The effect of pharmacological cessation and restoration of menstrual cycle on bone metabolism in premenopausal women with endometriosis

Athanasios D. Anastasilakis, Papachatzopoulos S, Stergios Papachatzopoulos, Makras P, Polyzois Makras, Gkiomisi A, Athina Gkiomisi, Panagiotis Nikolakopoulos, Nikolakopoulos P, Polyzos SA, Stergios A. Pοlyzos, Stergios A Polyzos, Charikleia Ntenti, Ballaouri I, Iris Ballaouri, Gerou S, Spyridon Gerou, Οlga Tsachouridou, Olga Tsachouridou, Tsachouridou O, Athanasios Papatheodorou, Αθανάσιος Παπαθεοδώρου, Papatheodorou A, Konstantinos Aliazis, Sofia Fermanoglou, Fermanoglou S, Bisbinas I, Ilias Bisbinas, Yavropoulou MP, Maria P. Yavropoulou
Bone · 2022 · vol. 158 , pp. 116354 · doi:10.1016/j.bone.2022.116354 · PMID:35150909 · W4210861666
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This study investigated how stopping and then restarting the menstrual cycle pharmacologically impacts bone metabolism in premenopausal women diagnosed with endometriosis.

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Abstract

IntroductionGnRH-analogs induce bone loss. We aimed to investigate the effects of goserelin-induced menstrual cessation (MC) and subsequent menstrual restoration (MR) on bone metabolism (BM).MethodsIn this prospective cohort study, premenopausal women (PMW) with histologically verified endometriosis (n = 21) received goserelin monthly for 6 months (6 m) resulting in MC and were followed up for another 6 m after MR (12 m). Age- and BMI-matched healthy PMW (n = 20) served as controls for bone mineral density (BMD) measurements. The primary endpoint was changes in lumbar spine (LS)-BMD at 6 m and 12 m; Secondary endpoints were changes in femoral neck (FN)-BMD, bone turnover markers (P1NP and CΤx), sclerostin, and expression of bone-related circulating microRNAs (miRNAs) at 6 m and 12 m.ResultsGoserelin-induced MC reduced LS- and FN-BMD at 6 m (both p < 0.001). From 6 m to 12 m, LS-BMD increased (p < 0.001) but remained below baseline values (p = 0.012), whereas FN-BMD remained stable (p = 1.000). CTx and P1NP levels increased at 6 m (both p < 0.001) and decreased at 12 m (p < 0.001 and p = 0.013, respectively), while CTx (p = 1.000) alone and not P1NP (p = 0.020) returned to baseline. Sclerostin levels did not change. Relative expression of miRNAs targeting RUNX 2 and beta-catenin was significantly downregulated at 6 m compared to baseline (p < 0.001), while the expression of miRNAs targeting osteoblast and osteoclast function at both directions demonstrated a robust increase (up to 400fold) at 12 m (p < 0.001).ConclusionsSix months of goserelin-induced MC lead to significant bone loss associated with increased bone turnover and changes in the expression of bone-related miRNAs, changes that are only partially reversed at 6 m after MR.

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Condition tags

endometriosis

MeSH descriptors

Endometriosis Endometriosis MicroRNAs MicroRNAs Biomarkers Bone Density Bone Remodeling Female Humans Menstrual Cycle Prospective Studies

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References (69)

Cited by (5)

SciLite annotations

chemicals 4
goserelin mineral goserelin goserelin

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