Gynecomastia in Men Following Antineoplastic Therapy

\s=b\Six men had painful gynecomastia develop during or following the administration of cytotoxic chemotherapy. Alternative causes of gynecomastia were not delineated in any patient. Sharp increases in levels of plasma follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were noted in five patients. Plasma testosterone concentrations were within or above the normal range in all five patients in whom they were determined. In three patients, plasma estradiol concentrations were modestly increased. One patient was studied prospectively: painful gynecomastia developed at a time when plasma FSH and LH levels were elevated, serum testosterone was decreasing from supranormal to low-normal concentrations, and plasma estradiol was rising to high levels. Plasma prolactin levels were increased in one of four patients in whom they were measured. The mechanisms leading to gynecomastia following cytotoxic chemotherapy were not defined. Damage to germinal epithelium and Leydig cells as well as changes in the peripheral metabolism of testosterone and estrogen may be important. Gynecomastia may occur following cytotoxic chemotherapy and does not necessarily represent recurrent or progressive cancer. (Arch Intern Med 1982;142:511-513) Amenorrhea, oligoazoospermia, disturbances in gonadal ^ estrogen and androgen secretion, and increased plas¬ ma content of gonadotropins are recognized consequences of the administration of cytotoxic drugs.15 Pubertal male subjects have been noted to have gynecomastia develop following the administration of cytotoxic chemotherapy; however, gynecomastia has been thought not to occur in adult men following cytotoxic therapy.6i7 This report de¬ scribes six adults in whom painful gynecomastia developed after cytotoxic therapy. The importance of recognizing this potential complication of cytotoxic chemotherapy is dis¬ cussed. REPORT OF CASES Case 1.—Six months following right orchiectomy and retroperitoneal node dissection for an embryonal carcinoma of the testis, this 19-year-old man had asymptomatic pulmonary metastases develop. Serum content of the beta subunit of human chorionic gonadotropin (/3HCG) was normal and reproductive hormone data were as noted in the Figure. Systemic chemotherapy using cisplatin, vinblastine sulfate, and bleomycin sulfate was initiated and administered monthly for four months. Pulmonary metastases resolved and therapy was discontinued after four months. Six weeks following the administration of the last cycle of chemotherapy, bilateral tender gynecomastia developed. The patient was taking no medications at this time and evaluation for recurrent testis cancer revealed no abnormalities. Sequential reproductive hormone data were obtained during therapy and are depicted in the Figure. The patient has been followed up for 14 months since the onset of gynecomastia. Breast tenderness has diminished but persists and there is no evidence of recurrent testis cancer. Case 2.—One year following left inguinal orchiectomy and retroperitoneal node dissection for an embryonal carcinoma of the testis, this 33-year-old man had asymptomatic pulmonary metastases develop. Serum content of /3HCG was normal. Administra¬ tion of combination chemotherapy (cyclophosphamide, vinblas¬ tine, bleomycin, dactinomycin, and cisplatin[VAB III]) resulted in a complete remission after two months. Maintenance chemother¬ apy (vinblastine, dactinomycin, and cisplatin) was begun and two months later painful enlargement of both breasts developed. Prochlorperazine (30 to 40 mg/mo) and two to four marijuana cigarettes per month were the only other drugs ingested during this time. Complete reevaluation failed to reveal evidence of recurrent testis cancer. Reproductive hormone data obtained are outlined in the Table. Maintenance therapy was completed and the patient remains free of disease years after the initiation of chemotherapy. Breast tenderness has resolved, though palpable breast tissue persists. Case 3.—At age 31, this patient underwent right inguinal orchiectomy and retroperitoneal lymph node dissection for a teratocarcinoma. Gynecomastia and increased urinary excretion of HCG were noted before orchiectomy, and both resolved follow¬ ing lymph node dissection. One and one-half years later, a pulmonary nodule was discovered. Gynecomastia and breast ten¬ derness had returned and the serum concentration of 0HCG was increased. A biopsy specimen of the pulmonary nodule confirmed the presence of teratocarcinoma. Combination chemotherapy (VAB III) was administered in the fashion described in case 2. Breast tenderness resolved over the next two months and the chest roentgenogram returned to normal. However, five months after the initial chemotherapy, pain and further enlargement of both breasts developed. Evaluation did not reveal recurrence of testis cancer. Prochlorperazine (30 to 40 mg/mo) and marijuana (four to six cigarettes per month) were the only other drugs ingested during this time. Reproductive hormone data are out¬ lined in the Table. Maintenance chemotherapy was completed and over the next six months gynecomastia and pain diminished. Three years after the initiation of chemotherapy, the patient is free of testis cancer; mildly painful gynecomastia persists.