Sherry Boschert

Having rheumatoid arthritis tripled the risk for developing deep vein thrombosis and doubled the risk for pulmonary embolism in an analysis of data on 146,190 Taiwan residents.

Investigators identified 29,238 people with new diagnoses of rheumatoid arthritis in 1998-2008 in a national database with health records on Taiwan’s entire population of 23.7 million people. They extended the monitoring period for the study to the end of 2010 and compared the rheumatoid arthritis cohort with 116,952 control patients matched by sex and age in the year of diagnosis.

Expressed in person-years of follow-up, the incidence density of deep vein thrombosis was significantly higher in patients with rheumatoid arthritis (11 per 1,000 person-years), compared with the control group patients (3 per 1,000 person-years). The incidence density of pulmonary thromboembolism also was significantly higher in patients with rheumatoid arthritis compared with controls (4 vs. 2 per 1,000 person-years), Dr. Wei-Sheng Chung and his associates reported Aug. 7 in the Annals of the Rheumatic Diseases.

Courtesy Dr. Chia-Hung Kao

In all, the data included 193,753 person-years of follow-up in the rheumatoid arthritis group and 792,941 person-years of follow-up in the control group.

After adjusting for age, sex, and comorbidities, the rheumatoid arthritis group had a 3.36-fold higher chance of developing deep vein thrombosis and a 2.07-fold higher risk for developing pulmonary embolism, compared with controls, reported Dr. Chung of Taichung (Taiwan) Hospital and his colleagues (Ann. Rheum. Dis. 2013 Aug. 7 [doi:10.1136/annrheumdis-2013-203380]).

The greatest rise in risk was seen in young adults (50 years or younger) with rheumatoid arthritis, who had a nearly six-fold increased risk for deep vein thrombosis and a tripled risk for pulmonary embolism, compared with controls. The increased risk for deep vein thrombosis was seen mainly in the first 4 years after diagnosis of rheumatoid arthritis, which relied on American College of Rheumatology 1987 criteria that may have identified the disease at a later stage, the investigators suggested. The ACR and the European League Against Rheumatism (EULAR) revised their classification criteria in 2010 to focus on features at earlier stages of the disease.

Patients with rheumatoid arthritis were significantly more likely than controls to have comorbidities, including hypertension, diabetes, hyperlipidemia, heart failure, or lower leg fracture or surgery. The presence of both rheumatoid arthritis and a comorbidity multiplied the risk for thromboembolism, with a six-fold increased risk for deep vein thrombosis and a four-fold increased risk for pulmonary embolism, compared with patients with neither rheumatoid arthritis nor a comorbidity.

"Providing adequate care for patients with rheumatoid arthritis with comorbidities is an important step in preventing further development of deep vein thrombosis and pulmonary embolism. Thus, a multidisciplinary team should guide the assessment, treatment and holistic care of patients with rheumatoid arthritis," Dr. Chung and his associates concluded.

In Taiwan, an estimated 0.1% of the population has rheumatoid arthritis, which is lower than rates of 0.5%-1% in Western countries, they noted. In general, venous thromboembolism leads to death within 30 days in 11%-30% of patients, previous data show.

Two recent population-based cohort studies of patients in Sweden (JAMA 2012;308:1350-6) and in the United Kingdom (Ann. Rheum. Dis. 2013;72:1182-7) reported a doubling in risk for venous thromboembolism in people with rheumatoid arthritis. The differences in increased risk seen in the Taiwan and Western studies may be associated with racial differences, the Taiwanese investigators suggested.

The study cohort was 77% female and had a mean age of 52 years.

The findings are limited by the fact that the Taiwanese database did not include information on smoking, body mass index, physical activity, severity of rheumatoid arthritis, and use of drugs that could affect risk, including hormone replacement therapy, anticonceptive drugs, or glucocorticoids.

Chronic inflammation in patients with rheumatoid arthritis has been associated with prothrombotic factors and endothelial dysfunction in the development of atherothrombosis in prior studies.

Dr. Chung reported having no financial disclosures. The Taiwan government and Taichung Hospital funded the study.

[email protected]

On Twitter @sherryboschert

Having rheumatoid arthritis tripled the risk for developing deep vein thrombosis and doubled the risk for pulmonary embolism in an analysis of data on 146,190 Taiwan residents.

Investigators identified 29,238 people with new diagnoses of rheumatoid arthritis in 1998-2008 in a national database with health records on Taiwan’s entire population of 23.7 million people. They extended the monitoring period for the study to the end of 2010 and compared the rheumatoid arthritis cohort with 116,952 control patients matched by sex and age in the year of diagnosis.

Expressed in person-years of follow-up, the incidence density of deep vein thrombosis was significantly higher in patients with rheumatoid arthritis (11 per 1,000 person-years), compared with the control group patients (3 per 1,000 person-years). The incidence density of pulmonary thromboembolism also was significantly higher in patients with rheumatoid arthritis compared with controls (4 vs. 2 per 1,000 person-years), Dr. Wei-Sheng Chung and his associates reported Aug. 7 in the Annals of the Rheumatic Diseases.

Courtesy Dr. Chia-Hung Kao

In all, the data included 193,753 person-years of follow-up in the rheumatoid arthritis group and 792,941 person-years of follow-up in the control group.

After adjusting for age, sex, and comorbidities, the rheumatoid arthritis group had a 3.36-fold higher chance of developing deep vein thrombosis and a 2.07-fold higher risk for developing pulmonary embolism, compared with controls, reported Dr. Chung of Taichung (Taiwan) Hospital and his colleagues (Ann. Rheum. Dis. 2013 Aug. 7 [doi:10.1136/annrheumdis-2013-203380]).

The greatest rise in risk was seen in young adults (50 years or younger) with rheumatoid arthritis, who had a nearly six-fold increased risk for deep vein thrombosis and a tripled risk for pulmonary embolism, compared with controls. The increased risk for deep vein thrombosis was seen mainly in the first 4 years after diagnosis of rheumatoid arthritis, which relied on American College of Rheumatology 1987 criteria that may have identified the disease at a later stage, the investigators suggested. The ACR and the European League Against Rheumatism (EULAR) revised their classification criteria in 2010 to focus on features at earlier stages of the disease.

Patients with rheumatoid arthritis were significantly more likely than controls to have comorbidities, including hypertension, diabetes, hyperlipidemia, heart failure, or lower leg fracture or surgery. The presence of both rheumatoid arthritis and a comorbidity multiplied the risk for thromboembolism, with a six-fold increased risk for deep vein thrombosis and a four-fold increased risk for pulmonary embolism, compared with patients with neither rheumatoid arthritis nor a comorbidity.

"Providing adequate care for patients with rheumatoid arthritis with comorbidities is an important step in preventing further development of deep vein thrombosis and pulmonary embolism. Thus, a multidisciplinary team should guide the assessment, treatment and holistic care of patients with rheumatoid arthritis," Dr. Chung and his associates concluded.

In Taiwan, an estimated 0.1% of the population has rheumatoid arthritis, which is lower than rates of 0.5%-1% in Western countries, they noted. In general, venous thromboembolism leads to death within 30 days in 11%-30% of patients, previous data show.

Two recent population-based cohort studies of patients in Sweden (JAMA 2012;308:1350-6) and in the United Kingdom (Ann. Rheum. Dis. 2013;72:1182-7) reported a doubling in risk for venous thromboembolism in people with rheumatoid arthritis. The differences in increased risk seen in the Taiwan and Western studies may be associated with racial differences, the Taiwanese investigators suggested.

The study cohort was 77% female and had a mean age of 52 years.

The findings are limited by the fact that the Taiwanese database did not include information on smoking, body mass index, physical activity, severity of rheumatoid arthritis, and use of drugs that could affect risk, including hormone replacement therapy, anticonceptive drugs, or glucocorticoids.

Chronic inflammation in patients with rheumatoid arthritis has been associated with prothrombotic factors and endothelial dysfunction in the development of atherothrombosis in prior studies.

Dr. Chung reported having no financial disclosures. The Taiwan government and Taichung Hospital funded the study.

[email protected]

On Twitter @sherryboschert

Having rheumatoid arthritis tripled the risk for developing deep vein thrombosis and doubled the risk for pulmonary embolism in an analysis of data on 146,190 Taiwan residents.

Investigators identified 29,238 people with new diagnoses of rheumatoid arthritis in 1998-2008 in a national database with health records on Taiwan’s entire population of 23.7 million people. They extended the monitoring period for the study to the end of 2010 and compared the rheumatoid arthritis cohort with 116,952 control patients matched by sex and age in the year of diagnosis.

Expressed in person-years of follow-up, the incidence density of deep vein thrombosis was significantly higher in patients with rheumatoid arthritis (11 per 1,000 person-years), compared with the control group patients (3 per 1,000 person-years). The incidence density of pulmonary thromboembolism also was significantly higher in patients with rheumatoid arthritis compared with controls (4 vs. 2 per 1,000 person-years), Dr. Wei-Sheng Chung and his associates reported Aug. 7 in the Annals of the Rheumatic Diseases.

Courtesy Dr. Chia-Hung Kao

In all, the data included 193,753 person-years of follow-up in the rheumatoid arthritis group and 792,941 person-years of follow-up in the control group.

After adjusting for age, sex, and comorbidities, the rheumatoid arthritis group had a 3.36-fold higher chance of developing deep vein thrombosis and a 2.07-fold higher risk for developing pulmonary embolism, compared with controls, reported Dr. Chung of Taichung (Taiwan) Hospital and his colleagues (Ann. Rheum. Dis. 2013 Aug. 7 [doi:10.1136/annrheumdis-2013-203380]).

The greatest rise in risk was seen in young adults (50 years or younger) with rheumatoid arthritis, who had a nearly six-fold increased risk for deep vein thrombosis and a tripled risk for pulmonary embolism, compared with controls. The increased risk for deep vein thrombosis was seen mainly in the first 4 years after diagnosis of rheumatoid arthritis, which relied on American College of Rheumatology 1987 criteria that may have identified the disease at a later stage, the investigators suggested. The ACR and the European League Against Rheumatism (EULAR) revised their classification criteria in 2010 to focus on features at earlier stages of the disease.

Patients with rheumatoid arthritis were significantly more likely than controls to have comorbidities, including hypertension, diabetes, hyperlipidemia, heart failure, or lower leg fracture or surgery. The presence of both rheumatoid arthritis and a comorbidity multiplied the risk for thromboembolism, with a six-fold increased risk for deep vein thrombosis and a four-fold increased risk for pulmonary embolism, compared with patients with neither rheumatoid arthritis nor a comorbidity.

"Providing adequate care for patients with rheumatoid arthritis with comorbidities is an important step in preventing further development of deep vein thrombosis and pulmonary embolism. Thus, a multidisciplinary team should guide the assessment, treatment and holistic care of patients with rheumatoid arthritis," Dr. Chung and his associates concluded.

In Taiwan, an estimated 0.1% of the population has rheumatoid arthritis, which is lower than rates of 0.5%-1% in Western countries, they noted. In general, venous thromboembolism leads to death within 30 days in 11%-30% of patients, previous data show.

Two recent population-based cohort studies of patients in Sweden (JAMA 2012;308:1350-6) and in the United Kingdom (Ann. Rheum. Dis. 2013;72:1182-7) reported a doubling in risk for venous thromboembolism in people with rheumatoid arthritis. The differences in increased risk seen in the Taiwan and Western studies may be associated with racial differences, the Taiwanese investigators suggested.

The study cohort was 77% female and had a mean age of 52 years.

The findings are limited by the fact that the Taiwanese database did not include information on smoking, body mass index, physical activity, severity of rheumatoid arthritis, and use of drugs that could affect risk, including hormone replacement therapy, anticonceptive drugs, or glucocorticoids.

Chronic inflammation in patients with rheumatoid arthritis has been associated with prothrombotic factors and endothelial dysfunction in the development of atherothrombosis in prior studies.

Dr. Chung reported having no financial disclosures. The Taiwan government and Taichung Hospital funded the study.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – Long-term mifepristone therapy for Cushing’s syndrome was associated with endometrial thickening, with some women showing histologic changes consistent with progesterone receptor modulator–associated endometrial changes, in two studies of a total of 35 patients.

The women received 300-1,200 mg/day of mifepristone in the 24-week open-label Study of the Efficacy and Safety of Mifepristone in the Treatment of Endogenous Cushing’s Syndrome (SEISMIC) and in an extension of the study in 18 patients who continued for a median of 27 months (range, 14-43 months).

The women received 300-1,200
mg/day of mifepristone (Korlym) in the 24-
week open-label Study of the Effica­
cy and Safety of Mifepristone in the
Treatment of Endogenous Cushing’s
Syndrome ( SEISMIC) and in an ex­
tension of the study in 18 patients
who continued for a median of 27
months (range, 14-43 months). Korlym is indicated to control hyperglycemia secondary to hypercortisolism in adults with endogenous Cushing's syndrome who have type 2 diabetes mellitus or glucose intolerance and have failed surgery or are not candidates for surgery, according to the product's labeling information.*

Transvaginal ultrasounds in 26 women at baseline and 27 women after the start of the study showed that mifepristone use was associated with endometrial thickening, especially in premenopausal women. The endometrium thickened by more than 5 mm in 8 of 26 premenopausal women (31%) and in two of nine postmenopausal women (22%), with thickening of more than 10 mm in 4 premenopausal women (15%) and one postmenopausal woman (11%), Dr. Ty Carroll reported.

Four (22%) of the 18 women in the extension study who’d been on mifepristone for 14 or more weeks and who had endometrial thickening greater than 20 mm developed clinically relevant endometrial bleeding and underwent hysterectomy (three patients) or dilation and curettage. The endometrial thickening ranged from 25 to 55 mm in these women, who remained on mifepristone therapy throughout the studies, Dr. Carroll and his associates reported in a featured poster presentation at the annual meeting of the Endocrine Society.

"Gynecologic consultation may be required in patients with persistent endometrial bleeding," said Dr. Carroll of the Medical College of Wisconsin, Milwaukee.

Vaginal bleeding of any kind occurred in 10 premenopausal women (38.5%) and two postmenopausal patients (7%). Three premenopausal women reported minor bleeding upon starting mifepristone, and one premenopausal woman reported minor bleeding after stopping mifepristone. Two premenopausal and two postmenopausal women reported intermittent, self-limited spotting or bleeding during treatment.

Bleeding did not always occur following endometrial thickening. Three patients with endometrial thickening greater than 20 mm after 6 months reported no bleeding.

Mifepristone use was not associated with precancerous endometrial lesions. In 33 endometrial biopsies obtained from 15 patients (11 premenopausal and 4 postmenopausal women), 31 biopsies (94%) had benign histology with variable findings of inactive, atrophic, disordered, or mixed-pattern endometrium, and 18 biopsies (56%) showed findings of progesterone receptor modulator–associated endometrial changes. Simple hyperplasia in one patient could not be confirmed on a repeat biopsy, and complex atypical endometrial hyperplasia in a second patient was thought to have existed prior to the study, Dr. Carroll reported. No patients showed evidence of endometrial carcinoma.

Previous studies have reported progesterone receptor modulator–associated endometrial changes from the use of mifepristone, a competitive progesterone receptor antagonist, in doses of 5-200 mg/day that are not associated with glucocorticoid receptor antagonism.

In the current study, median endometrial thickness for the premenopausal women was 5 mm at baseline and 11 mm at 6 months, and for postmenopausal women, was 3 mm at baseline and 6.4 mm at 6 months. The gain was statistically significant for premenopausal but not postmenopausal women. Endometrial thickness continued to increase in the extension study.

The SEISMIC study included adult females with endogenous Cushing’s syndrome and type 2 diabetes or impaired glucose function and/or hypertension. It excluded premenopausal women with an endometrial thickness greater than 20 mm, postmenopausal women with an endometrial thickness greater than 5 mm, patients with ovarian cysts with diameters measuring greater than 5 cm (premenopausal) or 2 cm (postmenopausal), or women with free fluid pockets greater than 4 cm. Premenopausal participants had a mean age of 39 years, and postmenopausal participants had a mean age of 57 years.

Dr. Carroll has been a speaker and researcher for Corcept Therapeutics, which markets mifepristone. His coinvestigators were employees, contractors, or consultants for Corcept, which provided some funding for the study.

*Clarification, 8/22/2013: An earlier version of this story did not state that the brand of mifepristone used in this study was Korlym, which is indicated for treating Cushing's syndrome.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – Long-term mifepristone therapy for Cushing’s syndrome was associated with endometrial thickening, with some women showing histologic changes consistent with progesterone receptor modulator–associated endometrial changes, in two studies of a total of 35 patients.

