Sarah E Lawrence, K Arnold Faught, Jennifer Vethamuthu, Margaret L Lawson
Beneficial effects of raloxifene and tamoxifen in the treatment of pubertal gynecomastia.
J Pediatr. 2004 Jul;145(1):71-6. doi: 10.1016/j.jpeds.2004.03.057.
Abstract/Text
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.
L N Parker, D R Gray, M K Lai, E R Levin
Treatment of gynecomastia with tamoxifen: a double-blind crossover study.
Metabolism. 1986 Aug;35(8):705-8.
Abstract/Text
Benign asymptomatic or painful enlargement of the male breast is a common problem, postulated to be due to an increased estrogen/testosterone ration or due to increased estrogenic or decreased androgenic stimulation via estrogen or androgen receptor interactions. Treatment at present consists of analgesic medication or surgery. However, treatment directed against the preponderance of estrogenic stimulation would seem to represent a more specific form of therapy. In the present double-blind crossover study, one-month courses of a placebo or the antiestrogen tamoxifen (10 mg given orally bid) were compared in random order. Seven of ten patients experienced a decrease in the size of their gynecomastia due to tamoxifen (P less than 0.005). Overall, the decrease for gynecomastia for the whole group was significant (P less than 0.01). There was no beneficial effect of placebo (P greater than 0.1). Additionally, all four patients with painful gynecomastia experienced symptomatic relief. There was no toxicity. The reduction of breast size was partial and may indicate the need for a longer course of therapy. A followup examination was performed in eight out of ten patients nine months to one year after discontinuing placebo and tamoxifen. There were no significant changes from the end of the initial study period except for one tamoxifen responder who developed a recurrence of breast tenderness after six months, and one nonresponder who demonstrated an increase in breast size and a new onset of tenderness after ten months. Therefore, antiestrogenic treatment with tamoxifen may represent a safe and effective mode of treatment for selected cases of cosmetically disturbing or painful gynecomastia.
M T McDermott, F D Hofeldt, G S Kidd
Tamoxifen therapy for painful idiopathic gynecomastia.
South Med J. 1990 Nov;83(11):1283-5.
Abstract/Text
We have evaluated the efficacy of the antiestrogen tamoxifen in six men with painful idiopathic gynecomastia. Subjects were given either tamoxifen or placebo for 2 to 4 months and then were given the other agent for an identical period. Breast size was considered to have been reduced only if it had decreased by one or more Marshall-Tanner stages during the treatment period. Pain reduction with tamoxifen therapy was statistically significant for the group, occurring in five of six subjects during tamoxifen treatment and in only one of six during the placebo period. Size reduction with tamoxifen was only marginally significant for the entire group, but occurred in all three subjects who were initially in Marshall-Tanner stage III and in none of the three subjects who were initially in stage V. During tamoxifen treatment, there was a significant increase in the serum levels of luteinizing hormone and total estradiol and a marginally significant increment in the total testosterone level.
Paul V Plourde, Edward O Reiter, Hann-Chang Jou, Paul E Desrochers, Stephen D Rubin, Barry B Bercu, Frank B Diamond, Philippe F Backeljauw
Safety and efficacy of anastrozole for the treatment of pubertal gynecomastia: a randomized, double-blind, placebo-controlled trial.
J Clin Endocrinol Metab. 2004 Sep;89(9):4428-33. doi: 10.1210/jc.2004-0082.
Abstract/Text
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.
A C Ting, L W Chow, Y F Leung
Comparison of tamoxifen with danazol in the management of idiopathic gynecomastia.
Am Surg. 2000 Jan;66(1):38-40.
Abstract/Text
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.
Adriana Cordova, Francesco Moschella
Algorithm for clinical evaluation and surgical treatment of gynaecomastia.
J Plast Reconstr Aesthet Surg. 2008;61(1):41-9. doi: 10.1016/j.bjps.2007.09.033. Epub 2007 Nov 5.
Abstract/Text
BACKGROUND: Gynaecomastia can be classified on the basis of the main characterising factors, i.e. pathogenesis, histopathology and morphology. The morphological classifications of gynaecomastia currently made often use subjective parameters and qualifying adjectives. In this paper the authors propose a scheme for morphological classification of gynaecomastia which can serve as a guide for choosing the surgical technique, once the diagnosis of gynaecomastia as a benign pathology has been confirmed by preoperative examinations.
