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Sperm quality linked to some recurrent pregnancy loss
NEW ORLEANS – Couples with recurrent pregnancy loss (RPL) might benefit from seminal parameter testing, based on results from a study presented at the annual meeting of the Endocrine Society.
Sperm quality was more likely to be impaired in the 50 male partners of women with recurrent pregnancy loss than it was in a control group of 63 similar-age men, reported Anastasia P. Dimakopoulou, MBBS, a clinical research fellow at Imperial College, London.
Recurrent pregnancy loss is defined as three pregnancy losses before 20 weeks of gestation.
The reported prevalence of RPL has been estimated at less than 2% in couples attempting pregnancy. About half of those cases are considered to be idiopathic, she said.
Sperm DNA plays a role in placentation, and previous study findings have shown that men in RPL couples are more likely to have higher rates of DNA fragmentation in their sperm. Male partners are not routinely evaluated when seeking a cause for RPL, however.
In this study, 50 men from RPL couples and 63 control men were screened for factors known to affect sperm quality, such as previous testicular surgery, sexually transmitted diseases, alcohol intake, and smoking. In patients and controls, semen reactive oxidative stress, a novel biomarker of sperm function, was measured with a chemiluminescence luminol assay.
The proportion of men with abnormal sperm morphology, although modest in both groups, was significantly more common in men from RPL couples than in controls (4.5% vs. 3.4%, respectively; P less than .001). In addition, the mean reactive oxidative stress levels were four times greater in the RPL men (9.3 vs. 2.3 relative light units/sec per 106 sperm; P less than .05).
Consistent with the higher median reactive oxidative stress levels, the median DNA fragmentation index, which is likely to be linked to increased reactive oxidative stress, was more than twice as high in the RPL men, compared with the controls (16.3 vs. 7.4; P less than .0001).
In addition, the sperm volume was significantly lower in men from the RPL couples, compared with controls. The levels of morning serum testosterone also were lower in men from RPL couples, but the difference did not reach significance relative to controls.
There has been relatively little attention directed toward the male partner in the evaluation and treatment of RPL, but that should change, according to Dr. Dimakopoulou. She said data encourage a new direction of study, including the effort to look for treatable causes of RPL in the male partner.
“By pursuing drugs that stop sperm DNA damage, it may be possible to identify new therapeutic pathways for couples who experience RPL,” Dr. Dimakopoulou maintained. However, even in advance of targeted therapies, she suggested these data encourage investigation of male partners in couples with RPL. Although evidence of reactive oxidative stress may not define a cause, it broadens the scope of investigation and might have value when counseling patients.
Dr. Dimakopoulou reported no relevant financial relationships to disclose.
SOURCE: Dimakopoulou AP et al. ENDO 2019, Session OR18-5.
NEW ORLEANS – Couples with recurrent pregnancy loss (RPL) might benefit from seminal parameter testing, based on results from a study presented at the annual meeting of the Endocrine Society.
Sperm quality was more likely to be impaired in the 50 male partners of women with recurrent pregnancy loss than it was in a control group of 63 similar-age men, reported Anastasia P. Dimakopoulou, MBBS, a clinical research fellow at Imperial College, London.
Recurrent pregnancy loss is defined as three pregnancy losses before 20 weeks of gestation.
The reported prevalence of RPL has been estimated at less than 2% in couples attempting pregnancy. About half of those cases are considered to be idiopathic, she said.
Sperm DNA plays a role in placentation, and previous study findings have shown that men in RPL couples are more likely to have higher rates of DNA fragmentation in their sperm. Male partners are not routinely evaluated when seeking a cause for RPL, however.
In this study, 50 men from RPL couples and 63 control men were screened for factors known to affect sperm quality, such as previous testicular surgery, sexually transmitted diseases, alcohol intake, and smoking. In patients and controls, semen reactive oxidative stress, a novel biomarker of sperm function, was measured with a chemiluminescence luminol assay.
The proportion of men with abnormal sperm morphology, although modest in both groups, was significantly more common in men from RPL couples than in controls (4.5% vs. 3.4%, respectively; P less than .001). In addition, the mean reactive oxidative stress levels were four times greater in the RPL men (9.3 vs. 2.3 relative light units/sec per 106 sperm; P less than .05).
Consistent with the higher median reactive oxidative stress levels, the median DNA fragmentation index, which is likely to be linked to increased reactive oxidative stress, was more than twice as high in the RPL men, compared with the controls (16.3 vs. 7.4; P less than .0001).
In addition, the sperm volume was significantly lower in men from the RPL couples, compared with controls. The levels of morning serum testosterone also were lower in men from RPL couples, but the difference did not reach significance relative to controls.
There has been relatively little attention directed toward the male partner in the evaluation and treatment of RPL, but that should change, according to Dr. Dimakopoulou. She said data encourage a new direction of study, including the effort to look for treatable causes of RPL in the male partner.
“By pursuing drugs that stop sperm DNA damage, it may be possible to identify new therapeutic pathways for couples who experience RPL,” Dr. Dimakopoulou maintained. However, even in advance of targeted therapies, she suggested these data encourage investigation of male partners in couples with RPL. Although evidence of reactive oxidative stress may not define a cause, it broadens the scope of investigation and might have value when counseling patients.
Dr. Dimakopoulou reported no relevant financial relationships to disclose.
SOURCE: Dimakopoulou AP et al. ENDO 2019, Session OR18-5.
NEW ORLEANS – Couples with recurrent pregnancy loss (RPL) might benefit from seminal parameter testing, based on results from a study presented at the annual meeting of the Endocrine Society.
Sperm quality was more likely to be impaired in the 50 male partners of women with recurrent pregnancy loss than it was in a control group of 63 similar-age men, reported Anastasia P. Dimakopoulou, MBBS, a clinical research fellow at Imperial College, London.
Recurrent pregnancy loss is defined as three pregnancy losses before 20 weeks of gestation.
The reported prevalence of RPL has been estimated at less than 2% in couples attempting pregnancy. About half of those cases are considered to be idiopathic, she said.
Sperm DNA plays a role in placentation, and previous study findings have shown that men in RPL couples are more likely to have higher rates of DNA fragmentation in their sperm. Male partners are not routinely evaluated when seeking a cause for RPL, however.
In this study, 50 men from RPL couples and 63 control men were screened for factors known to affect sperm quality, such as previous testicular surgery, sexually transmitted diseases, alcohol intake, and smoking. In patients and controls, semen reactive oxidative stress, a novel biomarker of sperm function, was measured with a chemiluminescence luminol assay.
The proportion of men with abnormal sperm morphology, although modest in both groups, was significantly more common in men from RPL couples than in controls (4.5% vs. 3.4%, respectively; P less than .001). In addition, the mean reactive oxidative stress levels were four times greater in the RPL men (9.3 vs. 2.3 relative light units/sec per 106 sperm; P less than .05).
Consistent with the higher median reactive oxidative stress levels, the median DNA fragmentation index, which is likely to be linked to increased reactive oxidative stress, was more than twice as high in the RPL men, compared with the controls (16.3 vs. 7.4; P less than .0001).
In addition, the sperm volume was significantly lower in men from the RPL couples, compared with controls. The levels of morning serum testosterone also were lower in men from RPL couples, but the difference did not reach significance relative to controls.
There has been relatively little attention directed toward the male partner in the evaluation and treatment of RPL, but that should change, according to Dr. Dimakopoulou. She said data encourage a new direction of study, including the effort to look for treatable causes of RPL in the male partner.
“By pursuing drugs that stop sperm DNA damage, it may be possible to identify new therapeutic pathways for couples who experience RPL,” Dr. Dimakopoulou maintained. However, even in advance of targeted therapies, she suggested these data encourage investigation of male partners in couples with RPL. Although evidence of reactive oxidative stress may not define a cause, it broadens the scope of investigation and might have value when counseling patients.
Dr. Dimakopoulou reported no relevant financial relationships to disclose.
SOURCE: Dimakopoulou AP et al. ENDO 2019, Session OR18-5.
REPORTING FROM ENDO 2019
CPAP use associated with greater weight loss in obese patients with sleep apnea
NEW ORLEANS – Contrary to previously published data suggesting continuous positive airway pressure (CPAP) produces weight gain in patients with obstructive sleep apnea (OSA), new study findings presented at the annual meeting of the Endocrine Society provided data supporting the exact opposite conclusion.