The women received 300-1,200 mg/day of mifepristone in the 24-week open-label Study of the Efficacy and Safety of Mifepristone in the Treatment of Endogenous Cushing’s Syndrome (SEISMIC) and in an extension of the study in 18 patients who continued for a median of 27 months (range, 14-43 months).

The women received 300-1,200
mg/day of mifepristone (Korlym) in the 24-
week open-label Study of the Effica­
cy and Safety of Mifepristone in the
Treatment of Endogenous Cushing’s
Syndrome ( SEISMIC) and in an ex­
tension of the study in 18 patients
who continued for a median of 27
months (range, 14-43 months). Korlym is indicated to control hyperglycemia secondary to hypercortisolism in adults with endogenous Cushing's syndrome who have type 2 diabetes mellitus or glucose intolerance and have failed surgery or are not candidates for surgery, according to the product's labeling information.*

Transvaginal ultrasounds in 26 women at baseline and 27 women after the start of the study showed that mifepristone use was associated with endometrial thickening, especially in premenopausal women. The endometrium thickened by more than 5 mm in 8 of 26 premenopausal women (31%) and in two of nine postmenopausal women (22%), with thickening of more than 10 mm in 4 premenopausal women (15%) and one postmenopausal woman (11%), Dr. Ty Carroll reported.

Four (22%) of the 18 women in the extension study who’d been on mifepristone for 14 or more weeks and who had endometrial thickening greater than 20 mm developed clinically relevant endometrial bleeding and underwent hysterectomy (three patients) or dilation and curettage. The endometrial thickening ranged from 25 to 55 mm in these women, who remained on mifepristone therapy throughout the studies, Dr. Carroll and his associates reported in a featured poster presentation at the annual meeting of the Endocrine Society.

"Gynecologic consultation may be required in patients with persistent endometrial bleeding," said Dr. Carroll of the Medical College of Wisconsin, Milwaukee.

Vaginal bleeding of any kind occurred in 10 premenopausal women (38.5%) and two postmenopausal patients (7%). Three premenopausal women reported minor bleeding upon starting mifepristone, and one premenopausal woman reported minor bleeding after stopping mifepristone. Two premenopausal and two postmenopausal women reported intermittent, self-limited spotting or bleeding during treatment.

Bleeding did not always occur following endometrial thickening. Three patients with endometrial thickening greater than 20 mm after 6 months reported no bleeding.

Mifepristone use was not associated with precancerous endometrial lesions. In 33 endometrial biopsies obtained from 15 patients (11 premenopausal and 4 postmenopausal women), 31 biopsies (94%) had benign histology with variable findings of inactive, atrophic, disordered, or mixed-pattern endometrium, and 18 biopsies (56%) showed findings of progesterone receptor modulator–associated endometrial changes. Simple hyperplasia in one patient could not be confirmed on a repeat biopsy, and complex atypical endometrial hyperplasia in a second patient was thought to have existed prior to the study, Dr. Carroll reported. No patients showed evidence of endometrial carcinoma.

Previous studies have reported progesterone receptor modulator–associated endometrial changes from the use of mifepristone, a competitive progesterone receptor antagonist, in doses of 5-200 mg/day that are not associated with glucocorticoid receptor antagonism.

In the current study, median endometrial thickness for the premenopausal women was 5 mm at baseline and 11 mm at 6 months, and for postmenopausal women, was 3 mm at baseline and 6.4 mm at 6 months. The gain was statistically significant for premenopausal but not postmenopausal women. Endometrial thickness continued to increase in the extension study.

The SEISMIC study included adult females with endogenous Cushing’s syndrome and type 2 diabetes or impaired glucose function and/or hypertension. It excluded premenopausal women with an endometrial thickness greater than 20 mm, postmenopausal women with an endometrial thickness greater than 5 mm, patients with ovarian cysts with diameters measuring greater than 5 cm (premenopausal) or 2 cm (postmenopausal), or women with free fluid pockets greater than 4 cm. Premenopausal participants had a mean age of 39 years, and postmenopausal participants had a mean age of 57 years.

Dr. Carroll has been a speaker and researcher for Corcept Therapeutics, which markets mifepristone. His coinvestigators were employees, contractors, or consultants for Corcept, which provided some funding for the study.

*Clarification, 8/22/2013: An earlier version of this story did not state that the brand of mifepristone used in this study was Korlym, which is indicated for treating Cushing's syndrome.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – Long-term mifepristone therapy for Cushing’s syndrome was associated with endometrial thickening, with some women showing histologic changes consistent with progesterone receptor modulator–associated endometrial changes, in two studies of a total of 35 patients.

The women received 300-1,200 mg/day of mifepristone in the 24-week open-label Study of the Efficacy and Safety of Mifepristone in the Treatment of Endogenous Cushing’s Syndrome (SEISMIC) and in an extension of the study in 18 patients who continued for a median of 27 months (range, 14-43 months).

The women received 300-1,200
mg/day of mifepristone (Korlym) in the 24-
week open-label Study of the Effica­
cy and Safety of Mifepristone in the
Treatment of Endogenous Cushing’s
Syndrome ( SEISMIC) and in an ex­
tension of the study in 18 patients
who continued for a median of 27
months (range, 14-43 months). Korlym is indicated to control hyperglycemia secondary to hypercortisolism in adults with endogenous Cushing's syndrome who have type 2 diabetes mellitus or glucose intolerance and have failed surgery or are not candidates for surgery, according to the product's labeling information.*

Transvaginal ultrasounds in 26 women at baseline and 27 women after the start of the study showed that mifepristone use was associated with endometrial thickening, especially in premenopausal women. The endometrium thickened by more than 5 mm in 8 of 26 premenopausal women (31%) and in two of nine postmenopausal women (22%), with thickening of more than 10 mm in 4 premenopausal women (15%) and one postmenopausal woman (11%), Dr. Ty Carroll reported.

Four (22%) of the 18 women in the extension study who’d been on mifepristone for 14 or more weeks and who had endometrial thickening greater than 20 mm developed clinically relevant endometrial bleeding and underwent hysterectomy (three patients) or dilation and curettage. The endometrial thickening ranged from 25 to 55 mm in these women, who remained on mifepristone therapy throughout the studies, Dr. Carroll and his associates reported in a featured poster presentation at the annual meeting of the Endocrine Society.

"Gynecologic consultation may be required in patients with persistent endometrial bleeding," said Dr. Carroll of the Medical College of Wisconsin, Milwaukee.

Vaginal bleeding of any kind occurred in 10 premenopausal women (38.5%) and two postmenopausal patients (7%). Three premenopausal women reported minor bleeding upon starting mifepristone, and one premenopausal woman reported minor bleeding after stopping mifepristone. Two premenopausal and two postmenopausal women reported intermittent, self-limited spotting or bleeding during treatment.

Bleeding did not always occur following endometrial thickening. Three patients with endometrial thickening greater than 20 mm after 6 months reported no bleeding.

Mifepristone use was not associated with precancerous endometrial lesions. In 33 endometrial biopsies obtained from 15 patients (11 premenopausal and 4 postmenopausal women), 31 biopsies (94%) had benign histology with variable findings of inactive, atrophic, disordered, or mixed-pattern endometrium, and 18 biopsies (56%) showed findings of progesterone receptor modulator–associated endometrial changes. Simple hyperplasia in one patient could not be confirmed on a repeat biopsy, and complex atypical endometrial hyperplasia in a second patient was thought to have existed prior to the study, Dr. Carroll reported. No patients showed evidence of endometrial carcinoma.

Previous studies have reported progesterone receptor modulator–associated endometrial changes from the use of mifepristone, a competitive progesterone receptor antagonist, in doses of 5-200 mg/day that are not associated with glucocorticoid receptor antagonism.

In the current study, median endometrial thickness for the premenopausal women was 5 mm at baseline and 11 mm at 6 months, and for postmenopausal women, was 3 mm at baseline and 6.4 mm at 6 months. The gain was statistically significant for premenopausal but not postmenopausal women. Endometrial thickness continued to increase in the extension study.

The SEISMIC study included adult females with endogenous Cushing’s syndrome and type 2 diabetes or impaired glucose function and/or hypertension. It excluded premenopausal women with an endometrial thickness greater than 20 mm, postmenopausal women with an endometrial thickness greater than 5 mm, patients with ovarian cysts with diameters measuring greater than 5 cm (premenopausal) or 2 cm (postmenopausal), or women with free fluid pockets greater than 4 cm. Premenopausal participants had a mean age of 39 years, and postmenopausal participants had a mean age of 57 years.

Dr. Carroll has been a speaker and researcher for Corcept Therapeutics, which markets mifepristone. His coinvestigators were employees, contractors, or consultants for Corcept, which provided some funding for the study.

*Clarification, 8/22/2013: An earlier version of this story did not state that the brand of mifepristone used in this study was Korlym, which is indicated for treating Cushing's syndrome.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – One California community-based hospital got a head start on tracking core measures of quality in perinatal care that all U.S. hospitals will have to report to The Joint Commission beginning January 2014.

Over the past 2 years, the ob.gyns. found it wasn’t easy, but that tracking core measures of quality significantly improved perinatal care.

Sutter Medical Center in Sacramento, Calif., formed a perinatal data committee in 2010 to identify barriers and develop processes for tracking six quality measures, including the five for The Joint Commission. They worked to overcome doubters on their staff, internally published individual doctors’ rates of cesarean section deliveries and episiotomies, and shared the results for each prenatal obstetrics group.

John Milne/IMNG Medical Media

Their overall rate of elective deliveries at less than 39 weeks’ gestation decreased from 25% of the 4,958 deliveries in October 2010 to 2% of the 5,577 deliveries in December 2012. The cesarean section rate for nulliparous women with a term, singleton fetus in a vertex position dropped from 31% in 2010 to 25% in 2012, Dr. William M. Gilbert reported at a meeting on antepartum and intrapartum management sponsored by the University of California, San Francisco.

They also improved significantly in two other core measures of quality mandated by The Joint Commission: The proportion of preterm infants who received antenatal steroids before delivery jumped from 80% to 100%, and the proportion of newborns who were fed exclusively breast milk during their entire hospitalization improved from 58% to 70%. The hospital has begun collecting data on a fifth core measure for The Joint Commission: the rate of health care-associated bloodstream infections in newborns.

Dr. Gilbert and his group also tracked two measures that are endorsed by the National Quality Forum but are not yet required by The Joint Commission. Their episiotomy rate decreased significantly from 5% to 2%, and the proportion of women undergoing cesarean section who received appropriate prophylaxis against deep vein thrombosis increased from 95% to 98% (Jt. Comm. J. Qual. Patient Saf. 2013;39:258-66).

"It took us 1-2 years to get the bugs worked out" in tracking core quality measures, said Dr. Gilbert, regional medical director of women’s services for Sutter Health’s Sacramento-Sierra Region, Sacramento, Calif. The effort required leadership from doctors and nurses, administrative and medical records support, and education for coders.

"If your hospital has done nothing to look at what you’re going to be submitting" to The Joint Commission, he added, "I can guarantee you that even if you think you’re doing great, the data are going to be awful, and you’re going to be scrambling to fix a problem that has occurred."

This kind of attention to quality measures in perinatal care is long overdue, he said. Despite the fact that the 4.2 million normal vaginal deliveries per year represent the No. 1 hospital discharge diagnosis in the United States, and studies show immense variation in perinatal practices between hospitals and geographical regions, efforts to measure the quality of hospital care largely have ignored obstetrics because those efforts have focused on Medicare, and few obstetrical patients are covered by Medicare.

Previous studies show a 10-fold variation in cesarean section rates around the country, and cesarean section rates in low-risk patients vary from 2% to 36%. "I would put to you, if you were making widgets or tanks, and you had such variation in the quality of your tanks that the government was paying for, you’d be out of work and probably in jail, but that’s what we tolerate" in health care, he said. Huge variations also have been reported in rates of induction, episiotomy, breastfeeding, and use of antenatal steroids.

The 40 ob.gyns. affiliated with Dr. Gilbert’s hospital had cesarean rates for nulliparous, term, singleton, vertex pregnancies ranging from approximately 8% to 60% when the tracking efforts began, he said. The committee assigned two-digit alphanumeric codes for each provider and posted individual rates of cesarean sections and episiotomies by provider code for 6 months, to start. It took a year of convincing before getting agreement, but then individual rates were posted in the doctors’ and labor and delivery lounges and were e-mailed to all medical staff.

"It’s amazing – amazing what that did," he said. Doctors with the highest cesarean section rates reduced their use of cesarean sections.

The category of elective deliveries at less than 39 weeks’ gestation excluded cases with medical indications for early delivery, but tracking ran into problems initially because ICD-9 codes did not exist for some exemptions, including prior classical cesarean section or prior myomectomy. "You got dinged for that" in the tracking despite the medical indication, he said. So the committee created tracking categories of "avoidable" and "unavoidable" early deliveries, and doctors didn’t get dinged for unavoidable cases.

Some doctors wrote the reason for early delivery as "intrahepatic cholestasis of pregnancy," which is an appropriate indication, but the medical coders told Dr. Gilbert that having the word "intrahepatic" flagged it as gall bladder disease, which is no reason to deliver early. "We had to work with our coders to help us understand," he said.

Every patient at risk of preterm delivery received antenatal steroids at his hospital, Dr. Gilbert said, "but we weren’t documenting it properly." There had been no uniform spot in the medical record to document administration of antenatal steroids, or to show that they had been given before the current hospitalization. Dr. Gilbert’s team worked with the medical records department to change the electronic health records. Nurses now check off if the patient received a full course of antenatal steroids. If this is missing, the doctor gets a pop-up window where a reason must be given.

"That really was effective," he said.

Tracking of episiotomy excluded cases of shoulder dystocia, but not episiotomy for fetal distress. Despite individual rates being internally publicized, the episiotomy rate seems to be stuck at around 2% because "I do have a couple of old-timers," he said. "Even public embarrassment will not get them to change."

"As an individual and as a hospital, we need to make sure we’re doing the best we can."

Capturing data on whether or not newborns are fed exclusively with breast milk can be difficult, in part because it’s often not clear whether the ob.gyn., the nursing staff, or the pediatrician is responsible for this. Dr. Gilbert’s team analyzed 18 cases at his hospital in which women came in saying they wanted to breastfeed the newborn exclusively, but that didn’t happen. In most cases, the babies received formula after a night nurse moved the baby to the nursery so the mother could sleep, a problem that was addressed. Publicizing exclusive breastfeeding rates for 20 different perinatal obstetrics groups – which ranged from 33% to 93% also helped improve breastfeeding rates.

The perinatal data committee also posted a color-coded "dashboard" showing trends in the hospital’s rates for all these measures over time.

Starting in 2014, The Joint Commission will publish hospital rates for cesarean sections and episiotomies, but not rates for individual doctors. Patient access to individual doctors’ rates of cesarean section, early elective delivery, and episiotomy is likely to come in the future, Dr. Gilbert said, and insurers eventually may select physicians and reimbursement rates based on these outcomes.

"As an individual and as a hospital, we need to make sure we’re doing the best we can," he said.

Dr. Gilbert reported having no financial disclosures.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – One California community-based hospital got a head start on tracking core measures of quality in perinatal care that all U.S. hospitals will have to report to The Joint Commission beginning January 2014.

Over the past 2 years, the ob.gyns. found it wasn’t easy, but that tracking core measures of quality significantly improved perinatal care.

Sutter Medical Center in Sacramento, Calif., formed a perinatal data committee in 2010 to identify barriers and develop processes for tracking six quality measures, including the five for The Joint Commission. They worked to overcome doubters on their staff, internally published individual doctors’ rates of cesarean section deliveries and episiotomies, and shared the results for each prenatal obstetrics group.

John Milne/IMNG Medical Media

Their overall rate of elective deliveries at less than 39 weeks’ gestation decreased from 25% of the 4,958 deliveries in October 2010 to 2% of the 5,577 deliveries in December 2012. The cesarean section rate for nulliparous women with a term, singleton fetus in a vertex position dropped from 31% in 2010 to 25% in 2012, Dr. William M. Gilbert reported at a meeting on antepartum and intrapartum management sponsored by the University of California, San Francisco.

