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PubMed2004

Beneficial effects of raloxifene and tamoxifen in the treatment of pubertal gynecomastia.

OBJECTIVES: To assess the efficacy of the anti-estrogens tamoxifen and raloxifen in the medical management of persistent pubertal gynecomastia. STUDY DESIGN: Retrospective chart review of 38 consecutive patients with persistent pubertal gynecomastia who presented to a pediatric endocrinology clinic. Patients received reassurance alone or a 3- to 9-month course of an estrogen receptor modifier (tamoxifen or raloxifene). RESULTS: Mean (SD) age of treated subjects was 14.6 (1.5) years with gynecomastia duration of 28.3 (16.4) months. Mean reduction in breast nodule diameter was 2.1 cm (95% CI 1.7, 2.7, P <.0001) after treatment with tamoxifen and 2.5 cm (95% CI 1.7, 3.3, P <.0001) with raloxifene. Some improvement was seen in 86% of patients receiving tamoxifen and in 91% receiving raloxifene, but a greater proportion had a significant decrease (>50%) with raloxifene (86%) than tamoxifen (41%). No side effects were seen in any patients. CONCLUSION: Inhibition of estrogen receptor action in the breast appears to be safe and effective in reducing persistent pubertal gynecomastia, with a better response to raloxifene than to tamoxifen. Further study is required to determine that this is truly a treatment effect.

Adolescent↗
PubMed1999

Indications for and results of surgical therapy for male gynecomastia.

BACKGROUND: The objective of our study was to analyze factors determining diagnostic versus cosmetic indication and postoperative results in the treatment of gynecomastia. PATIENTS AND METHODS: Data from 100 patients and 141 breasts were analyzed retrospectively, and reevaluated by questionnaire (n = 81) and clinical examination (n = 33). Except for 2 patients, all underwent subcutaneous mastectomy through various incisions. RESULTS: Diagnostic surgery was exclusively performed in unilateral, nodular gynecomastia being preferentially of grade I. Higher grade, bilateral gynecomastia led mainly to cosmetic surgery. Minor complications (skin retraction, hypertrophic scars, hypesthesia, skin redundancy) occurred in 53% of patients and significantly more often in grade III or II gynecomastia. Each incision was preferentially associated with specific sequelae. However, 86% of patients were satisfied with surgical results. CONCLUSIONS: Laterality, consistency, grade, and age at onset of symptoms determine surgical indication. Despite the high number of sequelae due to preoperative grade and selected incision, most patients are satisfied with postoperative results.

Adult↗
PubMed1991

Elevated serum estradiol associated with increased androstenedione-testosterone ratio in adolescent males with varicocele and gynecomastia.

OBJECTIVE: To investigate the testicular function in adolescents with pubertal gynecomastia associated with varicocele before and after varicocelectomy. DESIGN AND PATIENTS: We have studied six male adolescents 15 to 19 years of age with bilateral gynecomastia. They were selected among other adolescents with gynecomastia because of the presence of visible varicoceles. All of them had normal physical examination and secondary sexual characteristics. This was prospective study of 3 months' duration. All the patients that were included finished the study. SETTING: All the patients were evaluated in the Endocrine Clinic of Winthrop-University Hospital, a tertiary care unit. INTERVENTION: Serum testosterone (T), androstenedione (A), and estradiol (E2) responses to the administration of human chorionic gonadotropin (hCG) 2,000 IU for 3 consecutive days before and 3 months after varicocelectomy were determined. RESULTS: Varicocelectomy did not cause any significant changes in the basal (pre-hCG) levels of the steroid. However, the increase in T levels achieved with hCG was significantly (P less than 0.005) higher after varicocelectomy (before T, 925 +/- 212 ng%; after T, 1,649 +/- 406 ng%). Simultaneously, the stimulated levels of E2 and A were significantly lower (P less than 0.005) after varicocelectomy (E2, 62 +/- 12 pg/mL; A, 326 ng% +/- 80 ng%) than before (E2, 106 +/- 13 pg/mL; A, 580 ng% +/- 95 ng%). CONCLUSION: The reciprocal effect on the levels of T and its immediate precursor, A, suggests an impairment of the 17-ketoreductase enzyme activity. The increased levels of E2 after hCG and its normalization after varicocelectomy suggests that varicoceles may play a pathogenetic role in the development of gynecomastia.

