- Email: [email protected]
Current concepts in gynaecomastia
review H. L. Devalia1 G. T. Layer2 1
Royal Surrey County Hospital NHS Trust and University of Surrey, Egerton Road, Guildford GU2 7XX 2 Postgraduate medical school, University of Surrey Correspondence to: Mr Haresh Devalia 35 Fairway, Raynes Park, London SW20 9DN Tel: +44(0)7789773974 Fax: +44(0)2085421897 Email: hareshdevalia@doctors. org.uk
CURRENT CONCEPTS IN GYNAECOMASTIA Gynaecomastia is a common breast condition. Each case merits a careful and complete history, with thorough examination and investigations being required in selected patients with progressive disease or suspected sinister pathology. Treatment is usually indicated for any underlying cause, associated symptoms and the gynaecomastia itself. Treatment may be either medical or surgical but must be individualised. Medical treatment may be especially advocated in the symptomatic group. The indications for surgery include failure of medical treatment, intolerable side-effects of necessary drugs, malignancy, small lesions which cause signicant distress and patients with large and ptotic gynaecomastia. A careful programme of counselling, pre-operatively in particular, may help to minimise litigation. keywords: gynaecomastia, tamoxifen, danazol Surgeon, 1 April 2009, pp. 114-19
Introduction Gynaecomastia is usually a benign enlargement of the male breast. The term is derived from the Greek words ‘gyne’ meaning woman and ‘mastos’ meaning breast.1 In some cases it may be due to an imbalance between circulating oestrogens and androgens in the blood, but the aetiology is broad and varied. It may be seen as either ‘true’ or ‘pseudo’ gynaecomastia or a combination of both. True gynaecomastia indicates enlargement of male breast glandular tissue, whilst pseudo-gynaecomastia represents excessive adipose tissue. Clinically it may be either unilateral or bilateral, giving an indication of local or systemic underlying pathology.
Prevalence Asymptomatic palpable gynaecomastia is a common entity. Nuttall examined 306 Air Force personnel and showed that 36% suffered with gynaecomastia.2 Its overall prevalence is about 32% in hospital patients.3 It can be as high as 64% in adolescent boys and 40% in autopsy studies.4,5 Niewoehner et al. reported a prevalence of 80% in males with a BMI of 25kg/m2 or greater.6 It is probable that many of these statistics will have included cases of pseudo-gynaecomastia. Many males may notice breast enlargement but do not report it.
Aetiology Gynaecomastia can coexist with many other disorders. Many surgeons accept a classification based on physiological, pharmacological, pathological and idiopathic causes. Three distinct peaks are recognised in the age distribution of patients with physiological gynaecomastia. The first peak occurs in the neonatal period in which 60-90% of all newborns develop transient breast enlargement due 114
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to the transplacental passage of oestrogens. This is usually a self-limiting process and treatment is rarely sought or indeed indicated. The second peak originates in puberty during the early teenage years. This usually resolves over several months or years. A relative excess of plasma oestradiol compared with testosterone has been implicated in the pathogenesis of peri-pubertal gynaecomastia.7,8 The last peak is found in the more mature population, with the highest prevalence among 60- to 80-year-olds. This probably relates to declining levels of testosterone and its peripheral aromatisation to oestrogen, resulting in an increased plasma oestrogen to androgen ratio and is known as senile gynaecomastia.9,10 Pathological gynaecomastia occurs as a result of various metabolic disorders (e.g. alcoholic cirrhosis), endocrine disorders (e.g. hyperthyroidism, Cushing’s disease), congenital or acquired hypogonadal states (e.g. Klinefelter’s syndrome, congenital anorchia, orchitis) and increased oestrogenic states as a result of testicular tumours or bronchogenic carcinoma. Pharmacological gynaecomastia may occur due to increased direct oestrogen activity, increased secretion of oestrogens, decreased testosterone synthesis and decreased androgen sensitivity. It can also occur from increased oestrogenic effects from metabolic conversion of exogenous androgens into oestrogenic compounds. Many pharmaceutical preparations, prescription medicines and recreational drugs have been implicated within this group. Idiopathic gynaecomastia is, however, the commonest cause of breast enlargement, accounting for up to a quarter of cases.11 Up to 20% of cases can also be attributed to physiological causes while drug-induced gynaecomastia accounts for about 1/5 © 2009 Surgeon 7; 2: 114-19
table 1. Simon’s classication
Diagnosis
I
Minor breast enlargement without skin redundancy
IIa
Moderate breast enlargement without skin redundancy
IIb
Moderate breast enlargement with skin redundancy
III
Gross breast enlargement with skin redundancy that simulates a pendulous female breast
