Mary Ann Moon

Conjugated equine estrogen raises the risk of venous thrombosis in postmenopausal women who have undergone hysterectomy, particularly within the first 2 years of starting the therapy, according to Dr. J. David Curb and his associates in the Women's Health Initiative study.

The portion of the WHI trial that was designed to determine the incidence of cardiovascular events associated with conjugated equine estrogen (CEE) therapy was terminated early because interim analysis showed that risks, particularly stroke risk, outweighed benefit. The final adjudicated data on venous thrombosis from this portion of the WHI trial has now been reported by Dr. Curb, of the University of Hawaii and the Pacific Health Research Institute, Honolulu, and his WHI associates.

In this portion of the WHI trial, 10,739 women aged 50–79 years who had undergone hysterectomy were randomly assigned to receive either 0.625 mg of CEE (Premarin) or placebo. They were followed every 6 months for a mean of 7 years.

During that time, venous thromboembolism occurred in 111 women (0.30% per year) in the CEE group and 86 women (0.22% per year) in the placebo group, with a hazard ratio (HR) of 1.32.

Deep vein thrombosis occurred in 85 women (0.23% per year) in the CEE group and 59 women (0.15% per year); the HR was 1.47. Pulmonary embolism was reported in 52 women (0.14% per year) in the CEE group and 39 women (0.10% per year) in the placebo group, for an HR of 1.37. The increased risk was highest during the first 2 years of estrogen therapy (Arch. Intern. Med. 2006;166:772–80).

“Our data suggest that although the absolute incidence is relatively low, the use of CEE increases the relative risk of venous thrombosis in postmenopausal women without a uterus. Women with appropriate indications, such as short-term treatment of severe menopausal symptoms, should use CEE only after careful consideration of the relative risks and benefits, especially if the women have other risk factors for venous thrombosis, including previous venous thrombosis, older age, obesity, and perhaps factor V Leiden,” the researchers said.

Conjugated equine estrogen raises the risk of venous thrombosis in postmenopausal women who have undergone hysterectomy, particularly within the first 2 years of starting the therapy, according to Dr. J. David Curb and his associates in the Women's Health Initiative study.

The portion of the WHI trial that was designed to determine the incidence of cardiovascular events associated with conjugated equine estrogen (CEE) therapy was terminated early because interim analysis showed that risks, particularly stroke risk, outweighed benefit. The final adjudicated data on venous thrombosis from this portion of the WHI trial has now been reported by Dr. Curb, of the University of Hawaii and the Pacific Health Research Institute, Honolulu, and his WHI associates.

In this portion of the WHI trial, 10,739 women aged 50–79 years who had undergone hysterectomy were randomly assigned to receive either 0.625 mg of CEE (Premarin) or placebo. They were followed every 6 months for a mean of 7 years.

During that time, venous thromboembolism occurred in 111 women (0.30% per year) in the CEE group and 86 women (0.22% per year) in the placebo group, with a hazard ratio (HR) of 1.32.

Deep vein thrombosis occurred in 85 women (0.23% per year) in the CEE group and 59 women (0.15% per year); the HR was 1.47. Pulmonary embolism was reported in 52 women (0.14% per year) in the CEE group and 39 women (0.10% per year) in the placebo group, for an HR of 1.37. The increased risk was highest during the first 2 years of estrogen therapy (Arch. Intern. Med. 2006;166:772–80).

“Our data suggest that although the absolute incidence is relatively low, the use of CEE increases the relative risk of venous thrombosis in postmenopausal women without a uterus. Women with appropriate indications, such as short-term treatment of severe menopausal symptoms, should use CEE only after careful consideration of the relative risks and benefits, especially if the women have other risk factors for venous thrombosis, including previous venous thrombosis, older age, obesity, and perhaps factor V Leiden,” the researchers said.

Conjugated equine estrogen raises the risk of venous thrombosis in postmenopausal women who have undergone hysterectomy, particularly within the first 2 years of starting the therapy, according to Dr. J. David Curb and his associates in the Women's Health Initiative study.

The portion of the WHI trial that was designed to determine the incidence of cardiovascular events associated with conjugated equine estrogen (CEE) therapy was terminated early because interim analysis showed that risks, particularly stroke risk, outweighed benefit. The final adjudicated data on venous thrombosis from this portion of the WHI trial has now been reported by Dr. Curb, of the University of Hawaii and the Pacific Health Research Institute, Honolulu, and his WHI associates.

In this portion of the WHI trial, 10,739 women aged 50–79 years who had undergone hysterectomy were randomly assigned to receive either 0.625 mg of CEE (Premarin) or placebo. They were followed every 6 months for a mean of 7 years.

During that time, venous thromboembolism occurred in 111 women (0.30% per year) in the CEE group and 86 women (0.22% per year) in the placebo group, with a hazard ratio (HR) of 1.32.

Deep vein thrombosis occurred in 85 women (0.23% per year) in the CEE group and 59 women (0.15% per year); the HR was 1.47. Pulmonary embolism was reported in 52 women (0.14% per year) in the CEE group and 39 women (0.10% per year) in the placebo group, for an HR of 1.37. The increased risk was highest during the first 2 years of estrogen therapy (Arch. Intern. Med. 2006;166:772–80).

“Our data suggest that although the absolute incidence is relatively low, the use of CEE increases the relative risk of venous thrombosis in postmenopausal women without a uterus. Women with appropriate indications, such as short-term treatment of severe menopausal symptoms, should use CEE only after careful consideration of the relative risks and benefits, especially if the women have other risk factors for venous thrombosis, including previous venous thrombosis, older age, obesity, and perhaps factor V Leiden,” the researchers said.

The “changing hormonal milieu” of menopause is strongly associated with new-onset major depression as well as depressive symptoms in women with no history of mood disturbance, reported Ellen W. Freeman, Ph.D., of the departments of ob.gyn. and psychiatry at the University of Pennsylvania, Philadelphia, and her associates in the Penn Ovarian Aging Study.

Women are significantly more likely to develop a depressive disorder when their levels of estradiol fluctuate, levels of FSH and LH increase, and levels of inhibin B decrease, as happens during the transition to menopause. It appears that the hormonal changes characteristic of ovarian aging produce “destabilizing effects” that contribute to depression, the investigators said.

This finding should make a substantial contribution to what has been only “limited evidence” in the literature about mood symptoms in the perimenopausal years.

“Whether mood symptoms increase in the perimenopausal years and whether the occurrence of depressed mood is independently associated with ovarian changes or is secondary to vasomotor or other bothersome symptoms” has been controversial, they noted.

Dr. Freeman and her associates examined the issue by assessing fluctuations in reproductive hormone levels in 231 premenopausal women aged 35–47 years at baseline who were followed for 8 years. During that interval, 43% of the women entered the transition to menopause.

Hormone assays were conducted in 10 assessment periods, the first 6 at 8-month intervals. Blood samples were collected at the start of menstrual cycles, and subjects also were interviewed concerning their overall health, demographic factors, and menopausal symptoms.

Depressive symptoms were assessed using the CES-D (Center for Epidemiological Studies-Depression) scale; either the PRIME-MD (Primary Care Evaluation of Mental Disorders) or the PHQ (Patient Health Questionnaire) was used to detect major depressive disorder.

A total of 116 women (50%) was found to have depressive symptoms on the CES-D during follow-up.

Of these, 16 women had depressive symptoms on two consecutive assessments and 35 had them on three or more consecutive assessments.

Of the 231 women, 59 (26%) were found to have depressive disorders on the PRIME-MD or PHQ; 26 had major depressive disorder and 33 had other depressive disorders. Nine of the women had depressive disorders on two consecutive assessments and four had them on three or more consecutive assessments.

