The Pharmaceutical Cornucopia · 2006-09-22 17:00


Significant Misrepresentations
Mark Geier, David Geier & the Evolution of the Lupron Protocol
(Part Eleven) • Related articles

During his presentation at the 2006 Autism One conference, David Geier summarized the experimental protocol he and his father implemented upon autistic children.

What we’re doing is, sort of, we give Lupron, we then start chelating, and we look to see how basically each therapy is going, and we reevaluate and try to adjust as we go through. And this is just sort of the general framework. And it should be noted that when we do this, we try to be very careful, and we do this through LabCorp, and we do all kinds of monitoring to make sure that no kind of damage is being done. (David Geier, May 26, 2006)

A more detailed description of the experimental drug regimen followed.

The experimental treatment protocol employed consists of administering each child a 0.2mL test-dose of the non-depot form of Lupron.

Each child is carefully observed for three days for any adverse effects.

Children are then administered a Lupron Depot. Children also are supplemented with daily non-Depot Lupron dosing.

Three days following starting of the Lupron Depot and non-depot Lupron, children were administered oral DMSA (morning, mid-day and night, 10mg/kg bodyweight). If severe gastrointestinal disturbances (i.e. severe diarrhea or severe constipation) manifested following oral DMSA, trans-dermal DMSA was administered according to the same treatment schedule as the oral DMSA.

On the alternate days when the children are not receiving DMSA, vitamin and mineral supplementation is administered.

On Day 28 children are administered their second Lupron Depot, and continue to be administered additional Lupron Depots every 28 days.

Patients are monitored as successive doses of Lupron Depot are administered for persistent clinical/laboratory signs of increased androgens, and patients are supplemented with daily non-depot dosing and/or Androcur as necessary.

The following is a discussion of the drugs Lupron, DMSA and Androcur, including summaries of their actions, indications for their use in children, contraindications, research on usage and safety, adverse effects, dosage and methods of administration. Where applicable, instances are highlighted in which statements about these drugs made by Mark and David Geier in presentations and discussions of the “Lupron Protocol” differ from information and recommendations provided by the manufacturers.

Lupron by the Book

In TAP Pharmaceuticals’ package inserts for Lupron Depot-Ped (i.e., slow-release leuprolide) and Lupron Injection (i.e., multidose vials of leuprolide for daily subcutaneous injection), Lupron is described as a “synthetic nonapeptide analog of naturally occurring gonadotropin-releasing hormone” (GnRH), possessing greater potency than the natural hormone (1,2). Lupron acts as a GnRH agonist (GnRH-a); that is, it mimics the action of the hormone secreted by the pituitary gland that affects the function of the male or female reproductive organs. Lupron binds to GnRH cell receptors and triggers a response that is first similar to then significantly different from the response that would ordinarily be provoked by the body’s own GnRH.

In males, Lupron forces the pituitary to over-stimulate cells in the testicles, thereby reducing the ability of the body’s own hormones to stimulate those cells and resulting in lowered testosterone production. Women experience a corresponding reduction in natural ovarian stimulation and estrogen production. The use of Lupron for prostate cancer is known as Androgen Deprivation Therapy (ADT), or chemical castration, its purpose the mitigation of testosterone-dependent malignancy. The drug is also used to chemically castrate male sex offenders. In women, Lupron is used for the treatment of endometriosis, uterine fibroids and breast cancer. The only FDA-approved use of Lupron for children is the treatment of central precocious puberty (CPP), i.e., the premature development of secondary sexual characteristics.

Lupron is not recommended for individuals who are hypersensitive to any of its components. There exist no studies examining the pharmacological interaction of Lupron with other drugs, or the full reversibility of fertility suppression in children. There also exist no pharmacokinetic studies of leuprolide acetate in children.

Due to the initial stimulation of the pituitary, during the first few weeks of treatment, patients often experience an increase in their symptoms.

In two clinical trials involving children with CPP — a total of 395 patients — the following drug-related adverse reactions to Lupron were reported:

General Pain (7 / 2%)
Acne/Seborrhea (7 / 2%)
Injection Site Reactions (21 / 5%)
Rash (8 / 2%)
Vaginitis/Bleeding/Discharge (7 / 2%)

In those same studies, the following adverse reactions were reported in less than 2% of patients:

Body as a Whole: Body Odor, fever, headache, infection
Cardiovascular system: Syncope (fainting), vasodilation
Digestive system: Dysphagia (difficulty swallowing), gingivitis, nausea/vomiting
Endocrine system: Accelerated sexual maturity
Metabolic and nutritional disorders: Peripheral edema, weight gain
Nervous system: Emotional lability, nervousness, personality disorder, somnolence (excessive sleepiness)
Respiratory system: Epistaxis (nosebleeds)
Integumentary system: Alopecia (hair loss), skin striae (stretch marks)
Urogenital system: Cervix disorder, gynecomastia (breast enlargement), breast disorders, urinary incontinence

Postmarketing surveillance of Lupron Depot-Ped yielded a greatly expanded list of adverse events.

Anaphylactoid or asthmatic reactions (adverse immunologic responses that require early intervention to prevent life-threatening consequences)
Rash, hives, and photosensitivity reactions
Localized injection-site reactions, including hardening of soft tissue (induration) and abscess
Hypotension (low blood pressure)
Decreased white blood cell count (neutropenia)
Peripheral neuropathy
Spinal fracture/paralysis
Inflammation of tendons (tenosynovitis)
Prostate pain

Pituitary apoplexy is a life-threatening condition requiring immediate medical attention, and a rare but significant adverse effect of Lupron. An acute hemorrhage or infarction of the pituitary, heralded by the sudden onset of headache, visual symptoms, altered mental status, and hormonal dysfunction, pituitary apoplexy generally occurs in patients with previously nonsymptomatic pituitary tumors. A majority of Lupron-related pituitary apoplexy cases have occurred within two weeks of the first dose, and some within the first hour (3-7).

Several studies have found no negative effect on reproductive function in girls following long-term treatment with Lupron (8,9). There are no similar studies of the impact of Lupron treatment on reproductive function in boys, who represent a minority of children with CPP.

The package insert for Lupron Injection also warns of potential changes in bone mineral density (BMD). This is to be expected. All animal studies to date have demonstrated that both androgens and estrogens maintain bone mass and bone integrity, regardless of age or sex (10). Testosterone influences skeletal growth and maintenance by signaling through both androgen and estrogen receptors, which are present in nearly all bone cells; androgens exert direct effects upon bone cells and possibly indirect effects upon muscle or vascular cells (11).

Changes in bone mineral density induced by Lupron treatment are well documented in studies of men with prostate cancer. For example, researchers at Beth Israel Deaconess Medical Center and the University of Pittsburgh found that men with prostate cancer receiving GnRH-a therapy are at risk for low bone density and fractures; a significant correlation was demonstrated between duration of therapy and reduction in bone mineral density (12). In a a 12-month study, men with prostate cancer being treated with androgen deprivation therapy experienced a five to ten-fold decrease in bone mineral density compared with controls, placing them at increased risk of fracture. Bone loss was greatest in the first year after initiation of therapy (13).

Although the package insert for Lupron Injection indicates that Lupron’s effects on BMD had been little examined in children, research on the subject does exist. Some have concluded that Lupron has no long-term negative impact on BMD (14-17). A 1995 study found that levels of osteocalcin, a major component of bone, decreased significantly after nine and twelve months of treatment (18). A 1998 study determined that children with CPP had normal BMD for their chronological age but decreased BMD for their bone age after two years of treatment with GnRH-a therapy (19). In 2002, Dutch researchers reported that BMD in the lumbar spine decreased significantly during Lupron therapy, returning to normal within two years after cessation of therapy (20). Two years later, Italian researchers speculated that children’s genetic potential for bone accumulation could be limited not only by insufficient calcium intake and inadequate physical activity but also by disruption of puberty, and that treatment of CPP with GnRH agonists may have a detrimental effect on bone mass. Since peak body mass is not achieved at final height but later in life, the researchers recommended that the effects of treating CPP with Lupron should be reevaluated when patients are between twenty and thirty years of age. They also recommended an increase in calcium intake, in order to offset the deleterious effects of Lupron on the bones (21).

Assessments vary with regard to the effect of long-term Lupron therapy on body mass index (BMI). Some researchers have concluded that there is no relationship between the therapy and weight gain (22,23). Others have found increases in fat mass and percentage of body fat, and have found that mean BMI was significantly higher in girls on Lupron therapy than it was in controls, suggesting that the difference was due to the treatment rather than other factors (24-26). With regard to populations other than children, a 1998 study of short-term, Lupron-induced androgen deficiency in young men found marked changes in whole body metabolism, including decreased rates of protein turnover and protein synthesis, decreased lean body mass, increased fat, decreased lipid oxidation and energy expenditure rates, and decreased leg muscle strength (27). A 2002 study of prostate cancer patients documented similar results; in addition, the researchers found significantly decreased hemoglobin concentrations, with anemia developing in the majority of study participants (28). In September 2006, researchers at Harvard University announced the results of a study of non-cancer mortality rates in prostate cancer patients treated with GnRH agonists. Men with localized prostate cancer receiving GnRH agonist therapy were found to have a 44% higher risk of developing diabetes and a 16% percent higher risk of developing coronary heart disease than men not receiving hormone therapy (29).

