| ANTI-AGEING MEDICINE | PEER-REVIEW


genetic variants, the smallest possible dose of weak oestrogen over a short period of time ® preferably bioidentical hormone in transdermal application ® should be used together with supplements supporting methylation (e.g. vitamin B6, vitamin B12, choline, trimethylglycine (TMG), and folic acid). The potential genetic polymorphism of 5-MTHFR should also be ruled out, as folate in the form of L-5-MTHF is paramount for the synthesis of S-Adenosyl methionine (SAM; a methyl donor for the methylation of DNA). One should have a good overview of methylation activity by carrying out genetic testing for COMT and MTHFR SNPs, and checking homocysteine levels.


Encourage healthy intestinal excretion Checking UGT SNP for glucuronidation is not as important as supporting the healthy intestinal excretion of oestrogens and decreasing the enterohepatic circulation of oestrogens by eliminating the action of β-glucuronidase, by adding dietary fibre, phytoestrogens and probiotics.


Balance Environmental xenobiotics are Ôendocrine disruptorsÕ that modify intercellular communication and function. They produce a higher amount of the 4-OH and 16α-OH oestrogen metabolites that are potentially more genotoxic by modifying members of the CYP450 enzyme family (especially CYP1A1, CYP1B1 and GST). Xenobiotics can change DNA methylation (epigenetic modification), which can ultimately change oestrogen receptor activity. This may play a role in cancer pathology. A variety of pesticides have been shown in vitro to influence aromatase activity, increasing oestrogen conversion from androgens and adding an extra oestrogen burden in the body35


. High organochlorine levels promote high proliferation in Environmental xenobiotics are


Ôendocrine disruptorsÕ that modify intercellular communication and function.


oestrogen receptor-α positive breast cancers in postmenopausal women. All oestrogen receptor-α positive breast carcinomas from postmenopausal women had high cellular proliferation when levels of organochlorine residues were 2600 ppb or higher36


. All patients of HRT


should have a serological markers for toxicity checked, a toxicity questionnaire and SNP identification (FemGEN), and prior to any HRT, the elimination of environmental xenobiotics should be implemented.


Conclusions Conventional HRT, prescribed as Ôone-size-fits-allÕ , created a fear of breast cancer in patients and an uncomfortable decision for physicians who could not precisely estimate the risks described in the literature. By identifying womenÕs individual oestrogen metabolism and estimating the production of dangerous oestrogen


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metabolites in a particular case, it is possible to obtain a better picture of the actual risk.


 Declaration of interest The author is a speaker for Laboratories Reunis and uses genetic testing in every day practice


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