A total of 108 women (47%) showed no depressive symptoms on either measure, the researchers said (Arch. Gen. Psychiatry 2006;63:375–82).

Changes in individual women's levels of FSH, LH, and inhibin B were significantly associated with depressive symptoms and with major depression.

Similarly, variability in a woman's mean levels of estradiol, FSH, and LH also were linked to depression and depressive symptoms.

“On average, the women were 4.58 times more likely to have higher FSH levels … 3 times more likely to have higher LH levels … and 63% more likely to have lower inhibin B levels … at the time of high [depression] scores” compared with the time before high scores, the investigators said.

After the data were adjusted for several other depression risk factors, including change in employment status or marital status, the researchers found that a woman was, on average, more than five times “more likely to be in menopausal transition at the time of reporting high [depression] scores than she was before the onset of depressive symptoms.”

The “strongest risk factor for the new onset of diagnosed depressive disorders was the increased variability of estradiol (around the woman's own mean levels) at the time of the diagnosed disorder,” Dr. Freeman and her associates said.

However, other health and demographic factors also significantly affected depression risk, “confirming … the multifactorial nature of depressive symptoms.” These factors included hot flashes, body mass index, smoking status, and the presence or absence of PMS.

The researchers also observed that onsets of both major depression and depressive symptoms were more common in the earlier years of their study, raising the question of “whether [depressed] women entered the menopausal transition at an earlier age.” The study couldn't answer that question because it was “designed to examine all women starting at a similar premenopausal baseline,” they noted.

The strongest risk factor for new-onset depression was increased variability of estradiol at the time of diagnosis. DR. FREEMAN

The “changing hormonal milieu” of menopause is strongly associated with new-onset major depression as well as depressive symptoms in women with no history of mood disturbance, reported Ellen W. Freeman, Ph.D., of the departments of ob.gyn. and psychiatry at the University of Pennsylvania, Philadelphia, and her associates in the Penn Ovarian Aging Study.

Women are significantly more likely to develop a depressive disorder when their levels of estradiol fluctuate, levels of FSH and LH increase, and levels of inhibin B decrease, as happens during the transition to menopause. It appears that the hormonal changes characteristic of ovarian aging produce “destabilizing effects” that contribute to depression, the investigators said.

This finding should make a substantial contribution to what has been only “limited evidence” in the literature about mood symptoms in the perimenopausal years.

“Whether mood symptoms increase in the perimenopausal years and whether the occurrence of depressed mood is independently associated with ovarian changes or is secondary to vasomotor or other bothersome symptoms” has been controversial, they noted.

Dr. Freeman and her associates examined the issue by assessing fluctuations in reproductive hormone levels in 231 premenopausal women aged 35–47 years at baseline who were followed for 8 years. During that interval, 43% of the women entered the transition to menopause.

Hormone assays were conducted in 10 assessment periods, the first 6 at 8-month intervals. Blood samples were collected at the start of menstrual cycles, and subjects also were interviewed concerning their overall health, demographic factors, and menopausal symptoms.

Depressive symptoms were assessed using the CES-D (Center for Epidemiological Studies-Depression) scale; either the PRIME-MD (Primary Care Evaluation of Mental Disorders) or the PHQ (Patient Health Questionnaire) was used to detect major depressive disorder.

A total of 116 women (50%) was found to have depressive symptoms on the CES-D during follow-up.

Of these, 16 women had depressive symptoms on two consecutive assessments and 35 had them on three or more consecutive assessments.

Of the 231 women, 59 (26%) were found to have depressive disorders on the PRIME-MD or PHQ; 26 had major depressive disorder and 33 had other depressive disorders. Nine of the women had depressive disorders on two consecutive assessments and four had them on three or more consecutive assessments.

A total of 108 women (47%) showed no depressive symptoms on either measure, the researchers said (Arch. Gen. Psychiatry 2006;63:375–82).

Changes in individual women's levels of FSH, LH, and inhibin B were significantly associated with depressive symptoms and with major depression.

Similarly, variability in a woman's mean levels of estradiol, FSH, and LH also were linked to depression and depressive symptoms.

“On average, the women were 4.58 times more likely to have higher FSH levels … 3 times more likely to have higher LH levels … and 63% more likely to have lower inhibin B levels … at the time of high [depression] scores” compared with the time before high scores, the investigators said.

After the data were adjusted for several other depression risk factors, including change in employment status or marital status, the researchers found that a woman was, on average, more than five times “more likely to be in menopausal transition at the time of reporting high [depression] scores than she was before the onset of depressive symptoms.”

The “strongest risk factor for the new onset of diagnosed depressive disorders was the increased variability of estradiol (around the woman's own mean levels) at the time of the diagnosed disorder,” Dr. Freeman and her associates said.

However, other health and demographic factors also significantly affected depression risk, “confirming … the multifactorial nature of depressive symptoms.” These factors included hot flashes, body mass index, smoking status, and the presence or absence of PMS.

The researchers also observed that onsets of both major depression and depressive symptoms were more common in the earlier years of their study, raising the question of “whether [depressed] women entered the menopausal transition at an earlier age.” The study couldn't answer that question because it was “designed to examine all women starting at a similar premenopausal baseline,” they noted.

The strongest risk factor for new-onset depression was increased variability of estradiol at the time of diagnosis. DR. FREEMAN

The “changing hormonal milieu” of menopause is strongly associated with new-onset major depression as well as depressive symptoms in women with no history of mood disturbance, reported Ellen W. Freeman, Ph.D., of the departments of ob.gyn. and psychiatry at the University of Pennsylvania, Philadelphia, and her associates in the Penn Ovarian Aging Study.

Women are significantly more likely to develop a depressive disorder when their levels of estradiol fluctuate, levels of FSH and LH increase, and levels of inhibin B decrease, as happens during the transition to menopause. It appears that the hormonal changes characteristic of ovarian aging produce “destabilizing effects” that contribute to depression, the investigators said.

This finding should make a substantial contribution to what has been only “limited evidence” in the literature about mood symptoms in the perimenopausal years.

“Whether mood symptoms increase in the perimenopausal years and whether the occurrence of depressed mood is independently associated with ovarian changes or is secondary to vasomotor or other bothersome symptoms” has been controversial, they noted.

Dr. Freeman and her associates examined the issue by assessing fluctuations in reproductive hormone levels in 231 premenopausal women aged 35–47 years at baseline who were followed for 8 years. During that interval, 43% of the women entered the transition to menopause.

Hormone assays were conducted in 10 assessment periods, the first 6 at 8-month intervals. Blood samples were collected at the start of menstrual cycles, and subjects also were interviewed concerning their overall health, demographic factors, and menopausal symptoms.

Depressive symptoms were assessed using the CES-D (Center for Epidemiological Studies-Depression) scale; either the PRIME-MD (Primary Care Evaluation of Mental Disorders) or the PHQ (Patient Health Questionnaire) was used to detect major depressive disorder.

A total of 116 women (50%) was found to have depressive symptoms on the CES-D during follow-up.

Of these, 16 women had depressive symptoms on two consecutive assessments and 35 had them on three or more consecutive assessments.

Of the 231 women, 59 (26%) were found to have depressive disorders on the PRIME-MD or PHQ; 26 had major depressive disorder and 33 had other depressive disorders. Nine of the women had depressive disorders on two consecutive assessments and four had them on three or more consecutive assessments.

A total of 108 women (47%) showed no depressive symptoms on either measure, the researchers said (Arch. Gen. Psychiatry 2006;63:375–82).

Changes in individual women's levels of FSH, LH, and inhibin B were significantly associated with depressive symptoms and with major depression.

Similarly, variability in a woman's mean levels of estradiol, FSH, and LH also were linked to depression and depressive symptoms.