Careful history taking involves symptoms related to the patient’s age, onset of breast enlargement, its duration, use of medication, testicular insufficiency and use of recreational drugs. The history should incorporate direct questioning of symptoms referable to hepatic dysfunction, renal dysfunction and hyperthyroidism. Rarely a prolactinoma may present with eye problems related to pressure on the optic chiasma. Common drugs that produce gynaecomastia include spironolactone, digoxin, histamine H2 receptor antagonists, antipsychotics, methyldopa, griseofulvin, and recreational drugs such as alcohol, cannabis and heroin. Historical use of anabolic steroids in bodybuilders is also important. New mediations which are in common use causing gynaecomastia are antihypertensive medications, such as captopril and analapril, and the proton pump inhibitors like omeprazole. Gynaecomastia may cause a fear of male breast cancer and sometimes denial. It can cause physical embarrassment or emotional discomfort interfering with the patient’s daily life. It is important to assess these issues whilst taking the history. It is essential to differentiate fatty enlargement (pseudo-gynaecomastia) from true gynaecomastia.21 Sometimes, it may be difficult to determine this clinically and additional investigations may be warranted. Carcinoma of the male breast is a rare cause of breast enlargement, accounting for about 0.2% of all cancer in male patients.3 Asymmetric and eccentric enlargement needs to be differentiated from breast carcinoma. In patients with Klinefelter’s syndrome, the risk of breast cancer is 60 times higher than other males and demands careful triple assessment. The incidence is approximately 1:400 to 1:1000.22 It is critical that male breast cancer is considered in all men presenting with a new mass over the age of 50. The peak incidence is in the 60s and 70s. Men tend to present late with male breast cancer. There may be skin puckering, nipple indrawing and nipple destruction, Paget’s disease of the nipple or simply a hard subareolar mass. The axilla must be examined for possible lymphadenopathy. Clinical testicular examination is vital and the likelihood of testicular tumour must be considered in any younger man presenting with gynaecomastia. The reported incidence of testicular neoplasm is around 3-4%.23-25 In patients with testicular tumours, gynaecomastia is reported as an initial symptom in 7-11%. Investigations include a complete biochemical assessment including liver function tests, gamma-GT and prolactin, together with an MCV, mammography and/or ultrasound.23-25 The direct measurement of oestrogen and testosterone levels is not usually useful. A high index of suspicion with biochemical assessment of testicular tumour markers (beta-HCG, alpha-fetoprotein) is essential.11,23-26 Scrotal ultrasound is also a useful tool in determining the nature of testicular or epididymal swellings.27 Elevated prolactin levels should raise the suspicion of a pituitary adenoma.23-25 Magnetic resonance imaging of the pituitary fossa is recommended to exclude a prolactinoma.
of the cases. Important pathological causes are hepatic disease (8%), primary hypogonadism (8%), secondary hypogonadism (2%), testicular tumours (3%), hyperthyroidism (2%) and renal disease (1%). A classification of the physical aspects of gynaecomastia has been described by Simon et al. and is more applicable to modern surgical practice as it is based on the amount of breast enlargement with or without skin redundancy (Table 1).12
Pathophysiology Oestrogenism Normally, the adult testes secrete 15% of the oestradiol and less than 5% of oestrone in the circulation. Eighty five percent of oestradiol and 95% of oestrone are produced in extragonadal sites through the aromatisation of precursor compounds, which are produced either from the testes or adrenal glands. Testicular Leydig cell tumours and the rare feminising adrenocortical neoplasms can synthesise and secrete increased quantities of oestrogen which may lead to gynaecomastia.13,14 Increased aromatisation is found to occur physiologically because of ageing as well as in patients with Sertoli cell or sex cord tumour of the testes, trophoblastic and non-trophoblastic germ cell tumours, testicular disease, hyperthyroidism or Klinefelter’s syndrome and in those receiving spironolactone.15 Pharmacological gynaecomastia also includes increased oestrogenic effects from metabolic conversion of exogenous androgens into oestrogenic compounds. Imbalance of hormones The pubertal state is associated with a thirty-fold rise in testosterone concentration with only a threefold increase in the oestrogen level.16 This relative imbalance or altered ratio may lead to true gynaecomastia. Diminished androgen concentration This is commonly encountered in older men as a part of a normal ageing process and in patients with primary and secondary hypogonadism. Spironolactone and ketoconazole inhibit the biosynthesis of testosterone and can result in significant gynaecomastia.17,18 Receptor mediated pathogenesis Displacement of androgen from breast androgen receptors can occur with drugs such as spironolactone, cyproterone acetate, flutamide and cimetidine. This leads to unopposed oestrogenic effects on the breast tissue. Drugs such as digoxin, which have a structural homology to oestrogen, can lead to an activation of oestrogen receptors in the breast tissue.19 Enhanced oestrogen receptor sensitivity (hypersensitive breast tissue) has also been implicated in the cause of idiopathic gynaecomastia and the increased aromatisation of androgen to oestrogen within breast tissue may also be responsible.20 © 2009 Surgeon 7; 2: 114-19
Mammography Most patients with gynaecomastia have subareolar density of various degrees on mammography. Three mammographic patterns have been recognised: early nodular phase, later fibrous phase and a diffuse glandular pattern.28,29 Radiolucent fat is revealed on mammograms in patients with pseudo-gynaecomastia. An overall accuracy of 90% is reported for both benign and malignant conditions.30 Male breast cancer may manifest as a spiculated or circumscribed mass.
