Chemical Reactions of the Copper Intrauterine Device

Abstract

This study investigated the reactions of metallic copper with various biologic substrates to account for the loss of metallic copper in the IUD. Purified copper foil of .005 cm thickness was cut into strips and placed in solutions of the substrates then incubated at 37 degrees C. Loss of metallic copper was determined by measuring the cupricion concentration in the solutions with the diethyl ammonium salt of diethyldithiocarbamic acid. This compound forms a yellow chelate with cupricion which has an absorption maximum at 446 nm. The optical density of samples was compared with various mixtures of copper sulphate a chelating agent on a Cary 15 spectrophotometer at 446 nm. Human uterine secretion which had been aspirated at the midpoint of the menstrual cycle and similar material with saline solution added were studied. The uterine secretion with saline showed greater cupric ion concentration than when only saline was used with a similar size strip of copper or when an alkaline buffer was added to the saline. Secretion incubated with saline but without the copper showed a coherent and mucoid mass. 18 hour incubation of copper with midcycle mucus to which no saline had been added showed lyses of the mucoid material and the cupric ion concentration increased. Experiments with postovulatory cervical mucus gave similar results. Copper-inhibited cervical mucus brought into contact with washed sperm resulted in complete inactivation of the sperm within 2 hours. The sperm showed increased motility just prior to their demise. Such inactivation did not occur when no copper had been added to the incubated mucus. When bovine serum albumin solution was incubated with copper foil the amount of cupric ions formed was proportional to the surface area of the copper strip to the time of incubation and to serum albumin concentrations. The presence of oxygen was also found to be important. Oxidized and reduced glutathione were incubated with copper strips. The oxidized formed cupric ions while the reduced showed only a slight reaction indicating that the disulfide bond is a critical group in the dissolution process by biologic materials presumably acting as an oxidizing agent. Precipitation of modified albumin by cupric ions shown to be reversed at high albumin concentrations. Copper-incubated albumin samples showed less SH content than untreated albumin apparently because the copper ions catalyse the air oxidation of the SH groups present or formed by reduction with copper metal. The formation of SH groups in cystine can be demonstrated. When cystine is incubated with metallic copper in the presence of p-dichloroindophenol there is a fading of the blue color of the dye at the surface of the copper strip indicating formation of reducing groups. For disulfide substrates the metal reduces the S-S linkage. When alkaline phosphatase and carbonic anhydrase were incubated with copper inhibition of enzyme activity ensued after 1 hour. The amount of copper dissolved by uterine secretions from a 200 mm copper surface amounts to 60 mcg a day. The effectiveness of the copper IUD may arise in 2 general ways: 1) the scission of disulfide bonds resulting in a modification of S-S containing proteins and mucus causing precipitation of albumins which may change the internal wall in such a way as to prevent implantation.