“On average, the women were 4.58 times more likely to have higher FSH levels … 3 times more likely to have higher LH levels … and 63% more likely to have lower inhibin B levels … at the time of high [depression] scores” compared with the time before high scores, the investigators said.

After the data were adjusted for several other depression risk factors, including change in employment status or marital status, the researchers found that a woman was, on average, more than five times “more likely to be in menopausal transition at the time of reporting high [depression] scores than she was before the onset of depressive symptoms.”

The “strongest risk factor for the new onset of diagnosed depressive disorders was the increased variability of estradiol (around the woman's own mean levels) at the time of the diagnosed disorder,” Dr. Freeman and her associates said.

However, other health and demographic factors also significantly affected depression risk, “confirming … the multifactorial nature of depressive symptoms.” These factors included hot flashes, body mass index, smoking status, and the presence or absence of PMS.

The researchers also observed that onsets of both major depression and depressive symptoms were more common in the earlier years of their study, raising the question of “whether [depressed] women entered the menopausal transition at an earlier age.” The study couldn't answer that question because it was “designed to examine all women starting at a similar premenopausal baseline,” they noted.

The strongest risk factor for new-onset depression was increased variability of estradiol at the time of diagnosis. DR. FREEMAN

Women entering menopause are nearly twice as likely to develop depression as are women the same age who are not yet making the transition to menopause, reported Dr. Lee S. Cohen and his associates in the Harvard Study of Moods and Cycles.

“Transition to menopause has long been considered a period of increased risk for depressive symptoms,” Dr. Cohen and his colleagues wrote, but studies on the issue have yielded conflicting results. This is partly because of methodological inconsistencies, including a tendency to define menopause based on questionable criteria such as the subjects' age alone, and the lack of standardized assessment of psychiatric symptoms, the researchers said.

In contrast, their study involved a population-based, cross-sectional sample of women aged 36 to 45 years who were prospectively followed every 6 months for several years.

Changes in menstrual cycle length and menstrual flow amount and duration were carefully tracked, and depressive symptoms were assessed using the Structured Clinical Interview for DSM-IV, as well as the Center for Epidemiologic Studies Depression Scale. Significant adverse life experiences and vasomotor symptoms also were assessed, said Dr. Cohen and his associates at Harvard Medical School, Massachusetts General Hospital, and Brigham and Women's Hospital, all in Boston.

The 460 study subjects had no history of major depression. A total of 134 were still premenopausal at the end of the last follow-up period, which occurred between 59 and 92 months after study enrollment. The remaining 326 women had entered menopause during that interval.

The rate of new-onset major depression was 16.6% in the menopausal women, compared with 9.5% in those who had not yet entered menopause, after the data had been adjusted to account for age at study enrollment and history of negative life events. “To our knowledge, this prospective documentation of increased risk for depression among women without a history of depression is unique,” the investigators said (Arch. Gen. Psychiatry 2006;63:385–90).

This correlation between onset of depression and transition to menopause was noted both in women who used hormone therapy and in those who did not.

New-onset depression was more likely to develop in women who reported vasomotor symptoms than in those who did not. This association between depression and vasomotor symptoms is not yet fully understood. It is possible that hot flushes disrupt sleep “enough to adversely affect daytime functioning and to impact quality of life.” Alternatively, “abrupt changes in neuromodulatory function and/or in reproductive-hormone levels could contribute to the constellation of mood and vasomotor symptoms,” Dr. Cohen and his associates said.

Abrupt changes in hormone levels could contribute to mood and vasomotor symptoms. DR. COHEN

Women entering menopause are nearly twice as likely to develop depression as are women the same age who are not yet making the transition to menopause, reported Dr. Lee S. Cohen and his associates in the Harvard Study of Moods and Cycles.

“Transition to menopause has long been considered a period of increased risk for depressive symptoms,” Dr. Cohen and his colleagues wrote, but studies on the issue have yielded conflicting results. This is partly because of methodological inconsistencies, including a tendency to define menopause based on questionable criteria such as the subjects' age alone, and the lack of standardized assessment of psychiatric symptoms, the researchers said.

In contrast, their study involved a population-based, cross-sectional sample of women aged 36 to 45 years who were prospectively followed every 6 months for several years.

Changes in menstrual cycle length and menstrual flow amount and duration were carefully tracked, and depressive symptoms were assessed using the Structured Clinical Interview for DSM-IV, as well as the Center for Epidemiologic Studies Depression Scale. Significant adverse life experiences and vasomotor symptoms also were assessed, said Dr. Cohen and his associates at Harvard Medical School, Massachusetts General Hospital, and Brigham and Women's Hospital, all in Boston.

The 460 study subjects had no history of major depression. A total of 134 were still premenopausal at the end of the last follow-up period, which occurred between 59 and 92 months after study enrollment. The remaining 326 women had entered menopause during that interval.

The rate of new-onset major depression was 16.6% in the menopausal women, compared with 9.5% in those who had not yet entered menopause, after the data had been adjusted to account for age at study enrollment and history of negative life events. “To our knowledge, this prospective documentation of increased risk for depression among women without a history of depression is unique,” the investigators said (Arch. Gen. Psychiatry 2006;63:385–90).

This correlation between onset of depression and transition to menopause was noted both in women who used hormone therapy and in those who did not.

New-onset depression was more likely to develop in women who reported vasomotor symptoms than in those who did not. This association between depression and vasomotor symptoms is not yet fully understood. It is possible that hot flushes disrupt sleep “enough to adversely affect daytime functioning and to impact quality of life.” Alternatively, “abrupt changes in neuromodulatory function and/or in reproductive-hormone levels could contribute to the constellation of mood and vasomotor symptoms,” Dr. Cohen and his associates said.

Abrupt changes in hormone levels could contribute to mood and vasomotor symptoms. DR. COHEN

Women entering menopause are nearly twice as likely to develop depression as are women the same age who are not yet making the transition to menopause, reported Dr. Lee S. Cohen and his associates in the Harvard Study of Moods and Cycles.

“Transition to menopause has long been considered a period of increased risk for depressive symptoms,” Dr. Cohen and his colleagues wrote, but studies on the issue have yielded conflicting results. This is partly because of methodological inconsistencies, including a tendency to define menopause based on questionable criteria such as the subjects' age alone, and the lack of standardized assessment of psychiatric symptoms, the researchers said.

In contrast, their study involved a population-based, cross-sectional sample of women aged 36 to 45 years who were prospectively followed every 6 months for several years.

Changes in menstrual cycle length and menstrual flow amount and duration were carefully tracked, and depressive symptoms were assessed using the Structured Clinical Interview for DSM-IV, as well as the Center for Epidemiologic Studies Depression Scale. Significant adverse life experiences and vasomotor symptoms also were assessed, said Dr. Cohen and his associates at Harvard Medical School, Massachusetts General Hospital, and Brigham and Women's Hospital, all in Boston.

The 460 study subjects had no history of major depression. A total of 134 were still premenopausal at the end of the last follow-up period, which occurred between 59 and 92 months after study enrollment. The remaining 326 women had entered menopause during that interval.

The rate of new-onset major depression was 16.6% in the menopausal women, compared with 9.5% in those who had not yet entered menopause, after the data had been adjusted to account for age at study enrollment and history of negative life events. “To our knowledge, this prospective documentation of increased risk for depression among women without a history of depression is unique,” the investigators said (Arch. Gen. Psychiatry 2006;63:385–90).

This correlation between onset of depression and transition to menopause was noted both in women who used hormone therapy and in those who did not.

