Characterization of copper in uterine fluid of patients who use the copper T-380A intrauterine device

Pontifical Catholic University of Chile, CiudadSantiago, Santiago Metropolitan, Chile
Clinica Chimica Acta (Impact Factor: 2.82). 07/2003; 332(1-2):69-78. DOI: 10.1016/S0009-8981(03)00124-4
Source: PubMed


The copper intrauterine device (IUD) is a highly effective method of contraception that requires the dissolution of the copper into uterine cavity. However, there is little information about the amount and form of copper in the fluid and whether the presence of this element produces any change in the protein concentration.
Twenty-seven women were divided into three groups that had used IUD for about 6 months, 1 year and > or =3 years. The samples were collected during the proliferative phase (Pp), secretory phase (Sp) and menstruation (M). Square-wave anodic stripping voltammetry (SWASV), cyclic voltammetry (CV), high performance liquid chromatography (HPLC) and atomic absorption spectrometry (AAS) were used in this study.
Total copper concentrations were between 3.9 and 19.1 micro g/ml. The mean and standard deviations were as follows: 6 months, 11.4+/-4.7 micro g/ml of copper; 1 year, 11.5+/-7.0 micro g/ml of copper; and 3 years, 6.2+/-1.5 micro g/ml of copper. Total proteins were quantified by measuring the area under the chromatographic peaks. The mean areas obtained with uterine fluid samples from women who used IUDs for 6 months, 1 year and 3 years were 290,013, 538,934 and 201,863 arbitrary units (AU), respectively. The control sample was only 22323.
The amount of copper released from IUD, although high, is in the form of complexes with proteins. IUDs have a constant copper release for at least 6-12 months. Copper(I) was not detected in the fluid. Copper induces a change in the total protein concentration. The amount of copper released and the amount of proteins is slightly larger during the menstrual stage.

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    • "The contraceptive effect of the Cu-IUD is mainly dependent on the copper ions released by the corrosion of copper;35–39 the larger the release rate of cupric ions, the better the contraceptive effect. According to the literature, there is an extremely high corrosive rate during the first few months, known as a cupric ion “burst release” after Cu-IUD insertion.8 However, overexposure could produce a wide spectrum of effects on surrounding cells and may exert significant in situ adverse effects. "
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    ABSTRACT: A copper/low-density polyethylene nanocomposite (nano-Cu/LDPE), a potential intrauterine device component material, has been developed from our research. A logical extension of our previous work, this study was conducted to investigate the expression of plasminogen activator inhibitor 1 (PAI-1), substance P (SP), and substance P receptor (SP-R) in the endometrium of Sprague Dawley rats, New Zealand White rabbits, and Macaca mulatta implanted with nano-Cu/LDPE composite. The influence of the nano-Cu/LDPE composite on the morphology of the endometrium was also investigated. Animals were randomly divided into five groups: the sham-operated control group (SO group), bulk copper group (Cu group), LDPE group, and nano-Cu/LDPE groups I and II. An expression of PAI-1, SP, and SP-R in the endometrial tissues was examined by immunohistochemistry at day 30, 60, 90, and 180 postimplantation. The significant difference for PAI-1, SP, and SP-R between the nano-Cu/LDPE groups and the SO group (P<0.05) was identified when the observation period was terminated, and the changes of nano-Cu/LDPE on these parameters were less remarkable than those of the Cu group (P<0.05). The damage to the endometrial morphology caused by the nano-Cu/LDPE composite was much less than that caused by bulk copper. The nano-Cu/LDPE composite might be a potential substitute for conventional materials for intrauterine devices in the future because of its decreased adverse effects on the endometrial microenvironment.
    Full-text · Article · Feb 2014 · International Journal of Nanomedicine
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    • "In this sense, during insertion Cu-IUD probably represents a dangerous combination of variables since the metallic device is in intimate proximity with local tissue for a long period and a high amount of Cu ions is released, particularly in the first period after insertion (burst release). In fact, cellular and biochemical changes occurring in the endometrium and uterine fluid after Cu-IUD insertion [13] [14], as well as inflammatory response enhancement by cupric ions together with an increase of Cu ions in plasma, were reported [15] [16] [17]. On the other hand, it is worth mentioning that several hundreds of Cu alloys are also employed in odontology for prosthodontic restorations [18]. "
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    ABSTRACT: Some specific clinical problems, particularly those related to orthopedic trauma and some cardiovascular diseases need only temporary support for healing. This support can be provided by biodegradable metallic materials such as, Fe-, Mg- based alloys that avoid some of the side effects of traditional biomaterials. They are expected to support the healing process of a diseased tissue or organ with slowly degrading after fulfilling their function. However, the excess of metal ions may catalyze the formation of reactive oxygen and nitrogen species (ROS and RNS). An increase in the intracellular levels of free metal ions affects the normal balance ROS-antioxidant. ROS could cause lipid peroxidation with changes in the composition and fluidity of cell membrane and alterations in other macromolecules as proteins and DNA. Considering that the concentration of metal ions can reach high values in the biomaterial-tissue interface inducing ROS generation it is important to evaluate the possible adverse effects of the degradation products of biodegradable biomaterials.
    Full-text · Chapter · Jan 2014
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    • "Thus, copper-containing implant materials could modify the balance between necessary copper and toxicity at cellular, tissue and organ levels[34,35]. Copper concentrations in uterine fluid from copper T- 380A IUD users were measured by Arancibia et al.[4]. They found that the amounts of copper released from IUD were between 3.9–16.7 mg/L, 5.5–19.1 mg/L and 5.9–7.1 mg/L for women tested after 6, 12 and 36 months insertion, respectively. "
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    ABSTRACT: A high dissolution of copper from intrauterine devices (IUDs) occurs during the first days after insertion. This work is focused on the assessment of the possible cyto- and genotoxic effects of different concentrations of copper ions released from metallic copper on mammalian cells in vitro. Colorimetric tetrazolium/Trypan blue (TB) tests and Comet assay were used to evaluate potential cytotoxicity and genotoxicity, respectively, in Chinese hamster ovary cells (CHO-K1). Reduction of mitochondrial activity by copper ions was observed for extracts at >or=7.42 mg/L concentrations, while TB exclusion test for plasma membrane integrity showed significant decrease in cell viability (close to 90%) for 10.85 mg/L concentration. Additionally, copper-induced DNA damage was detected for 5.67-7.42 mg/L concentration range. Our results demonstrate cytotoxic and genotoxic effects of copper ions released from metallic copper on CHO-K1 cells and emphasize the importance of reducing the initial copper dissolution from IUD without affecting the contraceptive action.
    Full-text · Article · Apr 2010 · Contraception
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