The Dangerous Panic over Painkillers
By Maia Szalavitz, The Fix
As found on AlterNet.
Posted on January 27, 2012, Printed on January 31, 2012

While use of prescription opioids for cancer and other end-of-life pain is increasingly accepted, if you are going to suffer in agony for years, rather than months, mercy is harder to find. Indeed, it seems a given by the media that because addicts sometimes fake pain to get drugs, doctors should treat allpatients as likely liars—and if a physician is conned by an addict, the doctor has only herself to blame.

But do we really want our doctors to treat us as if we were guilty until proven innocent? Do we really want the routine use of invasive procedures—ranging from nerve conduction tests to repeated scans and surgeries—to “prove” we’re really hurting? And do we actually want physicians to be held responsible for the actions of a patient who dissembles and does not take drugs as prescribed?

The answers to these questions are at the heart of the bizarre way we view synthetic opioid medications and the suffering of the 116 million Americans who have moderate to severe chronic pain, according to Institute of Medicine estimates.

In recent weeks, for example, New York Sen. Charles Schumer, anti-drug abuse advocates and reporters have inveighed against the potential FDA approval of an experimental opioid painkiller called Zohydro—professing to be horrified by the introduction of a new class of “100% pure” hydrocodone “superdrugs” that they have already dubbed “the next OxyContins.” And many states are weighing laws like one now in place in Washington state, which limits the doses of opioids that can be used by chronic pain patients.

When people consider the use of these medications in chronic pain, addiction fears are typically the first thing that comes up. Moreover, media coverage rarely includes the perspective of pain patients— or does so only to knock those who advocate for access to opioids as pawns of the pharmaceutical industry.

If the press—often quoting leading public health officials like Dr. Thomas Frieden, the director of the CDC—is to be believed, the US is in the throes of an “epidemic” of prescription painkiller abuse. Frieden even claimed at a recent press conference on opioid-related deaths that doctors are now more responsible than drug dealers for America’s addiction problems. “The burden of dangerous drugs is being created more by a few irresponsible doctors than drug pushers on street corners,” Friedman said.

However, the opioid issue looks very different when you examine the numbers closely. For one, the rates of Americans addicted to OxyContin, Vicodin, percocet, fentanyl and other products in our synthetic narcotic medicine cabinet are not rising. In fact, they have been steady at 0.8% since 2002, according to the government’s own statistics.

Moreover, fewer than 1% of people over 30 (without a prior history of serious drug problems) become an addict while taking opioids; for chronic pain patients who are not screened for a history of previous drug problems, the addiction rate is 3.27%. That means, of course, that more than 96% do not become addicted.

Yet these statistics usually go unmentioned in media accounts because they do not confirm the preferred panic narrative. Also left out is the fact that around 80% of Oxy addicts (a) did not obtain the drug via legitimate prescription for pain and/or (b) had a prior experience of rehab. Their contact with the medical system—if any—was not what caused their addictions.

So, the first thing the public really needs to know about what doctors call “iatrogenic addiction” is that it is extremely rare. If you’ve made it out of your 20s without becoming an addict, the chances that you will get hooked on pain treatment are miniscule—and even young people are not at high risk in most medical settings.

Nonetheless, the media continue to love them some “innocent victims”—and the real story of not-so-blameless drug users who move from heavy drinking, cocaine use and marijuana smoking to prescription drug abuse is just not as compelling. This, sadly, only contributes to the delusion that anyone who is treated for chronic pain with opioids is at risk for drowning in the—gasp!—ubiquitous riptide of addiction.

The panic leads to policies that require pain patients to be urine-tested, to be called in to their doctors’ offices for random “pill counts” and to make frequent visits—all of which is not only humiliating but expensive and time-consuming. There’s little evidence that such policing prevents addiction or does anything else beyond inconveniencing and stigmatizing pain patients.

And indeed, the stigma of addiction is what’s behind the curtain here. Imagine suffering from incurable daily pain so severe that it feels like your legs are being dipped in molten iron or your spine is being scraped out by sharp talons. Even if you did, in a worst-case scenario, join the tiny percentage of patients who develop a new addiction and became obsessed with using opioids, would this really be worse, especially if you had safe and legal access to them?

Most of the physical and psychological horrors of addiction come with loss of control and with being unable to be present for family, work and friends. But pain can produce even greater dysfunction and emotional distance, and its ability to destroy relationships is at least as monstrous. Moreover, maintenance on opioids can typically stabilize people with addictions, without numbing or incapacitating them. So why do we panic?

In the absence of true pharmaceutical innovation (Zohydro and other “superdrugs” are mere purer versions of VIcodin without the acetaminophen ), opioids remain the only medications that can even begin to touch severe pain, though they are far from perfect. But since they rarely lead to addiction—and since addiction (or opioid maintenance treatment) may actually sometimes be the lesser of evils—does it really make sense to restrict and even deny their benefits to pain patients?

When the situation is considered rationally, our outsized fear of addiction has little to do with the reality of chronic pain. Instead, it’s about the way we see addicts: gun-toting robbers of Oxy from pharmacies and other scummy, lying, sociopathic criminals—people we don’t want to be around or become.

Even though readers of this site know that drugs don’t somehow “make” ordinary people into such demonic figures—and that addicts can also be as kind, compassionate and hard-working as anyone else— the stigma runs deep.

Much of it, I think, comes from the same evasion of responsibility that allows us to blame doctors for addictions. After all, it’s not doctors who tell their patients to inject or snort their oral painkillers, to drink while taking opioids, to take more than prescribed or to lie, cheat and steal to obtain them.

These actions are deliberately taken by drug seekers. Doctors don’t “make” anyone make the ongoing choices that lead to impaired self-control. While trauma histories, psychiatric disorders like depression and/or genetics do make some of us more vulnerable to taking this path, no one can force us to do it. And if we see doctors—or, for that matter, dealers—as having “caused” our addictions, we open ourselves up to be dehumanized and stigmatized.

That is because if we are seen as incapable of making good choices, how can we expect respect for our desires and preferences? If we can’t control ourselves, why shouldn’t we be incarcerated to protect others from our actions? After all, when the public sees us as mindless zombies, their response is not sympathy for our supposed powerlessness but fear and disgust at our imagined violence.