New-onset depression was more likely to develop in women who reported vasomotor symptoms than in those who did not. This association between depression and vasomotor symptoms is not yet fully understood. It is possible that hot flushes disrupt sleep “enough to adversely affect daytime functioning and to impact quality of life.” Alternatively, “abrupt changes in neuromodulatory function and/or in reproductive-hormone levels could contribute to the constellation of mood and vasomotor symptoms,” Dr. Cohen and his associates said.

Abrupt changes in hormone levels could contribute to mood and vasomotor symptoms. DR. COHEN

The “changing hormonal milieu” of menopause is strongly associated with new-onset major depression as well as depressive symptoms in women with no history of mood disturbance, reported Ellen W. Freeman, Ph.D., of the departments of ob.gyn. and psychiatry at the University of Pennsylvania, Philadelphia, and her associates.

Women are significantly more likely to develop a depressive disorder when their levels of estradiol fluctuate, levels of FSH and LH increase, and levels of inhibin B decrease, as happens during the transition to menopause. It appears that the hormonal changes characteristic of ovarian aging produce “destabilizing effects” that contribute to depression, Dr. Freeman and her associates in the Penn Ovarian Aging Study commented.

This finding should make a substantial contribution to what has been only “limited evidence” in the literature about mood symptoms in the perimenopausal years. “Whether mood symptoms increase in the perimenopausal years and whether the occurrence of depressed mood is independently associated with ovarian changes or is secondary to vasomotor or other bothersome symptoms” has been controversial, they noted.

Dr. Freeman and her associates examined the issue by assessing fluctuations in reproductive hormone levels in 231 premenopausal women aged 35–47 years at baseline who were followed for 8 years. During that interval, 43% of the women entered the transition to menopause.

Hormone assays were conducted in 10 assessment periods, the first 6 at 8-month intervals. Blood samples were collected at the start of menstrual cycles, and subjects also were interviewed concerning their overall health, demographic factors, and menopausal symptoms. Depressive symptoms were assessed using the CES-D (Center for Epidemiological Studies-Depression) scale; either the PRIME-MD (Primary Care Evaluation of Mental Disorders) or the PHQ (Patient Health Questionnaire) was used to detect major depressive disorder.

A total of 116 women (50%) was found to have depressive symptoms on the CES-D during follow-up. Of these, 16 women had depressive symptoms on two consecutive assessments and 35 had them on three or more consecutive assessments.

Of the 231 women, 59 (26%) were found to have depressive disorders on the PRIME-MD or PHQ; 26 had major depressive disorder and 33 had other depressive disorders. Nine of the women had depressive disorders on two consecutive assessments and four had them on three or more consecutive assessments.

A total of 108 women (47%) showed no depressive symptoms on either measure, the researchers said (Arch. Gen. Psychiatry 2006;63:375–82).

Changes in individual women's levels of FSH, LH, and inhibin B were significantly associated with depressive symptoms and with major depression. Similarly, variability in a woman's mean levels of estradiol, FSH, and LH also were linked to depression and depressive symptoms. “On average, the women were 4.58 times more likely to have higher FSH levels … 3 times more likely to have higher LH levels … and 63% more likely to have lower inhibin B levels … at the time of high [depression] scores” compared with the time before high scores, the investigators wrote.

After the data were adjusted for several other depression risk factors, including change in employment status or marital status, the researchers found that a woman was, on average, more than five times “more likely to be in menopausal transition at the time of reporting high [depression] scores than she was before the onset of depressive symptoms.”

The “strongest risk factor for the new onset of diagnosed depressive disorders was the increased variability of estradiol (around the woman's own mean levels) at the time of the diagnosed disorder,” Dr. Freeman and her associates said.

Changes in levels of FSH, LH, and inhibin B were associated with depressive symptoms. DR. FREEMAN

The “changing hormonal milieu” of menopause is strongly associated with new-onset major depression as well as depressive symptoms in women with no history of mood disturbance, reported Ellen W. Freeman, Ph.D., of the departments of ob.gyn. and psychiatry at the University of Pennsylvania, Philadelphia, and her associates.

Women are significantly more likely to develop a depressive disorder when their levels of estradiol fluctuate, levels of FSH and LH increase, and levels of inhibin B decrease, as happens during the transition to menopause. It appears that the hormonal changes characteristic of ovarian aging produce “destabilizing effects” that contribute to depression, Dr. Freeman and her associates in the Penn Ovarian Aging Study commented.

This finding should make a substantial contribution to what has been only “limited evidence” in the literature about mood symptoms in the perimenopausal years. “Whether mood symptoms increase in the perimenopausal years and whether the occurrence of depressed mood is independently associated with ovarian changes or is secondary to vasomotor or other bothersome symptoms” has been controversial, they noted.

Dr. Freeman and her associates examined the issue by assessing fluctuations in reproductive hormone levels in 231 premenopausal women aged 35–47 years at baseline who were followed for 8 years. During that interval, 43% of the women entered the transition to menopause.

Hormone assays were conducted in 10 assessment periods, the first 6 at 8-month intervals. Blood samples were collected at the start of menstrual cycles, and subjects also were interviewed concerning their overall health, demographic factors, and menopausal symptoms. Depressive symptoms were assessed using the CES-D (Center for Epidemiological Studies-Depression) scale; either the PRIME-MD (Primary Care Evaluation of Mental Disorders) or the PHQ (Patient Health Questionnaire) was used to detect major depressive disorder.

A total of 116 women (50%) was found to have depressive symptoms on the CES-D during follow-up. Of these, 16 women had depressive symptoms on two consecutive assessments and 35 had them on three or more consecutive assessments.

Of the 231 women, 59 (26%) were found to have depressive disorders on the PRIME-MD or PHQ; 26 had major depressive disorder and 33 had other depressive disorders. Nine of the women had depressive disorders on two consecutive assessments and four had them on three or more consecutive assessments.

A total of 108 women (47%) showed no depressive symptoms on either measure, the researchers said (Arch. Gen. Psychiatry 2006;63:375–82).

Changes in individual women's levels of FSH, LH, and inhibin B were significantly associated with depressive symptoms and with major depression. Similarly, variability in a woman's mean levels of estradiol, FSH, and LH also were linked to depression and depressive symptoms. “On average, the women were 4.58 times more likely to have higher FSH levels … 3 times more likely to have higher LH levels … and 63% more likely to have lower inhibin B levels … at the time of high [depression] scores” compared with the time before high scores, the investigators wrote.

After the data were adjusted for several other depression risk factors, including change in employment status or marital status, the researchers found that a woman was, on average, more than five times “more likely to be in menopausal transition at the time of reporting high [depression] scores than she was before the onset of depressive symptoms.”

The “strongest risk factor for the new onset of diagnosed depressive disorders was the increased variability of estradiol (around the woman's own mean levels) at the time of the diagnosed disorder,” Dr. Freeman and her associates said.

Changes in levels of FSH, LH, and inhibin B were associated with depressive symptoms. DR. FREEMAN

The “changing hormonal milieu” of menopause is strongly associated with new-onset major depression as well as depressive symptoms in women with no history of mood disturbance, reported Ellen W. Freeman, Ph.D., of the departments of ob.gyn. and psychiatry at the University of Pennsylvania, Philadelphia, and her associates.

Women are significantly more likely to develop a depressive disorder when their levels of estradiol fluctuate, levels of FSH and LH increase, and levels of inhibin B decrease, as happens during the transition to menopause. It appears that the hormonal changes characteristic of ovarian aging produce “destabilizing effects” that contribute to depression, Dr. Freeman and her associates in the Penn Ovarian Aging Study commented.

This finding should make a substantial contribution to what has been only “limited evidence” in the literature about mood symptoms in the perimenopausal years. “Whether mood symptoms increase in the perimenopausal years and whether the occurrence of depressed mood is independently associated with ovarian changes or is secondary to vasomotor or other bothersome symptoms” has been controversial, they noted.

