pain medications Archives - Hormones Matter

The Reality of Endometriosis in the ER

by RC

Published on June 16, 2022

14697 views

I’m lying on an emergency room bed, writhing in agony, screaming in pain, as though my insides are being torn to shreds. I curl up my body, protecting myself from the evil inner force that resides within me, stabbing me, shocking my organs. My mind is frantic, confused, and manic. Lights and sounds mix together around me and I close my eyes to minimize the sensory overload. The white sheets under me feel scratchy and irksome, I can’t deal with any added discomfort. Searing pain bubbles within me, threatening to boil over, and when it does, I let out a scream from the very depths of my soul.

I hear a voice and attempt agonizingly to open my eyes. A woman in a white coat stands in front of me, arms crossed in a stance that conveys a mixture of disdain and apathy.

“Rachel,” she demands, her voice both indifferent and annoyed, “want to tell me why you’re here?”

Is she joking? I wonder to myself while trying to gather my coherent thoughts, does she not see I’m in excruciating pain?

“Pain…” I manage to say, the word more a miserable moan than an answer. “I need meds…”

“I’ll decide what you need,” she replies nastily. “You’ve been here way too many times, asking for medicine each time. You don’t need meds, Rachel, you need to go to rehab. You’re an addict.”

I can’t control my tears any longer and I let them flow freely as I sob uncontrollably. Didn’t she see my chart? Doesn’t she see that I have endometriosis? Does she know how painful it is?

“I have endometriosis,” I muster, “I take normal pain meds every day but they are not working today. The pain is worse than usual!”

And then my senses can’t take the pain any longer, and I scream out desperately once more. All thoughts abscond from my brain, all I can think of is dying to get rid of the pain. The doctor looks at me like I am a dirty piece of clothing on the floor. She purses her lips and then spits out, “I suppose I can give you some Motrin or Tylenol.”

I am so desperate at this point I agree to her pointless suggestion. My head knows the meds will not help, but my body is starving for relief. Needless to say, thirty minutes later the Motrin has left me right where I was before I took it: in paralyzing pain.

A nurse comes into my cubicle a throws a glance at my miserable form. “You’re being discharged!” she sings, as though she is freeing me from jail. Her smile is grotesquely wide as she hands me a pen to sign my name on the discharge papers. I want to explode at her, to hurl words in her face that describe my agony, and wipe that inane grin right off her face. But I don’t. Instead, I meekly take the pen, wait for a moment in which my body is able to stop shaking, and then sign the papers.

“Wheelchair will be here in a minute!” she croons, then leaves me alone with my emotions.

I fold my beaten-up body into the wheelchair feeling completely empty and numb despite the pain. I am so shocked at the experience I just had. I left my heart, soul, and voice in that emergency room, trying my hardest to explain the agony I was in. I laid in front of a doctor trembling with pain, and she in turn called me an addict and sent me away. She didn’t bother to understand what I was going through and didn’t test me to see what drugs I had in my body. Instead, she took my trust, ruthlessly pummeled it, and carelessly threw it away. I leave feeling nothing more than a desire to give up and let it all go. Tonight, I have become one more casualty in the fight for us with endometriosis to be heard.

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This article was posted originally in February 2014.

Are Women More Sensitive to Pain? Hormones and Pain Killers

by Chandler Marrs, PhD

Published on May 11, 2017

2770 views

Are women more sensitive to pain? The question has been bandied about for years. Study after study answers affirmatively. Yes, women are more sensitive to pain. Not only that, women experience more pain than men for similar injuries and require more pain medication to achieve the same level of relief. And oh, by the way, for some strange reason, women suffer from more abdominal pain than men.

The question itself is encumbered with an all-knowing cultural and political ennui that subsumes the very possibility of an accurate answer. Instead it directs us toward the expected, and ultimately, uninteresting psychosocial babble; of course, women are more sensitive to pain, let us simply count the ways. While it is true that women do indeed require more pain medication than men and suffer from more abdominal pain than men, it rarely seems to occur to those conducting this research to re-frame the question from the tacit approbation of female ‘sensitivity’ to why might women require more pain medications than men. What is it about the medication or the female physiology that renders pain medications insufficient in women. Well, let me count the ways.