“We think the data are strong enough to conclude that combining CPAP with a weight-loss program should be considered for all OSA patients. The weight-loss advantage is substantial,” reported Yuanjie Mao, MD, PhD, of the University of Arkansas for Medical Sciences, Little Rock.
Both weight loss and CPAP have been shown to be effective for the treatment of OSA, but concern that CPAP produces a counterproductive gain in weight was raised by findings in a meta-analysis in which CPAP was associated with increased body mass index (Thorax. 2015 Mar;70:258-64). As a result of that finding, some guidelines subsequently advised intensifying a weight-loss program at the time that CPAP is initiated to mitigate the weight gain effect, according to Dr. Mao. However, he noted that prospective data were never collected, so a causal relationship was never proven. Now, his data support the opposite conclusion.
In the more recent study, 300 patients who had participated in an intensive weight-loss program at his institution were divided into three groups: OSA patients who had been treated with CPAP, symptomatic OSA patients who had not been treated with CPAP, and asymptomatic OSA patients not treated with CPAP. They were compared retrospectively for weight change over a 16-week period.
“This was a very simple study,” said Dr. Mao, who explained that several exclusions, such as thyroid dysfunction, active infection, and uncontrolled diabetes, were used to reduce variables that might also affect weight change. At the end of 16 weeks, the median absolute weight loss in the CPAP group was 26.7 lb (12.1 kg), compared with 21 lb (9.5 kg) for the symptomatic OSA group and 19.2 lb (8.7 kg) for the asymptomatic OSA group. The weight loss was significantly greater for the CPAP group (P less than .01), compared with either of the other two groups, but not significantly different between the groups that were not treated with CPAP.
“The differences remained significant after adjusting for baseline BMI [body mass index], age, and gender,” Dr. Mao reported.
Asked why his data contradicted the previously reported data, Dr. Mao said that the previous studies were not evaluating CPAP in the context of a weight-loss program. He contends that when CPAP is combined with a rigorous weight-reduction regimen, there is an additive benefit from CPAP.
According to Dr. Mao, these data bring the value of CPAP for weight loss full circle. Before publication of the 2015 meta-analysis, it was widely assumed that CPAP helped with weight loss based on the expectation that better sleep quality would increase daytime activity. However, in the absence of strong data confirming that effect, Dr. Mao believes the unexpected results of the 2015 study easily pushed the pendulum in the opposite direction.
“The conclusion that CPAP increases weight was drawn from studies not designed to evaluate a weight-loss effect in those participating in a weight-loss program,” Dr. Mao explained. His study suggests that it is this combination that is important. He believes the observed effect from better sleep quality associated with CPAP is not necessarily related to better daytime function alone.
“Patients who sleep well also have more favorable diurnal changes in factors that might be important to weight change, such as leptin resistance and hormonal secretion,” he said. Although more work is needed to determine whether these purported mechanisms are important, he thinks his study has an immediate clinical message.
“Patients with OSA who are prescribed weight loss should also be considered for CPAP for the goal of weight loss,” Dr. Mao said. “We think this therapy should be started right away.”
SOURCE: Mao Y et al. ENDO 2019, Session SAT-095.
NEW ORLEANS – Contrary to previously published data suggesting continuous positive airway pressure (CPAP) produces weight gain in patients with obstructive sleep apnea (OSA), new study findings presented at the annual meeting of the Endocrine Society provided data supporting the exact opposite conclusion.
“We think the data are strong enough to conclude that combining CPAP with a weight-loss program should be considered for all OSA patients. The weight-loss advantage is substantial,” reported Yuanjie Mao, MD, PhD, of the University of Arkansas for Medical Sciences, Little Rock.
Both weight loss and CPAP have been shown to be effective for the treatment of OSA, but concern that CPAP produces a counterproductive gain in weight was raised by findings in a meta-analysis in which CPAP was associated with increased body mass index (Thorax. 2015 Mar;70:258-64). As a result of that finding, some guidelines subsequently advised intensifying a weight-loss program at the time that CPAP is initiated to mitigate the weight gain effect, according to Dr. Mao. However, he noted that prospective data were never collected, so a causal relationship was never proven. Now, his data support the opposite conclusion.
In the more recent study, 300 patients who had participated in an intensive weight-loss program at his institution were divided into three groups: OSA patients who had been treated with CPAP, symptomatic OSA patients who had not been treated with CPAP, and asymptomatic OSA patients not treated with CPAP. They were compared retrospectively for weight change over a 16-week period.
“This was a very simple study,” said Dr. Mao, who explained that several exclusions, such as thyroid dysfunction, active infection, and uncontrolled diabetes, were used to reduce variables that might also affect weight change. At the end of 16 weeks, the median absolute weight loss in the CPAP group was 26.7 lb (12.1 kg), compared with 21 lb (9.5 kg) for the symptomatic OSA group and 19.2 lb (8.7 kg) for the asymptomatic OSA group. The weight loss was significantly greater for the CPAP group (P less than .01), compared with either of the other two groups, but not significantly different between the groups that were not treated with CPAP.
“The differences remained significant after adjusting for baseline BMI [body mass index], age, and gender,” Dr. Mao reported.
Asked why his data contradicted the previously reported data, Dr. Mao said that the previous studies were not evaluating CPAP in the context of a weight-loss program. He contends that when CPAP is combined with a rigorous weight-reduction regimen, there is an additive benefit from CPAP.
According to Dr. Mao, these data bring the value of CPAP for weight loss full circle. Before publication of the 2015 meta-analysis, it was widely assumed that CPAP helped with weight loss based on the expectation that better sleep quality would increase daytime activity. However, in the absence of strong data confirming that effect, Dr. Mao believes the unexpected results of the 2015 study easily pushed the pendulum in the opposite direction.
“The conclusion that CPAP increases weight was drawn from studies not designed to evaluate a weight-loss effect in those participating in a weight-loss program,” Dr. Mao explained. His study suggests that it is this combination that is important. He believes the observed effect from better sleep quality associated with CPAP is not necessarily related to better daytime function alone.
“Patients who sleep well also have more favorable diurnal changes in factors that might be important to weight change, such as leptin resistance and hormonal secretion,” he said. Although more work is needed to determine whether these purported mechanisms are important, he thinks his study has an immediate clinical message.
“Patients with OSA who are prescribed weight loss should also be considered for CPAP for the goal of weight loss,” Dr. Mao said. “We think this therapy should be started right away.”
SOURCE: Mao Y et al. ENDO 2019, Session SAT-095.
NEW ORLEANS – Contrary to previously published data suggesting continuous positive airway pressure (CPAP) produces weight gain in patients with obstructive sleep apnea (OSA), new study findings presented at the annual meeting of the Endocrine Society provided data supporting the exact opposite conclusion.
“We think the data are strong enough to conclude that combining CPAP with a weight-loss program should be considered for all OSA patients. The weight-loss advantage is substantial,” reported Yuanjie Mao, MD, PhD, of the University of Arkansas for Medical Sciences, Little Rock.
Both weight loss and CPAP have been shown to be effective for the treatment of OSA, but concern that CPAP produces a counterproductive gain in weight was raised by findings in a meta-analysis in which CPAP was associated with increased body mass index (Thorax. 2015 Mar;70:258-64). As a result of that finding, some guidelines subsequently advised intensifying a weight-loss program at the time that CPAP is initiated to mitigate the weight gain effect, according to Dr. Mao. However, he noted that prospective data were never collected, so a causal relationship was never proven. Now, his data support the opposite conclusion.
In the more recent study, 300 patients who had participated in an intensive weight-loss program at his institution were divided into three groups: OSA patients who had been treated with CPAP, symptomatic OSA patients who had not been treated with CPAP, and asymptomatic OSA patients not treated with CPAP. They were compared retrospectively for weight change over a 16-week period.
“This was a very simple study,” said Dr. Mao, who explained that several exclusions, such as thyroid dysfunction, active infection, and uncontrolled diabetes, were used to reduce variables that might also affect weight change. At the end of 16 weeks, the median absolute weight loss in the CPAP group was 26.7 lb (12.1 kg), compared with 21 lb (9.5 kg) for the symptomatic OSA group and 19.2 lb (8.7 kg) for the asymptomatic OSA group. The weight loss was significantly greater for the CPAP group (P less than .01), compared with either of the other two groups, but not significantly different between the groups that were not treated with CPAP.
