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PubMed1985

Gynecomastia in testicular cancer patients. Prognostic and therapeutic implications.

Eighty-one patients with advanced testicular cancer were evaluated for gynecomastia or severe breast tenderness at diagnosis and after platinum-based chemotherapy. The prognostic significance of gynecomastia in these two settings was explored. At presentation, 10% (8 patients) had gynecomastia or breast tenderness and elevated HCG levels. The likelihood of gynecomastia was greater with increasing HCG level (P = 0.002). However, gynecomastia at presentation was a more powerful independent discriminant of poor survival than the initial HCG level by multivariate analysis (P = 0.004). Fifteen percent (12 patients) developed transient gynecomastia after chemotherapy not attributable to other known causes. HCG levels were normal. Endocrine evaluation typically revealed elevated FSH, LH, and estradiol/testosterone ratios. This may have reflected damage to testicular germinal epithelium. All 12 patients are alive without disease in contrast to the 8 patients who had gynecomastia at diagnosis. Therapy decisions should therefore be based on the time of onset of gynecomastia and in the context of appropriate clinical markers and evaluation.

Adolescent↗

PubMed2005

Possible involvement of aromatase overexpression induced by cyclo-oxygenase-2 in the pathogenesis of idiopathic gynecomastia.

The pathogenesis of idiopathic gynecomastia, which shows no imbalance in serum estrogens and androgens levels unlike gynecomastia of other causes, is unknown. It seems to be of interest to study the in situ aromatase expression in idiopathic gynecomastia to investigate a possible involvement of intratumoral biosynthesis of estrogens in the pathogenesis of this disease. The expression level of aromatase mRNA was studied by a real-time polymerase chain reaction (PCR) assay in four idiopathic gynecomastia cases (two florid type and two fibrous type). In addition, the proportion of promoter usage (promoters I.3 I.4, l. 7, and PII) of the aromatase gene was determined by PCR-gel electrophoresis. Localization of aromatase and cyclo-oxygenase-2 (COX-2) expression was studied by immunohistochemistry. The aromatase mRNA level of the florid type gynecomastia (3.05 and 1.66) was higher than that in the fibrous type (0.76 and 0.04). The proportion of promoter Pll in the florid type (94.1% and 84.8%) was very high as compared with that of the fibrous type (0.7% and 0.5%). Immunohistochemical studies have revealed that aromatase and COX-2 were strongly expressed in the duct epithelial cells in the florid type, but they were weak or negative in the fibrous type. COX-2 is suggested to upregulate aromatase expression by enhancing the transcription via promoter Pll in idiopathic gynecomastia of the florid type but not of the fibrous type. Because idiopathic gynecomastia initially develops as the florid type and regresses as the fibrous type, a high estrogen milieu induced by increased aromatase expression is speculated to play some role in the pathogenesis of idiopathic gynecomastia.

Adolescent↗

PubMed2001

Gynecomastia associated with highly active antiretroviral therapy.

OBJECTIVE: To report four cases of HIV-associated gynecomastia diagnosed during treatment with nucleoside analogs with or without protease inhibitors. CASE SUMMARY: Four HIV-infected patients developed gynecomastia while taking two nucleoside analogs (stavudine combined with lamivudine in 3 patients, stavudine with didanosine in 1 patient) and protease inhibitors (indinavir, nelfinavir, ritonavir-saquinavir in 3 patients) all patients had received prior treatment with single or associated nucleoside analogs for > or = 21 months. Gynecomastia occurred three to seven months after the start of a triple regimen in the first three patients, and 17 months after initiating the last dual nucleoside analog therapy in the remaining patient. Liver, kidney, and thyroid function were normal; a routine endocrinologic workup showed slight follicle-stimulating hormone and luteinizing hormone abnormalities in one patient only. Other possible causes of drug- or disease-induced gynecomastia were excluded. A concurrent fat redistribution syndrome was present in three patients (including the patient who received nucleoside analogs only), while serum lipid and/or glucose concentration abnormalities were present in all patients. Gynecomastia remained unchanged during the subsequent seven- to 16-month follow-up, even after modification of antiretroviral therapy. DISCUSSION: Gynecomastia has been recently associated with antiretroviral therapy, and all reported cases but one occurred two to 17 months after the start of a protease inhibitor-based regimen. Our experience underlines the possible occurrence of gynecomastia in the absence of protease inhibitor administration, its persistence despite changes of antiretroviral regimen (thus resembling some signs related to lipodystrophy syndrome), and the apparently constant association with prolonged nucleoside analog administration (especially stavudine). CONCLUSIONS: Gynecomastia should be included among emerging adverse effects of antiretroviral therapy, although its etiopathogenesis deserves further investigation.

