Intrauterine device (IUD) is one of the most reliable methods of contraception. Worldwide, more than 15% of married women use intrauterine contraception . Copper-containing IUDs (Cu-IUDs), introduced in the late 1960s, are available in a variety of types and are mostly categorized based on their shape and their levels of Cu. The Cu T380-A is considered the most effective Cu-IUD .
Abnormal uterine bleeding is one of the most frequent causes for Cu-IUD discontinuation. Menorrhagia is defined as the amount of bleeding more than or equal to 80 ml per menstrual cycle or menses that lasts longer than 7 days .
NSAIDs, such as ibuprofen, act as inhibitors of prostaglandin synthetase and decrease the release of endometrial prostaglandin. Therefore, they potentially result in a reduction in menstrual bleeding, even in the presence of Cu-IUDs . Other medications, such as antifibrinolytic agents (e.g. tranexamic acid), are recommended by the WHO as the treatment for heavy or prolonged menstrual bleeding among Cu-IUD users .
Although intramuscular administration results in lower gastrointestinal adverse effects, tranexamic acid was administered orally in most studies, owing to its ease of use . Tranexamic acid was first approved in the 1980s as an injection to prevent or reduce bleeding during and following tooth extraction in patients with hemophilia. In clinical trials, menstrual blood loss was significantly reduced in women who received tranexamic acid tablets in comparison with those receiving a placebo .
In this study, we intend to compare the two most proposed medications for blood loss reduction in menorrhagic TCu380A-IUD users in Al-Hussein University Hospital for obstetrics and gynecology.
Patients and methods
A prospective randomized comparative parallel study between tranexamic acid and ibuprofen for treating Cu-IUD-induced menorrhagia included 100 women who attend outpatient clinic at Al-Hussein University Hospital from October 2019 to March 2020. The study population was grouped in two groups: groups 1 and 2. Each group comprised 50 cases. Group 1 (50 cases) was treated with tranexamic acid, and group 2 (50 cases) was treated with ibuprofen.
Women between 21 and 35 years who experienced more than 7 days of menstrual bleeding or menstrual blood volume of greater than 80 ml and have a history of regular spontaneous menstrual cycles (cycle length: 24–35 days) were included.
Patients with anatomical abnormalities such as uterine myoma; adenomyosis; ovarian cysts; coagulopathy, such as thromboembolism or stroke; on anticoagulant therapy; drug sensitivity to NSAID or tranexamic acid; gastrointestinal bleeding; genital infection; hypothyroidism or hyperthyroidism; other confounding factors that can lead to increased bleeding, and hypertension were excluded.
All patients were subjected to the following:
- Detailed history taking: personal history, menstrual history (including age of menarche, regularity or menstrual cycles, duration of menstruation, and amount of bleeding), present history, and obstetric history.
- General examination: vital signs (heart rate, temperature, respiratory rate, BMI, and blood pressure).
- Ultrasound examination: to localize the IUCD and to exclude uterine or ovarian pathologies.
- Routine investigation: including complete blood count to determine a base hemoglobin level before starting treatment.
- Blood loss volume calculation: to recognize IUD-induced menorrhagia, the women were given standard pads with the same size and shape and asked to use them in their next bleeding cycle. Patients then were asked to keep a daily record of the number of sanitary pads used and group them according to the pictures of pads that was lightly (10 ml), mildly (20 ml), moderately (30 ml), or completely (40 ml) saturated .
Informed consents were obtained from all participants after being informed about the aims and process of the study as well as applicable objectives.
Data management and statistical analysis
Data were fed to the computer and analyzed using IBM SPSS software package, version 22.0 (USA). Significance of the obtained results was judged at the 0.05 level.
There was no significant difference between the two groups regarding demographic data, as shown in Table 1. There was no significant difference in between the studied groups regarding the laboratory findings, as shown in [Tables 2 and 3].
Regarding menstrual days, there was no statistically significant difference in between the two groups, as shown in Table 2.
Menstrual days continue to decrease with treatment from the first months and for 6 months after treatment (Table 2).
Regarding blood loss volume, there was no statistical significant difference in between the two groups regarding blood loss volume before and after treatment, as shown in Table 4.
Menorrhagia is a debilitating problem that involves a large group of women and their doctors. Among women 30–49 years of age, one out of every 20 women are referred with menorrhagia, and ∼30% of the women report that 10–15% of their menorrhagia was caused by IUDs .