Adolescent↗
PubMed2001

Measurement of androgen and estrogen receptors in breast tissue from subjects with anabolic steroid-dependent gynecomastia.

In order to assess the relationship between anabolic steroid administration and gynecomastia, we studied the effects produced by administering nandrolone decanoate and a mixture of propionate, phenilpropionate, isocaproate and testosterone decanoate to bodybuilders during a six month period. The following significant changes occurred: a 53% reduction in serum testosterone; LH and FSH levels were suppressed to 77% and 87%, respectively, in comparison to control values; and although 45% of the subjects showed an increase in serum estradiol levels, no statistically significant differences were found compared with control estradiol levels. With regard to estradiol and androgen receptors, 85% of gynecomastia tissue contained estradiol or androgen receptors, while 40% contained both. The mean values of estradiol and androgen receptors in the cytosol were 65 +/- 10 and 52 +/- 5 fmol/mg protein, respectively. Nuclear androgen and estradiol receptor levels were 33 +/- 7 and 67.5 +/- 9 fmol/mg protein, respectively. The presence of hormone receptors in gynecomastia receptive cells provides support for the hypothesis that gynecomastia is steroid-dependent.

Adult↗
PubMed1997

Tamoxifen for flutamide/finasteride-induced gynecomastia.

OBJECTIVES: Current therapies for advanced prostate carcinoma lead to a marked decrease in serum testosterone levels, which renders patients impotent. In preliminary studies, combination therapy with flutamide and finasteride has been used as an alternative therapy for the treatment of prostate carcinoma because potency can be preserved. Both of these agents can cause gynecomastia and breast/nipple tenderness. METHODS: Six men being treated for advanced prostate carcinoma with flutamide/finasteride combination therapy developed painful gynecomastia, which was treated with tamoxifen 10 to 30 mg/day for 1 month. Clinical follow-up included breast measurements and determination of prostate-specific antigen (PSA), testosterone, and estradiol levels. RESULTS: While on this combination therapy for prostate carcinoma, 4 of 6 patients experienced a decrease in PSA level to less than 0.5 ng/mL. All patients remained potent. Serum testosterone increased in each patient who had a baseline level drawn. Estradiol levels were noted to be elevated in 4 of 6 patients at the time of evaluation for gynecomastia. After treatment with tamoxifen, circulating estradiol levels increased in 3 patients from 1.3 to 2.2 times the baseline level. Five patients experienced complete resolution of breast and nipple pain on tamoxifen 10 mg/day within the first month. The other patient had to be treated with 30 mg/day for 1 additional month, which subsequently resulted in pain resolution. CONCLUSIONS: These preliminary results suggest that low-dose tamoxifen is useful in treating painful gynecomastia for those patients on flutamide/finasteride combination therapy for advanced prostate carcinoma.

Aged↗
PubMed2000

Trisomy 4 in a case of gynecomastia.

Gynecomastia is an anomaly associated with alterations in the levels of hormones, especially estrogens. Sufferers of gynecomastia present a high risk of developing carcinomas. Only two cytogenetic descriptions of this type of mammary proliferation are available. In the present study, we analyzed chromosomally a sample of breast tissue from a patient with gynecomastia following short-term culture. The only clonal chromosomal alteration encountered was trisomy of chromosome 4. This alteration has not been described previously for samples of gynecomastia or breast cancer in males. We believe that the alterations in hormone levels in the male breast tissue that lead to this type of cellular proliferation induce the formation of chromosomal abnormalities, making the cells more susceptible to becoming malignant.

Adult↗
PubMed1978

Gynecomastia and gonadal dysfunction in adolescent boys treated with combination chemotherapy for Hodgkin's disease.

