Endo 2012

HOUSTON – Fifty-four percent of 219 obese adolescents being evaluated for bariatric surgery were deficient in vitamin D, including 9% who were severely deficient, a retrospective analysis of preoperative laboratory measures found.

Eighty-two percent of the adolescents had insufficient levels of 25-hydroxyvitamin D (25OHD) in their blood, Dr. Marisa Censani and her associates reported at the annual meeting of the Endocrine Society.

The findings are so striking that all morbidly obese adolescents should be screened for vitamin D deficiency, and those who are deficient should be treated to replete vitamin D levels, suggested Dr. Censani of Columbia University, New York.

It’s particularly important to screen adolescents before bariatric surgery procedures, some of which have been associated with bone loss, which results from weight loss and decreased calcium and vitamin D absorption. Preoperative vitamin D deficiency could put adolescent patients at greater risk because they have not reached their peak bone mass, she said.

Previous studies have shown that obese adults undergoing bariatric surgery commonly are vitamin D deficient before surgery, but these are some of the first data in preoperative adolescent patients.

Of all adolescents undergoing bariatric surgery at her institution from March 2006 to June 2011, 219 had records on serum 25OHD and parathyroid hormone levels. The cohort was 65% female, 43% white, 35% Hispanic, and 15% African American, with the rest being other races/ethnicities. Patients had a mean age of 16 years (ranging from 13-18 years) and a mean body mass index of 48 kg/m².

The mean serum 25OHD level was 21 ng/mL, which was considered insufficient. The study defined adequate levels of serum 25OHD as at least 30 ng/mL, insufficient levels as 20-29 ng/mL, deficient levels as less than 20 ng/mL, and severely deficient levels as less than 10 ng/mL.

Only 18% of patients had sufficient 25OHD levels. Twenty-nine percent had insufficient levels, 45% were vitamin D deficient, and 9% were severely deficient.

Patients with the highest BMIs were most likely to have deficient levels of 25OHD. Every kilogram increase in BMI correlated with a 0.2-ng decrease in 25OHD levels, Dr. Censani said.

Vitamin D deficiency was most common in African Americans, 82% of whom were deficient and none of whom had levels in the normal range. Fifty-nine percent of Hispanics and 37% of whites had vitamin D deficiency. Race was the strongest predictor of 25OHD levels.

Roughly 80% of African American patients were deficient in vitamin D and the rest had insufficient levels. In Hispanics, nearly 60% were deficient in vitamin D, close to 25% had insufficient levels, and about 25% had adequate levels. In whites, deficient or insufficient levels each were seen in nearly 40% of patients, with adequate levels in more than 20%.

Clear secondary hyperparathyroidism was seen in 5% of patients, though serum parathyroid levels varied inversely with 25OHD. African American race, BMI, and parathyroid levels explained 21% of the variance in 25OHD levels between patients.

To be eligible for bariatric surgery, adolescents had to have reached Tanner stage IV or V and had to have a BMI greater than 50, or above 35 kg/m² if they had comorbidities.

A physician in the audience challenged Dr. Censani’s recommendation that all obese adolescents be screened and possibly treated for vitamin D deficiency, saying there is no evidence yet of clinical benefit from that approach. Dr. Censani agreed that more research is needed to support this strategy.

The current study was limited by the lack of a community-based, nonobese control group and lack of data on dietary calcium and vitamin D intake, sun exposure, or bone mineral density. The study’s large size and relatively good ethnic diversity are strengths, she said.

The U.S. adolescent obesity rate has more than tripled in the past 30 years, with 16% of children and adolescents now overweight, 4% obese, and 4% morbidly obese, studies suggest.

Dr. Censani reported having no financial disclosures. The National Institutes of Health funded the study.

HOUSTON – Fifty-four percent of 219 obese adolescents being evaluated for bariatric surgery were deficient in vitamin D, including 9% who were severely deficient, a retrospective analysis of preoperative laboratory measures found.

Eighty-two percent of the adolescents had insufficient levels of 25-hydroxyvitamin D (25OHD) in their blood, Dr. Marisa Censani and her associates reported at the annual meeting of the Endocrine Society.

The findings are so striking that all morbidly obese adolescents should be screened for vitamin D deficiency, and those who are deficient should be treated to replete vitamin D levels, suggested Dr. Censani of Columbia University, New York.

It’s particularly important to screen adolescents before bariatric surgery procedures, some of which have been associated with bone loss, which results from weight loss and decreased calcium and vitamin D absorption. Preoperative vitamin D deficiency could put adolescent patients at greater risk because they have not reached their peak bone mass, she said.

Previous studies have shown that obese adults undergoing bariatric surgery commonly are vitamin D deficient before surgery, but these are some of the first data in preoperative adolescent patients.

Of all adolescents undergoing bariatric surgery at her institution from March 2006 to June 2011, 219 had records on serum 25OHD and parathyroid hormone levels. The cohort was 65% female, 43% white, 35% Hispanic, and 15% African American, with the rest being other races/ethnicities. Patients had a mean age of 16 years (ranging from 13-18 years) and a mean body mass index of 48 kg/m².

The mean serum 25OHD level was 21 ng/mL, which was considered insufficient. The study defined adequate levels of serum 25OHD as at least 30 ng/mL, insufficient levels as 20-29 ng/mL, deficient levels as less than 20 ng/mL, and severely deficient levels as less than 10 ng/mL.

Only 18% of patients had sufficient 25OHD levels. Twenty-nine percent had insufficient levels, 45% were vitamin D deficient, and 9% were severely deficient.

Patients with the highest BMIs were most likely to have deficient levels of 25OHD. Every kilogram increase in BMI correlated with a 0.2-ng decrease in 25OHD levels, Dr. Censani said.

Vitamin D deficiency was most common in African Americans, 82% of whom were deficient and none of whom had levels in the normal range. Fifty-nine percent of Hispanics and 37% of whites had vitamin D deficiency. Race was the strongest predictor of 25OHD levels.

Roughly 80% of African American patients were deficient in vitamin D and the rest had insufficient levels. In Hispanics, nearly 60% were deficient in vitamin D, close to 25% had insufficient levels, and about 25% had adequate levels. In whites, deficient or insufficient levels each were seen in nearly 40% of patients, with adequate levels in more than 20%.

