A Reluctant Discussion of Lupron and Autism

The much publicized Maryland Medical Board action against the license of Mark Geier MD has created a great deal of internet chatter and controversy. I cannot speak to the entirety of the charges since I have no independent evidence for much of the Boards complaint. 

I can and I think it important to discuss the general nature of the concept of Lupron in autism treatment.  Prof Baron- Cohen has popularized the hormonal theory of autism, first with his discussions of elevated androgens in amniotic fluid of children who then became autistic (Med Hypotheses. 2007;69(1):47-51. Epub 2007 Feb 5.).

Later he published this article:

Mol Autism. 2010 Jul 12;1(1):11.

Foetal testosterone and autistic traits in 18 to 24-month-old children.

Auyeung B, Taylor K, Hackett G, Baron-Cohen S.

Source

Autism Research Centre, Department of Psychiatry, University of Cambridge, Douglas House, 18B Trumpington Rd, Cambridge, CB2 8AH, UK. ba251@cam.ac.uk.

Abstract

ABSTRACT:

BACKGROUND:

Autism spectrum conditions have been characterised as an extreme presentation of certain male-typical psychological traits. In addition, several studies have established a link between prenatal exposure to testosterone and cognitive sex differences in later life, and one study found that foetal testosterone (FT) is positively correlated to autistic traits in 6 to 10 year-old children. In this study, we tested whether FT is positively correlated with autistic traits in toddlers aged 18-24 months.

METHODS:

Levels of FT were analysed in amniotic fluid and compared with autistic traits, measured using the Quantitative Checklist for Autism in Toddlers (Q-CHAT) in 129 typically developing toddlers aged between 18 and 24 months (mean +/- SD 19.25 +/- 1.52 months).

RESULTS:

Sex differences were observed in Q-CHAT scores, with boys scoring significantly higher (indicating more autistic traits) than girls. In addition, we confirmed a significant positive relationship between FT levels and autistic traits.

CONCLUSIONS:

The current findings in children between 18 and 24 months of age are consistent with observations in older children showing a positive association between elevated FT levels and autistic traits. Given that sex steroid-related gene variations are associated with autistic traits in adults, this new finding suggests that the brain basis of autistic traits may reflect individual differences in prenatal androgens and androgen-related genes. The consistency of findings in early childhood, later childhood and adulthood suggests that this is a robust association.

However, other observes find the opposite. These researchers from Belgium found what I typically see in MOST BUT NOT ALL CASES.  That is low testosterone in children with ASD. Baron-Cohen primarily found elevated androstenedione in older individuals (this is most likely from the adrenal glands).

Neuro Endocrinol Lett. 2010;31(4):483-8.

Serum testosterone concentration in male autistic youngsters.

Croonenberghs J, Van Grieken S, Wauters A, Van West D, Brouw L, Maes M, Deboutte D.

Source

University Center of Child and Adolescent Psychiatry, University of Antwerp, CAPRI youth, Belgium. jan.croonenberghs@zna.be

Abstract
OBJECTIVE:

Research on the biological pathophysiology of autism has found some evidence that alterations in androgenic hormones may play a role in the pathophysiology of that disorder. We studied morning concentrations of serum testosterone in a very homogenic group of postpubertal youngsters with autism and a group of normal controls.

METHODS:

This study examines the serum testosterone concentration on 9 consecutive time points between 08.00 AM and 12.00 AM in 18 high- functioning male youngsters with autism (age 12-18) and 22 healthy volunteers participated in this study. All subjects passed the onset of puberty (Tanner-stage III-IV) and were of the Caucasian race.

RESULTS:

Repeated measures ANOVA revealed a significant time effect, with a decline in the testosterone concentration during the test and time X diagnosis interaction.The total testosterone concentration was significantly lower in the autism group compared to the group of normal controls.

CONCLUSIONS:

The significant decrease in serum testosterone concentration in male youngsters with autism suggest that the turnover of testosterone may take part in the pathophysiology of autism. Suggestions for further research are discussed.

A few years ago I published this article on the basis of my observations regarding a subset of children with ASD.

image

In this study, we found a rationale and positive effect from a testosterone blocking agent in a child with elevated male hormones, but without evidence of central nervous system deregulation. This is complicated issue. 

