Oral Contraceptives and Copper Metabolism

Abstract

It has been known for many years that serum copper is increased during the later stages of pregnancy. Exogenous oestrogens produce an increase in both serum copper and the copper-binding globulin ceruloplasmin and it is therefore not surprising that that all of the popular oral contraceptives containing potent synthetic oestrogens have been reported to increase serum copper and ceruloplasmin. A recent development in oral contraception is the daily administration of a continuous small dose of a synthetic progestogen alone without added oestrogen. Because chronic increases of ceruloplasmin have been suspected as being implicated in the aetiology of certain side-effects of oral contraceptives - notably migraine and chloasma - it seemed worthwhile to investigate the effects of one of these new products on forms of blood copper. Six normal healthy young women received .3 mg daily of norethisterone acetate (a product available under the "SH-420C" Schreing code name). As a control two other similar healthy young women received the combined 21-day preparation "Minovlar" (1.0 mg norethisterone acetate + .05 mg ethinyl oestradiol). Blood samples were taken by venepuncture after an overnight fast serum was collected and copper was determined by the diethyldithiocarbamate method and ceruloplasmin by the p-phenylenediamine method. Results of these determinations are shown in Table 1:y It is clear that the oestrogen-containing product "Minovlar" produced a marked increase in serum copper and ceruloplasmin but that "SH-420C" had no significant effect. The progestogen component of "SH-420C" norethisterone acetate is known to produce in man oestrogenic metabolites but the extent of this production and its biological effect are still obscure. Our data indicate that at the dose level used no significant amount of oestrogenic substances could have been formed. Indeed the use of changes in serum ceruloplasmin offers a novel approach to the detection of oestrogenic effects in the human. We thank Mr. J.E.N. Kelly for technical assistance and Dr. Denise Pullen for access to her patients.(Full text)