Clear secondary hyperparathyroidism was seen in 5% of patients, though serum parathyroid levels varied inversely with 25OHD. African American race, BMI, and parathyroid levels explained 21% of the variance in 25OHD levels between patients.

To be eligible for bariatric surgery, adolescents had to have reached Tanner stage IV or V and had to have a BMI greater than 50, or above 35 kg/m² if they had comorbidities.

A physician in the audience challenged Dr. Censani’s recommendation that all obese adolescents be screened and possibly treated for vitamin D deficiency, saying there is no evidence yet of clinical benefit from that approach. Dr. Censani agreed that more research is needed to support this strategy.

The current study was limited by the lack of a community-based, nonobese control group and lack of data on dietary calcium and vitamin D intake, sun exposure, or bone mineral density. The study’s large size and relatively good ethnic diversity are strengths, she said.

The U.S. adolescent obesity rate has more than tripled in the past 30 years, with 16% of children and adolescents now overweight, 4% obese, and 4% morbidly obese, studies suggest.

Dr. Censani reported having no financial disclosures. The National Institutes of Health funded the study.

HOUSTON – Fifty-four percent of 219 obese adolescents being evaluated for bariatric surgery were deficient in vitamin D, including 9% who were severely deficient, a retrospective analysis of preoperative laboratory measures found.

Eighty-two percent of the adolescents had insufficient levels of 25-hydroxyvitamin D (25OHD) in their blood, Dr. Marisa Censani and her associates reported at the annual meeting of the Endocrine Society.

The findings are so striking that all morbidly obese adolescents should be screened for vitamin D deficiency, and those who are deficient should be treated to replete vitamin D levels, suggested Dr. Censani of Columbia University, New York.

It’s particularly important to screen adolescents before bariatric surgery procedures, some of which have been associated with bone loss, which results from weight loss and decreased calcium and vitamin D absorption. Preoperative vitamin D deficiency could put adolescent patients at greater risk because they have not reached their peak bone mass, she said.

Previous studies have shown that obese adults undergoing bariatric surgery commonly are vitamin D deficient before surgery, but these are some of the first data in preoperative adolescent patients.

Of all adolescents undergoing bariatric surgery at her institution from March 2006 to June 2011, 219 had records on serum 25OHD and parathyroid hormone levels. The cohort was 65% female, 43% white, 35% Hispanic, and 15% African American, with the rest being other races/ethnicities. Patients had a mean age of 16 years (ranging from 13-18 years) and a mean body mass index of 48 kg/m².

The mean serum 25OHD level was 21 ng/mL, which was considered insufficient. The study defined adequate levels of serum 25OHD as at least 30 ng/mL, insufficient levels as 20-29 ng/mL, deficient levels as less than 20 ng/mL, and severely deficient levels as less than 10 ng/mL.

Only 18% of patients had sufficient 25OHD levels. Twenty-nine percent had insufficient levels, 45% were vitamin D deficient, and 9% were severely deficient.

Patients with the highest BMIs were most likely to have deficient levels of 25OHD. Every kilogram increase in BMI correlated with a 0.2-ng decrease in 25OHD levels, Dr. Censani said.

Vitamin D deficiency was most common in African Americans, 82% of whom were deficient and none of whom had levels in the normal range. Fifty-nine percent of Hispanics and 37% of whites had vitamin D deficiency. Race was the strongest predictor of 25OHD levels.

Roughly 80% of African American patients were deficient in vitamin D and the rest had insufficient levels. In Hispanics, nearly 60% were deficient in vitamin D, close to 25% had insufficient levels, and about 25% had adequate levels. In whites, deficient or insufficient levels each were seen in nearly 40% of patients, with adequate levels in more than 20%.

Clear secondary hyperparathyroidism was seen in 5% of patients, though serum parathyroid levels varied inversely with 25OHD. African American race, BMI, and parathyroid levels explained 21% of the variance in 25OHD levels between patients.

To be eligible for bariatric surgery, adolescents had to have reached Tanner stage IV or V and had to have a BMI greater than 50, or above 35 kg/m² if they had comorbidities.

A physician in the audience challenged Dr. Censani’s recommendation that all obese adolescents be screened and possibly treated for vitamin D deficiency, saying there is no evidence yet of clinical benefit from that approach. Dr. Censani agreed that more research is needed to support this strategy.

The current study was limited by the lack of a community-based, nonobese control group and lack of data on dietary calcium and vitamin D intake, sun exposure, or bone mineral density. The study’s large size and relatively good ethnic diversity are strengths, she said.

The U.S. adolescent obesity rate has more than tripled in the past 30 years, with 16% of children and adolescents now overweight, 4% obese, and 4% morbidly obese, studies suggest.

Dr. Censani reported having no financial disclosures. The National Institutes of Health funded the study.

HOUSTON – A novel gene expression test could eliminate the need for a third of operations done for cytologically indeterminate thyroid nodules by winnowing out low-risk nodules, a large, prospective, double-blind, multicenter study suggests.

The study included fine-needle aspirates of thyroid nodules 1 cm or larger that were classified as indeterminate on cytology and that had corresponding histopathological specimens from excised lesions. A test that measures the expression of 167 genes was applied to 265 cytologically indeterminate nodules, with the patients, physicians, and pathology laboratories blinded to the results of the Afirma gene expression classifier test during management.

In general, cytologically indeterminate thyroid aspirates get classified one of three ways. The negative predictive value of results from the Afirma gene expression classifier test was 95% for the subset cytologically classified as "atypia (or follicular lesion) of undetermined clinical significance," 94% for "follicular neoplasm or lesion suspicious for follicular neoplasm," and 85% for "suspicious cytologic findings," Dr. Erik K. Alexander and his associates reported in a press briefing at the annual meeting of the Endocrine Society.

The Afirma test correctly identified as "suspicious" 78 of the 85 nodules that ultimately were found to be malignant, for a sensitivity of 92% and a specificity of 52%, he said.

A closer look at the seven aspirates that had false negative results from Afirma testing found that six samples lacked a sufficient quantity of thyroid follicular cells to be considered a sufficient sampling of the nodule, said Dr. Alexander of Brigham and Women’s Hospital and Harvard University, Boston.

The results are good enough that clinicians could take a conservative approach to managing most patients whose thyroid nodules are cytologically indeterminate on fine-needle aspiration but benign on the gene expression classifier test, he said.

The New England Journal of Medicine published the study online on June 25 (doi: 10.1056/NEJMoa1203208).

