Active patients are likely at an increased risk of experiencing a quadriceps injury compared with those who live a sedentary lifestyle. Female patients were not found to have an increased likelihood of quadriceps injury during the first year of filling testosterone prescriptions compared with their matched control cohort. Low testosterone levels have been linked to decreased muscle mass, increased fat accumulation, and reduced bone density, all of which can hinder recovery from injuries. The present chapter will focus on sex difference in tendon injury risk, tendon morphology and tendon collagen turnover, but also on the specific effects of estrogen and androgens. Surgical ACL specimens from young men and women have revealed that the ACL expresses ARs in both sexes, which suggests that it is a testosterone-responsive tissue.53,72 Furthermore, small preclinical and clinical studies have found that testosterone levels correlate with ACL stiffness, signifying a possible role in remodeling and tensile strength.72-74 As other sex steroids, namely estrogen and progesterone, have been shown in vitro to influence proliferation of fibroblasts and collagen synthesis in the ACL, testosterone may function similarly, but this has not been demonstrated.75,76 Although more work is needed to characterize the pathways through which testosterone acts on ligaments, the influence of sex steroid hormones has been proposed as one possible explanation for the sex disparity in ACL injury risk.77 With a chronic energy deficiency, women stop normal cycling, and estrogen levels drop to very low levels, resulting in amenorrhea, loss of bone mass, and increased risk of musculoskeletal injury (Heikura et al., 2017). In support of this hypothesis, Smith et al. (2014) found that fasting mixed muscle protein synthesis increased when postmenopausal women were given testosterone or progesterone, but not when given an acute estrogen injection. Despite reported adverse effects, this drug could help to strengthen the knee via its effect on ligament and tendon laxity, which could improve athletes’ short-term performance as well as reduce the risk of non-contact knee injury. The low level of estrogen in the OC would decrease the negative effects of the ovulatory rise in estrogen on tendon and ligament mechanics (Lee C. A. et al., 2015), whereas the work of Hansen et al. (2011) showed that only high progesterone OCs decrease muscle protein synthesis. In premenopausal women, a consistent moderate level of estrogen from OC decreases collagen synthesis; however, in postmenopausal women, estrogen replacement therapy, which provides a daily moderate rise in estrogen, is linked with increased tendon collagen synthesis (Hansen et al., 2009b). All together, the existing data suggest that acute treatment with estrogen does not improve basal muscle protein synthesis; however, estrogen increases the anabolic response to exercise and this may result in the increase in muscle mass reported in long term studies. In fact, these authors found that knee laxity increased between 1 and 5 mm between the first day of menstruation and the day following ovulation, depending on estrogen levels. In men and women with no history of knee injury, the men showed no statistical difference in knee laxity over time; however, in women laxity increased from 4.7 ± 0.8 mm in the follicular phase, to 5.3 ± 0.7 mm in the ovulatory phase (Deie et al., 2002). However, unlike bone and muscle where estrogen improves function, in tendons and ligaments estrogen decreases stiffness, and this directly affects performance and injury rates. In a large-sample, retrospective database analysis, the present study demonstrated that patients who filled a prescription for testosterone replacement therapy were much more likely to experience a quadriceps muscle or tendon injury within 1 year of filling their prescription. Female patients were not at an increased risk of injury during the 1-year follow-up period; however, when evaluated for injury risk any time after the initial 3 months of filling testosterone prescriptions, an association was observed. This limitation, however, may offset the fact that patients who live a more sedentary lifestyle have decreased muscle mass, placing them at greater risk of a quadriceps tendon injury. These findings are consistent within a 1-year follow-up period after the initial 3 months of filled testosterone prescriptions, as well as any time after the filled prescriptions during the 10-year study period. The number of patients in a cohort size less than 11 is not reportable per the Health Insurance Portability and Accountability Act. A comparison with a matched cohort of patients followed for 1 year; data presented as % (n). We queried the M151Ortho dataset in PearlDiver for all quadriceps injuries using ICD-9 and ICD-10 codes between 2011 and 2018. Comparison of patient demographics of unmatched and matched testosterone and control cohorts We subsequently subdivided both the testosterone and control groups into sex- and age-specific subgroups. Marketing narratives often exaggerate performance effects. Its effects center on tissue repair pathways, not hormone production. No evidence shows direct stimulation of testosterone production. It does not bind to androgen receptors or mimic testosterone. When side effects are reported, they are typically mild and temporary. This study has shown for the first time the direct effect of testosterone on knee passive ROM and Rxfp1 and Rxfp2 protein and mRNA expression in a rat model, which was mediated via DHT and involved androgen receptor binding. Additionally, the strength of the muscles controlling knee joint movement was also increased . Although we have shown evidence that DHT is most likely involved in causing a decrease in knee laxity, further studies are needed to support DHT participation such as identifying the expression and measuring the activity of 5α-reductase enzyme in the knee. In the group receiving 125 and 250 μg/kg/day testosterone treatment, the presence of relaxin did not significantly increase knee passive ROM. A recent finding by O’Leary et al. reported that a prolonged aerobic training in the eumenorrheic women induces a short-term elevation in the plasma testosterone levels, which appears to be unrelated to the level of estrogen and the phases of menstrual cycle. Similarly, a decrease in Rxfp2 protein expression was observed following treatment with both doses of testosterone which was antagonized by FLU and FIN (C). A dose-dependent decrease in Rxfp1 protein expression was noted following treatment with both doses of testosterone which was antagonized by FLU and FIN. Testosterone plays a key role in muscle mass and connective tissue strength. For most men the hormone that is most impactful is testosterone. Hormones are naturally present in everyone, men and women. Recent research suggests that hormone fluctuations can play a role in variability of hypermobility related symptoms, especially for women.