A 2000 case study of a thirteen year old girl who experienced seizures after her third dose of Lupron Depot concluded that the seizures were probably induced by the drug, and were associated with pre-existing brain damage (30). This finding should be of particular concern to parents of autistic children, many of whom experience seizures.

Autoimmune thyroiditis is a possible complication of Lupron recently documented in the medical literature. In 2005, clinicians in Cincinnati reported the development of autoimmune thyroiditis in a nine year old girl with CPP, eight months after initiation of therapy with Lupron (31).

In the largest study of Lupron therapy in women to date (n=3,153), patients reported various adverse effects in addition to those documented in the package insert, including night sweats, irritability, memory loss, bleeding, gas, palpitation, and headache. Nearly 15% of participants in the same study reported weight gain, 35% depression, and 76.7% joint pain, rates significantly higher rates than those reported on the manufacturers’ package insert. Further, 7.3% of participants developed hypertension serious enough to require antihypertensive medication, the incidence of which appeared to be dose-related (32).

The package insert for Lupron Depot-Ped, an intramuscular injection, specifies that the drug must be administered by a physician. Subcutaneous Lupron Injection, on the other hand, may be administered by patients or their parents.

The manufacturers’ label recommends a minimum starting dose of Lupron Depot-Ped of 7.5mg, administered as a single intramuscular injection. The starting dose is determined by the child’s weight.

up to 25 kg (55 lbs): 7.5 mg
25-37.5 kg (82.5 lbs): 11.25 mg
over 37.5 kg (82.5 lbs): 15 mg

The manufacturers’ label also recommends that after one to two months of initiating therapy or changing doses, the progress of treatment should be monitored by a GnRH stimulation test, sex steroid testing, and examination of physical characteristics of puberty. Measurements of bone age for advancement should also be monitored every six to twelve months. If the progression of puberty is not reversed, the manufacturers recommend that the dose be titrated upward in increments of 3.75mg every four weeks. Measurement of sex steroid levels is insufficient to evaluate the progress of treatment or manage dosage; endocrine researchers have observed that there is no single level of gonadal hormones that can be used to identify CPP with 100% specificity and 100% sensitivity (33,34).

The recommended starting dose of Lupron Injection is 50 mcg/kg/day administered as a single subcutaneous injection; the dose can be titrated upward by 10 mcg/kg/day if puberty continues to progress. These dosages are given with the assumption that only one or the other form of Lupron is being administered to a child at one time, not both.

Lupron’s manufacturer recommends discontinuation of Lupron therapy before age eleven for girls and twelve for boys. A 1998 study commissioned by TAP Pharmaceuticals indicated that treatment should cease once a patient reaches a bone age of twelve years (35).

Lupron á là Geier

Mark and David Geier’s descriptions of Lupron and their recommendations for its use in the experimental treatment of autistic children frequently differ from the descriptions and recommendations provided by its manufacturer, and from the knowledge base about the drug that has accumulated over two decades of use and research by experts.

In an August 2006 presentation at the U.S. Autism and Asperger Association (USAAA) conference, Mark Geier offered the following characterization of Lupron’s chemical structure and safety:

The interesting thing about Lupron is, when I first saw the molecule — it’s this big huge, lots of carbons, complex molecule — I actually asked the company that had the patent, “I’d like to talk to the chemist that invented this, since he must be a lot smarter than I am, I would have never figured this thing out, how did they know it was going to work? It’s so huge.” And the answer is, he isn’t any smarter than me. What he did is he took the natural releasing factor, which is this big molecule, and he added one carbon on the end, which makes it stick better. So it’s a molecule that’s like 99% natural and it only works on the hypothalamus, which is why it has virtually no side effects. It’s sort of like, you know, the penicillin is a natural molecule, they’ve modified it to make ampicillin. They didn’t change it, they just added one little side group. So it’s a semi-synthetic, 99% natural — don’t quote me on the 99, I don’t know the exact percent — but almost all natural, one small side group, and that’s how he made it, and that’s why it’s so specific and has so few side effects. (Mark Geier, August 12, 2006)

David Geier made similar assertions in his presentation at the 2006 Autism One conference:

And furthermore, regarding the safety, Lupron is extremely safe. Because Lupron binds to this one receptor, the GnRH receptor, and that’s all it does. So while it’s there, it blocks it from working. And actually, as far as the chemical compound, it is the natural — it’s basically identical to what your body naturally makes. What it does is it binds there and stays there longer. So that as long as it’s there, the normal signal doesn’t come through. And if you stop giving the drug, it’s going to make it basically go away and go back to the way it was. So it’s very, very safe. (David Geier, May 26, 2006)

In his June 2006 interview on Radio Liberty, Mark Geier also claimed unequivocally that Lupron is a safe and appropriate drug for autistic children.

It has been tested for many many years on young children, and because they don’t need testosterone or estrogen, it has virtually no side effects… But if you give it to children whose normal level of testosterone is zero, and you lower these kids to zero, there are virtually no side effects. (Mark Geier, June 23, 2006)

The assertion that Lupron is “semi-synthetic, 99% natural” is directly contradicted by the manufacturer’s unqualified description of Lupron as a synthetic substance. The statement that “it’s basically identical to what your body naturally makes” mischaracterizes the structure and action of the drug. The suggestion that a molecule is not “changed” by the addition of “one little side group” is illogical and inaccurate. Although Lupron is chemically similar enough to naturally-occurring GnRH to bind to GnRH receptors, it ultimately alters the action of naturally-occurring hormones, producing an effect exactly opposite that of GnRH.

The assertion that Lupron “only works on the hypothalamus” is simplistic and misleading. By definition, a hormone is a substance that acts upon an organ or organs to do one or many things; its ultimate effects are not local, but remote. Through its direct action on the hypothalamus and specifically the pituitary gland, Lupron indirectly affects any and all physiological systems affected by reproductive hormones.

Claims that Lupron has “virtually no side effects” are flatly contradicted by both the manufacturer’s prescribing information and by scientific research. The claims that children “don’t need testosterone or estrogen,” and that pre-pubescent children’s “normal” testosterone level is zero, are unsupported in the scientific literature. Although children are not sexually mature, the impact of testosterone and estrogen extends beyond the reproductive system to numerous physiological processes such as bone formation.

There is a wide range of benign variation in testosterone levels. Even among those children who do present with symptoms of premature sexual development, pharmaceutical treatment is not always warranted. One 2004 study of 104 children evaluated by a single endocrinologist over a three year period found that 78% had benign diagnoses generally regarded as variants of normal for which no treatment was indicated; these included premature breast enlargement or development of pubic hair. Only 4% of this group of patients ultimately required endocrine therapy or surgery (36).

Scientific understanding of the full role of sex hormones in human development is in its infancy and is in constant flux. For instance, a 2000 study challenged the long-standing assumption that since testosterone is the dominant sex steroid secreted in men, it is also is the major sex steroid regulating bone metabolism in men. The researchers demonstrated that estrogen plays a significant role in bone resorption and formation in men, a finding reaffirmed in a subsequent study (37,38).

Testosterone and estrogen also significantly influence brain function. Numerous studies have shown that testosterone deprivation has a deleterious effect on cognitive function in elderly men. In a 2004 study, a significant association was found between reduced testosterone levels and impaired cognition, including visuomotor slowing, slowed reaction times, impaired delayed recall and recognition speed of letters (38). Insufficient evidence currently exists, however, to identify either the specific cognitive processes altered by testosterone or their neural basis (40).

A recent study of the effects of Lupron Depot on women’s cognitive function found that women treated with Lupron performed worse on three different tests of working memory (that is, the maximum amount of information storage and manipulation that a person can sustain), and that even short-term use of Lupron induced mild to moderate depression (41). This provides additional confirmation to previously established findings regarding hormonal influences on cognitive function in females (42).

Sex hormones are also implicated in the establishment of sleep/wake patterns. In a 1997 sleep study, researchers found that short term, pharmacologically induced testosterone suppression in men caused significant decreases in the amount of stage 4 sleep and in secretion of prolactin, a hormone that affects sleep regulation (43).

Aggressive behavior and lack of frustration tolerance have been associated with high testosterone levels; however, not all aggression is dependent upon testosterone (44,45). Autistic individuals are particularly vulnerable to sensory and environmental overload, and to frustration arising from communication problems and difficult personal interactions, all of which can result in non-malicious behavior interpreted as aggression.

Eight states permit the use of Lupron and other anti-androgen drugs for the chemical castration of sex offenders. The Texas Council on Sex Offender Treatment recommends that Lupron be reserved for individuals who are predatory, violent, have had prior treatment failures, or are unable to control their sexual arousal (46). The Vermont Agency of Human Services recommends caution in the administration of Lupron to adolescent males who have not reached physical or sexual maturity (47). Recent newspaper articles have reported on the occurrence of osteoporosis in convict-patients on Lupron therapy; seven have sued the state of California, claiming that they were not adequately informed of the severity of the drug’s side effects (48,49).