“The differences remained significant after adjusting for baseline BMI [body mass index], age, and gender,” Dr. Mao reported.
Asked why his data contradicted the previously reported data, Dr. Mao said that the previous studies were not evaluating CPAP in the context of a weight-loss program. He contends that when CPAP is combined with a rigorous weight-reduction regimen, there is an additive benefit from CPAP.
According to Dr. Mao, these data bring the value of CPAP for weight loss full circle. Before publication of the 2015 meta-analysis, it was widely assumed that CPAP helped with weight loss based on the expectation that better sleep quality would increase daytime activity. However, in the absence of strong data confirming that effect, Dr. Mao believes the unexpected results of the 2015 study easily pushed the pendulum in the opposite direction.
“The conclusion that CPAP increases weight was drawn from studies not designed to evaluate a weight-loss effect in those participating in a weight-loss program,” Dr. Mao explained. His study suggests that it is this combination that is important. He believes the observed effect from better sleep quality associated with CPAP is not necessarily related to better daytime function alone.
“Patients who sleep well also have more favorable diurnal changes in factors that might be important to weight change, such as leptin resistance and hormonal secretion,” he said. Although more work is needed to determine whether these purported mechanisms are important, he thinks his study has an immediate clinical message.
“Patients with OSA who are prescribed weight loss should also be considered for CPAP for the goal of weight loss,” Dr. Mao said. “We think this therapy should be started right away.”
SOURCE: Mao Y et al. ENDO 2019, Session SAT-095.
REPORTING FROM ENDO 2019
First RCT with aromatase inhibitor for male hypogonadism shows promise
NEW ORLEANS – In obese men with hypogonadotropic hypogonadism, an experimental aromatase inhibitor (Ai) normalized testosterone, seemed to improve sperm function, and was not associated with any significant adverse safety signals, according to findings presented at the annual meeting of the Endocrine Society.
Unlike testosterone therapy, “leflutrozole was associated with positive effects on semen fertility parameters, such as semen volume and concentration,” reported Thomas Hugh Jones, MD, FRCP, of the Centre for Diabetes and Endocrinology, Barnsley Hospital NHS Foundation Trust, and the department of oncology and metabolism, University of Sheffield Medical School, both in England.
Although the impact of the experimental aromatase inhibitor leflutrozole on parameters of semen function was an exploratory analysis in this multicenter, placebo-controlled study, it is particularly noteworthy because it addresses one of the weaknesses of testosterone replacement, which is often the first choice in treating hypogonadism, Dr. Jones said.
“Testosterone replacement frequently results in negative feedback suppression of follicle stimulating hormone and luteinizing hormone so that along with lower sperm counts, these men have significant problems with fertility,” he explained.
In this phase 2, double-blind, randomized trial, 271 men with hypogonadism were randomized to placebo or to leflutrozole in a dose of 0.1 mg, 0.3 mg, or 1.0 mg taken orally once weekly. All patients had a serum testosterone level of less than 300 ng/dL at entry. The median body mass index was 38 kg/m2, and the average age was 50.9 years.
Results were presented after 24 weeks of treatment, but the blinded study continued for an additional 24 weeks.
Normalization of testosterone, defined as a level between 300 and 1,000 ng/dL, was the primary endpoint. The mean testosterone levels were essentially unchanged in the placebo group during the first 24-week phase of the study, but they climbed to means of 458 ng/dL in the 0.1-mg group, 512 ng/dL in the 0.3-mg group, and 586 ng/dL in the 1.0-mg group.
“Overall, 75% were in the normal range, but it reached 90% in the groups taking the two higher doses,” Dr. Jones reported. Testosterone levels never exceeded 1,500 ng/d.
For the effect on FSH and LH, which were secondary endpoints, both were increased in a dose-dependent manner at 12 and 20 weeks (P less than .001 for the highest dose relative to placebo).
For the semen analysis, also conducted at 12 and 20 weeks, all three doses were associated with a numerical increase in sperm count relative to placebo, with the highest dose achieving significant improvements in semen volume (P = .006), semen concentration (P = .01), and total motile sperm count (P = .03), Dr. Jones reported.
“The 48-week analysis has just been completed, and these types of improvements have been persistent,” Dr. Jones said in reference to the increase in sex hormones as well as measures of sperm function. Although he did not present the 48-week results in detail, he disclosed that this longer follow-up also supported favorable effects on bone density, which is among several prespecified substudies being performed.
Leflutrozole, which is chemically related to letrozole, has been well tolerated at the doses studied. An increase in hematocrit consistent with the rise in testosterone was observed, but Dr. Jones reported that there are no significant safety issues identified so far.
Aromatase inhibitors have been used off label to treat hypogonadism, but this is the first randomized controlled trial for this indication, Dr. Jones said.
Although leflutrozole was used in this study at far lower doses than the aromatase inhibitors currently available for treatment of breast cancer, it might provide an advance for a challenging condition, according to Dr. Jones. He did not speculate when a phase 3 registration trial might start, but he did say that the promise of this agent warrants further development.
Dr. Jones reported a financial relationship with Mereo BioPharma, the sponsor of this trial.
Source: Jones et al. ENDO 2019, Session OR18-4.
NEW ORLEANS – In obese men with hypogonadotropic hypogonadism, an experimental aromatase inhibitor (Ai) normalized testosterone, seemed to improve sperm function, and was not associated with any significant adverse safety signals, according to findings presented at the annual meeting of the Endocrine Society.
Unlike testosterone therapy, “leflutrozole was associated with positive effects on semen fertility parameters, such as semen volume and concentration,” reported Thomas Hugh Jones, MD, FRCP, of the Centre for Diabetes and Endocrinology, Barnsley Hospital NHS Foundation Trust, and the department of oncology and metabolism, University of Sheffield Medical School, both in England.
Although the impact of the experimental aromatase inhibitor leflutrozole on parameters of semen function was an exploratory analysis in this multicenter, placebo-controlled study, it is particularly noteworthy because it addresses one of the weaknesses of testosterone replacement, which is often the first choice in treating hypogonadism, Dr. Jones said.
“Testosterone replacement frequently results in negative feedback suppression of follicle stimulating hormone and luteinizing hormone so that along with lower sperm counts, these men have significant problems with fertility,” he explained.
In this phase 2, double-blind, randomized trial, 271 men with hypogonadism were randomized to placebo or to leflutrozole in a dose of 0.1 mg, 0.3 mg, or 1.0 mg taken orally once weekly. All patients had a serum testosterone level of less than 300 ng/dL at entry. The median body mass index was 38 kg/m2, and the average age was 50.9 years.
Results were presented after 24 weeks of treatment, but the blinded study continued for an additional 24 weeks.
Normalization of testosterone, defined as a level between 300 and 1,000 ng/dL, was the primary endpoint. The mean testosterone levels were essentially unchanged in the placebo group during the first 24-week phase of the study, but they climbed to means of 458 ng/dL in the 0.1-mg group, 512 ng/dL in the 0.3-mg group, and 586 ng/dL in the 1.0-mg group.
“Overall, 75% were in the normal range, but it reached 90% in the groups taking the two higher doses,” Dr. Jones reported. Testosterone levels never exceeded 1,500 ng/d.
For the effect on FSH and LH, which were secondary endpoints, both were increased in a dose-dependent manner at 12 and 20 weeks (P less than .001 for the highest dose relative to placebo).
For the semen analysis, also conducted at 12 and 20 weeks, all three doses were associated with a numerical increase in sperm count relative to placebo, with the highest dose achieving significant improvements in semen volume (P = .006), semen concentration (P = .01), and total motile sperm count (P = .03), Dr. Jones reported.
“The 48-week analysis has just been completed, and these types of improvements have been persistent,” Dr. Jones said in reference to the increase in sex hormones as well as measures of sperm function. Although he did not present the 48-week results in detail, he disclosed that this longer follow-up also supported favorable effects on bone density, which is among several prespecified substudies being performed.
Leflutrozole, which is chemically related to letrozole, has been well tolerated at the doses studied. An increase in hematocrit consistent with the rise in testosterone was observed, but Dr. Jones reported that there are no significant safety issues identified so far.
Aromatase inhibitors have been used off label to treat hypogonadism, but this is the first randomized controlled trial for this indication, Dr. Jones said.
