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Chronic opioid use linked to low testosterone levels
NEW ORLEANS – About two thirds of men who chronically use opioids have low testosterone levels, based on a literature search of more than 50 randomized and observational studies that examined endocrine function in patients on chronic opioid therapy.
Hypocortisolism, seen in about 20% of the men in these studies, was among the other potentially significant deficiencies in endocrine function, Amir H. Zamanipoor Najafabadi, PhD, reported at the annual meeting of the Endocrine Society.
Dr. Najafabadi of Leiden University in the Netherlands, and Friso de Vries, PhD, analyzed the link between opioid use and changes in the gonadal axis. Most of the subjects in their study were men (J Endocr Soc. 2019. doi. 10.1210/js.2019-SUN-489).
While the data do not support firm conclusions on the health consequences of these endocrine observations, Dr. Najafabadi said that a prospective trial is needed to determine whether there is a potential benefit from screening patients on chronic opioids for potentially treatable endocrine deficiencies.
NEW ORLEANS – About two thirds of men who chronically use opioids have low testosterone levels, based on a literature search of more than 50 randomized and observational studies that examined endocrine function in patients on chronic opioid therapy.
Hypocortisolism, seen in about 20% of the men in these studies, was among the other potentially significant deficiencies in endocrine function, Amir H. Zamanipoor Najafabadi, PhD, reported at the annual meeting of the Endocrine Society.
Dr. Najafabadi of Leiden University in the Netherlands, and Friso de Vries, PhD, analyzed the link between opioid use and changes in the gonadal axis. Most of the subjects in their study were men (J Endocr Soc. 2019. doi. 10.1210/js.2019-SUN-489).
While the data do not support firm conclusions on the health consequences of these endocrine observations, Dr. Najafabadi said that a prospective trial is needed to determine whether there is a potential benefit from screening patients on chronic opioids for potentially treatable endocrine deficiencies.
NEW ORLEANS – About two thirds of men who chronically use opioids have low testosterone levels, based on a literature search of more than 50 randomized and observational studies that examined endocrine function in patients on chronic opioid therapy.
Hypocortisolism, seen in about 20% of the men in these studies, was among the other potentially significant deficiencies in endocrine function, Amir H. Zamanipoor Najafabadi, PhD, reported at the annual meeting of the Endocrine Society.
Dr. Najafabadi of Leiden University in the Netherlands, and Friso de Vries, PhD, analyzed the link between opioid use and changes in the gonadal axis. Most of the subjects in their study were men (J Endocr Soc. 2019. doi. 10.1210/js.2019-SUN-489).
While the data do not support firm conclusions on the health consequences of these endocrine observations, Dr. Najafabadi said that a prospective trial is needed to determine whether there is a potential benefit from screening patients on chronic opioids for potentially treatable endocrine deficiencies.
REPORTING FROM ENDO 2019
Research, clinical practice come together at transgender care symposium
NEW ORLEANS – A well-attended afternoon symposium on transgender medicine gave participants at the annual meeting of the Endocrine Society a solid grounding in transgender care, from prepubescence through adulthood. Here, Joshua Safer, MD, and Michael Irwig, MD, discuss highlights of the symposium, which brought together research, best practices, and clinical practice pearls.
In his presentation, Dr. Safer focused on The basics, he said, begin with presenting well-established, scientific principles supporting current standards of transgender care.
Dr. Safer, executive director of the Mount Sinai Center for Transgender Medicine and Surgery, New York, pointed out the critical role of gonadotropin-releasing hormone antagonists in delaying puberty for transgender girls. Blockade of puberty – and elevated testosterone – can forestall otherwise irreversible male secondary sex characteristics. These include laryngeal enlargement and bony changes of facial structure, for example.
Dr. Irwig, director of andrology at George Washington University, Washington, laid out the basics of transgender hormone therapy, including clinical pearls, such as avoiding ethinyl estradiol because of the heightened risk of venous thromboembolism.
Dr. Safer is a member of the editorial advisory board of Clinical Endocrinology News. He reported that he has received consulting fees from Endo Pharmaceuticals and that his spouse is an employee of Parexel. Dr. Irwig reported no relevant conflicts of interest or financial disclosures.
NEW ORLEANS – A well-attended afternoon symposium on transgender medicine gave participants at the annual meeting of the Endocrine Society a solid grounding in transgender care, from prepubescence through adulthood. Here, Joshua Safer, MD, and Michael Irwig, MD, discuss highlights of the symposium, which brought together research, best practices, and clinical practice pearls.
In his presentation, Dr. Safer focused on The basics, he said, begin with presenting well-established, scientific principles supporting current standards of transgender care.
Dr. Safer, executive director of the Mount Sinai Center for Transgender Medicine and Surgery, New York, pointed out the critical role of gonadotropin-releasing hormone antagonists in delaying puberty for transgender girls. Blockade of puberty – and elevated testosterone – can forestall otherwise irreversible male secondary sex characteristics. These include laryngeal enlargement and bony changes of facial structure, for example.
Dr. Irwig, director of andrology at George Washington University, Washington, laid out the basics of transgender hormone therapy, including clinical pearls, such as avoiding ethinyl estradiol because of the heightened risk of venous thromboembolism.
Dr. Safer is a member of the editorial advisory board of Clinical Endocrinology News. He reported that he has received consulting fees from Endo Pharmaceuticals and that his spouse is an employee of Parexel. Dr. Irwig reported no relevant conflicts of interest or financial disclosures.
NEW ORLEANS – A well-attended afternoon symposium on transgender medicine gave participants at the annual meeting of the Endocrine Society a solid grounding in transgender care, from prepubescence through adulthood. Here, Joshua Safer, MD, and Michael Irwig, MD, discuss highlights of the symposium, which brought together research, best practices, and clinical practice pearls.
In his presentation, Dr. Safer focused on The basics, he said, begin with presenting well-established, scientific principles supporting current standards of transgender care.
Dr. Safer, executive director of the Mount Sinai Center for Transgender Medicine and Surgery, New York, pointed out the critical role of gonadotropin-releasing hormone antagonists in delaying puberty for transgender girls. Blockade of puberty – and elevated testosterone – can forestall otherwise irreversible male secondary sex characteristics. These include laryngeal enlargement and bony changes of facial structure, for example.
Dr. Irwig, director of andrology at George Washington University, Washington, laid out the basics of transgender hormone therapy, including clinical pearls, such as avoiding ethinyl estradiol because of the heightened risk of venous thromboembolism.
Dr. Safer is a member of the editorial advisory board of Clinical Endocrinology News. He reported that he has received consulting fees from Endo Pharmaceuticals and that his spouse is an employee of Parexel. Dr. Irwig reported no relevant conflicts of interest or financial disclosures.
EXPERT ANALYSIS FROM ENDO 2019
ATA risk stratification for DTC performs well in real-world cohort
NEW ORLEANS – The 2015 American Thyroid Association risk stratification system for patients with differentiated thyroid cancer performed well in a real-world cohort with a high proportion of high-risk patients, according to a study presented at the annual meeting of the Endocrine Society.
“The 2015 ATA Risk Stratification System is an excellent predictor of both persisting disease and survival,” wrote Evert F.S. van Velsen, MD, and his colleagues at Erasmus Medical Center, Rotterdam, the Netherlands, in a poster accompanying the presentation.
Among a group of 236 patients with differentiated thyroid cancer (DTC), Dr. van Velsen and his coauthors looked at how the ATA high-risk criteria influenced patient response to therapy. By the end of the 14-year study period, initial gross extrathyroidal disease extension meant patients were much less likely to have an excellent response (odds ratio, 0.26; P less than .001), and much more likely to have persistent disease (OR, 2.57; P = .001).
Odds of having an excellent response were reduced by having high postoperative thyroglobulin levels (OR, 0.21; P less than .001), and persistent disease was more likely (OR, 2.39; P = .002).
Other high-risk criteria associated with significantly lower odds of excellent response included distant metastases (OR, 0.36), incomplete resection (OR, 0.51), and having follicular thyroid carcinoma (FTC) with extensive vascular invasion (OR, 0.27). All these risk factors also were associated with higher odds of persistent disease.
“Recurrence after no evidence of disease occurred in 14%” of the study population, said Dr. van Velsen and his coauthors, adding, “Clinicians should be aware of the relatively high recurrence risk, even after an excellent response to therapy.”
The study aimed to evaluate the 2015 ATA risk stratification system’s prognostic value in a population that included a relatively large proportion of high-risk DTC patients, to include many FTC patients. This work, they noted, augments previous assessments of the risk stratification system in lower-risk populations.
The authors noted that, in addition to predicting disease recurrence, the risk stratification system also worked as a predictor of disease-specific survival. Patients with structural incomplete response fared the worst, with a survival probability below 0.5 at 200 months on a Kaplan-Meier curve of disease-specific survival. Survival probability remained at 1.0 for patients with excellent response after first therapy and was intermediate for those with indeterminate response and biochemical incomplete response.