METHODS: A retrospective analysis was made of 121 cases of gynaecomastia operated on in the last 5 years. The extent of the clinical picture, the technique employed, the complications and the need to re-operate were observed and related.
RESULTS: On the basis of this review the authors observed that when the nipple-areola complex is above the inframammary fold (grade I and grade II gynaecomastia), complete flattening of the thorax can be achieved by means of suction or ultrasound-assisted lipectomy and skin-sparing adenectomy. When the nipple-areola complex is at the same height as, or at most 1cm below the fold (grade III gynaecomastia), skin-sparing techniques are no longer sufficient to flatten the thorax, and it becomes necessary to remove the redundant skin by means of periareolar removal of epidermis. In cases of marked ptosis, when the nipple-areola complex is more than 1cm below the fold (grade IV gynaecomastia), reduction mastoplasty becomes necessary, with upper repositioning of the nipple-areola complex; in these cases central pedicle techniques make it possible to limit scarring in the periareolar areas.
CONCLUSIONS: In the preoperative phase this simple classification may help in choosing the most suitable treatment, thus avoiding insufficient or invasive treatments and undesirable scars.
Maria Antonietta Gioffrè Florio, Alessandro Russo Alfio, Fausto Famà, Giuseppa Giacobbe, Andrea Pollicino, Paola Scarfò
[Evaluation of complications and long-term results after surgery for gynaecomastia].
Chir Ital. 2004 Jan-Feb;56(1):113-6.
Abstract/Text
In an attempt to evaluate ten years of surgical treatment of gynaecomastia, we analysed the incidence of complications and the quality of the results in a group of patients classified according to Simon. Over the decade 1992-2002, 107 patients with gynaecomastia aged from 17 to 79 years were treated. The prevalent surgical approach was subcutaneous mastectomy. In 71 patients the surgical approach was via a periareolar inferior incision, superior in 15, inferior with bilateral extensions in 10; using a complete circumareolar approach (according to Padron) in 8 patients and a subcutaneous transareolar mastectomy in 3. No immediate complications were observed. Ten patients presented a modest postoperative haematoma. Only in one diabetic patient with chronic bronchitis and grade III gynaecomastia did partial dehiscence of the surgical wound occur. Most patients achieved good results. We judged the results excellent in 94 patients, good in 11, and unsatisfactory in 2. On the basis of our experience and in agreement with the literature data, we can affirm that the best results were obtained by subcutaneous mastectomy with a periareolar incision.
D J Jones, S D Holt, P Surtees, D J Davison, M J Coptcoat
A comparison of danazol and placebo in the treatment of adult idiopathic gynaecomastia: results of a prospective study in 55 patients.
Ann R Coll Surg Engl. 1990 Sep;72(5):296-8.
Abstract/Text
In an attempt to define the efficacy of danazol in the treatment of idiopathic gynaecomastia, 55 patients were enrolled into a randomised double-blind comparison of danazol 200 mg twice daily for 3 months against placebo. The results of 52 patients were evaluated, three patients being excluded because of protocol violations. Danazol improved breast tenderness to a significantly greater degree than did placebo (P = 0.022, danazol vs placebo) and was associated with statistically significant improvement in the degree of gynaecomastia and in its measured size (P less than 0.05). The intended management of patients who had received danazol was less likely to be surgery compared to the placebo group when assessed at the end of treatment (27% vs 50%). Minor side effects were common in both groups, but significant weight gain was noted in the danazol group alone. If there is no urgent need for rapid resolution of gynaecomastia, danazol 200 mg twice daily can provide effective control of symptoms and may obviate the need for surgery.
F Boccardo, A Rubagotti, M Battaglia, P Di Tonno, F P Selvaggi, G Conti, G Comeri, A Bertaccini, G Martorana, P Galassi, F Zattoni, A Macchiarella, A Siragusa, G Muscas, F Durand, D Potenzoni, A Manganelli, V Ferraris, F Montefiore
Evaluation of tamoxifen and anastrozole in the prevention of gynecomastia and breast pain induced by bicalutamide monotherapy of prostate cancer.
J Clin Oncol. 2005 Feb 1;23(4):808-15. doi: 10.1200/JCO.2005.12.013.
Abstract/Text
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.
