Aug 14, 2020 07:00 AM
(This post was last modified: Aug 14, 2020 04:44 PM by C C.)
Lack of females in drug dose trials leads to overmedicated women
https://news.berkeley.edu/2020/08/12/lac...ted-women/
RELEASE: Women are more likely than men to suffer adverse side effects of medications because drug dosages have historically been based on clinical trials conducted on men, suggests new research from UC Berkeley and the University of Chicago. Researchers analyzed data from several thousand medical journal articles and found clear evidence of a drug dose gender gap for 86 different medications approved by the Federal Drug Administration (FDA), including antidepressants, cardiovascular and anti-seizure drugs and analgesics, among others.
“When it comes to prescribing drugs, a one-size-fits-all approach, based on male-dominated clinical trials, is not working, and women are getting the short end of the stick,” said study lead author Irving Zucker, a professor emeritus of psychology and of integrative biology at UC Berkeley.
The findings, published in the journal Biology of Sex Differences, confirm the persistence of a drug dose gender gap stemming from a historic disregard of the fundamental biological differences between male and female bodies, Zucker said. Women in the studies analyzed by Zucker and University of Chicago psychologist Brian Prendergast were given the same drug dose as the men, yet had higher concentrations of the drug in their blood, and it took longer for the drug to be eliminated from their bodies.
And, in more than 90% of cases, women experienced worse side effects, such as nausea, headache, depression, cognitive deficits, seizures, hallucinations, agitation and cardiac anomalies. Overall, they were found to experience adverse drug reactions nearly twice as often as men.
For decades, women were excluded from clinical drug trials based, in part, on unfounded concerns that female hormone fluctuations render women difficult to study, Zucker said. Moreover, until the early 1990s, women of childbearing age were kept out of drug trial studies due to medical and liability concerns about exposing pregnant women to drugs and risking damage to their fetuses — as was the case in the 1950s and ‘60s with thalidomide, which caused limb birth defects in thousands of children worldwide.
“Neglect of females is widespread, even in cell and animal studies where the subjects have been predominantly male,” Zucker said. Zolpidem, the popular sleep medication marketed as Ambien, lingers longer in the blood of women than of men, causing next-morning drowsiness, substantial cognitive impairment and increased traffic accidents, Zucker said. For these reasons, the FDA in 2013 halved the recommended dosage prescribed to women.
In acknowledging the widespread male bias in both human and animal studies, the National Institutes of Health mandated in 2016 that grant applicants would be required to recruit male and female participants in their protocols. While the inclusion of females in drug trials has increased in recent years, many of these newer studies still fail to analyze the data for sex differences, Zucker said.
Going forward, Zucker and Prendergast make the case for a broader awareness — in medical research, the medical profession and the pharmaceutical industry — of the biological sex and gender differences that put women at a disadvantage when taking prescription drugs. They recommend dosage reductions for women for a wide range of drugs.
Aspirin Caution
https://hms.harvard.edu/news/aspirin-caution
RELEASE: Results from a recent clinical trial indicate that for older adults with advanced cancer, initiating aspirin may increase their risk of disease progression and early death. The study, which was conducted by a binational team led by researchers at Massachusetts General Hospital (MGH), the Berman Center in Minnesota, and Monash University in Australia, is published in the Journal of the National Cancer Institute.
Compelling evidence from clinical trials that included predominantly middle-aged adults demonstrates that aspirin may reduce the risk of developing cancer, especially colorectal cancer. Information is lacking for older adults, however.
To provide insights, investigators designed and initiated the ASPirin in Reducing Events in the Elderly (ASPREE) trial, the first randomized double-blind placebo-controlled trial of daily low-dose aspirin (100 mg) in otherwise healthy older adults. The study included 19,114 Australian and U.S. community-dwelling participants aged 70+ years (U.S. minorities 65+ years) without cardiovascular disease, dementia, or physical disability at the start of the study. Participants were randomized to aspirin or placebo and followed for a median of 4.7 years.
In October 2018, the investigators published a very surprising and concerning report showing an association between aspirin use and an elevated risk of death, primarily due to cancer. The current report now provides a more comprehensive analysis of the cancer-related effects of aspirin in the ASPREE participants. "We conducted this study as a more detailed examination of the effect of aspirin on the development of cancer as well as death from cancer," explained senior author Andrew T. Chan, MD, MPH, Chief of the Clinical and Translational Epidemiology Unit at MGH, Director of Epidemiology at the MGH Cancer Center, and a Professor of Medicine at Harvard Medical School.
Dr. Chan and his colleagues reported that 981 participants who were taking aspirin and 952 who were taking placebo developed cancer. There was no statistically significant difference between the groups for developing cancer overall or for developing specific types of cancer. Aspirin was associated with a 19% higher risk of being diagnosed with cancer that had spread (or metastasized) and a 22% higher risk of being diagnosed with stage 4, or advanced, cancer, however. Also, among participants who were diagnosed with advanced cancer, those taking aspirin had a higher risk of dying during follow-up than those taking placebo.
"Deaths were particularly high among those on aspirin who were diagnosed with advanced solid cancers, suggesting a possible adverse effect of aspirin on the growth of cancers once they have already developed in older adults," said Dr. Chan. He added that the findings suggest the possibility that aspirin might act differently, at the cellular or molecular level, in older people, which requires further study.
