Homocysteine, Ovarectomy and Estrogen Replacement Therapy
Kaprál A.1, Hyánek J.2, Fait T.1, Živný J.1, Haaková L.1, Pejznochová H.1, Dubská L.2, Hladíková E.2, Macek M. jr.2
1Gynekologicko-porodnická klinika, 1. LF UK a VFN Praha 2Oddělení klinické biochemie, hematologie a imunologie Nemocnice Na Homolce, Praha |
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Summary:
Objective: Metabolic study of plasma levels of homocysteine (Hcy) in 30 womenafter hysterectomy and bilateral
ovarectomy for benign diseases.
On the basis of a previous pilot study of 6 female patients, an increase in the level of Hcy has been supposed to
occur after ovarectomy. The objective of the new study was to confirm the previous results and to detect possible
changes in homocysteinemia after the application of estrogen replacement therapy (ERT). Hyperhomocysteinemia(
HHC) – increased level of the free amino acid homocysteine in blood – is considered a significant risk factor
in early development of cardiovascular diseases, independent of lipids. Homocysteinemia can be favorably
influenced by increased dietary intake of folate and vitamins B2, B6 and B12. HHC can also be caused by genetic
mutations. The deficiency of 5,10-methylatetetrahydrofolate reductase (mutation C677T) is a cause of decreased
remethylation of Hcy. The group of women heterozygous for the MTHFR mutation was compared to a group of
women without this mutation for a duration of 8 weeks monitoring plasma levels of Hcy, follicle stimulating
hormone (FSH), estradiol (E2), folate, and vitamin B12.
Methods: Total homocysteine in plasma was determined by a chromatographic method with the use of fluorescence
detection. The plasma hormone levels were determined by RIA test (DCL company). The mutation of the
gene for 5,10-MTHFR was determined by PCR. During the course of 8 weeks, 6 blood samples were taken. The 1st
sample was taken before ovarectomy, further on the 1st, 3rd, 7th, 28th, and 56th day after surgery. From the 28th day
after surgery 50 micrograms of 17-beta estradiol were substituted by weekly transdermal system.
Results: In the population studied no homozygote for 5,10-MTHFR was found in the group of operated women,
only 5 heterozygotes and 25 healthy homozygotes were found. The Hcy values did not significantly differ in the
two groups. The patients were distributed into two new groups according to their FSH level in the plasma (40
UI/I was stipulated as the limit). After ovarectomy the Hcy increased in both groups, and after hormonal
treatment the Hcy decreased. The folate level in both groups corresponded with the Hcy level, no dependence
was shown in the concentration of vitamin B12 (P<0.0001).
Conclusion:We confirmed a significant increase of Hcy levels after overectomy and a subsequent decrease after
substitution treatment by estradiol. This correlation was followed by folate levels. No difference or correlation
in monitored parameters was observed between heterozygotes for MTHFR and healthy homozygotes.
Key words:
homocysteine, homocysteinemia, ovarectomy, mutations, folate.
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