We studied 19 Ugandan boys with Hodgkin's disease who had been treated with mechlorethamine, vincristine, procarbazine and prednisone and who survived at least two years to assess testicular germ-cell depletion in pubescent boys on combination chemotherapy, as had previously been demonstrated in sexually mature men. Nine of 13 pubertal boys (ages 11 to 16) had moderate to severe gynecomastia and germinal aplasia, a 10-fold increase in mean (+/- S.D.) serum follicle-stimulating hormone (34.8 +/- 20.5 mlU per milliliter), a threefold increase in mean luteinizing hormone (17.8 +/- 9.8 mlU per milliliter) and reduced serum testosterone levels. Gynecomastia was not associated with an increase in either serum estradiol or prolactin concentrations. By contrast, six prepubertal boys (three to 10 years of age), similarly treated, showed no change in serum gonadotropins, and gynecomastia did not develop. The data confirm germ-cell depletion after combination chemotherapy and indicate further that Leydig-cell dysfunction, manifested by gynecomastia, may be a consequence of treatment in adolescent boys.

Adolescent↗
PubMed1993

Male hypogonadism with gynecomastia caused by late-onset deficiency of testicular 17-ketosteroid reductase.

BACKGROUND: 17-Ketosteroid reductase deficiency results in male pseudohermaphroditism because conversion of the weak androgen androstenedione to the more potent androgen testosterone is impaired. If a late-onset form exists, hypogonadism and gynecomastia caused by decreased testosterone production and increased estrogen production, respectively, would be expected as the major clinical manifestations in men. METHODS: We studied 48 male subjects, ranging from 14 to 26 years of age, who had idiopathic pubertal gynecomastia. Serum concentrations of gonadal and adrenal steroid hormones were measured before and after the administration of corticotropin and after the combined administration of chorionic gonadotropin and dexamethasone for three days. RESULTS: We identified three unrelated subjects (ages, 16, 17, and 26 years) with results indicative of a partial deficiency of testicular 17-ketosteroid reductase. The three subjects had gynecomastia as well as decreased libido and impotence. Their mean (+/- SD) base-line serum androstenedione and estrone concentrations were elevated as compared with the levels in the 45 subjects without this enzyme deficiency (androstenedione, 380 +/- 70 vs. 110 +/- 70 ng per deciliter [13 +/- 2 vs. 4 +/- 2 nmol per liter]; estrone, 138 +/- 12 vs. 46 +/- 9 pg per milliliter [511 +/- 44 vs. 170 +/- 33 pmol per liter]). After the administration of chorionic gonadotropin, the mean serum androstenedione concentration in these three subjects was 910 +/- 48 ng per deciliter (32 +/- 2 nmol per liter) and the mean serum estrone concentration was 260 +/- 16 pg per milliliter (962 +/- 59 pmol per liter). The mean serum testosterone concentration at base line was 210 +/- 80 ng per deciliter (7.4 +/- 2.8 nmol per liter) in the 3 subjects, as compared with a value of 410 +/- 12 ng per deciliter (14.4 +/- 0.42 nmol per liter) in the 45 other subjects, and it did not increase in response to the administration of chorionic gonadotropin. The concentrations of androstenedione and estrone in spermatic venous serum were 19 times higher and 73 times higher, respectively, than in normal men. The serum concentrations of follicle-stimulating hormone and luteinizing hormone in these three subjects were inappropriately low, suggesting the presence of hypogonadotropic hypogonadism. CONCLUSIONS: A late-onset form of testicular 17-ketosteroid reductase deficiency can cause gynecomastia and hypogonadism in men.

17-Hydroxysteroid Dehydrogenases↗
PubMed1983

Prepubertal gynecomastia with lobules and acini: a case report and review of the literature.