Even the overdose issue is mismanaged due to our hatred of addicts. Overdoses have now overtaken car accidents as a leading cause of accidental death, but it’s unclear how much of this increase is due to the actual rise in the use of opioids and how much to medical examiners simply attributing more deaths to these drugs since they are now found in more dead people. What is clear is that most of these deaths occur in the context of drug abuse—95%, according to one study of one of the hardest-hit states. A large number of these deaths could be prevented by providing the antidote to opioid poisoning, naloxone, with prescriptions for the drugs. But because we want the wages of sin to be death, however, drug warriors have largely prevented funding for programs to broadly distribute that lifesaving medication.

The opioid problem is really the stigma of addiction writ large. Consequently, if we want to stop getting in the way of access to painkillers for people who genuinely need them, we need to take responsibility for our own actions and help fight this stigma. No one but you can make yourself into an addict. But chronic pain can happen to anyone.

Aromatase inhibitors in post-menopausal endometriosis
Author: Nikolaos Polyzos, Human Fatemi, Apostolos Zavos, Grigoris Grimbizis, Dimitra Kyrou, Juan Garcia Velasco, Paul Devroey, Basil Tarlatzis, Evangelos Papanikolaou
7thSpace Interactive, made available via BioMedCentral (Open Access).
Credits/Source: Reproductive Biology and Endocrinology 2011, 9:90

Postmenopausal endometriosis is a rare clinical condition. The diagnosis and treatment of an endometriotic lesion in postmenopausal women is complicated.

First line treatment choice should be surgical, given that there is a potential risk of malignancy. Medical treatment may be considered as second line or as an alternate first line treatment whenever surgery is contradicted and aims to alter the hormonal pathway leading to endometriosis progress.

Different hormonal regimens have been administered to these patients, with conflicting however results. Aromatase inhibitors (AIs) represent one of the most recently used drugs for postmenopausal endometriosis.

Clinical data for the use of (AIs) in postmenopausal patients is scarce. Up to date only 5 case reports are available regarding the use of these agents in postmenopausal women.

Although definite conclusions may be premature, AIs appear to considerably improve patients’symptoms and reduce endometriotic lesions size. Nonetheless the subsequent induced reduction in estrogen production, leads to certain short-term and long-term adverse effects.

Despite the limited available data, AIs appear to represent a new promising method which may improve symptoms and treat these patients, either as first line treatment, when surgery is contraindicated or as a second line for recurrences following surgical treatment. However, careful monitoring of patients’risk profile and further research regarding long-term effects and side-effects of these agents is essential prior implementing them in everyday clinical practice.

FDA to limit acetaminophen in prescription drugs
The agency will cap the amount of the pain reliever in such drugs as Percocet and Vicodin, but it won’t affect over-the-counter preparations.
By Andrew Zajac, Washington Bureau
January 14, 2011
As found at the L.A. Times website.

Reporting from Washington — The Food and Drug Administration will limit the amount of the pain reliever acetaminophen allowed in commonly used prescription drugs such as Percocet and Vicodin to reduce the danger of harm to the liver.

But Thursday’s announcement, setting a maximum of 325 milligrams per prescription pill, will not affect over-the-counter products containing acetaminophen, which is best known by the brand name Tylenol.

The FDA also will require box warnings — its strongest labeling requirement — about possible liver damage on acetaminophen prescription products.

Acetaminophen is usually paired with painkilling opioids like hydrocodone or oxycodone and such combination products are prescribed nearly 200 million times per year, making them among the most widely used prescription drugs.

Acetaminophen is valued as a pain reliever in part because, unlike other common analgesics such as aspirin, ibuprofen and naproxen, it does not cause gastric bleeding or other stomach discomfort.

But regulators have long worried about liver damage from the drug, particularly when taken in excess of a 4,000-milligram daily limit or with alcohol.

Acetaminophen overdose is the leading cause of liver failure and the leading cause of death from liver failure in the U.S. Overdoses accounted for 56,000 hospital emergency room visits and were linked to an average of 458 deaths annually during the 1990s, according to FDA data.

Avoiding overdose can be challenging because the drug is blended into so many cold preparations and pain relievers.

The FDA is not taking any action affecting the levels of opioids in the drugs, and the lowering of the acetaminophen dosage won’t affect their pain-relieving quality, said Sandra Kweder, a senior official in the FDA’s drug office, who briefed reporters on the changes.

“We don’t believe we are making these products less effective,” said Kweder, who noted that the combination drugs were introduced with lower doses of acetaminophen that crept upward over time.

The elimination of versions of drugs containing up to 750 milligrams of acetaminophen will be phased in over three years and is not expected to create shortages of pain medication.

While the FDA’s action will lessen the strain of acetaminophen-opioid combinations on the liver, it may have the unintended consequence of increasing abuse of the drugs, said Frank Palumbo, director of the University of Maryland’s Center for Drugs and Public Policy.

“I think it’s a double-edged sword,” Palumbo said. “Some patients may be tempted to take more of the opioid.”

The FDA’s restrictions are less stringent than the suggestions of an agency advisory committee, which by a narrow margin in July 2009 recommended a ban on Percocet and Vicodin.

Kweder said limiting the amount of acetaminophen was “a more reasoned and reasonable” approach that would not disrupt pain management programs.

In a statement, Abbott Laboratories, the maker of Vicodin, said it was “evaluating the FDA’s guidance and will determine how best to comply.”

One prescription drug containing acetaminophen, known by the Darvocet brand name, was removed from the market at the FDA’s request in November because of concerns about the heart toxicity of propoxyphene, the other active ingredient in the product.

Elimination of acetaminophen in higher dosages in prescription compounds means that it will be available on its own in a higher strength — 500 milligrams — in both over-the-counter and prescription versions.

The 2009 advisory committee recommended imposing a maximum strength of 325 milligrams for over-the-counter acetaminophen, but Kweder said the FDA hadn’t decided what actions, if any, it would take.

Sidney Wolfe, director of the nonprofit Public Citizen’s Health Research Group and a member of the advisory committee, lauded the FDA for its action on prescriptions, but he said the agency also should have restricted the size of over-the-counter doses because they make up 80% of the acetaminophen market.