To treat menorrhagia, NSAIDs, progesterone, danazol, GnRH agonists, and antifibrinolytic drugs can be used .
Regarding the duration from the last delivery, it was 18.22 months in group 1 and 17.57 months in group 2, which coincides with the study done by Ali et al. , where it was 18.77 months in group 1 and 19.84 months in group 2.
In the study done by Kaviani et al. , who compared the effect of using tranexamic acid and mefenamic acid on the bleeding caused by planting IUD (TCu-380) on 84 females, there was a significant difference between the amount of bleeding before treatment and after the first cycle in both treatment groups (P=0.0001 and 0.0003, respectively), which coincides with our results, where a significant difference in between the studied groups regarding to blood loss volume at baseline and after the 6-month treatment (P=0.001 and 0.003, respectively).
Tranexamic acid has been 88% effective in the treatment of irregular uterine bleedings , which was in line with the results of the present study. The amount of bleeding was less in the case of tranexamic acid . Our findings were in line with other studies.
Endometrial fibrinolytic enzymes have an important role in homeostasis of menstrual bleeding. In dysfunctional bleeding, activities of plasmin and plasminogen activators increase, which is seemingly owing to fibrinolysis increase . Tranexamic acid applies its antifibrinolytic effects on plasminogen by inverting lysine binding and inhibits plasmin interaction with lysine residuals on fibrin polymers (which destroy fibrin) .
In a study by Sekhavat et al. , the participants were given 500-mg mefenamic acid every 8 h to one group and 500-mg tranexamic acid every 6 h to another group from the fifth day of menstruation. The results showed that tranexamic acid and mefenamic acid were effective for the treatment of hypermenorrhea by 50 and 20%, respectively.
In other various studies, tranexamic acid has been reported to be a more influential antifibrinolytic medicine than other types of menorrhagia treatment .
Tranexamic acid and medroxyprogesterone acetate were compared for treating dysfunctional uterine bleeding in a study by Kriplani et al. . These medicines were given to the patients in three cycles and were monitored during these three cycles. The results demonstrated that daily consumption of 2 g tranexamic acid was more influential than hormonal drugs in decreasing the amount of bleeding (60.3 vs. 57.7%). In addition, menorrhagia-induced hysterectomy was lower.
Other studies have also considered daily consumption of 3 g of tranexamic acid as an effective solution for treating menorrhagia in menstrual cycles along with ovulation .
Comparison between tranexamic acid and norethisterone by Preston et al. , in the treatment of menorrhagia along with ovulation showed that tranexamic acid decreased bleeding by 45%, whereas norethisterone decreased it by 20%.
Other researchers who used tranexamic acid in treating menorrhagia in six cycles found that menstrual bleeding decreased and the patients’ quality of life was enhanced . These results were consistent with those of the present work.
In terms of decreasing menstrual bleeding, it seems that tranexamic acid leads to stability of endometrial wall fibrin and consequently reduces bleeding . Moreover, this medicine has not increased the risk of thromboembolism in women of the reproductive age with the history of thrombosis .
On the contrary, one of the most accepted mechanisms in explaining heavy menstrual bleeding with Cu-IUDs users is that Cu-IUD has been associated with an increase in the prostaglandin production, which subsequently can cause an increase in the menstrual bleeding .
The implication of using ibuprofen was based on its ability to decrease prostaglandin production within the endometrium, an effect that leads to decrease in the uterine bleeding with Cu-IUDs . The NSAIDs are the most commonly tested medications for treatment of heavy bleeding with Cu-IUDs, not only for controlling the current bleeding attack but also as prophylactic against the uterine bleeding .
A Cochrane systematic review included 15 randomized controlled trials with more than 2700 women found that NSAIDs should be considered the first line for reducing bleeding associated with IUD insertion .
In our study, ibuprofen was effective in decreasing the uterine volume after 6 months of treatment. We are in the same track with the previous studies that proved a significant decrease in the mean uterine volume may lead to obvious improvement of uterine bleeding as well as the pain associated with IUD .
We recommend the use of tranexamic acid or ibuprofen in patients with menorrhagia owing to the use of IUD.
Based on this study, it seems that tranexamic acid as an antifibrinolytic agent, and ibuprofen as an NSAID, at dosage of 500-mg capsules of tranexamic acid three times a day, and 400-mg tablet of ibuprofen three times a day orally, have the same significant effects on Cu T-380A IUD-induced menorrhagia. Their effects are on both the volume of blood loss and the duration of menses.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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