The new gene expression test could eliminate the need for 25,000 of the 75,000 surgeries each year in patients with cytologically indeterminate thyroid aspirates, but at the risk of likely malignancy in 5%-10% of nodules classified as benign, particularly nodules that are cytologically indeterminate but suggestive of cancer, Dr. J. Larry Jameson said in an editorial published simultaneously online by the journal (doi: 10.1056/NEJMe1205893).

In this high-risk group, repeating the fine-needle aspiration biopsy or performing a diagnostic hemithyroidectomy might be reasonable even when the gene expression classifier suggests a benign nodule, said Dr. Jameson of the University of Pennsylvania, Philadelphia.

For patients with indeterminate aspirates and negative Afirma test results who are monitored rather than sent to surgery, clinicians should have a low threshold for repeating fine-needle aspiration if ultrasound tests show rapid nodule growth or characteristics suggestive of cancer, he suggested.

Dr. Jameson called the new gene expression classifier test a "welcome addition" to tools for managing thyroid nodules that could substantially reduce costs by avoiding operations, even when considering the added cost of the test.

One of the strengths of the 49-site study was that 80% of participants came from community-based sites and 20% from academic medical sites, representing a real-world sample, coinvestigator Dr. Bryan R. Haugen said at the press briefing.

He described recent use of the Afirma test at his institution on aspirates from 126 patients with indeterminate cytology results from January 2011 to April 2012. The gene expression classifier results said 56% were benign, 41% were suspicious, and 3% could not produce a result. Seventy patients avoided surgery. Among patients who underwent surgery, 52% of nodes were malignant, said Dr. Haugen, head of endocrinology, metabolism, and diabetes at the University of Colorado, Denver.

Dr. Haugen and Dr. Alexander emphasized that the Afirma test should only be used for aspirates with indeterminate cytology, not for biopsies classified as cytologically benign, because of the 70% specificity when used on benign lesions.

Thyroid nodules are common and can be found in 25%-50% of adults. When fine-needle aspiration biopsy produces indeterminate cytological results, most patients have undergone hemithyroidectomy or total thyroidectomy for diagnosis and treatment.

Veracyte, which makes the gene expression classifier, funded the study and tested the samples in its laboratory. Veracyte employees helped design and supervise the study, conducted the statistical analysis, and made up 6 of the 18 investigators. Dr. Alexander disclosed financial associations with Veracyte, Asuragen, Genzyme, and the Boston Clinical Research Institute. His coinvestigators disclosed financial associations with Veracyte and multiple other companies. Dr. Jameson disclosed financial associations with Quest Diagnostics, Novartis, and Ferring, and said that he knows some of the investigators professionally.

HOUSTON – A novel gene expression test could eliminate the need for a third of operations done for cytologically indeterminate thyroid nodules by winnowing out low-risk nodules, a large, prospective, double-blind, multicenter study suggests.

The study included fine-needle aspirates of thyroid nodules 1 cm or larger that were classified as indeterminate on cytology and that had corresponding histopathological specimens from excised lesions. A test that measures the expression of 167 genes was applied to 265 cytologically indeterminate nodules, with the patients, physicians, and pathology laboratories blinded to the results of the Afirma gene expression classifier test during management.

In general, cytologically indeterminate thyroid aspirates get classified one of three ways. The negative predictive value of results from the Afirma gene expression classifier test was 95% for the subset cytologically classified as "atypia (or follicular lesion) of undetermined clinical significance," 94% for "follicular neoplasm or lesion suspicious for follicular neoplasm," and 85% for "suspicious cytologic findings," Dr. Erik K. Alexander and his associates reported in a press briefing at the annual meeting of the Endocrine Society.

The Afirma test correctly identified as "suspicious" 78 of the 85 nodules that ultimately were found to be malignant, for a sensitivity of 92% and a specificity of 52%, he said.

A closer look at the seven aspirates that had false negative results from Afirma testing found that six samples lacked a sufficient quantity of thyroid follicular cells to be considered a sufficient sampling of the nodule, said Dr. Alexander of Brigham and Women’s Hospital and Harvard University, Boston.

The results are good enough that clinicians could take a conservative approach to managing most patients whose thyroid nodules are cytologically indeterminate on fine-needle aspiration but benign on the gene expression classifier test, he said.

The New England Journal of Medicine published the study online on June 25 (doi: 10.1056/NEJMoa1203208).

The new gene expression test could eliminate the need for 25,000 of the 75,000 surgeries each year in patients with cytologically indeterminate thyroid aspirates, but at the risk of likely malignancy in 5%-10% of nodules classified as benign, particularly nodules that are cytologically indeterminate but suggestive of cancer, Dr. J. Larry Jameson said in an editorial published simultaneously online by the journal (doi: 10.1056/NEJMe1205893).

In this high-risk group, repeating the fine-needle aspiration biopsy or performing a diagnostic hemithyroidectomy might be reasonable even when the gene expression classifier suggests a benign nodule, said Dr. Jameson of the University of Pennsylvania, Philadelphia.

For patients with indeterminate aspirates and negative Afirma test results who are monitored rather than sent to surgery, clinicians should have a low threshold for repeating fine-needle aspiration if ultrasound tests show rapid nodule growth or characteristics suggestive of cancer, he suggested.

Dr. Jameson called the new gene expression classifier test a "welcome addition" to tools for managing thyroid nodules that could substantially reduce costs by avoiding operations, even when considering the added cost of the test.

One of the strengths of the 49-site study was that 80% of participants came from community-based sites and 20% from academic medical sites, representing a real-world sample, coinvestigator Dr. Bryan R. Haugen said at the press briefing.

He described recent use of the Afirma test at his institution on aspirates from 126 patients with indeterminate cytology results from January 2011 to April 2012. The gene expression classifier results said 56% were benign, 41% were suspicious, and 3% could not produce a result. Seventy patients avoided surgery. Among patients who underwent surgery, 52% of nodes were malignant, said Dr. Haugen, head of endocrinology, metabolism, and diabetes at the University of Colorado, Denver.

Dr. Haugen and Dr. Alexander emphasized that the Afirma test should only be used for aspirates with indeterminate cytology, not for biopsies classified as cytologically benign, because of the 70% specificity when used on benign lesions.

