination oral contraceptives is based on a textbook that espouses this as being a treatment, and probably because it seems to work reasonably well, people perceive that a lot of research has been done in the area, but that is not the case.”

Currently, treatment options have been surgical therapy (D&C) or medical therapy with gonadal steroids, estrogen alone, progestins alone, or a combination estrogen-progestin formulation, Dr. Munro said.

He noted that only two studies of acute uterine bleeding have been reported in the literature. The first, a study of unopposed estrogen given intravenously in 32 women, was published in the early 1980s, and the second, a study of medroxyprogesterone acetate in 24 women, was published in 1997. “This is the sum total of the research, so clinicians need to know there's hardly any research in this area.”

In an open-label trial, Dr. Munro and his colleagues at Kaiser Permanente randomized 40 women with acute uterine bleeding, defined as excessively heavy or prolonged bleeding that was not related to pregnancy, to receive either medroxyprogesterone acetate, 20 mg three times a day for 7 days, and then 20 mg a day for 3 weeks, or combination oral contraceptive treatment with norethindrone (1 mg) and ethinyl estradiol (35 mcg) in one tablet three times a day for 7 days, followed by one tablet a day for 3 weeks.

At the end of the study, 33 of the original 40 patients remained, and in these patients both treatments were “roughly equivalent” with respect to efficacy, time to bleeding cessation, and nausea. Patient satisfaction in both groups was high, Dr. Munro reported.

“The degree of nausea was statistically even between the two but there was a trend toward more nausea in the oral contraceptive group, and this trend may have been significant if we had a larger sample size,” commented Dr. Munro.

One patient in the oral contraceptive group required an emergency procedure, compared with none in the medroxyprogesterone acetate group. “All of the women in the study had been bleeding for more than 10 days. They were the type of patient who is often taken to the operating room. At the very least, they needed emergent intervention, and only one required an emergent intervention in this study,” he added.

This study, although small, provides some support for clinicians who have been using oral contraceptives in some type of multidose format, feeling that it is the right thing to do, Dr. Munro noted. “And for those clinicians who are wedded to the notion of inpatient therapy, our results let them know that there are a couple of medical alternatives that may be effective.”

'People perceive that a lot of research has been done in the [OC] area, but that is not the case.' DR. MUNRO

WASHINGTON — Oral medroxyprogesterone acetate and oral contraceptives are equally effective in stopping nongestational acute uterine bleeding, according to a small randomized controlled trial presented at the annual meeting of the American College of Obstetricians and Gynecologists.

Cessation of bleeding occurred in 88% of the women randomized to oral contraceptives and in 76% of the women randomized to medroxyprogesterone. The mean time to cessation in the oral contraceptive group was 3.2 days vs. 3.8 days in the medroxyprogesterone group, reported Dr. Malcolm G. Munro, professor of obstetrics and gynecology at the University of California, Los Angeles, and chairman of the abnormal uterine bleeding working group for Kaiser Permanente, Southern California.

Women with nongestational acute uterine bleeding are seen frequently, and yet there has been a paucity of research on how best to treat them. Oral contraceptives are the most commonly used treatment in North America, but their efficacy for this indication has not been scientifically tested, Dr. Munro said. “There's never been a case report, a series, or a comparative trial. To my knowledge, the use of some type of combination oral contraceptives is based on a textbook that espouses this as being a treatment, and probably because it seems to work reasonably well, people perceive that a lot of research has been done in the area, but that is not the case.”

Currently, treatment options have been surgical therapy (D&C) or medical therapy with gonadal steroids, estrogen alone, progestins alone, or a combination estrogen-progestin formulation, Dr. Munro said.

He noted that only two studies of acute uterine bleeding have been reported in the literature. The first, a study of unopposed estrogen given intravenously in 32 women, was published in the early 1980s, and the second, a study of medroxyprogesterone acetate in 24 women, was published in 1997. “This is the sum total of the research, so clinicians need to know there's hardly any research in this area.”

In an open-label trial, Dr. Munro and his colleagues at Kaiser Permanente randomized 40 women with acute uterine bleeding, defined as excessively heavy or prolonged bleeding that was not related to pregnancy, to receive either medroxyprogesterone acetate, 20 mg three times a day for 7 days, and then 20 mg a day for 3 weeks, or combination oral contraceptive treatment with norethindrone (1 mg) and ethinyl estradiol (35 mcg) in one tablet three times a day for 7 days, followed by one tablet a day for 3 weeks.

At the end of the study, 33 of the original 40 patients remained, and in these patients both treatments were “roughly equivalent” with respect to efficacy, time to bleeding cessation, and nausea. Patient satisfaction in both groups was high, Dr. Munro reported.

“The degree of nausea was statistically even between the two but there was a trend toward more nausea in the oral contraceptive group, and this trend may have been significant if we had a larger sample size,” commented Dr. Munro.

One patient in the oral contraceptive group required an emergency procedure, compared with none in the medroxyprogesterone acetate group. “All of the women in the study had been bleeding for more than 10 days. They were the type of patient who is often taken to the operating room. At the very least, they needed emergent intervention, and only one required an emergent intervention in this study,” he added.

This study, although small, provides some support for clinicians who have been using oral contraceptives in some type of multidose format, feeling that it is the right thing to do, Dr. Munro noted. “And for those clinicians who are wedded to the notion of inpatient therapy, our results let them know that there are a couple of medical alternatives that may be effective.”

