Drospirenone promotes apoptosis in ectopic but inhibits proliferation in eutopic human endometrial stromal cells

Thanyarat Wongwananuruk, Somsin Petyim, Pawitra Suwannalert, Kittima Tungprasertpol, Supatra Klaymook
PloS one · 2026 · vol. 21(1) , pp. e0341590 · doi:10.1371/journal.pone.0341590 · PMID:41615969 · PMC12857992 · W7126250298
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⚙ AI-generated summary by claude@2026-06, 2026-06-07 ⓘ

Drospirenone inhibited proliferation in eutopic endometrial stromal cells while promoting apoptosis in ectopic endometrial stromal cells from endometriosis patients.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-07 ⓘ

This study compared the effects of the synthetic progestin drospirenone on eutopic (EU-ESCs) and ectopic (EC-ESCs) human endometrial stromal cells isolated from patients with endometriosis (n=12). Paired stromal cell cultures were treated with and without drospirenone, and antiproliferative markers (including Ki-67) and apoptotic pathway markers (caspase-3, BCL2/BAX, PTEN, p53, and BAK) were assessed; drospirenone at 1 µM significantly affected cell viability in both cell types, with Ki-67 reduced significantly in EU-ESCs and caspase-3 increased in both EU-ESCs and EC-ESCs, alongside changes consistent with apoptosis. The paper reports a limitation that statistical significance for some proliferation readouts (notably Ki-67) differed between EU-ESCs and EC-ESCs, and the excerpted methods indicate experiments were run in triplicate without broader mechanistic validation described here. This paper is centrally about endometriosis — it directly tests drospirenone’s antiproliferative and pro-apoptotic effects in paired eutopic versus ectopic endometrial stromal cells from women with endometriosis.

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Abstract

BACKGROUND: Endometriosis is a complex gynecological condition characterized by endometrial tissue growing outside the uterus. In many in vitro studies, almost all progestins have indicated the anti-proliferation and apoptosis of endometriotic stromal cells. Drospirenone, a synthetic progestin structurally distinct from traditional progestins, still lacks sufficient data regarding its effects on endometriosis, particularly in terms of antiproliferative and pro-apoptotic activity. This study investigates the antiproliferative effects of drospirenone on eutopic (EU-ESCs) and ectopic human endometrial stromal cells (EC-ESCs), and compare its impact on apoptotic effects in both cell types. METHODS AND FINDINGS: In the study, paired EU-ESCs and EC-ESCs were obtained from patients diagnosed with endometriosis (n = 12). EU-ESCs and EC-ESCs were treated with and without drospirenone. Antiproliferative markers and apoptotic markers were evaluated and compared between the two groups. Interestingly, drospirenone at a concentration of 1 µM significantly affected cell viability in both EU-ESCs and EC-ESCs. In EU-ESCs, Ki-67 expression was significantly reduced compared to controls (0.17 vs. 1; p = 0.003), while in EC-ESCs, the reduction was not statistically significant. Caspase-3 expression was significantly increased in both EU-ESCs (1.13 vs. 1) and EC-ESCs (1.57 vs. 1) (p= 0.02 and p = 0.05, respectively). Additionally, BCL2 expression decreased in both cell types following treatment. BAX expression increased in both EU-ESCs and EC-ESCs. Expression levels of PTEN and P53 also increased in both cell types, with statistical significance observed only in EC-ESCs (p = 0.03 and p = 0.04, respectively). BAK expression decreased in EU-ESCs but increased in EC-ESCs compared to controls. CONCLUSIONS: Drospirenone exhibits an antiproliferative effect on EU-ESCs and induces a more pronounced apoptotic response in EC-ESCs.

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Condition tags

endometriosis

MeSH descriptors

Androstenes Androstenes Androstenes Androstenes Androstenes Androstenes Androstenes Androstenes Androstenes Androstenes Androstenes Androstenes Androstenes Androstenes Androstenes Androstenes Apoptosis Apoptosis Apoptosis Apoptosis

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