Although the experimental protocol displayed by the Geiers at the 2006 Autism One and USAAA conferences includes a test-dose of subcutaneous Lupron and subsequent monitoring for signs of hypersensitivity to any of its components, this preliminary step is not included in either the Geiers’ U.S. application to patent the “Lupron Protocol,” or the WIPO patent application filed jointly by the Geiers and TAP Pharmaceuticals. In those applications, eight year old “Child X” and six year old “Child Y” were administered the highest available dose of three-month Lupron Depot, with no preliminary testing. At the 2005 Autism One conference, the Geiers acknowledged that they started out their first two patients on an extraordinarily high dose, but swiftly reassured their listeners that this was a safe thing to do.

DG: We gave enough, at 22.5 milligrams, this would bring down an adult male to zero for eighty-four days.
MG: It’s been widely studied, used for 25 years. (Autism One 2005)

According to the patent applications, “Child X” was injected with a second 22.5mg dose of Lupron Depot only eight weeks after the first, “because of the improvement exhibited… and the absence of observable side effects.” However, during her Autism One 2005 conference presentation, “Child X”‘s mother indicated that the second dose was given ahead of schedule after she reported that her son’s “behaviors were changing” in a manner that was distressing to her.

And somewhere in here I made another one of those panicky phone calls because the behaviors were changing and we were losing the ground we had covered, and I said, “I think it’s going back up.” (Lisa Sykes, May 28, 2005)

“Child X” received four subsequent 22.5mg depot shots, all spaced two months apart. “Child Y” received his shots six weeks apart.

During his presentation at the 2006 USAAA Conference, Dr. Geier described his current method of calculating pediatric Lupron doses:

What we find is that the combination of the slow release depot plus some daily dosing is adequate to control the testosterone in these children…. What we started seeing is that the kids would do great on days 1-20, after the depot shot, but towards day 28 they didn’t do as well, so we sometimes adjust. And if the child is a fast eliminator of Lupron, we might give a shot every 14 days, but we get it adjusted to the testosterone is absolutely even. That’s what we really want. (Mark Geier, August 12, 2006)
I can tell you the basic dose. The IM is 15mg usually given every 28 days, but if we have problems keeping things even, if like on Day 27 they regress, then it can be given every 14 days. That’s 15mg IM pediatric depot every 28 days is what the thing is listed at. And then we give Sub-Q. And the Sub-Q comes in a 2.8mL multidose vial that has five mg per ml. And what we do, is the ultimate dose has been published, probably if you want to fully control the average person, you need 100mcg/kg per day. We don’t start with that, we start lower and if they need more, we work our way up. Which is what the instructions say incidentally. But if you take for example a 40kg [96lb] child as a typical child, that means that they will ultimately probably for complete control need 4mg — that’s 40 times 100mcg/day — 4 mg a day. If you give them the IM shot, which is the 28 day shot — allow me to round it off to thirty — that gives about 1/2 mg a day, because it’s 15 mg divided by thirty. So that’s a half. So they will probably need eventually somewhere around 3-3.5mg of daily, and to give 3mg, you have to give 6/10 of a ml from that multidose vial. So they might need 6/10, 7/10, but we’d probably start around 4/10, and see if they do fine, great, and if not, we’ll bring them up some more. So this is the general dosing kinds of things. And an important thing, and we have everybody do this, is everybody keeps a log, a daily log, because we’re interested in good things, bad things, and we’re also interested in where they occur relative to when the shots are. That’s how we’ve learned to make the adjustments.

Initially when we did this, we had the testosterone coming down, and then it went up, and then it came down, and we had all kinds of ideas of why this dose doesn’t keep the testosterone down. And the real answer, it looks like is, we simply didn’t have enough dose, and we didn’t have it at the right times. I think if you give the dose correctly… And we were misled by the PDR, which sort of says, well you can just give the IM and it’s going to work, but then, they were thinking of working making the child taller, so they weren’t worried about Day 21 to Day 28 going back up, although they had no way to measure it either. If you read the Japanese — Lupron is, the patent is owned by Takeda Abbott, it’s a conglomeration of American and Japanese, it’s made actually in Japan — they did a study, and they showed that you need to give much higher doses than — the doses that we just told you are what were successful in Japan. And I think once you do that… (Mark Geier, August 12, 2006)

According to this description, children are first administered a 15mg depot shot, and simultaneous subcutanous dosing begins immediately. The 100mcg/kg “ultimate dose” is twice the 50mcg/kg starting dose recommended by the manufacturer for the treatment of CPP.

The 1991 Japanese study upon which Dr. Geier appears to have based his statement that a dose of 100mcg/kg was probably needed to “fully control the average person” involved 36 patients, only two of them boys. Eleven girls with central precocious puberty were given 10mcg/day of Lupron, eleven girls and the two boys were given 30mcg/day, and twelve girls were given 90mcg/day — that is, the dosage was tripled from one patient group to the next, and no assessment was performed of doses between 30mcg/kg and 90mcg/kg. All patients given 90mcg/kg and half those given 30mcg/kg experienced improvement of clinical symptoms. The question of whether a lower dose would have sufficed to improve symptoms in the girls administered 90mcg/kg remained unanswered. The researchers concluded that a dose of more than 30mcg/kg is effective in causing improvement of clinical symptoms of CPP. The occurrence of clinical improvement in twelve girls representing 33% of subjects in a single small study cannot be accurately characterized as proof that an “average” autistic person — a person from a population largely consisting of boys — would require a dose higher than the highest dose administered in the 1991 study (50).

The standard measures of success for the treatment of CPP are visible and quantifiable: regression of breast or testicular development, cessation of menses, and decrease in the rate of skeletal maturation. In contrast, the Geiers appear to rely upon parental reports of “regression” and a “daily log” as the basis for recommending dosage increases. This “daily log” presumably contains reports of children’s behavior; in addition to health problems, the “bad things” recorded in a parent-maintained log would presumably include instances of persistent autistically-typical behavioral, communicative and cognitive challenges. A child who might be called a “fast eliminator of Lupron” might alternately be called “a child who remains autistic two weeks after being administered Lupron.”

During their USAAA presentation, the Geiers also discussed how they have “branched out” into new territory — the evaluation of babies, and the the administration of Lupron to adolescents and young adults, contrary to the manufacturers’ recommendation that the drug be discontinued in early adolescence, when puberty normally begins.

Usually we’re looking for three years and older, although we have seen a few that are between the ages of one and two that seem to be in the progress of developing autism, and they had very high levels of testosterone. (David Geier, August 12, 2006)
And then we got so emboldened with this that we started branching out, doing some young teenage boys. My office manager has an Asperger’s who’s fourteen… He’s extremely bright; he’s probably the smartest kid in his high school. But he had a problem… And his little problem is, although he can solve everything and talk about rocket science, once a week he either hit a teacher, threatened to rape a girl, or knock a hole in the wall. Schools don’t like this… They suspended him eleven times, and they took him back. Finally they expelled him. Then he went home and started causing problems all around the neighborhood. I talked to his psychiatrist, who said, “the kid’s going to get arrested and go into an institution, obviously.” We did his testing, and he had the pattern, and of course, his testosterone is much higher because he’s partway in puberty. We treated him, and this year, we called the school and said, “look, you gave him twelve chances, give him one more. We can’t tell you why, but give him one more.” They took him back and now he hasn’t had any problems at all, he’s in an advanced program and he’s skipping a grade and going to a special program that’s going to go to college early on. (Mark Geier, August 12, 2006)
And let me just comment, so we got even bolder, and we ended up with — we have some eighteen and twenty-three year olds who, really, some of them are basically institutionalizable — I mean, these kids are hitting people, they’re putting their mothers in the hospital, their fathers in the hospital. So with these kids, what we’re trying to do is get rid of their aggressive behavior so the parents can keep them, because the state keeps saying they’re going to take them away. Now here, we’re not on new ground. The state does this a lot, and in fact, knock on wood, so far, I’ve gotten every health plan — we’ve got about eighty kids — we’ve gotten every health plan to pay for the Lupron. While on the fourteen-year old it was interesting. They said, “we can’t pay for the Lupron, he doesn’t have precocious puberty, he’s fourteen.” And I said, “I didn’t write he has precocious puberty, I wrote he has hyperandrogenemia, high testosterone.” And they said, “we never do that.” And I said, “Oh really? Don’t you have any eighteen to twenty year olds that the court orders —” “Oh yeah, once a month.” I said, “Look, I talked to your psychiatrist. You can talk to your psychiatrist. If you don’t give him this stuff, he’s going to end up being arrested and going into an institution and then you’re going to pay for it, and it’ll ruin his life, or you can pay for it now.” You know what — the health plan, they had a heart, they approved it. And the older ones in the institution, as I say, courts order it, so when we treat a twenty-three year old who’s being, you know, dangerously aggressive, and we make them less aggressive, we’re doing something that’s been done a long time. So now we have those categories. (Mark Geier, August 12, 2006)
And now we’re getting into girls of pubertal age. And this is an interesting thing. When I take my fourteen year old and I give him Lupron and I lower his testosterone, I don’t really have anything to give him back, but with the girls, I do know how to do this — Professor of OB-GYN at Hopkins. What you do is, you lower the, you give Lupron, you turn off the testosterone, you also turn off the estrogen. And then you give them low-dose birth control pills. Most of these girls if they start having periods on high testosterone, have very irregular periods that are very painful. And in fact, many of the OB’s don’t do the Lupron, but they’ll do the low-dose birth control pills again just to control it. Now you have the best of both worlds. They don’t have any testosterone, and they go on through puberty. I wish I could do the same for the boys. I have some ideas, but you’d need an androgen that had a specific effect to do that. So now we’re branching out into all sorts of areas and hopefully in the next year we’ll come back and give you more experience on those new areas. (Mark Geier, August 12, 2006)

By using the word “protocol” to describe their diagnostic and drug regimen, Dr. and Mr. Geier imply that their medical techniques are based in sound science and implemented in a rigorous and ethical manner. It has become apparent, however, that theirs is not so much a “protocol” as it is a springboard for “make it up as you go” experimentation in “new areas” such as the use of Lupron as a pediatric psychotropic medication.