'People perceive that a lot of research has been done in the [OC] area, but that is not the case.' DR. MUNRO

ORLANDO — Hospital teaching staff was more likely to adhere to American College of Obstetricians and Gynecologists' guidelines for scheduling cesarean deliveries than were physicians in private practice, according to a retrospective chart review, Dr. M. Ryan Laye said at the annual meeting of the South Atlantic Association of Obstetricians and Gynecologists.

However, this nonadherence did not result in an increase in adverse neonatal outcomes, said Dr. Laye, who was at Greenville (S.C.) Memorial Hospital when the study was conducted.

Of the 296 patients being delivered by scheduled cesarean section for elective indications at the hospital, 222 (75%) were delivered in accordance with the American College of Obstetricians and Gynecologists' recommendations for timing of elective delivery. Of those not adhering, 95.5% were private service patients, and 4.5% were teaching service patients. The admission rate for the neonatal intensive care unit in both groups was 3.7%, which is consistent with the rates for all cesarean deliveries, as reported in the neonatal literature, Dr. Laye said.

Teaching-staff patients were more likely to be nonwhite, younger, and more obese than were the private service patients. They were also less likely to undergo a primary elective cesarean delivery, with 4 of 109 teaching staff patients (3.6%), and 23 of 187 private service patients (12.3%) undergoing a primary elective cesarean delivery, said Dr. Laye, now at the University of Mississippi Medical Center in Jackson.

ORLANDO — Hospital teaching staff was more likely to adhere to American College of Obstetricians and Gynecologists' guidelines for scheduling cesarean deliveries than were physicians in private practice, according to a retrospective chart review, Dr. M. Ryan Laye said at the annual meeting of the South Atlantic Association of Obstetricians and Gynecologists.

However, this nonadherence did not result in an increase in adverse neonatal outcomes, said Dr. Laye, who was at Greenville (S.C.) Memorial Hospital when the study was conducted.

Of the 296 patients being delivered by scheduled cesarean section for elective indications at the hospital, 222 (75%) were delivered in accordance with the American College of Obstetricians and Gynecologists' recommendations for timing of elective delivery. Of those not adhering, 95.5% were private service patients, and 4.5% were teaching service patients. The admission rate for the neonatal intensive care unit in both groups was 3.7%, which is consistent with the rates for all cesarean deliveries, as reported in the neonatal literature, Dr. Laye said.

Teaching-staff patients were more likely to be nonwhite, younger, and more obese than were the private service patients. They were also less likely to undergo a primary elective cesarean delivery, with 4 of 109 teaching staff patients (3.6%), and 23 of 187 private service patients (12.3%) undergoing a primary elective cesarean delivery, said Dr. Laye, now at the University of Mississippi Medical Center in Jackson.

ORLANDO — Hospital teaching staff was more likely to adhere to American College of Obstetricians and Gynecologists' guidelines for scheduling cesarean deliveries than were physicians in private practice, according to a retrospective chart review, Dr. M. Ryan Laye said at the annual meeting of the South Atlantic Association of Obstetricians and Gynecologists.

However, this nonadherence did not result in an increase in adverse neonatal outcomes, said Dr. Laye, who was at Greenville (S.C.) Memorial Hospital when the study was conducted.

Of the 296 patients being delivered by scheduled cesarean section for elective indications at the hospital, 222 (75%) were delivered in accordance with the American College of Obstetricians and Gynecologists' recommendations for timing of elective delivery. Of those not adhering, 95.5% were private service patients, and 4.5% were teaching service patients. The admission rate for the neonatal intensive care unit in both groups was 3.7%, which is consistent with the rates for all cesarean deliveries, as reported in the neonatal literature, Dr. Laye said.

Teaching-staff patients were more likely to be nonwhite, younger, and more obese than were the private service patients. They were also less likely to undergo a primary elective cesarean delivery, with 4 of 109 teaching staff patients (3.6%), and 23 of 187 private service patients (12.3%) undergoing a primary elective cesarean delivery, said Dr. Laye, now at the University of Mississippi Medical Center in Jackson.

WASHINGTON — Cellulose sulfate, a new vaginal gel that is being developed as both a contraceptive and as a means of preventing human immunodeficiency virus and other sexually transmitted infections, is as effective as nonoxynol-9 in preventing pregnancy, and also appears to be safer, researchers wrote in a poster presented at the annual meeting of the American College of Obstetricians and Gynecologists.

The cumulative probability of pregnancy during “typical” and “perfect” use of cellulose sulfate was 13.9 and 3.9, respectively, in a population of 200 heterosexual, fertile couples who used the gel as their primary method of birth control for 6 months as part of a phase II, noncomparative contraceptive effectiveness trial, wrote Dr. Christine Mauck, of the Contraceptive Research and Development (CONRAD) program at the Eastern Virginia Medical School in Arlington, and associates.

Cellulose sulfate is an antimicrobial that stimulates acrosomal loss, inhibits hyaluronidase, and impedes sperm penetration into cervical mucus. Animal studies in rabbits have demonstrated its contraceptive ability. Cellulose sulfate is active against cell-free and cell-associated HIV-1 because it blocks glycoprotein 120-CD4-coreceptor interaction, thereby inhibiting HIV cell entry. Cellulose sulfate has been studied in multiple safety studies of both HIV-free and HIV-infected men and women in which it has been found to be safe, and is currently being studied in two phase III HIV prevention trials, Dr. Mauck wrote.

In this study, the 200 couples were demographically similar with regard to age (27 years for females; 29 years for males), race, and education. Clinic visits were scheduled at enrollment, after one menstrual cycle, and after 6 months or six menstrual cycles, whichever occurred later. Study participants were also asked to phone the clinic 7–10 days after the onset of the first menstrual period, and at the onset of each menses thereafter throughout the study.

