Can estrogen be administered to a patient with gastrointestinal upset associated with ibuprofen (ibuprofen) and prolonged bleeding while on Depo-Provera (medroxyprogesterone acetate), who also reports having pancreatitis?

From the Guidelines

I would not recommend adding estrogen to manage bleeding in a patient on Depo-Provera who has pancreatitis, upset stomach with ibuprofen, and prolonged bleeding. Adding estrogen could potentially worsen pancreatitis, as estrogen therapy is associated with increased risk of pancreatitis in susceptible individuals 1. For managing Depo-Provera-related bleeding, consider non-hormonal alternatives like tranexamic acid (1000-1300 mg orally three times daily for 5 days during heavy bleeding) or a trial of NSAIDs other than ibuprofen, such as naproxen (250-500 mg twice daily with food) if tolerated.

Key Considerations

• The patient's pancreatitis should be fully evaluated and managed before making significant changes to her medication regimen, as the underlying cause of pancreatitis may influence treatment decisions 2.
• The bleeding with Depo-Provera often improves after 3-6 months of use as the endometrium becomes atrophic.
• If bleeding remains problematic, consider switching to a different contraceptive method altogether, taking into account the patient's preferences, treatment goals, and medical history 1.

Management Options

• Non-hormonal alternatives for managing bleeding: + Tranexamic acid (1000-1300 mg orally three times daily for 5 days during heavy bleeding) + NSAIDs other than ibuprofen, such as naproxen (250-500 mg twice daily with food) if tolerated
• Consideration of underlying health conditions, such as interactions with other medications, sexually transmitted infections, pregnancy, thyroid disorders, or new pathologic uterine conditions (e.g., polyps or fibroids) 3, 2, 1

From the FDA Drug Label

A positive association has been observed between the amount of estrogen and progestogen in oral contraceptives and the risk of vascular disease. The activity and amount of both hormones should be considered in the choice of an oral contraceptive. Minimizing exposure to estrogen and progestogen is in keeping with good principles of therapeutics For any particular estrogen/progestogen combination, the dosage regimen prescribed should be one which contains the least amount of estrogen and progestogen that is compatible with a low failure rate and the needs of the individual patient

The patient is already taking Depo-provera, which contains a progestogen. Adding estrogen on top of Depo-provera may increase the risk of vascular disease.

• The patient has prolonged bleeding with Depo-provera, and adding estrogen may not necessarily decrease the bleeding.
• The patient also has pancreatitis, and there is no information in the drug label that suggests estrogen would be beneficial in this case.
• The safest option would be to avoid adding estrogen and consider alternative methods to manage the patient's bleeding. 4

From the Research

Estrogen Supplementation with Depo-Provera

• The use of estrogen supplementation during Depo-Provera initiation may decrease bleeding and improve continuation, as suggested by a prospective, randomized, controlled trial 5.
• Vaginal estrogen supplementation during DMPA initiation is acceptable to women and may decrease total bleeding, with a median number of bleeding or spotting days of 16 in the estrogen ring group versus 28 in the DMPA alone group 5.

Medical Management of Abnormal Uterine Bleeding

• In the treatment of women with abnormal uterine bleeding, medical management is the first-line approach, and determining the acuity of the bleeding, the patient's medical history, and assessing risk factors will individualize their medical regimen 6.
• Parenteral estrogen, a multidose combined oral contraceptive regimen, a multidose progestin-only regimen, and tranexamic acid are all viable options for treating acute abnormal uterine bleeding with a normal uterus 6.

Considerations for Estrogen Therapy

• The use of postmenopausal hormone replacement therapy has been associated with an increased risk of acute pancreatitis, with a multivariable-adjusted relative risk of 1.57 compared to never users 7.
• Estrogen treatments have been shown to reduce the number of days of an ongoing bleeding episode in DMPA and Norplant users, but treatment frequently leads to more discontinuation due to gastrointestinal upset 8.

Treatment of Bleeding Irregularities

• Various interventions, including estrogen, anti-progestin mifepristone, and nonsteroidal anti-inflammatory drugs (NSAIDs), have been evaluated for their ability to treat abnormal bleeding associated with progestin-only contraceptives, with mixed results 8.
• Some women may benefit from these interventions, particularly with cessation of current bleeding, but findings need to be reproduced in larger trials 8.