This confirms that GH stimulatory effects on tendinous collagen synthesis involves local IGF-1 production50. These studies have prompted specific experiments to ascertain whether GH-IGF1 could be an useful tool for tendon healing. Moreover, studies have shown that this activity is mainly due to local production of IGF rather than to circulating levels of GH/IGF-1 complex. As far as PTH is concerned, several studies have shown that recombinant PTH (rhPTH) accelerates bone healing and increases chondrocyte recruitment and differentiation44. Indeed, besides studies which report a lower rate of lesions in women who use the pill42, in other studies this evidence is lacking43. Tendonitis is an inflammatory condition that affects the tendons, commonly caused by repetitive motion, overuse, injury, age, and poor posture. While anyone can develop tendonitis, certain factors increase the risk of developing this condition. When tendons are overused or subjected to sudden stress, they can become damaged, leading to the pain and inflammation that characterizes tendonitis. For example, testosterone is known to help build muscle mass, which could support tendons and reduce the strain on them. Healthy tendons are strong and flexible, but they can become damaged or inflamed due to injury, overuse, or certain medical conditions. These include engaging in regular, but not excessive, exercise; avoiding repetitive motions that strain the tendons; and maintaining a healthy weight. Patients can reduce their risk of developing tendonitis by following certain strategies. Prevention is always better than cure, and this is particularly true when it comes to tendonitis in patients on TRT. Interestingly, some studies have explored the possibility that TRT could help with tendonitis. This may involve close monitoring by a healthcare provider, adjustments to the TRT dosage, or additional therapies to support tendon health. Standard treatments for tendonitis include rest, physical therapy, and anti-inflammatory medications. Considering the fact that OC use alters regular hormone level fluctuations, this might be a good tool to understand how estrogen affects myofibrillar protein synthesis in response to anabolic stimuli. By contrast, oral contraceptives (OCs) provide a moderate, but relatively constant, level of estrogen with or without progesterone. This suggests that a chronic decrease in estrogen attenuates the response to anabolic stimuli (Hansen and Kjaer, 2014). Muscle mass is largely dependent on the balance between the synthesis and degradation of muscle protein. Estrogen directly modulates both IGF-1 and IGF binding proteins (Hansen et al., 2009b) and can therefore mediate its positive effects through an increase in IGF-1 signaling. In these experiments, treating engineered ligaments with physiologically high estrogen for 48 h resulted in an 80% decrease in lysyl oxidase activity without changing LOX expression (Figure 3). However, the benefit of estrogen becomes less apparent with time in culture (Lee H. et al., 2015). One of the best characterized musculoskeletal differences between men and women, is the rupture rate of the anterior cruciate ligament (ACL). Therefore, in the sections below, we will address how estrogen affects sinew mechanics and adaptation to loading. Both enzymatic cross-linking, through LOX, and non-enzymatic cross-linking through AGEs increase the stiffness of the tissues (Reddy et al., 2002; Svensson et al., 2013; Marturano et al., 2014). These data suggest that ERT may decrease basal muscle protein synthesis while improving sensitivity to anabolic stimuli. Indeed, in these situations, GC administration, although beneficial in the short term, can worsen tendon degeneration. Therefore, the boundary between the good and the evil remains uncertain, and caution is required in patients with relapses of chronic overuse tendinopathies. Intratendinous and peritendinous corticosteroids injections are highly beneficial in trigger finger and De Quervain syndrome, whereas in rotator cuff, patellar and Achilles tendon diseases the results are deceiving and short lasting. Therefore, further research is needed to confirm the potential therapeutic effect of PTH in tendon-to-bone or tendon-to-tendon healing. In mice, the deep digital flexor tendon was transected and immediately repaired.