They also improved significantly in two other core measures of quality mandated by The Joint Commission: The proportion of preterm infants who received antenatal steroids before delivery jumped from 80% to 100%, and the proportion of newborns who were fed exclusively breast milk during their entire hospitalization improved from 58% to 70%. The hospital has begun collecting data on a fifth core measure for The Joint Commission: the rate of health care-associated bloodstream infections in newborns.

Dr. Gilbert and his group also tracked two measures that are endorsed by the National Quality Forum but are not yet required by The Joint Commission. Their episiotomy rate decreased significantly from 5% to 2%, and the proportion of women undergoing cesarean section who received appropriate prophylaxis against deep vein thrombosis increased from 95% to 98% (Jt. Comm. J. Qual. Patient Saf. 2013;39:258-66).

"It took us 1-2 years to get the bugs worked out" in tracking core quality measures, said Dr. Gilbert, regional medical director of women’s services for Sutter Health’s Sacramento-Sierra Region, Sacramento, Calif. The effort required leadership from doctors and nurses, administrative and medical records support, and education for coders.

"If your hospital has done nothing to look at what you’re going to be submitting" to The Joint Commission, he added, "I can guarantee you that even if you think you’re doing great, the data are going to be awful, and you’re going to be scrambling to fix a problem that has occurred."

This kind of attention to quality measures in perinatal care is long overdue, he said. Despite the fact that the 4.2 million normal vaginal deliveries per year represent the No. 1 hospital discharge diagnosis in the United States, and studies show immense variation in perinatal practices between hospitals and geographical regions, efforts to measure the quality of hospital care largely have ignored obstetrics because those efforts have focused on Medicare, and few obstetrical patients are covered by Medicare.

Previous studies show a 10-fold variation in cesarean section rates around the country, and cesarean section rates in low-risk patients vary from 2% to 36%. "I would put to you, if you were making widgets or tanks, and you had such variation in the quality of your tanks that the government was paying for, you’d be out of work and probably in jail, but that’s what we tolerate" in health care, he said. Huge variations also have been reported in rates of induction, episiotomy, breastfeeding, and use of antenatal steroids.

The 40 ob.gyns. affiliated with Dr. Gilbert’s hospital had cesarean rates for nulliparous, term, singleton, vertex pregnancies ranging from approximately 8% to 60% when the tracking efforts began, he said. The committee assigned two-digit alphanumeric codes for each provider and posted individual rates of cesarean sections and episiotomies by provider code for 6 months, to start. It took a year of convincing before getting agreement, but then individual rates were posted in the doctors’ and labor and delivery lounges and were e-mailed to all medical staff.

"It’s amazing – amazing what that did," he said. Doctors with the highest cesarean section rates reduced their use of cesarean sections.

The category of elective deliveries at less than 39 weeks’ gestation excluded cases with medical indications for early delivery, but tracking ran into problems initially because ICD-9 codes did not exist for some exemptions, including prior classical cesarean section or prior myomectomy. "You got dinged for that" in the tracking despite the medical indication, he said. So the committee created tracking categories of "avoidable" and "unavoidable" early deliveries, and doctors didn’t get dinged for unavoidable cases.

Some doctors wrote the reason for early delivery as "intrahepatic cholestasis of pregnancy," which is an appropriate indication, but the medical coders told Dr. Gilbert that having the word "intrahepatic" flagged it as gall bladder disease, which is no reason to deliver early. "We had to work with our coders to help us understand," he said.

Every patient at risk of preterm delivery received antenatal steroids at his hospital, Dr. Gilbert said, "but we weren’t documenting it properly." There had been no uniform spot in the medical record to document administration of antenatal steroids, or to show that they had been given before the current hospitalization. Dr. Gilbert’s team worked with the medical records department to change the electronic health records. Nurses now check off if the patient received a full course of antenatal steroids. If this is missing, the doctor gets a pop-up window where a reason must be given.

"That really was effective," he said.

Tracking of episiotomy excluded cases of shoulder dystocia, but not episiotomy for fetal distress. Despite individual rates being internally publicized, the episiotomy rate seems to be stuck at around 2% because "I do have a couple of old-timers," he said. "Even public embarrassment will not get them to change."

"As an individual and as a hospital, we need to make sure we’re doing the best we can."

Capturing data on whether or not newborns are fed exclusively with breast milk can be difficult, in part because it’s often not clear whether the ob.gyn., the nursing staff, or the pediatrician is responsible for this. Dr. Gilbert’s team analyzed 18 cases at his hospital in which women came in saying they wanted to breastfeed the newborn exclusively, but that didn’t happen. In most cases, the babies received formula after a night nurse moved the baby to the nursery so the mother could sleep, a problem that was addressed. Publicizing exclusive breastfeeding rates for 20 different perinatal obstetrics groups – which ranged from 33% to 93% also helped improve breastfeeding rates.

The perinatal data committee also posted a color-coded "dashboard" showing trends in the hospital’s rates for all these measures over time.

Starting in 2014, The Joint Commission will publish hospital rates for cesarean sections and episiotomies, but not rates for individual doctors. Patient access to individual doctors’ rates of cesarean section, early elective delivery, and episiotomy is likely to come in the future, Dr. Gilbert said, and insurers eventually may select physicians and reimbursement rates based on these outcomes.

"As an individual and as a hospital, we need to make sure we’re doing the best we can," he said.

Dr. Gilbert reported having no financial disclosures.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – One California community-based hospital got a head start on tracking core measures of quality in perinatal care that all U.S. hospitals will have to report to The Joint Commission beginning January 2014.

Over the past 2 years, the ob.gyns. found it wasn’t easy, but that tracking core measures of quality significantly improved perinatal care.

Sutter Medical Center in Sacramento, Calif., formed a perinatal data committee in 2010 to identify barriers and develop processes for tracking six quality measures, including the five for The Joint Commission. They worked to overcome doubters on their staff, internally published individual doctors’ rates of cesarean section deliveries and episiotomies, and shared the results for each prenatal obstetrics group.

John Milne/IMNG Medical Media

Their overall rate of elective deliveries at less than 39 weeks’ gestation decreased from 25% of the 4,958 deliveries in October 2010 to 2% of the 5,577 deliveries in December 2012. The cesarean section rate for nulliparous women with a term, singleton fetus in a vertex position dropped from 31% in 2010 to 25% in 2012, Dr. William M. Gilbert reported at a meeting on antepartum and intrapartum management sponsored by the University of California, San Francisco.

They also improved significantly in two other core measures of quality mandated by The Joint Commission: The proportion of preterm infants who received antenatal steroids before delivery jumped from 80% to 100%, and the proportion of newborns who were fed exclusively breast milk during their entire hospitalization improved from 58% to 70%. The hospital has begun collecting data on a fifth core measure for The Joint Commission: the rate of health care-associated bloodstream infections in newborns.

Dr. Gilbert and his group also tracked two measures that are endorsed by the National Quality Forum but are not yet required by The Joint Commission. Their episiotomy rate decreased significantly from 5% to 2%, and the proportion of women undergoing cesarean section who received appropriate prophylaxis against deep vein thrombosis increased from 95% to 98% (Jt. Comm. J. Qual. Patient Saf. 2013;39:258-66).

"It took us 1-2 years to get the bugs worked out" in tracking core quality measures, said Dr. Gilbert, regional medical director of women’s services for Sutter Health’s Sacramento-Sierra Region, Sacramento, Calif. The effort required leadership from doctors and nurses, administrative and medical records support, and education for coders.

"If your hospital has done nothing to look at what you’re going to be submitting" to The Joint Commission, he added, "I can guarantee you that even if you think you’re doing great, the data are going to be awful, and you’re going to be scrambling to fix a problem that has occurred."

This kind of attention to quality measures in perinatal care is long overdue, he said. Despite the fact that the 4.2 million normal vaginal deliveries per year represent the No. 1 hospital discharge diagnosis in the United States, and studies show immense variation in perinatal practices between hospitals and geographical regions, efforts to measure the quality of hospital care largely have ignored obstetrics because those efforts have focused on Medicare, and few obstetrical patients are covered by Medicare.

Previous studies show a 10-fold variation in cesarean section rates around the country, and cesarean section rates in low-risk patients vary from 2% to 36%. "I would put to you, if you were making widgets or tanks, and you had such variation in the quality of your tanks that the government was paying for, you’d be out of work and probably in jail, but that’s what we tolerate" in health care, he said. Huge variations also have been reported in rates of induction, episiotomy, breastfeeding, and use of antenatal steroids.

The 40 ob.gyns. affiliated with Dr. Gilbert’s hospital had cesarean rates for nulliparous, term, singleton, vertex pregnancies ranging from approximately 8% to 60% when the tracking efforts began, he said. The committee assigned two-digit alphanumeric codes for each provider and posted individual rates of cesarean sections and episiotomies by provider code for 6 months, to start. It took a year of convincing before getting agreement, but then individual rates were posted in the doctors’ and labor and delivery lounges and were e-mailed to all medical staff.

"It’s amazing – amazing what that did," he said. Doctors with the highest cesarean section rates reduced their use of cesarean sections.

The category of elective deliveries at less than 39 weeks’ gestation excluded cases with medical indications for early delivery, but tracking ran into problems initially because ICD-9 codes did not exist for some exemptions, including prior classical cesarean section or prior myomectomy. "You got dinged for that" in the tracking despite the medical indication, he said. So the committee created tracking categories of "avoidable" and "unavoidable" early deliveries, and doctors didn’t get dinged for unavoidable cases.

Some doctors wrote the reason for early delivery as "intrahepatic cholestasis of pregnancy," which is an appropriate indication, but the medical coders told Dr. Gilbert that having the word "intrahepatic" flagged it as gall bladder disease, which is no reason to deliver early. "We had to work with our coders to help us understand," he said.

Every patient at risk of preterm delivery received antenatal steroids at his hospital, Dr. Gilbert said, "but we weren’t documenting it properly." There had been no uniform spot in the medical record to document administration of antenatal steroids, or to show that they had been given before the current hospitalization. Dr. Gilbert’s team worked with the medical records department to change the electronic health records. Nurses now check off if the patient received a full course of antenatal steroids. If this is missing, the doctor gets a pop-up window where a reason must be given.

"That really was effective," he said.

Tracking of episiotomy excluded cases of shoulder dystocia, but not episiotomy for fetal distress. Despite individual rates being internally publicized, the episiotomy rate seems to be stuck at around 2% because "I do have a couple of old-timers," he said. "Even public embarrassment will not get them to change."

"As an individual and as a hospital, we need to make sure we’re doing the best we can."

Capturing data on whether or not newborns are fed exclusively with breast milk can be difficult, in part because it’s often not clear whether the ob.gyn., the nursing staff, or the pediatrician is responsible for this. Dr. Gilbert’s team analyzed 18 cases at his hospital in which women came in saying they wanted to breastfeed the newborn exclusively, but that didn’t happen. In most cases, the babies received formula after a night nurse moved the baby to the nursery so the mother could sleep, a problem that was addressed. Publicizing exclusive breastfeeding rates for 20 different perinatal obstetrics groups – which ranged from 33% to 93% also helped improve breastfeeding rates.

The perinatal data committee also posted a color-coded "dashboard" showing trends in the hospital’s rates for all these measures over time.

Starting in 2014, The Joint Commission will publish hospital rates for cesarean sections and episiotomies, but not rates for individual doctors. Patient access to individual doctors’ rates of cesarean section, early elective delivery, and episiotomy is likely to come in the future, Dr. Gilbert said, and insurers eventually may select physicians and reimbursement rates based on these outcomes.

"As an individual and as a hospital, we need to make sure we’re doing the best we can," he said.

Dr. Gilbert reported having no financial disclosures.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – The cause of stillbirth can be identified in two-thirds of cases by checking the placental histology, conducting an autopsy, and karyotype testing.

That’s a "major, major take-home point" that’s "very different than what I was taught" in medical training, Dr. Yair J. Blumenfeld said at a meeting on antepartum and intrapartum management sponsored by the University of California, San Francisco.

That finding from an important 2011 study and other new data in the past 5 years suggests that perhaps clinicians should take a staggered approach when ordering tests to search for the etiology of a stillbirth. "Maybe I shouldn’t do a $2,000 workup for thrombophilia and anticardiolipin antibodies if the autopsy showed me that there’s an underlying structural abnormality, or if there’s an abnormal karyotype," he suggested.

In general, a growing proportion of stillbirths is being attributed to maternal, fetal, or placental causes, shrinking the proportion relegated to "idiopathic" or unexplained stillbirth. The idea that most stillbirths are idiopathic is "somewhat old thinking" at this point, said Dr. Blumenfeld of Stanford (Calif.) University.

The Eunice Kennedy Shriver National Institute of Child Health and Human Development created the Stillbirth Collaborative Research Network, which developed a new system of determining the causes of stillbirth and tested it in a multicenter, population-based case-control study in five U.S. states during 2006-2008. Potential etiologies for each stillbirth were graded as a possible or probable cause of death based on a complete evaluation including autopsy, placental pathology, medical records, maternal interview, karyotype, and other laboratory tests.

Investigators found a probable cause in 61% of the 512 stillbirths from 500 women and a possible or probable cause in 76%. More than one possible or probable cause was found in 31% of stillbirths, showing some overlap in the causes of stillbirth. The leading causes of antepartum stillbirths were obstetric complications in 29% and placental pathology in 23%, although some of the causes of stillbirth varied significantly by race (JAMA 2011;306:2459-68).

Obstetric complications were less likely to be the cause of stillbirths in white women (in 22%) or Hispanic women (25%), compared with black women (44%) or women of other races (41%). Infection as a cause of stillbirth also was less likely in whites (7%) or Hispanics (8%), compared with blacks (25%) or other races (22%). Hispanics and whites, however, had higher rates of umbilical cord complications as a cause of stillbirth (13% for each), compared with blacks (4%) or other races (5%).

Among the clinically indicated tests for stillbirths, the placental histology identified a cause of stillbirth 52% of the time. An autopsy found a cause in 31% of cases, and karyotype testing identified a cause 9% of the time. Eight other screening tests found a cause for stillbirth in 0.4%-4.8% of cases, depending on the test. These included screens for antibodies, toxicology, or blood glucose; tests for syphilis, parvovirus, lupus anticoagulant, or anticardiolipin antibody; or detection of fetal blood in fetal-maternal hemorrhage.

"I’m not saying we shouldn’t do these things, but I think in today’s health care climate, especially with health care economics, you should start to think about maybe a staggered approach" in order to control costs, Dr. Blumenfeld said.

Controversy surrounds several topics in the search for stillbirth etiologies: whether chromosomal microarrays are better than karyotype testing; whether or not to order screening for thrombophilias and antiphospholipid antibodies; and what to do if the parents reject an autopsy.

In a study of 532 stillbirths, chromosomal microarray testing yielded results more often than did karyotyping – in 87% of cases vs. 71% – and detected aneuploidy or copy number variants more often, in 8.8% of cases vs. 6.5% (New Engl. J. Med. 2012;367:2185-93). Whether that difference is worth a price tag of approximately $2,000 for microarray testing remains to be seen, but "we’re going to see a lot more studies" of stillbirths using this and other new technologies, Dr. Blumenfeld said.

Practice bulletins from the American College of Obstetricians and Gynecologists are "all over the map" when it comes to deciding whether or not to test for thrombophilias and antiphospholipid antibodies when there’s a stillbirth," he said. "It’s still very, very controversial." It’s probably wise to use the results of autopsy, karyotyping, and placental histology to help decide whether to pursue these other tests, and to talk with patients about their family history of thrombophilia, what the placenta looked like, and other factors that could guide decision-making, he added.

How health care providers counseled parents affected parents’ decision to accept or decline an autopsy of their stillborn infant in 22% of cases, according to one study of 460 parents, 354 obstetricians, 21 perinatal pathologists, and 2,256 midwives (BJOG 2012;119:987-97). Altogether, 62% of parents agreed to an autopsy.

Parents who decline an autopsy still are likely to consent to a "fetal virtuopsy" – a physical exam and MRI or CT imaging of the stillborn infant, a separate study of 96 mothers suggests. Although 62% consented to autopsy, 99% consented to a virtuopsy. In a few cases, the MRI detected abnormalities that were missed on autopsy (Ultrasound Obstet. Gynecol. 2012;39:659-65).

"Clearly, this is not standard, but I think we’re going to see a lot more studies taking this kind of approach to women who are not accepting of an autopsy," Dr. Blumenfeld said. "Go back to your home institutions, find your favorite pediatrician, geneticist, or dysmorphologist, and ask them, ‘Are you willing to come and look at this stillbirth once it is born, and try to get some information just by looking at the infant?’ I guarantee that you will be able to find somebody like that in your institution. It’s something that we do at Stanford."