DMSA

The “Lupron Protocol” calls for the administration of succimer (trade name Chemet, manufactured by Sanofi-Synthelabo), described in the Physicians’ Desk Reference as an orally active heavy metal chelating agent that binds to metals, forming a water-soluble complex that is excreted in urine (51). Its chemical name, meso 2,3-dimercaptosuccinic acid, is commonly abbreviated as DMSA. DMSA’s only FDA-approved pediatric use is the treatment of acute lead poisoning. The medical literature includes limited reports of the use of DMSA for acute mercury and arsenic poisoning; however, no controlled studies have been conducted on the use of DMSA in the treatment of poisoning with metals besides lead. Neither have controlled studies been conducted on the interaction of DMSA with other drugs.

Dosage studies of DMSA are based on administration of the drug over a five-day period to patients with significantly elevated blood lead levels. The safety of uninterrupted dosing longer than three weeks has not been established and is not recommended by the manufacturer.

Since the extent of clinical experience with DMSA is limited, the full range of adverse reactions has not been determined. Adverse events associated with DMSA usage include:

Digestive: Nausea, vomiting, diarrhea, loss of appetite, hemorrhoids, loose stools, metallic taste in mouth
Body as a whole: Back pain, abdominal cramps, stomach pains, head pain, rib pain, chills, flank pain, fever, flu-like symptoms, heavy head/tired, head cold, headache, yeast infection
Metabolic: Elevated SGPT and SGOT (indicators of liver dysfunction), alkaline phosphatase, elevated serum cholesterol
Nervous system: Drowsiness, dizziness, sensorimotor neuropathy (i.e., nerve damage), sleepiness, paresthesia (tingling, pricking or numbness of the skin)
Skin: Rashes, ulceration of mucous membranes, itching
Sensory: Cloudy film in eye, watery eyes, plugged ears, ear infections
Respiratory: Sore throat, runny nose, nasal congestion, cough
Urogenital: Decreased urination, difficulty urinating, protein in urine
Cardiovascular: Irregular heartbeat (arrhythmia)
Blood/lymphatic: Decreased white blood cell count (neutropenia), increased platelet count, eosinophilia
Musculoskeletal: Kneecap pain, leg pains

Parents of autistic children with immune problems should be particularly concerned about the risk of decreased white blood cell count. The risk is significant enough that physicians are warned to obtain a complete blood count prior to and weekly during treatment with succimer, and to closely monitor any signs of infection. Due to the risk of dehydration, patients are warned to maintain adequate fluid intake during the course of treatment.

A course of treatment with DMSA should last no more than nineteen days. The manufacturer recommends that a minimum of two weeks pass between courses unless blood lead levels indicate that further treatment is required to alleviate acute toxicity.

Mark and David Geier’s treatment specifications call for the administration of transdermal DMSA (TD-DMSA) to children unable to tolerate the gastrointestinal distress all too often caused by oral DMSA. However, there exist no published data demonstrating that transdermal DMSA is effectively and consistently absorbed through the skin. Transdermal DMSA has not been approved for marketing by the FDA.

FDA pharmacy compounding regulations allow pharmacists to fill prescriptions for a named patient for an off-label use, or using a route of administration different from that for which approval exists. However, an off-label route of administration together with indication for use in treatment of autism in children — a vulnerable patient population — should trigger FDA investigational new drug (IND) regulations. If transdermal DMSA is being sold to treat mercury poisoning in children, the route of administration combined with the vulnerability of the patient population should also trigger FDA IND regulations.

FDA believes that an increasing number of establishments with retail pharmacy licenses are engaged in manufacturing and distributing unapproved new drugs for human use in a manner that is clearly outside the bounds of traditional pharmacy practice and that violates the Act… Some “pharmacies” that have sought to find shelter under and expand the scope of the exemptions applicable to traditional retail pharmacies have claimed that their manufacturing and distribution practices are only the regular course of the practice of pharmacy. Yet, the practices of many of these entities seem far more consistent with those of drug manufacturers and wholesalers than with those of retail pharmacies. For example, some firms receive and use large quantities of bulk drug substances to manufacture large quantities of unapproved drug products in advance of receiving a valid prescription for them. Moreover, some firms sell to physicians and patients with whom they have only a remote professional relationship. Pharmacies engaged in activities analogous to manufacturing and distributing drugs for human use may be held to the same provisions of the Act as manufacturers. (52)

A single US mail order dealer, Lee Silsby Compounding Pharmacy, sells TD-DMSA. Its online marketing materials for the preparation are targeted to parents of autistic children in a manner that tests the bounds of legality. Its head pharmacist, Alan Israel, regularly promotes TD-DMSA directly to parents on online discussion lists, making claims for its effectiveness and offering referrals to doctors willing to work with patients long-distance.

The TD-DMSA is much more effective then oral DMSA… [W]ith the ability to penetrate, it’s so much more effective. There are side effects (like yeast beast) with oral that you don’t get with Transdermal. (July 27, 2005)
So far (12 weeks) using a transdermal route of administration has given different response (more positive) than orally. (February 20, 2005)
TD-DMSA is rx in usa if he wants to purchase there are mds that will work with patients from out of the country . I can be contacted for a list of mds. We compound the TD-DMSA. (March 29, 2005)

Parent reports indicate that DMSA is often poorly tolerated by children, and that in spite of diagnoses of “mercury poisoning,” DMSA chelation in conjunction with Lupron does not result in excretion of additional mercury beyond that which might be chelated by DMSA alone. Some parents, dissatisfied with the outcome of chelation according to the Geiers’ instructions, faced with little clinical or laboratory evidence of mercury poisoning yet believing that their autistic children are chronically “heavy metal toxic,” have added other chelators to their children’s pharmaceutical regimen. The duration of chelation frequently exceeds the maximum duration for which safety has been determined. Children are often made sick by the treatment.

My son has been on the Lupron treatment for over a month now along with the DMSA and we just got his urine metals back and it showed no mercury, really no anything moving. Is anyone having any real progress with this treatment? (Mother of 6 year old boy; July 18, 2006)
My son has been on the Geier protocol for 55 days total. We give 10mg/kg DMSA by mouth 3 times a day, (every 8 hours) every other day. We supplement on “off” days. He has had 26 day on DMSA… He is dumping a ton of lead, arsenic, nickle, and other metals, no mercury as of yet. (Mother of 8 year old boy; January 25, 2006)
We started with oral DMSA, got a bit of nickel and a blip of lead… Oral gave horrendous gut problems, so we moved to TD-DMSA. This was easier on gut and we got even more nickel. After a few weeks, I added low dose ALA, and we pulled low levels of arsenice and nickel. Arsenic had always shown up in his blood (low levels, but always there). None came out in his urine until we added the ALA… Granted, we have only done 6 low dose rounds. I just wonder about getting ZERO mercury, ever… (Mother of 5.5 year old boy; August 6, 2006)
I am going to start ALA when my son stops dumping metals under DMSA Lupron. To prevent return to the brain when tons of it is in the body. My question is — we are on 1 on 1 off for DMSA with 500 mg total, 2-1-2 ~6 hours apart. When do we add in ALA. On DMSA day and 3 hours from the DMSA dose. I probably should ask My DAN as well. I seem to be on a unique protocol. (Father of 3 year old boy; June 30, 2006)
We stopped chelating because it was exacerbating my daughter’s gut problems (yeast, etc.) … [S]he’s doing so WELL on the Lupron that we decided to stop chelating. And her gut cleared up… partly due to stopping the chelation… but I think largely because the lupron suppresses testosterone and promotes the glutathione pathway, which is good for the gut. (Father of 7 year old girl; June 23, 2006)
[M]y daughter’s DAN doctor, Anju Usman, said that three of her patients have went through the Geier protocol… one of them developed hyperthyroidism and the other two didn’t dump any greater quantities of heavy metals than with standard chelation. They were all boys. (Father of 7 year old girl; February 8, 2006)
We worked with the Geiers when my son did their protocol. I think that the first few patients were diagnosed with precocious puberty. My son’s testosterone levels were as high as these kids but he didn’t have the other signs of precocious puberty that they had. He did have a lot of aggression so we decided to try it. We gave it a 2 month trial but my DAN and I did not think it was healthy to stop testosterone on an 8 yr old boy that is not having prec. puberty. Also, we did not see any changes in behavior or chelation output. (Mother of 8 year old boy; January 4, 2006)
We worked with the Geiers for several months and then have stopped since Lupron did nothing but make my son irritable (we saw no additional metal excretion). Before we started with Lupron, he did seem to have slightly high testosterone although no other signs of precocious puberty. Now, after we have stopped, it has gone back into the normal range — not sure why… From what I have heard from almost everyone in the Geier’s study (except the Geiers themselves) and my experience, no one is seeing the “mercury unbind from the testosterone” and be excreted at higher levels. Some doctors think high testosterone could be caused by chelation in general while other think as metals and viruses are removed, the testosterone will normalize… I am not a fan of Lupron as I did not see any additional excretion in metals while we were on it and my son’s behavior was not good. (Mother of 5 year old boy; January 20 and March 21, 2006)