GWEN IFILL: “The Journal of the American Medical Association” released a new study today that finds women on hormone replacement therapy are at greater risk for contracting more aggressive cancers. The study followed nearly 13,000 women between the ages of 50 and 79 for 11 years.

It found the women who took a combination of estrogen plus progestin had an increased risk of death compared to women not on the drugs. The use of hormone replacement therapy to relieve post-menopausal discomfort such as hot flashes has long been the subject of debate.

Dr. Rowan Chlebowski, the study’s lead author, is a medical oncologist at the Los Angeles Biomedical Research Institute. And Dr. Julie Gralow is director of breast medical oncology at the Seattle Cancer Care Alliance and the University of Washington School of Medicine.

Welcome to you both, Doctors. Dr. Chlebowski, you authored this report. At least you were one of the authors. Tell us a little bit about what you found about the increased cancer risk.

DR. ROWAN CHLEBOWSKI, Medical Oncologist, Los Angeles Biomedical Research Institute: Sure. We expanded our observations of the women’s health initiative trial, as you mentioned, of estrogen plus progestin vs. placebo.

Previously, we had reported that the breast cancers were increased and that they were at higher stage. Now we extend that to show that not only good-prognosis cancers, but also aggressive cancers, were increased. And for the first time, we report that deaths from breast cancer are statistically increased as well.

So, this means that cancers that originate on estrogen plus progestin are a real concern.

GWEN IFILL: Does that mean that they’re not diagnosed as soon or that they’re just more virulent in the first place?

DR. ROWAN CHLEBOWSKI: Well, it seems like a little bit of both. The stage is related to the delay in diagnosis. Estrogen plus progestin increases breast density. It acts like a veil over the breast, so it’s harder to see the tumors, yet they’re still growing. So, that’s one factor.

We also think that estrogen plus progestin may have direct effects on the biology of the cancer, making them grow more aggressively.

GWEN IFILL: Dr. Gralow, what is your thought about this after you read this report?

DR. JULIE GRALOW, Seattle Cancer Care Alliance: Well, I think it’s really important that we’re now showing a death.

I think no women should be going on hormone replacement therapy indefinitely after they go through menopause. But I also think it’s important to point out that a companion study that just showed estrogen alone, without the same progestin, really didn’t show an increase in breast cancer. So, there are some other options.

GWEN IFILL: Well, let me ask you about that a little bit. Are we talking about the duration, the amount of time that women are on these drugs, or which drugs they’re on?

DR. JULIE GRALOW: I think it’s probably part of both.

GWEN IFILL: No, go ahead, Dr. Gralow. I will ask you that as question, Dr. Chlebowski.

DR. ROWAN CHLEBOWSKI: Sure.

DR. JULIE GRALOW: I think it’s part of both. The women in this study, on average, were about 62 at the time that they started their hormone replacement therapy. They weren’t women in their late 40s, early 50s who were just starting to get menopausal symptoms. So, it doesn’t really address the age at which they started.

These women were a bit older than most women thinking about going on hormone therapy. Also, I will let Dr. Chlebowski answer the question about the duration. Probably shorter is better if you have to go on these drugs.

GWEN IFILL: Let me ask Dr. Chlebowski to respond to that.

DR. ROWAN CHLEBOWSKI: Sure. One thing is that, for heart disease, it may make a difference to start estrogen plus progestin closer to menopause. But, actually, in this study, we had 5,000 women in their 50s. And the women who started estrogen plus progestin within five years of menopause actually had a somewhat higher risk of breast cancer incidence. Their increase was 41 percent, which was higher than women who entered later.

But it’s true that the estrogen only, which can really be given practically to women who don’t have a uterus, didn’t show this effect. Now, in terms of duration, because the estrogen plus progestin hinders breast cancer diagnosis, it’s really not possible to define a safe interval for at least breast cancer risk. But women should really heed the short-duration FDA labeling indication.

And I think if they have been on it for a year or so, they should talk to their doctor about potentially stopping to see if they still have climacteric symptoms, hot flashes, night sweats that would require them to continue on therapy.

GWEN IFILL: Before I ask Dr. Gralow to respond to that, I want to ask you a little bit about this report, because the study, which began in 1993 — and periodically we get new results from it — have the drugs changed, have the treatments changed in the period of time since this study began?

DR. ROWAN CHLEBOWSKI: Well, of course we evaluate only one dose and schedule.

GWEN IFILL: That’s true.

DR. ROWAN CHLEBOWSKI: And that was the dose and schedule that was being used by 95 percent of U.S. women when the study started.

GWEN IFILL: Which is Prempro, right?

DR. ROWAN CHLEBOWSKI: Which is Prempro. Conjugated equine estrogen and medroxyprogesterone acetate is one pill.

Now the dosage is about half that’s commonly used. Other preparations are being used. But, of course, we don’t have safety information on lower dose or different schedules or different drugs. You would have to do a repeat safety study, which would again take years and years to complete.

GWEN IFILL: Dr. Gralow, how — how — what should people make of this? What should women make of this? What kinds of risks vs. benefits should they be applying to this kind of information?

DR. JULIE GRALOW: I think, if we’re talking estrogen plus progestin, we really no longer can feel that it’s safe to stay on it for a long period of time.

The main reason to use that combination is to help get through those hot flashes, the insomnia, the mood swings that go along with the period that we call perimenopause, as we’re kind of getting into menopause.

I do think serious considerations should be given to other ways of giving progestin. I agree with Dr. Chlebowski that we don’t have big, huge 10,000-, 20,000-patient studies with different forms of progestin.

But in a study without any progestin alone, we didn’t see increased breast cancer. Perhaps progestin can be used just a few times a year to help protect our uterus, or maybe different forms of progestin, such as an IUD giving progesterone, might be another alternative, if you have a uterus.

If you don’t have a uterus, don’t take progestin. That’s a clear answer.

GWEN IFILL: Dr. Chlebowski, I’m curious whether this is just indicated — the negative indications here are only about breast cancer, or about other cancers as well.