National statistics from 2006 suggest that 6 of every 1,000 live births will be stillbirths, a rate similar to the prevalence of congenital heart disease, he said. In 2006, there were 25,972 fetal deaths after 20 weeks’ gestation in the United States (Natl. Vital Stat. Rep. 2012:60;1-23). Long-term trends show that the rate of stillbirths has declined after 28 weeks’ gestation but not between 20 and 27 weeks’ gestation.

Dr. Blumenfeld reported having no financial disclosures.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – The cause of stillbirth can be identified in two-thirds of cases by checking the placental histology, conducting an autopsy, and karyotype testing.

That’s a "major, major take-home point" that’s "very different than what I was taught" in medical training, Dr. Yair J. Blumenfeld said at a meeting on antepartum and intrapartum management sponsored by the University of California, San Francisco.

That finding from an important 2011 study and other new data in the past 5 years suggests that perhaps clinicians should take a staggered approach when ordering tests to search for the etiology of a stillbirth. "Maybe I shouldn’t do a $2,000 workup for thrombophilia and anticardiolipin antibodies if the autopsy showed me that there’s an underlying structural abnormality, or if there’s an abnormal karyotype," he suggested.

In general, a growing proportion of stillbirths is being attributed to maternal, fetal, or placental causes, shrinking the proportion relegated to "idiopathic" or unexplained stillbirth. The idea that most stillbirths are idiopathic is "somewhat old thinking" at this point, said Dr. Blumenfeld of Stanford (Calif.) University.

The Eunice Kennedy Shriver National Institute of Child Health and Human Development created the Stillbirth Collaborative Research Network, which developed a new system of determining the causes of stillbirth and tested it in a multicenter, population-based case-control study in five U.S. states during 2006-2008. Potential etiologies for each stillbirth were graded as a possible or probable cause of death based on a complete evaluation including autopsy, placental pathology, medical records, maternal interview, karyotype, and other laboratory tests.

Investigators found a probable cause in 61% of the 512 stillbirths from 500 women and a possible or probable cause in 76%. More than one possible or probable cause was found in 31% of stillbirths, showing some overlap in the causes of stillbirth. The leading causes of antepartum stillbirths were obstetric complications in 29% and placental pathology in 23%, although some of the causes of stillbirth varied significantly by race (JAMA 2011;306:2459-68).

Obstetric complications were less likely to be the cause of stillbirths in white women (in 22%) or Hispanic women (25%), compared with black women (44%) or women of other races (41%). Infection as a cause of stillbirth also was less likely in whites (7%) or Hispanics (8%), compared with blacks (25%) or other races (22%). Hispanics and whites, however, had higher rates of umbilical cord complications as a cause of stillbirth (13% for each), compared with blacks (4%) or other races (5%).

Among the clinically indicated tests for stillbirths, the placental histology identified a cause of stillbirth 52% of the time. An autopsy found a cause in 31% of cases, and karyotype testing identified a cause 9% of the time. Eight other screening tests found a cause for stillbirth in 0.4%-4.8% of cases, depending on the test. These included screens for antibodies, toxicology, or blood glucose; tests for syphilis, parvovirus, lupus anticoagulant, or anticardiolipin antibody; or detection of fetal blood in fetal-maternal hemorrhage.

"I’m not saying we shouldn’t do these things, but I think in today’s health care climate, especially with health care economics, you should start to think about maybe a staggered approach" in order to control costs, Dr. Blumenfeld said.

Controversy surrounds several topics in the search for stillbirth etiologies: whether chromosomal microarrays are better than karyotype testing; whether or not to order screening for thrombophilias and antiphospholipid antibodies; and what to do if the parents reject an autopsy.

In a study of 532 stillbirths, chromosomal microarray testing yielded results more often than did karyotyping – in 87% of cases vs. 71% – and detected aneuploidy or copy number variants more often, in 8.8% of cases vs. 6.5% (New Engl. J. Med. 2012;367:2185-93). Whether that difference is worth a price tag of approximately $2,000 for microarray testing remains to be seen, but "we’re going to see a lot more studies" of stillbirths using this and other new technologies, Dr. Blumenfeld said.

Practice bulletins from the American College of Obstetricians and Gynecologists are "all over the map" when it comes to deciding whether or not to test for thrombophilias and antiphospholipid antibodies when there’s a stillbirth," he said. "It’s still very, very controversial." It’s probably wise to use the results of autopsy, karyotyping, and placental histology to help decide whether to pursue these other tests, and to talk with patients about their family history of thrombophilia, what the placenta looked like, and other factors that could guide decision-making, he added.

How health care providers counseled parents affected parents’ decision to accept or decline an autopsy of their stillborn infant in 22% of cases, according to one study of 460 parents, 354 obstetricians, 21 perinatal pathologists, and 2,256 midwives (BJOG 2012;119:987-97). Altogether, 62% of parents agreed to an autopsy.

Parents who decline an autopsy still are likely to consent to a "fetal virtuopsy" – a physical exam and MRI or CT imaging of the stillborn infant, a separate study of 96 mothers suggests. Although 62% consented to autopsy, 99% consented to a virtuopsy. In a few cases, the MRI detected abnormalities that were missed on autopsy (Ultrasound Obstet. Gynecol. 2012;39:659-65).

"Clearly, this is not standard, but I think we’re going to see a lot more studies taking this kind of approach to women who are not accepting of an autopsy," Dr. Blumenfeld said. "Go back to your home institutions, find your favorite pediatrician, geneticist, or dysmorphologist, and ask them, ‘Are you willing to come and look at this stillbirth once it is born, and try to get some information just by looking at the infant?’ I guarantee that you will be able to find somebody like that in your institution. It’s something that we do at Stanford."

National statistics from 2006 suggest that 6 of every 1,000 live births will be stillbirths, a rate similar to the prevalence of congenital heart disease, he said. In 2006, there were 25,972 fetal deaths after 20 weeks’ gestation in the United States (Natl. Vital Stat. Rep. 2012:60;1-23). Long-term trends show that the rate of stillbirths has declined after 28 weeks’ gestation but not between 20 and 27 weeks’ gestation.

Dr. Blumenfeld reported having no financial disclosures.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – The cause of stillbirth can be identified in two-thirds of cases by checking the placental histology, conducting an autopsy, and karyotype testing.

That’s a "major, major take-home point" that’s "very different than what I was taught" in medical training, Dr. Yair J. Blumenfeld said at a meeting on antepartum and intrapartum management sponsored by the University of California, San Francisco.

That finding from an important 2011 study and other new data in the past 5 years suggests that perhaps clinicians should take a staggered approach when ordering tests to search for the etiology of a stillbirth. "Maybe I shouldn’t do a $2,000 workup for thrombophilia and anticardiolipin antibodies if the autopsy showed me that there’s an underlying structural abnormality, or if there’s an abnormal karyotype," he suggested.

In general, a growing proportion of stillbirths is being attributed to maternal, fetal, or placental causes, shrinking the proportion relegated to "idiopathic" or unexplained stillbirth. The idea that most stillbirths are idiopathic is "somewhat old thinking" at this point, said Dr. Blumenfeld of Stanford (Calif.) University.

The Eunice Kennedy Shriver National Institute of Child Health and Human Development created the Stillbirth Collaborative Research Network, which developed a new system of determining the causes of stillbirth and tested it in a multicenter, population-based case-control study in five U.S. states during 2006-2008. Potential etiologies for each stillbirth were graded as a possible or probable cause of death based on a complete evaluation including autopsy, placental pathology, medical records, maternal interview, karyotype, and other laboratory tests.

Investigators found a probable cause in 61% of the 512 stillbirths from 500 women and a possible or probable cause in 76%. More than one possible or probable cause was found in 31% of stillbirths, showing some overlap in the causes of stillbirth. The leading causes of antepartum stillbirths were obstetric complications in 29% and placental pathology in 23%, although some of the causes of stillbirth varied significantly by race (JAMA 2011;306:2459-68).

Obstetric complications were less likely to be the cause of stillbirths in white women (in 22%) or Hispanic women (25%), compared with black women (44%) or women of other races (41%). Infection as a cause of stillbirth also was less likely in whites (7%) or Hispanics (8%), compared with blacks (25%) or other races (22%). Hispanics and whites, however, had higher rates of umbilical cord complications as a cause of stillbirth (13% for each), compared with blacks (4%) or other races (5%).

Among the clinically indicated tests for stillbirths, the placental histology identified a cause of stillbirth 52% of the time. An autopsy found a cause in 31% of cases, and karyotype testing identified a cause 9% of the time. Eight other screening tests found a cause for stillbirth in 0.4%-4.8% of cases, depending on the test. These included screens for antibodies, toxicology, or blood glucose; tests for syphilis, parvovirus, lupus anticoagulant, or anticardiolipin antibody; or detection of fetal blood in fetal-maternal hemorrhage.

"I’m not saying we shouldn’t do these things, but I think in today’s health care climate, especially with health care economics, you should start to think about maybe a staggered approach" in order to control costs, Dr. Blumenfeld said.

Controversy surrounds several topics in the search for stillbirth etiologies: whether chromosomal microarrays are better than karyotype testing; whether or not to order screening for thrombophilias and antiphospholipid antibodies; and what to do if the parents reject an autopsy.

In a study of 532 stillbirths, chromosomal microarray testing yielded results more often than did karyotyping – in 87% of cases vs. 71% – and detected aneuploidy or copy number variants more often, in 8.8% of cases vs. 6.5% (New Engl. J. Med. 2012;367:2185-93). Whether that difference is worth a price tag of approximately $2,000 for microarray testing remains to be seen, but "we’re going to see a lot more studies" of stillbirths using this and other new technologies, Dr. Blumenfeld said.

Practice bulletins from the American College of Obstetricians and Gynecologists are "all over the map" when it comes to deciding whether or not to test for thrombophilias and antiphospholipid antibodies when there’s a stillbirth," he said. "It’s still very, very controversial." It’s probably wise to use the results of autopsy, karyotyping, and placental histology to help decide whether to pursue these other tests, and to talk with patients about their family history of thrombophilia, what the placenta looked like, and other factors that could guide decision-making, he added.

How health care providers counseled parents affected parents’ decision to accept or decline an autopsy of their stillborn infant in 22% of cases, according to one study of 460 parents, 354 obstetricians, 21 perinatal pathologists, and 2,256 midwives (BJOG 2012;119:987-97). Altogether, 62% of parents agreed to an autopsy.

Parents who decline an autopsy still are likely to consent to a "fetal virtuopsy" – a physical exam and MRI or CT imaging of the stillborn infant, a separate study of 96 mothers suggests. Although 62% consented to autopsy, 99% consented to a virtuopsy. In a few cases, the MRI detected abnormalities that were missed on autopsy (Ultrasound Obstet. Gynecol. 2012;39:659-65).

"Clearly, this is not standard, but I think we’re going to see a lot more studies taking this kind of approach to women who are not accepting of an autopsy," Dr. Blumenfeld said. "Go back to your home institutions, find your favorite pediatrician, geneticist, or dysmorphologist, and ask them, ‘Are you willing to come and look at this stillbirth once it is born, and try to get some information just by looking at the infant?’ I guarantee that you will be able to find somebody like that in your institution. It’s something that we do at Stanford."

National statistics from 2006 suggest that 6 of every 1,000 live births will be stillbirths, a rate similar to the prevalence of congenital heart disease, he said. In 2006, there were 25,972 fetal deaths after 20 weeks’ gestation in the United States (Natl. Vital Stat. Rep. 2012:60;1-23). Long-term trends show that the rate of stillbirths has declined after 28 weeks’ gestation but not between 20 and 27 weeks’ gestation.

Dr. Blumenfeld reported having no financial disclosures.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – Dr. Meg Autry typically spends a first prenatal care visit talking about what her pregnant patient may have heard – the myths and the facts – regarding the dos and don’ts during pregnancy.

She’s not alone. Patients hear plenty of prenatal myths perpetuated not only by their peers but by some health care providers, she said at a meeting on antepartum and intrapartum management sponsored by the University of California, San Francisco.

An informal electronic poll of the physicians, nurses, and nurse-midwives at the meeting showed that 63% discuss diet at a new patient visit, 17% talk about environmental exposures, 12% discuss exercise, and 8% discuss dietary supplements. These topics were generated more by the health care providers than by the patients, they said.

Deli meats were the leading dietary topic, discussed by 34%, followed by cooked fish, sushi, vegetarian diets, and cheese, in that order. Most of the questions about exercise come from women who exercise a lot, 73% of respondents said, than from women who don’t exercise enough (27%). Iron led the list of supplements discussed (by 36%), followed by omega-3 fatty acids, and (in a third-place tie) calcium and vitamin D.

Dr. Autry, professor of ob.gyn. and reproductive sciences at the university, offered the following myth busters and evidence-based advice for prenatal care. "My goal is to give you a basis for what you talk about with patients," she said.

• Fish: A food that’s high in quality protein, low in saturated fat, and full of beneficial omega-3 fatty acids comes with a downside: Methylmercury that can impair fetal and newborn motor and cognitive skills. Two prospective studies of dietary fish’s effects in pregnancy produced conflicting results. One study that found adverse effects from daily eating of fish was conducted in the Danish Faeroe Islands, where much of what they ate was whale. The other study, in the Pacific Ocean’s Seychelles Islands, found infant neurodevelopmental benefits when mothers ate fish in 12 meals/week, including types of fish that were more similar to those eaten in the United States, Dr. Autry said.

The Food and Drug Administration and Environmental Protection Agency in 2004 advised consumers to eat up to 12 ounces (two average meals) per week of a variety of fish that are low in mercury and to check local advisories about the safety of locally caught fish.

Encourage women to eat fish, she said, "but don’t eat fish that live for a long time and that eat lots of other fish," such as shark, swordfish, king mackerel, tilefish, whale, or albacore tuna.

• Sushi: Very rare infectious diseases from raw fish are virtually a nonproblem in the United States, because most sushi is flash frozen, which kills most pathogens. "I don’t think you need to tell patients they need to stop eating sushi," she said. "Talk to them more about mercury" and talk about the benefits of eating moderate amounts of fish.

• Supplements: There’s no evidence that taking a supplement to get omega-3 fatty acids is beneficial, especially compared with eating fish. "We’re just supposed to eat it, we’re not supposed to have a pill to fix everything," she said.

A standard prenatal vitamin supplies the iron and other vitamins and minerals needed, and it’s good to advise patients to eat foods that promote iron absorption and are high in vitamin C, such as strawberries or broccoli. Warn women that their prenatal vitamin should be their maximum dose of vitamin A, a known teratogen. There’s no good evidence that taking extra calcium or vitamin D supplements generally is helpful in pregnancy, but the American College of Obstetricians and Gynecologists recommends considering vitamin D supplementation in women at risk of deficiency.

• Cheese: A third of U.S. cases of listeriosis occurs in pregnant women and is associated with miscarriage and stillbirth. Nationally, the bacteria Listeria reaches people most commonly through hot dogs. In California, it’s the queso fresco. The FDA and/or the U.S. Department of Agriculture advise pregnant women not to eat hot dogs or luncheon meats unless they’re reheating to steaming, and to avoid soft cheeses; refrigerated pâtés or meat spreads; smoked seafood; raw or unpasteurized milk; and raw or undercooked meats.

• Caffeine: Approximately 85% of U.S. women report eating or drinking caffeine-containing food or drinks, Dr. Autry said. Concerns that caffeine consumption might be associated with low birth weight, congenital anomalies, delay in conception, or miscarriage were poorly designed and confounded by an association between caffeine intake and cigarette smoking. More recent studies predominantly have been negative, and a randomized, controlled trial found no association between moderate caffeine intake and gestational age or birth weight (BMJ 2007;334:409).

• Alcohol: Bad news for the 10% of pregnant women who report ingesting alcohol and especially for the 2% who binge drink during pregnancy: There’s no safe level of alcohol intake during pregnancy. Federal data suggest that 1 in 6,000 U.S. newborns have fetal alcohol syndrome or fetal alcohol spectrum disorder.

• Nicotine: The tricky problem with nicotine is not just that it’s "associated with everything bad," Dr. Autry said, but that people know it’s bad, so an estimated 25%-50% of pregnant women don’t disclose that they smoke. Smoking in pregnancy is associated with miscarriage, abruption, ectopic pregnancy, preterm delivery, and more. Among mothers who quit smoking during pregnancy, 90% relapse after delivery. "It’s really important to continue the smoking cessation discussion during pregnancy," she said. "It’s important to say, ‘If you go back to smoking, don’t do it in the house, because it’s bad for the kid.’"

