First Department of Obstetrics and Gynecology, Unit of Reproductive Endocrinology, Aristotle University of Thessaloniki, Thessaloniki, Greece.
University Department of Growth and Reproduction, and International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, Copenhagen, Denmark.
Andrology. 2019 Nov;7(6):778-793. doi: 10.1111/andr.12636. Epub 2019 May 16.
Gynecomastia (GM) is a benign proliferation of the glandular tissue of the breast in men. It is a frequent condition with a reported prevalence of 32-65%, depending on the age and the criteria used for definition. GM of infancy and puberty are common, benign conditions resolving spontaneously in the majority of cases. GM of adulthood is more prevalent among the elderly and proper investigation may reveal an underlying pathology in 45-50% of cases.
The aim was to provide clinical practice guidelines for the evaluation and management of GM.
A literature search of articles in English for the term 'gynecomastia' was conducted. Evidence-based recommendations were developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system.
A set of five statements and fifteen clinical recommendations was formulated.
The purpose of GM assessment should be the detection of underlying pathological conditions, reversible causes (administration/abuse of aggravating substances), and the discrimination from other breast lumps, particularly breast cancer. Assessment should comprise a thorough medical history and physical examination of the breast and genitalia (including testicular ultrasound). A set of laboratory investigations may integrate the evaluation: testosterone (T), estradiol (E2), sex hormone-binding globulin (SHBG), luteinizing hormone (LH), follicular stimulating hormone (FSH), thyroid stimulating hormone (TSH), prolactin, human chorionic gonadotropin (hCG), alpha-fetal protein (AFP), liver and renal function tests. Breast imaging may be used whenever the clinical examination is equivocal. In suspicious lesions, core needle biopsy should be sought directly instead. Watchful waiting is recommended after treatment of underlying pathology or discontinuation of substances associated with GM. T treatment should be offered to men with proven T deficiency. The use of selective estrogen receptor modulators (SERMs), aromatase inhibitors (AIs) and non-aromatizable androgens is not justified in general. Surgical treatment is the therapy of choice for patients with long-lasting GM.
SUMMARY OF STATEMENTS (S) AND RECOMMENDATIONS (R): S1. Gynecomastia (GM) is a benign proliferation of glandular tissue of the breast in males. S2. GM of infancy is a common condition that usually resolves spontaneously, typically within the first year of life. S3. GM of puberty is a common condition, affecting approximately 50% of mid-pubertal boys; in more than 90% of cases, it resolves spontaneously within 24 months. S4. The prevalence of GM in adulthood increases with increasing age; proper investigation may reveal an underlying pathology in approximately 45-50% of the cases. S5. Male breast cancer is rare; GM should not be considered a premalignant condition. The following recommendations are divided into 'strong', denoted by the number 1 and associated with the terminology 'we recommend', and 'weak' denoted by the number 2 and associated with the phrase 'we suggest'. The grading of the quality of evidence is denoted as follows: ⊕○○○ for very low-quality evidence; ⊕⊕○○ for low quality; ⊕⊕⊕○ for moderate quality; and ⊕⊕⊕⊕ for high quality. R1. The presence of an underlying pathology should be considered in GM of adulthood. We recommend that the identification of an apparent reason for GM in adulthood, including the use of medication known to be associated with GM, should not preclude a detailed investigation (1 ⊕⊕⊕○). R2. We suggest that the initial screening to rule out lipomastia, obvious breast cancer, or testicular cancer might be performed by a general practitioner or another non-specialist (2 ⊕○○○). R3. We recommend that in those cases where a thorough diagnostic workup is warranted, it should be performed by a specialist (1 ⊕○○○). R4. We recommend that the medical history should include information on the onset and duration of GM, sexual development and function, and administration or abuse of substances associated with GM (1 ⊕⊕⊕○). R5. We recommend that the physical examination should detect signs of under-virilization or systemic disease (1 ⊕⊕⊕⊕). R6. We recommend that breast examination should confirm the presence of palpable glandular tissue to discriminate GM from lipomastia (pseudo-gynecomastia) and rule out the suspicion of malignant breast tumor (1 ⊕⊕⊕⊕). R7. We recommend that the physical examination should include the examination of the genitalia to rule out the presence of a palpable testicular tumor and to detect testicular atrophy (1 ⊕⊕⊕⊕). R8. We recommend that genitalia examination is aided by a testicular ultrasound, as the detection of a testicular tumor by palpation has low sensitivity (1 ⊕⊕○○). R9. We suggest that a set of evaluations may include T, E , SHBG, LH, FSH, TSH, prolactin, hCG, AFP, and liver and renal function tests (2 ⊕⊕○○). R10. We suggest that breast imaging may offer assistance, where the clinical examination is equivocal (2 ⊕⊕○○). R11. We suggest that, if the clinical picture is suspicious for a malignant lesion, core needle biopsy should be performed (2 ⊕⊕○○). R12. We recommend watchful waiting after treatment of underlying pathology or discontinuation of the administration/abuse of substances associated with GM (1 ⊕⊕○○). R13. We recommend that T treatment should be offered only to men with proven testosterone deficiency (1 ⊕⊕⊕○). R14. We do not recommend the use of selective estrogen receptor modulators (SERMs), aromatase inhibitors (AIs), or non-aromatizable androgens in the treatment of GM in general (1 ⊕⊕○○). R15. We suggest surgical treatment only for patients with long-lasting GM, which does not regress spontaneously or following medical therapy. The extent and type of surgery depend on the size of breast enlargement, and the amount of adipose tissue (2 ⊕⊕○○).