Thyroid nodules are common and can be found in 25%-50% of adults. When fine-needle aspiration biopsy produces indeterminate cytological results, most patients have undergone hemithyroidectomy or total thyroidectomy for diagnosis and treatment.

Veracyte, which makes the gene expression classifier, funded the study and tested the samples in its laboratory. Veracyte employees helped design and supervise the study, conducted the statistical analysis, and made up 6 of the 18 investigators. Dr. Alexander disclosed financial associations with Veracyte, Asuragen, Genzyme, and the Boston Clinical Research Institute. His coinvestigators disclosed financial associations with Veracyte and multiple other companies. Dr. Jameson disclosed financial associations with Quest Diagnostics, Novartis, and Ferring, and said that he knows some of the investigators professionally.

HOUSTON – A novel gene expression test could eliminate the need for a third of operations done for cytologically indeterminate thyroid nodules by winnowing out low-risk nodules, a large, prospective, double-blind, multicenter study suggests.

The study included fine-needle aspirates of thyroid nodules 1 cm or larger that were classified as indeterminate on cytology and that had corresponding histopathological specimens from excised lesions. A test that measures the expression of 167 genes was applied to 265 cytologically indeterminate nodules, with the patients, physicians, and pathology laboratories blinded to the results of the Afirma gene expression classifier test during management.

In general, cytologically indeterminate thyroid aspirates get classified one of three ways. The negative predictive value of results from the Afirma gene expression classifier test was 95% for the subset cytologically classified as "atypia (or follicular lesion) of undetermined clinical significance," 94% for "follicular neoplasm or lesion suspicious for follicular neoplasm," and 85% for "suspicious cytologic findings," Dr. Erik K. Alexander and his associates reported in a press briefing at the annual meeting of the Endocrine Society.

The Afirma test correctly identified as "suspicious" 78 of the 85 nodules that ultimately were found to be malignant, for a sensitivity of 92% and a specificity of 52%, he said.

A closer look at the seven aspirates that had false negative results from Afirma testing found that six samples lacked a sufficient quantity of thyroid follicular cells to be considered a sufficient sampling of the nodule, said Dr. Alexander of Brigham and Women’s Hospital and Harvard University, Boston.

The results are good enough that clinicians could take a conservative approach to managing most patients whose thyroid nodules are cytologically indeterminate on fine-needle aspiration but benign on the gene expression classifier test, he said.

The New England Journal of Medicine published the study online on June 25 (doi: 10.1056/NEJMoa1203208).

The new gene expression test could eliminate the need for 25,000 of the 75,000 surgeries each year in patients with cytologically indeterminate thyroid aspirates, but at the risk of likely malignancy in 5%-10% of nodules classified as benign, particularly nodules that are cytologically indeterminate but suggestive of cancer, Dr. J. Larry Jameson said in an editorial published simultaneously online by the journal (doi: 10.1056/NEJMe1205893).

In this high-risk group, repeating the fine-needle aspiration biopsy or performing a diagnostic hemithyroidectomy might be reasonable even when the gene expression classifier suggests a benign nodule, said Dr. Jameson of the University of Pennsylvania, Philadelphia.

For patients with indeterminate aspirates and negative Afirma test results who are monitored rather than sent to surgery, clinicians should have a low threshold for repeating fine-needle aspiration if ultrasound tests show rapid nodule growth or characteristics suggestive of cancer, he suggested.

Dr. Jameson called the new gene expression classifier test a "welcome addition" to tools for managing thyroid nodules that could substantially reduce costs by avoiding operations, even when considering the added cost of the test.

One of the strengths of the 49-site study was that 80% of participants came from community-based sites and 20% from academic medical sites, representing a real-world sample, coinvestigator Dr. Bryan R. Haugen said at the press briefing.

He described recent use of the Afirma test at his institution on aspirates from 126 patients with indeterminate cytology results from January 2011 to April 2012. The gene expression classifier results said 56% were benign, 41% were suspicious, and 3% could not produce a result. Seventy patients avoided surgery. Among patients who underwent surgery, 52% of nodes were malignant, said Dr. Haugen, head of endocrinology, metabolism, and diabetes at the University of Colorado, Denver.

Dr. Haugen and Dr. Alexander emphasized that the Afirma test should only be used for aspirates with indeterminate cytology, not for biopsies classified as cytologically benign, because of the 70% specificity when used on benign lesions.

Thyroid nodules are common and can be found in 25%-50% of adults. When fine-needle aspiration biopsy produces indeterminate cytological results, most patients have undergone hemithyroidectomy or total thyroidectomy for diagnosis and treatment.

Veracyte, which makes the gene expression classifier, funded the study and tested the samples in its laboratory. Veracyte employees helped design and supervise the study, conducted the statistical analysis, and made up 6 of the 18 investigators. Dr. Alexander disclosed financial associations with Veracyte, Asuragen, Genzyme, and the Boston Clinical Research Institute. His coinvestigators disclosed financial associations with Veracyte and multiple other companies. Dr. Jameson disclosed financial associations with Quest Diagnostics, Novartis, and Ferring, and said that he knows some of the investigators professionally.

HOUSTON – Applying transdermal gels containing off-label testosterone and an experimental nonandrogenic progestin showed promise as a form of reversible contraception for men in a randomized, double-blind, controlled pilot study in 99 men.

Healthy male volunteers were randomized in three groups to apply gels containing 10 g of testosterone plus placebo or testosterone plus either 8 mg or 12 mg of Nestorone, an investigational synthetic nonandrogenic progestin. They were asked to apply the gels daily for 20-24 weeks, and 56 complied.

Among those who completed the study, sperm concentrations in men on the combination gels were significantly more likely to decrease to 1 million/mL or lower (a level that previously has been proven to provide contraception), compared with men on testosterone/placebo gels. Eighty-nine percent of men in the 8-mg Nestorone group and 88% in the 12-mg group reached this sperm concentration threshold, compared with 23% on testosterone/placebo, Dr. Niloufar Ilani and her associates reported at the annual meeting of the Endocrine Society.

Men on the combination gels also were significantly more likely to have a complete absence of sperm. Azoospermia rates were 78% in the 8-mg group, 69% in the 12-mg group, and 23% on testosterone/placebo, said Dr. Ilani of Harbor–University of California, Los Angeles Medical Center.

Testosterone gel in the United States is approved to treat androgen deficiency in men but not for contraception. Long-term testosterone via injection is available in some non-U.S. countries.