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Calcifications are uncommon in male breast cancer compared to females.29 However, a biopsy is warranted if there is an eccentric mass clustered microcalcifications or if there is an overlying skin thickening.
week course of 100mg twice a day for a week followed by 100mg three times a day for two to six weeks. The dose can also be repeated for responders very satisfactorily.34 The drug is licensed for treatment of gynaecomastia in the UK.
Breast ultrasound The majority of benign and malignant lesions can be accurately differentiated with ultrasound. It is sometimes difficult to obtain mammograms in men. Ultrasound is easy to use and can be effectively carried in an outpatient one stop breast clinic. The use of both modalities can improve the diagnostic accuracy. Perpendicular measurements of the gynaecomastia and also its depth can be estimated objectively by ultrasound imaging to allow the observation of the results of medical therapies.
Fine needle aspiration cytology (FNAC) and core biopsy The diagnosis of gynaecomastia is made clinically and radiologically. Classically FNAC shows cohesive clusters of epithelial cells of ductal origin with superimposed myoepithelial cells.23-25 However, FNAC is associated with a high number of reports as ‘inadequate’ or ‘insufficient for diagnosis’ due to failure to sample epithelial cells. Frequently it leads to unsatisfactory and repetitive investigations. Moreover, it is a more painful procedure in men and is best avoided. Clinical distinction between male breast carcinoma and gynaecomastia can often be difficult. Core biopsy is the most appropriate procedure for histological confirmation.31 If a freehand sample is non-diagnostic, an ultrasound guided core should be requested. Core biopsy is associated with a lower false negative and false positive rate and is the investigation of choice for suspicious lesions.
Treatment After the diagnosis is made, the overall aim is to treat the underlying cause to prevent further breast enlargement and treat the patient’s symptom (e.g. pain, tenderness, swelling). Physiological gynaecomastia is often transient and patients only require reassurance. Obviously, withdrawal of the drug or change to an alternative should be considered in pharmacological gynaecomastia. An underlying cause needs to be treated in patients with pathological gynaecomastia (e.g. chronic liver disease, testicular tumour). Medical management benefits from a high success rate and avoidance of an operation. Imaging and clinical photography can be used to assess the response and to evaluate the success of the treatment objectively.
