Reply to L Brattström

¹ Unit of Preventive Medicine, Rovira i Virgili University, Sant Llorenç, 21, 43201 Reus, Spain. E-mail: mm{at}fmcs.urv.es.
² Biochemistry Department, Trinity College, Dublin, Ireland.

Dear Sir:

As Brattström has stated, we showed that fasting plasma total homocysteine (tHcy) concentrations are reduced during pregnancy (1). Being longitudinal and including the preconception period, our study was the first to confirm that this decrease is not due to bias and that the reduction occurs as early as 7.5–8 wk of pregnancy.

Brattström has suggested that the decline in tHcy during pregnancy may be due to the pregnancy-associated change in renal hemodynamics, possibly in response to an endocrine-based effect. We are currently investigating whether the reduction in tHcy during pregnancy is endocrine-based or not. Whether or not an endocrine effect causes an alteration in renal hemodynamics during pregnancy, evidence is accumulating in the literature for a hormonal effect on tHcy. Several studies have shown changes in tHcy that coincide with key physiologically or pharmacologically induced changes in female hormones throughout the female life cycle. tHcy is similar in males and females until puberty but is lower in girls after the onset of menarche (2). tHcy remains lower in women than in men from menarche to menopause. tHcy is lower during the luteal phase than during the follicular phase of the menstrual cycle, both of which are characterized by changes in hormonal activity (3). As we showed, tHcy is reduced in pregnancy (1), during which a series of complex hormonal changes occur. tHcy increases in women with the onset of menopause (4) and is reported to be reduced in women receiving hormone replacement therapy (5). tHcy was also shown to be reduced in men treated with 17ß-estradiol (6). As Brattström suggests, endocrine-based changes affecting renal function may in part explain the reduction observed in tHcy during pregnancy and may be considered as a possible line of research for future studies.

Preliminary results from a study of change in serum creatinine concentrations from preconception to pregnancy in the same group of women in which we reported tHcy to be reduced in pregnancy (1) show that the mean percentage reductions in serum creatinine were 1.5%, 5.2%, and 10.9% at weeks 7–8, 20, and 32 of pregnancy, respectively (MM Murphy, JD Fernández-Ballart, and JM Scott, unpublished observations, 2002). This suggests that the magnitude of the corresponding reductions in tHcy of 11.7%, 20.9%, and 21.6% (in women unsupplemented with folic acid) during pregnancy are considerably greater than the changes in serum creatinine, a marker of renal function. Moreover, given the evidence for endocrine-based changes in tHcy in many situations in which changes in renal hemodynamics such as those that occur in pregnancy seem an unlikely common denominator, we propose that other factors are involved.

REFERENCES

1. Murphy MM, Scott JM, McPartlin JM, Fernández-Ballart JD. The pregnancy-related decrease in fasting plasma homocysteine is not explained by folic acid supplementation, hemodilution, or a decrease in albumin in a longitudinal study. Am J Clin Nutr 2002;76:614–9.
2. Morris MS, Jacques PF, Selhub J, Rosenberg IH. Total homocysteine and estrogen status indicators in the third National Health and Nutrition Examination Survey. Am J Epidemiol 2000;152:140–8.
3. Tallova J, Tomandi J, Bicikova M, Hill M. Changes of plasma total homocysteine levels during the menstrual cycle. Eur J Clin Invest 1999;29:1041–4.
4. Wouters MG, Moorrees MT, van der Mooren, et al. Plasma homocysteine and menopausal status. Eur J Clin Invest 1995;25:801–5.
5. Madsen JS, Kristensen SR, Klitgaard NA, et al. Effect of long-term hormone replacement therapy on plasma homocysteine in postmenopausal women: a randomized controlled study. Am J Obstet Gynecol 2002;187:33–9.
6. Giri S, Thompson PD, Taxel P, et al. Oral estrogen improves serum lipids, homocysteine and fibrinolysis in elderly men. Atherosclerosis 1998;137:359–66.