In an effort to simplify this discussion lets try this picture to serve as the basis of our discussion.

image

The brain tells the body how to regulate sex homones via GnRH a chemical messanger that says make more testosterone or female hormones. Lupron blocks GnRH – hence disconnecting the brain’s up-regulation of the testis and ovaries.  GnRH importantly DOES NOT regulate adrenal production of androgens. There are TWO sources of sex hormones – one the gonads (ovaries or testis) and two the adrenal gland. However, the end hormones of testosterone and estrogen are nearly all gonadal in origin with only small amounts normally coming from the adrenal glands.

In our evaluations it seems most androgen excess issues in ASD (when present – which is in my experience uncommon) are adrenal NOT testis derived and usually DHEA-S or androstenedione – not testosterone.  This means Lupron would have NO effect on the adrenal issues. 

image

(credit: rbowen@colostate.edu)

All steroids are derived from cholesterol and as we know many children with autism (~20%) have cholesterol deficiency so it is inconceivable that this group could in anyway have elevated steroids UNLESS they were derived from the diet (which is remote at best).

See:

Am J Med Genet B Neuropsychiatr Genet. 2006 Sep 5;141B(6):666-8.

Abnormalities of cholesterol metabolism in autism spectrum disorders.

Tierney E, Bukelis I, Thompson RE, Ahmed K, Aneja A, Kratz L, Kelley RI.

Kennedy Krieger Institute, Baltimore, Maryland 21211, USA. Tierney@kennedykrieger.org

“Using gas chromatography/mass spectrometry, cholesterol, and its precursor sterols were quantified in 100 samples from subjects with ASD obtained from the Autism Genetic Resource Exchange (AGRE) specimen repository. Although no sample had sterol levels consistent with SLOS, 19 samples had total cholesterol levels lower than 100 mg/dl, which is below the 5th centile for children over age 2 years. These findings suggest that, in addition to SLOS, there may be other disorders of sterol metabolism or homeostasis associated with ASD.”

So it becomes critical to evaluate our cases individually and to check cholesterol levels as well as steroids.  Steroids may be deficient or in excess, but rarely will they be due to central brain mechanisms in younger children (hence younger children with autism would likely not need Lupron).

But there is another scenario where steroids get trickier and that is puberty which IS under the control of GnRH (the brain messenger and target for Lupron).  There are cases where sexual behavior and sexual obsessions are extremely difficult to regulate in puberty due to the underlying cognitive impairments in ASD.  In these cases there may be appropriate justification to reduce hormone levels to below the normal range and this may be safer than other psychotropic medications to control behavior.  These are not simple or easy choices to make.  

This is not a defense of either Mark Geier, MD or David Geier and their conduct. And clearly we differ in our views of the hormonal issues in ASD and the definition of precocious puberty.  Nor do I agree with their Lupron protocol as I understand it. However, I do not want to see the appropriate scientific discussion of hormones in autism discarded by their legal issues.

About Dr Bradstreet
Dr Bradstreet is a graduate of the University of South Florida College of Medicine and received his residency training at Wilford Hall USAF Medical Center. He is a Fellow of the American Academy of Family Physicians. He is an Adjunct Professor at the Southwest College of Naturopathic Medicine in Arizona. He is extensively published in the peer-reviewed literature on subjects of autism, oxidative stress, mitochondrial disorders, virology, hyperbaric oxygen, and toxicology (especially heavy metal chelation). He is trained in the the isolation and use of stem cells.