There was a mean of 11.5 coital acts per cycle, and 78% of the study subjects used the cellulose sulfate gel alone, as instructed. The gel was used alone, but incorrectly, in 4% of subjects, with an additional contraceptive method in 5% of subjects; 10% of subjects used another method alone, and 4% had unprotected intercourse, Dr. Mauck and her associates wrote.

At the end of the study, 18 women (9%) were pregnant, and 82 (41%) had not become pregnant. Another 14 women (7%) discontinued the study for gel-related reasons; 66 (33%) stopped for other reasons, 18 (9%) said they never used the gel, and 2 patients (1%) were lost to follow-up.

Nonoxynol-9 (N-9), currently the only vaginal contraceptive gel approved for use in the United States, has been associated with an increased risk of HIV, compared with placebo, when used frequently by women at high risk for HIV, Dr. Mauck commented in an interview. “This is why we need a new contraceptive gel. N-9 was found in a previous trial to be associated with a greater risk of HIV seroconversion when used frequently by women at risk of HIV because it's a surfactant and may cause damage to the vaginal epithelium. [Cellulose sulfate gel] appears to be safer than N-9 and may be safer than sexual lubricants like K-Y and at least as effective as N-9,” she said.

WASHINGTON — Cellulose sulfate, a new vaginal gel that is being developed as both a contraceptive and as a means of preventing human immunodeficiency virus and other sexually transmitted infections, is as effective as nonoxynol-9 in preventing pregnancy, and also appears to be safer, researchers wrote in a poster presented at the annual meeting of the American College of Obstetricians and Gynecologists.

The cumulative probability of pregnancy during “typical” and “perfect” use of cellulose sulfate was 13.9 and 3.9, respectively, in a population of 200 heterosexual, fertile couples who used the gel as their primary method of birth control for 6 months as part of a phase II, noncomparative contraceptive effectiveness trial, wrote Dr. Christine Mauck, of the Contraceptive Research and Development (CONRAD) program at the Eastern Virginia Medical School in Arlington, and associates.

Cellulose sulfate is an antimicrobial that stimulates acrosomal loss, inhibits hyaluronidase, and impedes sperm penetration into cervical mucus. Animal studies in rabbits have demonstrated its contraceptive ability. Cellulose sulfate is active against cell-free and cell-associated HIV-1 because it blocks glycoprotein 120-CD4-coreceptor interaction, thereby inhibiting HIV cell entry. Cellulose sulfate has been studied in multiple safety studies of both HIV-free and HIV-infected men and women in which it has been found to be safe, and is currently being studied in two phase III HIV prevention trials, Dr. Mauck wrote.

In this study, the 200 couples were demographically similar with regard to age (27 years for females; 29 years for males), race, and education. Clinic visits were scheduled at enrollment, after one menstrual cycle, and after 6 months or six menstrual cycles, whichever occurred later. Study participants were also asked to phone the clinic 7–10 days after the onset of the first menstrual period, and at the onset of each menses thereafter throughout the study.

There was a mean of 11.5 coital acts per cycle, and 78% of the study subjects used the cellulose sulfate gel alone, as instructed. The gel was used alone, but incorrectly, in 4% of subjects, with an additional contraceptive method in 5% of subjects; 10% of subjects used another method alone, and 4% had unprotected intercourse, Dr. Mauck and her associates wrote.

At the end of the study, 18 women (9%) were pregnant, and 82 (41%) had not become pregnant. Another 14 women (7%) discontinued the study for gel-related reasons; 66 (33%) stopped for other reasons, 18 (9%) said they never used the gel, and 2 patients (1%) were lost to follow-up.

Nonoxynol-9 (N-9), currently the only vaginal contraceptive gel approved for use in the United States, has been associated with an increased risk of HIV, compared with placebo, when used frequently by women at high risk for HIV, Dr. Mauck commented in an interview. “This is why we need a new contraceptive gel. N-9 was found in a previous trial to be associated with a greater risk of HIV seroconversion when used frequently by women at risk of HIV because it's a surfactant and may cause damage to the vaginal epithelium. [Cellulose sulfate gel] appears to be safer than N-9 and may be safer than sexual lubricants like K-Y and at least as effective as N-9,” she said.

WASHINGTON — Cellulose sulfate, a new vaginal gel that is being developed as both a contraceptive and as a means of preventing human immunodeficiency virus and other sexually transmitted infections, is as effective as nonoxynol-9 in preventing pregnancy, and also appears to be safer, researchers wrote in a poster presented at the annual meeting of the American College of Obstetricians and Gynecologists.

The cumulative probability of pregnancy during “typical” and “perfect” use of cellulose sulfate was 13.9 and 3.9, respectively, in a population of 200 heterosexual, fertile couples who used the gel as their primary method of birth control for 6 months as part of a phase II, noncomparative contraceptive effectiveness trial, wrote Dr. Christine Mauck, of the Contraceptive Research and Development (CONRAD) program at the Eastern Virginia Medical School in Arlington, and associates.

Cellulose sulfate is an antimicrobial that stimulates acrosomal loss, inhibits hyaluronidase, and impedes sperm penetration into cervical mucus. Animal studies in rabbits have demonstrated its contraceptive ability. Cellulose sulfate is active against cell-free and cell-associated HIV-1 because it blocks glycoprotein 120-CD4-coreceptor interaction, thereby inhibiting HIV cell entry. Cellulose sulfate has been studied in multiple safety studies of both HIV-free and HIV-infected men and women in which it has been found to be safe, and is currently being studied in two phase III HIV prevention trials, Dr. Mauck wrote.