Androcur

The third component of the “Lupron Protocol” is the powerful steroidal anti-androgen Androcur (cyproterone acetate). Androcur both reduces testosterone production and directly inhibits the action of testosterone. Androcur is not available from U.S. pharmacies, and must be ordered by mail from pharmacies abroad. Its use for the treatment of prostate cancer and precocious puberty has waned in the United States due to its lack of FDA approval, the increasing market dominance of Lupron for the treatment of these conditions, and its many side effects. These range far beyond the predictable consequences of suppression of hormonal function (such as breast changes, and changes in libido and reproductive function), and encompass practically every physiological system. From the Product Monograph for Androcur (53):

Liver function — Direct hepatic toxicity, including jaundice, hepatitis and hepatic failure, which has been fatal in some cases, has been reported in patients treated with 200-300 mg ANDROCUR® (cyproterone acetate). Most reported cases are in men with prostatic cancer. Toxicity is dose-related and develops usually, several months after treatment has begun. Liver function tests should be performed before treatment and whenever any symptoms or signs suggestive of hepatotoxicity occur.
Depression — Androcur® therapy has occasionally been associated with an increased incidence of depressive mood changes, especially during the first 6-8 weeks of therapy. Similar mood changes have also been seen following surgical castration and are considered to be due to androgen deprivation. Patients with tendencies to depressive reaction should be carefully observed.
Cardiovascular system — hypotension, tachycardia, heart failure, syncope, myocardial infarct, hemorrhage, cerebrovascular accident, cardiovascular disorder, retinal vascular disorder, embolus, pulmonary embolism, superficial and deep thrombophlebitis, thrombosis, retinal vein thrombosis, phlebitis, vascular headache, shock.

Gastrointestinal system — constipation, diarrhea, indigestion, anorexia, nausea, vomiting, cholestatic jaundice, cirrhosis of liver, hepatic coma, hepatitis, hepatoma, hepatomegaly, jaundice, liver carcinoma, liver failure, abnormal liver function test, liver necrosis, pancreatitis, glossitis.

Hematology — increased fibrinogen, decreased prothrombin, thrombocytopenia, anemia, hemolytic anemia, hypochromic anemia, normocytic anemia, leukopenia, leukocytosis.

Metabolism — negative nitrogen balance, decreased response to ACTH, hyperglycemia, lowered cortisol, hypercalcemia, increased SGOT, increased SGPT, increased creatinine, hypernatremia, edema, weight gain, weight loss, diabetes mellitus.

Musculoskeletal system — myasthenia, osteoporosis.

Nervous system — fatigue, lassitude, weakness, hot flashes, increased sweating, aphasia, coma, depression, dizziness, encephalopathy, hemiplegia, personality disorder, psychotic depression, abnormal gait, headache.

Respiratory system — asthma, increased cough, dyspnea, hyperventilation, respiratory disorder, shortness of breath on effort, lung fibrosis.

Skin — eczema, urticaria, erythema nodosum, exfoliative dermatitis, rash, maculopapular rash, dryness of the skin, pruritus, alopecia, hirsutism, skin discolouration, photosensitivity reactions, scleroderma.

Sensory system — ear disorder, optic atrophy, optic neuritis, abnormality of accommodation, abnormal vision, blindness, retinal disorder.

Urogenital system — enlarged uterine fibroids, uterine hemorrhage, increased urinary frequency, bladder carcinoma, kidney failure, hematuria, urate crystalluria, urine abnormality.

Other — ascites, allergic reaction, asthenia, chills, fetal chromosome abnormality, death, fever, hernia, malaise, injection site reaction.

Combined Administration

As previously mentioned, no clinical studies exist regarding drug-drug interactions for Lupron, DMSA or Androcur. However, a comparison of the manufacturer’s prescribing information for each drug reveals numerous shared side effects. Lupron and Androcur are both associated with weight gain and edema, depression and mood changes, and low blood pressure. All three drugs have been associated with nausea and vomiting, rash, fever, headache, lowered white blood cell count, and drowsiness. Most notable among shared side effects is the acceleration of bone demineralization by Lupron and Androcur. GnRH agonists are routinely administered in combination with antiandrogens (a regimen known as a “combined androgen blockade” or CAB) in the treatment of prostate cancer, in order to drive testosterone levels to zero as quickly as possible and thereby arrest the progress of this life-threatening disease. Treatment-induced bone loss (also known as secondary bone loss) is sufficiently common that men on CAB are routinely prescribed Fosamax (alendronate) — an osteoporosis drug — as a countermeasure. Reported adverse effects of CAB also include hot flashes, gynecomastia, osteoporosis, anemia, fatigue, and impaired cognition (54,55).

It is reasonable to anticipate that administration of drugs intended to disrupt mineral metabolism simultaneously with drugs intended to reduce testosterone and estrogen levels might increase the risk of treatment-induced bone loss. Although a number of studies have concluded that bone mineral density returns to normal after cessation of treatment with Lupron, risk of fracture is likely to increase during the course of treatment.

Mark Geier addressed the subject of bone demineralization at the August 2006 USAAA Conference.

And you might also possibly get bone demineralization like you do in the elderly, when a woman goes into menopause. But remember bone demineralization in women that go into menopause takes twenty years, and of course if you take estrogen, you stop it. So I don’t think we have a problem with that, but we don’t see it, because we cover with estrogen. (Mark Geier, August 12, 2006)

Such reassurances are inadequate given the fact that the great majority of autistic children are boys, and the consequent statistical likelihood that the great majority of autistic children on Lupron are boys.

Lupron, DMSA and Androcur are not the only courses in the chemical feast served up to children on the “Lupron Protocol.” Parents have referred to their children’s ingestion of many additional medications, quasi-medications and nutritional supplements, in pill, cream and injectable forms, including currently fashionable pharmaceutical autism treatments such as Valtrex and low-dose naltrexone. Each adds a confounding variable to the therapeutic equation, and increases the difficulty of assessing the cause of any improvement in the child to whom it is administered.

Neither Nystatin or Diflucan/Fluconazol did anything to help. So Vanco[mycin] was the last resort… and boy did it work. But as soon as she went off it, it came right back. Valtrex seemed to help her… the Valtrex and Lupron together cleared up her gut and she was normal until she ate a dozen cookies about a month ago. By then, we had run out of valtrex… and her gut regressed after the cookies. We’re struggling to get her back on track. (Father of 7 year old girl; July 28, 2006)
My guy has a possible diagnosis of precocious puberty, waiting on another test, but all signs are pointing to this. He just turned 9 years old weighs 108lbs. His DHEAS test showed 7.1 umol/L, reference range 0.5-2.6. Our DAN! has prescribed increasing LDN [low-dose naltrexone] to 1.0ml (6mg) nightly and 1 500mg Valtrex 2X day. If this doesn’t bring the test results down, he wants to start Lupron. (Mother of 9 year old boy; July 27, 2006)
My son is using M-B12 (Hopewell) since Dec 2003, Wellness Essential GSH (had been using TD-Glut but levels were always low), TD-DMSA (3 on and 4 off — 8 hr schedule) (Lee Silsby) since Oct 2005, (Used TD-DMPS Jan 2005-Oct 2005) TD-ALA (Lee Silsby) since Oct 2005, TD-LDN (Wellness) Since Oct 2005, (High Tech Health) FIR sauna, Magnetico bed, High Tech Health’s water machine, and a lot of supplements.) GFGFSF diet (Mother of 4.5 year old boy; January 14, 2006)
He is taking a multi vitamin with minerals, B Complex, Selinium, Vitamin E, Candex, and Melatonin. He also just started Chelation with DMSA and is on the Lurpon Protocal through the Geiers. Just started last week. I’ll try a low dose of DMG. Thanks for the tip. Also, my son takes 4 different meds if I haven’t mentioned that. He takes Effexor, Welbutrin, Buspar, and Allopurinol(sp?) for his uric acid levels. (Father of 14 year old boy; May 2, 2006)
[M]y son is also taking Lupron. Nothing worked on him — MB12, chelation, HBOT, vitamins, supplements… He frequently played with himself and was very hyper. He hardly could speak a word. He never sat in one place and his eyeballs kept moving around. He is now 5.5 and started Lupron 3.5 months ago and also chelates. Within 10 days he started repeating words — “daddy, momma, car…”. He started riding a tricycle, kicking and catching a ball and so much more! He is still not recovered — that’s why I am here — I will try valtrex and your protocal. (Father of 5.5 year old boy; August 29, 2006)
Our dose is actually .2ml, but after talking to them last week we might have to double that.. we are on a steady dose of Nystatin as well!.. My son… [has] been on it [Lupron] for 180 days, has made significant gains (until we started the MB 12 which he became “industrial” toxic and we made some major steps back with this on board, we have now since stopped using the MB 12 shots)… (Mother of 5.5 year old boy; March 20, 2006; August 29, 2006)
We are now chelating Andy’s way, doing the Geier’s Lupron protocol… and doing a good portion of Amy Yasko’s program, based on genetic results. I no longer subscribe to any one person having The Answer… My son has chelated 6 rounds, no mercury at all yet (in urine, at least) just some nickel and arsenic… We are working with the Geiers doing the Lupron therapy due to high testosterone… My son has messed up immune, endocrine, neurologic, and digestive systems. All the signs of mercury toxicity but no solid evidence of it and nothing coming out… My son is on BH4 now, low dose, for about 1 mo. Haven’t seen any positives — if anything, he looks worse. Go figure. (Mother of 5.5 year old boy; July 23 and August 4, 2006)