Decreases in sperm concentration were accompanied by decreases in sperm motility and normal morphology. The combination-gel groups showed greater suppression of median serum luteinizing hormone and follicular stimulating hormone concentrations, compared with the testosterone-alone group.

Median total and free testosterone concentrations increased with treatment but remained within the adult male range in all treatment groups.

After treatment stopped, sperm concentrations recovered to greater than 3 million/mL in all subjects by 40 weeks after the start of the study.

No serious side effects were seen. Adverse events that may be related to the medications included acne in 21% of the entire cohort (28% in the control group, 21% in the 8-mg group, and 15% in the 12-mg group). Using a lower dose of testosterone may limit this androgen-related effect, the investigators suggested.

Seven percent reported weight gain (3% in the control group, 12% in the 8-mg group, and 6% in the 12-mg group). Six percent of subjects in each group reported insomnia. Four percent of all subjects reported dry skin, among other potential side effects. Results of psychosocial measures and assessments of mood stability did not change significantly in any group during or after treatment, compared with baseline.

Now that this study has proved the concept, investigators may try to combine the testosterone gel and Nestorone gel into a single gel that men could apply more conveniently. They also will test the combination in a study that recruits couples and asks participants not to use other contraceptives. In the current study, men were required to use a proven method of contraception and not rely on the gels.

Combining 8 mg Nestorone and testosterone seemed to be the best dosing combination because the higher dose of Nestorone did not offer greater sperm suppression, Dr. Ilani said.

Patient and sperm characteristics were similar between groups at the start of the study.

Dr. Ilani reported having no financial disclosures. Besins Healthcare International provided the testosterone gel. The Population Council, a nonprofit organization that is developing Nestorone, supplied the drug. The Eunice Kennedy Shriver National Institute of Child Health and Human Development funded the study.

HOUSTON – Applying transdermal gels containing off-label testosterone and an experimental nonandrogenic progestin showed promise as a form of reversible contraception for men in a randomized, double-blind, controlled pilot study in 99 men.

Healthy male volunteers were randomized in three groups to apply gels containing 10 g of testosterone plus placebo or testosterone plus either 8 mg or 12 mg of Nestorone, an investigational synthetic nonandrogenic progestin. They were asked to apply the gels daily for 20-24 weeks, and 56 complied.

Among those who completed the study, sperm concentrations in men on the combination gels were significantly more likely to decrease to 1 million/mL or lower (a level that previously has been proven to provide contraception), compared with men on testosterone/placebo gels. Eighty-nine percent of men in the 8-mg Nestorone group and 88% in the 12-mg group reached this sperm concentration threshold, compared with 23% on testosterone/placebo, Dr. Niloufar Ilani and her associates reported at the annual meeting of the Endocrine Society.

Men on the combination gels also were significantly more likely to have a complete absence of sperm. Azoospermia rates were 78% in the 8-mg group, 69% in the 12-mg group, and 23% on testosterone/placebo, said Dr. Ilani of Harbor–University of California, Los Angeles Medical Center.

Testosterone gel in the United States is approved to treat androgen deficiency in men but not for contraception. Long-term testosterone via injection is available in some non-U.S. countries.

Decreases in sperm concentration were accompanied by decreases in sperm motility and normal morphology. The combination-gel groups showed greater suppression of median serum luteinizing hormone and follicular stimulating hormone concentrations, compared with the testosterone-alone group.

Median total and free testosterone concentrations increased with treatment but remained within the adult male range in all treatment groups.

After treatment stopped, sperm concentrations recovered to greater than 3 million/mL in all subjects by 40 weeks after the start of the study.

No serious side effects were seen. Adverse events that may be related to the medications included acne in 21% of the entire cohort (28% in the control group, 21% in the 8-mg group, and 15% in the 12-mg group). Using a lower dose of testosterone may limit this androgen-related effect, the investigators suggested.

Seven percent reported weight gain (3% in the control group, 12% in the 8-mg group, and 6% in the 12-mg group). Six percent of subjects in each group reported insomnia. Four percent of all subjects reported dry skin, among other potential side effects. Results of psychosocial measures and assessments of mood stability did not change significantly in any group during or after treatment, compared with baseline.

Now that this study has proved the concept, investigators may try to combine the testosterone gel and Nestorone gel into a single gel that men could apply more conveniently. They also will test the combination in a study that recruits couples and asks participants not to use other contraceptives. In the current study, men were required to use a proven method of contraception and not rely on the gels.

Combining 8 mg Nestorone and testosterone seemed to be the best dosing combination because the higher dose of Nestorone did not offer greater sperm suppression, Dr. Ilani said.

Patient and sperm characteristics were similar between groups at the start of the study.

Dr. Ilani reported having no financial disclosures. Besins Healthcare International provided the testosterone gel. The Population Council, a nonprofit organization that is developing Nestorone, supplied the drug. The Eunice Kennedy Shriver National Institute of Child Health and Human Development funded the study.

HOUSTON – Applying transdermal gels containing off-label testosterone and an experimental nonandrogenic progestin showed promise as a form of reversible contraception for men in a randomized, double-blind, controlled pilot study in 99 men.

Healthy male volunteers were randomized in three groups to apply gels containing 10 g of testosterone plus placebo or testosterone plus either 8 mg or 12 mg of Nestorone, an investigational synthetic nonandrogenic progestin. They were asked to apply the gels daily for 20-24 weeks, and 56 complied.

Among those who completed the study, sperm concentrations in men on the combination gels were significantly more likely to decrease to 1 million/mL or lower (a level that previously has been proven to provide contraception), compared with men on testosterone/placebo gels. Eighty-nine percent of men in the 8-mg Nestorone group and 88% in the 12-mg group reached this sperm concentration threshold, compared with 23% on testosterone/placebo, Dr. Niloufar Ilani and her associates reported at the annual meeting of the Endocrine Society.

Men on the combination gels also were significantly more likely to have a complete absence of sperm. Azoospermia rates were 78% in the 8-mg group, 69% in the 12-mg group, and 23% on testosterone/placebo, said Dr. Ilani of Harbor–University of California, Los Angeles Medical Center.

Testosterone gel in the United States is approved to treat androgen deficiency in men but not for contraception. Long-term testosterone via injection is available in some non-U.S. countries.