Overall mortality was higher in FTC patients. Over the study period, 31 of the 76 FTC patients (41%) died, compared with 39 of the PTC patients (24%; P = .010). In all, 28% of the FTC patients and 18% of the PTC patients died of thyroid cancer, but this difference didn’t reach statistical significance.
The retrospective study included adults with DTC meeting the 2015 ATA high-risk criteria who were diagnosed and/or treated at Erasmus Medical Center over a 13-year span ending in December 2015.
Overall, the investigators found 236 patients meeting inclusion criteria; 160 had papillary thyroid cancer (PTC), and the remaining 76 had FTC. The latter group were significantly older at baseline than PTC patients (64 versus 53 years), and were significantly less likely to undergo neck dissection (22% versus 55%).
In the full cohort, 96 patients (41%) had one high-risk factor, and an additional 74 (31%) had two risk factors. The remaining patients had three or more risk factors.
There was no between-group difference in the likelihood of receiving radioactive iodine treatment, but those with FTC had a lower cumulative radiation dose (195 versus 298 mCi; P less than .001).
More than half of patients (58%) had persistent disease after completing their first therapy. Of these, 51% had structural incomplete response and 7% had biochemical incomplete response. The response was indeterminate for about a quarter of the cohort, and the remaining 17% had an excellent initial response.
By the end of the study period, 55% of patients had persistent disease, and 51% had structural incomplete response (a more likely result for those with FTC than PTC). Just 4% had a biochemical incomplete response, and the response was indeterminate for 16%. Response was judged excellent for 29% of patients.
Dr. van Velsen and his coauthors reported that they had no relevant disclosures.
SOURCE: van Velsen EFS et al. ENDO 2019, Abstract MON-549.
NEW ORLEANS – The 2015 American Thyroid Association risk stratification system for patients with differentiated thyroid cancer performed well in a real-world cohort with a high proportion of high-risk patients, according to a study presented at the annual meeting of the Endocrine Society.
“The 2015 ATA Risk Stratification System is an excellent predictor of both persisting disease and survival,” wrote Evert F.S. van Velsen, MD, and his colleagues at Erasmus Medical Center, Rotterdam, the Netherlands, in a poster accompanying the presentation.
Among a group of 236 patients with differentiated thyroid cancer (DTC), Dr. van Velsen and his coauthors looked at how the ATA high-risk criteria influenced patient response to therapy. By the end of the 14-year study period, initial gross extrathyroidal disease extension meant patients were much less likely to have an excellent response (odds ratio, 0.26; P less than .001), and much more likely to have persistent disease (OR, 2.57; P = .001).
Odds of having an excellent response were reduced by having high postoperative thyroglobulin levels (OR, 0.21; P less than .001), and persistent disease was more likely (OR, 2.39; P = .002).
Other high-risk criteria associated with significantly lower odds of excellent response included distant metastases (OR, 0.36), incomplete resection (OR, 0.51), and having follicular thyroid carcinoma (FTC) with extensive vascular invasion (OR, 0.27). All these risk factors also were associated with higher odds of persistent disease.
“Recurrence after no evidence of disease occurred in 14%” of the study population, said Dr. van Velsen and his coauthors, adding, “Clinicians should be aware of the relatively high recurrence risk, even after an excellent response to therapy.”
The study aimed to evaluate the 2015 ATA risk stratification system’s prognostic value in a population that included a relatively large proportion of high-risk DTC patients, to include many FTC patients. This work, they noted, augments previous assessments of the risk stratification system in lower-risk populations.
The authors noted that, in addition to predicting disease recurrence, the risk stratification system also worked as a predictor of disease-specific survival. Patients with structural incomplete response fared the worst, with a survival probability below 0.5 at 200 months on a Kaplan-Meier curve of disease-specific survival. Survival probability remained at 1.0 for patients with excellent response after first therapy and was intermediate for those with indeterminate response and biochemical incomplete response.
Overall mortality was higher in FTC patients. Over the study period, 31 of the 76 FTC patients (41%) died, compared with 39 of the PTC patients (24%; P = .010). In all, 28% of the FTC patients and 18% of the PTC patients died of thyroid cancer, but this difference didn’t reach statistical significance.
The retrospective study included adults with DTC meeting the 2015 ATA high-risk criteria who were diagnosed and/or treated at Erasmus Medical Center over a 13-year span ending in December 2015.
Overall, the investigators found 236 patients meeting inclusion criteria; 160 had papillary thyroid cancer (PTC), and the remaining 76 had FTC. The latter group were significantly older at baseline than PTC patients (64 versus 53 years), and were significantly less likely to undergo neck dissection (22% versus 55%).
In the full cohort, 96 patients (41%) had one high-risk factor, and an additional 74 (31%) had two risk factors. The remaining patients had three or more risk factors.
There was no between-group difference in the likelihood of receiving radioactive iodine treatment, but those with FTC had a lower cumulative radiation dose (195 versus 298 mCi; P less than .001).
More than half of patients (58%) had persistent disease after completing their first therapy. Of these, 51% had structural incomplete response and 7% had biochemical incomplete response. The response was indeterminate for about a quarter of the cohort, and the remaining 17% had an excellent initial response.
By the end of the study period, 55% of patients had persistent disease, and 51% had structural incomplete response (a more likely result for those with FTC than PTC). Just 4% had a biochemical incomplete response, and the response was indeterminate for 16%. Response was judged excellent for 29% of patients.
Dr. van Velsen and his coauthors reported that they had no relevant disclosures.
SOURCE: van Velsen EFS et al. ENDO 2019, Abstract MON-549.
NEW ORLEANS – The 2015 American Thyroid Association risk stratification system for patients with differentiated thyroid cancer performed well in a real-world cohort with a high proportion of high-risk patients, according to a study presented at the annual meeting of the Endocrine Society.
“The 2015 ATA Risk Stratification System is an excellent predictor of both persisting disease and survival,” wrote Evert F.S. van Velsen, MD, and his colleagues at Erasmus Medical Center, Rotterdam, the Netherlands, in a poster accompanying the presentation.
Among a group of 236 patients with differentiated thyroid cancer (DTC), Dr. van Velsen and his coauthors looked at how the ATA high-risk criteria influenced patient response to therapy. By the end of the 14-year study period, initial gross extrathyroidal disease extension meant patients were much less likely to have an excellent response (odds ratio, 0.26; P less than .001), and much more likely to have persistent disease (OR, 2.57; P = .001).
Odds of having an excellent response were reduced by having high postoperative thyroglobulin levels (OR, 0.21; P less than .001), and persistent disease was more likely (OR, 2.39; P = .002).
Other high-risk criteria associated with significantly lower odds of excellent response included distant metastases (OR, 0.36), incomplete resection (OR, 0.51), and having follicular thyroid carcinoma (FTC) with extensive vascular invasion (OR, 0.27). All these risk factors also were associated with higher odds of persistent disease.
“Recurrence after no evidence of disease occurred in 14%” of the study population, said Dr. van Velsen and his coauthors, adding, “Clinicians should be aware of the relatively high recurrence risk, even after an excellent response to therapy.”
The study aimed to evaluate the 2015 ATA risk stratification system’s prognostic value in a population that included a relatively large proportion of high-risk DTC patients, to include many FTC patients. This work, they noted, augments previous assessments of the risk stratification system in lower-risk populations.
The authors noted that, in addition to predicting disease recurrence, the risk stratification system also worked as a predictor of disease-specific survival. Patients with structural incomplete response fared the worst, with a survival probability below 0.5 at 200 months on a Kaplan-Meier curve of disease-specific survival. Survival probability remained at 1.0 for patients with excellent response after first therapy and was intermediate for those with indeterminate response and biochemical incomplete response.
Overall mortality was higher in FTC patients. Over the study period, 31 of the 76 FTC patients (41%) died, compared with 39 of the PTC patients (24%; P = .010). In all, 28% of the FTC patients and 18% of the PTC patients died of thyroid cancer, but this difference didn’t reach statistical significance.
The retrospective study included adults with DTC meeting the 2015 ATA high-risk criteria who were diagnosed and/or treated at Erasmus Medical Center over a 13-year span ending in December 2015.
Overall, the investigators found 236 patients meeting inclusion criteria; 160 had papillary thyroid cancer (PTC), and the remaining 76 had FTC. The latter group were significantly older at baseline than PTC patients (64 versus 53 years), and were significantly less likely to undergo neck dissection (22% versus 55%).
In the full cohort, 96 patients (41%) had one high-risk factor, and an additional 74 (31%) had two risk factors. The remaining patients had three or more risk factors.
There was no between-group difference in the likelihood of receiving radioactive iodine treatment, but those with FTC had a lower cumulative radiation dose (195 versus 298 mCi; P less than .001).
More than half of patients (58%) had persistent disease after completing their first therapy. Of these, 51% had structural incomplete response and 7% had biochemical incomplete response. The response was indeterminate for about a quarter of the cohort, and the remaining 17% had an excellent initial response.