Danazol The first reported controlled trial investigating the efficacy of danazol was published in 1979 and showed marked to moderate regression in patients with gynaecomastia.32 Jones et al. were the first to investigate the efficacy of danazol in adult idiopathic gynaecomastia. In this double-blind, randomised, two centre study, 55 patients were enrolled and danazol was randomly allocated to 27 patients and placebo to 28 patients. There was a significant decrease in the mean diameter of the lump in patients with danazol treatment compared to that of placebo.33 Thus, it may obviate the need for surgery. Danazol is particularly effective in reducing tenderness. Weight gain seems to be the most significant side effect, but is rarely reported. It is effective in about 80% of the patients. The recommended dose is a short six 116
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Tamoxifen There are two randomised double blind controlled trials examining the efficacy of tamoxifen. These trials have shown that tamoxifen leads to a statistically significant reduction in breast size and breast pain without any major side effects.35,36 Complete regression was not noted in either of the studies. However, in an uncontrolled study, Alagaratnam (1987) reported a good response in 80% of patients.37 Similarly, a study from the Nottingham Unit involving 36 consecutive patients confirmed the resolution of gynaecomastia in 83% of them. A single dose of 20mg of tamoxifen for 6 to 12 weeks alleviated tenderness in 84% of cases. ‘Lump’ gynaecomastia (true) was more responsive to tamoxifen than the ‘fatty’ (pseudo) type of gynaecomastia (100% vs 62.5%). It was concluded that oral tamoxifen is an effective treatment for physiological gynaecomastia especially of the ‘lump’ type.38 In a double blind crossover study, Parker et al. reported no toxicity.39 They proposed that tamoxifen may represent a safe and effective treatment for selected cases of cosmetically disfiguring or symptomatic gynaecomastia in adults, although the drug is not licensed for use in this condition. Preliminary efficacy data from two crossover studies and a case series indicated that tamoxifen was associated with a reduction of breast size and decreased breast pain.36,39-41 No studies have yet correlated response with oestrogen and progesterone status although this is under way in our unit. Gynaecomastia may occur in men undergoing hormonal therapy for prostate cancer. Tamoxifen has been advocated as a prophylactic drug for its prevention.42 Tamoxifen is also being tested against anastrozole, a selective aromatase inhibitor, for prophylactic use in patients receiving anti-androgen hormone therapy for prostate cancer.43 Relative to placebo, and anastrozole, tamoxifen is associated with the lowest incidence of gynaecomastia and breast pain.44 Ting et al. compared the efficacy of tamoxifen and danazol in the treatment of idiopathic gynaecomastia.45 Seventy-eight percent of patients treated with tamoxifen showed complete resolution of idiopathic gynaecomastia, whereas only 40% in the danazol group had a complete response. Although tamoxifen showed promising initial responses, it is associated with trends towards a higher relapse rate than danazol. Despite these reports, there is no consensus as to the drug of choice or the optimal duration of treatment and danazol remains the only drug licensed for the treatment of gynaecomastia in the UK, although clomiphene and others have also been used with varying degrees of success.23-25
Surgery Traditionally, surgery has been the treatment of choice for gynaecomastia. The main objective of surgical treatment is to restore the normal male contour and leave an inconspicuous scar.46 Surgery is associated with complications such as doughnut deformity and scalloping, asymmetry, nipple necrosis, nipple flattening and loss of sensation. Cosmetically unsatisfactory results are reported to occur in as much as 50% of all patients.47 An unpleasant complication of surgery for gynaecomastia is tethering of the subareolar area to the chest wall (saucer deformity). Surgery should be carried out only by a specialist
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breast surgeon familiar with male breast reduction for gynaecomastia, to reduce the risk of unsatisfactory cosmesis. Special techniques are available to produce the best outcomes. If this is not available at the hospital where a patient is seen, a tertiary referral may be appropriate. Pre-operative photography is recommended. Surgery should only be undertaken in the following circumstances. • Patients with large ‘lumps’ (Simon’s grade IIb, III). • Even small lumps which significantly interfere with quality of life (e.g. persistent enlargement of the male breast) can be a source of embarrassment and/or distress. • Failure of medical therapy – persistent gynaecomastia for more than a year is considered a medical failure. It may be due to stromal hyalinisation and irreversible dense fibrosis48,49 • Patients on prolonged treatment with medical therapy. Drug treatment may not be appropriate due to the subsequent side effects of the medication. The following principles underlie the surgical treatment of gynaecomastia: • cosmetic scar • excision of the lump and restoration of the male chest shape • avoidance of saucer deformity by leaving adequate tissue between the nipple-areola complex and the pectoral fascia, to prevent adhesions and subsequent dimpling • skin flaps are kept thick to prevent the deformity and skin necrosis. The type of surgical treatment varies from minimally invasive surgery to traditional subcutaneous mastectomy. It is principally dependent on the amount and