在美国，近百分之二的人认为性别不合格。在女变男 (FTM) 变性人群中，通常在性别转变过程中使用睾酮进行男性化激素治疗。迄今为止，人们对外源性雄激素对乳腺组织的影响及其在改变乳腺癌风险中的作用知之甚少。本研究探讨了跨性别 FTM 患者性别确认乳房切除术 (GAM) 的组织病理学结果以及外源性雄激素对雌激素受体 (ER) 和雄激素受体 (AR) 的影响。对 2017 年至 2020 年期间获得的病理标本进行回顾性审查，比较暴露于雄激素的乳腺组织与未暴露于雄激素的乳腺组织。乳房样本取自接受 FTM GAM 并记录外源性雄激素暴露的患者。对照乳房标本是从与 GAM 队列年龄匹配的顺性别女性的乳房缩小成形术 (RM) 手术中获得的，以及接受良性/预防性乳房切除术的绝经后女性；所有对照均未暴露于雄激素。评估组织病理学结果。对 AR 和 ER 进行免疫组织化学分析，并通过数字图像分析解释评分。暴露于雄激素的乳腺组织显示致密纤维化基质、小叶萎缩、小叶基底膜增厚和男性乳突变化。雄激素暴露时间越长，效果越明显。 GAM 组的异型性或癌症发生率低于 RM 组。 ER 和 AR 表达在外源性雄激素暴露时间中等的变性男性乳腺组织中最高。雄激素暴露增加与乳腺实质中的小叶萎缩和男性乳突变化相关。总体而言，ER 和 AR 在长期雄激素暴露患者的小叶上皮中强烈表达。外源性睾酮似乎不会增加患乳腺癌的风险。需要更多的研究来调查细胞水平上这些变化的机制及其在癌症发展中的作用。由爱思唯尔有限公司出版。

Almost two percent of individuals in the United States identify as gender non-conforming. In the female-to-male (FTM) transgender population, masculinizing hormone therapy with testosterone is commonly prescribed in gender transition. To date, the effects of exogenous androgens on breast tissue and its roles in altering breast cancer risk are poorly understood. This study examines the histopathologic findings in gender affirming mastectomy (GAM) in transgender FTM patients and the effects of exogenous androgens on estrogen receptors (ER) and androgen receptors (AR).A retrospective review of pathology specimens obtained between 2017 and 2020 was performed comparing androgen exposed breast tissue with breast tissue without androgen exposure. Breast specimens were obtained from patients who underwent FTM GAM with recorded exogenous androgen exposure. Control breast specimens were obtained from reduction mammoplasty (RM) procedures in cisgender women which were aged matched to the GAM cohort, as well as postmenopausal women with benign/prophylactic mastectomy procedures; all controls were without androgen exposure. The histopathologic findings were assessed. Immunohistochemistry for AR and ER was performed and the score interpreted by digital image analysis.Androgen-exposed breast tissue revealed dense fibrotic stroma, lobular atrophy, thickened lobular basement membranes, and gynecomastoid changes. Longer duration of androgen exposure resulted in a more pronounced effect. The incidence of atypia or cancer was lower in GAM than RM cohort. ER and AR expression was highest in transgender male breast tissue with intermediate duration of exogenous androgen exposure.Increased androgen exposure is associated with lobular atrophy and gynecomastoid changes in breast parenchyma. Overall, ER and AR are expressed strongly in lobular epithelium in patients with prolonged androgen exposure. Exogenous testosterone does not appear to increase risk for breast cancer. Additional studies are needed to investigate the mechanism responsible for these changes at a cellular level and its role in cancer development.Published by Elsevier Ltd.