BACKGROUND Women are 2 to 9 times more likely to experience an anterior cruciate ligament (ACL) injury than men. Various hormones including relaxin, progesterone, and estrogen influence ACL strength. Oral contraceptives (OCs) alter these hormone levels; however, studies have yet to comprehensively compare different OCs' effects on the ACL. HYPOTHESIS OCs with increased progestin-to-estrogen ratios will (1) increase ACL collagen expression, (2) decrease ACL matrix metalloproteinase expression, and (3) increase ACL strength. STUDY DESIGN Controlled laboratory study. METHODS Untreated female rats were compared with rats treated with 1 of 5 clinically used OCs: norethindrone (NE) only, NE plus ethinylestradiol (EE), etynodiol diacetate (ED) plus EE, norgestimate (NG) plus EE, and drospirenone (DS) plus EE. Doses were scaled from human doses to account for differences in bioavailability and body weight, and OCs were administered daily via oral gavage for 4 rat estrous cycles (20 days). A total of 36 rats were then sacrificed (6 rats/group). ACLs underwent biomechanical testing to assess ACL strength, stiffness, and maximum load before failure. ACL specimens were also isolated for quantitative real-time polymerase chain reaction analysis to assess collagen, matrix metalloproteinase, and relaxin receptor-1 expression. RESULTS While the primary structural property of interest (ACL maximum load before failure) was not significantly improved by OC treatment, the main material property of interest (ACL strength) in rats treated with NE only, DS + EE, ED + EE, and NE + EE was significantly increased compared with untreated controls (P = .001, P = .004, P = .004, and P = .04, respectively). The order from strongest to weakest ACLs, which was also the same order as the highest to lowest progestin-to-estrogen ratios, was groups treated with NE only, DS + EE, ED + EE, NE + EE, and lastly NG + EE. Higher ratio formulations also increased the expression of type I collagen (P = .02) and decreased the expression of matrix metalloproteinase-1 (P = .04). CONCLUSION OC formulations with higher progestin-to-estrogen ratios may be more protective for the ACL than formulations with lower ratios. CLINICAL RELEVANCE OC formulations with high progestin-to-estrogen ratios may benefit female athletes by reducing their ACL injury risk by decreasing the effects of relaxin on the ACL.

中文翻译：

---

口服避孕药对前十字韧带强度的影响。

背景技术女性遭受前十字韧带（ACL）伤害的可能性是男性的2至9倍。各种激素（包括松弛素，孕激素和雌激素）都会影响ACL强度。口服避孕药（OCs）会改变这些激素水平；但是，研究尚未全面比较不同OC对ACL的影响。假设孕激素与雌激素比增加的OC将（1）增加ACL胶原蛋白的表达，（2）降低ACL基质金属蛋白酶的表达，以及（3）增加ACL强度。研究设计受控的实验室研究。方法将未经治疗的雌性大鼠与用5种临床使用的OC中的1种进行比较：仅炔诺酮（NE），NE加乙炔雌二醇（EE），乙炔二乙酸乙二酯（ED）加EE，诺孕酯（NG）加EE和屈螺酮（DS）加上EE。剂量是根据人的剂量而定，以考虑生物利用度和体重的差异，每天通过口服强饲法给予OC，持续4个大鼠发情周期（20天）。然后共处死36只大鼠（每组6只大鼠）。ACL进行了生物力学测试，以评估ACL的强度，刚度和失效前的最大负荷。还分离了ACL标本，用于定量实时聚合酶链反应分析，以评估胶原蛋白，基质金属蛋白酶和松弛素受体1的表达。结果虽然OC处理并未显着改善目标主要结构性质（ACL衰竭前最大负荷），但仅NE，DS + EE，ED + EE和NE处理的大鼠中主要目标材料性质（ACL强度）与未治疗的对照组相比，+ EE显着增加（P = .001，P = .004，P = .004和P = .04）。从最强的ACL到最弱的ACL的顺序，也与孕激素/雌激素比的最高到最低的顺序相同，是仅用NE，DS + EE，ED + EE，NE + EE和最后用NG + EE治疗的组。更高比例的配方还增加了I型胶原蛋白的表达（P = .02），并降低了基质金属蛋白酶-1的表达（P = .04）。结论孕激素与雌激素比例较高的OC制剂比ACL较低的制剂对ACL的保护作用更大。临床相关性高孕激素与雌激素比的OC制剂可通过降低松弛素对ACL的影响来降低其ACL伤害风险，从而使女运动员受益。孕激素/雌激素比最高至最低的顺序也相同，是仅使用NE，DS + EE，ED + EE，NE + EE和最后使用NG + EE进行治疗的组。更高比例的配方还增加了I型胶原蛋白的表达（P = .02），并降低了基质金属蛋白酶-1的表达（P = .04）。结论孕激素与雌激素比例较高的OC制剂比ACL较低的制剂对ACL的保护作用更大。临床相关性高孕激素与雌激素比的OC制剂可通过降低松弛素对ACL的影响来降低其ACL伤害风险，从而使女运动员受益。孕激素/雌激素比最高至最低的顺序也相同，是仅使用NE，DS + EE，ED + EE，NE + EE和最后使用NG + EE进行治疗的组。更高比例的配方还增加了I型胶原蛋白的表达（P = .02），并降低了基质金属蛋白酶-1的表达（P = .04）。结论孕激素与雌激素比例较高的OC制剂比ACL较低的制剂对ACL的保护作用更大。临床相关性高孕激素与雌激素比的OC制剂可通过降低松弛素对ACL的影响来降低其ACL伤害风险，从而使女运动员受益。02）并降低基质金属蛋白酶-1（P = .04）的表达。结论孕激素与雌激素比值较高的OC制剂对ACL的保护作用比低比率的OC制剂更好。临床相关性高孕激素与雌激素比的OC制剂可通过降低松弛素对ACL的影响来降低其ACL伤害风险，从而使女运动员受益。02）并降低基质金属蛋白酶-1（P = .04）的表达。结论孕激素与雌激素比例较高的OC制剂比ACL较低的制剂对ACL的保护作用更大。临床相关性高孕激素与雌激素比的OC制剂可通过降低松弛素对ACL的影响来降低其ACL伤害风险，从而使女运动员受益。