Original research articleBlood copper levels in Mexican users of the T380A IUD
Introduction
Copper intrauterine devices (Cu IUDs) are valuable birth control resources. Release of Cu from these devices is necessary for their contraceptive effects [1]. The Cu T380A is one of the most commonly prescribed IUDs; some of its advantages are fewer side effects in comparison with other method [2]. However, there are few reports of the T380A systemic side effects. The T380A is made of plastic with added barium sulfate for X-ray visibility, with a T-shape 36-mm height and 32-mm width. A copper wire twisted on its body and two copper sleeves on its arms, with a total Cu contact surface of 380 mm2 [2].
Release and absorption rates have been evaluated for different CU IUDs. A study carried out by Hagenfeldt [3] did not find a significant difference in plasma Cu concentrations levels between Cu T120 and T130 users and nonusers, but observed an increment in endometrial Cu concentration. The same author [3] estimated a T120 and T135 annual Cu liberation of 10.3 mg/year (range=7.4–13.5 mg/year) and a 5% annual endometrial Cu absorption (about 0.5 mg per year), and for T200, a daily release of 45 μg, around 18 mg/year. Timonen [4] reported a daily release that ranged from 26 to 74 μg Cu/day for different IUDs, and Thiery and Kosonen [5] reported a release of 23 μg Cu/d after 10 years of insertion for T220 devices without calcareous deposits. In 1972, Oster [6] observed that Cu ions in uterus could cross over to blood, increasing about 1% blood Cu concentration in T200A users. Later, Anteby et al. [7] found a nonstatistical difference between the serum levels of Cu before and after insertion of the T200A IUD. Prema et al. [8] studied 24-h urinary Cu excretion and did not find differences between a control group and Cu IUD users.
Copper is an essential trace element found in small amounts in different cells and tissues. Copper exists in both oxidized, cupric (Cu2+) or reduced (Cu+) state [9]. Copper's function as a cofactor is required for structural and catalytic properties of a variety of important enzymes, such as cytochrome c oxidase, Cu-zinc superoxide dismutase, tyrosinase, dopamine beta-hydrolase and others. Once Cu is absorbed, it is stored in several tissues and organs, among which, liver, kidney, brain and bone have the largest amount and blood the lowest [10]. Bile is the main route for Cu excretion, while urine represents a minor route [11], [12]. The daily recommended Cu intake is 1.5–3 mg/day [13], [14]. Food Cu concentrations are variable, chocolate and liver being among the highest in concentration, followed by cereals and fruits.
In the general population, a mean serum Cu concentration of 80 μg/dL with an upper range of 150 μg/dL [15], [16] and a whole blood Cu concentration with a mean value of 110 μg/dL have been reported [16], [17]. Although Cu is an essential element, it can become toxic for cells when present at high concentrations; as it is the case with cadmium and lead, Cu could displace metal ions such as calcium and magnesium [18]. In addition, the Cu2+ as other redox active metals can be toxic by generating free hydroxyl radicals [19], [20]. Free hydroxyl radicals resulting from catalytic Cu can bind to DNA and result in DNA strand breaks and DNA base modifications [21].
Toxic symptoms such as gastrointestinal symptoms have been reported at a serum level of 200 μg/dL and whole blood concentration above 287 μg/dL [16]. Hepatic symptoms appear at blood levels above 798 μg/dL [22]. Very high Cu levels can cause acute toxicity, and an oral dose of 200 mg/kg/day is considered fatal [23]. Individuals with Wilson's disease, an autosomal recessive disease, do not adequately metabolize and eliminate Cu and have a progressive accumulation of Cu in the brain, kidneys and liver [24].
In an effort to provide more information on Cu absorption in T380A IUD users, a group of users and nonusers was studied with the aim to measure their blood Cu levels and to evaluate potential Cu toxic effects.
Section snippets
Material and methods
The study was approved by the Research Committee of the Facultad de Estudios Superiores-Zaragoza, Universidad Nacional Autónoma de México (UNAM).
Results
Ninety-four women participated in the study, 86 were T380A users and 8 were controls. The mean ages for the cases and controls were 27.41±6.62 and 23.2±4.34 years old, respectively. No difference between the groups was found related to consumption of foods with relatively high Cu content such as chocolate, cereals, vegetables and fruits. Mean length of IUD use was 25±1.12 months with a minimum of 2 months and a maximum of 124 months.
Mean blood Cu level was significantly higher for cases (IUD
Discussion
According to Hagenfeldt [3], there was no significant increase of plasma Cu among T120 and T135 users as compared with controls. However, we found a significant increase in blood Cu levels among T380A users as compared with nonusers. Contrary to Hagenfeldt's [26] findings, in this study, Cu absorption has an observable effect in the metabolism of Cu in the body. In this case, the observed difference might be due to a greater Cu contact area, since the T380A has a 90% greater contact area than
Acknowledgments
We want to thank to Roberto Domínguez, Marylou Cárdenas and Silvia Maberti for their commentaries and useful suggestions to previous versions of this report. This project was partially funded by a UNAM-Health Research Program grant.
References (28)
- et al.
Contraception through the use of intrauterine metals. I. Copper as an adjunct to the ¨T¨ device
Am J Obstet Gynecol
(1971) Intrauterine contraception with the copper-T device. 1. Effect on trace elements in the endometrium, cervical mucus and plasma
Contraception
(1972)Copper release from copper-T intrauterine devices
Contraception
(1976)- et al.
The multi-sleeved copper T model TCu220C: effect of long-term use on corrosion and dissolution of copper
Contraception
(1987) - et al.
The effect of intrauterine devices containing zinc and copper on their levels in serum
Fertil Steril
(1978) - et al.
Serum copper in long-term users of copper intrauterine devices
Fertil Steril
(1980) Bioavailability of cooper
Am J Clin Nutr
(1996)- et al.
Acute copper sulfate poisoning
Am J Med
(1965) - et al.
Gastrointestinal symptoms and blood indicators of copper load in apparently healthy adults undergoing controlled copper exposure 1–3
Am J Clin Nutr
(2003) - Population Information Program. Population Reports. Dispositivos intrauterinos. Los DIU: un nuevo examen. Baltimore:...