Abstract：
OBJECTIVE: To explore the role of progestins as potential contributing factors for the development of hepatocellular adenoma (HA) METHODS: We describe 3 cases of adolescents and young adults who developed HA while on norethindrone (NET), as well as their management. In addition, we provide a comprehensive literature review on the association between progestins and HA.
RESULTS: Since 1983, 16 cases of HA in patients on progestins have been reported. Ten patients were on NET and 5 on a prodrug of NET (4 on norethindrone acetate [NETA] and 1 on lynestrenol). One individual had a norgestrel implant. Eight subsequently ceased all hormones: 4 experienced a size reduction, and 3 had complete resolution of their HA. Among our patients, 1 ceased NET and instead had a levonorgestrel intrauterine device inserted, and another swapped from NET to oral medroxyprogesterone acetate. Both experienced complete resolution of their HA. The third ceased NET and underwent a hysterectomy, with size reduction of her HA.
CONCLUSIONS: These cases and the literature review suggest an association between progestin exposure, in particular NET and its prodrugs, and the development of HA. The pathophysiology is unknown but may include peripheral conversion of NET and NETA to ethinyl estradiol or a specific action of 19-nortestosterone derivatives on hepatocytes, especially those with higher systemic doses compared with the levonorgestrel intrauterine device. There are no case reports relating to other forms of progestins, such as 17-hydroxyprogesterone, which may be important when considering alternative therapeutic options in females requiring effective menstrual management who have comorbidities.
RESULTS: Since 1983, 16 cases of HA in patients on progestins have been reported. Ten patients were on NET and 5 on a prodrug of NET (4 on norethindrone acetate [NETA] and 1 on lynestrenol). One individual had a norgestrel implant. Eight subsequently ceased all hormones: 4 experienced a size reduction, and 3 had complete resolution of their HA. Among our patients, 1 ceased NET and instead had a levonorgestrel intrauterine device inserted, and another swapped from NET to oral medroxyprogesterone acetate. Both experienced complete resolution of their HA. The third ceased NET and underwent a hysterectomy, with size reduction of her HA.
CONCLUSIONS: These cases and the literature review suggest an association between progestin exposure, in particular NET and its prodrugs, and the development of HA. The pathophysiology is unknown but may include peripheral conversion of NET and NETA to ethinyl estradiol or a specific action of 19-nortestosterone derivatives on hepatocytes, especially those with higher systemic doses compared with the levonorgestrel intrauterine device. There are no case reports relating to other forms of progestins, such as 17-hydroxyprogesterone, which may be important when considering alternative therapeutic options in females requiring effective menstrual management who have comorbidities.
摘要：
目的：探讨孕激素作为肝细胞腺瘤（HA）发展的潜在因素的作用以及他们的管理。此外,我们对孕激素与HA之间的关系进行了全面的文献综述.
结果：自1983年以来，已经报道了16例孕激素患者中的HA。10例患者使用NET，5例使用NET的前药（4例使用醋酸noretindrone[NETA]，1例使用lynestrenol）。一个人植入了Norgestrel。八个随后停止了所有激素：四个经历了尺寸缩小，和3已完全解决他们的HA。在我们的病人中，1停止了NET，而是插入了左炔诺孕酮宫内节育器，另一个从NET换成口服醋酸甲羟孕酮。两者都经历了他们的HA的完全解决。第三个停止了NET，接受了子宫切除术，随着她HA的大小减少。
结论：这些病例和文献综述表明，特别是NET及其前药，和HA的发展。病理生理学未知，但可能包括NET和NETA向乙炔雌二醇的外周转化或19-去甲睾酮衍生物对肝细胞的特定作用，尤其是与左炔诺孕酮宫内节育器相比，全身剂量较高的患者。没有与其他形式的孕激素有关的病例报告，如17-羟基孕酮，在考虑需要有效月经管理且有合并症的女性的替代治疗方案时，这一点可能很重要。
结果：自1983年以来，已经报道了16例孕激素患者中的HA。10例患者使用NET，5例使用NET的前药（4例使用醋酸noretindrone[NETA]，1例使用lynestrenol）。一个人植入了Norgestrel。八个随后停止了所有激素：四个经历了尺寸缩小，和3已完全解决他们的HA。在我们的病人中，1停止了NET，而是插入了左炔诺孕酮宫内节育器，另一个从NET换成口服醋酸甲羟孕酮。两者都经历了他们的HA的完全解决。第三个停止了NET，接受了子宫切除术，随着她HA的大小减少。
结论：这些病例和文献综述表明，特别是NET及其前药，和HA的发展。病理生理学未知，但可能包括NET和NETA向乙炔雌二醇的外周转化或19-去甲睾酮衍生物对肝细胞的特定作用，尤其是与左炔诺孕酮宫内节育器相比，全身剂量较高的患者。没有与其他形式的孕激素有关的病例报告，如17-羟基孕酮，在考虑需要有效月经管理且有合并症的女性的替代治疗方案时，这一点可能很重要。