By the end of the study period, 55% of patients had persistent disease, and 51% had structural incomplete response (a more likely result for those with FTC than PTC). Just 4% had a biochemical incomplete response, and the response was indeterminate for 16%. Response was judged excellent for 29% of patients.
Dr. van Velsen and his coauthors reported that they had no relevant disclosures.
SOURCE: van Velsen EFS et al. ENDO 2019, Abstract MON-549.
REPORTING FROM ENDO 2019
Key clinical point: in a cohort of high-risk patients.
Major finding: Gross extrathyroidal disease extension and high postoperative thyroglobulin levels predicted poor response (OR for excellent response, 0.26 and 0.21, respectively).
Study details: Retrospective single-center study of 236 patients with DTC meeting American Thyroid Association criteria for high risk.
Disclosures: The authors reported no external sources of funding and that they had no conflicts of interest.
Source: van Velsen EFS et al. ENDO 2019, Abstract MON-549.
Geroscience brings bench science to the real-world problems of aging
NEW ORLEANS – Patients ask their doctors whether dietary manipulation can extend lifespan and promote healthy aging. Right now, basic scientists and clinicians from many disciplines are teaming up under the broad umbrella of the field of geroscience to try to answer these and other concerns relevant to an aging population.
“The idea here is that, instead of going after each disease one at a time, as we do ... [we] instead go after disease vulnerability – and this is something that is shared, as a function of age,” Rozalyn Anderson, PhD, said of this new discipline. The work touches on disparate diseases such as cancer, dementia, and diabetes, she pointed out during a video interview at the annual meeting of the Endocrine Society.
“I separate these things out into ‘front-end’ and ‘back-end,’ work,” said Dr. Anderson of the University of Wisconsin-Madison’s aging and caloric restriction program. She explained that the caloric restriction she researches is back-end work to support the rapidly evolving field of nutritional modulation of aging.
When the basic science builds the framework, physicians and scientists can turn to front-end research, looking at humans to see which dietary manipulations are effective – and which are achievable.
“Take a paradigm that works, and then try to understand how it works,” said Dr. Anderson. “So [for example], we have this paradigm, and it’s tremendously effective in rodents. It’s effective in flies, in worms, in yeast, in spiders, in dogs – and in nonhuman primates.” Then, she and her team try to pull out clues “about the biology of aging itself, and what creates disease vulnerability as a function of age,” she said.
“The most important thing of all is that we can modify aging. This is not a foregone conclusion – no one would have believed it. But even in a primate species, we can change how they age. And the way in which we change is through nutrition.”
Dr Anderson added that “the paradigm of caloric restriction is tremendously effective, but [in reality], people are not going to do it.” It’s simply not practical to ask individuals to restrict calories by 30% or more over a lifespan, so “.”
Dr. Anderson reported no relevant conflicts of interest or disclosures.
NEW ORLEANS – Patients ask their doctors whether dietary manipulation can extend lifespan and promote healthy aging. Right now, basic scientists and clinicians from many disciplines are teaming up under the broad umbrella of the field of geroscience to try to answer these and other concerns relevant to an aging population.
“The idea here is that, instead of going after each disease one at a time, as we do ... [we] instead go after disease vulnerability – and this is something that is shared, as a function of age,” Rozalyn Anderson, PhD, said of this new discipline. The work touches on disparate diseases such as cancer, dementia, and diabetes, she pointed out during a video interview at the annual meeting of the Endocrine Society.
“I separate these things out into ‘front-end’ and ‘back-end,’ work,” said Dr. Anderson of the University of Wisconsin-Madison’s aging and caloric restriction program. She explained that the caloric restriction she researches is back-end work to support the rapidly evolving field of nutritional modulation of aging.
When the basic science builds the framework, physicians and scientists can turn to front-end research, looking at humans to see which dietary manipulations are effective – and which are achievable.
“Take a paradigm that works, and then try to understand how it works,” said Dr. Anderson. “So [for example], we have this paradigm, and it’s tremendously effective in rodents. It’s effective in flies, in worms, in yeast, in spiders, in dogs – and in nonhuman primates.” Then, she and her team try to pull out clues “about the biology of aging itself, and what creates disease vulnerability as a function of age,” she said.
“The most important thing of all is that we can modify aging. This is not a foregone conclusion – no one would have believed it. But even in a primate species, we can change how they age. And the way in which we change is through nutrition.”
Dr Anderson added that “the paradigm of caloric restriction is tremendously effective, but [in reality], people are not going to do it.” It’s simply not practical to ask individuals to restrict calories by 30% or more over a lifespan, so “.”
Dr. Anderson reported no relevant conflicts of interest or disclosures.
NEW ORLEANS – Patients ask their doctors whether dietary manipulation can extend lifespan and promote healthy aging. Right now, basic scientists and clinicians from many disciplines are teaming up under the broad umbrella of the field of geroscience to try to answer these and other concerns relevant to an aging population.
“The idea here is that, instead of going after each disease one at a time, as we do ... [we] instead go after disease vulnerability – and this is something that is shared, as a function of age,” Rozalyn Anderson, PhD, said of this new discipline. The work touches on disparate diseases such as cancer, dementia, and diabetes, she pointed out during a video interview at the annual meeting of the Endocrine Society.
“I separate these things out into ‘front-end’ and ‘back-end,’ work,” said Dr. Anderson of the University of Wisconsin-Madison’s aging and caloric restriction program. She explained that the caloric restriction she researches is back-end work to support the rapidly evolving field of nutritional modulation of aging.
When the basic science builds the framework, physicians and scientists can turn to front-end research, looking at humans to see which dietary manipulations are effective – and which are achievable.
“Take a paradigm that works, and then try to understand how it works,” said Dr. Anderson. “So [for example], we have this paradigm, and it’s tremendously effective in rodents. It’s effective in flies, in worms, in yeast, in spiders, in dogs – and in nonhuman primates.” Then, she and her team try to pull out clues “about the biology of aging itself, and what creates disease vulnerability as a function of age,” she said.
“The most important thing of all is that we can modify aging. This is not a foregone conclusion – no one would have believed it. But even in a primate species, we can change how they age. And the way in which we change is through nutrition.”
Dr Anderson added that “the paradigm of caloric restriction is tremendously effective, but [in reality], people are not going to do it.” It’s simply not practical to ask individuals to restrict calories by 30% or more over a lifespan, so “.”
Dr. Anderson reported no relevant conflicts of interest or disclosures.
REPORTING FROM ENDO 2019
Intermittent, but prolonged, calorie restriction may improve metabolic markers
NEW ORLEANS – Can a physician-supervised, intermittent fasting strategy improve metabolic risk? Yes, according to Valter Longo, PhD.
Dr. Longo is a proponent of 5 days of reduced calories, performed once monthly or even less frequently for at-risk individuals. He calls this the “fasting-mimicking diet.”
“If somebody is obese or overweight, and has high cholesterol, high fasting glucose, and is perhaps prediabetic, then a doctor may decide to do the diet once a month for 5 days, and for the rest of the month, the person can go back to whatever it is that they do,” he said in a video interview at the annual meeting of the Endocrine Society.
“We think we are going to see more and more of this approach in the future,” said Dr. Longo, the Edna M. Jones Professor of Gerontology at the University of Southern California, Los Angeles.
Dr. Longo sees two chief practical benefits from the diet. First, patients “don’t feel they are being pushed to revolutionize their lives” because they aren’t asked to make radical lifestyle changes that have to be adhered to on a daily basis, and second, “we are starting to see that the patient slowly moves in the direction of a better diet without being asked to do it.”
which includes some healthy fats from olive oil and nuts. Fasting blood glucose, blood pressure, and insulinlike growth factor 1 levels and other metabolic markers were all reduced in the randomized crossover trial after 3 months of the diet plan.
Dr. Longo noted that in the clinical trial, effects were more pronounced for individuals with a higher risk for disease.
Dr. Longo has a majority stake in L-Nutra, which markets a commercially available fasting-mimicking diet package. He donates his proceeds to a nonprofit corporation he founded.
NEW ORLEANS – Can a physician-supervised, intermittent fasting strategy improve metabolic risk? Yes, according to Valter Longo, PhD.
Dr. Longo is a proponent of 5 days of reduced calories, performed once monthly or even less frequently for at-risk individuals. He calls this the “fasting-mimicking diet.”
“If somebody is obese or overweight, and has high cholesterol, high fasting glucose, and is perhaps prediabetic, then a doctor may decide to do the diet once a month for 5 days, and for the rest of the month, the person can go back to whatever it is that they do,” he said in a video interview at the annual meeting of the Endocrine Society.
“We think we are going to see more and more of this approach in the future,” said Dr. Longo, the Edna M. Jones Professor of Gerontology at the University of Southern California, Los Angeles.
Dr. Longo sees two chief practical benefits from the diet. First, patients “don’t feel they are being pushed to revolutionize their lives” because they aren’t asked to make radical lifestyle changes that have to be adhered to on a daily basis, and second, “we are starting to see that the patient slowly moves in the direction of a better diet without being asked to do it.”
which includes some healthy fats from olive oil and nuts. Fasting blood glucose, blood pressure, and insulinlike growth factor 1 levels and other metabolic markers were all reduced in the randomized crossover trial after 3 months of the diet plan.