Although leflutrozole was used in this study at far lower doses than the aromatase inhibitors currently available for treatment of breast cancer, it might provide an advance for a challenging condition, according to Dr. Jones. He did not speculate when a phase 3 registration trial might start, but he did say that the promise of this agent warrants further development.
Dr. Jones reported a financial relationship with Mereo BioPharma, the sponsor of this trial.
Source: Jones et al. ENDO 2019, Session OR18-4.
NEW ORLEANS – In obese men with hypogonadotropic hypogonadism, an experimental aromatase inhibitor (Ai) normalized testosterone, seemed to improve sperm function, and was not associated with any significant adverse safety signals, according to findings presented at the annual meeting of the Endocrine Society.
Unlike testosterone therapy, “leflutrozole was associated with positive effects on semen fertility parameters, such as semen volume and concentration,” reported Thomas Hugh Jones, MD, FRCP, of the Centre for Diabetes and Endocrinology, Barnsley Hospital NHS Foundation Trust, and the department of oncology and metabolism, University of Sheffield Medical School, both in England.
Although the impact of the experimental aromatase inhibitor leflutrozole on parameters of semen function was an exploratory analysis in this multicenter, placebo-controlled study, it is particularly noteworthy because it addresses one of the weaknesses of testosterone replacement, which is often the first choice in treating hypogonadism, Dr. Jones said.
“Testosterone replacement frequently results in negative feedback suppression of follicle stimulating hormone and luteinizing hormone so that along with lower sperm counts, these men have significant problems with fertility,” he explained.
In this phase 2, double-blind, randomized trial, 271 men with hypogonadism were randomized to placebo or to leflutrozole in a dose of 0.1 mg, 0.3 mg, or 1.0 mg taken orally once weekly. All patients had a serum testosterone level of less than 300 ng/dL at entry. The median body mass index was 38 kg/m2, and the average age was 50.9 years.
Results were presented after 24 weeks of treatment, but the blinded study continued for an additional 24 weeks.
Normalization of testosterone, defined as a level between 300 and 1,000 ng/dL, was the primary endpoint. The mean testosterone levels were essentially unchanged in the placebo group during the first 24-week phase of the study, but they climbed to means of 458 ng/dL in the 0.1-mg group, 512 ng/dL in the 0.3-mg group, and 586 ng/dL in the 1.0-mg group.
“Overall, 75% were in the normal range, but it reached 90% in the groups taking the two higher doses,” Dr. Jones reported. Testosterone levels never exceeded 1,500 ng/d.
For the effect on FSH and LH, which were secondary endpoints, both were increased in a dose-dependent manner at 12 and 20 weeks (P less than .001 for the highest dose relative to placebo).
For the semen analysis, also conducted at 12 and 20 weeks, all three doses were associated with a numerical increase in sperm count relative to placebo, with the highest dose achieving significant improvements in semen volume (P = .006), semen concentration (P = .01), and total motile sperm count (P = .03), Dr. Jones reported.
“The 48-week analysis has just been completed, and these types of improvements have been persistent,” Dr. Jones said in reference to the increase in sex hormones as well as measures of sperm function. Although he did not present the 48-week results in detail, he disclosed that this longer follow-up also supported favorable effects on bone density, which is among several prespecified substudies being performed.
Leflutrozole, which is chemically related to letrozole, has been well tolerated at the doses studied. An increase in hematocrit consistent with the rise in testosterone was observed, but Dr. Jones reported that there are no significant safety issues identified so far.
Aromatase inhibitors have been used off label to treat hypogonadism, but this is the first randomized controlled trial for this indication, Dr. Jones said.
Although leflutrozole was used in this study at far lower doses than the aromatase inhibitors currently available for treatment of breast cancer, it might provide an advance for a challenging condition, according to Dr. Jones. He did not speculate when a phase 3 registration trial might start, but he did say that the promise of this agent warrants further development.
Dr. Jones reported a financial relationship with Mereo BioPharma, the sponsor of this trial.
Source: Jones et al. ENDO 2019, Session OR18-4.
REPORTING FROM ENDO 2019
New postmenopausal osteoporosis guidelines emphasize patient priorities
NEW ORLEANS – In new guidelines for the pharmacologic management of osteoporosis, bisphosphonates have been identified as the first-line therapy with denosumab (Prolia) listed as an acceptable alternative that is particularly well suited for high-risk patients, according to a presentation at the annual meeting of the Endocrine Society.
“We hope our guideline will not only improve patient care but provide confidence in treatment,” reported guideline writing committee member Clifford J. Rosen, MD, director of the Center for Clinical and Translational Research at Maine Medical Center Research Institute, Scarborough.
The new guidelines are evidence based, relying on randomized, controlled trials to evaluate the data quality of treatment options with GRADE methodology, but Dr. Rosen said that the guideline writing committee also considered patient preferences because of concerns about the abundant evidence that adherence to pharmacologic therapies for osteoporosis is poor.
“There is a considerable gap in the treatment of osteoporosis. Most women will not take anti-osteoporosis therapies despite their efficacy, and those who do often stop,” Dr. Rosen observed. He said it was the intention of the writing committee to provide acceptable recommendations with a clear outline of benefits and risks in order to enlist patients more successfully in understanding and participating in fracture prevention.
The Endocrine Society guidelines, which are available online and will soon appear in print (J Clin Endocrinol Metab. 2019;104:1-28), are focused on pharmacologic management and therefore differ from guidelines on diagnosis and treatment published previously by the American Association of Clinical Endocrinologists (AACE) (Endocr Pract. 2016;22[Suppl 4]:1-42).
The AACE guidelines, which devote considerable space to prevention, indicated that bisphosphonates should “be generally considered as initial options for most patients who are candidates for treatment.” The AACE guidelines identify denosumab as the “treatment of choice” in patients with renal insufficiency (although not in those on dialysis or with end-stage renal disease).
In outlining some of the key features of the new guidelines at ENDO 2019, Dr. Rosen drew attention to a call for reevaluation of the need for bisphosphonates after patients have been on this therapy for 3 or more years. For those found at this time to be at low or moderate risk of fracture, a drug holiday is recommended based on guideline-cited evidence that bisphosphonates offer a residual therapeutic effect after stopping.
However, stopping is not recommended in those who remain at high risk. In these patients, bone density should be monitored at regular intervals for the goal of switching or intensifying therapy if needed. This includes use of teriparatide (Forteo) or abaloparatide (Tymlos) for periods of up to 2 years in patients with a history of severe or multiple fractures. These and other choices are included in a detailed algorithm covering both low- and high-risk patients.
Although many postmenopausal women hope to avoid pharmacologic therapy with high dietary intake of calcium and vitamin D, Dr. Rosen stressed the limited benefit of these nutrients in preventing fracture for those with established osteoporosis. While acknowledging that calcium and vitamin D enhance mineralization and maintenance of bone mass, he characterized them as “supplements” once pharmacologic therapies are indicated.
Unsurprisingly, patients prefer oral therapies that are effective but with a low burden of adverse events, according to a review of evidence undertaken by the guideline committee. Cost was a less important consideration. Dr. Rosen indicated that recognizing patient goals and priorities while explaining relative risks might engage patients in selecting a therapy to which they are willing to adhere.
He reported having no relevant financial relationships.
NEW ORLEANS – In new guidelines for the pharmacologic management of osteoporosis, bisphosphonates have been identified as the first-line therapy with denosumab (Prolia) listed as an acceptable alternative that is particularly well suited for high-risk patients, according to a presentation at the annual meeting of the Endocrine Society.
“We hope our guideline will not only improve patient care but provide confidence in treatment,” reported guideline writing committee member Clifford J. Rosen, MD, director of the Center for Clinical and Translational Research at Maine Medical Center Research Institute, Scarborough.
The new guidelines are evidence based, relying on randomized, controlled trials to evaluate the data quality of treatment options with GRADE methodology, but Dr. Rosen said that the guideline writing committee also considered patient preferences because of concerns about the abundant evidence that adherence to pharmacologic therapies for osteoporosis is poor.
“There is a considerable gap in the treatment of osteoporosis. Most women will not take anti-osteoporosis therapies despite their efficacy, and those who do often stop,” Dr. Rosen observed. He said it was the intention of the writing committee to provide acceptable recommendations with a clear outline of benefits and risks in order to enlist patients more successfully in understanding and participating in fracture prevention.