Decreases in sperm concentration were accompanied by decreases in sperm motility and normal morphology. The combination-gel groups showed greater suppression of median serum luteinizing hormone and follicular stimulating hormone concentrations, compared with the testosterone-alone group.

Median total and free testosterone concentrations increased with treatment but remained within the adult male range in all treatment groups.

After treatment stopped, sperm concentrations recovered to greater than 3 million/mL in all subjects by 40 weeks after the start of the study.

No serious side effects were seen. Adverse events that may be related to the medications included acne in 21% of the entire cohort (28% in the control group, 21% in the 8-mg group, and 15% in the 12-mg group). Using a lower dose of testosterone may limit this androgen-related effect, the investigators suggested.

Seven percent reported weight gain (3% in the control group, 12% in the 8-mg group, and 6% in the 12-mg group). Six percent of subjects in each group reported insomnia. Four percent of all subjects reported dry skin, among other potential side effects. Results of psychosocial measures and assessments of mood stability did not change significantly in any group during or after treatment, compared with baseline.

Now that this study has proved the concept, investigators may try to combine the testosterone gel and Nestorone gel into a single gel that men could apply more conveniently. They also will test the combination in a study that recruits couples and asks participants not to use other contraceptives. In the current study, men were required to use a proven method of contraception and not rely on the gels.

Combining 8 mg Nestorone and testosterone seemed to be the best dosing combination because the higher dose of Nestorone did not offer greater sperm suppression, Dr. Ilani said.

Patient and sperm characteristics were similar between groups at the start of the study.

Dr. Ilani reported having no financial disclosures. Besins Healthcare International provided the testosterone gel. The Population Council, a nonprofit organization that is developing Nestorone, supplied the drug. The Eunice Kennedy Shriver National Institute of Child Health and Human Development funded the study.

HOUSTON – Long-term testosterone replacement therapy in men with hypogonadism brought impressive reductions in body weight and waist circumference in a 5-year observational study.

"This is an amazing response. I don’t know of many other therapies where you have more than 90% of treated patients respond in a positive way," observed Farid Saad, Ph.D. He referred to the fact that 90% of the 255 men treated for hypogonadism lost at least 5 kg from their initial body weight and 97% experienced shrinkage in waist circumference, with a 10-cm or greater reduction in 46% of men. That’s a lot of belt notches.

This 5-year study of testosterone replacement in hypogonadal men features what’s easily the longest follow-up reported anywhere to date. The average 36-pound weight loss and substantial waist shrinkage were "unintended and unexpected," because prior 1- to 2-year-long studies showed less impressive changes, explained Dr. Saad, at the annual meeting of the Endocrine Society.

The 255 study participants averaged just under 61 years of age. Nearly all were obese or overweight, as is typical in male hypogonadism. All had a serum testosterone level below 350 ng/dL, along with testosterone deficiency–related symptoms. Serum testosterone levels normalized within the first 6-9 months of treatment with slow-acting intramuscular testosterone undecanoate and remained in the normal range thereafter.

"If you can’t motivate men to deal with their subclinical coronary artery disease, they will definitely be motivated to deal with their erections and their frequent night urination."

The men went from a mean baseline body weight of 106 kg to 90 kg over the course of 5 years. A total of 76% of participants lost 10 kg or more of their initial body weight, 53% lost at least 15 kg, and 31% dropped at least 20 kg. The weight loss was continuous; the men lost a mean of 4% of their initial body weight at 1 year, 9% at 3 years, and 13.2% after 5 years. Only 5% of men gained weight during follow-up.

Waist circumference declined by a mean of 8.8 cm from 107.2 cm at baseline. And mean body mass index dropped from 34 to 29 kg/m².

Study participants were not placed on a structured diet or exercise program, although they did receive advice on the importance of making lifestyle changes.

Three men have developed prostate cancer, but that’s less than the background rate in the general population.

"I think now the general understanding at the major urologic conferences is that testosterone does not increase the risk of prostate cancer. And I wouldn’t expect other side effects because testosterone is a natural substance and we don’t use supraphysiologic doses, we just bring testosterone levels in these hypogonadal men back to normal. I say, in a maybe not very scientific way, that if testosterone [were] harmful to men, then nature would have made a major mistake," according to Dr. Saad, head of global medical affairs–andrology at Bayer Pharma in Berlin.

He added that it would be nice to confirm the findings of this observational study in a prospective randomized controlled trial, but no ethics committee in the world would approve such a study because testosterone deficiency carries elevated risks of osteoporosis, cardiovascular disease, and diabetes. And the treatment for testosterone deficiency as spelled out in Endocrine Society guidelines is testosterone replacement to normal physiologic levels.

Two other studies presented at the conference confirmed Dr. Saad’s weight loss and waist circumference shrinkage findings. Dr. Youssef El Douaihy of Maimonides Medical Center, New York, reported that during a median 6.7-year follow-up of 130 hypogonadal men on testosterone replacement therapy, the subjects lost a mean of 14.3 kg or 13% of their initial body weight. They also experienced a mean 11-cm decrease in waist circumference.

And Dr. Michael Zitzmann of the University of Munster, Germany, presented a series of 334 patients with male hypogonadism treated for up to 15 years with intramuscular testosterone undecanoate. The prevalence of metabolic syndrome dropped from 88% to 52% within the first 2 years. Highly significant reductions in blood pressure, resting heart rate, body weight, body mass index, waist circumference, fasting blood glucose, LDL cholesterol, and triglycerides were documented, all highly significant differences.

Why the big weight loss in patients on long-term testosterone replacement therapy? Dr. Saad speculated that the explanation might lie in the combined improvements in vitality, virility, and motivation to change, all of which in recent studies have been shown to be triggered by normalization of testosterone levels.

"Testosterone may be of value as a facilitator of lifestyle change," he asserted.

Dr. Gary Wittert concurred.

"It’s extremely motivating to men to see their testosterone level come up to normal and the associated improvement in body weight, erectile dysfunction, and the significant improvement in lower urinary tract symptoms. So the message is quite clear: If you can’t motivate men to deal with their subclinical coronary artery disease, they will definitely be motivated to deal with their erections and their frequent night urination," declared Dr. Wittert, professor of medicine at the University of Adelaide, Australia, who is a testosterone clinical trialist not involved in these studies.

