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The effect of environmental pollutants on thyroid and reproductive function Walter J. Crinnion ND Xenobiotics and Thyroid PCBs, Thyroxine, Bisphenol A all have two joined benzene rings with attached halogens (at similar sites). PCBs, PCDDs, PCDFs bind transthyrethrin in vitro, but not thyroxine-binding globulin. Also adversely effect thyroid hormone metabolizing enzymes in liver and brain PBDE and Thyroid Reduced thyroid hormone serum levels PBDE metabolites interfere with binding to thyroid hormone transport protein. PBDE increases metabolism of thyroid hormone Effect additive if PCBs also present PCBs and Thyroid PCB plant workers Elevated anti-TPO Elevated anti-thyroglobulin No out-of-range T4 or TSH Female Swedish fish eaters (Baltic fish) Inverse correlation with TT3 (significant) Inverse correlation with TT4 (insignificant) Polyhalogens and Thyroid German Children Pos. correlation PCB and TSH (significant) Inverse correlation PCB & fT4 (significant) Canadian Newborns PCP inversely correlated with fT4 German women PCP inversely correlated with basal T3 Acute OP poisoning 31.8 % experience sick euthyroid syndrome Low FT3, FT4 or TSH Other hormonal abnormalities Elevated cortisol, ACTH, prolactin Pesticides and thyroid Pesticide (OP) formulators Low TT3 (significant) Elevated TSH (non-significant) Pesticide (OP) applicators – low TSH (seasonal) Persons using dithiocarbamates from backpack sprayer Increased TSH TCDD and Thyroid Operation Ranch Hand Air Force personnel Serum levels of TCDD and TSH Those with highest TCDD had significantly elevated TSH. Heavy Metals and Thyroid Cadmium serum levels Lead Serum levels Elevated TSH and low FT4 (non significant) Low T4, TSH and TRH (significant) Hg vapor – workers Increased rT3 Female Fertility and Reproductive Outcomes Reproductive Outcomes Associated With Different Occupations Female Navy Personnel Exposed to petroleum products, solvents, heavy metals. 33% experienced adverse birth outcomes compared to 0% in civilian control group. Fetal distress - low birth weight Preterm delivery - Birth defects Small for gestational age babies Female Vietnam Vets OR 1.46 for having children with moderate to severe birth defects 2,4-D and 2,4,5-T ? Controls were contemporary female vets Ontario farmers Pesticide exposure and infertility RR 3.8 Dicamba – FR 0.51 Glyphosate – FR 0.61 2,4-D – FR 0.71 OP – FR 0.75 Thiocarbamates – FR 0.76 Reproductive Outcome Associated With Different Xenobiotics Organophosphates (OPs) Higher spontaneous abortion rates in Spanish greenhouse workers. Also more depression and headaches No reduction in acetylcholinesterase In California higher fetal death due to congenital anomalies (wk 3-8) OR 1.4 if spraying within 8 sq miles OR 2.2 if spraying within 1 sq miles Organochlorine compounds Serum HCH levels sign assoc w/ miscarriage and uterine fibroids. PCP assoc increased miscarriage and ANA HCH and PCB assoc w/ anti-thyroid and ANA Incr FSH, cortisol Decr T3, DHEA, Test, 17-OH progest, 17-OH-pregnen PCB assoc endometriosis and miscarriage DDT assoc reduced conception, preterm births and small for gestational age babies Generational Effects of DDT/E Women giving birth in Oakland, CA Serum frozen, later checked for DDT/DDE Daughters followed 28-31 years Maternal levels of serum DDT assoc. with reduced daughter fecundity (32% less). Maternal levels of serum DDE assoc. with increased daughter fecundity (16%) Cohn BA, Lancet 2003;361:2205-2206 Solvents OR 1.76 for infertility with occup exposure OR 1.95 for tubal factor infertility “ FR 0.47 with toluene workers FR 0.79 with occup organic solvent exp. Acetone FR 0.72 FR 0.36 for wives of solvent workers Solvents Chinese chemical workers OR 2.9 for spontaneous abortions OR 2.5 benzene OR 1.8 gasoline OR 2.3 hydrogen sulfide Pharmaceutical workers Increased risk spontaneous abortion from multiple solvent exposure (4 or more greatest) Still more on solvents Pharmacy assistants Incr risk spontaneous abortions and perinatal death with solvent exposure Forest workers Miscarriage OR 2.77 and 2.82 for use of certain paints to mark trees Miscarriage OR 1.87 for herbicide exp. Environmental Tobacco Smoke (ETS) Reduced fertility (FR 0.66) (OR 1.64) Higher rates ectopic pregnancy Higher rates spontaneous abortions Higher rates stillbirths (OR 2.0) Higher rates infant mortality (OR 1.8) Same even for moms who quit smoking in the first trimester. Outdoor air pollution PAHs Ambient air pollution sign assoc with PAHDNA adducts in maternal and cord WBCs Higher PAH-DNA adducts sign assoc w/ lower birth rates, birth length and head circumference. Inverse correlation with serum cotinine and birth length and weight PAH-DNA adducts higher in infertile males Phthalates DEHP in serum was highly significant in women with endometriosis. DEHP in cord blood gave a small but statistically significant increased risk of pre-term delivery. Love Potion # 9 Musk ketone Higher in women using perfume 4x wkly Greater PMS complaints Musk xylene Lower estradiol and progesterone Greater luteal insufficiency and infertility Higher in women with miscarriage hx. Hong Kong Seafood and Infertility & Hg levels Infertile Group Semen abn Control 40 26 Unexp Infertility Males N=176 40.6 44.2 31.2 Females N=181 33.2 37.0 17.5 Chlorination by-products Trihalomethanes Chloroform Bromodichloromethane Chlorodibromomethane Bromoform Increased risk of stillbirth OR 2.6 Increased risk miscarriages OR 1.98 BDCM Jeanette Sherman MD Takes on Chlorpyrifos (Dursban) Four children w/ multiple congenital defects Each with: Ventricular, eye & palate defects, growth retardation Three with: Hydrocephaly, microcephaly, mental retardation, blindness, hypotonia, wide-spread nipples, deformities of teeth, ears, genitals Jeanette Sherman MD Reviewed ALL known possible causative agents All were exposed in utero to chlorpyrifos Chlorpyrifos exposure previously associated with similar human defects in one published case. EPA banned chlorpyrifos for non-agricultural use. What to do in situations of infertility Review of exposure/burden Environmental Questionnaire Diet (EWG.org) Scorecard.org Other s&s associated with chemical overload Direct toxin measurement Flushed urine test for heavy metals Solvent & chlorinated serum levels for those with high exposure (Accu Chem 800-451-0116) Genetic polymorphisms T1/2 OP exposure Metabolite urine testing Avoidance of exposure (food) High antioxidants Hg and heavy metal burden DMSA or DMPS or EDTA/DMPS combo Supplementation Cleansing Solvent Overload Removal from exposure source Masks & air purifiers Enhancement of clearance Glycine, glutamine & taurine NAC Ascorbic acid Colonic irrigations