The Endocrine Society guidelines, which are available online and will soon appear in print (J Clin Endocrinol Metab. 2019;104:1-28), are focused on pharmacologic management and therefore differ from guidelines on diagnosis and treatment published previously by the American Association of Clinical Endocrinologists (AACE) (Endocr Pract. 2016;22[Suppl 4]:1-42).
The AACE guidelines, which devote considerable space to prevention, indicated that bisphosphonates should “be generally considered as initial options for most patients who are candidates for treatment.” The AACE guidelines identify denosumab as the “treatment of choice” in patients with renal insufficiency (although not in those on dialysis or with end-stage renal disease).
In outlining some of the key features of the new guidelines at ENDO 2019, Dr. Rosen drew attention to a call for reevaluation of the need for bisphosphonates after patients have been on this therapy for 3 or more years. For those found at this time to be at low or moderate risk of fracture, a drug holiday is recommended based on guideline-cited evidence that bisphosphonates offer a residual therapeutic effect after stopping.
However, stopping is not recommended in those who remain at high risk. In these patients, bone density should be monitored at regular intervals for the goal of switching or intensifying therapy if needed. This includes use of teriparatide (Forteo) or abaloparatide (Tymlos) for periods of up to 2 years in patients with a history of severe or multiple fractures. These and other choices are included in a detailed algorithm covering both low- and high-risk patients.
Although many postmenopausal women hope to avoid pharmacologic therapy with high dietary intake of calcium and vitamin D, Dr. Rosen stressed the limited benefit of these nutrients in preventing fracture for those with established osteoporosis. While acknowledging that calcium and vitamin D enhance mineralization and maintenance of bone mass, he characterized them as “supplements” once pharmacologic therapies are indicated.
Unsurprisingly, patients prefer oral therapies that are effective but with a low burden of adverse events, according to a review of evidence undertaken by the guideline committee. Cost was a less important consideration. Dr. Rosen indicated that recognizing patient goals and priorities while explaining relative risks might engage patients in selecting a therapy to which they are willing to adhere.
He reported having no relevant financial relationships.
NEW ORLEANS – In new guidelines for the pharmacologic management of osteoporosis, bisphosphonates have been identified as the first-line therapy with denosumab (Prolia) listed as an acceptable alternative that is particularly well suited for high-risk patients, according to a presentation at the annual meeting of the Endocrine Society.
“We hope our guideline will not only improve patient care but provide confidence in treatment,” reported guideline writing committee member Clifford J. Rosen, MD, director of the Center for Clinical and Translational Research at Maine Medical Center Research Institute, Scarborough.
The new guidelines are evidence based, relying on randomized, controlled trials to evaluate the data quality of treatment options with GRADE methodology, but Dr. Rosen said that the guideline writing committee also considered patient preferences because of concerns about the abundant evidence that adherence to pharmacologic therapies for osteoporosis is poor.
“There is a considerable gap in the treatment of osteoporosis. Most women will not take anti-osteoporosis therapies despite their efficacy, and those who do often stop,” Dr. Rosen observed. He said it was the intention of the writing committee to provide acceptable recommendations with a clear outline of benefits and risks in order to enlist patients more successfully in understanding and participating in fracture prevention.
The Endocrine Society guidelines, which are available online and will soon appear in print (J Clin Endocrinol Metab. 2019;104:1-28), are focused on pharmacologic management and therefore differ from guidelines on diagnosis and treatment published previously by the American Association of Clinical Endocrinologists (AACE) (Endocr Pract. 2016;22[Suppl 4]:1-42).
The AACE guidelines, which devote considerable space to prevention, indicated that bisphosphonates should “be generally considered as initial options for most patients who are candidates for treatment.” The AACE guidelines identify denosumab as the “treatment of choice” in patients with renal insufficiency (although not in those on dialysis or with end-stage renal disease).
In outlining some of the key features of the new guidelines at ENDO 2019, Dr. Rosen drew attention to a call for reevaluation of the need for bisphosphonates after patients have been on this therapy for 3 or more years. For those found at this time to be at low or moderate risk of fracture, a drug holiday is recommended based on guideline-cited evidence that bisphosphonates offer a residual therapeutic effect after stopping.
However, stopping is not recommended in those who remain at high risk. In these patients, bone density should be monitored at regular intervals for the goal of switching or intensifying therapy if needed. This includes use of teriparatide (Forteo) or abaloparatide (Tymlos) for periods of up to 2 years in patients with a history of severe or multiple fractures. These and other choices are included in a detailed algorithm covering both low- and high-risk patients.
Although many postmenopausal women hope to avoid pharmacologic therapy with high dietary intake of calcium and vitamin D, Dr. Rosen stressed the limited benefit of these nutrients in preventing fracture for those with established osteoporosis. While acknowledging that calcium and vitamin D enhance mineralization and maintenance of bone mass, he characterized them as “supplements” once pharmacologic therapies are indicated.
Unsurprisingly, patients prefer oral therapies that are effective but with a low burden of adverse events, according to a review of evidence undertaken by the guideline committee. Cost was a less important consideration. Dr. Rosen indicated that recognizing patient goals and priorities while explaining relative risks might engage patients in selecting a therapy to which they are willing to adhere.
He reported having no relevant financial relationships.
REPORTING FROM ENDO 2019
Hormones taken by transgender female teens affect fat levels, muscle mass
NEW ORLEANS – Transgender adolescents who take hormones and gonadotropin-releasing hormone analogs have body composition measures that vary between those seen in control females and males, according to results of a pilot study presented during a poster session at the annual meeting of the Endocrine Society.
“Between 0.7% and 1.6% of adolescents in the United States identify as transgender,” Natalie Nokoff, MD, of the University of Colorado Anschutz, so there will be a large population of teens who may be taking gender-affirming medications over the course of their lives. At the transgender care clinic at the university, the population of these patients has recently climbed to nearly 1,000 patients.
“There have been a few studies that have come out about the health of transgender female adults” – individuals born with a male sex but a female gender identity – for whom standard of care includes blocking puberty with a gonadotropin-releasing hormone (GnRH) analog to prevent development of male secondary sex characteristics at puberty, said Dr. Nokoff. Estradiol is used later, as well.
The impact of these regimens on overall health was examined in a cross-sectional pilot study of 14 adolescent transgender females, average age 16 years. The patients had been on estradiol for an average of about a year. Control groups were adolescent males and females who were matched by age and body mass index.
“Really, my main question of interest as a pediatric endocrinologist is what is the impact of not only hormones on short- and long-term heart health, and diabetes risk, and long-term health, but also, what [is] the impact of the puberty blockers, or GnRH analogs, with subsequent hormones on health as well,” said Dr. Nokoff. “That’s really the understudied area – what people don’t understand.
“We found that there were several differences in terms of markers of metabolic health between transgender females on estradiol” and the controls, Dr. Nokoff said. “Most notably ... they had a higher (level of) body fat than males, and lower (level) than females” in the control group.
The difference between transgender females and control females and control males for percent body fat was statistically significant (P = .03 and .003, respectively). Differences in lean body mass were also significant when comparing the transgender females and the control males and females (P = .001 and .001, respectively).
“In terms of insulin sensitivity, our other outcome of interest, there was no difference in insulin sensitivity between transgender females and control females, but they were more insulin resistant – or less insulin sensitive – than control males.” This latter difference was statistically significant (P = .01).
Dr. Nokoff reported that she had no relevant conflicts of interest.
NEW ORLEANS – Transgender adolescents who take hormones and gonadotropin-releasing hormone analogs have body composition measures that vary between those seen in control females and males, according to results of a pilot study presented during a poster session at the annual meeting of the Endocrine Society.
“Between 0.7% and 1.6% of adolescents in the United States identify as transgender,” Natalie Nokoff, MD, of the University of Colorado Anschutz, so there will be a large population of teens who may be taking gender-affirming medications over the course of their lives. At the transgender care clinic at the university, the population of these patients has recently climbed to nearly 1,000 patients.
“There have been a few studies that have come out about the health of transgender female adults” – individuals born with a male sex but a female gender identity – for whom standard of care includes blocking puberty with a gonadotropin-releasing hormone (GnRH) analog to prevent development of male secondary sex characteristics at puberty, said Dr. Nokoff. Estradiol is used later, as well.