Dr. Saad noted that another attribute of testosterone normalization that may be highly relevant to progressive long-term weight loss is that testosterone increases fat-free mass. He cited a recent pilot study in which hypogonadal men with spinal cord injury received transdermal testosterone replacement. In 1 year, their fat-free mass increased by an average of 3.5 kg and their resting energy expenditure rose by 112 kcal/day (Horm. Metab. Res. 2011;43:574-9).

"If you accumulate that over 5 years, it could be a major contributor to the weight loss the men in our study experienced," Dr. Saad observed.

Dr. Vineeth Mohan, who chaired a session where Dr. Saad presented his findings, said the new data raise the possibility that a large weight loss in a patient treated for male hypogonadism could be an indicator that natural testosterone production has recovered and replacement therapy is no longer needed. That would make sense, since adipose tissue is a powerful suppressor of testosterone production.

"I might look at that loss of a significant amount of body weight as a signal that the testosterone axis has improved, and perhaps as an opportunity for reassessment," said Dr. Mohan, an endocrinologist at the Cleveland Clinic Foundation in Weston, Fla.

He reported having no financial conflicts.

HOUSTON – Long-term testosterone replacement therapy in men with hypogonadism brought impressive reductions in body weight and waist circumference in a 5-year observational study.

"This is an amazing response. I don’t know of many other therapies where you have more than 90% of treated patients respond in a positive way," observed Farid Saad, Ph.D. He referred to the fact that 90% of the 255 men treated for hypogonadism lost at least 5 kg from their initial body weight and 97% experienced shrinkage in waist circumference, with a 10-cm or greater reduction in 46% of men. That’s a lot of belt notches.

This 5-year study of testosterone replacement in hypogonadal men features what’s easily the longest follow-up reported anywhere to date. The average 36-pound weight loss and substantial waist shrinkage were "unintended and unexpected," because prior 1- to 2-year-long studies showed less impressive changes, explained Dr. Saad, at the annual meeting of the Endocrine Society.

The 255 study participants averaged just under 61 years of age. Nearly all were obese or overweight, as is typical in male hypogonadism. All had a serum testosterone level below 350 ng/dL, along with testosterone deficiency–related symptoms. Serum testosterone levels normalized within the first 6-9 months of treatment with slow-acting intramuscular testosterone undecanoate and remained in the normal range thereafter.

"If you can’t motivate men to deal with their subclinical coronary artery disease, they will definitely be motivated to deal with their erections and their frequent night urination."

The men went from a mean baseline body weight of 106 kg to 90 kg over the course of 5 years. A total of 76% of participants lost 10 kg or more of their initial body weight, 53% lost at least 15 kg, and 31% dropped at least 20 kg. The weight loss was continuous; the men lost a mean of 4% of their initial body weight at 1 year, 9% at 3 years, and 13.2% after 5 years. Only 5% of men gained weight during follow-up.

Waist circumference declined by a mean of 8.8 cm from 107.2 cm at baseline. And mean body mass index dropped from 34 to 29 kg/m².

Study participants were not placed on a structured diet or exercise program, although they did receive advice on the importance of making lifestyle changes.

Three men have developed prostate cancer, but that’s less than the background rate in the general population.

"I think now the general understanding at the major urologic conferences is that testosterone does not increase the risk of prostate cancer. And I wouldn’t expect other side effects because testosterone is a natural substance and we don’t use supraphysiologic doses, we just bring testosterone levels in these hypogonadal men back to normal. I say, in a maybe not very scientific way, that if testosterone [were] harmful to men, then nature would have made a major mistake," according to Dr. Saad, head of global medical affairs–andrology at Bayer Pharma in Berlin.

He added that it would be nice to confirm the findings of this observational study in a prospective randomized controlled trial, but no ethics committee in the world would approve such a study because testosterone deficiency carries elevated risks of osteoporosis, cardiovascular disease, and diabetes. And the treatment for testosterone deficiency as spelled out in Endocrine Society guidelines is testosterone replacement to normal physiologic levels.

Two other studies presented at the conference confirmed Dr. Saad’s weight loss and waist circumference shrinkage findings. Dr. Youssef El Douaihy of Maimonides Medical Center, New York, reported that during a median 6.7-year follow-up of 130 hypogonadal men on testosterone replacement therapy, the subjects lost a mean of 14.3 kg or 13% of their initial body weight. They also experienced a mean 11-cm decrease in waist circumference.

And Dr. Michael Zitzmann of the University of Munster, Germany, presented a series of 334 patients with male hypogonadism treated for up to 15 years with intramuscular testosterone undecanoate. The prevalence of metabolic syndrome dropped from 88% to 52% within the first 2 years. Highly significant reductions in blood pressure, resting heart rate, body weight, body mass index, waist circumference, fasting blood glucose, LDL cholesterol, and triglycerides were documented, all highly significant differences.

Why the big weight loss in patients on long-term testosterone replacement therapy? Dr. Saad speculated that the explanation might lie in the combined improvements in vitality, virility, and motivation to change, all of which in recent studies have been shown to be triggered by normalization of testosterone levels.

"Testosterone may be of value as a facilitator of lifestyle change," he asserted.

Dr. Gary Wittert concurred.

"It’s extremely motivating to men to see their testosterone level come up to normal and the associated improvement in body weight, erectile dysfunction, and the significant improvement in lower urinary tract symptoms. So the message is quite clear: If you can’t motivate men to deal with their subclinical coronary artery disease, they will definitely be motivated to deal with their erections and their frequent night urination," declared Dr. Wittert, professor of medicine at the University of Adelaide, Australia, who is a testosterone clinical trialist not involved in these studies.

Dr. Saad noted that another attribute of testosterone normalization that may be highly relevant to progressive long-term weight loss is that testosterone increases fat-free mass. He cited a recent pilot study in which hypogonadal men with spinal cord injury received transdermal testosterone replacement. In 1 year, their fat-free mass increased by an average of 3.5 kg and their resting energy expenditure rose by 112 kcal/day (Horm. Metab. Res. 2011;43:574-9).

"If you accumulate that over 5 years, it could be a major contributor to the weight loss the men in our study experienced," Dr. Saad observed.

Dr. Vineeth Mohan, who chaired a session where Dr. Saad presented his findings, said the new data raise the possibility that a large weight loss in a patient treated for male hypogonadism could be an indicator that natural testosterone production has recovered and replacement therapy is no longer needed. That would make sense, since adipose tissue is a powerful suppressor of testosterone production.

