Effects of Oral Contraceptives and Hormone Replacement Therapy on Markers of Cobalamin Status

Abstract

Low serum concentrations of vitamin B12 (cobalamin) have been observed in users of oral contraceptives (OCs) (1), in women during pregnancy (2), and in men treated with high doses of ethinylestradiol for prostate cancer (3). Similar effects of hormone replacement therapy (HRT) have been noticed by some (4) but not all investigators (5). Serum cobalamin has low diagnostic accuracy as a marker of vitamin B12 status (6). Because of the long-term consequences of cobalamin deficiency [see Ref. (7) for a review], it is important to investigate whether decreased total cobalamin in OC or HRT users is associated with other evidence of impaired cobalamin status, such as increased plasma concentrations of methylmalonic acid (MMA) and total homocysteine (tHcy) and decreased plasma concentrations of holo-transcobalamin (holoTC) (8). We performed a cross-sectional study on 264 female healthcare students and workers. All participants gave written informed consent, and the study was approved by the Regional Ethical Committee and by the Norwegian Social Science Data Services. Study groups were OC users (n = 54) and controls (n = 81; age range, 18–40 years) and HRT users (n = 51) and controls (n = 78; age range, 41–65 years). The most frequently used OCs were triphasic combination tablets containing the synthetic estrogen ethinylestradiol and the progestogens levonorgestrel or drospirenon [Trinordiol™ (Wyeth-Lederle) or Trionetta™ or Yasmin™ (Schering AG)]. The most commonly used HRTs were either tibolone (Livial™; Organon) or the naturally occurring estradiol in combination with the progestogen noretisterone (Trisekvens™, Kliogest™, or Activelle™; Novo Nordisk A/S). We did not collect data on menstrual cycle or menopause. Detailed characteristics of the study population are given in Table 1 of the Data Supplement that accompanies the online version of this Technical Brief at http://www.clinchem.org/content/vol51/issue4/. Venous blood samples were collected over 6 months on a …