Primary amenorrhea is common after fontan circulation and independently predicted by elevated adolescent BNP
K Matsuo, H Kawaguchi, D Asada, Y Ishii, H AokiAbstract
Background
Improved survival after Fontan circulation has resulted in a growing population of women reaching reproductive age. However, female-specific long-term complications are not incorporated into current risk assessment, and the prevalence and determinants of primary amenorrhea remain unclear.
Purpose
To determine the prevalence and endocrine phenotype of primary amenorrhea after Fontan circulation and to identify adolescent predictors.
Methods
We retrospectively studied 87 females aged ≥15 years after Fontan circulation. After excluding Turner syndrome and missing menstrual data, 72 women were analyzed (median age 22 years, range 15–38). Menstrual status was classified as normal, secondary amenorrhea, or primary amenorrhea (no menarche by age 15). Haemodynamic and laboratory parameters obtained at 10–14 years were evaluated as predictors. Logistic regression identified independent associations.
Results
Primary amenorrhea occurred in 24/72 women (33%). Median age at menarche was 14 years, later than the Japanese population average of 12.2 years. Among the 48 who achieved menarche, 7 (15%) later developed secondary amenorrhea. Endocrine evaluation within the primary amenorrhea group showed heterogeneous patterns: predominantly normogonadotropic (21/24), with central hypogonadism (n=1) and hypergonadotropic profiles suggestive of primary ovarian insufficiency (n=2). Conventional haemodynamic parameters—including inferior vena cava pressure, ventricular end-diastolic pressure, oxygen saturation, pulmonary vascular resistance, and cardiac index—were not associated with primary amenorrhea. In contrast, adolescent BNP levels were higher in affected patients (30.1 vs 11.0 pg/mL, p=0.01). Log-transformed BNP independently predicted primary amenorrhea (OR 3.16, 95% CI 1.44–6.95, p=0.004).
Conclusion
Primary amenorrhea is a frequent and under-recognized long-term complication after Fontan circulation. Endocrine phenotypes are heterogeneous, ranging from functional suppression to profiles suggestive of primary ovarian insufficiency. Elevated adolescent BNP independently predicts later reproductive dysfunction, suggesting that chronic neurohormonal stress during adolescence may influence hypothalamic–pituitary–ovarian axis regulation. Conventional haemodynamic parameters alone may be insufficient for reproductive risk stratification. Reproductive health should be incorporated into comprehensive, standardized lifelong follow-up of Fontan survivors.Primary Amenorrhea and BNP in Fontan Women