In this study, the 200 couples were demographically similar with regard to age (27 years for females; 29 years for males), race, and education. Clinic visits were scheduled at enrollment, after one menstrual cycle, and after 6 months or six menstrual cycles, whichever occurred later. Study participants were also asked to phone the clinic 7–10 days after the onset of the first menstrual period, and at the onset of each menses thereafter throughout the study.

There was a mean of 11.5 coital acts per cycle, and 78% of the study subjects used the cellulose sulfate gel alone, as instructed. The gel was used alone, but incorrectly, in 4% of subjects, with an additional contraceptive method in 5% of subjects; 10% of subjects used another method alone, and 4% had unprotected intercourse, Dr. Mauck and her associates wrote.

At the end of the study, 18 women (9%) were pregnant, and 82 (41%) had not become pregnant. Another 14 women (7%) discontinued the study for gel-related reasons; 66 (33%) stopped for other reasons, 18 (9%) said they never used the gel, and 2 patients (1%) were lost to follow-up.

Nonoxynol-9 (N-9), currently the only vaginal contraceptive gel approved for use in the United States, has been associated with an increased risk of HIV, compared with placebo, when used frequently by women at high risk for HIV, Dr. Mauck commented in an interview. “This is why we need a new contraceptive gel. N-9 was found in a previous trial to be associated with a greater risk of HIV seroconversion when used frequently by women at risk of HIV because it's a surfactant and may cause damage to the vaginal epithelium. [Cellulose sulfate gel] appears to be safer than N-9 and may be safer than sexual lubricants like K-Y and at least as effective as N-9,” she said.

WASHINGTON — The contraceptive vaginal ring has fewer metabolic adverse effects than do oral contraceptives and may be a better alternative for insulin-resistant women, those with diabetes, and women with metabolic syndrome at increased risk for cardiovascular disease, Dr. Karen Elkind-Hirsch and colleagues wrote in a poster presented at the annual meeting of the American College of Obstetricians and Gynecologists.

Combined oral contraceptives remain the first line of treatment for women who desired birth control or cycle control with contraceptive steroids. Although much effort has been directed toward minimizing their potential thromboembolic and cardiovascular disease risks, much less attention has been given to their metabolic effects, wrote Dr. Elkind-Hirsch, scientific director of the Woman's Health Research Institute in Baton Rouge, La.

There is some evidence that oral contraceptives may aggravate insulin resistance and exert other untoward metabolic effects that might increase a woman's long-term risk for diabetes and heart disease. Delivering low-dose oral contraceptives via a nonoral route such as the vaginal ring might provide efficacy and good cycle control with less risk, they wrote.

To test this, the investigators randomized 30 women aged 18–40 years to either the vaginal ring or to a low-dose monophasic oral contraceptive for five continuous menstrual cycles. They tested the effects of both methods of birth control on carbohydrate metabolism, using insulin sensitivity indices derived from fasting and oral glucose tolerance tests.

All patients were similar with regard to age, weight, and metabolic parameters at baseline. However, by the end of the treatment period, the researchers noted that insulin sensitivity measured with a glucose tolerance test was significantly decreased in women taking the oral contraceptive pill, compared with women using the vaginal ring. The pill also significantly increased insulin resistance from baseline to after the treatment period when fasting levels alone were measured.

The study results confirm that low-dose oral contraceptives can adversely impact metabolic function, Dr. Elkind-Hirsch and her colleagues concluded. “So many women of reproductive age have insulin resistance or type 2 diabetes now,” she said in an interview. “What birth control can we put them on that will not make this worse?

“The other issue is obesity. When you give the contraceptive drug vaginally, you're right at the source, so you can give less. We don't have to go orally, thus bypass the liver, and the ring delivers the drug at a more steady state than the pill,”she added.

She added that the “women loved the ring. Everyone who had been randomized to the ring really loved it. There was no breakthrough bleeding, no matter how high their [body mass indexes] were. Not to get the breakthrough bleeding on such a low dose was very nice, and I think that was due to the steady-state vaginal delivery.”

WASHINGTON — The contraceptive vaginal ring has fewer metabolic adverse effects than do oral contraceptives and may be a better alternative for insulin-resistant women, those with diabetes, and women with metabolic syndrome at increased risk for cardiovascular disease, Dr. Karen Elkind-Hirsch and colleagues wrote in a poster presented at the annual meeting of the American College of Obstetricians and Gynecologists.

Combined oral contraceptives remain the first line of treatment for women who desired birth control or cycle control with contraceptive steroids. Although much effort has been directed toward minimizing their potential thromboembolic and cardiovascular disease risks, much less attention has been given to their metabolic effects, wrote Dr. Elkind-Hirsch, scientific director of the Woman's Health Research Institute in Baton Rouge, La.

There is some evidence that oral contraceptives may aggravate insulin resistance and exert other untoward metabolic effects that might increase a woman's long-term risk for diabetes and heart disease. Delivering low-dose oral contraceptives via a nonoral route such as the vaginal ring might provide efficacy and good cycle control with less risk, they wrote.

To test this, the investigators randomized 30 women aged 18–40 years to either the vaginal ring or to a low-dose monophasic oral contraceptive for five continuous menstrual cycles. They tested the effects of both methods of birth control on carbohydrate metabolism, using insulin sensitivity indices derived from fasting and oral glucose tolerance tests.