The case of an 11-year-old boy with prepubertal gynecomastia is presented. Endocrine workup, including sex steroid and pituitary hormone concentrations, as well as chromosome analysis, was normal. Microscopy of the mastectomy specimen demonstrated, in addition to ductal proliferation and fibrosis, formation of lobules and acini, simulating female breast tissue. The authors report the fourth case with this histologic feature. Review of the literature identified 41 cases of prepubertal gynecomastia; associated or underlying conditions were: adrenal adenoma or carcinoma in nine cases, testicular tumor in two, 11-beta-hydroxylase deficiency in four, familial gynecomastia in two, tuberous sclerosis in two, and, in part overlapping, sexual precocity in four. Gynecomastia usually regressed after tumor removal or cortisol replacement therapy. Histologic examination of breast tissue was performed in 18 cases. Lobule and acinus formation was described in only three.

Breast↗
PubMed1991

Potential use of monoclonal antibodies in the diagnostic distinction of gynecomastia from breast carcinoma in men.

Immunohistochemical (IHC) assays using the monoclonal antibodies (MoAbs) B72.3 and B6.2, recognizing two distinct and independently expressed breast tumor-associated antigens (BTAAs), recently have been shown to significantly improve the accuracy of cytodiagnosis of breast nodules by fine-needle aspiration (FNA). To evaluate whether the same method may be useful diagnostically in distinguishing gynecomastia from breast cancer in men, a retrospective avidin-biotin immunoperoxidase assay study was performed on 50 cases of gynecomastia and 30 cases of breast carcinoma in men, using a panel of five MoAbs known to recognize different BTAAs. The results of this study demonstrated that MoAbs B1.1, HMFG2, and MBr1 displayed a strong reactivity with gynecomastia and carcinoma, but MoAbs B72.3 and B6.2 separated benign and malignant lesions in a high percentage of cases. When used in combination, the latter two reagents reacted with 96% of the carcinomas that were analyzed but labeled only 67% of gynecomastia cases. Thus, the conjoint use of these two reagents may enhance the use of FNA biopsy as a valuable tool in the presurgical diagnosis of breast nodules in men.

Adolescent↗
PubMed2000

Estrogen and progesterone receptors in gynecomastia.

The etiology of gynecomastia is unknown. There seems to be no increased incidence of malignancies in patients with idiopathic gynecomastia; however, patients with Klinefelter syndrome exhibit an increased incidence of malignancy. The authors reviewed the results of 34 patients with gynecomastia diagnosed in adolescence who, following initial evaluation, had a mastectomy. The estrogen and progesterone receptors were analyzed in these patients. Three of the patients were diagnosed with Klinefelter syndrome. These three patients exhibited elevated amounts of estrogen and progesterone receptors. None of the patients who were not diagnosed with this syndrome demonstrated significant elevation of their estrogen or progesterone receptors. The presence of elevated estrogen and progesterone receptors in patients with Klinefelter syndrome provides a potential mechanism by which these patients may develop breast neoplasms. The absence of elevated estrogen and progesterone receptors in patients with idiopathic gynecomastia may serve to clarify why these patients' disease rarely degenerates into malignancy.

Adolescent↗
PubMed2001

Gynecomastia and the complete circumareolar approach in the surgical management of skin redundancy.

Gynecomastia is a benign enlargement of the male breast due to a physiological or pathological factor that interferes with the balance between estrogens and androgens in the serum. Gynecomastia itself requires no treatment unless the persistent enlargement of the male breast is a source of embarrassment and/or distress for the adolescent or adult man. The indications for the surgical treatment of gynecomastia are founded on two main objectives: (1) the restoration of male chest shape and (2) diagnostic evaluation of suspected breast lesions. The diagnostic evaluation begins with an adequate history and a thorough breast examination helped by laboratory tests and instrumental research. Several approaches for surgical treatment have been described in the literature. Some problems arise in patients who have significant enlargement and ptosis of the breast that will require skin reduction and in some patients requiring nipple-areola complex reduction. The authors believe that the complete circumareolar technique with purse-string suture creates the best aesthetic results, with fewer complications, in patients with moderate and severe ptotic glandular breast enlargements that have skin redundancy combined with areolar enlargement. From 1995 through 1999, a total of 10 male patients with moderate to severe gynecomastia were treated surgically using a complete circumareolar approach. All patients achieved a good aesthetic contour of the chest. Only two patients required a revision of the circumareolar scar to correct postoperative enlargement.