DR. ROWAN CHLEBOWSKI: Yes. I think, in the last October, we reported from the WHI in the same study that lung cancer mortality was increased by 71 percent. That was statistically significant. And so these two taken together really are really quite a tandem, when you say that estrogen plus progestin taken for about five years significantly increases the risk of deaths in the two most common causes of cancer death in women.

So that I think raises the bar for women to think how serious their symptoms or limiting their symptoms should be before they should consider starting this therapy.

GWEN IFILL: Is it raising the bar for doctors as well when it comes to prescribing it?

DR. ROWAN CHLEBOWSKI: I think so. I have been looking at the news reports coming out this afternoon. And I think there’s been a number of people who, surprisingly, are saying now that they have more reservations than they did before these last two reports.

GWEN IFILL: Dr. Gralow, do you have more reservations?

DR. JULIE GRALOW: Well, I’m a breast cancer physician. Most of my patients have breast cancer. And I’m not recommending estrogen for them. So, it doesn’t really change my standard practice.

As for what I will be discussing with patients at increased risk for breast cancer, if you really need, for symptoms — and symptoms only — to go on some estrogen, do it at the lowest dose for the shortest amount of time. For osteoporosis, for cholesterol, for other issues, or vaginal, urogenital health, we have other options. And we should be using those first.

GWEN IFILL: Dr. Chlebowski, is there an immediate action that the medical industry or the pharmaceutical industry can take, say, put warning labels on these kinds of drugs?

DR. ROWAN CHLEBOWSKI: Well, I guess the FDA, you know, is responsible for the labeling.

And I, for one, would like to see a little bit more emphasis on the cancer risk on the label. There is a — there is a label warning for breast cancer risk, not for lung cancer risk. Again, that’s a Federal Drug Administration decision as to what the labeling should be.

GWEN IFILL: Is that something which is at all useful, Dr. Gralow?

DR. JULIE GRALOW: Well, I think that, you know, it’s helpful. It will make physicians and make patients think a little bit harder about it. It really doesn’t help you make the decision.

GWEN IFILL: And that’s a decision that still has to be up to the woman, rather than just the doctors or the FDA, I gather?

Dr. Julie Gralow…

DR. JULIE GRALOW: Well, it’s a complicated…

GWEN IFILL: Oh, go ahead.

DR. JULIE GRALOW: It’s a complicated discussion…

GWEN IFILL: Yes.

DR. JULIE GRALOW: … you know, between the patient and the physician. And there are risks and there are benefits. And it’s a very individualized decision.

GWEN IFILL: It’s finding that balance. Dr. Julie Gralow and Dr. Rowan Chlebowski, thank you both very much.

DR. ROWAN CHLEBOWSKI: You’re welcome.

DR. JULIE GRALOW: Thanks.

 
See also In The News – Pharmaceuticals Can Be Dangerous.

See also the MSNBC video report, “Study: Hormone Therapy Increases Health Risk”. Hopefully you won’t have to sit through the political commercial before the news report. But if you do, sorry. :/

Many thanks to Jeanne for posting about this on Facebook!

You have got to be kidding me. I just learned that the drug Thalidomide, which I thought was banned in the 1970s, is still prescribed for illnesses. I learned further that there’s been an ongoing study since 2006 of Thalidomide treatments in women with endometriosis.

Thalidomide. The drug which is known to have a side effects list a mile long, including neuropathy in people taking the drug, and severe birth defects in children born to parents taking the drug. The drug which comes with the following warning, “you should know that thalidomide is present in your blood and body fluids. Anyone who may come into contact with these fluids should wear gloves or wash any exposed areas of skin with soap and water.”
Does that mean that people taking Thalidomide should not be working? I’m a school teacher with stage III endometriosis and ovarian endometrioma – I’m your perfect candidate for treatment, but I work with children – wouldn’t they be at risk? Therefore people on this treatment are likely treated as patients – homebound – isolated from the general population, like those with Hepatitis C – unable to share eating utensils and bathrooms, right?

Thalidomide. The drug with such known side effects as “uncontrollable shaking of a part of the body”, “seizures”, and “nerve damage that can be severe and permanent. This damage may occur any time during or after your treatment”.

The first wind I got of Thalidomide being used to treat endometriosis was when I checked my Google News Alerts today and found the article titled, Health News: A pill to treat endometriosis:
By DAILY MAIL REPORTER
Last updated at 1:41 AM on 21st July 2010

“The controversial drug thalidomide is being used to treat endometriosis in a new trial.
Previous smaller studies have shown eight out of ten women went into remission after treatment.
The drug is thought to work by stopping new blood vessels growing.
Endometriosis is a condition where cells that usually line the womb are found elsewhere in the body, such as in the ovaries.
These cells behave in the same way as womb cells, so every month they grow and shed as a bleed. This leads to pain and swelling. It may also cause fertility problems.
The new treatment focuses on a side-effect of thalidomide – blocking the growth of new blood vessels. As endometriosis requires a blood supply in order for the cells to implant and grow, the theory is that thalidomide prevents any new development.
During the U.S. trial, women will take the drug daily for 14 to 16 weeks, and will be followed up six months later.”

I then googled “thalidomide endometriosis” and found the following:

Open Label of Thalidomide in Treatment of Women With Chronic Pelvic Pain Associated With Endometriosis
Summary:
Patients will undergo a standard history and physical examination detailing objective clinical exam findings performed by one of the co-investigators. The research coordinator will obtain baseline values for intensity of pain, quality of life, and coping strategies. Baseline serum levels inflammatory markers will then be measured. Over the course of 12 weeks Thalidomide will be titrated as tolerated to achieve a minimum of a 30% reduction of pain on VAS from week 2.

