Overview of Reproductive Health Concerns in Lymphangioleiomyomatosis
Lymphangioleiomyomatosis (LAM) is a rare lung disease mainly seen in women. LAM can occur either in association with a heritable syndrome known as Tuberous Sclerosis Complex (TSC-LAM), or occur in women without TSC (Sporadic LAM or S-LAM). LAM leads to progressive destruction of lung tissue and formation of multiple air-filled pockets (cysts). Patients with LAM are also at increased risk of developing pneumothorax (collapsed lung). Treatment with sirolimus has been shown to stabilize lung function decline in LAM patients.
The relationship between female hormones, especially estrogen, and LAM has long been speculated. Following is a summary of select reproductive health concerns for LAM patients.
Hormonal therapy
Anti-estrogen therapy in various forms, ranging from progesterone to hysterectomy, has been long been tried to treat LAM patients with mixed results. However, hormonal therapy has not been studied in a rigorous fashion. As such, routine use of hormonal therapy is not currently recommended in LAM pending the conduct of well-done controlled studies.
Contraception
LAM patients should avoid contraception with estrogen containing compounds. Non-estrogen forms of contraception such as barrier methods, tubal ligation, or progesterone-only formulations are preferred.
Pregnancy
Pregnancy in LAM has been associated with increased risk of disease progression and increased risk of pneumothoraces. The risk factors associated with worse outcomes during pregnancy are not well understood. As such, it is not possible to estimate the exact risks of pregnancy in individual LAM patients. In general, it stands to reason that patients with preserved lung function at baseline are better positioned to assume the risk of pregnancy, while those with severe lung impairment, rapidly declining disease, or recurrent pneumothoraces may have limited reserves. LAM patients who choose to pursue pregnancy should be followed closely by their obstetrician and pulmonologist to closely monitor lung function throughout pregnancy.
The decision to pursue vaginal delivery or caesarian section should generally be made based on the obstetric indications. Careful attention should be paid to the signs and symptoms of pneumothorax during labor and delivery.
On occasion, LAM patients choose to pursue egg harvesting. While there is no high-quality evidence, there are anecdotal reports of disease worsening in LAM patients undergoing ovarian stimulation to facilitate egg harvesting. Low estrogen egg harvesting protocols have been successfully employed in patients with breast cancer, and in a few LAM patients. Whenever possible, LAM patients pursuing egg harvesting should aim to use the lowest possible dose of estrogen. These procedures should be conducted in close collaboration with maternal fetal specialist and pulmonologist.
There is no known report of disease transmission from mother to child in S-LAM. However, TSC could be passed from mother to offspring. TSC patients contemplating pregnancy should be educated about this possibility and encouraged to seek genetic counseling prior to conception.
Sirolimus
Pregnancy: In general, sirolimus should be avoided during pregnancy. Although safe use of sirolimus through pregnancy has been reported in a few LAM patients, the long-term safety and efficacy of this approach for mother and child requires further investigation. The decision to continue sirolimus during pregnancy should be made on a case-by-case basis.
Lactation: It is unknown whether sirolimus is secreted in breast milk, and breast-feeding while taking sirolimus should be avoided.
Other reproductive health issues: Sirolimus can lead to menstrual irregularities and also cause the formation/enlargement of ovarian cysts. Most ovarian cysts due to sirolimus tend to be asymptomatic and can be safely monitored without intervention.