Adolescent↗
PubMed2004

Gynecomastia: an outcome analysis.

BACKGROUND: Gynecomastia refers to the presence of femalelike mammary glands in a male. This disorder can lead to significant psychologic stress and self-consciousness. This study consists of a chart review of 174 patients treated surgically between July 1, 1976, and February 27, 2001. RESULTS: Operative procedures were excision, excision with suction-assisted lipectomy (SAL), SAL, skin excision (skin) and skin excision with SAL. Overall complication rate was 20%. No significant difference in complication rates was found between grades or procedures. Revision rates between grades were I = 10.3%, II = 14.5% and III = 34.8% (P < 0.001). In grade III, gynecomastia revision rates for excision +/- SAL was 29% and skin +/- SAL was 38.1% (P = 0.644). Of the 8 revisions in the skin-sparing procedures, 6 were revised with a scar-forming procedure. Therefore, 77% of patients with grade III gynecomastia were adequately treated with a skin-sparing procedure. CONCLUSION: Skin-sparing operations should be the initial procedure chosen for most grade III gynecomastia patients.

Adolescent↗
PubMed2006

Lighted retractor-assisted transaxillary approach in gynecomastia correction.

Gynecomastia is an excessive development of the male breast. Surgery is the accepted standard method for treatment. In our department, 5 male patients ranging in age from 18 to 24 years who had grade I-IIA-IIB gynecomastia according to Simon's classification were operated on with a lighted retractor-assisted transaxillary approach. Dissection, excision, and hemostasis were performed under direct vision by using the lighted retractor. The glands and adjacent fat were removed en bloc. The axillary scar was barely visible. The patients were satisfied with the results. Gynecomastia correction with a lighted retractor-assisted transaxillary approach is feasible for those who have grade I-IIA-IIB gynecomastia according to Simon's classification and also for those who do not want to have scars on their breasts' esthetic units and have a tendency towards keloid formation. Scars can be kept in the hidden area, with no considerable complication. The lighted retractor facilitates the transaxillary approach and provides appropriate dissection, excision, and hemostasis.

Adolescent↗
PubMedDate not supplied

Efavirenz-associated gynecomastia: report of five cases and review of the literature.

The prognosis of HIV infection has improved dramatically since the introduction of highly active antiretroviral therapy (HAART). However, numerous adverse effects and limitations regarding tolerability remain a concern. Lipomastia (pseudogynecomastia), a breast enlargement due to central adiposity, may occur as part of a fat redistribution syndrome which has been associated with HAART regimens and several pathogenic mechanisms have been advocated in its development. Here we report an observational longitudinal study of five patients diagnosed of gynecomastia associated with efavirenz-based HAART regimens. All cases reached successful immunologic and virologic responses to HAART. The delay of appearance of gynecomastia from the beginning of HAART ranged between 4 to 15 months. In all five cases, gynecomastia regressed after efavirenz withdrawal (mean period of 5 months). In summary, we think that HAART induced gynecomastia should be suspected in HIV patients receiving efavirenz-containing regimens. Although pathogenesis is unclear, this study and a review of the English literature implicates two possible mechanisms: (a) immune restoration processes and (b) efavirenz mediated estradiol-like effects.

Adult↗
PubMed1985

Familial gynecomastia with increased extraglandular aromatization of plasma carbon19-steroids.

