Goserelin-induced menstrual cessation promotes bone loss

Menstrual cessation associated with the use of goserelin raises bone turnover and leads to bone loss, which in turn is associated with alterations in the expression of relevant circulating microRNAs (miRNAs), according to a study.

The study included 21 premenopausal women with histologically confirmed endometriosis. All of them received goserelin monthly for 6 months, resulting in menstrual cessation. They were followed for another 6 months after menstrual restoration (12 months). Twenty healthy premenopausal women matched for age and body mass index were also included as controls.

Researchers measured bone mineral density (BMD) and designated changes in lumbar spine (LS)-BMD at 6 and 12 months as the primary endpoint. They also assessed changes in femoral neck (FN)-BMD, bone turnover markers (P1NP and CΤx), sclerostin, and expression of bone-related circulating miRNAs at the two time points as secondary endpoints.

Goserelin-induced menstrual cessation resulted in significantly lower LS- and FN-BMD at 6 months (both p<0.001). From 6 to 12 months, after restoration of menstruation, LS-BMD increased (p<0.001) but remained below baseline values (p=0.012), whereas FN-BMD was relatively unchanged (p=1.000).

CTx and P1NP levels increased at 6 months (both p<0.001) and declined at 12 months (p<0.001 and p=0.013, respectively). Only CTx (p=1.000) and not P1NP (p=0.020) returned to baseline levels. On the other hand, sclerostin levels remained stable throughout.

There was a significant downregulation seen in the relative expression of miRNAs targeting RUNX 2 and beta-catenin at 6 months compared to baseline (p<0.001), while the expression of miRNAs targeting osteoblast and osteoclast function at both directions showed a robust increase (up to 400-fold) at 12 months (p<0.001).

The present data indicate that the bone loss seen following goserelin-induced menstrual cessation is only partially reversed at 6 months after menstrual restoration.