What is the recommended prescription and contraindications for norethindrone in a 22-year-old female with Cornelia de Lange syndrome and irregular vaginal bleeding?

Prescribing Norethindrone for Irregular Vaginal Bleeding in Cornelia de Lange Syndrome

For a 22-year-old woman with Cornelia de Lange syndrome and irregular vaginal bleeding, norethindrone (progestin-only pill) should be prescribed as one 0.35 mg tablet taken orally at the same time every single day without interruption, after first ruling out pregnancy and underlying gynecological pathology. 1

Initial Evaluation Before Prescribing

Before initiating norethindrone, you must evaluate for:

• Pregnancy status - ensure it is reasonably certain the patient is not pregnant 2
• Underlying gynecological problems including sexually transmitted infections, new pathologic uterine conditions (polyps, fibroids), or medication interactions 2
• Special consideration for Cornelia de Lange syndrome: This population may have abnormal uterine contractile function (atony) that can contribute to bleeding issues 3

Prescribing Instructions

Dosing regimen:

• Norethindrone 0.35 mg orally once daily 1
• Must be taken at the exact same time every day 1
• Continuous administration with no pill-free intervals 1
• No interruption between pill packs 1

Timing of initiation:

• Can be started at any time if reasonably certain the patient is not pregnant 2
• If started within 5 days of menstrual bleeding onset: no backup contraception needed 2
• If started >5 days after menstrual bleeding started: use backup contraception (condoms) or abstain from intercourse for 7 days 2

Expected Bleeding Patterns and Counseling

Critical pre-treatment counseling:

• Irregular bleeding patterns are extremely common with progestin-only pills 2
• Approximately one-fifth of cycles may last less than 17 days 4
• Bleeding irregularities are not harmful and typically improve with continued use 2
• Enhanced counseling about expected bleeding patterns reduces discontinuation rates 5

Typical effectiveness:

• Failure rate of approximately 1.9-2.5 pregnancies per 100 woman-years with regular use 6
• Approximately 9 out of 100 women become pregnant in the first year with typical use 2

Managing Persistent Irregular Bleeding

If irregular bleeding persists despite norethindrone use:

First-line treatment:

• NSAIDs for 5-7 days during active bleeding episodes (e.g., mefenamic acid 500 mg three times daily or ibuprofen) 2, 7

Second-line treatment (if medically eligible):

• Low-dose combined oral contraceptives for 10-20 days 2
• OR estrogen therapy for 10-20 days 2

Re-evaluation needed if:

• Bleeding pattern changes abruptly 2
• Heavy or prolonged bleeding develops 2
• Patient finds bleeding unacceptable despite treatment 2

Absolute Contraindications (Category 4 - Do Not Use)

Cardiovascular conditions:

• Current or history of ischemic heart disease 2
• Stroke (history of cerebrovascular accident) 2
• Current breast cancer 2

Thrombotic conditions:

• Current deep vein thrombosis or pulmonary embolism 2
• Acute deep vein thrombosis or pulmonary embolism 2

Liver disease:

• Severe (decompensated) cirrhosis 2
• Malignant hepatoma 2
• Hepatocellular adenoma 2

Gynecological conditions:

• Current endometrial cancer 2
• Unexplained vaginal bleeding suspicious for serious condition (before evaluation) - this is Category 3 for progestin-only pills 2

Relative Contraindications and Precautions

Category 3 conditions (risks usually outweigh benefits):

• Multiple risk factors for cardiovascular disease 2
• Hypertension with vascular disease 2
• Migraine with aura at any age 2
• Current pelvic inflammatory disease 2
• Systemic lupus erythematosus with positive antiphospholipid antibodies 2

Category 2 conditions (benefits generally outweigh risks, but caution advised):

• Superficial thrombophlebitis 2
• Valvular heart disease (uncomplicated) 2
• Migraine without aura in women <35 years 2
• Undiagnosed breast mass 2
• Severe thrombocytopenia 2

Follow-Up Recommendations

Routine monitoring:

• No routine follow-up visit required 2
• Advise patient to return at any time to discuss side effects or concerns 2
• Assess satisfaction with method and any concerns about use 2
• Assess changes in health status or medications that would affect medical eligibility 2

When to consider method switching:

• If bleeding persists despite treatment and patient finds it unacceptable, counsel on alternative contraceptive methods (such as DMPA, implants, or IUDs) 2, 5

Special Considerations for Cornelia de Lange Syndrome

Given the documented case of hematometra secondary to abnormal uterine contractile function in a patient with Cornelia de Lange syndrome 3, maintain heightened vigilance for:

• Abdominal pain with bleeding 3
• Signs of blood accumulation despite patent cervical canal 3
• Need for imaging if symptoms suggest hematometra 3

This population may require more frequent clinical assessment than typical users, despite general guidelines not requiring routine follow-up. 2