Adipose Tissue↗

PubMed1990

Gynecomastia and cirrhosis of the liver.

Hepatic cirrhosis is frequently listed as a cause of gynecomastia. We found previously that in hospitalized men the prevalence of gynecomastia was correlated with body mass index and with age. The mean body mass index and the prevalence of gynecomastia in the cirrhotic subjects (nonedematous) did not differ from those in the overall population. Because more severely cirrhotic subjects with ascites, peripheral edema, or both usually are thin, we examined 18 more severely cirrhotic subjects and 18 nonobese (mean body mass index, 20.9 +/- 0.6 kg/m2), age-matched control subjects for the prevalence of palpable gynecomastia. Total testosterone, free testosterone, total estrogen, and estradiol concentrations also were measured. Fifty percent of the control subjects had gynecomastia. Breast tissue diameter was correlated with body mass index. The prevalence of gynecomastia in the cirrhotic subjects was 44%. In these subjects no significant correlation was noted between breast tissue diameter and body mass index, presumably because the body mass index was increased owing to fluid retention. The results could not be accounted for based on medications. Serum free testosterone concentrations were lower in the cirrhotic patients than in the controls (0.11 +/- 0.02 vs 0.22 +/- 0.03 nmol/L). The total estrogen-free testosterone ratio was higher in cirrhotic patients (10.3 +/- 2.5 vs 2.6 +/- 0.5), as was the estradiol-free testosterone ratio (2.2 +/- 0.7 vs 0.5 +/- 0.1). These ratios did not differ significantly in cirrhotic subjects with and without gynecomastia. Therefore, these data indicate that factors other than the estrogen-testosterone ratio are playing a role in the development of gynecomastia in both cirrhotic subjects and controls or that breast tissue sensitivity to an elevated estrogen-testosterone ratio is highly varible.

Age Factors↗

PubMed1979

Gynecomastia after chemotherapy for lymphoma.

Although development of gynecomastia in a patient with cancer may indicate persistence or regrowth of a tumor, we studied three patients with lymphoma in whom development of gynecomastia during or after chemotherapy did not portend a poor outcome. In all patients, serum testosterone levels were normal, serum luteinizing hormone (LH) levels were high-normal or elevated, and serum follicle-stimulating hormone (FSH) levels were clearly elevated. The serum estradiol level of one patient was elevated at the onset of gynecomastia, but it fell to normal as the gynecomastia resolved spontaneously over a three-month period during which the patient received no chemotherapy. In a second patient, gynecomastia resolved over a period of eight months while the patient continued on maintenance chemotherapy, and he remains clinically well in remission 21/2 years after onset of gynecomastia. In the third patient, gynecomastia developed while the patient was in complete remission and off of all therapy, and it remained unchanged for the duration of a 21/2-year remission without therapy. Gynecomastia after chemotherapy for lymphoma is not an ominous prognostic sign and does not necessarily indicate the need for alteration of the treatment regimen.

Adult↗

PubMedDate not supplied

Epidemic of gynecomastia among illegal Haitian entrants.

