Pharmaceutical Drug Side Effects May Be Worse for Women
Recent and older research has unfolded a new paradigm for those who manufacture and distribute pharmaceutical drugs – as well as those who take them: Evidence is showing that women may absorb pharmaceuticals at a greater rate than men – meaning they could also be more affected by the side effects of those pharmaceuticals.
Worse is the fact that most of the studies been done on pharmacuticals have been done using men – or in the case of animal studies – males.
A study that has brought this to the forefront is from the Tufts University School of Medicine. The researchers gave adult males and females the pharmaceutical drug zolpidem – trademarked name Ambien prescribed for sleep – sublingual tablets and immediate release zolpidem oral doses, and tested their absorption and blood-levels of the drug.
At fifteen minutes after the dosing, the researchers found that the women absorbed the drug at significantly greater levels – both the sublingual and oral dose. The same oral doses were seen in the women’s blood at 17 ng/mL concentrations (nanograms per milliliter of blood) and only 10 ng/mL in the men, on average. Other measures found similar absorption differences between the genders.
The researchers concluded:
“Systemic exposure of zolpidem was higher in females for both formulations. Plasma levels and AUC were higher, and clearance was lower, in females with both zolpidem formulations.”
This means the drug entered the bloodstream faster and stayed longer (lower “clearance”).
In fact, a 1992 study by the FDA – called “Effect of Gender” – found that the pharmaceutical drug Ambien (zolpidem) will affect women at least 45 percent greater than men.
What makes matters worse is that a majority of the research over the past 50 years performed on pharmaceuticals has been conducted on men. Oddly enough, it was assumed that women would assimilate and utilize the drug similarly to men.
University of California neurobiology expert, Larry Cahill, Ph.D., reflected on the 40 million prescriptions of ambient given in the U.S. since its been approved:
“How did it happen that for 20 some years, women, millions of them, were essentially overdosing on Ambien?”
In terms of just Ambien, this means women will experience greater side effects, such as drowsiness, confusion, fever, loss of appetite, lightheadedness, tiredness, sleep troubles and others.
This of course means that many other pharmaceutical drugs may be being incorrectly dosed to women, resulting in a greater risk of negative side effects across the board. This relates to the fact that women simply metabolize medications differently than men.
And – more oddly – the reason men have been primarily used in human clinical research just as male rats and mice have been used in animal studies – is that women’s hormones have been considered a deterrent to reliable findings.
In other words, because women have periodic menses and swings in hormone levels, researchers have considered women or female animals – a potential source of unreliable findings.
The FDA admits oversight, changes dosing on only Ambien
The FDA recently adjusted suggested doses of ambient between men and woman in a 2013 safety announcement:
“The recommended initial dose of zolpidem extended-release (Ambien CR) is 6.25 mg for women and either 6.25 or 12.5 mg for men.”
They underscored one of the risks of over-dosing:
“However, use of the higher dose can increase the risk of next-day impairment of driving and other activities that require full alertness.”
Sandra Kweder, M.D., Liaison from the Federal discussed the rationale for this significant oversight among pharmaceutical research in a recent interview with 60 Minutes:
“That’s because there was no evidence at the time that the difference mattered. That was 20 years ago, when if someone said “women’s health,” it usually meant what they call “bikini medicine” — breast and ovarian cancer, pregnancy, menstrual cycles. But for parts of the body men and women share — hearts, kidneys, the brain — most of the studies were done predominantly on men.”
The fact that even animal studies are conducted primarily on men was confirmed by Melina Kibbe, M.D. a surgeon who also conducts mice and rat studies at Northwestern University Medical School. When asked the likelihood of a study only using male rats or mice, she said, “Very large.”
“Today?” she was asked. “Correct,” she replied.
What about herbal medicines?
One might conjecture that herbal medicines might be subject to the same issues relative to gender bias in the research. This, however, does not hold much water because of the nature and history of herbal medicine.
Herbal medicine has arrived into the 21st century with many centuries of trial and error among populations of both men and women in clinical settings. The knowledge related to which products have what health effects – along with dosage issues and gender issues – has been passed down from generation to generation of herbal medicine doctors who used these among both men and women according to personalized diagnostic data.
This knowledge has been passed down through mentorship – and to a smaller degree – through various Materia Medica over the centuries.
The mentorship issue creates a completely different paradigm than conventional pharmaceutical medicine. Yes, the information being passed down from doctor to medical trainee is based on clinical evidence possibly without randomization and placebo.
But the evidence passed down through herbal medicine’s clinical mentorship program has benefits not offered by modern clinical research: This first of which is the application of certain herbal medicines on not just thousands, but millions of people over the centuries. This produces a much larger database of information for clinicians to pass down to their trainees.
Another benefit of this type of clinical testing is that it arrives with personal applications upon different genders, different ages and different metabolisms. This reality that everyone’s metabolism – not just between men and women – is slightly different is even the primary rationale for pharmaceutical medicine needing to be prescribed by one’s personal physician rather than a vending machine for example.
Therefore, experience handed down through centuries of clinical observation adds the individual metabolism issue. A personal practitioner can tease out the metabolism issues as they interview the patient, just as any medical doctor needs to do before prescribing a medication.
Yes, we are certainly proving the evidence-based safety and efficacy of herbal medicine with the research as researchers investigate herbal medicine. But beyond that raw evidence is an intelligence of practitioners arrived at with more information about herbal medicine than these studies reflect.
But one thing has been proven out from the research: The level of adverse side effects among herbal medicine is practically absent when an herb is employed by herbal practitioners after centuries of use.
For example, one multicenter, randomized and controlled study gave either Shenqi qiangjing or prednisone to 132 patients with nephrotic syndrome. More than 14% of the prednisone group experienced negative side effects, while none of the Shenqi group had a negative side effect. There are hundreds of similar examples in the research.
In some cases this safety is established because certain extracts are employed – again arrived at over centuries of trial. But in most cases, herbal medicines employed over centuries by traditional practitioners have few if any negative side effects – as evidenced by five decades of clinical research.
Greenblatt DJ, Harmatz JS, Roth T, Singh NN, Moline ML, Harris SC, Kapil RP. Comparison of pharmacokinetic profiles of zolpidem buffered sublingual tablet and zolpidem oral immediate-release tablet: results from a single-center, single-dose, randomized, open-label crossover study in healthy adults. Clin Ther. 2013 May;35(5):604-11. doi: 10.1016/j.clinthera.2013.03.007.
FDA. The Effect of Gender. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022196s000_ClinPharmR_P3.pdf Acc. March 13, 2014
CBS News: 60 Minutes: “Sex matters: Drugs can affect sexes differently.” Feb. 9, 2014. http://www.cbsnews.com/news/sex-matters-drugs-can-affect-sexes-differently/
Chen Y, Deng Y, Ni Z, Chen N, Chen X, Shi W, Zhan Y, Yuan F, Deng W, Zhong Y. Efficacy and safety of traditional chinese medicine (Shenqi particle) for patients with idiopathic membranous nephropathy: a multicenter randomized controlled clinical trial. Am J Kidney Dis. 2013 Dec;62(6):1068-76. doi: