A Reluctant Discussion of Lupron and Autism
May 12, 2011 7 Comments
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.
Autism Research Centre, Department of Psychiatry, University of Cambridge, Douglas House, 18B Trumpington Rd, Cambridge, CB2 8AH, UK. firstname.lastname@example.org.
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.
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).
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.
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.
University Center of Child and Adolescent Psychiatry, University of Antwerp, CAPRI youth, Belgium. email@example.com
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.
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.
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.
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.
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.
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.
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).
Am J Med Genet B Neuropsychiatr Genet. 2006 Sep 5;141B(6):666-8.
Abnormalities of cholesterol metabolism in autism spectrum disorders.
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.