Serum androstenedione levels are associated with dysmenorrhea and pain severity among women without endometriosis: an exploratory cross-sectional study

Tingting Li, Yu S, Sihui Yu, Peipei Shi, Shi P, Sheng Yin, Zhang J, Jiarong Zhang
BMC women's health · 2026 · vol. 26(1) · doi:10.1186/s12905-026-04725-3 · PMID:42897519 · PMC13681882 · W7170601736
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Serum androstenedione levels were significantly higher in women with dysmenorrhea but without endometriosis, and correlated with pain severity in this subgroup.

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This exploratory cross-sectional study analyzed serum steroid and reproductive hormone profiles in 139 premenopausal women to determine their association with dysmenorrhea and pain severity. The researchers stratified participants by endometriosis status and found that elevated serum androstenedione levels were significantly associated with dysmenorrhea and higher pain scores specifically among women without the disease. Although androstenedione showed modest discriminatory value, the authors noted that these associations did not remain significant after false discovery rate adjustment in the overall cohort, highlighting a limitation in standalone predictive utility. Relevance to endometriosis: listed as a key exclusion criterion for the primary finding, which focuses on hormonal markers in patients explicitly confirmed to be free of endometriosis.

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Abstract

BACKGROUND: Dysmenorrhea is a common gynecological condition with heterogeneous etiologies. Endometriosis is an important condition associated with dysmenorrhea, but the serum steroid and reproductive hormone profiles related to dysmenorrhea, and whether these associations differ by endometriosis status, remain unclear. This study aimed to investigate the associations of serum hormone profiles with dysmenorrhea and pain severity. METHODS: This exploratory cross-sectional study was conducted from October 2022 to January 2024 at Zhongshan Hospital, Fudan University. A total of 139 premenopausal participants were classified into dysmenorrhea (n = 73) and non-dysmenorrhea (n = 66) groups and further stratified by endometriosis status. Serum steroid and reproductive hormones were measured using liquid chromatography-tandem mass spectrometry and immunoassays. Group comparisons were performed according to data distribution, and false discovery rate (FDR) adjustment was applied for multiple hormone comparisons. Multivariable logistic regression was used to evaluate the association between androstenedione (A4) and dysmenorrhea. RESULTS: In the overall cohort, women with dysmenorrhea showed higher A4 levels and a higher luteinizing hormone/follicle-stimulating hormone (LH/FSH) ratio, although these differences did not remain significant after FDR adjustment. After stratification by endometriosis status, these differences were mainly observed among women without endometriosis. In this subgroup, A4 levels were significantly higher in women with dysmenorrhea than in those without dysmenorrhea (0.85 ± 0.36 vs. 0.65 ± 0.28 ng/mL, P = 0.004; FDR-adjusted P = 0.024), as was the LH/FSH ratio (2.11 ± 1.47 vs. 1.44 ± 1.02, P = 0.013; FDR-adjusted P = 0.047). Among women without endometriosis, A4 was modestly correlated with visual analogue scale score (Spearman r = 0.285, P = 0.006) and remained associated with dysmenorrhea after multivariable adjustment (odds ratio = 8.07, 95% confidence interval: 1.60-40.65, P = 0.011). A4 and the LH/FSH ratio showed modest discrimination, with area under the curve values of 0.660 and 0.655, respectively. CONCLUSIONS: Serum A4 levels were associated with dysmenorrhea and pain severity, particularly among women without endometriosis. The LH/FSH ratio showed a weaker supportive association. These exploratory findings support further investigation of androgen-related endocrine profiles in dysmenorrhea without endometriosis, but A4 and the LH/FSH ratio showed limited standalone discriminatory value. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2400079587, Retrospectively registered on 2024-01-08.
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Abstract

Background Dysmenorrhea is a common gynecological condition with heterogeneous etiologies. Endometriosis is an important condition associated with dysmenorrhea, but the serum steroid and reproductive hormone profiles related to dysmenorrhea, and whether these associations differ by endometriosis status, remain unclear. This study aimed to investigate the associations of serum hormone profiles with dysmenorrhea and pain severity.

Methods

This exploratory cross-sectional study was conducted from October 2022 to January 2024 at Zhongshan Hospital, Fudan University. A total of 139 premenopausal participants were classified into dysmenorrhea (n = 73) and non-dysmenorrhea (n = 66) groups and further stratified by endometriosis status. Serum steroid and reproductive hormones were measured using liquid chromatography–tandem mass spectrometry and immunoassays. Group comparisons were performed according to data distribution, and false discovery rate (FDR) adjustment was applied for multiple hormone comparisons. Multivariable logistic regression was used to evaluate the association between androstenedione (A4) and dysmenorrhea.