Dr. Freeman and her associates examined the issue by assessing fluctuations in reproductive hormone levels in 231 premenopausal women aged 35–47 years at baseline who were followed for 8 years. During that interval, 43% of the women entered the transition to menopause.

Hormone assays were conducted in 10 assessment periods, the first 6 at 8-month intervals. Blood samples were collected at the start of menstrual cycles, and subjects also were interviewed concerning their overall health, demographic factors, and menopausal symptoms. Depressive symptoms were assessed using the CES-D (Center for Epidemiological Studies-Depression) scale; either the PRIME-MD (Primary Care Evaluation of Mental Disorders) or the PHQ (Patient Health Questionnaire) was used to detect major depressive disorder.

A total of 116 women (50%) was found to have depressive symptoms on the CES-D during follow-up. Of these, 16 women had depressive symptoms on two consecutive assessments and 35 had them on three or more consecutive assessments.

Of the 231 women, 59 (26%) were found to have depressive disorders on the PRIME-MD or PHQ; 26 had major depressive disorder and 33 had other depressive disorders. Nine of the women had depressive disorders on two consecutive assessments and four had them on three or more consecutive assessments.

A total of 108 women (47%) showed no depressive symptoms on either measure, the researchers said (Arch. Gen. Psychiatry 2006;63:375–82).

Changes in individual women's levels of FSH, LH, and inhibin B were significantly associated with depressive symptoms and with major depression. Similarly, variability in a woman's mean levels of estradiol, FSH, and LH also were linked to depression and depressive symptoms. “On average, the women were 4.58 times more likely to have higher FSH levels … 3 times more likely to have higher LH levels … and 63% more likely to have lower inhibin B levels … at the time of high [depression] scores” compared with the time before high scores, the investigators wrote.

After the data were adjusted for several other depression risk factors, including change in employment status or marital status, the researchers found that a woman was, on average, more than five times “more likely to be in menopausal transition at the time of reporting high [depression] scores than she was before the onset of depressive symptoms.”

The “strongest risk factor for the new onset of diagnosed depressive disorders was the increased variability of estradiol (around the woman's own mean levels) at the time of the diagnosed disorder,” Dr. Freeman and her associates said.

Changes in levels of FSH, LH, and inhibin B were associated with depressive symptoms. DR. FREEMAN

Three additional cases of Guillain-Barré syndrome related to the Menactra MCV4 meningococcal conjugate vaccine have been reported, according to the Centers for Disease Control and Prevention, Atlanta.

Even with these additional cases, the incidence of this adverse effect does not exceed the incidence that might be expected to occur by chance alone, so the CDC has not changed its recommendations regarding the vaccine.

However, the timing of the onset of Guillain-Barré syndrome (GBS) within 2–5 weeks of vaccination “is still a concern,” so monitoring continues and controlled clinical trials are planned, the CDC said.

Clinicians are advised to share information about the CDC investigation with adolescents and parents before administering the vaccine.

Fact sheets for patients and those for health-care workers are available at www.cdc.gov

The CDC alerted physicians to a possible association between the Menactra MCV4 vaccine and GBS in October 2005, based on five cases in teenagers that were reported to the Vaccine Adverse Events Reporting System.

The vaccine manufacturer, Sanofi Pasteur Inc., and the Food and Drug Administration updated the package insert, listing previous GBS as a new contraindication to the vaccine and warning clinicians of a possible temporal relation with GBS.

At that time the CDC and the FDA also advised clinicians to report any cases of GBS occurring in patients who had received the vaccine.

As of February 2006, three additional cases had been reported to VAERS and confirmed.

GBS, a serious neurologic disorder involving demyelination of the peripheral nerves, is characterized by numbness or tingling in the feet or hands which often progresses to the legs and arms and is accompanied by muscle weakness or paralysis and loss of deep tendon reflexes.

The CDC provided details on two of the three newly reported cases that occurred since October 2005. Both involved teenage males who were hospitalized and treated with intravenous immunoglobulin. Both patients recovered fully (MMWR 2006;255:364–6).

The third case is undergoing detailed clinical investigation but meets the provisional case definition for GBS, the CDC said.

The CDC continues to advise that people with a history of GBS should not be vaccinated with the Menactra MCV4 vaccine unless they are at high risk for meningococcal disease.

The vaccine is still recommended for others at risk, including first-year college students, military recruits, travelers, scientists who are exposed to meningitis, patients with anatomic or functional asplenia, and patients with terminal complement deficiency.

Also, in February 2005, the Advisory Committee on Immunization Practices recommended routine vaccination of adolescents at the preadolescent health care visit (at ages 11–12 years).

For persons not previously vaccinated, the committee recommended vaccination before high-school entry (at approximately age 15 years).

To report adverse events related to the MCV4 vaccine or any other vaccine, clinicians should go to www.vaers.hhs.gov

Three additional cases of Guillain-Barré syndrome related to the Menactra MCV4 meningococcal conjugate vaccine have been reported, according to the Centers for Disease Control and Prevention, Atlanta.

Even with these additional cases, the incidence of this adverse effect does not exceed the incidence that might be expected to occur by chance alone, so the CDC has not changed its recommendations regarding the vaccine.

However, the timing of the onset of Guillain-Barré syndrome (GBS) within 2–5 weeks of vaccination “is still a concern,” so monitoring continues and controlled clinical trials are planned, the CDC said.

Clinicians are advised to share information about the CDC investigation with adolescents and parents before administering the vaccine.

Fact sheets for patients and those for health-care workers are available at www.cdc.gov

The CDC alerted physicians to a possible association between the Menactra MCV4 vaccine and GBS in October 2005, based on five cases in teenagers that were reported to the Vaccine Adverse Events Reporting System.

The vaccine manufacturer, Sanofi Pasteur Inc., and the Food and Drug Administration updated the package insert, listing previous GBS as a new contraindication to the vaccine and warning clinicians of a possible temporal relation with GBS.

At that time the CDC and the FDA also advised clinicians to report any cases of GBS occurring in patients who had received the vaccine.

As of February 2006, three additional cases had been reported to VAERS and confirmed.

GBS, a serious neurologic disorder involving demyelination of the peripheral nerves, is characterized by numbness or tingling in the feet or hands which often progresses to the legs and arms and is accompanied by muscle weakness or paralysis and loss of deep tendon reflexes.

The CDC provided details on two of the three newly reported cases that occurred since October 2005. Both involved teenage males who were hospitalized and treated with intravenous immunoglobulin. Both patients recovered fully (MMWR 2006;255:364–6).

The third case is undergoing detailed clinical investigation but meets the provisional case definition for GBS, the CDC said.

The CDC continues to advise that people with a history of GBS should not be vaccinated with the Menactra MCV4 vaccine unless they are at high risk for meningococcal disease.

The vaccine is still recommended for others at risk, including first-year college students, military recruits, travelers, scientists who are exposed to meningitis, patients with anatomic or functional asplenia, and patients with terminal complement deficiency.

Also, in February 2005, the Advisory Committee on Immunization Practices recommended routine vaccination of adolescents at the preadolescent health care visit (at ages 11–12 years).

For persons not previously vaccinated, the committee recommended vaccination before high-school entry (at approximately age 15 years).

To report adverse events related to the MCV4 vaccine or any other vaccine, clinicians should go to www.vaers.hhs.gov

Three additional cases of Guillain-Barré syndrome related to the Menactra MCV4 meningococcal conjugate vaccine have been reported, according to the Centers for Disease Control and Prevention, Atlanta.

Even with these additional cases, the incidence of this adverse effect does not exceed the incidence that might be expected to occur by chance alone, so the CDC has not changed its recommendations regarding the vaccine.