The impact of these regimens on overall health was examined in a cross-sectional pilot study of 14 adolescent transgender females, average age 16 years. The patients had been on estradiol for an average of about a year. Control groups were adolescent males and females who were matched by age and body mass index.
“Really, my main question of interest as a pediatric endocrinologist is what is the impact of not only hormones on short- and long-term heart health, and diabetes risk, and long-term health, but also, what [is] the impact of the puberty blockers, or GnRH analogs, with subsequent hormones on health as well,” said Dr. Nokoff. “That’s really the understudied area – what people don’t understand.
“We found that there were several differences in terms of markers of metabolic health between transgender females on estradiol” and the controls, Dr. Nokoff said. “Most notably ... they had a higher (level of) body fat than males, and lower (level) than females” in the control group.
The difference between transgender females and control females and control males for percent body fat was statistically significant (P = .03 and .003, respectively). Differences in lean body mass were also significant when comparing the transgender females and the control males and females (P = .001 and .001, respectively).
“In terms of insulin sensitivity, our other outcome of interest, there was no difference in insulin sensitivity between transgender females and control females, but they were more insulin resistant – or less insulin sensitive – than control males.” This latter difference was statistically significant (P = .01).
Dr. Nokoff reported that she had no relevant conflicts of interest.
NEW ORLEANS – Transgender adolescents who take hormones and gonadotropin-releasing hormone analogs have body composition measures that vary between those seen in control females and males, according to results of a pilot study presented during a poster session at the annual meeting of the Endocrine Society.
“Between 0.7% and 1.6% of adolescents in the United States identify as transgender,” Natalie Nokoff, MD, of the University of Colorado Anschutz, so there will be a large population of teens who may be taking gender-affirming medications over the course of their lives. At the transgender care clinic at the university, the population of these patients has recently climbed to nearly 1,000 patients.
“There have been a few studies that have come out about the health of transgender female adults” – individuals born with a male sex but a female gender identity – for whom standard of care includes blocking puberty with a gonadotropin-releasing hormone (GnRH) analog to prevent development of male secondary sex characteristics at puberty, said Dr. Nokoff. Estradiol is used later, as well.
The impact of these regimens on overall health was examined in a cross-sectional pilot study of 14 adolescent transgender females, average age 16 years. The patients had been on estradiol for an average of about a year. Control groups were adolescent males and females who were matched by age and body mass index.
“Really, my main question of interest as a pediatric endocrinologist is what is the impact of not only hormones on short- and long-term heart health, and diabetes risk, and long-term health, but also, what [is] the impact of the puberty blockers, or GnRH analogs, with subsequent hormones on health as well,” said Dr. Nokoff. “That’s really the understudied area – what people don’t understand.
“We found that there were several differences in terms of markers of metabolic health between transgender females on estradiol” and the controls, Dr. Nokoff said. “Most notably ... they had a higher (level of) body fat than males, and lower (level) than females” in the control group.
The difference between transgender females and control females and control males for percent body fat was statistically significant (P = .03 and .003, respectively). Differences in lean body mass were also significant when comparing the transgender females and the control males and females (P = .001 and .001, respectively).
“In terms of insulin sensitivity, our other outcome of interest, there was no difference in insulin sensitivity between transgender females and control females, but they were more insulin resistant – or less insulin sensitive – than control males.” This latter difference was statistically significant (P = .01).
Dr. Nokoff reported that she had no relevant conflicts of interest.
REPORTING FROM ENDO 2019
NIH director updates study enrolling one million participants
NEW ORLEANS – It is not too late to enroll your patients or yourself into the largest longitudinal cohort study ever initiated, according to Francis S. Collins, MD, PhD, who is director of the National Institutes of Health (NIH).
Since May 2018, when it was initiated, the NIH-funded All of Us Research Program has already enrolled 200,000 of the planned goal of one million participants in the United States. Of these, approximately half have already provided baseline demographics and health information as well as their consent to use the slew of health data that is being collected.
“The only way to do this kind of thing is to have data – a lot of it,” said Dr. Collins, explaining the premise of the All of Us Research Program in an interview conducted at the annual meeting of the Endocrine Society.
The data are not limited to medical records: Blood samples, whole genome sequencing, wearable activity monitors, and subject-completed questionnaires are among a long list of sources of information to be collected from participants, who are expected to be followed indefinitely.
According to Dr. Collins, who delivered a plenary address at the meeting, these data will become more valuable over time, one of the most important goals of this study is to prepare the way for precision medicine. As opposed to the traditional one-size-fits-all approach to treating disease, he believes that this large dataset will allow researchers to understand differences in common diseases at the individual level.
In relation to endocrinology, Dr. Collins said that a cohort of one million participants would be expected to have close to 100,000 individuals with diabetes mellitus.
“This is going to be transformative,” said Dr. Collins, who emphasized that the enrollment is specifically designed to capture participants from diverse ethnic and racial groups.
All of the data collected will be made broadly available to research initiatives of all kinds, many of which have not yet even been envisioned.
Information on enrollment is available on line: joinallofus.org.
NEW ORLEANS – It is not too late to enroll your patients or yourself into the largest longitudinal cohort study ever initiated, according to Francis S. Collins, MD, PhD, who is director of the National Institutes of Health (NIH).
Since May 2018, when it was initiated, the NIH-funded All of Us Research Program has already enrolled 200,000 of the planned goal of one million participants in the United States. Of these, approximately half have already provided baseline demographics and health information as well as their consent to use the slew of health data that is being collected.
“The only way to do this kind of thing is to have data – a lot of it,” said Dr. Collins, explaining the premise of the All of Us Research Program in an interview conducted at the annual meeting of the Endocrine Society.
The data are not limited to medical records: Blood samples, whole genome sequencing, wearable activity monitors, and subject-completed questionnaires are among a long list of sources of information to be collected from participants, who are expected to be followed indefinitely.
According to Dr. Collins, who delivered a plenary address at the meeting, these data will become more valuable over time, one of the most important goals of this study is to prepare the way for precision medicine. As opposed to the traditional one-size-fits-all approach to treating disease, he believes that this large dataset will allow researchers to understand differences in common diseases at the individual level.
In relation to endocrinology, Dr. Collins said that a cohort of one million participants would be expected to have close to 100,000 individuals with diabetes mellitus.
“This is going to be transformative,” said Dr. Collins, who emphasized that the enrollment is specifically designed to capture participants from diverse ethnic and racial groups.
All of the data collected will be made broadly available to research initiatives of all kinds, many of which have not yet even been envisioned.
Information on enrollment is available on line: joinallofus.org.
NEW ORLEANS – It is not too late to enroll your patients or yourself into the largest longitudinal cohort study ever initiated, according to Francis S. Collins, MD, PhD, who is director of the National Institutes of Health (NIH).
Since May 2018, when it was initiated, the NIH-funded All of Us Research Program has already enrolled 200,000 of the planned goal of one million participants in the United States. Of these, approximately half have already provided baseline demographics and health information as well as their consent to use the slew of health data that is being collected.
“The only way to do this kind of thing is to have data – a lot of it,” said Dr. Collins, explaining the premise of the All of Us Research Program in an interview conducted at the annual meeting of the Endocrine Society.
The data are not limited to medical records: Blood samples, whole genome sequencing, wearable activity monitors, and subject-completed questionnaires are among a long list of sources of information to be collected from participants, who are expected to be followed indefinitely.
According to Dr. Collins, who delivered a plenary address at the meeting, these data will become more valuable over time, one of the most important goals of this study is to prepare the way for precision medicine. As opposed to the traditional one-size-fits-all approach to treating disease, he believes that this large dataset will allow researchers to understand differences in common diseases at the individual level.
In relation to endocrinology, Dr. Collins said that a cohort of one million participants would be expected to have close to 100,000 individuals with diabetes mellitus.
“This is going to be transformative,” said Dr. Collins, who emphasized that the enrollment is specifically designed to capture participants from diverse ethnic and racial groups.
All of the data collected will be made broadly available to research initiatives of all kinds, many of which have not yet even been envisioned.
Information on enrollment is available on line: joinallofus.org.
REPORTING FROM ENDO 2019
Simple screening for risk of falling in elderly can guide prevention
NEW ORLEANS – , according to an update on this field at the annual meeting at the Endocrine Society.