Results

In the overall cohort, women with dysmenorrhea showed higher A4 levels and a higher luteinizing hormone/follicle-stimulating hormone (LH/FSH) ratio, although these differences did not remain significant after FDR adjustment. After stratification by endometriosis status, these differences were mainly observed among women without endometriosis. In this subgroup, A4 levels were significantly higher in women with dysmenorrhea than in those without dysmenorrhea (0.85 ± 0.36 vs. 0.65 ± 0.28 ng/mL, P = 0.004; FDR-adjusted P = 0.024), as was the LH/FSH ratio (2.11 ± 1.47 vs. 1.44 ± 1.02, P = 0.013; FDR-adjusted P = 0.047). Among women without endometriosis, A4 was modestly correlated with visual analogue scale score (Spearman r = 0.285, P = 0.006) and remained associated with dysmenorrhea after multivariable adjustment (odds ratio = 8.07, 95% confidence interval: 1.60–40.65, P = 0.011). A4 and the LH/FSH ratio showed modest discrimination, with area under the curve values of 0.660 and 0.655, respectively.

Conclusions

Serum A4 levels were associated with dysmenorrhea and pain severity, particularly among women without endometriosis. The LH/FSH ratio showed a weaker supportive association. These exploratory findings support further investigation of androgen-related endocrine profiles in dysmenorrhea without endometriosis, but A4 and the LH/FSH ratio showed limited standalone discriminatory value. Trial registration Chinese Clinical Trial Registry, ChiCTR2400079587, Retrospectively registered on 2024–01-08. Similar content being viewed by others Abbreviations - 17-OHP: - 17α-Hydroxyprogesterone - 17-Preg: - 17α-Hydroxypregnenolone - A4: - Androstenedione - AMH: - Anti-Müllerian hormone - AUC: - Area under the curve - BMI: - Body mass index - DHEAS: - Dehydroepiandrosterone sulfate - E1: - Estrone - E2: - Estradiol - FDR: - False discovery rate - FSH: - Follicle-stimulating hormone - LC–MS/MS: - Liquid chromatography–tandem mass spectrometry - LH: - Luteinizing hormone - LMP: - Last menstrual period - PCOS: - Polycystic ovary syndrome - PREG: - Pregnenolone - PROG: - Progesterone - ROC: - Receiver operating characteristic - T: - Testosterone - VAS: - Visual analogue scale

Acknowledgements

We are grateful to all the patients and their families for participating in this study. Funding This research did not receive funding. Author information Authors and Affiliations Corresponding authors Ethics declarations Ethics approval and consent to participate The study was approved by the Ethics Committee of Zhongshan Hospital, Fudan University (Approval No. B2022-500R2). Written informed consent was obtained from all participants. The study was conducted in accordance with the Declaration of Helsinki. Consent for publication Not applicable. Competing interests The authors declare no competing interests. Additional information Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Supplementary Information 12905_2026_4725_MOESM1_ESM.pdf (download PDF ) Supplementary Material 1. Supplementary Figure S1. Spearman correlation matrix of measured steroid hormones. Pairwise Spearman correlation analysis was performed using available observations for each hormone pair. Correlation coefficients are shown as Spearman’s rho. Asterisks indicate FDR-adjusted P values: * q < 0.05, ** q < 0.01, *** q < 0.001. FDR, false discovery rate; PREG, pregnenolone; 17-Preg, 17α-hydroxypregnenolone; 17-OHP, 17α-hydroxyprogesterone; PROG, progesterone; A4, androstenedione; T, testosterone; DHEAS, dehydroepiandrosterone sulfate; E1, estrone; E2, estradiol. Rights and permissions Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/. About this article Cite this article Li, T., Yu, S., Shi, P. et al. Serum androstenedione levels are associated with dysmenorrhea and pain severity among women without endometriosis: an exploratory cross-sectional study. BMC Women's Health (2026). https://doi.org/10.1186/s12905-026-04725-3 Received: Accepted: Published: DOI: https://doi.org/10.1186/s12905-026-04725-3

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MeSH descriptors

Androstenedione Androstenedione Androstenedione Androstenedione Androstenedione Androstenedione Androstenedione Androstenedione Androstenedione Androstenedione Androstenedione Androstenedione Dysmenorrhea Dysmenorrhea Dysmenorrhea Dysmenorrhea Dysmenorrhea Dysmenorrhea Dysmenorrhea Dysmenorrhea

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SciLite annotations

chemicals 74
prostaglandin prostaglandin estrogen progesterone estrogen progesterone steroid steroid hormone dehydroepiandrosterone sulfate pregnenolone pregnenolone pregnenolone progesterone testosterone estradiol steroid steroid estradiol androgen androgen steroid steroid steroid glucocorticoid opioid analgesic serotonin pregnenolone estradiol estrone progesterone dehydroepiandrosterone sulfate testosterone progesterone steroid hormone pregnenolone hydroxypregnenolone medroxyprogesterone progesterone estradiol testosterone estrone estradiol steroid hormone progesterone steroid steroid hormone steroid hormone steroid hormone androgen steroid estradiol androgen testosterone estrone androgen estrone progesterone +14 more
organisms 3
noordeloos 2009062 noordeloos 2009062 noordeloos 2009062

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