From the Guidelines
Anticoagulation therapy can significantly impact a woman's reproductive cycle, particularly in terms of bleeding risks and pregnancy outcomes, and therefore, careful management and counseling are essential to minimize these risks. The effects of anticoagulation on the reproductive cycle are multifaceted, involving potential increases in menstrual bleeding due to the interference with normal clotting mechanisms, as well as considerations for pregnancy planning and management due to the teratogenic effects of certain anticoagulants like warfarin 1.
Key Considerations for Anticoagulation in Women of Childbearing Potential
- Women on anticoagulants may experience menorrhagia, with potential increases in blood loss by 30-70% due to the disruption of normal clotting mechanisms that limit menstrual flow.
- Management options for heavy menstrual bleeding include hormonal therapies (combined oral contraceptives, progesterone-only pills, or levonorgestrel-releasing intrauterine devices) and tranexamic acid for acute bleeding, if not contraindicated.
- Planned pregnancy requires medication adjustments due to the teratogenic effects of warfarin; switching to therapeutic-dose low molecular weight heparin before conception and throughout pregnancy is a common approach 1.
- The choice of anticoagulation strategy during pregnancy should be based on a balance between minimizing maternal and fetal risks, with considerations for the woman's values and priorities, and should involve shared decision-making with her physician 1.
Guidance for Anticoagulation Use in Pregnancy
- For women who become pregnant while on a direct oral anticoagulant (DOAC), it is recommended to discontinue the DOAC immediately and commence low molecular weight heparin (LMWH), as per the guidance from the International Society on Thrombosis and Haemostasis 1.
- Women taking warfarin should switch to a heparin preparation before planned delivery to minimize the risk of fetal intracranial hemorrhage 1.
- The use of LMWH during pregnancy requires careful monitoring, with dose adjustments based on anti-Xa levels to ensure therapeutic efficacy and minimize risks 1.
Importance of Counseling and Monitoring
- All women of childbearing potential should receive documented counseling prior to commencement of anticoagulation therapy, emphasizing the importance of avoiding pregnancy while on anticoagulants and the need for adequate contraception 1.
- Regular follow-up is crucial to assess the woman's understanding of her anticoagulation therapy, adherence to medication, and to monitor for any complications or changes in her condition that may require adjustments to her treatment plan.
From the FDA Drug Label
Females of reproductive potential requiring anticoagulation should discuss pregnancy planning with their physician The risk of clinically significant uterine bleeding, potentially requiring gynecological surgical interventions, identified with oral anticoagulants including apixaban should be assessed in females of reproductive potential and those with abnormal uterine bleeding.
The effect of anticoagulation therapy on the reproductive cycle of women is not directly addressed in terms of hormonal or menstrual cycle changes. However, it is noted that anticoagulation therapy, including apixaban, may increase the risk of uterine bleeding in females of reproductive potential. Women requiring anticoagulation should discuss pregnancy planning with their physician 2.
From the Research
Effect of Anticoagulation Therapy on the Reproductive Cycle of Women
- Anticoagulation poses unique challenges for women of reproductive age, including issues related to menstruation, teratogenic risks, and safety with breastfeeding 3.
- Abnormal uterine bleeding affects up to 70% of young women treated with anticoagulation, highlighting the need for thoughtful clinical guidance to manage menstrual issues and prevent premature discontinuation of anticoagulation therapy 3, 4.
- The subdermal implant may be considered a first-line option for women requiring anticoagulation, given its superior contraceptive effectiveness and ability to reliably reduce the risk of hemorrhagic ovarian cysts 3.
- All progestin-only formulations, such as the subdermal implant, intrauterine device, injection, or pills, are generally preferred over combined hormonal pills, patch, or ring for managing menorrhagia and dysmenorrhea in women on anticoagulation therapy 3, 4.
Anticoagulation Therapy and Menstruation
- Patients taking rivaroxaban appear to experience higher rates of heavy menstrual bleeding compared to those on apixaban, dabigatran, or warfarin 4.
- Heavy menstrual bleeding can be diagnosed with a good menstrual history and managed with hormonal therapies, including those associated with venous thromboembolism risk, such as combined hormonal contraceptives and depot-medroxyprogesterone acetate (DMPA) 4.
- Tranexamic acid and, in rare cases, endometrial ablation may also be useful in managing menorrhagia and dysmenorrhea in women on anticoagulation therapy 3.
Anticoagulation Therapy and Pregnancy
- Low-molecular-weight heparin (LMWH) is still the standard of care during pregnancy, while warfarin is contraindicated due to its teratogenic effects 3, 4.
- Enoxaparin remains the preferred anticoagulant during pregnancy, and breastfeeding women may use warfarin, but direct oral anticoagulants are not recommended due to limited safety data 3, 4.
- Women with double thrombophilias do not appear to have a greater risk for obstetric complications compared to those with single thrombophilias when treated with anticoagulation 5.
Interaction between Hormone Replacement Therapy and Anticoagulation Therapy
- The introduction of tibolone, a hormone replacement therapy preparation, can lead to acute over-anticoagulation and requires anticoagulant dose modification to re-establish target international normalized ratio (INR) 6.
- Non-tibolone hormone replacement therapy preparations do not consistently alter anticoagulant control or dose requirements 6.