However, the timing of the onset of Guillain-Barré syndrome (GBS) within 2–5 weeks of vaccination “is still a concern,” so monitoring continues and controlled clinical trials are planned, the CDC said.

Clinicians are advised to share information about the CDC investigation with adolescents and parents before administering the vaccine.

Fact sheets for patients and those for health-care workers are available at www.cdc.gov

The CDC alerted physicians to a possible association between the Menactra MCV4 vaccine and GBS in October 2005, based on five cases in teenagers that were reported to the Vaccine Adverse Events Reporting System.

The vaccine manufacturer, Sanofi Pasteur Inc., and the Food and Drug Administration updated the package insert, listing previous GBS as a new contraindication to the vaccine and warning clinicians of a possible temporal relation with GBS.

At that time the CDC and the FDA also advised clinicians to report any cases of GBS occurring in patients who had received the vaccine.

As of February 2006, three additional cases had been reported to VAERS and confirmed.

GBS, a serious neurologic disorder involving demyelination of the peripheral nerves, is characterized by numbness or tingling in the feet or hands which often progresses to the legs and arms and is accompanied by muscle weakness or paralysis and loss of deep tendon reflexes.

The CDC provided details on two of the three newly reported cases that occurred since October 2005. Both involved teenage males who were hospitalized and treated with intravenous immunoglobulin. Both patients recovered fully (MMWR 2006;255:364–6).

The third case is undergoing detailed clinical investigation but meets the provisional case definition for GBS, the CDC said.

The CDC continues to advise that people with a history of GBS should not be vaccinated with the Menactra MCV4 vaccine unless they are at high risk for meningococcal disease.

The vaccine is still recommended for others at risk, including first-year college students, military recruits, travelers, scientists who are exposed to meningitis, patients with anatomic or functional asplenia, and patients with terminal complement deficiency.

Also, in February 2005, the Advisory Committee on Immunization Practices recommended routine vaccination of adolescents at the preadolescent health care visit (at ages 11–12 years).

For persons not previously vaccinated, the committee recommended vaccination before high-school entry (at approximately age 15 years).

To report adverse events related to the MCV4 vaccine or any other vaccine, clinicians should go to www.vaers.hhs.gov

Women entering menopause are nearly twice as likely to develop depression as are women the same age who are not yet making the transition to menopause, reported Dr. Lee S. Cohen and his associates in the Harvard Study of Moods and Cycles.

A cross-sectional sample of 460 women, aged 36 to 45 years, were prospectively followed every 6 months for several years. Changes in menstrual cycle length and menstrual flow amount and duration were tracked, and symptoms were assessed, said Dr. Cohen and his associates at Harvard Medical School, Massachusetts General Hospital, and Brigham and Women's Hospital, all of Boston.

None of the women had a history of major depression. A total of 134 were still premenopausal at the end of the last follow-up period, which occurred between 59 and 92 months after study enrollment. The remaining 326 women had entered menopause during that interval.

The rate of new-onset major depression was 16.6% in the menopausal women, compared with 9.5% in those who had not yet entered menopause, after the data had been adjusted to account for age at study enrollment and history of negative life events. “To our knowledge, this prospective documentation of increased risk for depression among women without a history of depression is unique,” the investigators said (Arch. Gen. Psychiatry 2006;63:385–90).

Women entering menopause are nearly twice as likely to develop depression as are women the same age who are not yet making the transition to menopause, reported Dr. Lee S. Cohen and his associates in the Harvard Study of Moods and Cycles.

A cross-sectional sample of 460 women, aged 36 to 45 years, were prospectively followed every 6 months for several years. Changes in menstrual cycle length and menstrual flow amount and duration were tracked, and symptoms were assessed, said Dr. Cohen and his associates at Harvard Medical School, Massachusetts General Hospital, and Brigham and Women's Hospital, all of Boston.

None of the women had a history of major depression. A total of 134 were still premenopausal at the end of the last follow-up period, which occurred between 59 and 92 months after study enrollment. The remaining 326 women had entered menopause during that interval.

The rate of new-onset major depression was 16.6% in the menopausal women, compared with 9.5% in those who had not yet entered menopause, after the data had been adjusted to account for age at study enrollment and history of negative life events. “To our knowledge, this prospective documentation of increased risk for depression among women without a history of depression is unique,” the investigators said (Arch. Gen. Psychiatry 2006;63:385–90).

Women entering menopause are nearly twice as likely to develop depression as are women the same age who are not yet making the transition to menopause, reported Dr. Lee S. Cohen and his associates in the Harvard Study of Moods and Cycles.

A cross-sectional sample of 460 women, aged 36 to 45 years, were prospectively followed every 6 months for several years. Changes in menstrual cycle length and menstrual flow amount and duration were tracked, and symptoms were assessed, said Dr. Cohen and his associates at Harvard Medical School, Massachusetts General Hospital, and Brigham and Women's Hospital, all of Boston.

None of the women had a history of major depression. A total of 134 were still premenopausal at the end of the last follow-up period, which occurred between 59 and 92 months after study enrollment. The remaining 326 women had entered menopause during that interval.

The rate of new-onset major depression was 16.6% in the menopausal women, compared with 9.5% in those who had not yet entered menopause, after the data had been adjusted to account for age at study enrollment and history of negative life events. “To our knowledge, this prospective documentation of increased risk for depression among women without a history of depression is unique,” the investigators said (Arch. Gen. Psychiatry 2006;63:385–90).

High-dose external beam radiotherapy (EBRT) was effective in controlling locally advanced, differentiated thyroid cancer in a retrospective study.

Dr. Kenyon M. Meadows and his associates at the University of Florida, Gainesville reviewed the records and assessed outcomes in all 42 patients who were treated for advanced or recurrent thyroid cancer with adjuvant high-dose EBRT at their university between April 1962 and January 2003. The median patient age was 58 years. Ten patients died from thyroid cancer during a mean follow-up of 7 years, while 16 died from unrelated causes. The rate of local or regional recurrence at 5 years was 0% for patients who had no gross residual disease when they underwent EBRT and 30% for those who did have gross residual disease at the time of EBRT (Am. J. Otolaryngol. 2006;27:24–8).

There were no cases of local or regional recurrences in patients who received doses greater than 64 Gy, suggesting a dose-response relationship.

Five-year cause-specific survival was 90% for patients who had no gross residual tumor when they underwent EBRT and 69% for those with gross residual disease. Five-year survival free of distant metastases was 82% for those without evidence of metastasis at the time of EBRT.

High-dose external beam radiotherapy (EBRT) was effective in controlling locally advanced, differentiated thyroid cancer in a retrospective study.

Dr. Kenyon M. Meadows and his associates at the University of Florida, Gainesville reviewed the records and assessed outcomes in all 42 patients who were treated for advanced or recurrent thyroid cancer with adjuvant high-dose EBRT at their university between April 1962 and January 2003. The median patient age was 58 years. Ten patients died from thyroid cancer during a mean follow-up of 7 years, while 16 died from unrelated causes. The rate of local or regional recurrence at 5 years was 0% for patients who had no gross residual disease when they underwent EBRT and 30% for those who did have gross residual disease at the time of EBRT (Am. J. Otolaryngol. 2006;27:24–8).

There were no cases of local or regional recurrences in patients who received doses greater than 64 Gy, suggesting a dose-response relationship.

Five-year cause-specific survival was 90% for patients who had no gross residual tumor when they underwent EBRT and 69% for those with gross residual disease. Five-year survival free of distant metastases was 82% for those without evidence of metastasis at the time of EBRT.

High-dose external beam radiotherapy (EBRT) was effective in controlling locally advanced, differentiated thyroid cancer in a retrospective study.