男性乳房发育症(GM)是男性乳腺腺体组织的良性增生。它是一种常见的疾病,其患病率为 32-65%,具体取决于年龄和定义的标准。婴儿期和青春期的 GM 是常见的良性疾病,大多数情况下会自发缓解。成年期的 GM 在老年人中更为常见,适当的调查可能会在 45-50%的病例中发现潜在的病理。
旨在为 GM 的评估和管理提供临床实践指南。
对“gynecomastia”一词的英文文献进行了检索。使用 Grading of Recommendations, Assessment, Development, and Evaluation(GRADE)系统制定了基于证据的建议。
制定了一套五项陈述和十五项临床建议。
GM 评估的目的应该是发现潜在的病理状况、可纠正的原因(药物/滥用可导致 GM 的物质)以及与其他乳腺肿块,特别是乳腺癌的鉴别。评估应包括对乳房和生殖器(包括睾丸超声)的全面病史和体格检查。一组实验室检查可纳入评估:睾酮(T)、雌二醇(E2)、性激素结合球蛋白(SHBG)、黄体生成素(LH)、卵泡刺激素(FSH)、促甲状腺激素(TSH)、催乳素、人绒毛膜促性腺激素(hCG)、甲胎蛋白(AFP)、肝肾功能检查。如果临床检查不确定,可使用乳腺影像学检查。如果病变可疑,应直接进行核心针活检。在治疗潜在病理或停止使用与 GM 相关的物质后,建议进行观察等待。只有在证实存在睾酮缺乏的情况下,才应向男性提供 T 治疗。一般情况下,不建议使用选择性雌激素受体调节剂(SERMs)、芳香化酶抑制剂(AIs)和非芳香化雄激素治疗 GM。对于长期存在且不能自发消退或药物治疗无效的 GM 患者,手术治疗是首选。手术类型取决于乳腺增大的程度和脂肪组织的多少。
声明(S)和建议(R)总结:S1. GM 是男性乳腺腺体组织的良性增生。S2. 婴儿期 GM 是一种常见的疾病,通常会在生命的第一年自发缓解,典型病例约占 50%。S3. 青春期 GM 是一种常见的疾病,约 50%的青春期男孩会出现这种情况;超过 90%的病例会在 24 个月内自发缓解。S4. 成年期 GM 的患病率随年龄增长而增加,适当的调查可能会在 45-50%的病例中发现潜在的病理。S5. 男性乳腺癌罕见;GM 不应被视为癌前病变。以下建议分为“强”,用数字 1 表示,并与“我们建议”一词相关联,以及“弱”,用数字 2 表示,并与“我们建议”一词相关联。证据质量的分级表示为:极低质量证据为 ⊕○○○;低质量证据为 ⊕⊕○○;中等质量证据为 ⊕⊕⊕○;高质量证据为 ⊕⊕⊕⊕。R1. 成年期 GM 应考虑潜在的病理。我们建议,如果在成年期 GM 中发现明显的原因,包括使用已知与 GM 相关的药物,不应排除详细调查(1 ⊕⊕⊕○)。R2. 我们建议,为了排除脂肪瘤、明显的乳腺癌或睾丸癌,可能需要由全科医生或其他非专家进行初步筛查(2 ⊕○○○)。R3. 我们建议,如果需要进行彻底的诊断性检查,应由专家进行(1 ⊕○○○)。R4. 我们建议,病史应包括 GM 的发病和持续时间、性发育和功能以及与 GM 相关的药物/滥用的使用情况(1 ⊕⊕⊕○)。R5. 我们建议,体格检查应发现男性特征减退或系统性疾病的迹象(1 ⊕⊕⊕⊕)。R6. 我们建议,乳房检查应确认可触及的腺体组织的存在,以区分 GM 与脂肪瘤(假性男性乳房发育症)并排除恶性乳腺肿瘤的怀疑(1 ⊕⊕⊕⊕)。R7. 我们建议,生殖器检查应包括睾丸超声检查,因为触诊检测睾丸肿瘤的敏感性较低(1 ⊕⊕○○)。R8. 我们建议,通过睾丸超声检查辅助生殖器检查,因为触诊发现睾丸肿瘤的敏感性较低(1 ⊕⊕○○)。R9. 我们建议,一套评估可能包括 T、E、SHBG、LH、FSH、TSH、催乳素、hCG、AFP 和肝肾功能检查(2 ⊕⊕○○)。R10. 我们建议,乳腺影像学检查可能会有所帮助,如果临床检查不确定(2 ⊕⊕○○)。R11. 我们建议,如果临床图像可疑为恶性病变,应进行核心针活检(2 ⊕⊕○○)。R12. 我们建议,在治疗潜在病理或停止使用与 GM 相关的药物/滥用后,应进行观察等待(1 ⊕⊕○○)。R13. 我们建议,只有在证实存在睾酮缺乏的情况下,才应向男性提供 T 治疗(1 ⊕⊕⊕○)。R14. 我们不建议一般情况下使用选择性雌激素受体调节剂(SERMs)、芳香化酶抑制剂(AIs)或非芳香化雄激素治疗 GM(1 ⊕⊕○○)。R15. 我们建议仅对长期存在且不能自发消退或药物治疗无效的 GM 患者进行手术治疗。手术类型取决于乳腺增大的程度和脂肪组织的多少。