Plasma Homocysteine, Fasting Insulin, and Serum Androgens

Objective:  
Experience with in vitro fertilization-embryo transfer has shown poor oocyte quality to be associated with polycystic ovary syndrome (PCOS), a multisystem endocrinopathy typified sonographically by abnormal ovarian vascular flow patterns. Impaired oocyte competence has been linked to follicular vascularity and oxygenation defects by some investigators. Since homocysteine has been identified as a useful clinical marker for vascular disease and thromboembolism, we sought to measure plasma homocysteine concentrations with androgens and insulin in women with normal and polycystic-appearing ovaries presenting for infertility evaluation.

Design:  
Observational, cross-sectional clinical report.

Materials & Methods:  
Plasma specimens were collected from healthy female volunteers (n=54) by peripheral venipuncture. Study subjects received regular diets and had not yet begun to take prenatal vitamins. Samples were obtained after an overnight fast and stored at –20°C for batch analysis. Homocysteine was measured by dual immunoanalysis/fluorescent polarization method with calibration determined by assaying controls on 5 days (2 runs/d) across ten instruments in two replicates using single lot reagents (sensitivity=0.05mmol/l, CV=1.8%). Fasting insulin (serum) measurements were obtained by double antibody radioimmunoassay (sensitivity=2mU/ml, CV=6.2%). Serum total testosterone (TT), androstenedione and DHEAS were measured by conventional direct chemiluminescent competitive immunoassay. Ovaries were classified as “polycystic” when </=10 small (<10mm) peripheral cysts with central stromal sparing were identified by transvaginal sonographic exam.

Results: 
All values reported as median (IQR [25;75]).

Conclusion:  
Results from this investigation agree with previously published associations among polycystic-appearing ovaries, high BMI, hyperandrogenism and elevated fasting insulin. However, no abnormally high homocysteine levels were identified in our patients, and median plasma homocysteine levels were the same irrespective of ovarian morphology. Although the diagnosis of PCOS/insulin resistance confers an increased risk for type-2 diabetes, hyperlipidemia, hypertension, and coronary vascular disease, these preliminary data suggest that when standard sonographic, fasting insulin and androgen criteria are used to define PCOS, concomitant plasma homocysteine derangements are unlikely. Further studies are needed to clarify the role of homocysteine in human reproductive physiology.

Notes: BMI=body mass index H=plasma homocysteine I=fasting insulin TT=total testosterone ¹by student’s t-test