All patients were similar with regard to age, weight, and metabolic parameters at baseline. However, by the end of the treatment period, the researchers noted that insulin sensitivity measured with a glucose tolerance test was significantly decreased in women taking the oral contraceptive pill, compared with women using the vaginal ring. The pill also significantly increased insulin resistance from baseline to after the treatment period when fasting levels alone were measured.

The study results confirm that low-dose oral contraceptives can adversely impact metabolic function, Dr. Elkind-Hirsch and her colleagues concluded. “So many women of reproductive age have insulin resistance or type 2 diabetes now,” she said in an interview. “What birth control can we put them on that will not make this worse?

“The other issue is obesity. When you give the contraceptive drug vaginally, you're right at the source, so you can give less. We don't have to go orally, thus bypass the liver, and the ring delivers the drug at a more steady state than the pill,”she added.

She added that the “women loved the ring. Everyone who had been randomized to the ring really loved it. There was no breakthrough bleeding, no matter how high their [body mass indexes] were. Not to get the breakthrough bleeding on such a low dose was very nice, and I think that was due to the steady-state vaginal delivery.”

WASHINGTON — The contraceptive vaginal ring has fewer metabolic adverse effects than do oral contraceptives and may be a better alternative for insulin-resistant women, those with diabetes, and women with metabolic syndrome at increased risk for cardiovascular disease, Dr. Karen Elkind-Hirsch and colleagues wrote in a poster presented at the annual meeting of the American College of Obstetricians and Gynecologists.

Combined oral contraceptives remain the first line of treatment for women who desired birth control or cycle control with contraceptive steroids. Although much effort has been directed toward minimizing their potential thromboembolic and cardiovascular disease risks, much less attention has been given to their metabolic effects, wrote Dr. Elkind-Hirsch, scientific director of the Woman's Health Research Institute in Baton Rouge, La.

There is some evidence that oral contraceptives may aggravate insulin resistance and exert other untoward metabolic effects that might increase a woman's long-term risk for diabetes and heart disease. Delivering low-dose oral contraceptives via a nonoral route such as the vaginal ring might provide efficacy and good cycle control with less risk, they wrote.

To test this, the investigators randomized 30 women aged 18–40 years to either the vaginal ring or to a low-dose monophasic oral contraceptive for five continuous menstrual cycles. They tested the effects of both methods of birth control on carbohydrate metabolism, using insulin sensitivity indices derived from fasting and oral glucose tolerance tests.

All patients were similar with regard to age, weight, and metabolic parameters at baseline. However, by the end of the treatment period, the researchers noted that insulin sensitivity measured with a glucose tolerance test was significantly decreased in women taking the oral contraceptive pill, compared with women using the vaginal ring. The pill also significantly increased insulin resistance from baseline to after the treatment period when fasting levels alone were measured.

The study results confirm that low-dose oral contraceptives can adversely impact metabolic function, Dr. Elkind-Hirsch and her colleagues concluded. “So many women of reproductive age have insulin resistance or type 2 diabetes now,” she said in an interview. “What birth control can we put them on that will not make this worse?

“The other issue is obesity. When you give the contraceptive drug vaginally, you're right at the source, so you can give less. We don't have to go orally, thus bypass the liver, and the ring delivers the drug at a more steady state than the pill,”she added.

She added that the “women loved the ring. Everyone who had been randomized to the ring really loved it. There was no breakthrough bleeding, no matter how high their [body mass indexes] were. Not to get the breakthrough bleeding on such a low dose was very nice, and I think that was due to the steady-state vaginal delivery.”

FORT LAUDERDALE, FLA. — Topical estrogen is important to the success of treatment for urogenital atrophy and also has therapeutic value for the management of urinary urgency, frequency, and, most importantly, nocturia, Dr. G. Willy Davila said at a symposium on pelvic floor disorders sponsored by the Cleveland Clinic Florida.

However, overcoming the fears of patients and oncologists about the safety of localized estrogen remains an uphill battle, said Dr. Davila, chairman of the department of gynecology, urology, and reconstructive pelvic surgery at the Cleveland Clinic Florida, Weston.

“Our task is to allay the fears of patients who come in and have this almost paranoid fear of any estrogen therapy. The main challenge is having the patient be compliant with therapy,” he said.

Patients may be concerned that any form of estrogen might get into the bloodstream. But with vaginal estrogen, the dosage can be tailored so that it is not absorbed systemically, with the result that blood levels of estrogen are negligible, Dr. Davila said.

If vaginal atrophy is not treated, it will progress; advanced urogenital atrophy with increasing degrees of labial fusion is a common occurrence. The traditional treatment has been to lyse the labia, but this will be a stopgap measure only. “The most important issue is not that you lyse the labia, but rather that the patient continue using local estrogen. If the patient does not use local estrogen cream, this fusion will recur fairly promptly,” he said.

Other conditions that respond well to local estrogen therapy include nocturia, dyspareunia, and stress incontinence. For the latter, adding an α-agonist to the estrogen preparation will have a synergistic effect and this can be very useful for stress incontinence in cases of significant atrophy. Local estrogen should also be applied if a woman is using a pessary to prevent erosion and ulceration, Dr. Davila said. Routine measurement of estradiol levels can reassure the patient that she is not absorbing estrogen systemically, he added.

Dr. Vincent Lucente of Temple University School of Medicine, Philadelphia, commented that there are no well-designed clinical trials that look specifically at topical applications of estrogen and urged continued investigation of the subject.