"I might look at that loss of a significant amount of body weight as a signal that the testosterone axis has improved, and perhaps as an opportunity for reassessment," said Dr. Mohan, an endocrinologist at the Cleveland Clinic Foundation in Weston, Fla.

He reported having no financial conflicts.

HOUSTON – Long-term testosterone replacement therapy in men with hypogonadism brought impressive reductions in body weight and waist circumference in a 5-year observational study.

"This is an amazing response. I don’t know of many other therapies where you have more than 90% of treated patients respond in a positive way," observed Farid Saad, Ph.D. He referred to the fact that 90% of the 255 men treated for hypogonadism lost at least 5 kg from their initial body weight and 97% experienced shrinkage in waist circumference, with a 10-cm or greater reduction in 46% of men. That’s a lot of belt notches.

This 5-year study of testosterone replacement in hypogonadal men features what’s easily the longest follow-up reported anywhere to date. The average 36-pound weight loss and substantial waist shrinkage were "unintended and unexpected," because prior 1- to 2-year-long studies showed less impressive changes, explained Dr. Saad, at the annual meeting of the Endocrine Society.

The 255 study participants averaged just under 61 years of age. Nearly all were obese or overweight, as is typical in male hypogonadism. All had a serum testosterone level below 350 ng/dL, along with testosterone deficiency–related symptoms. Serum testosterone levels normalized within the first 6-9 months of treatment with slow-acting intramuscular testosterone undecanoate and remained in the normal range thereafter.

"If you can’t motivate men to deal with their subclinical coronary artery disease, they will definitely be motivated to deal with their erections and their frequent night urination."

The men went from a mean baseline body weight of 106 kg to 90 kg over the course of 5 years. A total of 76% of participants lost 10 kg or more of their initial body weight, 53% lost at least 15 kg, and 31% dropped at least 20 kg. The weight loss was continuous; the men lost a mean of 4% of their initial body weight at 1 year, 9% at 3 years, and 13.2% after 5 years. Only 5% of men gained weight during follow-up.

Waist circumference declined by a mean of 8.8 cm from 107.2 cm at baseline. And mean body mass index dropped from 34 to 29 kg/m².

Study participants were not placed on a structured diet or exercise program, although they did receive advice on the importance of making lifestyle changes.

Three men have developed prostate cancer, but that’s less than the background rate in the general population.

"I think now the general understanding at the major urologic conferences is that testosterone does not increase the risk of prostate cancer. And I wouldn’t expect other side effects because testosterone is a natural substance and we don’t use supraphysiologic doses, we just bring testosterone levels in these hypogonadal men back to normal. I say, in a maybe not very scientific way, that if testosterone [were] harmful to men, then nature would have made a major mistake," according to Dr. Saad, head of global medical affairs–andrology at Bayer Pharma in Berlin.

He added that it would be nice to confirm the findings of this observational study in a prospective randomized controlled trial, but no ethics committee in the world would approve such a study because testosterone deficiency carries elevated risks of osteoporosis, cardiovascular disease, and diabetes. And the treatment for testosterone deficiency as spelled out in Endocrine Society guidelines is testosterone replacement to normal physiologic levels.

Two other studies presented at the conference confirmed Dr. Saad’s weight loss and waist circumference shrinkage findings. Dr. Youssef El Douaihy of Maimonides Medical Center, New York, reported that during a median 6.7-year follow-up of 130 hypogonadal men on testosterone replacement therapy, the subjects lost a mean of 14.3 kg or 13% of their initial body weight. They also experienced a mean 11-cm decrease in waist circumference.

And Dr. Michael Zitzmann of the University of Munster, Germany, presented a series of 334 patients with male hypogonadism treated for up to 15 years with intramuscular testosterone undecanoate. The prevalence of metabolic syndrome dropped from 88% to 52% within the first 2 years. Highly significant reductions in blood pressure, resting heart rate, body weight, body mass index, waist circumference, fasting blood glucose, LDL cholesterol, and triglycerides were documented, all highly significant differences.

Why the big weight loss in patients on long-term testosterone replacement therapy? Dr. Saad speculated that the explanation might lie in the combined improvements in vitality, virility, and motivation to change, all of which in recent studies have been shown to be triggered by normalization of testosterone levels.

"Testosterone may be of value as a facilitator of lifestyle change," he asserted.

Dr. Gary Wittert concurred.

"It’s extremely motivating to men to see their testosterone level come up to normal and the associated improvement in body weight, erectile dysfunction, and the significant improvement in lower urinary tract symptoms. So the message is quite clear: If you can’t motivate men to deal with their subclinical coronary artery disease, they will definitely be motivated to deal with their erections and their frequent night urination," declared Dr. Wittert, professor of medicine at the University of Adelaide, Australia, who is a testosterone clinical trialist not involved in these studies.

Dr. Saad noted that another attribute of testosterone normalization that may be highly relevant to progressive long-term weight loss is that testosterone increases fat-free mass. He cited a recent pilot study in which hypogonadal men with spinal cord injury received transdermal testosterone replacement. In 1 year, their fat-free mass increased by an average of 3.5 kg and their resting energy expenditure rose by 112 kcal/day (Horm. Metab. Res. 2011;43:574-9).

"If you accumulate that over 5 years, it could be a major contributor to the weight loss the men in our study experienced," Dr. Saad observed.

Dr. Vineeth Mohan, who chaired a session where Dr. Saad presented his findings, said the new data raise the possibility that a large weight loss in a patient treated for male hypogonadism could be an indicator that natural testosterone production has recovered and replacement therapy is no longer needed. That would make sense, since adipose tissue is a powerful suppressor of testosterone production.

"I might look at that loss of a significant amount of body weight as a signal that the testosterone axis has improved, and perhaps as an opportunity for reassessment," said Dr. Mohan, an endocrinologist at the Cleveland Clinic Foundation in Weston, Fla.

He reported having no financial conflicts.

The Endocrine Society annual meeting is taking place June 23-26 in Houston. Our reporting team will cover this meeting on-site. Check here for the latest from this important meeting.

The Endocrine Society annual meeting is taking place June 23-26 in Houston. Our reporting team will cover this meeting on-site. Check here for the latest from this important meeting.

The Endocrine Society annual meeting is taking place June 23-26 in Houston. Our reporting team will cover this meeting on-site. Check here for the latest from this important meeting.