Dr. Kenyon M. Meadows and his associates at the University of Florida, Gainesville reviewed the records and assessed outcomes in all 42 patients who were treated for advanced or recurrent thyroid cancer with adjuvant high-dose EBRT at their university between April 1962 and January 2003. The median patient age was 58 years. Ten patients died from thyroid cancer during a mean follow-up of 7 years, while 16 died from unrelated causes. The rate of local or regional recurrence at 5 years was 0% for patients who had no gross residual disease when they underwent EBRT and 30% for those who did have gross residual disease at the time of EBRT (Am. J. Otolaryngol. 2006;27:24–8).

There were no cases of local or regional recurrences in patients who received doses greater than 64 Gy, suggesting a dose-response relationship.

Five-year cause-specific survival was 90% for patients who had no gross residual tumor when they underwent EBRT and 69% for those with gross residual disease. Five-year survival free of distant metastases was 82% for those without evidence of metastasis at the time of EBRT.

People with kidney disease have a somewhat different symptom profile when they present with acute myocardial infarction than those without kidney disease, reported Dr. Jonathan Sosnov of Tufts-New England Medical Center, Boston, and his associates.

More patients with kidney disease die from cardiovascular causes than from any other cause. “Accurate and rapid diagnosis of MI in these high-risk patients might decrease their risk for subsequent morbidity and mortality by providing definitive treatment in a more timely manner,” the investigators said.

They reviewed data from a large, ongoing prospective epidemiologic study of MI to examine whether kidney disease might alter the symptom profile of MI, much as diabetes recently has been shown to do. They analyzed the medical records of 4,482 patients hospitalized for MI at 11 medical centers in the Worcester, Mass., area in 1997, 1999, 2001, and 2003.

Patients with kidney disease were significantly less likely to present with chest pain as their chief complaint (44%) than patients without kidney disease (72%), Dr. Sosnov and his associates said (Am. J. Kidney Dis. 2006;47:378–84).

Patients with kidney disease were significantly less likely to complain of arm pain, numbness or tingling in the arm or hand, shoulder pain, jaw pain, or neck pain.

People with kidney disease have a somewhat different symptom profile when they present with acute myocardial infarction than those without kidney disease, reported Dr. Jonathan Sosnov of Tufts-New England Medical Center, Boston, and his associates.

More patients with kidney disease die from cardiovascular causes than from any other cause. “Accurate and rapid diagnosis of MI in these high-risk patients might decrease their risk for subsequent morbidity and mortality by providing definitive treatment in a more timely manner,” the investigators said.

They reviewed data from a large, ongoing prospective epidemiologic study of MI to examine whether kidney disease might alter the symptom profile of MI, much as diabetes recently has been shown to do. They analyzed the medical records of 4,482 patients hospitalized for MI at 11 medical centers in the Worcester, Mass., area in 1997, 1999, 2001, and 2003.

Patients with kidney disease were significantly less likely to present with chest pain as their chief complaint (44%) than patients without kidney disease (72%), Dr. Sosnov and his associates said (Am. J. Kidney Dis. 2006;47:378–84).

Patients with kidney disease were significantly less likely to complain of arm pain, numbness or tingling in the arm or hand, shoulder pain, jaw pain, or neck pain.

People with kidney disease have a somewhat different symptom profile when they present with acute myocardial infarction than those without kidney disease, reported Dr. Jonathan Sosnov of Tufts-New England Medical Center, Boston, and his associates.

More patients with kidney disease die from cardiovascular causes than from any other cause. “Accurate and rapid diagnosis of MI in these high-risk patients might decrease their risk for subsequent morbidity and mortality by providing definitive treatment in a more timely manner,” the investigators said.

They reviewed data from a large, ongoing prospective epidemiologic study of MI to examine whether kidney disease might alter the symptom profile of MI, much as diabetes recently has been shown to do. They analyzed the medical records of 4,482 patients hospitalized for MI at 11 medical centers in the Worcester, Mass., area in 1997, 1999, 2001, and 2003.

Patients with kidney disease were significantly less likely to present with chest pain as their chief complaint (44%) than patients without kidney disease (72%), Dr. Sosnov and his associates said (Am. J. Kidney Dis. 2006;47:378–84).

Patients with kidney disease were significantly less likely to complain of arm pain, numbness or tingling in the arm or hand, shoulder pain, jaw pain, or neck pain.

Lipid-lowering agents, particularly statins, significantly reduce cardiovascular risk in people with diabetes, to the extent that these patients may benefit from the drugs even more than nondiabetics do, according to Dr. Joào Costa of the University of Lisbon and associates.

Dr. Costa and associates reviewed 12 large studies that addressed lipid-lowering treatments and also included diabetic patients in all treatment arms.

Their metaanalysis showed that lipid-lowering drugs were equally effective in diabetic and nondiabetic patients in primary prevention. The use of statins or gemfibrozil reduced the risk of a first major coronary event by 21% in diabetic patients and by 23% in nondiabetics.

The results were similar for secondary prevention, except that diabetic patients benefited more than did nondiabetics. The use of statins or gemfibrozil reduced the risk of coronary artery disease death, nonfatal MI, revascularization procedures, and stroke to a greater degree in diabetic patients than it did in nondiabetics.

The magnitude of change in blood lipids for diabetic patients was comparable to that for nondiabetics. “Most trials showed a decrease of 15%–20% in total cholesterol and increases of 5%–7.5% in HDL cholesterol,” the investigators said (BMJ 2006 April 3 [Epub doi:10.1136/bmj.38793.468449.AE]).

“Our metaanalysis clearly confirms that reduction of LDL cholesterol concentrations results in an important decrease in major coronary events in diabetic patients and shows similar relative risk reductions and odds ratios for … diabetic and nondiabetic patients … in primary and secondary prevention. However, the absolute risk difference was three times higher in secondary prevention, reflecting the higher baseline cardiovascular risk of [diabetic] patients,” they noted.

Lipid-lowering agents, particularly statins, significantly reduce cardiovascular risk in people with diabetes, to the extent that these patients may benefit from the drugs even more than nondiabetics do, according to Dr. Joào Costa of the University of Lisbon and associates.

Dr. Costa and associates reviewed 12 large studies that addressed lipid-lowering treatments and also included diabetic patients in all treatment arms.

Their metaanalysis showed that lipid-lowering drugs were equally effective in diabetic and nondiabetic patients in primary prevention. The use of statins or gemfibrozil reduced the risk of a first major coronary event by 21% in diabetic patients and by 23% in nondiabetics.

The results were similar for secondary prevention, except that diabetic patients benefited more than did nondiabetics. The use of statins or gemfibrozil reduced the risk of coronary artery disease death, nonfatal MI, revascularization procedures, and stroke to a greater degree in diabetic patients than it did in nondiabetics.

The magnitude of change in blood lipids for diabetic patients was comparable to that for nondiabetics. “Most trials showed a decrease of 15%–20% in total cholesterol and increases of 5%–7.5% in HDL cholesterol,” the investigators said (BMJ 2006 April 3 [Epub doi:10.1136/bmj.38793.468449.AE]).

“Our metaanalysis clearly confirms that reduction of LDL cholesterol concentrations results in an important decrease in major coronary events in diabetic patients and shows similar relative risk reductions and odds ratios for … diabetic and nondiabetic patients … in primary and secondary prevention. However, the absolute risk difference was three times higher in secondary prevention, reflecting the higher baseline cardiovascular risk of [diabetic] patients,” they noted.

Lipid-lowering agents, particularly statins, significantly reduce cardiovascular risk in people with diabetes, to the extent that these patients may benefit from the drugs even more than nondiabetics do, according to Dr. Joào Costa of the University of Lisbon and associates.

