1. Estrogen and testosterone supplementation improves tendon healing and functional recovery after rotator cuff repair.
- Author
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Tashjian RZ, Zitnay J, Kazmers NH, Veerabhadraiah SR, Zelada AC, Honeggar M, Chalmers PN, Henninger HB, and Jurynec MJ
- Subjects
- Humans, Male, Mice, Animals, Testosterone pharmacology, Testosterone therapeutic use, Tendons surgery, Estrogens therapeutic use, Estrogens pharmacology, Dietary Supplements, Biomechanical Phenomena, Rotator Cuff pathology, Rotator Cuff Injuries drug therapy, Rotator Cuff Injuries surgery, Rotator Cuff Injuries pathology
- Abstract
Failure of healing after rotator cuff repair (RCR) is common. The purpose of the current study was to evaluate the effect of systemic estrogen or testosterone supplementation on tendon healing after RCR. Seventy-two adult male mice were utilized for all experiments. The supraspinatus tendon was transected and repaired with 6-0 Prolene suture on the left shoulder of 51 animals. Mice were segregated into three groups postoperative: (1) vehicle group (VG; n = 18), (2) estrogen group (EST; n = 17), and (3) testosterone group (TST; n = 16). An unrepaired control group (unrepaired, n = 21) did not have surgery. Utilizing these animals, histological analysis, activity testing, biomechanical testing and RNA sequencing (RNA-seq) was performed. At 8 weeks post-RCR, TST, and EST supplementation improved the overall histologic structure of the repaired enthesis site. No differences in ultimate failure loads or stiffness were detected between VG, EST, and TST groups after biomechanical testing. RCR caused a reduction in wheel activity compared to unrepaired controls and supplementation with TST restored wheel activity. RNA-seq analysis indicated that estrogen and testosterone regulated different pathways associated with enthesis healing, including a suppression of inflammatory signaling. Supplementation with sex hormones improved the structure of the repaired tendon enthesis and significantly regulated expression of diverse pathways regulating multiple biological processes. Testosterone administration following RCR restored wheel activity without having a detrimental impact on biomechanical strength. Future human studies of sex hormone supplementation after RCR are warranted as supplementation in an animal model may improve tendon enthesis healing., (© 2023 Orthopaedic Research Society.)
- Published
- 2024
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