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Fertility Drugs and Autism

Posted Sep 27 2010 1:08pm

On May 20, 2010, researchers from the Harvard School of Public Health presented their findings from a study exploring the possible relationship between the use of fertility drugs and autism spectrum disorder (ASD). The scientists reported to attendees at the International Meeting for Autism Research in Philadelphia that women who used fertility drugs to get pregnant had almost double the risk of having a child with ASD verses nonusers. The drugs studied included Clomid (clomiphene citrate) and Pergonal (gonadotropin).

Some have expressed skepticism about the study. However, although its value cannot be fully assessed until it appears in a peer-reviewed journal, there are several factors that argue in favor of its merits. In an effort to rule out other causes, Dr. Lyall and her colleagues made an “adjustment for pregnancy complications, maternal age, and other possible risk factors,” before making a determination that use of fertility drugs represented a 91% increased risk. This was at a highly significant statistical level – namely, the odds that their data did not occur by chance were 993 out of 1,000 (P=0.007). They also determined that a history of infertility – exclusive of fertility drugs – was not significantly associated with ASD, and that the “odds ratio for autism spectrum disorder increased with the number of reports of use of ovulation inducing drugs” (P=0.008).      

This recent study is part of a growing body of research that strengthens the argument that Clomid and other fertility drugs are a cause of ASD via their ability to deny cholesterol to a developing embryo shortly after conception. About 58% of ASD children have low total cholesterol (<160 mg/dL) and about 19% have extremely low total cholesterol (<100 mg/dL). The average level for children is about 165 mg/dL. It has also been observed that a high percentage of children (71-86%) born with Smith-Lemli-Opitz syndrome (SLOS), in addition to a wide array of birth defects are also born with ASD. Infants with SLOS are born with a defective enzyme that impairs the body’s ability to convert a precursor (7-dehydrocholesterol) to cholesterol. Cholesterol is essential for growth of the myelin membranes that cover the brain and abnormalities in the myelin sheath are believed to be a contributing cause of ASD. Many experts thus believe that low cholesterol during early embryonic development is one of the causes of ASD.      

Clomid has a long half-life and is present during the embryonic period (first 8 weeks) even when taken before conception. Studies have shown it to be biologically active for up to 54 days after ingestion and that it can accumulate over successive cycles of treatment. As mentioned, in the Harvard study they found that the longer the use of fertility drugs, the higher the risk of developing ASD. A critically important fact – and one not known by most physicians prescribing the drug – is that Clomid is a cholesterol inhibitor and impairs its production by acting upon enzymes in the body similar to Lipitor and other statin drugs. Its chemical structure is also similar to the cholesterol-reducing drug, Triparanol, which was briefly available during the 1960s. Animal studies have shown that Clomid and Triparanol both act on the same enzyme and affect developing organs in a similar way, with Triparanol being slightly more potent.

Pergonal (also known as human menopausal gonadotropin or hMG) likewise reduces cholesterol, but by way of a different mechanism. Namely, it suppresses cholesterol levels in early pregnancy via its ability to elevate estrogen production. Studies have established that following hyperstimulation of the ovaries by Pergonal, the resulting elevated estrogen during the luteal (post-ovulation) phase of the cycle suppresses the level of total cholesterol.   In fact, there is an inverse correlation between concentrations of estrogen and the level of total cholesterol – the higher the level of estrogen, the lower the concentration of total cholesterol.    

The GOOD NEWS is that many ASD children with low cholesterol, treated with cholesterol supplementation, have shown dramatic improvement. Scientists at Johns Hopkins University Medical Center, led by Dr. Richard Kelley, have shown such treatment resulting in improved mobility, verbalization, growth, behavior, sociability and alertness. Better yet, once we have a full understanding about one of the causes of ASD, some day in the future we might be in a position to eliminate that cause. As I postulated over two years ago, maintaining an optimum level of cholesterol throughout pregnancy could likely eliminate many cases of birth defects and autism spectrum disorder.   


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