Plasma Homocysteine Levels in Polycystic Ovary Syndrome and Congenital Adrenal Hyperplasia

Abstract

Abstract. The purpose of this study was to determine whether polycystic ovary syndrome (PCOS) and nonclassic 21-hydroxylase deficiency (CAH) are related to hyperhomocysteinemia, and to investigate if there is a correlation between homocysteine levels and insulin sensitivity in women with PCOS and CAH. Fifty patients with PCOS, 50 patients with CAH and 25 control women were included in the study. Blood samplings were performed in the early follicular phase for measuring hormone profile, Vitamin B 12 , folate, homocysteine levels and fasting blood glucose. Ovulatory status was assessed with timed serum progesterone measurements. Homeostasis model assessment-insulin resistance (HOMA-IR) was calculated as a measure of insulin resistance. Mean homocysteine levels were found as (8.9 + 1.9 umol/l and 17.7 + 3.6 umol/l) in the normal group and PCOS respectively (p<0.001), but there was no statistical significance between nonclassic 21-hydroxylase deficiency (9.0 + 2.2 umol/l) and control group. Most of the patients in PCOS group (35 of 50) were significantly insulin resistant. However, there was no insulin resistant patient in CAH or control group. When we compare the two subgroups of PCOS women, the patients with insulin resistance had significantly higher homocysteine levels than the ones who were not insulin resistant. There were positive correlations among serum homocysteine, insulin and androgen levels in PCOS patients. There were no correlations among these parameters in CAH and control groups. Increased homocysteine levels may contribute to increased cardiovascular disease risk in patients with PCOS. The reason for hyperhomocysteinemia seems to be related to insulin resistance but not high androgen levels.

Cardiovascular risk, metabolic profile, and body composition in adult males with congenital adrenal hyperplasia due to 21-hydroxylase deficiency

“…Most studies of lipids in CAH have shown normal values (9,18,20). We found similar lipid levels in patients and controls, but an unfavorable HDL/LDL ratio in older male patients compared with younger ones.…”

“…We found similar lipid levels in patients and controls, but an unfavorable HDL/LDL ratio in older male patients compared with younger ones. Homocysteine, another marker of increased cardiovascular risk, has been analyzed in one NC-CAH study and found to be similar to that in controls (18). In contrast, our younger CAH males had decreased homocysteine, which may give cardiovascular protection.…”

“…Our patients had increased insulin release during the OGTT and older patients tended to have higher HbA1c than younger ones, suggesting an increased risk of T2DM in the older CAH males. Insulin resistance has been found in adult CAH by all investigators (6,8,9,12,13,18,(20)(21)(22)(23), but one (18) and has most commonly been expressed as homeostasis model assessment (HOMA) index. We did not calculate this index because fasting glucose was low in our patients, which may lead to a falsely low estimation of insulin resistance.…”

“…Inadequate mineralocorticoid therapy for aldosterone deficiency may also have negative impact on the vascular system (11). Previous reports on cardiovascular and metabolic profiles in CAH adults have mainly included young females, in spite of the fact that males in general have a higher cardiovascular risk, and the results have been contradictory (6,8,9,(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22). A very recent publication described however a cohort of 203 individuals with CAH including 62 males reporting adverse metabolic profiles (23).…”

Impact of folate and homocysteine metabolism on human reproductive health

“…Thus a number of studies have investigated homocysteine and folate metabolism and confirmed the presence of increased serum homocysteine concentration in obese as well as in non-obese PCOS patients (Yilmaz et al, 2005). MTHFR polymorphism does not seem to be more frequent in these patients than in healthy controls (Tsanadis et al, 2002), and the possible determinants of elevated homocysteine concentration are still debated among authors who found significant correlations between homocysteine and insulin resistance or hyperandrogenism (Yarali et al, 2001;Schachter et al, 2003;Vrbikova et al, 2003;Bayraktar et al, 2004;Wijeyaratne et al, 2004) and those who did not (Loverro et al, 2002;Kilic-Okman et al, 2004;Yilmaz et al, 2005). Interestingly, administration of insulin sensitizers, such as metformin, as it is proposed in PCOS patients to improve ovulation induction and other parameters (Stadtmauer and Oehninger, 2005), has led to a further increase of serum homocysteine in these patients, despite the decrease in insulin resistance (Vrbikova et al, 2002;Kilicdag et al, 2005b).…”