• Hot tubs: Soaking during the first trimester, or any time in pregnancy in water heated to 100  F or higher, is potentially teratogenic, two studies suggest. Maternal hyperthermia from hot tubs has been associated with first trimester fetal loss and with a nearly doubling in risk for neural tube defects.

• Exercise: The general recommendation to get 30 minutes or more of moderate exercise on most days applies to pregnant women unless they have some medical or obstetric complication. Exercise is believed to help prevent gestational diabetes, reduce the risk for preeclampsia and premature labor, and decrease the risk for postpartum depression. ACOG recommends avoiding scuba diving, contact sports, and supine activities or motionless standings. Yoga is fine, but avoid so-called "hot yoga," Dr. Autry said.

For high-performance athletes, exertion at high altitudes appears to be safe. There is no pregnancy-specific maximum heart rate.

"Just don’t do anything in pregnancy that you wouldn’t do before," Dr. Autry said. If you’ve never run a marathon, pregnancy is not the time to start.

• Hair dye: There are no data to support the idea of teratogenic effects from the chemicals in hair dyes. But it’s probably still a good idea to look at the labels and choose products with ingredients that are less long acting and organic, if possible, she said.

For resources on environmental exposures during pregnancy, see the university’s Program on Reproductive Health and the Environment.

Dr. Autry reported having no financial disclosures.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – Dr. Meg Autry typically spends a first prenatal care visit talking about what her pregnant patient may have heard – the myths and the facts – regarding the dos and don’ts during pregnancy.

She’s not alone. Patients hear plenty of prenatal myths perpetuated not only by their peers but by some health care providers, she said at a meeting on antepartum and intrapartum management sponsored by the University of California, San Francisco.

An informal electronic poll of the physicians, nurses, and nurse-midwives at the meeting showed that 63% discuss diet at a new patient visit, 17% talk about environmental exposures, 12% discuss exercise, and 8% discuss dietary supplements. These topics were generated more by the health care providers than by the patients, they said.

Deli meats were the leading dietary topic, discussed by 34%, followed by cooked fish, sushi, vegetarian diets, and cheese, in that order. Most of the questions about exercise come from women who exercise a lot, 73% of respondents said, than from women who don’t exercise enough (27%). Iron led the list of supplements discussed (by 36%), followed by omega-3 fatty acids, and (in a third-place tie) calcium and vitamin D.

Dr. Autry, professor of ob.gyn. and reproductive sciences at the university, offered the following myth busters and evidence-based advice for prenatal care. "My goal is to give you a basis for what you talk about with patients," she said.

• Fish: A food that’s high in quality protein, low in saturated fat, and full of beneficial omega-3 fatty acids comes with a downside: Methylmercury that can impair fetal and newborn motor and cognitive skills. Two prospective studies of dietary fish’s effects in pregnancy produced conflicting results. One study that found adverse effects from daily eating of fish was conducted in the Danish Faeroe Islands, where much of what they ate was whale. The other study, in the Pacific Ocean’s Seychelles Islands, found infant neurodevelopmental benefits when mothers ate fish in 12 meals/week, including types of fish that were more similar to those eaten in the United States, Dr. Autry said.

The Food and Drug Administration and Environmental Protection Agency in 2004 advised consumers to eat up to 12 ounces (two average meals) per week of a variety of fish that are low in mercury and to check local advisories about the safety of locally caught fish.

Encourage women to eat fish, she said, "but don’t eat fish that live for a long time and that eat lots of other fish," such as shark, swordfish, king mackerel, tilefish, whale, or albacore tuna.

• Sushi: Very rare infectious diseases from raw fish are virtually a nonproblem in the United States, because most sushi is flash frozen, which kills most pathogens. "I don’t think you need to tell patients they need to stop eating sushi," she said. "Talk to them more about mercury" and talk about the benefits of eating moderate amounts of fish.

• Supplements: There’s no evidence that taking a supplement to get omega-3 fatty acids is beneficial, especially compared with eating fish. "We’re just supposed to eat it, we’re not supposed to have a pill to fix everything," she said.

A standard prenatal vitamin supplies the iron and other vitamins and minerals needed, and it’s good to advise patients to eat foods that promote iron absorption and are high in vitamin C, such as strawberries or broccoli. Warn women that their prenatal vitamin should be their maximum dose of vitamin A, a known teratogen. There’s no good evidence that taking extra calcium or vitamin D supplements generally is helpful in pregnancy, but the American College of Obstetricians and Gynecologists recommends considering vitamin D supplementation in women at risk of deficiency.

• Cheese: A third of U.S. cases of listeriosis occurs in pregnant women and is associated with miscarriage and stillbirth. Nationally, the bacteria Listeria reaches people most commonly through hot dogs. In California, it’s the queso fresco. The FDA and/or the U.S. Department of Agriculture advise pregnant women not to eat hot dogs or luncheon meats unless they’re reheating to steaming, and to avoid soft cheeses; refrigerated pâtés or meat spreads; smoked seafood; raw or unpasteurized milk; and raw or undercooked meats.

• Caffeine: Approximately 85% of U.S. women report eating or drinking caffeine-containing food or drinks, Dr. Autry said. Concerns that caffeine consumption might be associated with low birth weight, congenital anomalies, delay in conception, or miscarriage were poorly designed and confounded by an association between caffeine intake and cigarette smoking. More recent studies predominantly have been negative, and a randomized, controlled trial found no association between moderate caffeine intake and gestational age or birth weight (BMJ 2007;334:409).

• Alcohol: Bad news for the 10% of pregnant women who report ingesting alcohol and especially for the 2% who binge drink during pregnancy: There’s no safe level of alcohol intake during pregnancy. Federal data suggest that 1 in 6,000 U.S. newborns have fetal alcohol syndrome or fetal alcohol spectrum disorder.

• Nicotine: The tricky problem with nicotine is not just that it’s "associated with everything bad," Dr. Autry said, but that people know it’s bad, so an estimated 25%-50% of pregnant women don’t disclose that they smoke. Smoking in pregnancy is associated with miscarriage, abruption, ectopic pregnancy, preterm delivery, and more. Among mothers who quit smoking during pregnancy, 90% relapse after delivery. "It’s really important to continue the smoking cessation discussion during pregnancy," she said. "It’s important to say, ‘If you go back to smoking, don’t do it in the house, because it’s bad for the kid.’"

• Hot tubs: Soaking during the first trimester, or any time in pregnancy in water heated to 100  F or higher, is potentially teratogenic, two studies suggest. Maternal hyperthermia from hot tubs has been associated with first trimester fetal loss and with a nearly doubling in risk for neural tube defects.

• Exercise: The general recommendation to get 30 minutes or more of moderate exercise on most days applies to pregnant women unless they have some medical or obstetric complication. Exercise is believed to help prevent gestational diabetes, reduce the risk for preeclampsia and premature labor, and decrease the risk for postpartum depression. ACOG recommends avoiding scuba diving, contact sports, and supine activities or motionless standings. Yoga is fine, but avoid so-called "hot yoga," Dr. Autry said.

For high-performance athletes, exertion at high altitudes appears to be safe. There is no pregnancy-specific maximum heart rate.

"Just don’t do anything in pregnancy that you wouldn’t do before," Dr. Autry said. If you’ve never run a marathon, pregnancy is not the time to start.

• Hair dye: There are no data to support the idea of teratogenic effects from the chemicals in hair dyes. But it’s probably still a good idea to look at the labels and choose products with ingredients that are less long acting and organic, if possible, she said.

For resources on environmental exposures during pregnancy, see the university’s Program on Reproductive Health and the Environment.

Dr. Autry reported having no financial disclosures.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – Dr. Meg Autry typically spends a first prenatal care visit talking about what her pregnant patient may have heard – the myths and the facts – regarding the dos and don’ts during pregnancy.

She’s not alone. Patients hear plenty of prenatal myths perpetuated not only by their peers but by some health care providers, she said at a meeting on antepartum and intrapartum management sponsored by the University of California, San Francisco.

An informal electronic poll of the physicians, nurses, and nurse-midwives at the meeting showed that 63% discuss diet at a new patient visit, 17% talk about environmental exposures, 12% discuss exercise, and 8% discuss dietary supplements. These topics were generated more by the health care providers than by the patients, they said.

Deli meats were the leading dietary topic, discussed by 34%, followed by cooked fish, sushi, vegetarian diets, and cheese, in that order. Most of the questions about exercise come from women who exercise a lot, 73% of respondents said, than from women who don’t exercise enough (27%). Iron led the list of supplements discussed (by 36%), followed by omega-3 fatty acids, and (in a third-place tie) calcium and vitamin D.

Dr. Autry, professor of ob.gyn. and reproductive sciences at the university, offered the following myth busters and evidence-based advice for prenatal care. "My goal is to give you a basis for what you talk about with patients," she said.

• Fish: A food that’s high in quality protein, low in saturated fat, and full of beneficial omega-3 fatty acids comes with a downside: Methylmercury that can impair fetal and newborn motor and cognitive skills. Two prospective studies of dietary fish’s effects in pregnancy produced conflicting results. One study that found adverse effects from daily eating of fish was conducted in the Danish Faeroe Islands, where much of what they ate was whale. The other study, in the Pacific Ocean’s Seychelles Islands, found infant neurodevelopmental benefits when mothers ate fish in 12 meals/week, including types of fish that were more similar to those eaten in the United States, Dr. Autry said.

The Food and Drug Administration and Environmental Protection Agency in 2004 advised consumers to eat up to 12 ounces (two average meals) per week of a variety of fish that are low in mercury and to check local advisories about the safety of locally caught fish.

Encourage women to eat fish, she said, "but don’t eat fish that live for a long time and that eat lots of other fish," such as shark, swordfish, king mackerel, tilefish, whale, or albacore tuna.

• Sushi: Very rare infectious diseases from raw fish are virtually a nonproblem in the United States, because most sushi is flash frozen, which kills most pathogens. "I don’t think you need to tell patients they need to stop eating sushi," she said. "Talk to them more about mercury" and talk about the benefits of eating moderate amounts of fish.

• Supplements: There’s no evidence that taking a supplement to get omega-3 fatty acids is beneficial, especially compared with eating fish. "We’re just supposed to eat it, we’re not supposed to have a pill to fix everything," she said.

A standard prenatal vitamin supplies the iron and other vitamins and minerals needed, and it’s good to advise patients to eat foods that promote iron absorption and are high in vitamin C, such as strawberries or broccoli. Warn women that their prenatal vitamin should be their maximum dose of vitamin A, a known teratogen. There’s no good evidence that taking extra calcium or vitamin D supplements generally is helpful in pregnancy, but the American College of Obstetricians and Gynecologists recommends considering vitamin D supplementation in women at risk of deficiency.

• Cheese: A third of U.S. cases of listeriosis occurs in pregnant women and is associated with miscarriage and stillbirth. Nationally, the bacteria Listeria reaches people most commonly through hot dogs. In California, it’s the queso fresco. The FDA and/or the U.S. Department of Agriculture advise pregnant women not to eat hot dogs or luncheon meats unless they’re reheating to steaming, and to avoid soft cheeses; refrigerated pâtés or meat spreads; smoked seafood; raw or unpasteurized milk; and raw or undercooked meats.

• Caffeine: Approximately 85% of U.S. women report eating or drinking caffeine-containing food or drinks, Dr. Autry said. Concerns that caffeine consumption might be associated with low birth weight, congenital anomalies, delay in conception, or miscarriage were poorly designed and confounded by an association between caffeine intake and cigarette smoking. More recent studies predominantly have been negative, and a randomized, controlled trial found no association between moderate caffeine intake and gestational age or birth weight (BMJ 2007;334:409).

• Alcohol: Bad news for the 10% of pregnant women who report ingesting alcohol and especially for the 2% who binge drink during pregnancy: There’s no safe level of alcohol intake during pregnancy. Federal data suggest that 1 in 6,000 U.S. newborns have fetal alcohol syndrome or fetal alcohol spectrum disorder.

• Nicotine: The tricky problem with nicotine is not just that it’s "associated with everything bad," Dr. Autry said, but that people know it’s bad, so an estimated 25%-50% of pregnant women don’t disclose that they smoke. Smoking in pregnancy is associated with miscarriage, abruption, ectopic pregnancy, preterm delivery, and more. Among mothers who quit smoking during pregnancy, 90% relapse after delivery. "It’s really important to continue the smoking cessation discussion during pregnancy," she said. "It’s important to say, ‘If you go back to smoking, don’t do it in the house, because it’s bad for the kid.’"

• Hot tubs: Soaking during the first trimester, or any time in pregnancy in water heated to 100  F or higher, is potentially teratogenic, two studies suggest. Maternal hyperthermia from hot tubs has been associated with first trimester fetal loss and with a nearly doubling in risk for neural tube defects.

• Exercise: The general recommendation to get 30 minutes or more of moderate exercise on most days applies to pregnant women unless they have some medical or obstetric complication. Exercise is believed to help prevent gestational diabetes, reduce the risk for preeclampsia and premature labor, and decrease the risk for postpartum depression. ACOG recommends avoiding scuba diving, contact sports, and supine activities or motionless standings. Yoga is fine, but avoid so-called "hot yoga," Dr. Autry said.

For high-performance athletes, exertion at high altitudes appears to be safe. There is no pregnancy-specific maximum heart rate.

"Just don’t do anything in pregnancy that you wouldn’t do before," Dr. Autry said. If you’ve never run a marathon, pregnancy is not the time to start.

• Hair dye: There are no data to support the idea of teratogenic effects from the chemicals in hair dyes. But it’s probably still a good idea to look at the labels and choose products with ingredients that are less long acting and organic, if possible, she said.

For resources on environmental exposures during pregnancy, see the university’s Program on Reproductive Health and the Environment.

Dr. Autry reported having no financial disclosures.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – Nonwhite patients with well-differentiated thyroid cancer were at least 36% more likely than were whites to present with metastatic disease, and these significant racial disparities could not be explained fully by differences in socioeconomic status or other obvious factors in a study of 25,945 California cases.

The risk of remote (metastatic) disease at presentation was 89% higher in Hispanics, 82% higher in Asians or Pacific Islanders, and 36% higher in non-Hispanic blacks than in whites, Dr. Avital Harari and her associates reported at the Endocrine Society’s Annual Meeting. The investigators adjusted for the effects of age, socioeconomic status, sex, and type of insurance when assessing the effects of race on disease stage at presentation.

The odds of regional-stage disease at presentation also were significantly higher compared with whites among Hispanics (a 59% higher likelihood of regional disease) and Asian/Pacific Islanders (32% higher).

Compared with patients with the highest socioeconomic status, those with the lowest socioeconomic status were 45% more likely to present with remote disease, a significant difference. Patients who were poorly insured, uninsured, or covered by Medicaid insurance were more than twice as likely to present with remote disease as were privately insured patients. Age and sex increased risk too, with double the odds of metastatic disease at presentation in patients who were male or at least 45 years old.

"Despite the fact that three races seem to have presented with more remote disease than white patients, their survival analysis differs from what we might expect," Dr. Harari said. Asian/Pacific Islanders were significantly less likely than whites to die (a 14% lower odds ratio), and Hispanics had essentially the same overall survival rates as whites. The risk of death was significantly higher in black patients, who were 38% more likely than whites to die, after adjustment for the effects of age, sex, and comorbidities, said Dr. Harari, an endocrine surgeon at the University of California, Los Angeles.

Remote disease quadrupled the odds of dying and regional disease increased the risk of death by 46% compared with localized disease at presentation. Older age significantly increased the risk of death by 7%.

Among patients with metastatic disease at presentation, overall survival rates were not significantly different between racial groups after adjustment for age, sex, and comorbidity. Older age significantly increased the risk of death by 5%.

The chances of dying of thyroid cancer, however, were significantly greater for blacks than for patients of other races.

Differences in the biology of thyroid disease by race, disparities in access to care and resources that might delay diagnosis and treatment, and inherent provider bias are likely at play, said Dr. Harari.

"I challenge you to think about how you might change your practice in regard to the information noted here," she said.

Dr. Harari and her colleagues analyzed data on all new cases of thyroid cancer during 1999-2008 from the California Cancer Registry, a population-based cancer surveillance system. Cases were excluded if they were not well differentiated, had unknown stage at diagnosis, or were second cases in patients already in the registry. The researchers scored socioeconomic status using Yost’s index and scored comorbidity using the Charlson system.