Needles Every Day

Mark and David Geier’s 2004 and 2005 descriptions of the “Lupron Protocol” generally referred to a single monthly depot injection of Lupron, with DMSA and Androcur taken orally. As outlined in their 2006 Autism One and USAAA presentations, however, they have recently doubled the number of depot shots given to many children, and have also incorporated into the regimen daily subcutaneous injections drawn from a multidose vial. Long-release depot injections were developed, in part, to increase the effectiveness of pharmaceutical treatments requiring constant exposure to a drug, to minimize the number of injections needed and thereby make the therapeutic experience more bearable (56). Daily subcutaneous injections are therefore no longer in widespread use for the treatment of CPP. Nonetheless, increasing numbers of autistic children, adolescents and young adults now receive as many as sixty-six needle-sticks per month — one or two intramuscular depot shots per month, one or two subcutaneous injections per day, and biweekly blood draws — all performed for the purpose of micromanaging their testosterone levels, and ostensibly “reducing the toxicity of mercury” that supposedly rendered them autistic.

The Geiers’ recommendation of daily Lupron “supplementation” seems to reflect as little consideration of the traumatic potential of invasive medical procedures upon children as does the bloody “eligibility assessment” performed on every child brought to them. Procedure-related pain is a source of significant emotional distress to children being treated for chronic medical conditions (57,58). It has been estimated that needle phobia is experienced by up to 10% of children and adults; young children are particularly vulnerable (59-61). Studies have found that children with cancer consider painful procedures to be the worst part of their cancer experience, and that frequent repetition of painful procedures does not desensitize or acclimate them, but increases their anxiety (62,63). These findings should be of particular concern to parents of autistic children, many of whom experience chronic anxiety.

Parent accounts suggest that frequent encounters with hypodermic needles are indeed painful and frightening to their autistic children. Although the prescribing information for Lupron Depot-Ped (as well as Aetna, Cigna and Blue Shield coverage guidelines) calls for administration by a qualified medical professional, parents have reported giving intramuscular injections to their children at home. Children are frequently restrained for both intramuscular and subcutaneous injections, increasing the risk of injection site reactions, bruising, infection, needle-stick injuries, and psychological trauma.

The shots have a pretty big needle and hurt, but are very fast. They are intramuscular (straight down into the thigh). (Mother of 4 year old boy; March 21, 2006)
This is our son’s 21st day (he’ll receive his 21st shot tonight!)!… We do the daily subcue shot, and I draw it out of a vial, the vial last for 14 days for the dose we give our son, it would cost almost $700.00, but with our insurance we only pay the co pay of $60.00! (Mother of 5 year old boy; March 20-21, 2006)
Yesterday, we gave R[…] her second Depo shot (intramuscularly, with the big, 2-inch needle) in her buttocks. We did this one while she was awake, by holding her down while she lay on her belly. We were able to hold her still for the injection by sitting/straddling her back, while my wife held her legs still. (Father of 7 year old girl; May 22, 2006)
[W]e give our son Lupron daily. His dosing has changed since we began just as any dosing on other meds seem to need adjusting once starting a protocol. At present we have had to increase his daily Lupron injection from .2 ml to .4 ml, and also increased his Lupron Depot Injection from every 28 days to now giving every 14 days. We give them with a very small needle (about the size of the MB 12 shots) and I use a smaller needle on the depot shots both given IM. (Mother of 5 year old boy; August 29, 2006)
I asked my son a couple days ago if he wanted the lupron shot… he lay in his mom’s lap face down (the usual procedure) and was emitting a high pitched crying noise… but she didn’t have to drag him there… unfortunately… that was a one off and the next day he went back to being dragged… (Father of 3 year old boy; June 21, 2006)
Normally, you do 1 IM injection monthly but I opted for the daily subcutaneous. (I know that sounds ridiculous but my son is quite familiar with how painful the IMs are and the daily SQs are less traumatic, beleive it or not).. We do lab draws every 3-4 weeks and Lupron injections 2x/day. Those are tolerable, the IMs are just awful. I wish there was a better way. (Mother of 5.5 year old boy; March 16, 2006; September 4, 2006)

Routine injections are an inconvenient necessity for individuals managing life-threatening medical conditions such as insulin-dependent diabetes. However, the discomfort and risk of harm of insulin therapy is offset by its readily-apparent and irreplaceable benefit — survival. The efficacy of insulin therapy is supported by a well-validated body of scientific and clinical evidence. In contrast, the “Lupron Protocol” shares none of insulin therapy’s level of scientific validation, its favorable risk/benefit ratio, and its standardized, objective outcome measures. Upon close examination, the Geiers’ fundamental scientific rationale for administering Lupron to autistic children concurrently with chelation has proven to be erroneous — a fact which even they have publicly acknowledged. At the end of the USAAA presentation, when asked whether mercury was “still bonding” to testosterone in children on Lupron, David Geier responded:

It’s theoretically possible, but not demonstrated. (David Geier, August 12, 2006)

With these words, Mr. Geier confessed to the inadequacy of a claim that remains intact and uncorrected in informational videos and in both of their pending patent applications:

It is known in the art that mercuric chloride binds and forms a complex with testosterone in subjects.

The “Lupron Protocol” is a treatment of indefinite duration, presumably continuing as long as an autistic child or adolescent remains autistic.

The question arises “What happens to a child receiving Lupron when he/she is supposed to naturally be going through puberty?” Because this study has only gone on for a short time, that question cannot be answered yet in how to handle that. They are currently doing trials on 13 and 14 year olds. Also, the question arises, “When do we stop administering the Lupron, or can we/should we?” (Mother of 14 year old boy, quoting Mark and David Geier; March 4, 2006)
And the question is, can you eventually remove enough mercury that you don’t have to keep giving them Lupron. And the answer to that is, we’ve only been doing this less than two years. I don’t know the long term… I don’t know how long I have to keep treating these kids, if I stop treating them will they go back to the way they were? That I don’t know. (Mark Geier, June 23, 2006)

In May 2006, a father described his seven-year old daughter’s chelation-induced ordeal, and his vision of the time frame in which the “Lupron Protocol” might work its promised magic.

We’re using the TD-DMSA with the Geier protocol… This poor kid is being put through so much. I hope we can verify that we’re successfully depleting the mercury and lead so we don’t have to do this protocol any longer than is necessary. I’m hoping Lupron therapy won’t be needed after, say, four or five months. (Father of 7 year old girl; May 11, 2006)

Several months later, the same father reported that he was administering close to the “ultimate” dose of Lupron to his daughter.

[O]ver time… it seems to require a higher dose of the drug to get the same effect. When we started with a daily subcutaneous dose of 0.2ml, she had miraculous results after just the fourth day. Today, we’re at 0.5 ml per day… plus a 28-day depo shot once a month… in order to get that same result we had at the beginning… When we happen to run out of lupron (and she goes dry for awhile), we see her testosterone come back up, and the negative behaviors, etc. come back. Once her gut has been healed for awhile longer, we’re going to do another round of metals testing to see if starting up the chelation again is warranted. (Father of 7 year old girl; August 21, 2006)

In an August 2006 interview on Autism One Radio, Rev. Lisa Sykes — Methodist minister, mother of “Child X,” and member of the Institutional Review Board by which the Geiers approve and supervise their own research — stated that her now ten-year old son has been on the “Lupron Protocol” continuously since November 2004, almost two years.

According to Dr. Geier, approximately eighty autistic children, adolescents and young adults are currently being medicated according to the “Lupron Protocol.” If the measure of therapeutic success is their transformation from an autistic to a non-autistic state, “these poor kids” may find themselves “being put through so much” for a very, very, very long time.