“The risk of falling in older adults is very high, but risk can be evaluated, and there are effective strategies for risk reduction,” reported Kenton R. Kaufman, PhD, codirector of the Biomechanics and Motion Analysis Laboratory at the Mayo Clinic, Rochester, Minn.
There is not much debate that aging individuals are at an increased risk of falls, but Dr. Kaufman presented his own set of data to reinforce this point. In a longitudinal study of 125 individuals over the age of 65 years who were followed for a year at his institution, 59% had at least one fall even though all were healthy and functional when enrolled.
“It was more common to fall in summer than in winter, and most occurred on a level surface,” said Dr. Kaufman citing data from a study published 2 years ago (Arch Gerontol Geriatr. 2017;73:240-7). About half of the falls occurred at home.
Only 20%-30% of falls lead to moderate to severe injuries, but this is enough to make fall prevention an appropriate and important focus of public health initiatives to reduce morbidity and lower health costs, according to Dr. Kaufman, citing data suggesting that the medical costs total in the billions of dollars.
As a result of a substantial body of research in this area, there are now multiple clinical tests, such as grip strength, the functional reach test, and the 5-minute walk, that provide some degree of predictive value for identifying elderly individuals at risk for falls.
In addition, simple questionnaires that measure the fear of falling, such as the Activities-Specific Balance Confidence Scale (ABC test), and the Falls Efficacy Scale, also identify individuals at higher risk of falling. According to Dr. Kaufman, the predictive value of these questionnaires stems from the fact that those with more fears are more likely to fall.
Dr. Kaufman advised using these simple measures alone or in combination to screen aging patients for risk of failing. Although he singled out grip strength and the ABC test as the clinical test and the questionnaire he is most likely to employ, he believes others are also reasonable. When performed by primary care physicians, although not specialists, evaluating patients for risk of falling is Medicare-reimbursable, according to Dr. Kaufman.
There are two components to effective prophylaxis. One is improving muscle strength. The other is improving neuromuscular response, which means moving quickly enough to compensate when one’s center of gravity is disturbed. According to Dr. Kaufman, who cited two randomized trials, exercise to restore muscle strength can by itself reduce the risk of falling by 10%-20%.
Neuromuscular training is more intensive and not widely available but very effective. This involves training patients to improve their reaction time in the event of an impending fall. This approach, called postural perturbation training, employs a harness to prevent injury.
“The elderly can lose their facility for rapid recovery but this can be relearned,” said Dr. Kaufman, who cited another two randomized trials with this approach that reduced falls by 45% and 55%.
Postural perturbation training, although used to train amputees to gain comfort ambulating on artificial limbs, has so far had limited use in the elderly, but Dr. Kaufman said it might have utility in selected individuals, and he noted that there is at least one commercial device now being marketed.
Many elderly patients will not be candidates for training to reduce falls due to frailty or comorbid conditions that prevent exercise, but Dr. Kaufman encouraged clinicians to evaluate risk of falls in aging individuals who are active because there are strategies to reduce risk, and falls are a major source of morbidity and mortality.
Even for those who are not suitable for risk reduction strategies, testing for risk of falls has the ancillary benefit of raising awareness, according to Dr. Kaufman.
Dr. Kaufman reported no relevant financial relationships to disclose.
NEW ORLEANS – , according to an update on this field at the annual meeting at the Endocrine Society.
“The risk of falling in older adults is very high, but risk can be evaluated, and there are effective strategies for risk reduction,” reported Kenton R. Kaufman, PhD, codirector of the Biomechanics and Motion Analysis Laboratory at the Mayo Clinic, Rochester, Minn.
There is not much debate that aging individuals are at an increased risk of falls, but Dr. Kaufman presented his own set of data to reinforce this point. In a longitudinal study of 125 individuals over the age of 65 years who were followed for a year at his institution, 59% had at least one fall even though all were healthy and functional when enrolled.
“It was more common to fall in summer than in winter, and most occurred on a level surface,” said Dr. Kaufman citing data from a study published 2 years ago (Arch Gerontol Geriatr. 2017;73:240-7). About half of the falls occurred at home.
Only 20%-30% of falls lead to moderate to severe injuries, but this is enough to make fall prevention an appropriate and important focus of public health initiatives to reduce morbidity and lower health costs, according to Dr. Kaufman, citing data suggesting that the medical costs total in the billions of dollars.
As a result of a substantial body of research in this area, there are now multiple clinical tests, such as grip strength, the functional reach test, and the 5-minute walk, that provide some degree of predictive value for identifying elderly individuals at risk for falls.
In addition, simple questionnaires that measure the fear of falling, such as the Activities-Specific Balance Confidence Scale (ABC test), and the Falls Efficacy Scale, also identify individuals at higher risk of falling. According to Dr. Kaufman, the predictive value of these questionnaires stems from the fact that those with more fears are more likely to fall.
Dr. Kaufman advised using these simple measures alone or in combination to screen aging patients for risk of failing. Although he singled out grip strength and the ABC test as the clinical test and the questionnaire he is most likely to employ, he believes others are also reasonable. When performed by primary care physicians, although not specialists, evaluating patients for risk of falling is Medicare-reimbursable, according to Dr. Kaufman.
There are two components to effective prophylaxis. One is improving muscle strength. The other is improving neuromuscular response, which means moving quickly enough to compensate when one’s center of gravity is disturbed. According to Dr. Kaufman, who cited two randomized trials, exercise to restore muscle strength can by itself reduce the risk of falling by 10%-20%.
Neuromuscular training is more intensive and not widely available but very effective. This involves training patients to improve their reaction time in the event of an impending fall. This approach, called postural perturbation training, employs a harness to prevent injury.
“The elderly can lose their facility for rapid recovery but this can be relearned,” said Dr. Kaufman, who cited another two randomized trials with this approach that reduced falls by 45% and 55%.
Postural perturbation training, although used to train amputees to gain comfort ambulating on artificial limbs, has so far had limited use in the elderly, but Dr. Kaufman said it might have utility in selected individuals, and he noted that there is at least one commercial device now being marketed.
Many elderly patients will not be candidates for training to reduce falls due to frailty or comorbid conditions that prevent exercise, but Dr. Kaufman encouraged clinicians to evaluate risk of falls in aging individuals who are active because there are strategies to reduce risk, and falls are a major source of morbidity and mortality.
Even for those who are not suitable for risk reduction strategies, testing for risk of falls has the ancillary benefit of raising awareness, according to Dr. Kaufman.
Dr. Kaufman reported no relevant financial relationships to disclose.
NEW ORLEANS – , according to an update on this field at the annual meeting at the Endocrine Society.
“The risk of falling in older adults is very high, but risk can be evaluated, and there are effective strategies for risk reduction,” reported Kenton R. Kaufman, PhD, codirector of the Biomechanics and Motion Analysis Laboratory at the Mayo Clinic, Rochester, Minn.
There is not much debate that aging individuals are at an increased risk of falls, but Dr. Kaufman presented his own set of data to reinforce this point. In a longitudinal study of 125 individuals over the age of 65 years who were followed for a year at his institution, 59% had at least one fall even though all were healthy and functional when enrolled.
“It was more common to fall in summer than in winter, and most occurred on a level surface,” said Dr. Kaufman citing data from a study published 2 years ago (Arch Gerontol Geriatr. 2017;73:240-7). About half of the falls occurred at home.
Only 20%-30% of falls lead to moderate to severe injuries, but this is enough to make fall prevention an appropriate and important focus of public health initiatives to reduce morbidity and lower health costs, according to Dr. Kaufman, citing data suggesting that the medical costs total in the billions of dollars.
As a result of a substantial body of research in this area, there are now multiple clinical tests, such as grip strength, the functional reach test, and the 5-minute walk, that provide some degree of predictive value for identifying elderly individuals at risk for falls.
In addition, simple questionnaires that measure the fear of falling, such as the Activities-Specific Balance Confidence Scale (ABC test), and the Falls Efficacy Scale, also identify individuals at higher risk of falling. According to Dr. Kaufman, the predictive value of these questionnaires stems from the fact that those with more fears are more likely to fall.
Dr. Kaufman advised using these simple measures alone or in combination to screen aging patients for risk of failing. Although he singled out grip strength and the ABC test as the clinical test and the questionnaire he is most likely to employ, he believes others are also reasonable. When performed by primary care physicians, although not specialists, evaluating patients for risk of falling is Medicare-reimbursable, according to Dr. Kaufman.