Pain Medications Designed by Males, for Males, with Males

Exclusive of the pain medications discovered accidentally, like the early opium-based or morphine derivatives on which no research was ever conducted, most pain medications developed in the 20th century were never tested on women. Indeed, women were prohibited from being included in clinical trials until 1993-1998. (Instead, we simply gave women the meds and hoped for the best). Even post 1998 when the new regulations were implemented to permit women in clinical trials, there were no requirements for drug developers to analyze the data based on sex and determine if a particular medication worked better or worse in women or even if the medication had more or different adverse events for women. As a result, many researchers have noted that women suffer disproportionately more adverse events per capita than men and that those adverse events are often quantitatively more serious. For more details, see: Women in Clinical Trials – So That’s Why My Meds Don’t Work.

Even in early medication development, the animal research, uses males to develop and test the efficacy of a particular medication. A recent report suggests that 79% of all animal studies published over a 10 year period in the journal Pain, were done on male rodents. Only 8% used both males and females and only 4% tested the response differences between males and females. As the comments in this pain post suggest, testing on female rodents is expensive and difficult because of the animal’s estrus cycle (menstrual cycle for humans) – e.g. the hormone changes are rapid and complicated. It’s much easier and less costly to measure in male rats.

I would argue, adverse events in human females are exponentially more costly and difficult than conducting the appropriate research early in development. However, with the exception of the class action fines that pharmaceutical companies pay, it is not often that the pharmaceutical company – the drug developers – must bear the brunt of the early research costs or even bulk of the adverse event costs. Rather, it is governmental agencies that fund early stage research and insurance companies, governmental and private, respectively, who pay for the negative outcomes. With this bit of a misalignment that means no one pays for or is accountable for, what perhaps, could be avoided, if funds were allocated in the earlier testing phases.

Given that so few pain medications were developed using females (rodent or human), it is entirely possible that many pain medications simply do not work as well or even by the same mechanisms in females versus males. There is some evidence that this is true. Researchers have noted that while standard morphine type medications (opioid agonists) don’t work as well in women as in men, other medications appear to work better, such as the opioid agonist-antagonist butorphanol or pentazocine – pain killers that work on different types of receptors and by different mechanisms.

Female Biochemistry, Pharmacokinetics and Pharmacodynamics

What is it about the female physiology that makes some medications less effective than when given to males? Well, to state the obvious, females are genetically, physiologically, structurally and biochemically different than males. Why would anyone presuppose that placing a compound into two discretely different environments would exact the same response? And yet, that is exactly what we do.

Drug disposition is sex-specific. How a drug moves through the body (pharmacokinetics)and what effects it elicits (pharmacodynamics) are determined by number of factors, most of which differ significantly in males and females. In one of the better written reviews of Sex Differences in Drug Disposition, researchers note that even in the few studies with sex-analytics, it is clear that women process drugs differently than men.

Drug transit through the GI tract is considerably longer in women than men (91.7 hours versus 44.8 hours).
Bile acid composition is different and acidity levels are different
Women show a higher maximum dose and AUC 87% and 71% of the time
CYP enzymes (the enzymes that break down drugs in the liver) vary with some variants consistently increased and others decreased by sex.
Food by medication interactions vary directionally by sex – that is they are not consistent, some increase metabolism, some decrease metabolism
Sex differences in kidney function
Sex differences in liver function
Sex differences in pain and opioid receptor density and activity
Women exhibit different pharmacodynamic profiles for a wide array of drugs
Cycling hormones dynamically change drug metabolism (pharmacokinetics) and drug effects (pharmacodynamics); pregnancy hormones change these drug parameters even more radically

Bottom-line, women are different than men. Existing medications need to be tested in women to see which ones work and which ones don’t, and then, prescribed accordingly. New medications should be developed for these differences. (Imagine, a whole new market by simply recognizing the obvious differences in the population). For medications already in development, sex analytics must be conducted before the drug is released.

Are women more sensitive to pain? Probably not, but we have different types of pain (frequently, undiagnosed or misdiagnosed and chronic) and respond differently to pain medications than men.

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This article was published originally on Hormones Matter on June 27, 2013.

Women in Pain: Problems and Mistreatment

by Philippa Bridge-Cook, PhD

Published on July 23, 2015

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Chronic pain in North America is a major problem for men and women alike, affecting about one-third of adults. Many people of both genders do not receive adequate treatment for their pain. This causes great personal suffering, as well as high costs to the economy through direct health care costs and loss of work productivity for those in pain. However, women with pain face additional problems that suggests there is a systematic bias in the way healthcare is delivered to women. Diseases that affect mostly women are generally poorly understood and understudied, and although women report pain that is more frequent, more severe, and of longer duration than men, in general women’s pain is treated much less aggressively.

