Can a healthcare provider prescribe Provera (medroxyprogesterone acetate) to a 22-year-old female with Cornelia de Lange syndrome and irregular vaginal bleeding, and what are the dosing and contraindications?

Can Healthcare Providers Prescribe Provera for Irregular Vaginal Bleeding?

Yes, healthcare providers can prescribe Provera (medroxyprogesterone acetate) for a 22-year-old female with Cornelia de Lange syndrome and irregular vaginal bleeding, as it is an appropriate progestogen-only option for managing abnormal uterine bleeding in young women. 1, 2

Dosing Recommendations

For Irregular Vaginal Bleeding (Sequential Regimen)

• Medroxyprogesterone acetate 10 mg orally daily for 12-14 days per month is the gold standard dose for endometrial protection and bleeding control 1, 2
• This sequential regimen induces withdrawal bleeding and provides proven endometrial protection 1
• Alternative dosing: 2.5-5 mg daily continuously can be used if avoidance of withdrawal bleeding is desired 1, 2

For Contraceptive Purposes (If Needed)

• Depot medroxyprogesterone acetate (DMPA) 150 mg intramuscularly every 12 weeks (84 days, with up to 5-day grace period) is highly effective 1, 3
• DMPA 104 mg subcutaneously every 13 weeks (can be given up to 15 weeks) is an alternative formulation 1
• DMPA is particularly useful for women requiring menstrual suppression and is independent of daily adherence 1, 3

Absolute Contraindications to Provera

The FDA label specifies the following absolute contraindications 4:

• Known or suspected pregnancy (or use as a pregnancy diagnostic test)
• Undiagnosed vaginal bleeding (must evaluate cause before initiating therapy)
• Known or suspected breast malignancy
• Active thrombophlebitis, current or past history of thromboembolic disorders, or cerebrovascular disease
• Liver dysfunction or disease
• Known hypersensitivity to medroxyprogesterone acetate or any ingredients

Special Considerations for This Patient

Cornelia de Lange Syndrome Context

• Cornelia de Lange syndrome involves multiple system involvement including cardiac, gastrointestinal, and musculoskeletal abnormalities 5
• Screen for cardiac abnormalities before prescribing, as cardiovascular disease is a contraindication to hormonal therapy 4, 5
• Assess liver function, as liver dysfunction is an absolute contraindication and gastrointestinal involvement is common in this syndrome 4, 5

Evaluation Before Prescribing

• Rule out pregnancy with urine or serum hCG testing 4
• Investigate the cause of irregular bleeding through pelvic ultrasound to assess endometrial thickness and rule out structural abnormalities, as undiagnosed vaginal bleeding is a contraindication 4
• Obtain baseline liver function tests given the gastrointestinal involvement in Cornelia de Lange syndrome 4, 5
• Screen for personal or family history of thromboembolism 4

Advantages of MPA in This Population

• No effect on blood pressure or thrombosis risk compared to combined hormonal contraceptives, making it safer for patients with potential cardiovascular concerns 3
• Does not require daily adherence if using depot formulation, which may be beneficial for patients with developmental delay 1, 3
• Provides menstrual suppression with long-term use, which can improve quality of life for patients with disabilities 1

Important Counseling Points

Expected Side Effects

• Menstrual irregularities are nearly universal initially and typically improve over 3-6 months of continuous use 1, 6
• Breakthrough bleeding during the first 3-6 months is not harmful and decreases with persistent use 1, 6
• Weight gain is a common side effect that should be discussed upfront 1, 7

Management of Breakthrough Bleeding

• Continue the regimen for at least 3 months before considering it ineffective 6
• If bleeding persists beyond 3 months and is bothersome, consider adding short-term low-dose estrogen supplementation or switching to a sequential regimen 1, 6, 8
• Assess endometrial thickness by ultrasound if clinically indicated 6

Bone Health Considerations

• While DMPA has been associated with reversible bone mineral density loss, this is generally not a contraindication in young women 1
• Recommend 1300 mg calcium daily plus 600 IU vitamin D and weight-bearing exercise 1

Alternative Progestogen Options

If MPA is not tolerated or contraindicated:

• Norethisterone acetate 1 mg daily offers superior cardiovascular and metabolic profile compared to MPA while maintaining endometrial protection 2
• Levonorgestrel intrauterine system (Mirena) provides local endometrial protection with minimal systemic effects and may be beneficial for menstrual suppression 1, 2
• Micronized progesterone 200 mg daily (oral or vaginal) is the preferred first-line option when available due to the most favorable safety profile 1, 2