Dr. Longo noted that in the clinical trial, effects were more pronounced for individuals with a higher risk for disease.
Dr. Longo has a majority stake in L-Nutra, which markets a commercially available fasting-mimicking diet package. He donates his proceeds to a nonprofit corporation he founded.
NEW ORLEANS – Can a physician-supervised, intermittent fasting strategy improve metabolic risk? Yes, according to Valter Longo, PhD.
Dr. Longo is a proponent of 5 days of reduced calories, performed once monthly or even less frequently for at-risk individuals. He calls this the “fasting-mimicking diet.”
“If somebody is obese or overweight, and has high cholesterol, high fasting glucose, and is perhaps prediabetic, then a doctor may decide to do the diet once a month for 5 days, and for the rest of the month, the person can go back to whatever it is that they do,” he said in a video interview at the annual meeting of the Endocrine Society.
“We think we are going to see more and more of this approach in the future,” said Dr. Longo, the Edna M. Jones Professor of Gerontology at the University of Southern California, Los Angeles.
Dr. Longo sees two chief practical benefits from the diet. First, patients “don’t feel they are being pushed to revolutionize their lives” because they aren’t asked to make radical lifestyle changes that have to be adhered to on a daily basis, and second, “we are starting to see that the patient slowly moves in the direction of a better diet without being asked to do it.”
which includes some healthy fats from olive oil and nuts. Fasting blood glucose, blood pressure, and insulinlike growth factor 1 levels and other metabolic markers were all reduced in the randomized crossover trial after 3 months of the diet plan.
Dr. Longo noted that in the clinical trial, effects were more pronounced for individuals with a higher risk for disease.
Dr. Longo has a majority stake in L-Nutra, which markets a commercially available fasting-mimicking diet package. He donates his proceeds to a nonprofit corporation he founded.
REPORTING FROM ENDO 2019
Oxytocin dampens the brain’s food-related reward circuitry
NEW ORLEANS – Oxytocin shows promise as a weight-loss medication, with encouraging results in animal models and small human studies. Now, in a calorie-rich environment.
“It is clear by now that obesity is a very serious health concern,” Liya Kerem, MD, said in a video interview at the annual meeting of the Endocrine Society. “The most adopted strategy, which is lifestyle modification, does not help [with losing or maintaining] weight in many cases, so we really need to find new treatments for obesity.”
Functional magnetic resonance imaging (fMRI) is a good tool for investigating the neurobiologic basis of overeating, said Dr. Kerem, a pediatric endocrinology fellow at Massachusetts General Hospital, Boston. In previous studies, fMRI has shown that “individuals with obesity have hyperactivation of the reward circuitry in the brain.”
Oxytocin is produced in the hypothalamus and is active in many brain areas associated with reward processing, said Dr. Kerem. Animal studies have shown a decrease in food intake and weight gain with oxytocin administration.
The hormone, which is generally seen as very safe, has had limited study in humans as a weight-loss strategy. Findings from one small study have shown that in men, a single intranasal dose of 24 IU of oxytocin resulted in less hunger-driven eating as well as lower consumption of a postmeal palatable snack, with the latter representing hedonic eating, said Dr. Kerem. A second small pilot study showed that significant weight loss occurred in obese humans after 8 weeks of daily oxytocin administration.
Findings from another study showed that participants who were overweight or obese, unlike their normal-weight counterparts, had reduced activation in the ventral tegmental area (VTA) after oxytocin administration. The VTA is an important region in the brain’s reward network, explained Dr. Kerem.
She and her colleagues used fMRI to probe dynamic changes in brain reward circuitry under the effect of oxytocin. They wanted to understand how oxytocin would “change the dialog between the VTA and the key brain areas involved in processing visual food stimuli.”
The hypothesis was that oxytocin would reduce functional connectivity between the VTA and other brain areas that are important for food reward and sensory processing when the participants were exposed to pictures of high-calorie food.
To test that hypothesis, the researchers showed the participants 100 each of four different kinds of images: high-calorie foods, low-calorie foods, nonfood images, and “fixation” images, used for calibration. The 10 participants had a mean body mass index of 29 kg/m2, and the mean age was 31 years.
Oxytocin did indeed attenuate functional connectivity between the VTA and several brain regions that are “key food motivation areas,” said Dr. Kerem. In particular, connections between the VTA and the insula were reduced with oxytocin. The insula is the “gustatory hub of the brain, key to subjective perception of food stimuli,” she explained.
Other attenuated associations included the oral area of the somatosensory cortex; the operculum, which shows fMRI activation to taste; the temporal gyrus, which is important for sensory processing; and, importantly, both the amygdala and hippocampus, known to be important for stimulus-reward learning, said Dr. Kerem. “We found that oxytocin targets exactly that hyperactivation in an overweight and obese population.”
It “reduced the functional connectivity between the VTA, a key hedonic brain region that drives efforts to obtain desired foods, and multiple brain areas involved in the cognitive, sensory, and emotional processing of food cues in men with overweight and obesity,” she said at a press conference highlighting the research. She emphasized that the effect was seen only with exposure to high-calorie food images. “Targeting hyperactivation of reward areas with oxytocin may inhibit overeating behavior,” she added.
Dr. Kerem and her colleagues are currently enrolling men and women for a larger clinical trial of oxytocin for weight loss.
Dr. Kerem reported no conflicts of interest. One of the study’s coauthors is a consultant for OXT Therapeutics, which is investigating obesity-related uses for oxytocin.
NEW ORLEANS – Oxytocin shows promise as a weight-loss medication, with encouraging results in animal models and small human studies. Now, in a calorie-rich environment.
“It is clear by now that obesity is a very serious health concern,” Liya Kerem, MD, said in a video interview at the annual meeting of the Endocrine Society. “The most adopted strategy, which is lifestyle modification, does not help [with losing or maintaining] weight in many cases, so we really need to find new treatments for obesity.”
Functional magnetic resonance imaging (fMRI) is a good tool for investigating the neurobiologic basis of overeating, said Dr. Kerem, a pediatric endocrinology fellow at Massachusetts General Hospital, Boston. In previous studies, fMRI has shown that “individuals with obesity have hyperactivation of the reward circuitry in the brain.”
Oxytocin is produced in the hypothalamus and is active in many brain areas associated with reward processing, said Dr. Kerem. Animal studies have shown a decrease in food intake and weight gain with oxytocin administration.
The hormone, which is generally seen as very safe, has had limited study in humans as a weight-loss strategy. Findings from one small study have shown that in men, a single intranasal dose of 24 IU of oxytocin resulted in less hunger-driven eating as well as lower consumption of a postmeal palatable snack, with the latter representing hedonic eating, said Dr. Kerem. A second small pilot study showed that significant weight loss occurred in obese humans after 8 weeks of daily oxytocin administration.
Findings from another study showed that participants who were overweight or obese, unlike their normal-weight counterparts, had reduced activation in the ventral tegmental area (VTA) after oxytocin administration. The VTA is an important region in the brain’s reward network, explained Dr. Kerem.
She and her colleagues used fMRI to probe dynamic changes in brain reward circuitry under the effect of oxytocin. They wanted to understand how oxytocin would “change the dialog between the VTA and the key brain areas involved in processing visual food stimuli.”
The hypothesis was that oxytocin would reduce functional connectivity between the VTA and other brain areas that are important for food reward and sensory processing when the participants were exposed to pictures of high-calorie food.
To test that hypothesis, the researchers showed the participants 100 each of four different kinds of images: high-calorie foods, low-calorie foods, nonfood images, and “fixation” images, used for calibration. The 10 participants had a mean body mass index of 29 kg/m2, and the mean age was 31 years.
Oxytocin did indeed attenuate functional connectivity between the VTA and several brain regions that are “key food motivation areas,” said Dr. Kerem. In particular, connections between the VTA and the insula were reduced with oxytocin. The insula is the “gustatory hub of the brain, key to subjective perception of food stimuli,” she explained.
Other attenuated associations included the oral area of the somatosensory cortex; the operculum, which shows fMRI activation to taste; the temporal gyrus, which is important for sensory processing; and, importantly, both the amygdala and hippocampus, known to be important for stimulus-reward learning, said Dr. Kerem. “We found that oxytocin targets exactly that hyperactivation in an overweight and obese population.”
It “reduced the functional connectivity between the VTA, a key hedonic brain region that drives efforts to obtain desired foods, and multiple brain areas involved in the cognitive, sensory, and emotional processing of food cues in men with overweight and obesity,” she said at a press conference highlighting the research. She emphasized that the effect was seen only with exposure to high-calorie food images. “Targeting hyperactivation of reward areas with oxytocin may inhibit overeating behavior,” she added.
Dr. Kerem and her colleagues are currently enrolling men and women for a larger clinical trial of oxytocin for weight loss.