Gynecomastia may occur as a normal physiologic development at certain ages or as a result of a variety of pathological conditions. An outbreak of gynecomastia was investigated at two processing centers of the Immigration and Naturalization Service (INS) between December 2, 1981, and May 14, 1982. At the Fort Allen Service Processing Center, Puerto Rico, gynecomastia was initially detected in 77 of 540 Haitian male entrants (14 percent) and in only 6 of 186 male employees of the center (3 percent) who were 18-50 years old; the difference in prevalence was statistically significant. At the Krome North Service Processing Center in Miami, Fla., gynecomastia was initially detected in 52 of 512 Haitian males 18-50 years old (10 percent). Two case-control studies did not demonstrate an association between gynecomastia and a number of factors that might have been related to an exogenous estrogen or to a substance with an estrogenic effect. Estrogen or estrogen-like substances were not found in food, water, or environmental samples. When the populations were rescreened several months later, 76 of the persons with gynecomastia detected in the first screening had had total or partial remission. Persons with remission had arrived earlier--a mean of 21.6 days for those at Fort Allen and 36.7 for those at Krome--than did those with newly detected gynecomastia and those with continuing cases. The difference in arrival dates was significant (P less than .005 for Fort Allen and P less than .001 for Krome). These results, in view of nutritional deprivation in Haiti, suggest that these cases may have been an outbreak of refeeding gynecomastia.

Adult↗

PubMed1997

[Feminizing syndrome and gynecomastia in males].

Gynecomastia is one of the common symptoms of feminizing syndrome in males. Causes of feminizing syndrome are considered the increase of serum level of estrogen, prolactin, LH and hCG and testosterone deficiency. The condition of gynecomastia was commonly silent. Gynecomastia is classified three groups those are physiological, pathological and ideopathic gynecomastia. Physiological gynecomastia was reported to break out healthy males. Ideopathic gynecomastia is the main cause in medicine. Characterization of pathological gynecomastia are known side effect of drugs, testosterone deficiency and increased estrogen production. Gynecomastia is making satisfactory progress by treatment of the causes, but long term of the history merely have need resection.

Adolescent↗

PubMed1984

Gynecomastia in a hospitalized male population.

Two hundred fourteen hospitalized adult men, aged 27 to 92, were examined for the presence of palpable gynecomastia. The overall prevalence was 65 percent. Gynecomastia was bilateral in all but 11 subjects. The prevalence was greatest in the 50 to 69-year-old group (72 percent). It was lower in the 70- to 89-year-old (47 percent, p less than 0.01) and the 30- to 49-year-old (54 percent, p less than 0.05) groups. The prevalence of gynecomastia increased with body mass index. More than 80 percent of those with a body mass index of 25 kg/m2 or greater had gynecomastia. The diameter of breast tissue also increased with increasing body mass index (r = 0.52, p less than 0.001). The decreased prevalence of gynecomastia after the seventh decade could be explained by the lower body mass index in this group. The youngest group did not have a lower body mass index; an independent age factor appeared to be present. Because of the high overall prevalence of gynecomastia, independent effects of diseases or medications could not be determined. It is concluded that palpable bilateral gynecomastia is present in most older men, is correlated with the amount of body fat, and does not require clinical evaluation unless symptomatic or of recent onset.

Adult↗

PubMedDate not supplied

Gynecomastia: cytologic features and diagnostic pitfalls in fine needle aspirates.

OBJECTIVE: To illustrate some of the uncommon cytologic findings of gynecomastia, such as apocrine metaplasia, cellular atypia and foamy macrophages, that can be misinterpreted as evidence of malignancy. STUDY DESIGN: The clinical data and fine needle aspiration (FNA) cytologic material from 100 men with the diagnosis of gynecomastia were retrospectively reviewed. The excisional biopsy slides were available for 16 cases. For comparison, FNA smears from five men with breast lesions other than gynecomastia were studied. RESULTS: The patients ranged in age from 23 to 91 years. Cytologic findings were as follows: cohesive sheets of cells containing 20-1,000 cells (98%); scattered, single, bipolar cells (78%); spindle cells (68%); ductal epithelial atypia (26%); apocrine metaplasia (8%); and foamy histiocytes (12%). In nine cases the atypia was marked, and in two of them the possibility of malignancy could not be ruled out. Surgical follow-up on 16 patients, including the cases with marked atypia, showed gynecomastia. In one case, gynecomastia was associated with intraductal papilloma. No correlation between the underlying etiology and atypical cytologic features of gynecomastia was identified. CONCLUSION: Apocrine metaplasia and epithelial atypia are common findings in gynecomastia. Attention to the cell patterns, the presence of sheets of ductal cells and absence of atypical single cells will point to the correct diagnosis.