 

 

Lupron physicians’ prescribing information
1. Lupron Depot-Ped Package Insert
2. Lupron Injection Package Insert

Lupron and pituitary apoplexy
3. A. Davis et al, Pituitary apoplexy after leuprolide, Pituitary, 2006 Jul 10
4. G. Engel et al, Pituitary apoplexy after leuprolide injection for ovum donation, J Adolesc Health. 2003 Jan;32(1):89-93
5. M.B. Guven et al, Pituitary apoplexy as a cause of coma, Eastern Journal of Medicine 4 (1): 32-33, 1999
6. Y. Reznik et al, Pituitary apoplexy of a gonadotroph adenoma following gonadotrophin releasing hormone agonist therapy for prostatic cancer, J Endocrinol Invest. 1997 Oct;20(9):566-8
7. A. Morsi et al, Pituitary apoplexy after leuprolide administration for carcinoma of the prostate, Clin Endocrinol (Oxf). 1996 Jan;44(1):121-4)

Lupron and reproductive function
8. Sabine Hager et al, Long-Term Outcome after Depot Gonadotropin-Releasing Hormone Agonist Treatment of Central Precocious Puberty, J Clin Endocrinol Metab. 1999 Dec;84(12):4583-90
9. Toshiaki Tanaka et al, Results of Long-Term Follow-Up after Treatment of Central Precocious Puberty with Leuprorelin Acetate, J Clin Endocrinol Metab. 2005 Mar;90(3):1371-6)

Lupron and bone mineral density
10. Johannes D. Veldhuis et al, Endocrine control of body composition in infancy, childhood and puberty, Endocr Rev. 2006 Feb;26(1):114-46
11. Dirk Vanderschueren et al, Androgens and bone, Endocr Rev. 2004 Jun;25(3):389-425
12. S. Aubrey Stoch et al, Bone Loss in Men with Prostate Cancer Treated with Gonadotropin-Releasing Hormone Agonists, J Clin Endocrinol Metab. 2001 Jun;86(6):2787-91
13. Susan L. Greenspan et al, Bone Loss after Initiation of Androgen Deprivation Therapy in Patients with Prostate Cancer, J Clin Endocrinol Metab. 2005 Dec;90(12):6410-7
14. Sabine Hager et al, Long-Term Outcome after Depot Gonadotropin-Releasing Hormone Agonist Treatment of Central Precocious Puberty, J Clin Endocrinol Metab. 1999 Dec;84(12):4583-90
15. EK Neely et al, Bone mineral density during treatment of central precocious puberty, J Pediatr. 1995 Nov;127(5):819-22
16. O. Unal et al, Effects on bone mineral density of gonadotropin releasing hormone analogs used in the treatment of central precocious puberty, J Pediatr Endocrinol Metab. 2003 Mar;16(3):407-11)
17. Inge M. van der Sluis et al, Longitudinal follow-up of bone density and body composition in children with precocious or early puberty before, during and after cessation of GnRH agonist therapy, J Clin Endocrinol Metab. 2002 Feb;87(2):506-12)
18. Franco Antoniazzi et al, Bone mineral metabolism in girls with precocious puberty during gonadotrophin-releasing hormone agonist treatment, Eur J Endocrinol. 1995 Oct;133(4):412-7)
19. Annemieke M. Boot et al, Bone Mineral Density and Body Composition before and during Treatment with Gonadotropin-Releasing Hormone Agonist in Children with Central Precocious and Early Puberty, J Clin Endocrinol Metab. 1998 Feb;83(2):370-3)
20. Inge M. van der Sluis et al, Longitudinal Follow-Up of Bone Density and Body Composition in Children with Precocious or Early Puberty before, during and after Cessation of GnRH Agonist Therapy, J Clin Endocrinol Metab. 2002 Feb;87(2):506-12)
21. Franco Antoniazzi et al, Bone Mass at Final Height in Precocious Puberty after Gonadotropin-Releasing Hormone Agonist with and without Calcium Supplementation, J Clin Endocrinol Metab. 2003 Mar;88(3):1096-101

Lupron and body mass index
22. Mark R. Palmert et al, Is Obesity an Outcome of Gonadotropin-Releasing Hormone Agonist Administration? Analysis of Growth and Body Composition in 110 Patients with Central Precocious Puberty. J Clin Endocrinol Metab. 1999 Dec;84(12):4480-8
23. T Arrigo et al, Reduction of baseline body mass index under gonadotropin-suppressive therapy in girls with idiopathic precocious puberty, Eur J Endocrinol. 2004 Apr;150(4):533-7)
24. G. Chiumello et al, Precocious puberty and body composition: effects of GnRH analog treatment, J Pediatr Endocrinol Metab. 2000 Jul;13 Suppl 1:791-4
25. Annemieke M. Boot et al, Bone Mineral Density and Body Composition before and during Treatment with Gonadotropin-Releasing Hormone Agonist in Children with Central Precocious and Early Puberty, J Clin Endocrinol Metab. 1998 Feb;83(2):370-3)
26. C Traggiai et al, Outcome after depot gonadotrophin-releasing hormone agonist treatment for central precocious puberty: effects on body mass index and final height. Eur J Endocrinol. 2004 Apr;150(4):533-7)
27. Nelly Mauras et al, Testosterone Deficiency in Young Men: Marked Alterations in Whole Body Protein Kinetics, Strength, and Adiposity, J Clin Endocrinol Metab. 1998 Jun;83(6):1886-92
28. Matthew R. Smith et al, Changes in Body Composition during Androgen Deprivation Therapy for Prostate Cancer, J Clin Endocrinol Metab. 2002 Feb;87(2):599-603
29. Nancy Keating et al, Diabetes and Cardiovascular Disease During Androgen Deprivation Therapy for Prostate Cancer, J Clin Oncol. 2006 Sep 20;24(27):4448-56

Lupron and seizure
30. S. Akaboshi, A case of atypical absence seizures induced by leuprolide acetate, Pediatr Neurol. 2000 Sep;23(3):266-8

Lupron and autoimmune thyroiditis
31. O. Eyal et al, Autoimmune thyroiditis during leuprolide acetate treatment, J Pediatr. 2004 Mar;144(3):394-6

Lupron and newly-reported side-effects in women
32. Marie Nolbert et al, Impact of leuprolide acetate disease management program on patient outcomes, Clin. Research and Reg. Affairs, 19(1), 33-42 (2002)

Lupron and precocious puberty
33. Karen Oerter Klein, Precocious Puberty: Who Has It? Who Should Be Treated? J Clin Endocrinol Metab. 1999 84(2):411-414
34. J.S. Cook et al, Assessment of depot leuprolide acetate dose-adequacy for central precocious puberty J Clin Endocrinol Metab. 1992 May;74(5):1206-9
35. K. Ohyama et al, Timing for discontinuation of treatment with a long-acting gonadotropin-releasing hormone analog in girls with central precocious puberty, Endocr J. 1998 Jun;45(3):351-6
36. Paul Kaplowitz, Clinical Characteristics of 104 Children Referred for Evaluation of Precocious Puberty. J Clin Endocrinol Metab. 2004 Aug;89(8):3644-50

Reproductive Hormones and Bone Formation
37. Alireza Falahati-Nini et al, Relative contributions of testosterone and estrogen in regulating bone resorption and formation in normal elderly men, J Clin Invest, December 2000, Volume 106, Number 12, 1553-1560
38. Luigi Gennari et al, Aromatase Activity and Bone Homeostasis in Men, J Clin Endocrinol Metab. 2004 Dec;89(12):5898-907

Reproductive Hormones and Cognitive Function
39. Eeva K. Salminen et al, Associations between Serum Testosterone Fall and Cognitive Function in Prostate Cancer Patients, Clin Cancer Res. 2004 Nov 15;10(22):7575-82
40. Jeri Janowsky, Thinking with your gonads: testosterone and cognition. Trends Cogn Sci. 2006 Feb;10(2):77-82
41. Miglena Grigorova et al, Effects of treatment with leuprolide acetate depot on working memory and executive functions in young premenopausal women. Psychoneuroendocrinology. 2006 Sep;31(8):935-47
42. Karen Faith Berman et al, Modulation of cognition-specific cortical activity by gonadal steroids: A positron-emission tomography study in women. Proc Natl Acad Sci U S A. 1997 Aug 5;94(16):8836-41

Reproductive Hormones and Sleep
43. Ellen Leibenluft et al, Effects of Leuprolide-Induced Hypogonadism and Testosterone Replacement on Sleep, Melatonin, and Prolactin Secretion in Men. J Clin Endocrinol Metab. 1997 Oct;82(10):3203-7

Aggression
44. Dan Olweus et al, Testosterone, aggression, physical, and personality dimensions in normal adolescent males, Psychosom Med. 1980 Mar;42(2):253-69
45. D.J. Albert et al, Aggression in humans: what is its biological foundation? Neurosci Biobehav Rev. 1993 Winter;17(4):405-25