Start Date: October 2006
Projected Completion Date: February 2010
Status: Recruiting
Phase of Study: Phase 4
Study Type: Interventional
Study Design: Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Study Information Provided By: University of North Carolina, Chapel Hill
Oversight Provided By: United States: Food and Drug Administration
Sponsors:
Celgene Corporation
University of North Carolina, Chapel Hill

Health Issues Studied:
Endometriosis

Study Interventions:
Drug: Thalidomide

Description:

Study Eligibility Requirements
Genders Eligible for Study: Female
Ages Eligible for Study: 18 Years – N/A
Does Study Accept Healthy Volunteers: No

Inclusion Criteria:
1. Age > 18 years

2. Histologically/laparoscopically confirmed endometriosis

3. Chronic pelvic pain defined as non-menstrual pain for at least two weeks in the
previous month for at least 6 months

4. VAS of 6 or more at baseline

5. Failure, completion or intolerance of standard treatment modalities (oral
contraceptive therapy, danazol, Depo-Provera, Depo-Lupron)

6. Patients must give written informed consent.

7. Patients must be willing and able to comply with the FDA-mandated S.T.E.P.S.
program.

Exclusion Criteria:

1. Pregnant and/or lactating female

2. Users of other angiogenesis inhibitors

3. Current use of Rifampin, rifabutin, barbiturates, glucocorticoids, phenytoin,
carbamazepine, chlorpromazine, reserpine, penicillin derivatives, or St. Johns Wart
in user of oral contraceptive therapy

4. Use of aromatase inhibitors, Etanercept (Enbrel), GnRH agonists (Depo-Lupron), and
Danazol within the past 3 months

5. Use of norethindrone acetate (Aygestin) in the prior month

6. Seizure disorder

7. Hepatitis, or any active infection (upper respiratory infection, PID, etc)

8. History of thromboembolic disease.

9. Baseline neutropenia (ANC < 1000/mm3) 10. Any severe physical or metal illness that would interfere with the completion of the protocol 11. Illicit drug or alcohol abuse Study Contacts
Primary Contact Information:
Name: Denniz Zolnoun, MD, MPH
Phone: 919 966 9189
Email: zolnound@med.unc.edu

Study Locations:
UNC Chapel Hill
Chapel Hill, North Carolina 27599 United States

University of North Carolina at Chapel Hill
Chapel Hill, North Carolina 27599 United States

In 2008, the following research was published:
Mechanistic and Therapeutic Implications of Angiogenesis in Endometriosis
Robert N. Taylor, MD, PhD, Jie Yu, MD, MSc, Paulo B. Torres, MD, Aimee C. Schickedanz, MD, John K. Park, MD, MSc, Michael D. Mueller, MD, and Neil Sidell, PhD
Department of Gynecology and Obstetrics, Human Uterine Biology Program, Emory University School of Medicine, Atlanta, Georgia
Address correspondence to: Robert N. Taylor, MD, PhD, Woodruff Memorial Building 4217, Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, Georgia 30322. Email: robert.n.taylor@emory.edu

Published in final edited form as:
Reprod Sci. 2009 February; 16(2): 140–146.
Published online 2008 November 11. doi: 10.1177/1933719108324893.

“…At the present time, the authors are aware of only 1 clinical trial of an antiangiogenic agent for the treatment of pain associated with ovarian endometrioma. In an abstract presented at the 2002 meeting of the ASRM (Seattle), Scarpellini et al59 reported that 8 of 10 women with stage IV endometriosis achieved remission of pain and resolution of ovarian cysts following a 6-month course of combined goserelin (GnRH analog) and thalidomide (300 mg/d). In some women, the symptom relief persisted following discontinuation of the GnRH analog while the patients received only thalidomide therapy. These promising pilot findings are well supported by a series of studies examining antiangiogenesis in preclinical models of endometriosis. Thalidomide was shown to inhibit IL-8, an angiogenic cytokine, in endometriotic stromal cells via interference with the transcription factor NF-κB.6.”

“…Future therapeutic strategies to target VEGF have the potential to block the establishment or progressive growth and invasion of endometriotic lesions. However, we must not ignore the likely teratogenic* actions of these same antiangiogenic drugs and cotreatment with effective contraceptives is prudent in reproductive-age women.”

*te·rat·o·gen
–noun Biology .
a drug or other substance capable of interfering with the development of a fetus, causing birth defects.

This study was reupped in December, 2009, and was supposed to have been completed in January or February 2010, which is why we’re now reading about it in mainstream media like The Daily Mail, UK.

Based upon the last Clinical Trial news in December, 2009, it looks like only 14 women enrolled in this program. That’s an embarrassingly small sample of women. If the researchers are backed by huge Pharma and the FDA, this will pass as legitimate and be marketed to women, if it is not already being done.

And so a whole new generation of women and their offspring will be wrecked by Thalidomide.

Wonderful.

I must note that once again, not only is the treatment worse than the disease itself, but we are still being used as guinea pigs.
Not only do endometriosis patients treated with Thalidomide have to watch where their precious bodily fluids end up, for fear of poisoning others with the toxic Thalidomide, but those women who embark on this treatment must understand that they can NEVER have children, EVER, after putting Thalidomide into their bodies. You KNOW that is not going to get communicated properly.

Why, in the 21st century, must we still be experimented on, just because we are female?

There truly is no hope for humankind.

Endometriosis not predicted by hormone effect
Internal Medicine News, Feb 1, 2008 by Miriam E. Tucker

WASHINGTON — Response to hormonal therapy does not accurately predict whether a patient has endometriosis, Dr. Todd R. Jenkins reported at the annual meeting of the AAGL.

Laparoscopy has long been considered the standard for diagnosing endometriosis. However, a 1999 paper by Dr. Frank W. Ling called into question the necessity for doing laparoscopy in women with chronic pelvic pain (Obstet. Gynecol. 1999;93:51-8). The findings of that study, which was sponsored in part by depot leuprolide manufacturer TAP Holdings Inc., suggested instead that a diagnostic algorithm plus a reduction in symptoms with a 3-month trial of depot leuprolide could non-invasively identify those women for whom endometriosis was the cause of pain.

“Our clinical impression has been that many women who failed to respond to hormonal treatment did, in fact, have endometriosis. Unfortunately, many women have been told that they did not have endometriosis since they did not respond to hormonal treatment,” said Dr. Jenkins, director of the division of women’s reproductive health care in the department of obstetrics and gynecology at the University of Alabama at Birmingham.

In a retrospective study conducted by Dr. Jenkins and his then-associates at the Chattanooga (Tenn.) Women’s Laser Center, chart reviews identified 486 patients at the private endometriosis referral center who had undergone laparoscopy for chronic pelvic pain and who had received at least 3 months of preoperative hormonal therapy. Of those, a total of 105 met the study criteria, which included complete information regarding response to treatment and less than 3 months between completion of hormonal therapy and the laparoscopy.

