SUN-106 - Impact of Perceived Stress on Vascular Function in Women with Functional Hypothalamic Amenorrhea

Introduction:
Functional hypothalamic amenorrhea (FHA) is the loss of menstrual cycles due to suppression of hypothalamic GnRH secretion without structural disease, and is triggered by stress, energy deficit, and/or excessive exercise. Prior research demonstrates that approximately one in three women with FHA exhibits endothelial dysfunction, a preclinical marker of cardiovascular disease. Although estrogen deficiency has been associated with endothelial dysfunction, prior studies show that estrogen replacement in women with FHA does not improve vascular impairment, suggesting that factors beyond estrogen loss are involved. This study evaluates the association between perceived stress and vascular function in women with FHA.

Methods:
FHA was defined as ≥3 consecutive months of amenorrhea, estradiol < 50 pg/mL, FSH < 10 mIU/L, LH < 10 mIU/L, and LH:FSH < 1, after excluding other causes such as polycystic ovary syndrome, hyperprolactinemia, thyroid dysfunction, and pregnancy. Perceived stress was measured using the 10-item Perceived Stress Scale (PSS-10) and dichotomized as high (>18) or low (≤18) using the sample mean as the cutoff. Serum blood samples were collected at the study visit, with all samples obtained under standardized conditions to minimize variation. Vascular function was assessed using the EndoPAT 2000 (ZOLL Itamar® Medical Ltd) to calculate the reactive hyperemic index (RHI), with an RHI ≤1.67 indicating endothelial dysfunction. Group differences were evaluated using Mann-Whitney U and chi-square tests.

Results:
We included 99 participants with a median [IQR] age of 27 [24–32] years, BMI of 21.2 [19.5–23.2] kg/m², and serum estradiol level of 29.0 [18.0–37.7] pg/mL; the cohort was predominantly White (n = 86, 87%). Consistent with literature, nearly 30% of participants had an RHI ≤1.67, indicating endothelial dysfunction (n = 28, 28%). Compared with those with lower perceived stress, participants with higher stress had significantly lower RHI (1.89 [1.60–2.40] vs 2.21 [1.83–2.67]; p = 0.035) and greater odds of endothelial dysfunction (OR 2.72, 95% CI 1.06–6.98). Additionally, a higher proportion of participants with RHI ≤1.67 had high stress scores (71% vs 48%, p = 0.034).

Conclusions:
Our findings suggest that perceived stress may be a contributing driver of vascular impairment in women with FHA. Given the high stress burden observed in women with FHA and its central role in disease pathophysiology, stress-reduction interventions may offer a strategy to improve vascular health. Future studies in this cohort will expand and examine other hormonal stress markers, such as cortisol, and other metabolic and psychogenic stressors.

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