A clinical trial of combined anti-androgen and anti-heavy metal therapy in autistic disorders

Authors:
Geier, D.A. and Geier, M.R.

https://pubmed.ncbi.nlm.nih.gov/17187010/

PMID: 17187010

Summary of study

This clinical trial suggests that combining Lupron and Chemet may improve behavioral symptoms and reduce hyperandrogenemia in some children with ASDs, with evidence of increased heavy metal excretion and decreased androgen levels. The treatment appears safe in the short term, but its small scale, lack of controls, and potential side effects call for larger, controlled studies to validate and refine this approach.

Findings

The study explored a novel treatment combining Lupron (an anti-androgen) and Chemet (a heavy metal chelator) in 11 children with autism spectrum disorders (ASDs). The treatment was based on the hypothesis that some ASDs may result from interactions between the methionine cycle-transsulfuration and androgen pathways, potentially triggered by mercury exposure. Here are the key findings:

• Behavioral Improvements:

  • The Autism Treatment Evaluation Checklist (ATEC) showed a significant overall improvement (p < 0.01). The median ATEC score dropped from 87 (70-79th percentile of severity) at baseline to 63 (40-49th percentile) after treatment.

  • Specific improvements were statistically significant in:

    • Sociability (p < 0.05)

    • Cognitive Awareness (p < 0.005)

    • Behavior (p < 0.05)

  • Parents reported enhancements in socialization, cognition, and behavior, corroborated by independent school evaluations in some cases (e.g., improved skills mastery and reduced disruptive behaviors).

• Reduction in Hyperandrogenemia Symptoms:

  • Clinical examinations revealed significant reductions in symptoms linked to elevated androgens, such as early growth spurts, premature secondary sexual changes, body/facial hair, and aggressive behaviors.

• Laboratory Results:

  • Urinary Heavy Metal Concentrations: Increased significantly (p < 0.05) from a baseline median of 0 μg/L (range 0-15) to 2.5 μg/L (range 0-112) after ~3 months, indicating metal excretion.

  • Blood Androgen Levels: Serum testosterone decreased significantly (p < 0.05) from a baseline median of 1.96 times the age- and sex-adjusted mean to 1.16 times the mean after ~3 months.

• Safety:

  • No significant adverse effects were observed on essential minerals (e.g., potassium, calcium, iron) or kidney, thyroid, or liver function.

  • Some children experienced gastrointestinal disturbances (e.g., diarrhea, constipation), which were managed by switching to transdermal DMSA when needed.

Type of Chelator Used

• Chelator: Chemet, which is meso-2,3-dimercaptosuccinic acid (DMSA).

  • DMSA is an oral chelating agent known for binding heavy metals like mercury, lead, and arsenic, facilitating their removal from the body via urine.

Dose

• Lupron (Leuprolide Acetate):

  • Initial Test Dose: 0.2 mL subcutaneous injection, observed for 3 days for adverse reactions.

  • Lupron Depot: 15 mg intramuscular injection every 28 days.

  • Daily Supplement: Subcutaneous Lupron adjusted to achieve a total dose of 50 μg/kg/day.

• Chemet (DMSA):

  • Oral Dose: 10 mg/kg body weight, administered three times daily (morning, mid-day, night) every other day throughout the treatment.

  • Alternative: If severe gastrointestinal issues occurred, transdermal DMSA was used at the same dose and schedule.

Time Until Symptoms Improved

• Treatment Duration: The median duration was ~4 months (111 days, range 60-196 days).

  • Improvements were assessed at the end of this period, implying symptom improvement occurred within 2 to 7 months.

• Early Observations: Some parents noted rapid behavioral improvements (e.g., better sleep, attention, socialization) within days of starting Lupron, even before chelation began.