Women are at higher risk of developing a chronic pain condition than men. For example, women have triple the risk of autoimmune diseases, which are often associated with chronic pain, compared to men. Women also suffer from certain painful diseases that are rare in men, such as endometriosis and vulvodynia. Endometriosis alone affects one in ten women, and women who have endometriosis often have other painful diseases as well, such as interstitial cystitis/painful bladder syndrome.

However, research into causes and treatments for these diseases that disproportionately affect women is sadly lacking. A report written by the Campaign to End Chronic Pain in Women looked at six conditions common in women that are routinely misdiagnosed and ineffectively treated: endometriosis, vulvodynia, chronic fatigue syndrome, fibromyalgia, interstitial cystitis/painful bladder syndrome, and temporomandibular (TMJ) disorders. Examining funding to these six conditions by the National Institutes of Health (NIH) revealed that on average, the NIH spends $1.33 per affected patient on research into these conditions, compared to $186 per patient for Parkinsons’s disease, or $53 per patient for diabetes.

However, one need not look at diseases that are underfunded, poorly understood, and lacking effective treatments to find evidence of a gender bias in medicine. One of the best examples of gender bias is, surprisingly, in coronary heart disease. When presenting to emergency rooms or hospitalized for a heart attack, multiple studies have shown that men receive faster access to diagnostic tests and treatments, and men are more likely to receive advanced procedures and better care (for example,see here, here, here and here), and these disparities have not changed over time.

Although heart disease can present differently in men and women, atypical presentation in women does not account for all of the difference in delayed or lack of access to tests and treatments. In one study of doctors evaluating hypothetical patients— male patients and female patients presenting with typical heart attack symptoms and identical risk factors– the doctors did not make different recommendations for the male and female patients. However, when stress was included as a risk factor, only 15 percent of doctors diagnosed heart disease in the women, compared to 56 percent for the men. This study suggests that doctors are much more likely to write symptoms off as psychological when the patient is a woman. And women are medicated as if their pain is emotional instead of physical: for example, after coronary artery bypass graft surgery, women are less likely than men to receive opioid pain medication, and more likely to receive sedatives instead.

Many studies have shown that female gender is a major risk factor for the undertreatment of pain, across many different types of pain. After abdominal surgery and appendectomies, women receive less pain medication than men, even though many studies have shown that women are more likely to report higher levels of pain than men. For cancer pain, and pain caused by HIV, women are significantly more likely to be undertreated for pain. Even paramedics are more likely to give opioid analgesics to men suffering from pain pre-hospital admission than to women. In general, doctors and other medical professionals are more likely to view women’s pain as caused by emotional factors even in the presence of positive test results, and are more likely to administer tranquilizers, antidepressants, and non-opioid analgesics to treat women’s pain.

Women face obstacles to getting appropriate care for many different diseases, at every step of the process. Women’s diseases tend to be underfunded, underresearched, and poorly understood, so getting a diagnosis is difficult, especially when there is the additional obstacle of health care providers tending to assume that women’s symptoms are psychosomatic. Once diagnosed, women do not receive the same level of care for their diseases that men do. And if women can be shortchanged on care for cardiac conditions, which tend to be taken seriously in our society, well researched, and have evidence-based guidelines to guide treatment, imagine how poorly women may be treated for diseases like endometriosis, for which myths about causes and effective treatment abound, and their pain cannot be measured with any objective tests.

Until medical care for women’s diseases moves from the 1950s into the present day, the only solution for women is to be extremely persistent. Women need to seek out the few care providers who understand their disease and are up to date on the latest, albeit sparse, research, and they need to be persistent about having their symptoms acknowledged and treated by their care providers. And in general, we need to keep pushing for better awareness of these problems, and funding for research so that women can receive the medical care they deserve.

Hypersensitivity to pain, my ass!

by Chandler Marrs, PhD

Published on October 10, 2014

2228 views

A multitude of reports have emerged in recent years denoting the over use of pain killers and other medications. With narcotic pain killers, in particular, data suggest a four-fold increase in opioid use since 1999, and over 100,000 deaths by opioid overdose during same time period. The data also indicate a close correspondence between the increase in prescriptions for pain killers and pharma sponsored marketing, ‘research’ and policy changes that have inculcated medical agency guidelines over the last decade.