7 Responses to A Reluctant Discussion of Lupron and Autism

  1. Crystal says:

    Thank you for sharing this information. There was a time I checked into the lupron protocol for my son when he tested high in testosterone and his behavior was out of control. Through the expertice of a good doctor, we addressed these issues in a different and what seemed like a safer way. I remember asking myself what I would have done if my son had had this aggressive and out of control behavior and was older and stronger?
    At the time, there was an article in our local paper about a 14 yr. old boy with autism who had thrown a family member through a glass door. They had basically replaced the majority of their glass doors and windows in their home with plexiglass because he’d also shoved his fist through a window. I knew that I had to do something for my son so this wouldn’t be us one day. IF what we have done had not helped my child, I would have tried lupron if my son qualified.
    I don’t feel like the mainstream medical community is doing any better of a service to families than the lupron protocol by just dosing out heavy psychotics, yet that is legal. Parents are desperate for help and instead of pointing fingers at doctors trying to help our kids, I wish this would be seen as an eye opener for society.
    As far as the allegations are concerned, I also think this has more to do with money and how much it was costing insurance companies than the health effects on our children. I don’t agree with the lupron protocol, but I can see where I would have been desperate enough to use it and I think the Geier’s hearts are in the right place…just trying to help the families that are suffering.

    • Crystal – this is a very good comment. I echoed much of what you stated in my post. These are complicated and challenging situations and psychotropic medications carry the potential for permanent side-effects. There is nothing “illegal” about using Lupron for out of control behavior. The off-label use of many medications is completely common in the US. We docs can use any medication we think appropriate to the needs of our patients – even if the FDA did not approve of the use. What is illegal is telling the insurance company the patient has something that they don’t have in order to get it paid for. That is insurance fraud and plenty of doctors have lost their license or gone to jail over that process. Insurance is a contract between the owner (usually your employer) and the insurance company. In the complex legal language of every insurance contract the insurer gives themselves discretion to not pay for expensive treatment they deem to be “experimental”. That term is actually inaccurate but always used by companies. What they mean is they want to limit their budget to FDA indicated reasons. That is their choice but it severely limits a doctor’s ability to help in challenging cases unless the family has deep pockets. Insurance reform is necessary but I doubt we as health care consumers will ever see what we want from the insurance industry or our governments.

  2. marilina says:

    thank you dr.Bradstreet , this is another piece of the puzzle poorly addressed …( in our case: very low cholesterol, low cortisol high DHEA)

    have you read this one?

    http://www.ageofautism.com/2011/05/autism-estrogen-seizures.html

    • Then you are in the 20% or so of children with low cholesterol. Since ALL steroid molecules are built from cholesterol it follows that the resultant sex steroids or their precursors (DHEA) would be low. And as you can see on the steroid pathway chart on the blog – cortisol also comes from cholesterol. There are two options for therapy: 1) supplemental or increased dietary cholesterol, and 2) supplemental pregnenolone. Going back to the chart for a moment you can see pregnenolone comes after cholesterol and before cortisol or DHEA. Since most children I see are allergic to eggs it is hard to get dietary cholesterol adequately supplemented. I often use pregnenolone in those cases. You also want to make sure fats are being absorbed. I see fat malabsorption in a significant population of children. Bile salt deficiency would follow from cholesterol deficiency as well. Here is the bile salt pathway – derived from cholesterol as you can see. So we get into a vicious cycle of poor absorption of fat – low cholesterol and then worse absorption of fat. Cannot put pictures in responses so here is the link. http://www.jlr.org/content/50/Supplement/S120.full

      • marilina says:

        thank you so much ( it’s amazing how well you explain)
        I’m translating your post for italian parents as these issues really are not addressed and we have a percentual of children-young-adult with very low cholesterol
        I submit everything to my doctor
        Fortunately there are remedies….I think that DHEA can not balance the low cortisol for a long time ….In our case
        on the basis of what we read on age of autism (the post of Teresa Conrick) we are going to check the estrogen levels too
        thank you again

      • Actually DHEA can never balance cortisol. Cortisol is derived from pregnenolone via progesterone and DHEA is derived from pregenolone but down a different path via 17 hydroxypregnenolone. Study that steroid pathway on the blog and I think you will see why correcting hormones requires either Pregnenolone or Cholesterol.

  3. marilina says:

    even worse than I thought …
    the fact that “high DHEA balance low cortisol” was the interpretation that was given to us by the italian laboratory, adding “no problem” : I suspected I was reading a horoscope rather than a serious interpretation of data: now I have confirmation.
    terrifying in whose hands we put our children
    thank you again
    You opened my eyes (which were already open ,but did not know if they saw good)

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