What are the implications of Medroxyprogesterone (Provera) use with vaginal bleeding and clots?

From the Guidelines

If you're experiencing vaginal blood clots while taking Provera, it is essential to contact your healthcare provider to discuss these symptoms, as they can be a normal side effect but also may indicate an underlying condition that needs evaluation. Provera (medroxyprogesterone acetate) can sometimes cause vaginal bleeding with clots as a side effect, particularly when used to treat abnormal uterine bleeding or as part of hormone therapy. The presence of clots is often normal during Provera-induced withdrawal bleeding, which occurs when the medication is stopped after a course of treatment. Typically, this bleeding starts 3-7 days after completing Provera and may last 5-7 days.

According to the U.S. Selected Practice Recommendations for Contraceptive Use, 2013, adapted from the World Health Organization Selected Practice Recommendations for Contraceptive Use, 2nd edition 1, if clinically indicated, consider an underlying gynecological problem, such as interactions with other medications, an STD, pregnancy, or new pathologic uterine conditions (e.g., polyps or fibroids). If an underlying gynecological problem is found, treat the condition or refer for care.

Some key points to consider:

• The standard dosage for treating abnormal uterine bleeding is usually 5-10mg daily for 5-10 days.
• Provera works by stabilizing the endometrial lining and, when stopped, causes this lining to shed, sometimes resulting in clots.
• While small to moderate clots are generally expected, very large clots, extremely heavy bleeding, severe pain, or bleeding lasting longer than 7-10 days warrant immediate medical attention, as indicated by the guidelines 1.
• If irregular bleeding persists and the woman finds it unacceptable, counsel her on alternative methods, and offer another method if it is desired 1.
• Treatment options during days of bleeding can be considered, including NSAIDs for short-term treatment (5–7 days) or hormonal treatment (if medically eligible) with low-dose COCs or estrogen for short-term treatment (10–20 days) 1.

It is crucial to stay hydrated and use appropriate menstrual products during this time. If you experience any severe symptoms or concerns, do not hesitate to seek medical attention.

From the FDA Drug Label

Abnormal uterine bleeding (irregular, increase, decrease), change in menstrual flow, breakthrough bleeding, spotting, amenorrhea, changes in cervical erosion and cervical secretions. Abnormal uterine bleeding/spotting, or flow; breakthrough bleeding; spotting; dysmenorrheal/pelvic pain; increase in size of uterine leiomyomata; vaginitis, including vaginal candidiasis; change in amount of cervical secretion; changes in cervical ectropion;

The FDA drug label mentions abnormal uterine bleeding, breakthrough bleeding, and spotting as possible side effects of medroxyprogesterone acetate tablets. However, it does not specifically mention vaginal blood clots.

• Vaginal bleeding is mentioned as a possible side effect, but it is not clear if this includes blood clots.
• The label does advise to see a healthcare provider right away if vaginal bleeding occurs while taking medroxyprogesterone acetate tablets 2.
• It is recommended to talk with a healthcare provider regularly to discuss any side effects or concerns 2.

From the Research

Provera and Vaginal Blood Clots

• Provera, also known as medroxyprogesterone acetate, is a progestin medication used to treat abnormal uterine bleeding, including heavy menstrual bleeding 3, 4, 5.
• Studies have shown that progestin-only regimens, such as Provera, can be effective in reducing menstrual blood loss and improving quality of life in women with heavy menstrual bleeding 4, 5.
• However, progestin-only regimens may also be associated with side effects such as bleeding irregularity, which can include vaginal blood clots 4.
• A study comparing the efficacy of medroxyprogesterone acetate and tranexamic acid for treating heavy menstrual bleeding found that both treatments were effective in reducing menstrual blood loss, but medroxyprogesterone acetate was associated with more drug complications and less patient satisfaction 4.
• Another study found that the levonorgestrel-releasing intrauterine system was more effective than oral medroxyprogesterone acetate in reducing menstrual blood loss and improving treatment success in women with idiopathic heavy menstrual bleeding 5.

Management of Abnormal Uterine Bleeding

• The medical management of abnormal uterine bleeding involves a thorough history, physical examination, and indicated imaging studies to exclude significant structural causes 3.
• Medical management options for abnormal uterine bleeding include parenteral estrogen, combined oral contraceptives, progestin-only regimens, and tranexamic acid 3.
• Nonsteroidal anti-inflammatory drugs may also be used to decrease menstrual bleeding, and gonadotropin-releasing hormone agonists may be used in patients with leiomyoma and abnormal uterine bleeding 3.
• Women with inherited bleeding disorders may require specialized management, including the use of hormonal methods and tranexamic acid 3.
• Iron supplementation may also be necessary to manage iron deficiency and iron deficiency anemia associated with abnormal uterine bleeding 6.

Risks and Side Effects

• Hormonal contraception, including progestin-only regimens like Provera, has been associated with an increased risk of venous thrombosis, including deep vein thrombosis and pulmonary emboli 7.
• The risk of venous thrombosis varies depending on the type of hormonal contraception used, with some forms of contraception increasing the risk more than others 7.
• Women should be informed of the risks and side effects associated with hormonal contraception and offered education on alternative methods of family planning 7.