de Jong CMM, Blondon M, Ay C, et al. Incidence and impact of anticoagulation-associated abnormal menstrual bleeding in women after venous thromboembolism. Blood. 2022;140(16):1764-1773.

The impact of abnormal uterine bleeding (AUB) on health-related quality of life (QoL) is being increasingly underscored, with AUB repeatedly shown to cause productivity loss, exclusion from daily activities, and social and economic repercussions.1-3  However, systemic sexism and stigmatization result in AUB’s underdiagnosis and undertreatment, leaving the true prevalence and impact of AUB relatively unknown.4  Particularly among patients with venous thromboembolism (VTE), there is a lack of reliable data on how oral anticoagulation (OAC) therapy may exacerbate AUB.

To address this knowledge gap, Dr. de Jong and colleagues conducted the TEAM-VTE study, which evaluated the incidence of new-onset AUB, as well as its predictors and mitigators, among women on OAC therapy (Figure). In this multicenter prospective study, the authors observed women aged 18 to 50 years with venous thromboembolism (VTE) and an active menstrual cycle who started OAC therapy. Participants were followed until OAC discontinuation or six months, whichever occurred first. The International Society on Thrombosis and Haemostasis (ISTH) Bleeding Assessment Tool (BAT), Menstrual Bleeding Questionnaire (MBQ), and pictorial blood loss assessment charts (PBACs) were used to collect data at baseline; PBACs were then repeated for each menstrual cycle. The study’s primary outcomes were the incidence of AUB during follow-up, as well as new-onset AUB. Secondary outcomes included change in QoL, diagnostic work-up results, and treatment necessitated by AUB.

A total of 98 women with a first or recurrent VTE (mean age, 34 years) were enrolled; of these, two-thirds of the events were considered provoked, typically by oral contraception (OCP) or hormonal treatment. Most patients were started on a direct oral anticoagulant (DOAC; 87%; n=85) at time of diagnosis. AUB was defined in three ways: PBAC score >100 during one menstrual period, PBAC score >150 during one menstrual period, or self-reported increased menstrual volume. At least one of the three definitions was met by 66% (n=65) at any time in follow-up, although the majority experienced AUB within the first two months of VTE diagnosis.

Regarding secondary outcomes, QoL decreased over time, particularly among women with new-onset AUB. Of the 65 women with AUB, 32% (n=21) received AUB-related treatment, including: red blood cell transfusion, iron (oral or intravenous), anticoagulation reduction or cessation, tranexamic acid, or a form of contraception (OCP or intrauterine device). Two women underwent more invasive procedures — one woman underwent hysterectomy and another polypectomy. Concerningly, 15 of 40 women who were using estrogen-containing contraceptives discontinued them at the time of VTE diagnosis, despite data showing these agents are not associated with an increased recurrent VTE risk in patients receiving anticoagulant therapy.5  This practice may have further exacerbated the negative impact of anticoagulation on AUB. While dabigatran was not found to be associated with worsening AUB when compared with other anticoagulants, the patients who initiated on dabigatran often had preexisting AUB, and the study was not powered specifically to detect differences among agents.

Strengths of this study include a prospective design, a follow-up period that allowed assessment for multiple menstrual cycles, and the use of definitions that allowed for self-reporting. The latter point is particularly important because AUB may be underrecognized or normalized6-8  and because AUB definitions are increasingly moving from quantitative to qualitative approaches.9-10  Limitations include the relatively small sample size and the small subgroups that disallowed any subgroup analysis. Furthermore, for future work, we would encourage more inclusive language such as “individuals who menstruate” as opposed to “women.” The collection of additional baseline demographic data is also recommended, as sociocultural factors may influence patients’ abilities to recognize and report AUB or to utilize the aforementioned study tools.

This study collected prospective observational data to examine the incidence of AUB among women started on OAC for VTE. Two-thirds of patients who began OAC experienced AUB, there was a detrimental effect on QoL among patients with AUB, and approximately one-third of women required medical or surgical treatment. The authors reported a higher incidence of AUB than has been previously reported in the literature and invoked a call to action to increase awareness of AUB in this population. Specifically, menstrual blood loss should be assessed regularly among menstruating patients on OAC therapy, though further work is needed to delineate optimal management strategies in this patient population.

We are grateful that this area of research, where progress has historically been halted due to the stigmatization of AUB, is receiving more attention. Since Dr. de Jong’s publication, another prospective observational study (The PERIOD study) has been published11 ; similarly, the authors found that AUB occurred in two-thirds of women on anticoagulation therapy, with significantly worse QoL scores among anticoagulated women than a control group.

As we collectively appreciate the incontrovertible prevalence and impact of AUB among menstruating individuals on OAC therapy, mitigating strategies — ideally with patient involvement and input — are needed.

Dr. Arya and Dr. Scott indicated no relevant conflicts of interest.

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