There are two components to effective prophylaxis. One is improving muscle strength. The other is improving neuromuscular response, which means moving quickly enough to compensate when one’s center of gravity is disturbed. According to Dr. Kaufman, who cited two randomized trials, exercise to restore muscle strength can by itself reduce the risk of falling by 10%-20%.
Neuromuscular training is more intensive and not widely available but very effective. This involves training patients to improve their reaction time in the event of an impending fall. This approach, called postural perturbation training, employs a harness to prevent injury.
“The elderly can lose their facility for rapid recovery but this can be relearned,” said Dr. Kaufman, who cited another two randomized trials with this approach that reduced falls by 45% and 55%.
Postural perturbation training, although used to train amputees to gain comfort ambulating on artificial limbs, has so far had limited use in the elderly, but Dr. Kaufman said it might have utility in selected individuals, and he noted that there is at least one commercial device now being marketed.
Many elderly patients will not be candidates for training to reduce falls due to frailty or comorbid conditions that prevent exercise, but Dr. Kaufman encouraged clinicians to evaluate risk of falls in aging individuals who are active because there are strategies to reduce risk, and falls are a major source of morbidity and mortality.
Even for those who are not suitable for risk reduction strategies, testing for risk of falls has the ancillary benefit of raising awareness, according to Dr. Kaufman.
Dr. Kaufman reported no relevant financial relationships to disclose.
REPORTING FROM ENDO 2019
No birth rate gains from levothyroxine in pregnancy
Treatment with levothyroxine does not improve the live birth rate in women with thyroid peroxidase antibodies before conception, according to data presented at the annual meeting of the Endocrine Society.
Until now, the evidence for the use of levothyroxine in pregnant women with thyroid peroxidase antibodies but normal thyroid function has been inconclusive, Rima K. Dhillon-Smith, MBChB, PhD, of the University of Birmingham (England), and her coauthors said in a paper published simultaneously with the meeting presentation March 23 in the New England Journal of Medicine.
Previous studies have shown that women with thyroid peroxidase antibodies but normal thyroid function have a nearly fourfold higher risk of miscarriage and twofold higher risk of preterm birth, compared with women who don’t have the antibodies.
In the new double-blind study, 952 women with thyroid peroxidase antibodies, normal thyroid function, and a history of miscarriage or infertility were randomized either to daily 50 mcg levothyroxine or placebo, taken from conception to the end of pregnancy.
The rate of pregnancy was similar in the levothyroxine and placebo groups (56.6% vs. 58.3%, respectively), as was the live birth rate (37.4% vs. 37.9%), despite the observation that the levothyroxine group had consistently lower serum thyrotropin and higher free T4 concentrations than did the placebo group.
There were also no significant differences between the two groups in secondary outcomes of miscarriage, preterm birth, or neonatal outcomes such as birth weight.
Researchers also saw no statistically significant differences in the rate of serious adverse events or in the number of women who showed abnormal results on thyroid function tests.
The authors noted that the dosage of levothyroxine used in the study was fixed, leaving the possibility that “the dose may need to be adjusted depending on the participant’s body weight, thyroid peroxidase antibody level, or thyrotropin concentration.”
Existing guidelines from the American Thyroid Association acknowledge the lack of evidence in favor of levothyroxine decreasing the risk of pregnancy loss. However, the guidelines also state that it can be considered in antibody-positive, euthyroid women with a history of loss, “given its potential benefits in comparison with its minimal risk.”
The study was supported by the National Institute for Health Research. No conflicts of interest were declared.
SOURCE: Dhillon-Smith R et al. N Engl J Med. 2019 March 23. doi: 10.1056/NEJMoa1812537
Treatment with levothyroxine does not improve the live birth rate in women with thyroid peroxidase antibodies before conception, according to data presented at the annual meeting of the Endocrine Society.
Until now, the evidence for the use of levothyroxine in pregnant women with thyroid peroxidase antibodies but normal thyroid function has been inconclusive, Rima K. Dhillon-Smith, MBChB, PhD, of the University of Birmingham (England), and her coauthors said in a paper published simultaneously with the meeting presentation March 23 in the New England Journal of Medicine.
Previous studies have shown that women with thyroid peroxidase antibodies but normal thyroid function have a nearly fourfold higher risk of miscarriage and twofold higher risk of preterm birth, compared with women who don’t have the antibodies.
In the new double-blind study, 952 women with thyroid peroxidase antibodies, normal thyroid function, and a history of miscarriage or infertility were randomized either to daily 50 mcg levothyroxine or placebo, taken from conception to the end of pregnancy.
The rate of pregnancy was similar in the levothyroxine and placebo groups (56.6% vs. 58.3%, respectively), as was the live birth rate (37.4% vs. 37.9%), despite the observation that the levothyroxine group had consistently lower serum thyrotropin and higher free T4 concentrations than did the placebo group.
There were also no significant differences between the two groups in secondary outcomes of miscarriage, preterm birth, or neonatal outcomes such as birth weight.
Researchers also saw no statistically significant differences in the rate of serious adverse events or in the number of women who showed abnormal results on thyroid function tests.
The authors noted that the dosage of levothyroxine used in the study was fixed, leaving the possibility that “the dose may need to be adjusted depending on the participant’s body weight, thyroid peroxidase antibody level, or thyrotropin concentration.”
Existing guidelines from the American Thyroid Association acknowledge the lack of evidence in favor of levothyroxine decreasing the risk of pregnancy loss. However, the guidelines also state that it can be considered in antibody-positive, euthyroid women with a history of loss, “given its potential benefits in comparison with its minimal risk.”
The study was supported by the National Institute for Health Research. No conflicts of interest were declared.
SOURCE: Dhillon-Smith R et al. N Engl J Med. 2019 March 23. doi: 10.1056/NEJMoa1812537
Treatment with levothyroxine does not improve the live birth rate in women with thyroid peroxidase antibodies before conception, according to data presented at the annual meeting of the Endocrine Society.
Until now, the evidence for the use of levothyroxine in pregnant women with thyroid peroxidase antibodies but normal thyroid function has been inconclusive, Rima K. Dhillon-Smith, MBChB, PhD, of the University of Birmingham (England), and her coauthors said in a paper published simultaneously with the meeting presentation March 23 in the New England Journal of Medicine.
Previous studies have shown that women with thyroid peroxidase antibodies but normal thyroid function have a nearly fourfold higher risk of miscarriage and twofold higher risk of preterm birth, compared with women who don’t have the antibodies.
In the new double-blind study, 952 women with thyroid peroxidase antibodies, normal thyroid function, and a history of miscarriage or infertility were randomized either to daily 50 mcg levothyroxine or placebo, taken from conception to the end of pregnancy.
The rate of pregnancy was similar in the levothyroxine and placebo groups (56.6% vs. 58.3%, respectively), as was the live birth rate (37.4% vs. 37.9%), despite the observation that the levothyroxine group had consistently lower serum thyrotropin and higher free T4 concentrations than did the placebo group.
There were also no significant differences between the two groups in secondary outcomes of miscarriage, preterm birth, or neonatal outcomes such as birth weight.
Researchers also saw no statistically significant differences in the rate of serious adverse events or in the number of women who showed abnormal results on thyroid function tests.
The authors noted that the dosage of levothyroxine used in the study was fixed, leaving the possibility that “the dose may need to be adjusted depending on the participant’s body weight, thyroid peroxidase antibody level, or thyrotropin concentration.”
Existing guidelines from the American Thyroid Association acknowledge the lack of evidence in favor of levothyroxine decreasing the risk of pregnancy loss. However, the guidelines also state that it can be considered in antibody-positive, euthyroid women with a history of loss, “given its potential benefits in comparison with its minimal risk.”
The study was supported by the National Institute for Health Research. No conflicts of interest were declared.
SOURCE: Dhillon-Smith R et al. N Engl J Med. 2019 March 23. doi: 10.1056/NEJMoa1812537
FROM ENDO 2019
Key clinical point:
Major finding: Pregnancy rates and outcomes were similar in women treated with levothyroxine and those treated with placebo.
Study details: Double-blind, randomized, placebo-controlled trial in 952 women.
Disclosures: The study was supported by the National Institute for Health Research. No conflicts of interest were declared.
Source: Dhillon-Smith R et al. N Engl J Med. 2019 March 23. doi: 10.1056/NEJMoa1812537