FORT LAUDERDALE, FLA. — Topical estrogen is important to the success of treatment for urogenital atrophy and also has therapeutic value for the management of urinary urgency, frequency, and, most importantly, nocturia, Dr. G. Willy Davila said at a symposium on pelvic floor disorders sponsored by the Cleveland Clinic Florida.

However, overcoming the fears of patients and oncologists about the safety of localized estrogen remains an uphill battle, said Dr. Davila, chairman of the department of gynecology, urology, and reconstructive pelvic surgery at the Cleveland Clinic Florida, Weston.

“Our task is to allay the fears of patients who come in and have this almost paranoid fear of any estrogen therapy. The main challenge is having the patient be compliant with therapy,” he said.

Patients may be concerned that any form of estrogen might get into the bloodstream. But with vaginal estrogen, the dosage can be tailored so that it is not absorbed systemically, with the result that blood levels of estrogen are negligible, Dr. Davila said.

If vaginal atrophy is not treated, it will progress; advanced urogenital atrophy with increasing degrees of labial fusion is a common occurrence. The traditional treatment has been to lyse the labia, but this will be a stopgap measure only. “The most important issue is not that you lyse the labia, but rather that the patient continue using local estrogen. If the patient does not use local estrogen cream, this fusion will recur fairly promptly,” he said.

Other conditions that respond well to local estrogen therapy include nocturia, dyspareunia, and stress incontinence. For the latter, adding an α-agonist to the estrogen preparation will have a synergistic effect and this can be very useful for stress incontinence in cases of significant atrophy. Local estrogen should also be applied if a woman is using a pessary to prevent erosion and ulceration, Dr. Davila said. Routine measurement of estradiol levels can reassure the patient that she is not absorbing estrogen systemically, he added.

Dr. Vincent Lucente of Temple University School of Medicine, Philadelphia, commented that there are no well-designed clinical trials that look specifically at topical applications of estrogen and urged continued investigation of the subject.

FORT LAUDERDALE, FLA. — Topical estrogen is important to the success of treatment for urogenital atrophy and also has therapeutic value for the management of urinary urgency, frequency, and, most importantly, nocturia, Dr. G. Willy Davila said at a symposium on pelvic floor disorders sponsored by the Cleveland Clinic Florida.

However, overcoming the fears of patients and oncologists about the safety of localized estrogen remains an uphill battle, said Dr. Davila, chairman of the department of gynecology, urology, and reconstructive pelvic surgery at the Cleveland Clinic Florida, Weston.

“Our task is to allay the fears of patients who come in and have this almost paranoid fear of any estrogen therapy. The main challenge is having the patient be compliant with therapy,” he said.

Patients may be concerned that any form of estrogen might get into the bloodstream. But with vaginal estrogen, the dosage can be tailored so that it is not absorbed systemically, with the result that blood levels of estrogen are negligible, Dr. Davila said.

If vaginal atrophy is not treated, it will progress; advanced urogenital atrophy with increasing degrees of labial fusion is a common occurrence. The traditional treatment has been to lyse the labia, but this will be a stopgap measure only. “The most important issue is not that you lyse the labia, but rather that the patient continue using local estrogen. If the patient does not use local estrogen cream, this fusion will recur fairly promptly,” he said.

Other conditions that respond well to local estrogen therapy include nocturia, dyspareunia, and stress incontinence. For the latter, adding an α-agonist to the estrogen preparation will have a synergistic effect and this can be very useful for stress incontinence in cases of significant atrophy. Local estrogen should also be applied if a woman is using a pessary to prevent erosion and ulceration, Dr. Davila said. Routine measurement of estradiol levels can reassure the patient that she is not absorbing estrogen systemically, he added.

Dr. Vincent Lucente of Temple University School of Medicine, Philadelphia, commented that there are no well-designed clinical trials that look specifically at topical applications of estrogen and urged continued investigation of the subject.

WASHINGTON — The combination of drospirenone (a progestin with antialdosterone effects) and 17-β-estradiol as hormone therapy for hypertensive postmenopausal women not only reduces their hot flashes, but lowers their blood pressure as well, according to a poster presented at the annual meeting of the American College of Obstetricians and Gynecologists.

Treatment with the combination of drospirenone and 17-β-estradiol for an 8-week period produced significant reductions in systolic and diastolic 24-hour ambulatory and clinic blood pressure at 2- and 3-mg doses of drospirenone, reported Dr. William B. White, professor of medicine at the University of Connecticut, Farmington.

Drospirenone plus estradiol has been used for the treatment of menopausal symptoms and is Food and Drug Administration-approved for this indication at a dose of 0.5 mg drospirenone/1 mg estradiol (marketed in the United States as Angeliq by Berlex Laboratories Inc.). During its development, it was noted that at a higher drospirenone dose, the combination also had antihypertensive properties. It is currently being used in Europe, Asia, and the rest of the world at a dose of 2 mg drospirenone/1 mg estradiol, Dr. White told this news organization.

In a multicenter (42 U.S. centers and 22 European centers) trial, Dr. White and his colleagues evaluated the blood pressure-lowering efficacy of various doses of drospirenone (1, 2, or 3 mg) combined with 1 mg of estradiol in 750 postmenopausal women aged 45–75 years, with an untreated systolic blood pressure of 140–179 mm Hg and untreated diastolic blood pressure of 90–109 mm Hg. They also evaluated estradiol alone to elicit data on the effects of estrogen on ambulatory blood pressure, about which little is known, wrote Dr. White.

In addition, because drugs which induce aldosterone blockade have been shown to increase serum potassium, the researchers evaluated the metabolic effects of the combination therapy.