We evaluated a family in which gynecomastia occurred in five males in two generations. In each affected subject, gynecomastia and male sexual maturation began at an early age. The ratio of the concentration of plasma estradiol-17 beta to that of plasma testosterone was elevated in each affected subject. In the three siblings with gynecomastia, the transfer constant of conversion of androstenedione to estrone (i.e., the fraction of plasma androstenedione that was converted to estrone as measured in the urine) was 10 times that of normal persons. The transfer constant of conversion of testosterone to estradiol-17 beta in the one subject studied also was 8-10 times that of normal men, whereas the transfer constants of conversion of estrone to estradiol-17 beta and of estradiol-17 beta to estrone were normal. Despite the elevation in extraglandular aromatase activity, there was a normal response of the hypothalamic-pituitary axis to provocative stimuli. This is the second documentation of gynecomastia that is associated with increased extraglandular aromatase activity, and the first time that the defect was found to be familial with a probable X-linked (or autosomal dominant, sex limited) mode of inheritance.

Adolescent↗
PubMed2005

Evaluation of tamoxifen and anastrozole in the prevention of gynecomastia and breast pain induced by bicalutamide monotherapy of prostate cancer.

PURPOSE: To determine whether tamoxifen or anastrozole prevents gynecomastia and breast pain caused by bicalutamide (150 mg) without compromising efficacy, safety, or sexual functioning. PATIENTS AND METHODS: A double-blind, placebo-controlled trial was performed in patients with localized, locally advanced, or biochemically recurrent prostate cancer. Patients (N = 114) were randomly assigned to either bicalutamide (150 mg/d) plus placebo or in combination with tamoxifen (20 mg/d) or anastrozole (1 mg/d) for 48 weeks. Gynecomastia, breast pain, prostate-specific antigen (PSA), sexual functioning, and serum levels of hormones were assessed. RESULTS: Gynecomastia developed in 73% of patients in the bicalutamide group, 10% of patients in the bicalutamide-tamoxifen group, and 51% of patients in the bicalutamide-anastrozole group (P < .001); breast pain developed in 39%, 6%, and 27% of patients, respectively (P = .006). Baseline PSA level decreased by > or = 50% in 97%, 97%, and 83% of patients in the bicalutamide, bicalutamide-tamoxifen, and bicalutamide-anastrozole groups, respectively (P = .07); and adverse events were reported in 37%, 35%, and 69% of patients, respectively (P = .004). There were no major differences among treatments in sexual functioning parameters from baseline to month 6. Elevated testosterone levels occurred in each group; however, free testosterone levels remained unchanged in the bicalutamide-tamoxifen group because of increased sex hormone-binding globulin levels. CONCLUSION: Anastrozole did not significantly reduce the incidence of bicalutamide-induced gynecomastia and breast pain. In contrast, tamoxifen was effective, without increasing adverse events, at least in the short-term follow-up. These data support the need for a larger study to determine any effect on mortality.

Aged↗
PubMed2004

Safety and efficacy of anastrozole for the treatment of pubertal gynecomastia: a randomized, double-blind, placebo-controlled trial.

Pubertal gynecomastia is thought to result from transient imbalances between estrogen and androgen concentrations. Anastrozole (ARIMIDEX), a potent and selective aromatase inhibitor, decreases estrogen and increases testosterone concentrations in pubertal boys. The safety and efficacy of anastrozole for the treatment of pubertal gynecomastia were evaluated. In a randomized, double-blind, placebo-controlled study of 80 boys, aged 11-18 yr, with pubertal gynecomastia that had not reduced over a 3-month interval, subjects received either anastrozole (1 mg) or placebo once daily for 6 months. A response was defined as a 50% or greater reduction in the calculated volume of both breasts combined using ultrasonography measurements. A comparison of response rates was performed using logistic regression analysis. Secondary end points included changes in serum hormone concentrations. The percentage of patients with a response was 38.5% for the anastrozole group and 31.4% for the placebo group (odds ratio, 1.513; 95% confidence interval, 0.496-4.844; P = 0.47). At 6 months, the median percent change in the testosterone/estradiol ratio was 166% for the anastrozole group and 39% for the placebo group. Anastrozole treatment was well tolerated. In patients with pubertal gynecomastia, no significant difference in the percentage of patients with a 50% or greater reduction in total breast volume, as calculated from ultrasonography measurements, was demonstrated between the anastrozole and placebo groups.

Adolescent↗