The hormonal treatments were oral contraceptive pills in 80% of the patients and gonadotropin-releasing hormone (GnRH) agonists in 20%. Response to the hormones, defined as either partial or complete symptom relief, was achieved in 46% (48), while 54% (57) had no relief of symptoms. Endometriosis was identified subjectively during laparoscopy in 84% (88) of the women, and a pathological diagnosis was made in 67% (70). These findings confirm those of Dr. Ling and others that endometriosis is present in approximately 80%-85% of women with well-defined chronic pelvic pain, Dr. Jenkins noted.

There was no significant difference in the rate of endometriosis between all hormonal therapy responders and nonresponders, either by subjective impression or pathological diagnosis. Subjective diagnoses of endometriosis were made for 85% of responders (41/48) and 81% of nonresponders (46/57), and pathological diagnoses in 65% (31/48) and 68% (39/57), respectively. Endometriosis rates also did not differ between the 35 responders and 48 nonresponders to oral contraceptives specifically.

Differences were significant for those who took GnRH agonists: Subjective diagnoses of endometriosis were made in 100% (9/9) of responders, compared with just 50% (4/8) of nonresponders, and pathological diagnoses in 89% (8/9) of responders vs. 25% (2/8) of nonresponders. However, the number of cases was too small to be conclusive, he said.

Response to hormonal therapy also did not predict the diagnosis of endometriosis at any specific location except for the anterior bladder wall peritoneum (70% of responders vs. 30% of nonresponders), but only 10 patients had endometriosis at that site. The same was found for pathologically confirmed diagnoses: Only endometriosis of the anterior peritoneum was statistically more likely among responders than nonresponders (85% vs. 15%), and again, the data were limited because the numbers were very small, Dr. Jenkins added.

He noted that these findings should not be interpreted to mean that a trial of GnRH agonists isn’t a good idea, since they were found to be the most effective hormonal treatment for the relief of symptoms. “We do not disagree with a trial of empiric therapy in patients with chronic pelvic pain. But no judgment should be made regarding the diagnosis of endometriosis based on the response to hormonal therapy without a laparoscopic evaluation. A laparoscopic diagnosis is still the gold standard.”

BY MIRIAM E. TUCKER

Senior Writer
COPYRIGHT 2008 International Medical News Group
COPYRIGHT 2008 Gale, Cengage Learning

Part II: Overpriced poison?
Posted: Nov 2, 2009 03:53 PM
Updated: Nov 2, 2009 06:22 PM

28-year-old Rachelle Fenner finds it hard some days to just get out of bed.

“Right now, my face is numb, my shoulders are numb, I feel dizzy, I just don’t ever feel good.”

“It’s horrible,” says 30-year-old Mary Orseno. “It’s debilitating. I can’t work full-time. I suffer quite a bit. I can’t play with my son the way I used to be able to play with my son.”

The stories told by Rachelle Fenner and Mary Orseno echo those of young women across the country.

Women whose doctors have prescribed Lupron for Endometriosis: a medical condition that causes pelvic pain, irregular bleeding and possible infertility.

“After I took the Lupron,” Mary recalls, “I started having more and more things go wrong.”

Mary’s been off Lupron for nearly five years.

“I was told that those things should go away after stopping taking the Lupron and for awhile they did but then came back worse.”

Dr. Rachel McConnell didn’t treat Mary, but she does prescribe Lupron for some of her Endometriosis patients.

“One of the biggest side effects I’ve always been concerned about has been Osteoporosis or Osteopenia developing, so I’m very limited. I limit the use of that medication. If a patient has used it once then I pretty much do not want them to use it again.”

Osteoporosis is a known side effect, but the seriousness has been downplayed according to a lawsuit that was filed in Clark County District Court but is now a federal case.

It centers on a woman who took Lupron when she was just 17.

By age 20, she’d developed bone loss so severe that she’s been diagnosed as totally and permanently disabled.

Lupron is made by Illinois-based Abbot Labs. They wouldn’t give us anyone to talk to on camera, but did provide a statement.

It says: “Lupron has had more than two decades of clinical experience and is an important treatment option for patients with advanced prostate cancer and endometriosis. Both the benefits and risks of therapy are well known and clearly outlined in the label for consideration by physicians before recommending treatment.”

But medical records filed with the lawsuit document other serious side effects that aren’t on Lupron’s label, like back and neck pain, severely debilitating bone loss, and thyroid disorder.

Endometriosis expert Dr. David Redwine doesn’t use Lupron because he says its risks far outweigh the benefit of temporary pelvic pain relief.

“One of the disturbing things is that some of these side effects seem to be long-lasting in women. Even women who have been off Lupron for months or years.”

In a document Abbott filed in the federal case, the manufacturer says: “Lupron is neither defective nor unreasonably dangerous when properly prepared and accompanied by proper warnings and instructions for use.”

But Dr. John Gueriguian, who spent 20 years reviewing drugs for the FDA, disputes that.

In an expert opinion he submitted for the federal lawsuit, he says the manufacturer “intentionally suppressed knowledge about the real danger associated with the use of Lupron… misleading both prescribers and patients.”

He says their studies are inadequate and they’ve “failed to put warnings in the Lupron labeling about known adverse events which were reported to FDA and known throughout the medical community.”

“I really wish the FDA would take a harder look at that,” Mary says. “Something needs to be done. And I don’t know if they’re ignoring it or they’re just not realizing it but I think they really need to take a harder look at Lupron itself.”

The FDA has more than 12,000 adverse events from Lupron patients on file right now, including more than 1100 deaths.

Most are men taking Lupron for advanced prostate cancer, and as a result of our inquiry, the FDA is evaluating Lupron’s safety as a prostate cancer treatment.

But women are dying too and we wanted to know who’s looking out for them.

We wanted to ask the FDA how many reports it takes before the government takes action?

Contact 13 sent numerous e-mails and made repeated phone calls to ask why they keep the data if they don’t use it or it doesn’t trigger something?

When does a red flag go up?

They haven’t answered any of those questions.

