Management of Neurofibromatosis in Perimenopausal and Menopausal Women

Hormone Therapy and Contraception Considerations

The American College of Medical Genetics and Genomics recommends that oral estrogen-progestogen or pure progestogen contraceptives are safe for women with NF1 approaching or undergoing menopause, with 89% showing no associated neurofibroma growth, but high-dose depot progesterone formulations should be avoided due to risk of significant tumor growth 1, 2.
High-dose depot contraceptives containing synthetic progesterone should be avoided, as 3% of women experienced significant tumor growth with these formulations 1, 2.

The National Comprehensive Cancer Network recommends that women with NF1 require intensified breast cancer screening starting at age 30, with annual mammography and consideration of breast MRI between ages 30-50, as they face a five-fold increased breast cancer risk before age 50 4, 5, 6, 7, 8.
Annual mammography should begin at age 30 years, 20 years earlier than the general population, for women with NF1 4, 5, 6, 7, 8.
Breast MRI with contrast should be considered between ages 30-50 years, particularly for women with NF1 who may have greater breast density that limits mammogram interpretation 4, 5, 6, 7, 8.

The American Academy of Neurology recommends that annual medical evaluation should systematically assess for malignant peripheral nerve sheath tumor (MPNST), pheochromocytoma, chronic pain, depression, and bone health, as these complications peak in the perimenopausal and menopausal age range 4, 1, 5, 6, 7, 8.
Medical history questions should include inquiry about progressive severe pain or changes in tumor volume, diaphoresis, palpitations, or paroxysmal hypertension, chronic fingertip or toe pain with cold sensitivity, depression, and chronic pain assessment using pain-interference scales 4, 1, 5, 6, 7, 8, 9, 10.
Physical examination should include blood pressure measurement at every visit, clinical evaluation for scoliosis with Adam's forward bend test, and assessment of cutaneous neurofibromas for symptomatic changes 4, 5, 6, 7, 8, 9.
Laboratory and imaging studies should include serum vitamin D concentrations with supplementation to sufficient range, consideration of dual energy X-ray absorptiometry (DEXA) for bone mineral density assessment, and baseline MRI of known or suspected nonsuperficial plexiform neurofibromas 4, 5, 6, 7, 8, 9.

The American Academy of Pain Medicine recommends that chronic pain affects the majority of NF1 adults and requires systematic screening with pain-interference scales and referral to pain clinics employing both pharmacologic and non-pharmacologic approaches 4, 1, 2, 3, 10.
Pain assessment should include screening for glomus tumors, distinguishing pain etiology, and red flag assessment for new-onset or increasingly severe pain that mandates immediate evaluation for MPNST 4, 1, 2, 10.
Treatment options should include medication, physical therapy, and transcutaneous electrical nerve stimulation (TENS) for general NF1 pain, surgery for glomus tumors and compressive tumors causing neuropathy, and standard medications for NF1-associated migraine, seizures, and sleep disorders 3, 10, 4, 1, 2.

The Children's Tumor Foundation recommends that evaluation by and care coordination with a specialized NF1 clinic is strongly recommended, as the complexity of perimenopausal management requires multidisciplinary expertise including medical genetics, oncology, endocrinology, and pain management 4, 7, 3, 9.
The multidisciplinary team should include medical genetics, neurology, oncology, ophthalmology, orthopedics, dermatology, and endocrinology, and patient education about worrisome signs is essential for early complication detection 3, 9, 4, 7.