Dr. Kerem reported no conflicts of interest. One of the study’s coauthors is a consultant for OXT Therapeutics, which is investigating obesity-related uses for oxytocin.
NEW ORLEANS – Oxytocin shows promise as a weight-loss medication, with encouraging results in animal models and small human studies. Now, in a calorie-rich environment.
“It is clear by now that obesity is a very serious health concern,” Liya Kerem, MD, said in a video interview at the annual meeting of the Endocrine Society. “The most adopted strategy, which is lifestyle modification, does not help [with losing or maintaining] weight in many cases, so we really need to find new treatments for obesity.”
Functional magnetic resonance imaging (fMRI) is a good tool for investigating the neurobiologic basis of overeating, said Dr. Kerem, a pediatric endocrinology fellow at Massachusetts General Hospital, Boston. In previous studies, fMRI has shown that “individuals with obesity have hyperactivation of the reward circuitry in the brain.”
Oxytocin is produced in the hypothalamus and is active in many brain areas associated with reward processing, said Dr. Kerem. Animal studies have shown a decrease in food intake and weight gain with oxytocin administration.
The hormone, which is generally seen as very safe, has had limited study in humans as a weight-loss strategy. Findings from one small study have shown that in men, a single intranasal dose of 24 IU of oxytocin resulted in less hunger-driven eating as well as lower consumption of a postmeal palatable snack, with the latter representing hedonic eating, said Dr. Kerem. A second small pilot study showed that significant weight loss occurred in obese humans after 8 weeks of daily oxytocin administration.
Findings from another study showed that participants who were overweight or obese, unlike their normal-weight counterparts, had reduced activation in the ventral tegmental area (VTA) after oxytocin administration. The VTA is an important region in the brain’s reward network, explained Dr. Kerem.
She and her colleagues used fMRI to probe dynamic changes in brain reward circuitry under the effect of oxytocin. They wanted to understand how oxytocin would “change the dialog between the VTA and the key brain areas involved in processing visual food stimuli.”
The hypothesis was that oxytocin would reduce functional connectivity between the VTA and other brain areas that are important for food reward and sensory processing when the participants were exposed to pictures of high-calorie food.
To test that hypothesis, the researchers showed the participants 100 each of four different kinds of images: high-calorie foods, low-calorie foods, nonfood images, and “fixation” images, used for calibration. The 10 participants had a mean body mass index of 29 kg/m2, and the mean age was 31 years.
Oxytocin did indeed attenuate functional connectivity between the VTA and several brain regions that are “key food motivation areas,” said Dr. Kerem. In particular, connections between the VTA and the insula were reduced with oxytocin. The insula is the “gustatory hub of the brain, key to subjective perception of food stimuli,” she explained.
Other attenuated associations included the oral area of the somatosensory cortex; the operculum, which shows fMRI activation to taste; the temporal gyrus, which is important for sensory processing; and, importantly, both the amygdala and hippocampus, known to be important for stimulus-reward learning, said Dr. Kerem. “We found that oxytocin targets exactly that hyperactivation in an overweight and obese population.”
It “reduced the functional connectivity between the VTA, a key hedonic brain region that drives efforts to obtain desired foods, and multiple brain areas involved in the cognitive, sensory, and emotional processing of food cues in men with overweight and obesity,” she said at a press conference highlighting the research. She emphasized that the effect was seen only with exposure to high-calorie food images. “Targeting hyperactivation of reward areas with oxytocin may inhibit overeating behavior,” she added.
Dr. Kerem and her colleagues are currently enrolling men and women for a larger clinical trial of oxytocin for weight loss.
Dr. Kerem reported no conflicts of interest. One of the study’s coauthors is a consultant for OXT Therapeutics, which is investigating obesity-related uses for oxytocin.
REPORTING FROM ENDO 2019
Nasal testosterone gel preserves fertility in men with hypogonadism
NEW ORLEANS – according to an interim analysis of a postapproval clinical trial.
Testosterone nasal gel is a shorter-acting formulation of testosterone that “can mimic normal physiology,” said John Masterson, MD, a urology resident at the University of Miami. The 4.5% formulation, which was approved by the Food and Drug Administration in 2014 and is marketed as Natesto, delivers 11 mg of testosterone per dose and is dosed three times daily for testosterone replacement therapy.
The negative feedback exerted by other exogenous testosterone formulations on the hypothalamic-pituitary-gonadal (HPG) axis is known to inhibit spermatogenesis, Dr. Masterson said in a video interview at the annual meeting of the Endocrine Society.
Dr. Masterson, senior author Ranjith Ramasamy, MD, and their colleagues hypothesized that the shorter duration of action of testosterone in the nasal gel formulation would result in some conservation of gonadotropin-releasing hormone (GnRH) pulsatility, less inhibition of the HPG axis, and preservation of spermatogenesis.
In the same interview, Dr. Ramasamy, director of reproductive urology at the University of Miami, noted that “the levels of testosterone in men rise about an hour or 2 after administration [of the gel] and seem to drop off about 2 to 4 hours after the peak.” That is closer to normal physiology than other delivery systems in which “the levels of testosterone are pretty high during the day and therefore could lead to some of the side effects that we see with testosterone.”
The phase 4 prospective study enrolled 56 men aged between 18 and 55 years who had low levels of testosterone (baseline mean, 233.97 ng/dL). The mean age was 37 years.
“There are mostly younger men in our study ... and they’re usually coming in with one or two hypogonadal complaints – lack of energy, fatigue, some with erectile dysfunction,” Dr. Masterson explained in the interview. Improvement was seen in those realms, but the differences didn’t reach statistical significance, because baseline quality of life was already fairly high for these otherwise healthy men. “What we can say is that on the drug, quality of life certainly did not get worse,” he said.
At baseline, the mean luteinizing hormone (LH) level was 3.66 IU/mL, and the mean follicle stimulating hormone (FSH) level was 4.01 IU/mL.
Men were eligible to participate if they had two morning blood samples with age-adjusted low testosterone levels, and a total motile sperm count more than 5 million/ejaculation. Participants received 11-mg nasal testosterone gel three times daily for 6 months.
By 1 month into the study, 43 patients had a median testosterone level of 573 ng/dL. Fifteen patients have thus far completed all 6 months of the study and they had a median testosterone level of 604 ng/dL.
At baseline, sperm concentration was a mean 21.32 million/mL with 50% motility, and a total sperm count of 32.23 million/ejaculation. Sperm concentration at 6 months was unchanged at a median 21 million/mL.
Motility was preserved at a median 51.5% after 6 months of therapy, a statistically insignificant difference from 54% motility at baseline. Total motile sperm count decreased from a median 29.3 million/ejaculation at baseline to 19.5 million/ejaculation, a difference that didn’t reach statistical significance.
“What that means is that this nasal testosterone gel [could] be used in men who have low testosterone and are interested in preserving fertility,” said Dr. Masterson.
Dr. Ramasamy said that they’re seeing early confirmation of their initial hypothesis about the nasal gel formulation in this interim analysis. “Because it’s short acting, we believe some of the GnRH pulses and the LH and FSH that are released by the pituitary gland are still maintained, compared with the other forms of testosterone therapy, which can cause complete suppression of the [HPG] axis.”
In discussion with attendees at the poster session at which the research was featured, Dr. Masterson explained that quality-of-life measures were also collected as part of the study and will be presented separately. In addition to information about erectile function, men were asked about libido – a more complex phenomenon than erectile function alone – and early analysis showed a robust response, he said.
He acknowledged that it is not known whether craniofacial circulation facilitates testosterone transport to the brain when the nasal gel testosterone formulation is used, but that it is mechanistically plausible.
Dr. Masterson added that, practically speaking, patients should be aware that the formulation is a gel. “It sort of has to be painted on” the nasal septum within the nostrils, he said.
Aytu BioScience, which markets Natesto, partially supported the study. Dr Masterson reported no disclosures or conflicts of interest.
NEW ORLEANS – according to an interim analysis of a postapproval clinical trial.
Testosterone nasal gel is a shorter-acting formulation of testosterone that “can mimic normal physiology,” said John Masterson, MD, a urology resident at the University of Miami. The 4.5% formulation, which was approved by the Food and Drug Administration in 2014 and is marketed as Natesto, delivers 11 mg of testosterone per dose and is dosed three times daily for testosterone replacement therapy.
The negative feedback exerted by other exogenous testosterone formulations on the hypothalamic-pituitary-gonadal (HPG) axis is known to inhibit spermatogenesis, Dr. Masterson said in a video interview at the annual meeting of the Endocrine Society.
Dr. Masterson, senior author Ranjith Ramasamy, MD, and their colleagues hypothesized that the shorter duration of action of testosterone in the nasal gel formulation would result in some conservation of gonadotropin-releasing hormone (GnRH) pulsatility, less inhibition of the HPG axis, and preservation of spermatogenesis.