Adult↗

PubMed2002

Male gynecomastia and risk for malignant tumours--a cohort study.

BACKGROUND: Men with gynecomastia may suffer from absolute or relative estrogen excess and their risk of different malignancies may be increased. We tested whether men with gynecomastia were at greater risk of developing cancer. METHODS: A cohort was formed of all the men having a histopathological diagnosis of gynecomastia at the Department of Pathology, University of Lund, following an operation for either uni- or bilateral breast enlargement between 1970-1979. All possible causes of gynecomastia were accepted, such as endogenous or exogenous hormonal exposure as well as cases of unknown etiology. Prior to diagnosis of gynecomastia eight men had a diagnosis of prostate carcinoma, two men a diagnosis of unilateral breast cancer and one had Hodgkin's disease. These patients were included in the analyses. The final cohort of 446 men was matched to the Swedish Cancer Registry, Death Registry and General Population Registry. RESULTS: At the end of the follow up in December 1999, the cohort constituted 8375.2 person years of follow-up time. A total of 68 malignancies versus 66.07 expected were observed; SIR = 1.03 (95% CI 0.80-1.30). A significantly increased risk for testicular cancer; SIR = 5.82 (95% CI 1.20-17.00) and squamous cell carcinoma of the skin; SIR = 3.21 (95% CI 1.71-5.48) were noted. The increased risk appeared after 2 years of follow-up. A non-significantly increased risk for esophageal cancer was also seen while no new cases of male breast cancer were observed. However, in the prospective cohort, diagnostic operations for gynecomastia may substantially have reduced this risk CONCLUSIONS: There is a significant increased risk of testicular cancer and squamous cell carcinoma of the skin in men who have been operated on for gynecomastia.

Adolescent↗

PubMed1983

Painful gynecomastia following cytotoxic therapy for testis cancer: a potentially favorable prognostic sign?

Ninety-six patients who received cytotoxic chemotherapy for germ cell neoplasms of the testis were studied. Painful gynecomastia developed in eight patients (8%) between 6 and 24 weeks after the initiation of cytotoxic therapy (mean 18 wk). Serum content of the beta subunit of human chorionic gonadotropin was normal in each patient when gynecomastia developed. Gynecomastia occurred following cytotoxic therapy for advanced disease in seven patients, and one patient was receiving adjunctive drug therapy for stage I disease. Six of the seven patients with advanced disease were in complete remission when gynecomastia developed; survival was superior in patients who developed treatment-related gynecomastia compared to those patients who did not (p less than 0.05). Gynecomastia may occur in adult males after cytotoxic therapy for testis cancer; such gynecomastia does not necessarily indicate recurrent malignancy and may be a favorable prognostic sign.

Adolescent↗

PubMed1996

Aromatase and steroid receptors in gynecomastia and male breast carcinoma: an immunohistochemical study.

Hormonal factors have been implicated in the development of male breast disorders, including carcinoma and gynecomastia. We studied the expression of aromatase and estrogen (ER), progesterone (PR), and androgen (AR) receptors by immunohistochemistry in male breast carcinoma (15 cases) and gynecomastia (30 cases) to evaluate their possible significance in these disorders. Relatively strong aromatase immunoreactivity was observed in all cases of carcinoma, but in only 11 of 30 cases (37%) of gynecomastia. ER and PR expression was observed in the nuclei of ductal cells in all the cases of gynecomastia. More than 10% of the carcinoma cells were positive for ER and PR in 9 of 15 (60%) and 10 of 15 (67%) carcinomas, respectively. AR immunoreactivity was observed in nuclei of both epithelial and non-epithelial cells. AR was present in ductal or carcinoma cells in 13 of 15 (87%) cases of carcinoma and in all 30 (100%) cases of gynecomastia. The mean percentage of ER-, PR-, and AR-positive cells were significantly higher in gynecomastia than in carcinoma. There was a close association of AR with ER (P < 0.01) and PR (P < 0.01) in cases of gynecomastia, but there was a significant inverse correlation between AR and ER (P < 0.01) or PR (P < 0.05) expression in carcinoma cases. Increased aromatase expression in the stromal cells is considered to contribute to the increment in the in situ estrogen concentration and the development of male breast carcinoma.