Dr. Costa and associates reviewed 12 large studies that addressed lipid-lowering treatments and also included diabetic patients in all treatment arms.

Their metaanalysis showed that lipid-lowering drugs were equally effective in diabetic and nondiabetic patients in primary prevention. The use of statins or gemfibrozil reduced the risk of a first major coronary event by 21% in diabetic patients and by 23% in nondiabetics.

The results were similar for secondary prevention, except that diabetic patients benefited more than did nondiabetics. The use of statins or gemfibrozil reduced the risk of coronary artery disease death, nonfatal MI, revascularization procedures, and stroke to a greater degree in diabetic patients than it did in nondiabetics.

The magnitude of change in blood lipids for diabetic patients was comparable to that for nondiabetics. “Most trials showed a decrease of 15%–20% in total cholesterol and increases of 5%–7.5% in HDL cholesterol,” the investigators said (BMJ 2006 April 3 [Epub doi:10.1136/bmj.38793.468449.AE]).

“Our metaanalysis clearly confirms that reduction of LDL cholesterol concentrations results in an important decrease in major coronary events in diabetic patients and shows similar relative risk reductions and odds ratios for … diabetic and nondiabetic patients … in primary and secondary prevention. However, the absolute risk difference was three times higher in secondary prevention, reflecting the higher baseline cardiovascular risk of [diabetic] patients,” they noted.

Elite athletes with a syndrome of fatigue, recurrent sore throat, and shedding of Epstein-Barr virus in the saliva appear to have an exercise-induced defect of mucosal T-cell immunity that can be reversed with probiotic therapy, said Dr. R.L. Clancy of the University of Newcastle, Australia, and associates.

This is the first study to report reduced gamma interferon secretion in athletes with the fatigue syndrome, and the first to suggest a possible treatment. Further study is needed to clarify the mechanisms of the immune impairment and the therapy. Future research should also assess whether the findings can be applied to patients with other chronic fatigue illnesses, Dr. Clancy and associates said.

The researchers noted that protracted, intense training can cause recurrent upper respiratory tract symptoms and fatigue along with the appearance of Epstein-Barr virus (EBV) DNA in the saliva. They reasoned that intensive exercise, like other stressors, can impair T-cell -mediated immunity, which in turn impairs the containment of latent EBV infection and leads to viral reactivation.

They assessed saliva and blood samples in 9 athletes (mean age 25 years) with fatigue and recurrent sore throat and in 18 healthy volunteer athletes (mean age 26) who served as control subjects.

Gamma interferon levels from CD4 cells in blood samples were significantly lower in the fatigued athletes. Eight of the nine (90%) also were seropositive for previous EBV infection, and five of these eight subjects (63%) were actively shedding EBV DNA in their saliva.

After observing that isolates of Lactobacillus acidophilus enhanced T-cell function and protected against mucosal infection in mouse studies, the researchers treated the fatigued athletes with daily capsules of the organism for 4 weeks. This treatment raised gamma interferon secretion in the fatigued athletes to levels comparable to those in the control group (Br. J. Sports Med. 2006;40:351–4).

Before treatment, 6 of 24 saliva samples (25%) from fatigued athletes had detectable levels of EBV DNA; after treatment only 1 of 24 samples (4%) did.

The findings “suggest that a subtle T-cell defect in control mechanisms contributes to EBV reactivation and virus shedding,” and that probiotic therapy reverses the defect. The results must be confirmed in a larger study so clinicians can devise treatment strategies for affected athletes and possibly for patients with other fatigue syndromes, they said.

Elite athletes with a syndrome of fatigue, recurrent sore throat, and shedding of Epstein-Barr virus in the saliva appear to have an exercise-induced defect of mucosal T-cell immunity that can be reversed with probiotic therapy, said Dr. R.L. Clancy of the University of Newcastle, Australia, and associates.

This is the first study to report reduced gamma interferon secretion in athletes with the fatigue syndrome, and the first to suggest a possible treatment. Further study is needed to clarify the mechanisms of the immune impairment and the therapy. Future research should also assess whether the findings can be applied to patients with other chronic fatigue illnesses, Dr. Clancy and associates said.

The researchers noted that protracted, intense training can cause recurrent upper respiratory tract symptoms and fatigue along with the appearance of Epstein-Barr virus (EBV) DNA in the saliva. They reasoned that intensive exercise, like other stressors, can impair T-cell -mediated immunity, which in turn impairs the containment of latent EBV infection and leads to viral reactivation.

They assessed saliva and blood samples in 9 athletes (mean age 25 years) with fatigue and recurrent sore throat and in 18 healthy volunteer athletes (mean age 26) who served as control subjects.

Gamma interferon levels from CD4 cells in blood samples were significantly lower in the fatigued athletes. Eight of the nine (90%) also were seropositive for previous EBV infection, and five of these eight subjects (63%) were actively shedding EBV DNA in their saliva.

After observing that isolates of Lactobacillus acidophilus enhanced T-cell function and protected against mucosal infection in mouse studies, the researchers treated the fatigued athletes with daily capsules of the organism for 4 weeks. This treatment raised gamma interferon secretion in the fatigued athletes to levels comparable to those in the control group (Br. J. Sports Med. 2006;40:351–4).

Before treatment, 6 of 24 saliva samples (25%) from fatigued athletes had detectable levels of EBV DNA; after treatment only 1 of 24 samples (4%) did.

The findings “suggest that a subtle T-cell defect in control mechanisms contributes to EBV reactivation and virus shedding,” and that probiotic therapy reverses the defect. The results must be confirmed in a larger study so clinicians can devise treatment strategies for affected athletes and possibly for patients with other fatigue syndromes, they said.

Elite athletes with a syndrome of fatigue, recurrent sore throat, and shedding of Epstein-Barr virus in the saliva appear to have an exercise-induced defect of mucosal T-cell immunity that can be reversed with probiotic therapy, said Dr. R.L. Clancy of the University of Newcastle, Australia, and associates.

This is the first study to report reduced gamma interferon secretion in athletes with the fatigue syndrome, and the first to suggest a possible treatment. Further study is needed to clarify the mechanisms of the immune impairment and the therapy. Future research should also assess whether the findings can be applied to patients with other chronic fatigue illnesses, Dr. Clancy and associates said.

The researchers noted that protracted, intense training can cause recurrent upper respiratory tract symptoms and fatigue along with the appearance of Epstein-Barr virus (EBV) DNA in the saliva. They reasoned that intensive exercise, like other stressors, can impair T-cell -mediated immunity, which in turn impairs the containment of latent EBV infection and leads to viral reactivation.

They assessed saliva and blood samples in 9 athletes (mean age 25 years) with fatigue and recurrent sore throat and in 18 healthy volunteer athletes (mean age 26) who served as control subjects.

Gamma interferon levels from CD4 cells in blood samples were significantly lower in the fatigued athletes. Eight of the nine (90%) also were seropositive for previous EBV infection, and five of these eight subjects (63%) were actively shedding EBV DNA in their saliva.

After observing that isolates of Lactobacillus acidophilus enhanced T-cell function and protected against mucosal infection in mouse studies, the researchers treated the fatigued athletes with daily capsules of the organism for 4 weeks. This treatment raised gamma interferon secretion in the fatigued athletes to levels comparable to those in the control group (Br. J. Sports Med. 2006;40:351–4).

Before treatment, 6 of 24 saliva samples (25%) from fatigued athletes had detectable levels of EBV DNA; after treatment only 1 of 24 samples (4%) did.

The findings “suggest that a subtle T-cell defect in control mechanisms contributes to EBV reactivation and virus shedding,” and that probiotic therapy reverses the defect. The results must be confirmed in a larger study so clinicians can devise treatment strategies for affected athletes and possibly for patients with other fatigue syndromes, they said.