The cohort was 57% white, 24% Hispanic, 15% Asian/Pacific Islander, and 4% black. The racial groups differed significantly by mean age, sex, mean comorbidity score, and socioeconomic score.

Hispanics were younger at diagnosis (mean age, 44 years) compared with Asian/Pacific Islanders (48 years) or whites or Hispanics (50 years each). Hispanics were less likely to be male (18%) than were whites (26%). Mean Charlson comorbidity scores were highest for blacks (0.69) compared with whites (0.41), Hispanics (0.39), and Asian/Pacific Islanders (0.34). Overall, black patients were more likely to be older and to have higher comorbidity scores than other patients, she said.

The two highest quintiles of socioeconomic scores included 60% of whites and 55% of Asian/Pacific Islanders. The two lowest quintiles of socioeconomic scores included 55% of Hispanics and 47% of blacks.

The results support a 2012 review by the Endocrine Society in which people with low socioeconomic status were more likely than more affluent groups to present with advanced thyroid cancer. That study also found that racial minorities had less access to high-volume thyroid surgeons (J. Clin. Endocrinol. Metab. 2012;97:E1579-639).

Dr. Harari reported having no financial disclosures.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – Nonwhite patients with well-differentiated thyroid cancer were at least 36% more likely than were whites to present with metastatic disease, and these significant racial disparities could not be explained fully by differences in socioeconomic status or other obvious factors in a study of 25,945 California cases.

The risk of remote (metastatic) disease at presentation was 89% higher in Hispanics, 82% higher in Asians or Pacific Islanders, and 36% higher in non-Hispanic blacks than in whites, Dr. Avital Harari and her associates reported at the Endocrine Society’s Annual Meeting. The investigators adjusted for the effects of age, socioeconomic status, sex, and type of insurance when assessing the effects of race on disease stage at presentation.

The odds of regional-stage disease at presentation also were significantly higher compared with whites among Hispanics (a 59% higher likelihood of regional disease) and Asian/Pacific Islanders (32% higher).

Compared with patients with the highest socioeconomic status, those with the lowest socioeconomic status were 45% more likely to present with remote disease, a significant difference. Patients who were poorly insured, uninsured, or covered by Medicaid insurance were more than twice as likely to present with remote disease as were privately insured patients. Age and sex increased risk too, with double the odds of metastatic disease at presentation in patients who were male or at least 45 years old.

"Despite the fact that three races seem to have presented with more remote disease than white patients, their survival analysis differs from what we might expect," Dr. Harari said. Asian/Pacific Islanders were significantly less likely than whites to die (a 14% lower odds ratio), and Hispanics had essentially the same overall survival rates as whites. The risk of death was significantly higher in black patients, who were 38% more likely than whites to die, after adjustment for the effects of age, sex, and comorbidities, said Dr. Harari, an endocrine surgeon at the University of California, Los Angeles.

Remote disease quadrupled the odds of dying and regional disease increased the risk of death by 46% compared with localized disease at presentation. Older age significantly increased the risk of death by 7%.

Among patients with metastatic disease at presentation, overall survival rates were not significantly different between racial groups after adjustment for age, sex, and comorbidity. Older age significantly increased the risk of death by 5%.

The chances of dying of thyroid cancer, however, were significantly greater for blacks than for patients of other races.

Differences in the biology of thyroid disease by race, disparities in access to care and resources that might delay diagnosis and treatment, and inherent provider bias are likely at play, said Dr. Harari.

"I challenge you to think about how you might change your practice in regard to the information noted here," she said.

Dr. Harari and her colleagues analyzed data on all new cases of thyroid cancer during 1999-2008 from the California Cancer Registry, a population-based cancer surveillance system. Cases were excluded if they were not well differentiated, had unknown stage at diagnosis, or were second cases in patients already in the registry. The researchers scored socioeconomic status using Yost’s index and scored comorbidity using the Charlson system.

The cohort was 57% white, 24% Hispanic, 15% Asian/Pacific Islander, and 4% black. The racial groups differed significantly by mean age, sex, mean comorbidity score, and socioeconomic score.

Hispanics were younger at diagnosis (mean age, 44 years) compared with Asian/Pacific Islanders (48 years) or whites or Hispanics (50 years each). Hispanics were less likely to be male (18%) than were whites (26%). Mean Charlson comorbidity scores were highest for blacks (0.69) compared with whites (0.41), Hispanics (0.39), and Asian/Pacific Islanders (0.34). Overall, black patients were more likely to be older and to have higher comorbidity scores than other patients, she said.

The two highest quintiles of socioeconomic scores included 60% of whites and 55% of Asian/Pacific Islanders. The two lowest quintiles of socioeconomic scores included 55% of Hispanics and 47% of blacks.

The results support a 2012 review by the Endocrine Society in which people with low socioeconomic status were more likely than more affluent groups to present with advanced thyroid cancer. That study also found that racial minorities had less access to high-volume thyroid surgeons (J. Clin. Endocrinol. Metab. 2012;97:E1579-639).

Dr. Harari reported having no financial disclosures.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – Nonwhite patients with well-differentiated thyroid cancer were at least 36% more likely than were whites to present with metastatic disease, and these significant racial disparities could not be explained fully by differences in socioeconomic status or other obvious factors in a study of 25,945 California cases.

The risk of remote (metastatic) disease at presentation was 89% higher in Hispanics, 82% higher in Asians or Pacific Islanders, and 36% higher in non-Hispanic blacks than in whites, Dr. Avital Harari and her associates reported at the Endocrine Society’s Annual Meeting. The investigators adjusted for the effects of age, socioeconomic status, sex, and type of insurance when assessing the effects of race on disease stage at presentation.

The odds of regional-stage disease at presentation also were significantly higher compared with whites among Hispanics (a 59% higher likelihood of regional disease) and Asian/Pacific Islanders (32% higher).

Compared with patients with the highest socioeconomic status, those with the lowest socioeconomic status were 45% more likely to present with remote disease, a significant difference. Patients who were poorly insured, uninsured, or covered by Medicaid insurance were more than twice as likely to present with remote disease as were privately insured patients. Age and sex increased risk too, with double the odds of metastatic disease at presentation in patients who were male or at least 45 years old.

"Despite the fact that three races seem to have presented with more remote disease than white patients, their survival analysis differs from what we might expect," Dr. Harari said. Asian/Pacific Islanders were significantly less likely than whites to die (a 14% lower odds ratio), and Hispanics had essentially the same overall survival rates as whites. The risk of death was significantly higher in black patients, who were 38% more likely than whites to die, after adjustment for the effects of age, sex, and comorbidities, said Dr. Harari, an endocrine surgeon at the University of California, Los Angeles.

Remote disease quadrupled the odds of dying and regional disease increased the risk of death by 46% compared with localized disease at presentation. Older age significantly increased the risk of death by 7%.

Among patients with metastatic disease at presentation, overall survival rates were not significantly different between racial groups after adjustment for age, sex, and comorbidity. Older age significantly increased the risk of death by 5%.

The chances of dying of thyroid cancer, however, were significantly greater for blacks than for patients of other races.

Differences in the biology of thyroid disease by race, disparities in access to care and resources that might delay diagnosis and treatment, and inherent provider bias are likely at play, said Dr. Harari.

"I challenge you to think about how you might change your practice in regard to the information noted here," she said.

Dr. Harari and her colleagues analyzed data on all new cases of thyroid cancer during 1999-2008 from the California Cancer Registry, a population-based cancer surveillance system. Cases were excluded if they were not well differentiated, had unknown stage at diagnosis, or were second cases in patients already in the registry. The researchers scored socioeconomic status using Yost’s index and scored comorbidity using the Charlson system.

The cohort was 57% white, 24% Hispanic, 15% Asian/Pacific Islander, and 4% black. The racial groups differed significantly by mean age, sex, mean comorbidity score, and socioeconomic score.

Hispanics were younger at diagnosis (mean age, 44 years) compared with Asian/Pacific Islanders (48 years) or whites or Hispanics (50 years each). Hispanics were less likely to be male (18%) than were whites (26%). Mean Charlson comorbidity scores were highest for blacks (0.69) compared with whites (0.41), Hispanics (0.39), and Asian/Pacific Islanders (0.34). Overall, black patients were more likely to be older and to have higher comorbidity scores than other patients, she said.

The two highest quintiles of socioeconomic scores included 60% of whites and 55% of Asian/Pacific Islanders. The two lowest quintiles of socioeconomic scores included 55% of Hispanics and 47% of blacks.

The results support a 2012 review by the Endocrine Society in which people with low socioeconomic status were more likely than more affluent groups to present with advanced thyroid cancer. That study also found that racial minorities had less access to high-volume thyroid surgeons (J. Clin. Endocrinol. Metab. 2012;97:E1579-639).

Dr. Harari reported having no financial disclosures.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – Assessing renal health using a modified Cockroft-Gault equation to measure creatinine clearance was more sensitive than using the Modification of Diet in Renal Disease equation to estimate glomerular filtration rate when estimating risk for osteoporosis and fracture, an award-winning study of 400 postmenopausal Puerto Rican women showed.

The study found a high prevalence of mild renal dysfunction (stage 2 chronic kidney disease) in 54%-59% of women, depending on the equation used. With the Cockroft-Gault equation adjusted for body surface area, a determination of mild renal dysfunction was associated with significantly decreased bone mineral density and with a doubling in risk for vertebral or nonvertebral fractures. When the Modification of Diet in Renal Disease (MDRD) equation was used, however, no significant associations were found between mild renal dysfunction and fracture risk, Dr. Loida A. González-Rodriguez reported.

Previous data have shown that severe renal dysfunction is associated with reduced bone mineral density and fractures, and that a creatinine clearance below 65 mL/min per 1.73 m² is associated with a higher risk for falls and hip fractures in elderly people. Less is known about the effects of mild renal dysfunction on bone mineral density.

"We are postulating that this Cockroft-Gault equation is better to estimate bone," because it includes factors such as weight and age, and is adjusted for body surface area, Dr. González-Rodriguez said in an interview at the annual meeting of the Endocrine Society. She received an award at the meeting for her retrospective secondary analysis of data from the Latin American Vertebral Osteoporosis Study, the first population-based study of vertebral fractures in Latin America.

Many clinicians use the MDRD equation to estimate renal function. Dr. González-Rodriguez of the University of Puerto Rico, San Juan, said she has switched to using the Cockroft-Gault equation, and is trying to get colleagues at her institution to do the same. The MDRD equation will miss some patients who are at risk for osteopenia, osteoporosis, and fracture, she said.

Seventeen percent of patients in the study had normal bone mineral density, 43% had osteopenia, and 41% had osteoporosis. (Percentages were rounded and so exceed 100%.)

When the Cockroft-Gault equation was used to categorize renal function, 9% of patients had stage 1 chronic kidney disease, 54% had stage 2, 35% had stage 3, and 2% had stage 4. When the MDRD equation was used, 2% of patients had stage 1 chronic kidney disease, 59% had stage 2, 38% had stage 3, and 1% had stage 4.

Among patients with stage 2 chronic kidney disease as assessed by the Cockroft-Gault equation, 19% had normal bone mineral density, 49% had osteopenia, and 32% had osteoporosis. Among patients with stage 2 disease assessed using the MDRD equation, 4% had normal bone mineral density, 35% had osteopenia, and 60% had osteoporosis.

Vertebral fractures occurred in 9% and nonvertebral fractures occurred in 18% of patients with stage 2 disease assessed with the Cockroft-Gault equation. When the MDRD equation was used, 9% of patients with stage 2 disease developed vertebral fractures and 24% developed nonvertebral fractures.

Among patients with stage 3 chronic kidney disease assessed using the Cockroft-Gault equation, 18% developed vertebral fractures and 31% developed nonvertebral fractures, compared with vertebral fractures in 16% and nonvertebral fractures in 22% of patients with stage 3 disease assessed using the MDRD equation.

"One of the most important risk factors for vertebral and nonvertebral fractures is osteoporosis," Dr. González-Rodriguez noted. "So, if we can identify earlier the patients that have mild renal dysfunction" using the Cockroft-Gault equation and manage the osteoporosis risk, some fractures may be prevented.

The findings are limited by the retrospective design of the study, a lack of blood pressure measurements to assess arterial hypertension, self-reported nonvertebral fractures, and a lack of measurements of intact parathyroid hormone, 25-hydroxyvitamin D, and microalbuminuria.

Dr. González-Rodriguez reported having no relevant financial disclosures. The National Center for Research Resources and the National Institute on Minority Health and Health Disparities funded the study.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – Assessing renal health using a modified Cockroft-Gault equation to measure creatinine clearance was more sensitive than using the Modification of Diet in Renal Disease equation to estimate glomerular filtration rate when estimating risk for osteoporosis and fracture, an award-winning study of 400 postmenopausal Puerto Rican women showed.

The study found a high prevalence of mild renal dysfunction (stage 2 chronic kidney disease) in 54%-59% of women, depending on the equation used. With the Cockroft-Gault equation adjusted for body surface area, a determination of mild renal dysfunction was associated with significantly decreased bone mineral density and with a doubling in risk for vertebral or nonvertebral fractures. When the Modification of Diet in Renal Disease (MDRD) equation was used, however, no significant associations were found between mild renal dysfunction and fracture risk, Dr. Loida A. González-Rodriguez reported.

Previous data have shown that severe renal dysfunction is associated with reduced bone mineral density and fractures, and that a creatinine clearance below 65 mL/min per 1.73 m² is associated with a higher risk for falls and hip fractures in elderly people. Less is known about the effects of mild renal dysfunction on bone mineral density.

"We are postulating that this Cockroft-Gault equation is better to estimate bone," because it includes factors such as weight and age, and is adjusted for body surface area, Dr. González-Rodriguez said in an interview at the annual meeting of the Endocrine Society. She received an award at the meeting for her retrospective secondary analysis of data from the Latin American Vertebral Osteoporosis Study, the first population-based study of vertebral fractures in Latin America.

Many clinicians use the MDRD equation to estimate renal function. Dr. González-Rodriguez of the University of Puerto Rico, San Juan, said she has switched to using the Cockroft-Gault equation, and is trying to get colleagues at her institution to do the same. The MDRD equation will miss some patients who are at risk for osteopenia, osteoporosis, and fracture, she said.

Seventeen percent of patients in the study had normal bone mineral density, 43% had osteopenia, and 41% had osteoporosis. (Percentages were rounded and so exceed 100%.)

When the Cockroft-Gault equation was used to categorize renal function, 9% of patients had stage 1 chronic kidney disease, 54% had stage 2, 35% had stage 3, and 2% had stage 4. When the MDRD equation was used, 2% of patients had stage 1 chronic kidney disease, 59% had stage 2, 38% had stage 3, and 1% had stage 4.

Among patients with stage 2 chronic kidney disease as assessed by the Cockroft-Gault equation, 19% had normal bone mineral density, 49% had osteopenia, and 32% had osteoporosis. Among patients with stage 2 disease assessed using the MDRD equation, 4% had normal bone mineral density, 35% had osteopenia, and 60% had osteoporosis.

Vertebral fractures occurred in 9% and nonvertebral fractures occurred in 18% of patients with stage 2 disease assessed with the Cockroft-Gault equation. When the MDRD equation was used, 9% of patients with stage 2 disease developed vertebral fractures and 24% developed nonvertebral fractures.

Among patients with stage 3 chronic kidney disease assessed using the Cockroft-Gault equation, 18% developed vertebral fractures and 31% developed nonvertebral fractures, compared with vertebral fractures in 16% and nonvertebral fractures in 22% of patients with stage 3 disease assessed using the MDRD equation.

"One of the most important risk factors for vertebral and nonvertebral fractures is osteoporosis," Dr. González-Rodriguez noted. "So, if we can identify earlier the patients that have mild renal dysfunction" using the Cockroft-Gault equation and manage the osteoporosis risk, some fractures may be prevented.

The findings are limited by the retrospective design of the study, a lack of blood pressure measurements to assess arterial hypertension, self-reported nonvertebral fractures, and a lack of measurements of intact parathyroid hormone, 25-hydroxyvitamin D, and microalbuminuria.

Dr. González-Rodriguez reported having no relevant financial disclosures. The National Center for Research Resources and the National Institute on Minority Health and Health Disparities funded the study.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – Assessing renal health using a modified Cockroft-Gault equation to measure creatinine clearance was more sensitive than using the Modification of Diet in Renal Disease equation to estimate glomerular filtration rate when estimating risk for osteoporosis and fracture, an award-winning study of 400 postmenopausal Puerto Rican women showed.

