Diagnostic value of the blood steroid profile in secondary amenorrhea

BACKGROUND. Secondary amenorrhea is a pathological condition that may develop as a result of either functional hypothalamic amenorrhea (FHA) or primary ovarian insufficiency (POI). In recent years, metabolomic studies in gynecology have gained importance for improving diagnostics, optimizing pharmacological treatment, and monitoring therapeutic outcomes. It is well established that cortisol production increases in response to chronic stress and relative energy deficiency syndrome. Therefore, it is reasonable to expect elevated cortisol levels in patients with functional amenorrhea associated with weight loss, which may adversely affect menstrual function.

OBJECTIVE. To investigate and compare the parameters of the multicomponent blood steroid profile (multisteroid analysis), including androstenedione, corticosterone, testosterone, cortisol, cortisone, and dehydroepiandrosterone (DHEA), in patients with secondary amenorrhea of different origins (FHA, POI), and to identify alterations in target markers using high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS).

MATERIALS AND METHODS. A single-center cross-sectional comparative study was conducted involving two populations of women aged 18–39 years: (1) patients with secondary amenorrhea of various origins (FHA, POI) (n=120), and (2) healthy women (n=34). Blood steroid profile parameters were assessed using HPLC-MS/MS.

RESULTS. A total of 154 women were examined. The lowest corticosterone levels were observed in the POI group — 3.95 nmol/L [2.4; 5.7] (p<0.0001). No statistically significant differences were found between other groups. Hypercortisolemia was not detected in any of the study participants, nor were there significant differences in cortisol, cortisone, or DHEA levels between groups.

CONCLUSION. In this study, based on a targeted quantitative analysis of steroid hormones, their precursors, and metabolites using HPLC-MS/MS technology, we characterized the features of the blood steroid profile in patients with secondary amenorrhea. The profile demonstrated similar characteristics across all amenorrhea types, regardless of etiology, suggesting a common underlying mechanism. However, the observed decrease in corticosterone levels in POI patients and the absence of hypercortisolemia in FHA women are of particular interest and warrant further investigation.

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