In the same interview, Dr. Ramasamy, director of reproductive urology at the University of Miami, noted that “the levels of testosterone in men rise about an hour or 2 after administration [of the gel] and seem to drop off about 2 to 4 hours after the peak.” That is closer to normal physiology than other delivery systems in which “the levels of testosterone are pretty high during the day and therefore could lead to some of the side effects that we see with testosterone.”
The phase 4 prospective study enrolled 56 men aged between 18 and 55 years who had low levels of testosterone (baseline mean, 233.97 ng/dL). The mean age was 37 years.
“There are mostly younger men in our study ... and they’re usually coming in with one or two hypogonadal complaints – lack of energy, fatigue, some with erectile dysfunction,” Dr. Masterson explained in the interview. Improvement was seen in those realms, but the differences didn’t reach statistical significance, because baseline quality of life was already fairly high for these otherwise healthy men. “What we can say is that on the drug, quality of life certainly did not get worse,” he said.
At baseline, the mean luteinizing hormone (LH) level was 3.66 IU/mL, and the mean follicle stimulating hormone (FSH) level was 4.01 IU/mL.
Men were eligible to participate if they had two morning blood samples with age-adjusted low testosterone levels, and a total motile sperm count more than 5 million/ejaculation. Participants received 11-mg nasal testosterone gel three times daily for 6 months.
By 1 month into the study, 43 patients had a median testosterone level of 573 ng/dL. Fifteen patients have thus far completed all 6 months of the study and they had a median testosterone level of 604 ng/dL.
At baseline, sperm concentration was a mean 21.32 million/mL with 50% motility, and a total sperm count of 32.23 million/ejaculation. Sperm concentration at 6 months was unchanged at a median 21 million/mL.
Motility was preserved at a median 51.5% after 6 months of therapy, a statistically insignificant difference from 54% motility at baseline. Total motile sperm count decreased from a median 29.3 million/ejaculation at baseline to 19.5 million/ejaculation, a difference that didn’t reach statistical significance.
“What that means is that this nasal testosterone gel [could] be used in men who have low testosterone and are interested in preserving fertility,” said Dr. Masterson.
Dr. Ramasamy said that they’re seeing early confirmation of their initial hypothesis about the nasal gel formulation in this interim analysis. “Because it’s short acting, we believe some of the GnRH pulses and the LH and FSH that are released by the pituitary gland are still maintained, compared with the other forms of testosterone therapy, which can cause complete suppression of the [HPG] axis.”
In discussion with attendees at the poster session at which the research was featured, Dr. Masterson explained that quality-of-life measures were also collected as part of the study and will be presented separately. In addition to information about erectile function, men were asked about libido – a more complex phenomenon than erectile function alone – and early analysis showed a robust response, he said.
He acknowledged that it is not known whether craniofacial circulation facilitates testosterone transport to the brain when the nasal gel testosterone formulation is used, but that it is mechanistically plausible.
Dr. Masterson added that, practically speaking, patients should be aware that the formulation is a gel. “It sort of has to be painted on” the nasal septum within the nostrils, he said.
Aytu BioScience, which markets Natesto, partially supported the study. Dr Masterson reported no disclosures or conflicts of interest.
NEW ORLEANS – according to an interim analysis of a postapproval clinical trial.
Testosterone nasal gel is a shorter-acting formulation of testosterone that “can mimic normal physiology,” said John Masterson, MD, a urology resident at the University of Miami. The 4.5% formulation, which was approved by the Food and Drug Administration in 2014 and is marketed as Natesto, delivers 11 mg of testosterone per dose and is dosed three times daily for testosterone replacement therapy.
The negative feedback exerted by other exogenous testosterone formulations on the hypothalamic-pituitary-gonadal (HPG) axis is known to inhibit spermatogenesis, Dr. Masterson said in a video interview at the annual meeting of the Endocrine Society.
Dr. Masterson, senior author Ranjith Ramasamy, MD, and their colleagues hypothesized that the shorter duration of action of testosterone in the nasal gel formulation would result in some conservation of gonadotropin-releasing hormone (GnRH) pulsatility, less inhibition of the HPG axis, and preservation of spermatogenesis.
In the same interview, Dr. Ramasamy, director of reproductive urology at the University of Miami, noted that “the levels of testosterone in men rise about an hour or 2 after administration [of the gel] and seem to drop off about 2 to 4 hours after the peak.” That is closer to normal physiology than other delivery systems in which “the levels of testosterone are pretty high during the day and therefore could lead to some of the side effects that we see with testosterone.”
The phase 4 prospective study enrolled 56 men aged between 18 and 55 years who had low levels of testosterone (baseline mean, 233.97 ng/dL). The mean age was 37 years.
“There are mostly younger men in our study ... and they’re usually coming in with one or two hypogonadal complaints – lack of energy, fatigue, some with erectile dysfunction,” Dr. Masterson explained in the interview. Improvement was seen in those realms, but the differences didn’t reach statistical significance, because baseline quality of life was already fairly high for these otherwise healthy men. “What we can say is that on the drug, quality of life certainly did not get worse,” he said.
At baseline, the mean luteinizing hormone (LH) level was 3.66 IU/mL, and the mean follicle stimulating hormone (FSH) level was 4.01 IU/mL.
Men were eligible to participate if they had two morning blood samples with age-adjusted low testosterone levels, and a total motile sperm count more than 5 million/ejaculation. Participants received 11-mg nasal testosterone gel three times daily for 6 months.
By 1 month into the study, 43 patients had a median testosterone level of 573 ng/dL. Fifteen patients have thus far completed all 6 months of the study and they had a median testosterone level of 604 ng/dL.
At baseline, sperm concentration was a mean 21.32 million/mL with 50% motility, and a total sperm count of 32.23 million/ejaculation. Sperm concentration at 6 months was unchanged at a median 21 million/mL.
Motility was preserved at a median 51.5% after 6 months of therapy, a statistically insignificant difference from 54% motility at baseline. Total motile sperm count decreased from a median 29.3 million/ejaculation at baseline to 19.5 million/ejaculation, a difference that didn’t reach statistical significance.
“What that means is that this nasal testosterone gel [could] be used in men who have low testosterone and are interested in preserving fertility,” said Dr. Masterson.
Dr. Ramasamy said that they’re seeing early confirmation of their initial hypothesis about the nasal gel formulation in this interim analysis. “Because it’s short acting, we believe some of the GnRH pulses and the LH and FSH that are released by the pituitary gland are still maintained, compared with the other forms of testosterone therapy, which can cause complete suppression of the [HPG] axis.”
In discussion with attendees at the poster session at which the research was featured, Dr. Masterson explained that quality-of-life measures were also collected as part of the study and will be presented separately. In addition to information about erectile function, men were asked about libido – a more complex phenomenon than erectile function alone – and early analysis showed a robust response, he said.
He acknowledged that it is not known whether craniofacial circulation facilitates testosterone transport to the brain when the nasal gel testosterone formulation is used, but that it is mechanistically plausible.
Dr. Masterson added that, practically speaking, patients should be aware that the formulation is a gel. “It sort of has to be painted on” the nasal septum within the nostrils, he said.
Aytu BioScience, which markets Natesto, partially supported the study. Dr Masterson reported no disclosures or conflicts of interest.
REPORTING FROM ENDO 2019
High levels of estradiol in older men may be associated with young biological age
NEW ORLEANS – In a large community-based study that evaluated sex hormone levels in older men, suggesting that sex hormones influence the aging process.
“There was a large effect size, comparable with being 2 or 3 years younger for those with relatively high levels of estradiol, compared with those with lower levels of the hormone,” said Bu Yeap, MBBS, PhD, professor of medicine, University of Western Australia Medical School, Perth, who reported the results at the annual meeting of the Endocrine Society.
In a video interview conducted at the meeting, Dr. Yeap explained the basis of the study, which is the variety of evidence showing that decline in sex hormones correlates with higher rates of age-related disease processes. For example, increasing rates of cardiovascular disease, dementia, and mortality in men all correlate with declining levels of testosterone.
In the study, 2,913 men between the ages of 70 and 89 years and living in the community were recruited. The average age of the men was 77 years. Serum levels of testosterone, dihydrotestosterone, and estradiol were measured. Telomere length was calculated with a polymerase chain reaction test.
Serum levels of testosterone and dihydrotestosterone did not correlate with telomere length, but incremental increases in serum estradiol levels were associated with incremental increases in telomere length.
“Telomeres are both a mediator and a biomarker for biological aging,” according to Dr. Yeap, who added that the telomeres protect chromosomes from degradation. As the telomeres shorten, cell senescence is increased along with an array of age-related diseases.
The next step for researchers is to evaluate whether administering exogenous sex hormones can favorably alter telomere length. If such an effect is demonstrated, then it could provide a step toward understanding how to slow the aging process, he said.
Dr Yeap and his colleagues reported no disclosures or financial conflicts of interest.
NEW ORLEANS – In a large community-based study that evaluated sex hormone levels in older men, suggesting that sex hormones influence the aging process.
