Associations between serum cytokine levels and postmenopausal depression in postmenopausal women with and without menopause hormone therapy

Ketan Chu; Xi Lin; Saisai Li; Linjuan Ma; Yizhou Huang; Fan Wu; Mengna Shou; Nazaré Alva Galang Cabarrabang; Yibing Lan; Jianhong Zhou

doi:10.1186/s12905-025-03560-2

Associations between serum cytokine levels and postmenopausal depression in postmenopausal women with and without menopause hormone therapy

BMC Womens Health. 2025 Jan 15;25(1):24. doi: 10.1186/s12905-025-03560-2.

Authors

Ketan Chu^#^{1

2}, Xi Lin^#³, Saisai Li⁴, Linjuan Ma^{1

2}, Yizhou Huang^{1

2}, Fan Wu⁵, Mengna Shou⁶, Nazaré Alva Galang Cabarrabang⁷, Yibing Lan^{8

9}, Jianhong Zhou^{10

11}

Affiliations

¹ Women's Hospital, School of Medicine, Zhejiang University, 1st Xueshi Rd, Hangzhou, 310006, Zhejiang Province, People's Republic of China.
² Zhejiang Provincial Clinical Research Center for Obstetrics and Gynecology, Hangzhou, 310006, Zhejiang Province, China.
³ Department of Gynecology, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou, Zhejiang Province, China.
⁴ Department of Gynecology, The Affiliated Hangzhou First People's Hospital, School of Medicine, Zhejiang University, Hangzhou, 310006, Zhejiang Province, China.
⁵ Department of Pharmacy, The First Affliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310006, Zhejiang Province, China.
⁶ Department of Gynecology, Shaoxing Maternity and Child Health Care Hospital, Shaoxing, Zhejiang Province, China.
⁷ School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.
⁸ Women's Hospital, School of Medicine, Zhejiang University, 1st Xueshi Rd, Hangzhou, 310006, Zhejiang Province, People's Republic of China. [email protected].
⁹ Zhejiang Provincial Clinical Research Center for Obstetrics and Gynecology, Hangzhou, 310006, Zhejiang Province, China. [email protected].
¹⁰ Women's Hospital, School of Medicine, Zhejiang University, 1st Xueshi Rd, Hangzhou, 310006, Zhejiang Province, People's Republic of China. [email protected].
¹¹ Zhejiang Provincial Clinical Research Center for Obstetrics and Gynecology, Hangzhou, 310006, Zhejiang Province, China. [email protected].

^# Contributed equally.

PMID: 39815263
DOI: 10.1186/s12905-025-03560-2

Abstract

Background: The etiology of depression involves many biological and environmental factors, among which the inflammatory process is an important contributor. However, the role of pro-inflammatory cytokines in postmenopausal depression is unclear. Therefore, we aimed to explore the association between the serum concentrations of four pro-inflammatory cytokines (IL-1β, IL-6, IL-18, and TNF-α) and depressive symptoms in postmenopausal women who had been receiving menopause hormone therapy (MHT) for at least 6 months and postmenopausal women who had not received MHT.

Methods: This study included a total of 136 Chinese postmenopausal women aged 40 to 65 years who visited the gynecology outpatient department between June 2020 and December 2022. They were divided into the POST group (n = 94) and the POST + MHT (n = 42) group. Demographic information was collected, and the Hamilton Rating Scale for Depression (HAMD) was used to assess depression. The circulating levels of IL-1β, IL-6, IL-18, and TNF-α were determined using ELISA kits.

Results: According to the HAMD score, 39.36% of the participants in the POST group and 14.29% in the POST + MHT group were considered to have depression. The POST + MHT group had significantly lower serum concentrations of IL-18 and TNF-α than the POST group. Multiple linear regression analysis showed that the serum IL-18 (β = 3.996, 95% CI = 0.508-7.484), and TNF-α levels (β = 4.784, 95% CI = 0.939-8.629) were significant predictors of the HAMD-24 scores in women in the POST group. In addition, age was found to be positively related with the level of depression (β = 0.531, 95% CI = 0.063-0.999).

Conclusions: Postmenopausal women who received MHT had a lower HAMD-24 score as well as lower serum TNF-α and IL-18 levels than women who did not receive MHT. Further, the TNF-α and IL-18 level were positively associated with the HAMD-24 score in women who had not received MHT.

Keywords: Cytokines; Depression; Estrogen therapy; Hormone therapy; IL-18; Inflammation; Inflammatory cytokines; Postmenopausal depression; Postmenopausal women; TNF-α.

Abstract

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