@article{3076792,
    title = "The effect of pharmacological cessation and restoration of menstrual cycle on bone metabolism in premenopausal women with endometriosis",
    author = "Anastasilakis, A.D. and Papachatzopoulos, S. and Makras, P. and Gkiomisi, A. and Nikolakopoulos, P. and Polyzos, S.A. and Ntenti, C. and Ballaouri, I. and Gerou, S. and Tsachouridou, O. and Papatheodorou, A. and Aliazis, K. and Fermanoglou, S. and Bisbinas, I. and Yavropoulou, M.P.",
    journal = "Bone",
    year = "2022",
    volume = "158",
    publisher = "W B SAUNDERS CO-ELSEVIER INC",
    issn = "8756-3282",
    doi = "10.1016/j.bone.2022.116354",
    keywords = "beta catenin;  carboxy terminal telopeptide;  circulating microRNA;  gonadorelin derivative;  goserelin;  procollagen;  procollagen type 1 n terminal propeptide;  sclerostin;  transcription factor RUNX2;  unclassified drug, adult;  Article;  body mass;  bone density;  bone metabolism;  bone turnover;  cell differentiation;  cell function;  clinical article;  cohort analysis;  controlled clinical trial;  controlled study;  correlation analysis;  down regulation;  drug induced mentrual cessation;  endometriosis;  female;  femoral neck;  follow up;  gene expression;  histology;  human;  lumbar spine;  menstrual cycle;  metabolic bone disease;  molecular mechanics;  osteoblast;  osteoclast;  osteolysis;  premenopause;  prospective study;  protein blood level;  protein expression",
    abstract = "Introduction: GnRH-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). Methods: In 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. Results: Goserelin-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). Conclusions: Six 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. © 2022 Elsevier Inc."
}