Notably, the vast majority of the study participants did not previously take aspirin before age 70. “Although these results suggest that we should be cautious about starting aspirin therapy in otherwise healthy older adults, this does not mean that individuals who are already taking aspirin—particularly if they began taking it at a younger age—should stop their aspirin regimen,” Dr. Chan added.
https://news.berkeley.edu/2020/08/12/lac...ted-women/
RELEASE: Women are more likely than men to suffer adverse side effects of medications because drug dosages have historically been based on clinical trials conducted on men, suggests new research from UC Berkeley and the University of Chicago. Researchers analyzed data from several thousand medical journal articles and found clear evidence of a drug dose gender gap for 86 different medications approved by the Federal Drug Administration (FDA), including antidepressants, cardiovascular and anti-seizure drugs and analgesics, among others.
“When it comes to prescribing drugs, a one-size-fits-all approach, based on male-dominated clinical trials, is not working, and women are getting the short end of the stick,” said study lead author Irving Zucker, a professor emeritus of psychology and of integrative biology at UC Berkeley.
The findings, published in the journal Biology of Sex Differences, confirm the persistence of a drug dose gender gap stemming from a historic disregard of the fundamental biological differences between male and female bodies, Zucker said. Women in the studies analyzed by Zucker and University of Chicago psychologist Brian Prendergast were given the same drug dose as the men, yet had higher concentrations of the drug in their blood, and it took longer for the drug to be eliminated from their bodies.
And, in more than 90% of cases, women experienced worse side effects, such as nausea, headache, depression, cognitive deficits, seizures, hallucinations, agitation and cardiac anomalies. Overall, they were found to experience adverse drug reactions nearly twice as often as men.
For decades, women were excluded from clinical drug trials based, in part, on unfounded concerns that female hormone fluctuations render women difficult to study, Zucker said. Moreover, until the early 1990s, women of childbearing age were kept out of drug trial studies due to medical and liability concerns about exposing pregnant women to drugs and risking damage to their fetuses — as was the case in the 1950s and ‘60s with thalidomide, which caused limb birth defects in thousands of children worldwide.
“Neglect of females is widespread, even in cell and animal studies where the subjects have been predominantly male,” Zucker said. Zolpidem, the popular sleep medication marketed as Ambien, lingers longer in the blood of women than of men, causing next-morning drowsiness, substantial cognitive impairment and increased traffic accidents, Zucker said. For these reasons, the FDA in 2013 halved the recommended dosage prescribed to women.
In acknowledging the widespread male bias in both human and animal studies, the National Institutes of Health mandated in 2016 that grant applicants would be required to recruit male and female participants in their protocols. While the inclusion of females in drug trials has increased in recent years, many of these newer studies still fail to analyze the data for sex differences, Zucker said.
Going forward, Zucker and Prendergast make the case for a broader awareness — in medical research, the medical profession and the pharmaceutical industry — of the biological sex and gender differences that put women at a disadvantage when taking prescription drugs. They recommend dosage reductions for women for a wide range of drugs.
Aspirin Caution
https://hms.harvard.edu/news/aspirin-caution
RELEASE: Results from a recent clinical trial indicate that for older adults with advanced cancer, initiating aspirin may increase their risk of disease progression and early death. The study, which was conducted by a binational team led by researchers at Massachusetts General Hospital (MGH), the Berman Center in Minnesota, and Monash University in Australia, is published in the Journal of the National Cancer Institute.
Compelling evidence from clinical trials that included predominantly middle-aged adults demonstrates that aspirin may reduce the risk of developing cancer, especially colorectal cancer. Information is lacking for older adults, however.
To provide insights, investigators designed and initiated the ASPirin in Reducing Events in the Elderly (ASPREE) trial, the first randomized double-blind placebo-controlled trial of daily low-dose aspirin (100 mg) in otherwise healthy older adults. The study included 19,114 Australian and U.S. community-dwelling participants aged 70+ years (U.S. minorities 65+ years) without cardiovascular disease, dementia, or physical disability at the start of the study. Participants were randomized to aspirin or placebo and followed for a median of 4.7 years.
In October 2018, the investigators published a very surprising and concerning report showing an association between aspirin use and an elevated risk of death, primarily due to cancer. The current report now provides a more comprehensive analysis of the cancer-related effects of aspirin in the ASPREE participants. "We conducted this study as a more detailed examination of the effect of aspirin on the development of cancer as well as death from cancer," explained senior author Andrew T. Chan, MD, MPH, Chief of the Clinical and Translational Epidemiology Unit at MGH, Director of Epidemiology at the MGH Cancer Center, and a Professor of Medicine at Harvard Medical School.
Dr. Chan and his colleagues reported that 981 participants who were taking aspirin and 952 who were taking placebo developed cancer. There was no statistically significant difference between the groups for developing cancer overall or for developing specific types of cancer. Aspirin was associated with a 19% higher risk of being diagnosed with cancer that had spread (or metastasized) and a 22% higher risk of being diagnosed with stage 4, or advanced, cancer, however. Also, among participants who were diagnosed with advanced cancer, those taking aspirin had a higher risk of dying during follow-up than those taking placebo.
"Deaths were particularly high among those on aspirin who were diagnosed with advanced solid cancers, suggesting a possible adverse effect of aspirin on the growth of cancers once they have already developed in older adults," said Dr. Chan. He added that the findings suggest the possibility that aspirin might act differently, at the cellular or molecular level, in older people, which requires further study.
Notably, the vast majority of the study participants did not previously take aspirin before age 70. “Although these results suggest that we should be cautious about starting aspirin therapy in otherwise healthy older adults, this does not mean that individuals who are already taking aspirin—particularly if they began taking it at a younger age—should stop their aspirin regimen,” Dr. Chan added.