“There was a large effect size, comparable with being 2 or 3 years younger for those with relatively high levels of estradiol, compared with those with lower levels of the hormone,” said Bu Yeap, MBBS, PhD, professor of medicine, University of Western Australia Medical School, Perth, who reported the results at the annual meeting of the Endocrine Society.
In a video interview conducted at the meeting, Dr. Yeap explained the basis of the study, which is the variety of evidence showing that decline in sex hormones correlates with higher rates of age-related disease processes. For example, increasing rates of cardiovascular disease, dementia, and mortality in men all correlate with declining levels of testosterone.
In the study, 2,913 men between the ages of 70 and 89 years and living in the community were recruited. The average age of the men was 77 years. Serum levels of testosterone, dihydrotestosterone, and estradiol were measured. Telomere length was calculated with a polymerase chain reaction test.
Serum levels of testosterone and dihydrotestosterone did not correlate with telomere length, but incremental increases in serum estradiol levels were associated with incremental increases in telomere length.
“Telomeres are both a mediator and a biomarker for biological aging,” according to Dr. Yeap, who added that the telomeres protect chromosomes from degradation. As the telomeres shorten, cell senescence is increased along with an array of age-related diseases.
The next step for researchers is to evaluate whether administering exogenous sex hormones can favorably alter telomere length. If such an effect is demonstrated, then it could provide a step toward understanding how to slow the aging process, he said.
Dr Yeap and his colleagues reported no disclosures or financial conflicts of interest.
NEW ORLEANS – In a large community-based study that evaluated sex hormone levels in older men, suggesting that sex hormones influence the aging process.
“There was a large effect size, comparable with being 2 or 3 years younger for those with relatively high levels of estradiol, compared with those with lower levels of the hormone,” said Bu Yeap, MBBS, PhD, professor of medicine, University of Western Australia Medical School, Perth, who reported the results at the annual meeting of the Endocrine Society.
In a video interview conducted at the meeting, Dr. Yeap explained the basis of the study, which is the variety of evidence showing that decline in sex hormones correlates with higher rates of age-related disease processes. For example, increasing rates of cardiovascular disease, dementia, and mortality in men all correlate with declining levels of testosterone.
In the study, 2,913 men between the ages of 70 and 89 years and living in the community were recruited. The average age of the men was 77 years. Serum levels of testosterone, dihydrotestosterone, and estradiol were measured. Telomere length was calculated with a polymerase chain reaction test.
Serum levels of testosterone and dihydrotestosterone did not correlate with telomere length, but incremental increases in serum estradiol levels were associated with incremental increases in telomere length.
“Telomeres are both a mediator and a biomarker for biological aging,” according to Dr. Yeap, who added that the telomeres protect chromosomes from degradation. As the telomeres shorten, cell senescence is increased along with an array of age-related diseases.
The next step for researchers is to evaluate whether administering exogenous sex hormones can favorably alter telomere length. If such an effect is demonstrated, then it could provide a step toward understanding how to slow the aging process, he said.
Dr Yeap and his colleagues reported no disclosures or financial conflicts of interest.
REPORTING FROM ENDO 2019
Noninfected children of HIV-positive mothers have high rates of obesity
NEW ORLEANS – than are those with no such exposure, according to research that provides a compelling link between inflammatory activity in utero and subsequent risk of metabolic disorders.
Most supportive of that link was a near-linear inverse relationship between CD4 counts during the time of pregnancy and risk of both obesity and reactive respiratory disease more than a decade later, according to research presented by Lindsay Fourman, MD, an instructor in medicine at Massachusetts General Hospital, Boston, during the annual meeting of the Endocrine Society.
In this video interview, Dr. Fourman discusses the effort to understand the long-term health consequences of being exposed to HIV and antiretroviral therapies while in utero, a group known by the acronym HIV-exposed uninfected (HEU). With effective therapies now routinely preventing mother-to-child transmission, this population of children is growing quickly.
For this study, 50 HEU individuals were identified from a patient database. They were matched in a 3:1 ratio to a control group for a variety of demographic and socioeconomic variables. At a median age of 18 years, the HEU population was found to have a “strikingly” higher rate of obesity, compared with controls (42% vs. 25%, respectively; P = .04). The rate of reactive airway disease was similarly increased in the HEU group (40% vs. 24%; P = .04).
These data are important for considering health risks in an HEU population, but Dr. Fourman explained that it provides support for looking at metabolic risks from other in utero exposures linked to upregulated inflammation, such as gestational diabetes or obesity.
Dr Fourman and her colleagues reported no disclosures or financial conflicts of interest.
SOURCE: Fourman L et al. ENDO 2019, Session P10 (SAT-256).
NEW ORLEANS – than are those with no such exposure, according to research that provides a compelling link between inflammatory activity in utero and subsequent risk of metabolic disorders.
Most supportive of that link was a near-linear inverse relationship between CD4 counts during the time of pregnancy and risk of both obesity and reactive respiratory disease more than a decade later, according to research presented by Lindsay Fourman, MD, an instructor in medicine at Massachusetts General Hospital, Boston, during the annual meeting of the Endocrine Society.
In this video interview, Dr. Fourman discusses the effort to understand the long-term health consequences of being exposed to HIV and antiretroviral therapies while in utero, a group known by the acronym HIV-exposed uninfected (HEU). With effective therapies now routinely preventing mother-to-child transmission, this population of children is growing quickly.
For this study, 50 HEU individuals were identified from a patient database. They were matched in a 3:1 ratio to a control group for a variety of demographic and socioeconomic variables. At a median age of 18 years, the HEU population was found to have a “strikingly” higher rate of obesity, compared with controls (42% vs. 25%, respectively; P = .04). The rate of reactive airway disease was similarly increased in the HEU group (40% vs. 24%; P = .04).
These data are important for considering health risks in an HEU population, but Dr. Fourman explained that it provides support for looking at metabolic risks from other in utero exposures linked to upregulated inflammation, such as gestational diabetes or obesity.
Dr Fourman and her colleagues reported no disclosures or financial conflicts of interest.
SOURCE: Fourman L et al. ENDO 2019, Session P10 (SAT-256).
NEW ORLEANS – than are those with no such exposure, according to research that provides a compelling link between inflammatory activity in utero and subsequent risk of metabolic disorders.
Most supportive of that link was a near-linear inverse relationship between CD4 counts during the time of pregnancy and risk of both obesity and reactive respiratory disease more than a decade later, according to research presented by Lindsay Fourman, MD, an instructor in medicine at Massachusetts General Hospital, Boston, during the annual meeting of the Endocrine Society.
In this video interview, Dr. Fourman discusses the effort to understand the long-term health consequences of being exposed to HIV and antiretroviral therapies while in utero, a group known by the acronym HIV-exposed uninfected (HEU). With effective therapies now routinely preventing mother-to-child transmission, this population of children is growing quickly.
For this study, 50 HEU individuals were identified from a patient database. They were matched in a 3:1 ratio to a control group for a variety of demographic and socioeconomic variables. At a median age of 18 years, the HEU population was found to have a “strikingly” higher rate of obesity, compared with controls (42% vs. 25%, respectively; P = .04). The rate of reactive airway disease was similarly increased in the HEU group (40% vs. 24%; P = .04).
These data are important for considering health risks in an HEU population, but Dr. Fourman explained that it provides support for looking at metabolic risks from other in utero exposures linked to upregulated inflammation, such as gestational diabetes or obesity.
Dr Fourman and her colleagues reported no disclosures or financial conflicts of interest.
SOURCE: Fourman L et al. ENDO 2019, Session P10 (SAT-256).
REPORTING FROM ENDO 2019
In obesity-related asthma, a new hormonal target
NEW ORLEANS – A hormone that is oversecreted in obesity may provide a pathway from adipose to lung tissue in individuals with both obesity and asthma, according to new research presented at the annual meeting of the Endocrine Society.
“Obesity-related asthma is a really understudied and new phenomenon. It’s a unique complication of obesity,” said Furkan Burak, MD, in a video interview after an obesity-focused press conference.
“In addition to being a standalone disease, obesity mostly comes as a package. And that’s the problem,” said Dr. Burak, pointing to obesity-related asthma’s clustering with diseases such as diabetes and atherosclerosis.
Asthma affects 10% of the world population, and it’s becoming increasingly understood that said Dr. Burak, an endocrinology fellow at Brigham and Women’s Hospital, Boston.
“There are two types of asthma related to obesity,” he said. Classic allergic asthma can get worse with obesity; however, asthma can sometimes occur de novo in adults, particularly women, with obesity. “What is important is … that they are less responsive to classic treatments,” such as steroids and beta-agonists. “And the problem is not small: Of asthmatics, 40% are obese. It’s a therapeutic problem, and we are not able to treat them well.”
The fatty acid binding protein 4, aP2, a hormone that is released by adipose tissue, travels to distant organs and regulates metabolic responses. Levels of aP2 are known to be increased in obesity, particularly in individuals with asthma, said Dr. Burak.