But they say they continue to monitor patient complaints, and if they see potential for a widespread problem, the agency will take action as needed.

“I think the FDA is just as much a victim of Big Pharma marketing as consumers are,” says Dr. Redwine.

Unless and until Congress or the FDA does something, consumers feel like they’ve got little help and even less hope.

“Pack your bags and run,” says Derrick Fenner.

We spoke to his wife, Rachelle, at the beginning of this story.

“If your doctor says the word Lupron, get up and walk out. It’s not worth it! It’s just not worth it,” he says.

Abbot Labs says everything about Lupron, from design through marketing, complied with federal law.

But here’s a little perspective for you.

According to Dr. Gueriguian–the former FDA medical officer–the pharmaceutical industry is responsible for performing all studies needed to develop a new drug.

So FDA approval is based on information provided by the drug company.

The manufacturer is also largely responsible for pre- and post-marketing safety and contents of their labeling.

FDA acknowledges the agency rarely takes a drug off the market without the approval of its manufacturer.

Many thanks to Melissa Ralston, moderator of the Goddesses of Endometriosis email list, for finding this hair-raising story.

Overpriced Poison?
Posted: Oct 30, 2009 04:15 PM
Updated: Nov 1, 2009 11:56 PM

Doctors and a drug company may be getting rich at the expense of patients and taxpayers. Devastating side effects kept secret and ineffective government oversight.

It sounds like a movie script, but it’s playing out in reality.

Contact 13 Chief Investigator Darcy Spears talked to women in Las Vegas and across the country who are begging federal authorities to investigate and recall what they say is nothing short of overpriced poison.

“I have pain in my chest and in my ribs, the bone pain,” says 28-year-old Rachelle Fenner.

“I have severe pain in my neck and shoulder,” echoes 30-year-old Mary Orseno.

Rachelle can’t feel her shoulders or her face. Mary often can’t feel hot and cold.

Rachelle’s eyes go blurry.

Mary says, “There are some days I just burst into tears just thinking about getting out of bed.”

Both women were prescribed the same drug, Lupron Depot, for the same reason endometriosis–a medical condition in women that causes pelvic pain, irregular bleeding and possible infertility.

Rachelle recalls a couple weeks she got the shot, “I swelled up like I was five months pregnant.”

She’s been off the drug for months.

“It’s taken a lot from us,” says her husband, Derrick, with tears sliding down his face. “It really has. Every day’s a fight. You just don’t know.”

Mary took it almost five years ago.

“I could do normal things like play with my son and go out and go for a walk and go for a bike ride and all of that is just nearly impossible at this point to do those things,” she says.

Like millions of women across the country, Mary and Rachelle were told their pain would go away if they took this highly toxic cancer drug.

“Is there ever a day when you say, you know what, getting rid of the pain was worth it?” Darcy Spears asked.

“No,” Rachelle answers emphatically.

She and Mary both say they’d gladly take it all back.

“I would have lived with the endometriosis pain. That pain compared to the pain that I experience every day is nothing,” Mary said.

Lupron was originally approved in the 1980s to help men with advanced prostate cancer live longer.

But it doesn’t work for dying men, and it has significant side effects.

That’s according to two recent studies published in the Journal of the American Medical Association.

In 1990 the FDA approved it as a pain reliever for women with endometriosis.

But it’s so toxic, it’s not recommended for more than 12 months in a lifetime.

Renowned endometriosis experts like Dr. David Redwine steer clear of it altogether.

“Lupron does not make endometriosis go away so the cure rate with Lupron is zero,” Redwine explains. “So if you take the rate of essentially 100-percent side effects and compare that with a zero percent cure rate, I think it’s clear that the risks and side effects far outweigh the benefits.”

Entire websites are devoted to those who call themselves Lupron victims.

There’s a petition to Congress and letters to the FDA demanding a recall.

And an ongoing federal lawsuit filed here in Las Vegas centers on a woman who took Lupron when she was just 17 years old.

By the age of 20, she’d developed severe bone loss and has been medically diagnosed as totally and permanently disabled.

Still, many doctors keep prescribing it, citing medical studies as support.

“I would choose Lupron as a treatment for endometriosis because there’s been very good clinical studies that show that patients respond to the drug,” says Dr. Rachel McConnell of Nevada Fertility C.A.R.E.S.

“These articles come out like wolves in sheep’s clothing,” counters Dr. Redwine. “They are cloaked in what appears to be science and in many respects the results sound too good to be true.”

In some cases, they are.

The U.S. Department of Health and Human Services issued a scientific misconduct finding against a former Harvard Medical School professor who falsified and fabricated 80-percent of the data in his pro-Lupron studies.

But Dr. McConnell says she wouldn’t use Lupron if she felt there was too much risk.

“There’s a certain group of patients for whom I think it is worth it.”

Lupron is manufactured by Illinois-based Abbott Laboratories–formerly Takeda Abbott Pharmaceuticals, called TAP.

In 2001, TAP pled guilty to civil and criminal misconduct over Lupron.

They agreed to the then-largest healthcare fraud fine in history–$875 million dollars.

The U.S. Department of Justice found TAP bribed doctors to prescribe Lupron.

In addition to cash and trips, the doctors would get Lupron for free and then bill Medicare or Medicaid at $500 per dose.

Redwine says, “Doctors have been trained by medical journal articles favoring Lupron, they have been trained by listening to speakers hired by Lupron to speak at major national and international medical meetings.”

No one from Abbott Labs would go on camera.

They provided a statement saying: “Lupron has had more than two decades of clinical experience and is an important treatment option for patients with advanced prostate cancer and endometriosis. Both the benefits and risks of therapy are well known and clearly outlined in the label for consideration by physicians before recommending treatment.”

But some serious side effects reported by patients aren’t on the label.

“I’m assuming that no one ever told you that this drug can cause an immune disorder or attack your thyroid or your nervous system?” Spears asked Mary Orseno.

“No,” Mary says. “Never told, never warned. I read pretty thoroughly through the package insert before I ever took it and none of that was in there.”

She says she was only counseled about the menopause-like side-effects and the possibility of Osteoporosis.

Both Mary and the Fenners feel there’s only one answer.