Davide Bedognetti, Alessandra Rubagotti, Giario Conti, Francesco Francesca, Ottavio De Cobelli, Luca Canclini, Michele Gallucci, Francesco Aragona, Pasquale Di Tonno, Pietro Cortellini, Giuseppe Martorana, Alberto Lapini, Francesco Boccardo
An open, randomised, multicentre, phase 3 trial comparing the efficacy of two tamoxifen schedules in preventing gynaecomastia induced by bicalutamide monotherapy in prostate cancer patients.
Eur Urol. 2010 Feb;57(2):238-45. doi: 10.1016/j.eururo.2009.05.019. Epub 2009 May 19.
Abstract/Text
BACKGROUND: Bicalutamide monotherapy is a valuable option for prostate cancer (PCa) patients who wish to avoid the consequences of androgen deprivation; however, this treatment induces gynaecomastia and mastalgia in most patients. Tamoxifen is safe and effective in preventing breast events induced by bicalutamide monotherapy without affecting antitumor activity, but possible interference between bicalutamide and tamoxifen remains a matter of concern. To reduce the exposure to tamoxifen, we considered the putative advantages of weekly administration.
OBJECTIVE: To compare the efficacy of two different schedules of tamoxifen in preventing breast events. Toxicity, prostate-specific antigen behaviour, and sexual-functioning scores were also evaluated.
DESIGN, SETTING, AND PARTICIPANTS: This was a noninferiority trial. From December 2003 to February 2006, 80 patients with localised/locally advanced or biochemically recurrent PCa who were also candidates for bicalutamide single therapy were randomised to receive two different schedules of tamoxifen: daily (n=41) and weekly (n=39). Median follow-up was 24.2 mo.
INTERVENTION: Daily bicalutamide (150 mg) plus daily tamoxifen 20mg continuously (daily group) or the same but with tamoxifen at 20mg weekly after the first 8 wk of daily treatment (weekly group). Three patients in the weekly group and one in the daily group were discontinued for adverse events.
MEASUREMENTS: For gynaecomastia, we used ultrasonography. For mastalgia and sexual functioning, we used questionnaires.
RESULTS AND LIMITATIONS: Gynaecomastia developed in 31.7% of patients in the daily group and in 74.4% of patients in the weekly group (p<0.0001), and it was more severe in patients who switched to weekly tamoxifen (p=0.001). Mastalgia occurred in 12.2% and 46.1% of patients, respectively (p=0.001). There were no major differences among treatment schedules relative to sexual functioning scores and incidence and severity of adverse events. No differences between groups in PSA behaviour and disease progression have been detected so far.
CONCLUSIONS: This study demonstrated that tamoxifen 20mg/wk is inferior to tamoxifen 20mg/d in preventing the incidence and severity of bicalutamide-induced breast events. The safety and efficacy of tamoxifen at the common daily dose of 20mg for the prophylaxis of bicalutamide-induced breast events were confirmed.
Copyright 2009 European Association of Urology. Published by Elsevier B.V. All rights reserved.
Yves Fradet, Blair Egerdie, Morten Andersen, Teuvo L J Tammela, Mahmoud Nachabe, Jon Armstrong, Thomas Morris, Sunil Navani
Tamoxifen as prophylaxis for prevention of gynaecomastia and breast pain associated with bicalutamide 150 mg monotherapy in patients with prostate cancer: a randomised, placebo-controlled, dose-response study.
Eur Urol. 2007 Jul;52(1):106-14. doi: 10.1016/j.eururo.2007.01.031. Epub 2007 Jan 16.
Abstract/Text
OBJECTIVE: To define the optimum tamoxifen dose for reducing bicalutamide (CASODEX) 150 mg monotherapy-induced breast events (ie, gynaecomastia or breast pain or both) without compromising disease control.
METHODS: This was a double-blind, parallel-group, multicentre trial in which 282 patients with prostate cancer were randomised to receive bicalutamide 150 mg/d plus either daily tamoxifen (1, 2.5, 5, 10, or 20mg) or placebo for 12 mo, followed by 12 mo of treatment with bicalutamide only. Primary end points were incidence of breast events and prostate-specific antigen (PSA) inhibition and were analysed at 6 mo (the primary analysis) and also at 12 and 24 mo.
