Functional Hypothalamic Amenorrhea and Preclinical Cardiovascular Disease.

CONTEXT: Endothelial dysfunction is a preclinical cardiovascular disease (CVD) marker. Due to various neuroendocrine aberrations, functional hypothalamic amenorrhea (FHA) may be a sex-specific risk factor for CVD in young women.

OBJECTIVE: To investigate endothelial function in women with FHA, compared to eumenorrheic controls and recently menopausal women.

DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional analysis among women with FHA (n = 30), eumenorrheic controls (n = 29), and recently menopausal women (n = 30). FHA was defined as amenorrhea ≥3 consecutive months, estradiol <50 pg/mL, follicle-stimulating hormone (FSH) < 10 mIU/L, and luteinizing hormone (LH) < 10 mIU/L, with excluding other etiologies. Participants were recruited through obstetrics and gynecology referrals, social media advertising, and review of electronic health records.

MAIN OUTCOME MEASURE: Preclinical CVD was measured using EndoPAT 2000 to calculate reactive hyperemic index (RHI). RHI ≤1.67 indicates endothelial dysfunction.

RESULTS: Comparing women with FHA to eumenorrheic controls and recently menopausal women, mean estradiol levels were 29.0 ± 18.1, 46.4 ± 15.7, and 10.9 ± 14.4 pg/ml (p < 0.0001), respectively. Women with FHA had lower insulin (p = 0.0095) and higher cortisol (p = 0.0004) compared to controls. RHI was significantly lower in FHA compared to eumenorrheic controls and recently menopausal women (1.8 ± 0.5 vs 2.2 ± 0.5 vs 2.2 ± 0.6; p = 0.008, respectively); and 35% of women with FHA had RHI ≤1.67 consistent with endothelial dysfunction.

CONCLUSIONS: These results demonstrate endothelial dysfunction in one out of three young women with FHA. FHA may be a contributor to preclinical CVD, and it is not explained by hypoestrogenemia alone.