The study found a high prevalence of mild renal dysfunction (stage 2 chronic kidney disease) in 54%-59% of women, depending on the equation used. With the Cockroft-Gault equation adjusted for body surface area, a determination of mild renal dysfunction was associated with significantly decreased bone mineral density and with a doubling in risk for vertebral or nonvertebral fractures. When the Modification of Diet in Renal Disease (MDRD) equation was used, however, no significant associations were found between mild renal dysfunction and fracture risk, Dr. Loida A. González-Rodriguez reported.

Previous data have shown that severe renal dysfunction is associated with reduced bone mineral density and fractures, and that a creatinine clearance below 65 mL/min per 1.73 m² is associated with a higher risk for falls and hip fractures in elderly people. Less is known about the effects of mild renal dysfunction on bone mineral density.

"We are postulating that this Cockroft-Gault equation is better to estimate bone," because it includes factors such as weight and age, and is adjusted for body surface area, Dr. González-Rodriguez said in an interview at the annual meeting of the Endocrine Society. She received an award at the meeting for her retrospective secondary analysis of data from the Latin American Vertebral Osteoporosis Study, the first population-based study of vertebral fractures in Latin America.

Many clinicians use the MDRD equation to estimate renal function. Dr. González-Rodriguez of the University of Puerto Rico, San Juan, said she has switched to using the Cockroft-Gault equation, and is trying to get colleagues at her institution to do the same. The MDRD equation will miss some patients who are at risk for osteopenia, osteoporosis, and fracture, she said.

Seventeen percent of patients in the study had normal bone mineral density, 43% had osteopenia, and 41% had osteoporosis. (Percentages were rounded and so exceed 100%.)

When the Cockroft-Gault equation was used to categorize renal function, 9% of patients had stage 1 chronic kidney disease, 54% had stage 2, 35% had stage 3, and 2% had stage 4. When the MDRD equation was used, 2% of patients had stage 1 chronic kidney disease, 59% had stage 2, 38% had stage 3, and 1% had stage 4.

Among patients with stage 2 chronic kidney disease as assessed by the Cockroft-Gault equation, 19% had normal bone mineral density, 49% had osteopenia, and 32% had osteoporosis. Among patients with stage 2 disease assessed using the MDRD equation, 4% had normal bone mineral density, 35% had osteopenia, and 60% had osteoporosis.

Vertebral fractures occurred in 9% and nonvertebral fractures occurred in 18% of patients with stage 2 disease assessed with the Cockroft-Gault equation. When the MDRD equation was used, 9% of patients with stage 2 disease developed vertebral fractures and 24% developed nonvertebral fractures.

Among patients with stage 3 chronic kidney disease assessed using the Cockroft-Gault equation, 18% developed vertebral fractures and 31% developed nonvertebral fractures, compared with vertebral fractures in 16% and nonvertebral fractures in 22% of patients with stage 3 disease assessed using the MDRD equation.

"One of the most important risk factors for vertebral and nonvertebral fractures is osteoporosis," Dr. González-Rodriguez noted. "So, if we can identify earlier the patients that have mild renal dysfunction" using the Cockroft-Gault equation and manage the osteoporosis risk, some fractures may be prevented.

The findings are limited by the retrospective design of the study, a lack of blood pressure measurements to assess arterial hypertension, self-reported nonvertebral fractures, and a lack of measurements of intact parathyroid hormone, 25-hydroxyvitamin D, and microalbuminuria.

Dr. González-Rodriguez reported having no relevant financial disclosures. The National Center for Research Resources and the National Institute on Minority Health and Health Disparities funded the study.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – Patients with acromegaly struggle with issues that they often don’t share with their physicians, and they have specific suggestions about actions that health care providers can take to help them cope with their disease, a qualitative study of 19 patients found.

Most described a long journey to a correct diagnosis, and other data suggest that an acromegaly diagnosis typically is delayed by 4-10 years. The delay is frustrating for patients but is followed by relief when they finally have a name for their disease, Michelle H. Gurel, R.N., reported at the Endocrine Society’s Annual Meeting.

She and her associates conducted online interviews with 10 patients recruited through AcromegalyCommunity.com and live interviews with 9 patients at the 2012 Acromegaly Community Conference.

The patients said they were shocked at the idea of needing "brain surgery" (pituitary surgery) when discussing treatment with their physicians, and that they felt unsatisfied or left out of the treatment decision process.

Acromegaly is a rare chronic disease characterized by abnormal skeletal growth and soft tissue enlargement caused by excessive secretion of growth hormone by a pituitary adenoma.

Patients also hesitated to raise quality-of-life issues with their physicians and said they were concerned that health care providers did not care about quality of life. "Patients said that they were uncomfortable bringing this up; so you have to open the discussion," said Ms. Gurel of the neuroendocrine unit at Massachusetts General Hospital, Boston.

For a successful physician-patient partnership, patients want to feel that they are being listened to and treated as a person first and as someone with a disease second, they said. Health care providers should take the time to explain in detail the disease and treatment options, covering a slew of questions that patients had in four main categories: What is acromegaly? Will I ever feel like myself again? What is treatment like, and what will I experience? How do I survive financially?

Patients want to know why they are experiencing symptoms, feel bad, and no longer look like themselves, they said. They wonder if their levels of growth hormone and insulin-like growth factor 1 will return to normal, if symptoms will resolve, if the pain will stop, and if the disease can be cured. They question whether they will ever look like themselves again, feel energetic, live a normal life, and be able to forget, even for a moment, that they have acromegaly.

When discussing treatment, patients want to know why "brain surgery" is needed and how it will feel, as well as the pros and cons of radiation. They wonder why they have to take medications, and how to cope with side effects. Most of the medical therapies are expensive, raising questions about whether insurance will cover the costs, how to afford copays, and what happens if patients lose or change insurance.

Patients said they do want to be asked detailed questions about their quality of life during follow-up visits. They want health care providers who are educated about acromegaly and up-to-date in their knowledge of treatments, which they found mainly at Centers of Excellence and at pituitary centers, Ms. Gurel said. Patients wanted physicians to be aggressive in treatment without downplaying the patient’s physical, emotional, and psychological pain and suffering. "They felt stronger support from health care providers if they thought the physician cared," she said.

Nonphysician staff also are key to a successful partnership, patients said. Having a well-run office with courteous, friendly, and competent staff who can help patients with financial questions is important, from a patient’s point of view.

Participants in the study had a mean age of 43 years, and 12 of the 19 were female, although acromegaly generally affects men and women at the same rate. Among 10 patients who described their presenting symptoms, the most common were acral changes or changes in height, in six patients (60%). The disease presented with joint or muscle pain, diabetes, weight gain, headaches, and amenorrhea or an irregular menstrual cycle in 30% of patients each, and hypertension or visual changes affected 20% each at presentation. (Some patients had more than one symptom.)

Twelve of the 19 patients were currently being treated with somatostatin analogues (63%) and 3 with growth hormone receptor antagonists (16%), while 4 patients were not receiving medical therapy (21%) because they had been cured after surgery and/or radiation or because they had not yet chosen a medical therapy. Most medical therapies for acromegaly are expensive and are administered through injection, Ms. Gurel noted.

"(Patients) felt stronger support from health care providers if they thought the physician cared."

Treatment histories from 10 patients showed that 9 had undergone surgery since diagnosis, 2 had radiotherapy, 3 were treated with one medication, 4 had tried two medications, 1 patient had been treated with three drugs, and 2 patients had gone through four medications. (Patients could report more than one treatment category.)

Because patients felt left out of the treatment decision process, they felt motivated to talk to other patients, and many used online resources for support such as AcromegalyCommunity.com or other disease-specific websites. Patients who were not connected to a patient support group reported feeling lonely and helpless. Many of the patients expressed a desire to help improve knowledge about acromegaly in order to shorten the time to diagnosis for future patients.

Acromegaly typically appears in the fourth decade of life, with an annual incidence of 3 or 4 patients per million and a prevalence of 40-90 cases per million people. People with acromegaly are more likely to develop hypertension and heart disease, cardiovascular events and headaches, arthritis and acral changes, sleep apnea, and insulin-resistant diabetes. The disease is associated with premature death, with a doubling or tripling of mortality risk.

Most patients with acromegaly are treated with surgery. Medical therapies include the somatostatin analogues lanreotide and octreotide, the growth hormone receptor antagonist pegvisomant, or the dopamine agonist cabergoline.

The study was funded by Ipsen Biopharmaceuticals, which makes lanreotide (Somatuline). Ms. Gurel reported having no other financial disclosures.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – Patients with acromegaly struggle with issues that they often don’t share with their physicians, and they have specific suggestions about actions that health care providers can take to help them cope with their disease, a qualitative study of 19 patients found.

Most described a long journey to a correct diagnosis, and other data suggest that an acromegaly diagnosis typically is delayed by 4-10 years. The delay is frustrating for patients but is followed by relief when they finally have a name for their disease, Michelle H. Gurel, R.N., reported at the Endocrine Society’s Annual Meeting.

She and her associates conducted online interviews with 10 patients recruited through AcromegalyCommunity.com and live interviews with 9 patients at the 2012 Acromegaly Community Conference.

The patients said they were shocked at the idea of needing "brain surgery" (pituitary surgery) when discussing treatment with their physicians, and that they felt unsatisfied or left out of the treatment decision process.

Acromegaly is a rare chronic disease characterized by abnormal skeletal growth and soft tissue enlargement caused by excessive secretion of growth hormone by a pituitary adenoma.

Patients also hesitated to raise quality-of-life issues with their physicians and said they were concerned that health care providers did not care about quality of life. "Patients said that they were uncomfortable bringing this up; so you have to open the discussion," said Ms. Gurel of the neuroendocrine unit at Massachusetts General Hospital, Boston.

For a successful physician-patient partnership, patients want to feel that they are being listened to and treated as a person first and as someone with a disease second, they said. Health care providers should take the time to explain in detail the disease and treatment options, covering a slew of questions that patients had in four main categories: What is acromegaly? Will I ever feel like myself again? What is treatment like, and what will I experience? How do I survive financially?

Patients want to know why they are experiencing symptoms, feel bad, and no longer look like themselves, they said. They wonder if their levels of growth hormone and insulin-like growth factor 1 will return to normal, if symptoms will resolve, if the pain will stop, and if the disease can be cured. They question whether they will ever look like themselves again, feel energetic, live a normal life, and be able to forget, even for a moment, that they have acromegaly.

When discussing treatment, patients want to know why "brain surgery" is needed and how it will feel, as well as the pros and cons of radiation. They wonder why they have to take medications, and how to cope with side effects. Most of the medical therapies are expensive, raising questions about whether insurance will cover the costs, how to afford copays, and what happens if patients lose or change insurance.

Patients said they do want to be asked detailed questions about their quality of life during follow-up visits. They want health care providers who are educated about acromegaly and up-to-date in their knowledge of treatments, which they found mainly at Centers of Excellence and at pituitary centers, Ms. Gurel said. Patients wanted physicians to be aggressive in treatment without downplaying the patient’s physical, emotional, and psychological pain and suffering. "They felt stronger support from health care providers if they thought the physician cared," she said.

Nonphysician staff also are key to a successful partnership, patients said. Having a well-run office with courteous, friendly, and competent staff who can help patients with financial questions is important, from a patient’s point of view.

Participants in the study had a mean age of 43 years, and 12 of the 19 were female, although acromegaly generally affects men and women at the same rate. Among 10 patients who described their presenting symptoms, the most common were acral changes or changes in height, in six patients (60%). The disease presented with joint or muscle pain, diabetes, weight gain, headaches, and amenorrhea or an irregular menstrual cycle in 30% of patients each, and hypertension or visual changes affected 20% each at presentation. (Some patients had more than one symptom.)

Twelve of the 19 patients were currently being treated with somatostatin analogues (63%) and 3 with growth hormone receptor antagonists (16%), while 4 patients were not receiving medical therapy (21%) because they had been cured after surgery and/or radiation or because they had not yet chosen a medical therapy. Most medical therapies for acromegaly are expensive and are administered through injection, Ms. Gurel noted.

"(Patients) felt stronger support from health care providers if they thought the physician cared."

Treatment histories from 10 patients showed that 9 had undergone surgery since diagnosis, 2 had radiotherapy, 3 were treated with one medication, 4 had tried two medications, 1 patient had been treated with three drugs, and 2 patients had gone through four medications. (Patients could report more than one treatment category.)

Because patients felt left out of the treatment decision process, they felt motivated to talk to other patients, and many used online resources for support such as AcromegalyCommunity.com or other disease-specific websites. Patients who were not connected to a patient support group reported feeling lonely and helpless. Many of the patients expressed a desire to help improve knowledge about acromegaly in order to shorten the time to diagnosis for future patients.

Acromegaly typically appears in the fourth decade of life, with an annual incidence of 3 or 4 patients per million and a prevalence of 40-90 cases per million people. People with acromegaly are more likely to develop hypertension and heart disease, cardiovascular events and headaches, arthritis and acral changes, sleep apnea, and insulin-resistant diabetes. The disease is associated with premature death, with a doubling or tripling of mortality risk.

Most patients with acromegaly are treated with surgery. Medical therapies include the somatostatin analogues lanreotide and octreotide, the growth hormone receptor antagonist pegvisomant, or the dopamine agonist cabergoline.

The study was funded by Ipsen Biopharmaceuticals, which makes lanreotide (Somatuline). Ms. Gurel reported having no other financial disclosures.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – Patients with acromegaly struggle with issues that they often don’t share with their physicians, and they have specific suggestions about actions that health care providers can take to help them cope with their disease, a qualitative study of 19 patients found.

Most described a long journey to a correct diagnosis, and other data suggest that an acromegaly diagnosis typically is delayed by 4-10 years. The delay is frustrating for patients but is followed by relief when they finally have a name for their disease, Michelle H. Gurel, R.N., reported at the Endocrine Society’s Annual Meeting.

She and her associates conducted online interviews with 10 patients recruited through AcromegalyCommunity.com and live interviews with 9 patients at the 2012 Acromegaly Community Conference.

The patients said they were shocked at the idea of needing "brain surgery" (pituitary surgery) when discussing treatment with their physicians, and that they felt unsatisfied or left out of the treatment decision process.

Acromegaly is a rare chronic disease characterized by abnormal skeletal growth and soft tissue enlargement caused by excessive secretion of growth hormone by a pituitary adenoma.

Patients also hesitated to raise quality-of-life issues with their physicians and said they were concerned that health care providers did not care about quality of life. "Patients said that they were uncomfortable bringing this up; so you have to open the discussion," said Ms. Gurel of the neuroendocrine unit at Massachusetts General Hospital, Boston.

For a successful physician-patient partnership, patients want to feel that they are being listened to and treated as a person first and as someone with a disease second, they said. Health care providers should take the time to explain in detail the disease and treatment options, covering a slew of questions that patients had in four main categories: What is acromegaly? Will I ever feel like myself again? What is treatment like, and what will I experience? How do I survive financially?

Patients want to know why they are experiencing symptoms, feel bad, and no longer look like themselves, they said. They wonder if their levels of growth hormone and insulin-like growth factor 1 will return to normal, if symptoms will resolve, if the pain will stop, and if the disease can be cured. They question whether they will ever look like themselves again, feel energetic, live a normal life, and be able to forget, even for a moment, that they have acromegaly.

When discussing treatment, patients want to know why "brain surgery" is needed and how it will feel, as well as the pros and cons of radiation. They wonder why they have to take medications, and how to cope with side effects. Most of the medical therapies are expensive, raising questions about whether insurance will cover the costs, how to afford copays, and what happens if patients lose or change insurance.

Patients said they do want to be asked detailed questions about their quality of life during follow-up visits. They want health care providers who are educated about acromegaly and up-to-date in their knowledge of treatments, which they found mainly at Centers of Excellence and at pituitary centers, Ms. Gurel said. Patients wanted physicians to be aggressive in treatment without downplaying the patient’s physical, emotional, and psychological pain and suffering. "They felt stronger support from health care providers if they thought the physician cared," she said.

Nonphysician staff also are key to a successful partnership, patients said. Having a well-run office with courteous, friendly, and competent staff who can help patients with financial questions is important, from a patient’s point of view.