Following a single-blind, placebo phase for 3–4 weeks to establish baseline blood pressure and laboratory values, the women were randomized to one of the three combination treatment arms, to estradiol alone, or to placebo. Twenty-four-hour ambulatory blood pressure monitoring was done at baseline and at 8 weeks.

Drospirenone at the 2-mg dose reduced clinical systolic and diastolic blood pressures by a mean of 12.1 and 9.2 mm Hg, respectively; and by a mean of 13.8 and 8.5 mm Hg, respectively at the 3-mg dose. Drospirenone at the 1-mg dose was less effective, reducing systolic BP by a mean of 9.8 mm Hg and diastolic BP by a mean of 7.0 mm Hg. The blood pressure-lowering effect of estradiol (−7.6 mm Hg systolic and −5.9 mm Hg diastolic) was similar to that seen with placebo, Dr. White wrote.

Reductions in ambulatory blood pressure showed findings similar to clinic readings, although the combination with 1 mg of drospirenone also had marginal benefits compared with placebo and estradiol alone, he added.

Changes in potassium levels were similar in all groups: Five patients in each of the drospirenone groups and five in the placebo group developed a serum potassium less than or equal to 5.5 mEq/L. The mean maximal change from baseline in drospirenone-treated patients was not significantly different among the five treatment groups and ranged between 0.29 mEq/L and 0.37 mEq/L.

Regarding the combination's effect on lipid levels, total and LDL cholesterol levels also were lowered significantly in women taking drospirenone and estradiol, with a 13.6-mg/dL drop in LDL cholesterol at the 3-mg dose, a 10.4-mg/dL drop at the 2-mg dose, and a 12.2 drop at the 1-mg dose. Triglyceride levels were not affected, Dr. White wrote.

Side effects varied according to drospirenone dose; those seen with a frequency greater than 2% included breast discomfort, vaginal bleeding or spotting, and upper respiratory infection, according to the researchers.

“This is a novel progestin which actually impacts upon aldosterone and therefore has a dose-related reduction in blood pressure—especially the systolic blood pressure—which is associated with cardiovascular risk. We actually studied a full spectrum of doses, along with estradiol alone and placebo, so the strength of the study is that we actually had these two control groups showing that, in fact, it was the drospirenone that was the important component that lowered the blood pressure. And it did that without any significant metabolic consequences,” Dr. White said in an interview. Dr. White disclosed that he serves as a consultant for Berlex Laboratories Inc., which markets Angeliq, as well as other pharmaceutical companies.

WASHINGTON — The combination of drospirenone (a progestin with antialdosterone effects) and 17-β-estradiol as hormone therapy for hypertensive postmenopausal women not only reduces their hot flashes, but lowers their blood pressure as well, according to a poster presented at the annual meeting of the American College of Obstetricians and Gynecologists.

Treatment with the combination of drospirenone and 17-β-estradiol for an 8-week period produced significant reductions in systolic and diastolic 24-hour ambulatory and clinic blood pressure at 2- and 3-mg doses of drospirenone, reported Dr. William B. White, professor of medicine at the University of Connecticut, Farmington.

Drospirenone plus estradiol has been used for the treatment of menopausal symptoms and is Food and Drug Administration-approved for this indication at a dose of 0.5 mg drospirenone/1 mg estradiol (marketed in the United States as Angeliq by Berlex Laboratories Inc.). During its development, it was noted that at a higher drospirenone dose, the combination also had antihypertensive properties. It is currently being used in Europe, Asia, and the rest of the world at a dose of 2 mg drospirenone/1 mg estradiol, Dr. White told this news organization.

In a multicenter (42 U.S. centers and 22 European centers) trial, Dr. White and his colleagues evaluated the blood pressure-lowering efficacy of various doses of drospirenone (1, 2, or 3 mg) combined with 1 mg of estradiol in 750 postmenopausal women aged 45–75 years, with an untreated systolic blood pressure of 140–179 mm Hg and untreated diastolic blood pressure of 90–109 mm Hg. They also evaluated estradiol alone to elicit data on the effects of estrogen on ambulatory blood pressure, about which little is known, wrote Dr. White.

In addition, because drugs which induce aldosterone blockade have been shown to increase serum potassium, the researchers evaluated the metabolic effects of the combination therapy.

Following a single-blind, placebo phase for 3–4 weeks to establish baseline blood pressure and laboratory values, the women were randomized to one of the three combination treatment arms, to estradiol alone, or to placebo. Twenty-four-hour ambulatory blood pressure monitoring was done at baseline and at 8 weeks.

Drospirenone at the 2-mg dose reduced clinical systolic and diastolic blood pressures by a mean of 12.1 and 9.2 mm Hg, respectively; and by a mean of 13.8 and 8.5 mm Hg, respectively at the 3-mg dose. Drospirenone at the 1-mg dose was less effective, reducing systolic BP by a mean of 9.8 mm Hg and diastolic BP by a mean of 7.0 mm Hg. The blood pressure-lowering effect of estradiol (−7.6 mm Hg systolic and −5.9 mm Hg diastolic) was similar to that seen with placebo, Dr. White wrote.

Reductions in ambulatory blood pressure showed findings similar to clinic readings, although the combination with 1 mg of drospirenone also had marginal benefits compared with placebo and estradiol alone, he added.

Changes in potassium levels were similar in all groups: Five patients in each of the drospirenone groups and five in the placebo group developed a serum potassium less than or equal to 5.5 mEq/L. The mean maximal change from baseline in drospirenone-treated patients was not significantly different among the five treatment groups and ranged between 0.29 mEq/L and 0.37 mEq/L.