For women, this is a particularly troubling trend, as other research indicates we are the primary targets of narcotic prescribing; women take 50% more pain killers than men. We also take 36% more medications than men in general. Speculation about why women take more pain killers than men, often involves psychosocial characteristics including a reduced sensitivity to pain, a predisposition to pain causing diseases, and a predilection to report the pain to one’s physician. Women seek out medical treatment at a much higher rate than men.

What often fails to get mentioned is that:

Pain medications don’t work as well in women because as we’ve reported before few females, rodents or otherwise, are used in the development of these medications.
Even when female animals or women are used in drug development research, cycling hormones are not analyzed as factors in the effectiveness of the medication.
For the myriad of pain related disorders affecting women, many lack evidence-based diagnostic criteria (less than 30% of Ob/Gyn practice guidelines are based on actual evidence) and frequently physicians and the lack of effective diagnostic criteria hastens many to presume an underlying psychosocial or mental health issue.

I personally think the psychosocial arguments that women are more sensitive to pain than men are nonsense. Rather, I think there is a lot more inherent to our physiology that makes pain related conditions not only more likely, but more difficult to treat.

Consider for example, the menstrual cycle and childbirth. These amazingly complex, biochemically radical, pain-inducing, often life-altering experiences are just a ‘normal’ part of female existence. I dare any man to experience the exponential and repeated cyclic change in biochemistry, akin to a repeated drug addiction and withdrawal pattern, that is the female menstrual cycle. The myth of female hypersensitivity to pain, based largely upon the ineffectiveness of pain or medications that were never designed for her changing biochemistry, is just that, a myth. And though I do admit, some humans are more sensitive to pain than others, the contrived experimental methods that designate women as hyper-sensitive do great damage to our understanding of women’s health and the differing pharmacokinetics across the menstrual cycle, pregnancy, postpartum or menopause.

And then of course, there is endometrial sloughing, necessitating a cramping mechanism to propel the tissue outward or the grandmother of all pain experience, childbirth where women deliver 8lb humans through a cavity opening that expands only to 10 centimeters, often times choosing to not utilize pain medications. These ‘normal’ events of a woman’s life are not indicative of a ‘hypersensitivity to pain’.

No, I don’t buy this mumbo jumbo that women are somehow more sensitive to pain than men. If anything, most women have a higher tolerance to everyday pain than most men. But there is a rationale to perpetuating this myth; it limits innovation in women’s health.

Why innovate when a company can make billions prescribing the same old medications at higher and higher dosages, to more and more people? Why address the needs of half the population, when one can blanket the market with drugs for the entire population? And to that point, why develop more accurate diagnostic criteria or more effective medications for conditions that only effect a small subset of the total population; especially when medications developed over 50 years ago can be used? If these medications are addictive, have side effects that necessitate other medications and are extremely difficult to withdraw from, well then, those are just added bonuses. It’s a wonderful business model, albeit a little less than ethical.

Despite the obvious marketing excess, we as consumers bear as much responsibility for the increase in narcotic prescriptions as does the pharmaceutical industry. We are letting this happen. Let’s face it, it is much easier to take a pill to make the pain go away (or eat a pint of ice cream to alleviate stress) than go after the root problem. It is difficult to address root causes. It is especially difficult if one is suffering from a medical condition that is chronic, pain-inducing, poorly understood, not easily diagnosed, and for which there are no effective medications. Women disproportionately suffer from these types of conditions – think fibromyalgia, endometriosis or even migraines. We also make 80% of all family medical decisions. So ladies, we need to stand up and begin educating ourselves and our families about health and disease. We must demand more research and we will probably have to lead it ourselves.

What do male rodents and human females have in common?

by Chandler Marrs, PhD

Published on September 14, 2011

3150 views

Drug Development Conducted mostly in Male Rodents

According to most researchers, male rodents share enough in common with human females to extrapolate findings about the mechanisms and treatment of pain. A review of research in the journal Pain (2007) found that over a ten year period, fully 79% of all animal studies published, performed drug testing on male animals only. Only 8% of the published research included female animals and a mere 4% investigated the possible differences between males and females.

The preponderance of male rodents in animal research is in stark contrast to the higher prevalence of women suffering from pain related disorders. I find it difficult to justify using male rodents for drug research that will be translated to the female population, especially when the estrus and menstrual cycles influence so many pharmacokinetic variables.

What do you think? How do the numbers stack up in other areas of research?

Greenspan et al. Pain. 2007 Nov;132 Suppl 1:S26-45. Epub 2007 Oct 25.
To read the full article click here.

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