Citing work done at Brigham and Women’s Hospital and at Boston’s Harvard Medical School, as well as elsewhere, Dr. Burak and his collaborators noted in the abstract accompanying the presentation that “increased serum aP2 levels strongly correlate with poor metabolic, inflammatory, and cardiovascular outcomes in multiple independent human studies.”
Dr. Burak said he and his colleagues are trying to sort out “how a fat-tissue–borne hormone could potentially cause a problem in the lung.”
A big clue came with the discovery that patients with asthma and obesity have elevated levels of aP2 within their airways when bronchoalveolar lavage is performed, suggesting that the hormone may be the pathological mediator linking obesity to asthma – “a direct link between the fat tissue and the lung,” he said.
Serum aP2 levels were available from the Nurse’s Health Study, so Dr. Burak and his colleagues looked at those levels in randomly selected study participants. “We found that aP2 levels were elevated 25.6% – significantly – in asthmatics, compared with nonasthmatics, but only in obese and overweight [participants, and] not in lean” participants, he said.
Dr. Burak and his colleagues compared 525 individuals with body mass indices of less than 25 kg/m2, of whom 15 had asthma, with 385 individuals with body mass indices of more than 25, of whom 15 of whom had asthma.
Collecting bronchoalveolar lavage fluid from individuals with asthma showed a mean increase of 23% in aP2 levels in patients with obesity compared with lean individuals.
These data taken together show both systemic and local elevations of aP2 in human obesity. “That could contribute to the airway hyperreactivity and to the asthma pathogenesis,” which would confirm findings from animal studies, said Dr. Burak.
Further investigation will focus on individuals who are haploinsufficient for aP2. The group already is known to have lower risk for dyslipidemia, diabetes, and cardiovascular disease, but Dr. Burak and his collaborators also will determine whether asthma incidence is also lower.
The eventual goal is to attack aP2 as a therapeutic target. “Can we inhibit and target aP2 therapeutically in the context of obesity to treat obesity-related asthma? We have a big hope for that.”
Dr. Burak and his colleagues reported no disclosures or financial conflicts of interest.
SOURCE: Burak MF et al. ENDO 2019, Session OR01-1.
NEW ORLEANS – A hormone that is oversecreted in obesity may provide a pathway from adipose to lung tissue in individuals with both obesity and asthma, according to new research presented at the annual meeting of the Endocrine Society.
“Obesity-related asthma is a really understudied and new phenomenon. It’s a unique complication of obesity,” said Furkan Burak, MD, in a video interview after an obesity-focused press conference.
“In addition to being a standalone disease, obesity mostly comes as a package. And that’s the problem,” said Dr. Burak, pointing to obesity-related asthma’s clustering with diseases such as diabetes and atherosclerosis.
Asthma affects 10% of the world population, and it’s becoming increasingly understood that said Dr. Burak, an endocrinology fellow at Brigham and Women’s Hospital, Boston.
“There are two types of asthma related to obesity,” he said. Classic allergic asthma can get worse with obesity; however, asthma can sometimes occur de novo in adults, particularly women, with obesity. “What is important is … that they are less responsive to classic treatments,” such as steroids and beta-agonists. “And the problem is not small: Of asthmatics, 40% are obese. It’s a therapeutic problem, and we are not able to treat them well.”
The fatty acid binding protein 4, aP2, a hormone that is released by adipose tissue, travels to distant organs and regulates metabolic responses. Levels of aP2 are known to be increased in obesity, particularly in individuals with asthma, said Dr. Burak.
Citing work done at Brigham and Women’s Hospital and at Boston’s Harvard Medical School, as well as elsewhere, Dr. Burak and his collaborators noted in the abstract accompanying the presentation that “increased serum aP2 levels strongly correlate with poor metabolic, inflammatory, and cardiovascular outcomes in multiple independent human studies.”
Dr. Burak said he and his colleagues are trying to sort out “how a fat-tissue–borne hormone could potentially cause a problem in the lung.”
A big clue came with the discovery that patients with asthma and obesity have elevated levels of aP2 within their airways when bronchoalveolar lavage is performed, suggesting that the hormone may be the pathological mediator linking obesity to asthma – “a direct link between the fat tissue and the lung,” he said.
Serum aP2 levels were available from the Nurse’s Health Study, so Dr. Burak and his colleagues looked at those levels in randomly selected study participants. “We found that aP2 levels were elevated 25.6% – significantly – in asthmatics, compared with nonasthmatics, but only in obese and overweight [participants, and] not in lean” participants, he said.
Dr. Burak and his colleagues compared 525 individuals with body mass indices of less than 25 kg/m2, of whom 15 had asthma, with 385 individuals with body mass indices of more than 25, of whom 15 of whom had asthma.
Collecting bronchoalveolar lavage fluid from individuals with asthma showed a mean increase of 23% in aP2 levels in patients with obesity compared with lean individuals.
These data taken together show both systemic and local elevations of aP2 in human obesity. “That could contribute to the airway hyperreactivity and to the asthma pathogenesis,” which would confirm findings from animal studies, said Dr. Burak.
Further investigation will focus on individuals who are haploinsufficient for aP2. The group already is known to have lower risk for dyslipidemia, diabetes, and cardiovascular disease, but Dr. Burak and his collaborators also will determine whether asthma incidence is also lower.
The eventual goal is to attack aP2 as a therapeutic target. “Can we inhibit and target aP2 therapeutically in the context of obesity to treat obesity-related asthma? We have a big hope for that.”
Dr. Burak and his colleagues reported no disclosures or financial conflicts of interest.
SOURCE: Burak MF et al. ENDO 2019, Session OR01-1.
NEW ORLEANS – A hormone that is oversecreted in obesity may provide a pathway from adipose to lung tissue in individuals with both obesity and asthma, according to new research presented at the annual meeting of the Endocrine Society.
“Obesity-related asthma is a really understudied and new phenomenon. It’s a unique complication of obesity,” said Furkan Burak, MD, in a video interview after an obesity-focused press conference.
“In addition to being a standalone disease, obesity mostly comes as a package. And that’s the problem,” said Dr. Burak, pointing to obesity-related asthma’s clustering with diseases such as diabetes and atherosclerosis.
Asthma affects 10% of the world population, and it’s becoming increasingly understood that said Dr. Burak, an endocrinology fellow at Brigham and Women’s Hospital, Boston.
“There are two types of asthma related to obesity,” he said. Classic allergic asthma can get worse with obesity; however, asthma can sometimes occur de novo in adults, particularly women, with obesity. “What is important is … that they are less responsive to classic treatments,” such as steroids and beta-agonists. “And the problem is not small: Of asthmatics, 40% are obese. It’s a therapeutic problem, and we are not able to treat them well.”
The fatty acid binding protein 4, aP2, a hormone that is released by adipose tissue, travels to distant organs and regulates metabolic responses. Levels of aP2 are known to be increased in obesity, particularly in individuals with asthma, said Dr. Burak.
Citing work done at Brigham and Women’s Hospital and at Boston’s Harvard Medical School, as well as elsewhere, Dr. Burak and his collaborators noted in the abstract accompanying the presentation that “increased serum aP2 levels strongly correlate with poor metabolic, inflammatory, and cardiovascular outcomes in multiple independent human studies.”
Dr. Burak said he and his colleagues are trying to sort out “how a fat-tissue–borne hormone could potentially cause a problem in the lung.”
A big clue came with the discovery that patients with asthma and obesity have elevated levels of aP2 within their airways when bronchoalveolar lavage is performed, suggesting that the hormone may be the pathological mediator linking obesity to asthma – “a direct link between the fat tissue and the lung,” he said.
Serum aP2 levels were available from the Nurse’s Health Study, so Dr. Burak and his colleagues looked at those levels in randomly selected study participants. “We found that aP2 levels were elevated 25.6% – significantly – in asthmatics, compared with nonasthmatics, but only in obese and overweight [participants, and] not in lean” participants, he said.
Dr. Burak and his colleagues compared 525 individuals with body mass indices of less than 25 kg/m2, of whom 15 had asthma, with 385 individuals with body mass indices of more than 25, of whom 15 of whom had asthma.
Collecting bronchoalveolar lavage fluid from individuals with asthma showed a mean increase of 23% in aP2 levels in patients with obesity compared with lean individuals.
These data taken together show both systemic and local elevations of aP2 in human obesity. “That could contribute to the airway hyperreactivity and to the asthma pathogenesis,” which would confirm findings from animal studies, said Dr. Burak.
Further investigation will focus on individuals who are haploinsufficient for aP2. The group already is known to have lower risk for dyslipidemia, diabetes, and cardiovascular disease, but Dr. Burak and his collaborators also will determine whether asthma incidence is also lower.
The eventual goal is to attack aP2 as a therapeutic target. “Can we inhibit and target aP2 therapeutically in the context of obesity to treat obesity-related asthma? We have a big hope for that.”
Dr. Burak and his colleagues reported no disclosures or financial conflicts of interest.
SOURCE: Burak MF et al. ENDO 2019, Session OR01-1.
REPORTING FROM ENDO 2019