Adult↗

PubMedDate not supplied

Gynecomastia attributable to human chorionic gonadotropin-secreting giant cell carcinoma of lung.

OBJECTIVE: To describe a patient with human chorionic gonadotropin (hCG)-secreting giant cell carcinoma of the lung manifesting as painful gynecomastia, which resolved after surgical treatment. METHODS: We present the clinical, radiologic, and clinical course of our patient, who presented with painful gynecomastia. RESULTS: A 51-year-old man presented with a lung mass and rapidly progressing bilateral painful gynecomastia. Hormonal evaluation revealed high levels of hCG beta subunit, estradiol, and total and free testosterone and suppressed levels of luteinizing hormone and follicle-stimulating hormone. The patient underwent resection of the right upper and middle lobes of the lung. After the surgical procedure, the levels of hCG and estradiol rapidly decreased, and the gynecomastia resolved completely within 3 months. Fluctuation in the levels of serum hCG paralleled the clinical course of the lung tumor. CONCLUSION: Although gynecomastia is a common disorder, hormonal work-up including hCG beta subunit should be done in an adult male patient presenting with rapidly progressing or recent onset of painful gynecomastia. Lung cancer should be considered in the differential diagnosis of gynecomastia attributable to ectopic production of hCG beta subunit.

Carcinoma, Giant Cell↗

PubMed2000

Cytologic atypia in a 53-year-old man with finasteride-induced gynecomastia.

Finasteride has been associated with the development of gynecomastia. Although cytoplasmic vacuolization has been noted in prostatic epithelium in men taking this drug, we found no documentation of the cytologic changes in finasteride-associated gynecomastia. We present the case of a 53-year-old man who developed unilateral gynecomastia following finasteride therapy for alopecia. A fine-needle aspiration biopsy of the mass was diagnosed as adenocarcinoma on the basis of nuclear atypia and particularly because of cytoplasmic vacuolization. Subsequent excisional biopsy revealed benign gynecomastia with no evidence of malignant change. The ductal epithelium did exhibit cytoplasmic vacuolization similar to that described in the prostate following finasteride therapy. We believe this is the first reported case documenting the cytologic changes seen in gynecomastia secondary to finasteride therapy. Cytoplasmic vacuolization in this setting should not be considered evidence of malignancy in men with gynecomastia. As with gynecomastia in general, extreme caution should be used before rendering a cytologic diagnosis of malignancy.

Alopecia↗

PubMed2000

Comparison of tamoxifen with danazol in the management of idiopathic gynecomastia.

Idiopathic gynecomastia, unilateral or bilateral, is a common physical finding in normal men. Successful treatment using tamoxifen (antiestrogen) and danazol (antiandrogen) has recently been reported. We compared the efficacy of tamoxifen and danazol in the treatment of idiopathic gynecomastia. We reviewed the clinical records of patients with idiopathic gynecomastia presenting to the Department of Surgery, University of Hong Kong, between August 1990 and September 1995. Medical treatment with either tamoxifen (20 mg/d) or danazol (400 mg/d) was offered and continued until a static response was achieved. The treatment response was compared. Sixty-eight patients with idiopathic gynecomastia were seen in the Breast Clinic. The median age was 39.5 years (range, 13-82), with a median duration of symptoms of 3 months (range, 1-90). The median size was 3 cm (range, 1-7). Twenty-three patients were treated with tamoxifen and 20 with danazol. Complete resolution of the gynecomastia was recorded in 18 patients (78.2%) treated with tamoxifen, whereas only 8 patients (40%) in the danazol group had complete resolution. Five patients, all from the tamoxifen group, developed recurrence of breast mass. In conclusion, hormonal manipulation is effective in the treatment of patients with idiopathic gynecomastia. Although the effect is more marked for tamoxifen compared with danazol, the relapse rate is higher for tamoxifen. Further prospective randomized studies would be useful in defining the role of these drugs in the management of patients with idiopathic gynecomastia.

Adolescent↗

PubMed2004

Another emerging event occurring during HIV infection treated with any antiretroviral therapy: frequency and role of gynecomastia.