RESULTS: At 6 and 12 mo, tamoxifen decreased the incidence of breast events in a dose-dependent manner, with breast events observed in 86.2%, 60.0%, 55.3%, 23.5%, and 8.8% of patients receiving tamoxifen 1, 2.5, 5, 10, and 20 mg, respectively, compared with 96.7% of patients receiving placebo at 6 mo. At 24 mo (ie, after 12 mo of bicalutamide monotherapy), a high incidence of breast events was seen in all groups. There was no evidence of a negative effect on PSA inhibition at any assessment. Other nonbreast adverse effects were similar across groups, except for an increase in hot flushes with tamoxifen doses > or =5 mg.
CONCLUSION: These findings suggest that prophylactic tamoxifen 20 mg/d is an effective dose for reduction of bicalutamide-induced breast events and does not appear to affect disease control based on PSA suppression.
良性疾患の放射線治療ガイドライン 日本放射線腫瘍学会.
D M O'Hanlon, P Kent, M J Kerin, H F Given
Unilateral breast masses in men over 40: a diagnostic dilemma.
Am J Surg. 1995 Jul;170(1):24-6.
Abstract/Text
BACKGROUND: Breast enlargement in men is a common condition with advancing age. The main problem in this age group is to differentiate gynecomastia or benign enlargement from carcinoma.
PATIENTS AND METHODS: Over a 14-year period, 60 patients > or = 40 years old were operated on four unilateral breast masses (11 carcinoma, 49 gynecomastia) at the University College Hospital, Galway, Ireland. The medical records of these patients were reviewed and data were collected from patients' charts and histopathology records.
RESULTS: Patients with carcinoma delayed significantly longer before presentation than patients with gynecomastia, a median of 33 versus 3.4 months, respectively. A lump was the presenting complaint in patients with carcinoma unless the disease was advanced. Patients with gynecomastia were more likely to present with pain; and the majority of these patients described tenderness on clinical examination. A history of carcinoma (18% and 0%) or a family history of breast carcinoma (36% and 14%) was more common in the patients with carcinoma than in those with gynecomastia, respectively (P < 0.05; P = NS, respectively). Histories of consuming alcohol and smoking cigarettes were more common in those with gynecomastia (67% and 43%) than in those with carcinoma (55% and 18%). A similar proportion of patients in both groups were taking drugs known or suspected to cause gynecomastia (29% and 27%).
CONCLUSIONS: Carcinoma must be excluded in patients presenting with unilateral breast masses, particularly in those patients who present with painless masses. Clues to the diagnosis are provided by a history of carcinoma or a family history of breast carcinoma. A history of consumption of drugs known to cause gynecomastia should not influence the decision to perform a biopsy on unilateral breast masses in older men.
Oren Lapid, Folkert Jolink, Sybren L Meijer
Pathological findings in gynecomastia: analysis of 5113 breasts.
Ann Plast Surg. 2015 Feb;74(2):163-6. doi: 10.1097/SAP.0b013e3182920aed.
Abstract/Text
OBJECTIVE: This study aimed to analyze the histopathology results of surgically excised breast specimens with the diagnosis of gynecomastia (GM).
SUMMARY BACKGROUND DATA: Gynecomastia is a term used to describe benign hypertrophy of the breast in men; it is a common, mostly transient, phenomenon in adolescents, but may also be seen in older men. Breast enlargement can lead to psychological problems; if it persists it can be surgically corrected. The obtained breast tissue specimens are routinely submitted for pathological examination. We performed this study to assess the prevalence of pathological findings after surgical management of GM.
METHODS: Pathology reports were obtained from the nationwide network and registry of histopathology and cytopathology in the Netherlands (PALGA). The reports of 5113 breasts were analyzed for the prevalence of pathologies in different age groups.
RESULTS: The average age of the patients was 35.3 ± 18.3 years (range, 1-88 years). The most common finding was GM followed by pseudo-GM. The overall prevalence of invasive carcinomas was 0.11% and of in situ carcinomas was 0.18%. The youngest patient with invasive cancer was 65 years old and the youngest patient with carcinoma in situ was 24 years old. The overall prevalence of atypical ductal hyperplasia was 0.4%; in patients younger than 20 years, it was 0.23%. The youngest patient with atypical ductal hyperplasia was 16 years old. Pathological findings were found more often in unilateral procedures.
CONCLUSIONS: The prevalence of malignancies in GM resection specimens is low; however, it increases with patient age. Unilateral cases have a statistically nonsignificant higher prevalence of pathologies.
LEVEL OF EVIDENCE: Prognostic/risk II.