Lupron and Sex Offenders
46. Council on Sex Offender Treatment, The management and containment of sex offenders, 2005
47. Vermont Agency of Human Services, Supervision and treatment of sex offenders with developmental disabilities, March 2005
48. Jim Doyle, Therapy dissects sex crimes, strives to reduce urges, San Francisco Chronicle, July 11, 2004
49. Miho Nagano, Lowering testosterone in sex offenders leads to osteoporosis, Medill News Service, March 3, 2005

Lupron Dosage
50. T. Tanaka et al, A dose finding study of a super long-acting luteinizing hormone-releasing hormone analog (leuprolide acetate depot, TAP-144-SR) in the treatment of central precocious puberty, Endocrinol Jpn 1992 Jun;39(3):following 329

DMSA
51. Physicians’ Desk Reference: DMSA

FDA Compounding Pharmacy Guidelines
52. Guidance for FDA Staff and Industry: Compliance Policy Guides Manual, Sec. 460.200: Pharmacy Compounding

Androcur
53. Berlex Corporation, Product Monograph for Androcur

Combined Androgen Blockade
54. Fernand Labrie et al, Gonadotropin-Releasing Hormone Agonists in the Treatment of Prostate Cancer. Endocrine Reviews 26 (3): 361-379
55. Beth A. Hellerstedt et al, The Current State of Hormonal Therapy for Prostate Cancer, CA Cancer J Clin 2002; 52:154-179

Procedural Pain
56. J.C. Carel et al, Treatment of Central Precocious Puberty by Subcutaneous Injections of Leuprorelin 3-Month Depot, J Clin Endocrinol Metab. 2002 Sep;87(9):4111-6
57. Keith J. Slifer et al, Helping Children and Caregivers Cope with Repeated Invasive Procedures, Journal of Clinical Psychology in Medical Settings Volume 9, Number 2/June, 2002, 131-152
58. Ronald L. Blount et al, Pediatric Procedural Pain, Behavior Modification, Vol. 30, No. 1, 24-49 (2006)
59. James G. Hamilton, Needle phobia: a neglected diagnosis, Journal of Family Practice, August, 1995
60. Hessel Willimsen et al, Needle Phobia in Children: A Discussion of Aetiology and Treatment Options, Clinical Child Psychology and Psychiatry, Vol. 7, No. 4, 609-619, 2002
61. Yael Nir et al, Fear of Injections in Young Adults: Prevalence and Associations, Am J Trop Med Hyg. 2003 Mar;68(3):341-4
62. Nancy Olson Hester, Assessment of Pain in Children with Cancer, chapter excerpted from CR Chapman and K Foley, editors, Current and Emerging Issues in Cancer Pain: Research and Practice, Lipincott-Raven, 1993
63. Agency for Health Care Policy and Research, Procedure-Related Pain in Adults and Children, Clinical Guideline Number 9, AHCPR Publication No. 94-0592, March 1994

to Part Twelve:
Letter to Autoimmunity Reviews

Comments


  1. Thank-you, Kathleen. This piece of yours answered all of the pharmaceutical related questions I’d had about Lupron. The cites are exceptional. Fantastic work on your part.

    BTW, I still see no mention of evalution/consultation with a Ped. Endo. I thought I might find reference to it in their stated protocol, but didn’t see it there. Surely, what with David Geier stating: ” ... we do all kinds of monitoring”, that they’ve got a Ped. Endo. reviewing each case?

    — HJ    2006-09-22 17:42    #

  2. I think that this protocol would not be allowed to be used against POWs even under Bush’s original plan.

    — TheProbe    2006-09-22 17:50    #

  3. To me, that protocol looks like a lot of trouble for the future.

    — David N. Andrews MEd (Dec 2006)    2006-09-22 18:21    #

  4. What can be surprising about the Geiers anymore? Their claims about the safety of Lupron are simply irresponsible and reprehensible.

    It was interesting to read the anecdotal experiences of parents. Is it likely the Geiers are causing measurable harm to some children?

    Great work as usual Kathleen.

    — Joseph    2006-09-22 18:26    #

  5. The Geiers, in my opinion, must surely be two of the most evil people on earth. But they’ll be in that new “Evidence of Harm” movie, won’t they? Maybe Anthony Hopkins will play Dr. Geier.

    The “father of the seven year old girl” who doesn’t have signs of precocious puberty at all, is right up their with the most evil people, too, as he is actively promoting this stuff to other parents.

    Sick. I think Child Protective Services needs to be called in to look at some of these parents.

    — Ms Clark    2006-09-22 18:33    #

  6. Great work, Kathleen.

    “At the end of the USAAA presentation, when asked whether mercury was “still bonding” to testosterone in children on Lupron, David Geier responded: It’s theoretically possible, but not demonstrated.”

    It’s also theoretically possible that their love of money has completely blinded any judgement that they once had. It’s also theoretically possible that they haven’t even thought through mixing potions together to form their potpourri of endocrine nightmare. Why? Because they’re not smart enough to think these things through.

    Anyone holding a kid down and injecting them with Lupron because they want to cure the kid’s autism is reckless, and now because of this blog, knowingly reckless.

    Stick with the blankets over the head and the Bradstreet exorcisms. Actually, I’ll put the light powered sauna and magic crystal people above a Lupron child experimenter any day.

    — Just Hold 'er Down and Stick 'er    2006-09-22 18:50    #

  7. This piece made me cry. I am so sorry for all those children and their deluded parents.

    — Jennifer    2006-09-22 19:46    #

  8. The last researcher on the Tuskegee experiment died this week. Despite our safeguards, such misuse of humans in experiments (I won’t say science because this isn’t science) continues. My daughter remembers a great deal from her nonverbal days. What will these still autistic kids have to say to their parents in 10 years?

    — Ruth    2006-09-22 22:10    #

  9. “So it’s a semi-synthetic, 99% natural — don’t quote me on the 99, I don’t know the exact percent — but almost all natural, one small side group, and that’s how he made it, and that’s why it’s so specific and has so few side effects.”

    The Geiers are 99% lying vultures – don’t quote me on that I don’t know the exact percent — but they rarely tell the truth.

    — clone3g    2006-09-23 14:05    #

  10. The Geiers are 100 per cent vultures if you go with the old german translation of their name.

    Kathleen. This must be such unpleasant work for you, but so necessary. Thank you

    — mike stanton    2006-09-23 18:26    #

  11. This series is always compelling reading and always makes my jaw drop at the arrogant audacity the Geier’s are prepared to employ with other peoples kids.

    This time I couldn’t finish reading after the graphic descriptions of the way certain parents choose to administer these needless medications to their own children. That’s not your fault Kathleen, you are doing what needs to be done and reporting accurately, but it was just too distressing to finish. I’ll come back and finish it in a few days.

    — Kev    2006-09-24 02:53    #

  12. Thank you Kathleen for the enormous amount of time you have spent showing what is actually happening here in autism world. It’s a scary place.

    — Junior    2006-09-24 11:07    #

  13. How can insurers know about this and approve of it?

    Ironic that anti-vaccine crusaders are up in arms about how post-administration surveillance of vaccines doesn’t go on for years, yet they apparently aren’t concerned about the later effects of giving Lupron to children.

    — Lisa Randall    2006-09-24 14:59    #

  14. Forget about the insurers. Does anyone know who to contact in the State of Maryland about physical and emotional abuse of children, which this is?

    — Alyric    2006-09-24 22:58    #

  15. Thank you for your efforts at exposing these frauds. I hope that it pays off and that someone gets these children out of their clutches and into the hands of real doctors soon.
    I remember my son’s early days in school, he would cry and throw things simply to clear space. He was working within the rules, he wasn’t allowed to leave the class, he couldn’t explain what he felt and so he would just clear space in the only way he had left to him. Yes, it looks like aggressive behaviour but it was only ‘fight or flight’ when flight is eliminated.

    — Hawise    2006-09-25 08:36    #

  16. This scares the crap out of me. We’re not talking about woo that probably doesn’t work, or restrictive diets that are more likely to pad the pockets of “special doctors” and “supplement manufacturers”. We’re talking about a cocktail of potentially dangerous drugs, given to purportedly reverse a condition that is most likely not reversible. (or even something that should be “cured” in the first place)

    Would we be suggesting trying similar cocktails to “cure” CP or Down’s Syndrome?

    This is disgusting, but considering how disgusting the Geiers have behaved to date, it’s completely not shocking.

    — anonimouse    2006-09-25 10:43    #

  17. Thanks to everyone for reading this article. Writing it was difficult to begin with, and got even worse once I began to count the needles.

    — Kathleen Seidel    2006-09-25 16:54    #

  18. Well done, Kathleen…

    You deserve some sort of honour for this work. Can’t wait for the book to come out (I find books easier to read than webpages…) – do hurry! :)

    — David N. Andrews MEd (Dec 2006)    2006-09-25 21:13    #

  19. Tried to post yesterday, Kathleen, but it got lost somehow. This made me very sick… how can any parent do that to their child?

    For the posters who asked about insurance fraud… if you know of someone using this technique, contact the insurance company and let them know. Most companies have a fraud hotline you can call anonymously (or not, if you choose) and they will investigate. Thanks to Kathleen’s articles, the insurance company I work for is looking into this, but we can’t look at people we don’t cover.

    — Maggie Rosethorn    2006-09-27 06:56    #