Participants in the study had a mean age of 43 years, and 12 of the 19 were female, although acromegaly generally affects men and women at the same rate. Among 10 patients who described their presenting symptoms, the most common were acral changes or changes in height, in six patients (60%). The disease presented with joint or muscle pain, diabetes, weight gain, headaches, and amenorrhea or an irregular menstrual cycle in 30% of patients each, and hypertension or visual changes affected 20% each at presentation. (Some patients had more than one symptom.)

Twelve of the 19 patients were currently being treated with somatostatin analogues (63%) and 3 with growth hormone receptor antagonists (16%), while 4 patients were not receiving medical therapy (21%) because they had been cured after surgery and/or radiation or because they had not yet chosen a medical therapy. Most medical therapies for acromegaly are expensive and are administered through injection, Ms. Gurel noted.

"(Patients) felt stronger support from health care providers if they thought the physician cared."

Treatment histories from 10 patients showed that 9 had undergone surgery since diagnosis, 2 had radiotherapy, 3 were treated with one medication, 4 had tried two medications, 1 patient had been treated with three drugs, and 2 patients had gone through four medications. (Patients could report more than one treatment category.)

Because patients felt left out of the treatment decision process, they felt motivated to talk to other patients, and many used online resources for support such as AcromegalyCommunity.com or other disease-specific websites. Patients who were not connected to a patient support group reported feeling lonely and helpless. Many of the patients expressed a desire to help improve knowledge about acromegaly in order to shorten the time to diagnosis for future patients.

Acromegaly typically appears in the fourth decade of life, with an annual incidence of 3 or 4 patients per million and a prevalence of 40-90 cases per million people. People with acromegaly are more likely to develop hypertension and heart disease, cardiovascular events and headaches, arthritis and acral changes, sleep apnea, and insulin-resistant diabetes. The disease is associated with premature death, with a doubling or tripling of mortality risk.

Most patients with acromegaly are treated with surgery. Medical therapies include the somatostatin analogues lanreotide and octreotide, the growth hormone receptor antagonist pegvisomant, or the dopamine agonist cabergoline.

The study was funded by Ipsen Biopharmaceuticals, which makes lanreotide (Somatuline). Ms. Gurel reported having no other financial disclosures.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – Hormonal therapies for transgender patients that block puberty and/or deliver opposite-sex hormones did not adversely affect bone development in adolescents and caused no serious side effects in teens or adults, two studies found.

The separate European studies, presented at the Endocrine Society Annual Meeting, looked at 127 adolescents aged 12-18 years in one study and 104 adults in the other study who were followed for 1 year after starting hormonal therapy.

The adolescents started gonadotropin-releasing hormone analogues (GnRHa) at ages 12-16 years to block production of sex hormones that initiate puberty, and at age 16 years they began receiving cross-sex hormones (either estrogen or testosterone) to induce sexual characteristics of the opposite sex to which they were transitioning. Adolescence is a key period for developing bone mass, so investigators followed patients’ bone density and other measures to see if there were any long-term adverse effects.

All patients had normal whole-body and hip-bone mineral density before hormonal therapy started. Bone density gradually increased in younger patients during GnRHa treatment, but less than would be expected without GnRHa. In patients who started GnRHa at relatively older ages, bone density decreased slightly, but both groups caught up to normal or near-normal bone density once they got cross-sex hormones and developed physiologic puberty. Patients who started the medical intervention with GnRHa at a young age and, thus, an early pubertal stage, showed the best bone density, reported Dr. Henriette Delemarre-van de Waal and her associates.

"The medical intervention in young transsexuals appears to be safe and effective," said Dr. Delemarre-van de Waal, professor of pediatric endocrinology at Leiden (Netherlands) University.

Patients reported satisfaction and no regrets about GnRHa therapy, but many commented that they would have liked to take cross-sex hormones earlier than age 16, she added at a press briefing on her study. Current Dutch law and Endocrine Society guidelines for treating transgender persons, which Dr. Delemarre-van de Waal helped develop, recommend waiting until age 16 to start cross-sex hormones. Efforts are underway to talk with the Dutch government about lowering the starting age of cross-sex hormonal therapy for selected patients, she said in an interview. Puberty in European girls starts at 10-11 years of age, so starting GnRHa before age 12 and cross-sex hormones before age 16 might optimize bone mass development, "but I think we need a little more data," she said.

Neither lipid levels nor insulin sensitivity per Tanner stage were adversely affected by puberty suppression or cross-sex hormones. GnRHa therapy delayed growth not only in bone age but in height, which was a concern especially for female-to-male transitioning patients who hoped to achieve the average taller height of males. Individualizing the addition of the anabolic steroid oxandrolone to cross-sex therapy helped achieve appropriate height in these patients, and estrogen therapy in male-to-female transgender patients suppressed growth velocity in height as desired by those patients.

A separate ongoing, prospective study analyzed data from four established gender-treatment teams in Belgium, the Netherlands, Norway, and Italy on 104 transgender adults in order to increase the limited knowledge about side effects from hormonal therapy. Females transitioning to males received standardized treatment with intramuscular testosterone undecanoate for 12 weeks. Males transitioning to females who were 45 years of age or younger were treated with standardized regimens of cyproterone acetate and estradiol valerate. Older male-to-female transsexuals received cyproterone acetate and a transdermal estradiol patch.

A year after starting therapy, no patients had developed adverse events serious enough to stop therapy, reported Dr. Katrien Wierckx of Ghent (Belgium) University and her associates. There were no deaths, cardiovascular events, osteoporotic fractures, venous thrombosis, pulmonary embolism, or prolactinomas.

Female-to-male transmen reported a significant increase in sex drive, voice instability, and androgenetic alopecia. Investigators observed significant increases in acne scores and total body lean mass, lower total body fat mass, and development of a less favorable lipid profile with lower high-density lipoprotein (HDL) levels and higher triglyceride levels, Dr. Wierckx said.

Male-to-female transwomen reported a significant decrease in sex drive and significant increases in breast tenderness, emotionality, and hot flashes. The hot flashes surprised investigators because this side effect had not been reported in previous studies. Measurements showed significant gains in fat mass, losses in muscle mass, and decreased insulin sensitivity. They developed a more favorable lipid profile with significantly reduced levels of total and low-density lipoprotein (LDL) cholesterol and triglycerides.

The findings suggest that current treatment regimens for transsexual women and men carry a low risk for short-term adverse events, Dr. Wierckx said. "These results are somewhat in contrast with most previously published studies, which observed a high incidence of venous thrombosis or pulmonary embolism during the first year of treatment," she said. This may suggest that treatment regimens avoiding the use of high-dose estradiol and high-dose cyproterone acetate have less detrimental effects on the coagulation system, she suggested.

Plenty of questions remain about the long-term effects of hormonal therapy for sex transitions. "There are a lot of concerns. It’s still a controversial subject," said Dr. Delemarre-van de Waal. Effects on brain development are a key concern, but preliminary data from serial MRIs and functional MRIs of transgender patients have not produced any alarming findings, she said.

Both speakers reported having no financial disclosures.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – Hormonal therapies for transgender patients that block puberty and/or deliver opposite-sex hormones did not adversely affect bone development in adolescents and caused no serious side effects in teens or adults, two studies found.

The separate European studies, presented at the Endocrine Society Annual Meeting, looked at 127 adolescents aged 12-18 years in one study and 104 adults in the other study who were followed for 1 year after starting hormonal therapy.

The adolescents started gonadotropin-releasing hormone analogues (GnRHa) at ages 12-16 years to block production of sex hormones that initiate puberty, and at age 16 years they began receiving cross-sex hormones (either estrogen or testosterone) to induce sexual characteristics of the opposite sex to which they were transitioning. Adolescence is a key period for developing bone mass, so investigators followed patients’ bone density and other measures to see if there were any long-term adverse effects.

All patients had normal whole-body and hip-bone mineral density before hormonal therapy started. Bone density gradually increased in younger patients during GnRHa treatment, but less than would be expected without GnRHa. In patients who started GnRHa at relatively older ages, bone density decreased slightly, but both groups caught up to normal or near-normal bone density once they got cross-sex hormones and developed physiologic puberty. Patients who started the medical intervention with GnRHa at a young age and, thus, an early pubertal stage, showed the best bone density, reported Dr. Henriette Delemarre-van de Waal and her associates.

"The medical intervention in young transsexuals appears to be safe and effective," said Dr. Delemarre-van de Waal, professor of pediatric endocrinology at Leiden (Netherlands) University.

Patients reported satisfaction and no regrets about GnRHa therapy, but many commented that they would have liked to take cross-sex hormones earlier than age 16, she added at a press briefing on her study. Current Dutch law and Endocrine Society guidelines for treating transgender persons, which Dr. Delemarre-van de Waal helped develop, recommend waiting until age 16 to start cross-sex hormones. Efforts are underway to talk with the Dutch government about lowering the starting age of cross-sex hormonal therapy for selected patients, she said in an interview. Puberty in European girls starts at 10-11 years of age, so starting GnRHa before age 12 and cross-sex hormones before age 16 might optimize bone mass development, "but I think we need a little more data," she said.

Neither lipid levels nor insulin sensitivity per Tanner stage were adversely affected by puberty suppression or cross-sex hormones. GnRHa therapy delayed growth not only in bone age but in height, which was a concern especially for female-to-male transitioning patients who hoped to achieve the average taller height of males. Individualizing the addition of the anabolic steroid oxandrolone to cross-sex therapy helped achieve appropriate height in these patients, and estrogen therapy in male-to-female transgender patients suppressed growth velocity in height as desired by those patients.

A separate ongoing, prospective study analyzed data from four established gender-treatment teams in Belgium, the Netherlands, Norway, and Italy on 104 transgender adults in order to increase the limited knowledge about side effects from hormonal therapy. Females transitioning to males received standardized treatment with intramuscular testosterone undecanoate for 12 weeks. Males transitioning to females who were 45 years of age or younger were treated with standardized regimens of cyproterone acetate and estradiol valerate. Older male-to-female transsexuals received cyproterone acetate and a transdermal estradiol patch.

A year after starting therapy, no patients had developed adverse events serious enough to stop therapy, reported Dr. Katrien Wierckx of Ghent (Belgium) University and her associates. There were no deaths, cardiovascular events, osteoporotic fractures, venous thrombosis, pulmonary embolism, or prolactinomas.

Female-to-male transmen reported a significant increase in sex drive, voice instability, and androgenetic alopecia. Investigators observed significant increases in acne scores and total body lean mass, lower total body fat mass, and development of a less favorable lipid profile with lower high-density lipoprotein (HDL) levels and higher triglyceride levels, Dr. Wierckx said.

Male-to-female transwomen reported a significant decrease in sex drive and significant increases in breast tenderness, emotionality, and hot flashes. The hot flashes surprised investigators because this side effect had not been reported in previous studies. Measurements showed significant gains in fat mass, losses in muscle mass, and decreased insulin sensitivity. They developed a more favorable lipid profile with significantly reduced levels of total and low-density lipoprotein (LDL) cholesterol and triglycerides.

The findings suggest that current treatment regimens for transsexual women and men carry a low risk for short-term adverse events, Dr. Wierckx said. "These results are somewhat in contrast with most previously published studies, which observed a high incidence of venous thrombosis or pulmonary embolism during the first year of treatment," she said. This may suggest that treatment regimens avoiding the use of high-dose estradiol and high-dose cyproterone acetate have less detrimental effects on the coagulation system, she suggested.

Plenty of questions remain about the long-term effects of hormonal therapy for sex transitions. "There are a lot of concerns. It’s still a controversial subject," said Dr. Delemarre-van de Waal. Effects on brain development are a key concern, but preliminary data from serial MRIs and functional MRIs of transgender patients have not produced any alarming findings, she said.

Both speakers reported having no financial disclosures.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – Hormonal therapies for transgender patients that block puberty and/or deliver opposite-sex hormones did not adversely affect bone development in adolescents and caused no serious side effects in teens or adults, two studies found.

The separate European studies, presented at the Endocrine Society Annual Meeting, looked at 127 adolescents aged 12-18 years in one study and 104 adults in the other study who were followed for 1 year after starting hormonal therapy.

The adolescents started gonadotropin-releasing hormone analogues (GnRHa) at ages 12-16 years to block production of sex hormones that initiate puberty, and at age 16 years they began receiving cross-sex hormones (either estrogen or testosterone) to induce sexual characteristics of the opposite sex to which they were transitioning. Adolescence is a key period for developing bone mass, so investigators followed patients’ bone density and other measures to see if there were any long-term adverse effects.

All patients had normal whole-body and hip-bone mineral density before hormonal therapy started. Bone density gradually increased in younger patients during GnRHa treatment, but less than would be expected without GnRHa. In patients who started GnRHa at relatively older ages, bone density decreased slightly, but both groups caught up to normal or near-normal bone density once they got cross-sex hormones and developed physiologic puberty. Patients who started the medical intervention with GnRHa at a young age and, thus, an early pubertal stage, showed the best bone density, reported Dr. Henriette Delemarre-van de Waal and her associates.

"The medical intervention in young transsexuals appears to be safe and effective," said Dr. Delemarre-van de Waal, professor of pediatric endocrinology at Leiden (Netherlands) University.

Patients reported satisfaction and no regrets about GnRHa therapy, but many commented that they would have liked to take cross-sex hormones earlier than age 16, she added at a press briefing on her study. Current Dutch law and Endocrine Society guidelines for treating transgender persons, which Dr. Delemarre-van de Waal helped develop, recommend waiting until age 16 to start cross-sex hormones. Efforts are underway to talk with the Dutch government about lowering the starting age of cross-sex hormonal therapy for selected patients, she said in an interview. Puberty in European girls starts at 10-11 years of age, so starting GnRHa before age 12 and cross-sex hormones before age 16 might optimize bone mass development, "but I think we need a little more data," she said.

Neither lipid levels nor insulin sensitivity per Tanner stage were adversely affected by puberty suppression or cross-sex hormones. GnRHa therapy delayed growth not only in bone age but in height, which was a concern especially for female-to-male transitioning patients who hoped to achieve the average taller height of males. Individualizing the addition of the anabolic steroid oxandrolone to cross-sex therapy helped achieve appropriate height in these patients, and estrogen therapy in male-to-female transgender patients suppressed growth velocity in height as desired by those patients.

A separate ongoing, prospective study analyzed data from four established gender-treatment teams in Belgium, the Netherlands, Norway, and Italy on 104 transgender adults in order to increase the limited knowledge about side effects from hormonal therapy. Females transitioning to males received standardized treatment with intramuscular testosterone undecanoate for 12 weeks. Males transitioning to females who were 45 years of age or younger were treated with standardized regimens of cyproterone acetate and estradiol valerate. Older male-to-female transsexuals received cyproterone acetate and a transdermal estradiol patch.

A year after starting therapy, no patients had developed adverse events serious enough to stop therapy, reported Dr. Katrien Wierckx of Ghent (Belgium) University and her associates. There were no deaths, cardiovascular events, osteoporotic fractures, venous thrombosis, pulmonary embolism, or prolactinomas.

Female-to-male transmen reported a significant increase in sex drive, voice instability, and androgenetic alopecia. Investigators observed significant increases in acne scores and total body lean mass, lower total body fat mass, and development of a less favorable lipid profile with lower high-density lipoprotein (HDL) levels and higher triglyceride levels, Dr. Wierckx said.

Male-to-female transwomen reported a significant decrease in sex drive and significant increases in breast tenderness, emotionality, and hot flashes. The hot flashes surprised investigators because this side effect had not been reported in previous studies. Measurements showed significant gains in fat mass, losses in muscle mass, and decreased insulin sensitivity. They developed a more favorable lipid profile with significantly reduced levels of total and low-density lipoprotein (LDL) cholesterol and triglycerides.

The findings suggest that current treatment regimens for transsexual women and men carry a low risk for short-term adverse events, Dr. Wierckx said. "These results are somewhat in contrast with most previously published studies, which observed a high incidence of venous thrombosis or pulmonary embolism during the first year of treatment," she said. This may suggest that treatment regimens avoiding the use of high-dose estradiol and high-dose cyproterone acetate have less detrimental effects on the coagulation system, she suggested.

Plenty of questions remain about the long-term effects of hormonal therapy for sex transitions. "There are a lot of concerns. It’s still a controversial subject," said Dr. Delemarre-van de Waal. Effects on brain development are a key concern, but preliminary data from serial MRIs and functional MRIs of transgender patients have not produced any alarming findings, she said.

Both speakers reported having no financial disclosures.

[email protected]

On Twitter @sherryboschert