“In my opinion, it’s too dangerous to be on the market,” says Mary.

“I think it’s pretty hostile stuff, what it does to the human body,” says Derrick Fenner, recalling what his wife endures on a daily basis. “I would be happy to see it off the market.”

Abbott’s rap sheet with the federal government doesn’t stop with Lupron.

Just last year, the FDA sent them a warning letter about an HIV drug they make.

FDA cites numerous violations of federal law in Abbott’s promotional materials, which “minimize the serious risks of the drug while overstating its efficacy and including unsubstantiated claims.”

Back on June 30, 2009, I posted an article informing you that the FDA had just voted to remove prescription acetaminophen combination drugs, such as Percocet, Vicodin and Tylenol 3 from the market.

Check out more in this PDF from The Pain Foundation.

The petition has already closed, but you might still be able to get your word in via Regulations.gov. Refer to docket FDA-2009-N-0138-0001.

To anyone who uses Vicodin, Percoset, Darvocet, Lortab, and any meds that contain Acetaminophen, read this!
This has been in the news before, when a group originally petitioned the FDA, but the FDA has now voted. The ban could be real and official very soon.

Excerpt:
“If the combination products are eliminated, the acetaminophen and the other ingredients could be prescribed separately. In effect, patients would take two pills instead of one, and be more aware of the acetaminophen they are consuming.”

I currently take Tylenol 3 and Motrin for endometriosis pain each month. Last year, my liver enzymes were high, and I had to go off of Tylenol for three months until my liver stabilised again. I’ve tried codeine directly without any Tylenol in it, because my GYN is so against the use of Tylenol. But I have bad side effects to codeine. Mixing it with Tylenol seems to work better for me. See my growing list of medications I’ve tried to fight the pain.

So this whole advisory vote is a bit unnerving for me. I need to find alternate working choices for medication, and fast.

FDA panel: Lower maximum daily dose of Tylenol
By MATTHEW PERRONE, The Associated Press
7:51 p.m. June 30, 2009

ADELPHI, Md. — Government experts called for sweeping safety restrictions Tuesday on the most widely used painkiller, including reducing the maximum dose of Tylenol and eliminating prescription drugs such as Vicodin and Percocet.

The Food and Drug Administration assembled 37 experts to recommend ways to reduce deadly overdoses with acetaminophen, which is the leading cause of liver failure in the U.S. and sends 56,000 people to the emergency room annually. About 200 die each year.

“We’re here because there are inadvertent overdoses with this drug that are fatal and this is the one opportunity we have to do something that will have a big impact,” said Dr. Judith Kramer of Duke University Medical Center.

But over-the-counter cold medicines – such as Nyquil and Theraflu – that combine other drugs with acetaminophen can stay on the market, the panel said, rejecting a proposal to take them off store shelves.

The FDA is not required to follow the advice of its panels, though it usually does. The agency gave no indication when it would act on the recommendations.

In a series of votes Tuesday, the panel recommended 21-16 to lower the current maximum daily dose of over-the-counter acetaminophen from 4 grams, or eight pills of a medication such as Extra Strength Tylenol. They did not specify how much it should be lowered.

The panel also endorsed limiting the maximum single dose of the drug to 650 milligrams. That would be down from the 1,000-milligram dose, or two tablets of Extra Strength Tylenol.

A majority of panelists also said the 1,000-milligram dose should only be available by prescription.

The industry group that represents Johnson & Johnson, Wyeth and other companies defended the current dosing that appears on over-the-counter products.

“I think it’s a very useful dose and one that is needed for treating chronic pain, such as people with chronic osteoarthritis,” said Linda Suydam, president of the Consumer Healthcare Products Association.

The experts narrowly ruled that prescription drugs that combine acetaminophen with other painkilling ingredients should be eliminated. They cited FDA data indicating that 60 percent of acetaminophen-related deaths are related to prescription products.

But some on the panel opposed a sweeping withdraw of products that are widely used to control severe, chronic pain. Prescription acetaminophen combination drugs were prescribed 200 million times last year, according to the FDA.

“To make this shift without very clear understanding of the implications on the management of pain would be a huge mistake,” said Dr. Robert Kerns of Yale University.

If the drugs stay on the market, they should carry a black box warning, the most serious safety label available, the panel decided.

“If we don’t eliminate the combination products we should at least lower the levels of acetaminophen contained in those medicines,” said Sandra Kewder, FDA’s deputy director for new drugs, summarizing the panel’s vote.

Percocet and similar treatments combine acetaminophen with more powerful pain relieving narcotics, such as oxycodone.

If the combination products are eliminated, the acetaminophen and the other ingredients could be prescribed separately. In effect, patients would take two pills instead of one, and be more aware of the acetaminophen they are consuming.

Vicodin is marketed by Abbott Laboratories, while Percocet is marketed by Endo Pharmaceuticals. Both painkillers also are available in cheaper generic versions.

“The panel recommending banning Vicodin and Percocet seems a little draconian,” said Les Funtleyder, an analyst for Miller Tabak & Co.

Drug companies avoided the most damaging potential outcome with the defeat of proposal to pull NyQuil and other over-the-counter cold and cough medicines that combine acetaminophen with other drugs.

These drugs can be dangerous when taken with Tylenol or other drugs containing acetaminophen, according to the FDA, but cause only 10 percent of acetaminophen-related deaths.

“I don’t think we should be advocating a solution to a problem that really is not there,” said Dr. Osemwota Omoigui, of the Los Angeles pain clinic.

A recall of combination cold medicines would have cost manufacturers hundreds of millions of dollars in revenue. Total sales of all acetaminophen drugs reached $2.6 billion last year, with 80 percent of the market comprised of over-the-counter products, according to IMS Health, a health care analysis firm.

“The acetaminophen people dodged a bullet,” said Erik Gordon, a University of Michigan business professor who studies the biomedical industry.

Even with the lower daily dosage recommendation, consumers will likely keep taking as many pills as they think they need to ease their pain, Gordon said.

Analyst Steve Brozak of WBB Securities said the panel votes were a “shot across the bow” of the pharmaceutical industry.

“This basically puts more government oversight into something that heretofore has been less than present,” Brozak said.