Bone mineral density in women with functional hypothalamic amenorrhea compared to eumenorrheic controls and recently menopausal women

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Introduction: Functional hypothalamic amenorrhea (FHA) accounts for 30% of secondary amenorrhea and is characterized by hypothalamic hypercortisolemia, hypothalamic hypothyroidism, and anovulation with hypoestrogenemia due to disrupted GnRH drive. While FHA is associated with decreased bone mineralization; it remains unclear how bone health compares to menopausal women, who also experience bone loss. This study compared dual-energy x-ray absorptiometry (DXA) bone health parameters among women with FHA, eumenorrheic controls, and recently menopausal women. It also examined the impact of prior combined oral contraceptive (COC) use on bone mineral density (BMD) in women with FHA. Methods: This cross-sectional study included 20 women with FHA, 9 eumenorrheic controls, and 12 recently menopausal women who underwent hip and spine DXA. None of the participants were taking hormone therapy. FHA was defined as ≥3 months of amenorrhea, estradiol <50 pg/ml, FSH and LH <10 mIU/L, excluding other etiologies. DXA bone parameters were measured using Lunar iDXA (GE) including BMD from lumbar spine (L1-L4) and hip. Results: By design, age differed significantly across groups (p < 0.0001), with median ages of 27.8 years [23.4, 34.1] in women with FHA, 29.6 years [28.3, 32.4] in eumenorrheic controls, and 55.3 years [53.5, 56.6] in recently menopausal women. There were no significant differences in weight or BMI across groups. Significant differences were observed at all measured skeletal sites, including all lumbar spine levels, femur neck, total femur, and total BMD (all p < 0.05). Pairwise comparisons revealed that lumbar spine BMD was significantly lower in FHA compared to eumenorrheic controls (p = 0.04), while FHA and menopausal women did not significantly differ from each other (p = 0.07). Among FHA women with prior COC use, L1-4 BMD was not significantly different from controls (p = 0.19). Conclusions: Lumbar spine BMD in young women with FHA was comparable to that of recently menopausal women, highlighting the profound skeletal impact of chronic estrogen deficiency. Prior COC use may partially attenuate FHA-associated bone loss, though larger studies are needed to confirm this observation. Future studies should explore whether skeletal outcomes vary by FHA etiology and the potential role of COC duration in preserving BMD.

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