Regarding the combination's effect on lipid levels, total and LDL cholesterol levels also were lowered significantly in women taking drospirenone and estradiol, with a 13.6-mg/dL drop in LDL cholesterol at the 3-mg dose, a 10.4-mg/dL drop at the 2-mg dose, and a 12.2 drop at the 1-mg dose. Triglyceride levels were not affected, Dr. White wrote.

Side effects varied according to drospirenone dose; those seen with a frequency greater than 2% included breast discomfort, vaginal bleeding or spotting, and upper respiratory infection, according to the researchers.

“This is a novel progestin which actually impacts upon aldosterone and therefore has a dose-related reduction in blood pressure—especially the systolic blood pressure—which is associated with cardiovascular risk. We actually studied a full spectrum of doses, along with estradiol alone and placebo, so the strength of the study is that we actually had these two control groups showing that, in fact, it was the drospirenone that was the important component that lowered the blood pressure. And it did that without any significant metabolic consequences,” Dr. White said in an interview. Dr. White disclosed that he serves as a consultant for Berlex Laboratories Inc., which markets Angeliq, as well as other pharmaceutical companies.

WASHINGTON — The combination of drospirenone (a progestin with antialdosterone effects) and 17-β-estradiol as hormone therapy for hypertensive postmenopausal women not only reduces their hot flashes, but lowers their blood pressure as well, according to a poster presented at the annual meeting of the American College of Obstetricians and Gynecologists.

Treatment with the combination of drospirenone and 17-β-estradiol for an 8-week period produced significant reductions in systolic and diastolic 24-hour ambulatory and clinic blood pressure at 2- and 3-mg doses of drospirenone, reported Dr. William B. White, professor of medicine at the University of Connecticut, Farmington.

Drospirenone plus estradiol has been used for the treatment of menopausal symptoms and is Food and Drug Administration-approved for this indication at a dose of 0.5 mg drospirenone/1 mg estradiol (marketed in the United States as Angeliq by Berlex Laboratories Inc.). During its development, it was noted that at a higher drospirenone dose, the combination also had antihypertensive properties. It is currently being used in Europe, Asia, and the rest of the world at a dose of 2 mg drospirenone/1 mg estradiol, Dr. White told this news organization.

In a multicenter (42 U.S. centers and 22 European centers) trial, Dr. White and his colleagues evaluated the blood pressure-lowering efficacy of various doses of drospirenone (1, 2, or 3 mg) combined with 1 mg of estradiol in 750 postmenopausal women aged 45–75 years, with an untreated systolic blood pressure of 140–179 mm Hg and untreated diastolic blood pressure of 90–109 mm Hg. They also evaluated estradiol alone to elicit data on the effects of estrogen on ambulatory blood pressure, about which little is known, wrote Dr. White.

In addition, because drugs which induce aldosterone blockade have been shown to increase serum potassium, the researchers evaluated the metabolic effects of the combination therapy.

Following a single-blind, placebo phase for 3–4 weeks to establish baseline blood pressure and laboratory values, the women were randomized to one of the three combination treatment arms, to estradiol alone, or to placebo. Twenty-four-hour ambulatory blood pressure monitoring was done at baseline and at 8 weeks.

Drospirenone at the 2-mg dose reduced clinical systolic and diastolic blood pressures by a mean of 12.1 and 9.2 mm Hg, respectively; and by a mean of 13.8 and 8.5 mm Hg, respectively at the 3-mg dose. Drospirenone at the 1-mg dose was less effective, reducing systolic BP by a mean of 9.8 mm Hg and diastolic BP by a mean of 7.0 mm Hg. The blood pressure-lowering effect of estradiol (−7.6 mm Hg systolic and −5.9 mm Hg diastolic) was similar to that seen with placebo, Dr. White wrote.

Reductions in ambulatory blood pressure showed findings similar to clinic readings, although the combination with 1 mg of drospirenone also had marginal benefits compared with placebo and estradiol alone, he added.

Changes in potassium levels were similar in all groups: Five patients in each of the drospirenone groups and five in the placebo group developed a serum potassium less than or equal to 5.5 mEq/L. The mean maximal change from baseline in drospirenone-treated patients was not significantly different among the five treatment groups and ranged between 0.29 mEq/L and 0.37 mEq/L.

Regarding the combination's effect on lipid levels, total and LDL cholesterol levels also were lowered significantly in women taking drospirenone and estradiol, with a 13.6-mg/dL drop in LDL cholesterol at the 3-mg dose, a 10.4-mg/dL drop at the 2-mg dose, and a 12.2 drop at the 1-mg dose. Triglyceride levels were not affected, Dr. White wrote.

Side effects varied according to drospirenone dose; those seen with a frequency greater than 2% included breast discomfort, vaginal bleeding or spotting, and upper respiratory infection, according to the researchers.

“This is a novel progestin which actually impacts upon aldosterone and therefore has a dose-related reduction in blood pressure—especially the systolic blood pressure—which is associated with cardiovascular risk. We actually studied a full spectrum of doses, along with estradiol alone and placebo, so the strength of the study is that we actually had these two control groups showing that, in fact, it was the drospirenone that was the important component that lowered the blood pressure. And it did that without any significant metabolic consequences,” Dr. White said in an interview. Dr. White disclosed that he serves as a consultant for Berlex Laboratories Inc., which markets Angeliq, as well as other pharmaceutical companies.