Blood copper levels in Mexican users of the T380A IUD

Cruz, Dolores De la; Cruz, Angeles; Arteaga, Manuel; Castillo, Leonardo García-Rojas; Tovalín, Horacio

doi:10.1016/j.contraception.2005.02.009

Cited by 35 publications

(18 citation statements)

References 18 publications

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“…Cu ion concentration in burst release extracts (up to 160 μg/ml) for TCu380A is lethal to fibroblasts, and exposure of uterine tissues to such lethal concentrations (>100 μg/ml) should be viewed as a cause of concern. Furthermore, there is growing clinical evidence to suggest the deleterious cytotoxic and overloading effects due to TCu380A (Arnal et al 2010;Aston et al 2000;Beltran-Garcia et al 2000;De la Cruz et al 2005;Grillo et al 2010). As a result, it is advisable to encourage the use of alternative TCuIUDs that release Cu ions well within the cytotoxic limit, yet highly effective for contraception.…”

Section: Discussionmentioning

confidence: 96%

“…Furthermore, the sustained daily release of Cu 2+ ions also causes chronic systemic exposure (De la Cruz et al 2005;Okereke et al 1972;Shubber et al 1998). For instance, irrespective of the age of the user or the length of time of using TCu380A, De la Cruz et al, reported the sustenance of nearly double the normal values for Cu concentration in blood (De la Cruz et al 2005).…”

Section: Introductionmentioning

confidence: 98%

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Concentration-dependent cytotoxicity of copper ions on mouse fibroblasts in vitro: effects of copper ion release from TCu380A vs TCu220C intra-uterine devices

Cao

Zheng

et al. 2012

Biomed Microdevices

118

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Sustained release of copper (Cu) ions from Cu-containing intrauterine devices (CuIUD) is quite efficient for contraception. However, the tissue surrounding the CuIUD is exposed to toxic Cu ion levels. The objective for this study was to quantify the concentration dependent cytotoxic effects of Cu ions and correlate the toxicity due to Cu ion burst release for two popular T-shaped IUDs - TCu380A and TCu220C on L929 mouse fibroblasts. Fibroblasts were cultured in 98 well tissue culture plates and 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphehyltetrazolium bromide (MTT) assay was used to determine their viability and proliferation as a function of time. For cell seeding numbers ranging from 10,000 to 100,000, a maximum culture time of 48 h was identified for fibroblasts without significant reduction in cell proliferation due to contact inhibition. Thus, for Cu cytotoxicity assays, a cell seeding density of 50,000 and a maximum culture time of 48 h in 96 well plates were used. 24 h after cell seeding, culture media were replaced with Cu ion containing media solutions of different concentrations, including 24 and 72 h extracts from TCuIUDs and incubated for a further 24 h. Cell viability decreased with increasing Cu ion concentration, with 30 % and 100 % reduction for 40 μg/ml and 100 μg/ml respectively at 24 h. The cytotoxic effects were further evaluated using light microscopy, apoptosis and cell cycle analysis assays. Fibroblasts became rounded and eventually detached from TCP surface due to Cu ion toxicity. A linear increase in apoptotic cell population with increasing Cu ion concentration was observed in the tested range of 0 to 50 μg/ml. Cell cycle analysis indicated the arrest of cell division for the tested 25 to 50 μg/ml Cu ion treatments. Among the TCuIUDs, TCu220C having 265 mm(2) Cu surface area released 9.08 ± 0.16 and 26.02 ± 0.25 μg/ml, while TCu380A having 400 mm(2) released 96.7 ± 0.11 and 159.3 ± 0.15 μg/ml respectively following 24 and 72 h extractions. The effects of TCuIUD extracts on viability, morphology, apoptosis and cell cycle assay on L929 mouse fibroblasts cells, were appropriate for their respective Cu ion concentrations. Thus, a concentration of about 46 μg/ml (~29 μM) was identified as the LD50 dose for L929 mouse fibroblasts when exposed for 24 h based on our MTT cell viability assay. The burst release of lethal concentration of Cu ions from TCu380A, especially at the implant site, is a cause of concern, and it is advisable to use TCuIUD designs that release Cu ions within cytotoxic limits yet therapeutic, similar to TCu220C.

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Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 98%

Concentration-dependent cytotoxicity of copper ions on mouse fibroblasts in vitro: effects of copper ion release from TCu380A vs TCu220C intra-uterine devices

Cao

Zheng

et al. 2012

Biomed Microdevices

118

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“…Bleeding volume and frequency were assessed through subjective reports. It is known that copper IUD users can have up to a 50%–100% increase in their volume of menstrual flow in comparison to their menstrual flow prior to device placement; this in itself could justify the reported augmentation of blood flow independent of device position.…”

Section: Discussionmentioning

confidence: 99%

The influence of the levonorgestrel‐releasing intrauterine system position on bleeding patterns in reproductive age women

Alves

Rabelo

Andrade

et al. 2019

Intl J Gynecology & Obste

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Objective To determine whether users of the non‐fundal levonorgestrel‐releasing intrauterine system (LNG‐IUS) present with unfavorable bleeding patterns more frequently than fundal LNG‐IUS users. Methods A prospective cohort was conducted from June, 2016 to January, 2018 involving women aged 18–45 years who wished to use the LNG‐IUS as contraception and had no contraindications, endometrial polyps, submucosal myomas, irregular menstrual cycle, or anticoagulant use. Two study groups comprised women using fundal insertion and non‐fundal insertion LNG‐IUS. Bleeding was evaluated using a diary and pictogram chart. Results Of the 92 women who participated in the study, those with non‐fundal LNG‐IUS insertion sustained bleeding at rates greater than 83% (31) in the first 3 months of use, and 58% (14) at 6 months, versus 51% (22) at 3 months and 33% (19) at 6 months in those with fundal insertion (P=0.002 at 3 months; P=0.037 at 6 months). Blood loss in the non‐fundal LNG‐IUS group was higher than in the fundal LNG‐IUS group according to pictograms drawn by participants. Conclusion Women with non‐fundal LNG‐IUS placement had a higher frequency of sustained bleeding and blood loss volume according to self‐reported charts than those with fundal LNG‐IUS placement.

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“…The usual concentration of copper in human plasma (as determined by us and other groups) is between the range 0.3 to 2.1 mg/L for intakes of 1.4 to 2.0 mg copper/day [90]. Considering the available data, we can say that our experimental conditions resemble those Cu levels commonly found as a consequence of involuntary exposure through air, food and water pollution [88], in professionals engaged in agrochemical activities [22,28], or female users of Cu-based intrauterine devices [29,90,93].…”

Section: Days Of Culturementioning

confidence: 99%

Cytotoxic effects of copper overload on human-derived lung and liver cells in culture

Arnal

Alaniz

Marra

2012

Biochimica et Biophysica Acta (BBA) - General Subjects

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Blood copper levels in Mexican users of the T380A IUD

Cited by 35 publications

References 18 publications

Concentration-dependent cytotoxicity of copper ions on mouse fibroblasts in vitro: effects of copper ion release from TCu380A vs TCu220C intra-uterine devices

Concentration-dependent cytotoxicity of copper ions on mouse fibroblasts in vitro: effects of copper ion release from TCu380A vs TCu220C intra-uterine devices

The influence of the levonorgestrel‐releasing intrauterine system position on bleeding patterns in reproductive age women

Cytotoxic effects of copper overload on human-derived lung and liver cells in culture

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