To identify HIV-associated episodes of gynecomastia occurred during antiretroviral therapy in a cohort of around 1,000 patients, and to investigate potential correlations with demographic and epidemiological variables, clinical-laboratory markers of HIV disease, metabolic disturbances, and antiretroviral treatment, a cross-sectional survey of 1.007 patients treated for at least 12 months (669 males: 66.4%), identified all subjects with true (ultrasonography-confirmed) gynecomastia, after exclusion of all other predisposing conditions. Special attention was paid to eventual metabolic alterations, including lipodystrophy syndrome, dyslipidemia, and hyperglycemia, and administered antiretrovirals. Fifteen of the 516 evaluable male subjects (2.9%), developed gynecomastia when aged 12-58 years. A concurrent lipodystrophy was present in all cases, while hypertriglyceridemia, hypercholesterolemia, and hyperglycemia were found in 11, 6, and 3 patients, respectively. Duration of seropositivity and time from start of antiretroviral therapy varied significantly, and no correlation was found with HIV disease progression, but 5 patients never received protease inhibitors, while an efavirenz-based treatment apparently prompted gynecomastia in 4 protease inhibitor-naive patients, and worsened this sign in other 4 patients switching from a protease inhibitor-based HAART. One patient developed gynecomastia while on isolated nucleoside analogue therapy. In the whole patient group, stavudine proved the nucleoside analogue administered more frequently and for a more prolonged time. During the follow-up, no significant ameliorament of gynecomastia was observed despite eventual therapeutic changes. Gynecomastia, as an emerging untoward event of treated HIV infection, deserves further investigation, from an epidemiological, clinical, and especially pathogenetic point of view. The frequent association with metabolic abnormalities suggests some common ethiologic pathway with other HAART-related disturbances.

Adipose Tissue↗

PubMed1998

Chromosome banding analysis of gynecomastias and breast carcinomas in men.

Male breast cancer is 100 times less frequent than its female counterpart and accounts for less than 1% of all cancers in men. Although men with breast cancer also often have gynecomastia, it is still unknown whether gynecomastia per se predisposes the male breast to malignant disease. We describe the cytogenetic analysis of three gynecomastias and four breast cancers in men. No chromosome abnormalities were detected in two cases of gynecomastia, with no other concomitant breast disease. The third gynecomastia sample, taken from a site where a breast carcinoma had previously been removed, had a t(2;11)(p24;p13) as the sole chromosome change; this is the first time that an abnormal karyotype has been described in gynecomastia. All four cancers had clonal chromosome abnormalities. Several cytogenetically unrelated clones were found in the breast tumor and in a metastasis from case 1. In the carcinoma of case 2, a single abnormal clone was found, characterized by loss of the Y chromosome, monosomy 17, and a deletion of the long arm of chromosome 18. In the carcinoma of case 3, a clone with loss of the Y chromosome as the sole change dominated, accompanied by the gain of an X chromosome in a subclone. In the lymph node metastasis examined from case 4, a single clone carrying trisomies for chromosomes 5 and 16 was detected. Our findings, especially when collated with data on the six karyotypically abnormal breast carcinomas in men described previously, indicate that gain of the X chromosome, gain of chromosome 5, loss of the Y chromosome, loss of chromosome 17, and del(18)(q21) are nonrandom abnormalities in male breast carcinomas.

Adult↗

PubMed1998

[Incidence of gynecomastia in dermatology patients].

Gynecomastia is an enlargement of the male breast. We studied a group of 115 men attending a dermatological clinic to evaluate the frequency of possible risk factors and hormonal findings. Gynecomastia was diagnosed, if a horizontal skinfold exceeded 2-3 cm, and if the diameter of the areola wa greater than 3 cm. In 32 patients (27.8%) the criteria for gynecomastia were fulfilled. The frequency increased significantly with the body mass index. 18 different medications were identified, but only two were take by more than two patients (allopurinol, coronary dilators). None of the 15 underlying diseases was associated with a significant increase or decrease in the risk of gynecomastia. Serum cortisol was the only endocrine study which was associated with an increased incidence of gynecomastia. As gynecomastia appears frequently as a phenomenon unrelated to other diseases or medications, it may be a condition per se.

Adolescent↗