character of breast hypertrophy, the degree of skin redundancy, the relative enlargement of the nipple areola complex and the degree of breast ptosis. Paulus Aegineta (625-690 A.D.) was apparently the first to report surgical excision of enlarged male breast tissue. Semicircular circumareolar incisions have gained wide acceptance. Although a semicircular infra-areolar incision is attributed to Webster in 1946, it was first described by Dufourmental in 1928.1,50-52 Some authors believe that a complete circumareolar technique with purse string sutures produces a better aesthetic result with fewer complications.1 This technique is particularly effective in those breast enlargements that have skin redundancy.1 This is often useful in unilateral cases as it reduces inequality. In principle, it involves the preservation of vascularity to the nipple-areola complex and may avoid necrosis. In patients with moderate and large gynaecomastia associated with skin redundancy (Simon’s grade IIb and III) the excess skin needs to be excised. These patients may require a procedure similar to reduction mammoplasty or mastopexy.12,46,53 An alternative technique is to perform a ‘round block excision’ which renders an almost invisible scar and allows performance of an internal mastopexy.54 Free nipple grafting can also be performed after the excision of a large amount of breast tissue.55 Scaphoid deformity as a resultant of traditional subcutaneous mastectomy may be unacceptable to many patients and surgeons. Over the last thirty years, there has been an increase in the use of minimally invasive techniques in the surgical treatment of gynaecomastia. The mammotome is a newly emerging minimally invasive device, which is safe and is associated with a high patient satisfaction rate. The mammotome is inserted through a cosmetically placed small © 2009 Surgeon 7; 2: 114-19
scar under ultrasound guidance. It sequentially resects the breast tissue using suction.56,57 The entire procedure can be performed under local anaesthetic. Other minimally invasive techniques are laser therapy, radiofrequency ablation, and cryosurgery and focused ultrasound waves.58,59 All of them are unsuitable for large volume reduction. As with all minimally invasive surgery, a learning curve exists with the mammotome. Furthermore, there are theoretical risks of skin injury and haemorrhage. Use of liposuction has been advocated since the early 1980s. This is particularly useful in the management of pseudo-gynaecomastia. Ultrasound assisted liposuction has recently emerged as a safe and effective method. It is particularly efficient in the removal of dense and fibrous male breast tissue rather than simply fatty tissue, while offering advantages with minimal skin scarring. It seems to be effective in treating most grades of gynaecomastia. Considerable skin retraction is known to occur depending on patient age and skin elasticity. Rohrich et al. demonstrated that more than 85% of patients treated with this technique did not require an extensive skin incision for removal of remaining breast tissue.56 However, patients with firm and fibrous discs still probably require open surgery. Thermal injury to the overlying skin is a specific complication with this technique.
Summary and conclusions with recommendations Gynaecomastia is the most common benign breast condition in men. There are two types of gynaecomastia, true and pseudo, which may coexist as mixed pattern. A detailed history and thorough clinical examination with a diagnostic protocol is recommended in most patients. Fine needle biopsy in men is particularly painful and unrewarding. Radiographic investigation using mammography or ultrasound is recommended to confirm the diagnosis. After the diagnosis is made, the overall aim is to treat the underlying cause to prevent further breast enlargement and treat the patient’s symptoms (e.g. pain, tenderness, swelling). Gynaecomastia is often transient so reassurance may be all that is required. Danazol therapy is effective in 80% and can be repeated for the non-responders. Tamoxifen may represent a safe and effective treatment method of therapy, although the drug is not licensed in the UK for this condition. Also, it is associated with a high relapse rate. The indications for surgery are failure of medical treatment, intolerable side-effects of drugs and patients with large gynaecomastia. The spectrum of surgical treatment varies from simple liposuction to subcutaneous mastectomy. Use of a mammotome is a newly emerging minimally invasive technique. All patients should be thoroughly counselled before surgery and cautioned about potential complications to minimise litigation.
Copyright © 5 September 2008
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20. Bulard J, Mowszowicz I, Schaison G. Increased aromatase activity in pubic skin broblasts from patients with isolated gynaecomastia. J Clin Endocrinol Metab 1987; 64(3): 618-23 21. Webster JP. Mastectomy for gynaecomastia through a semicircular intra-areolar incision. Ann Surg 1946; 124: 557 22. Jackson AW, Muldal S, Ockey CH et al. Carcinoma of male breast in association with the Kinefelter syndrome. Br Med J. 1965; 1(5429): 223-25 23. Daniels IR, Layer GT. Testicular tumours presenting as gynaecomastia. Eur J Surg Oncol 2003; 29(5): 437-39 24. Daniels IR, Layer GT. How should gynaecomastia be managed? ANZ J Surg 2003; 73(4): 213-6 25. Daniels IR, Layer GT. Gynaecomastia. Eur J Surg 2001;167(12):885-92. 26. Harris M, Rizvi S, Hindmarsh J, Bryan R. Testicular tumour presenting as gynaecomastia. BMJ 2006; 332(7545): 837 27. Bowers SP, Pearlman NW, McIntyre RC Jr. Et al. Cost- effective management of gynaecomastia. Am J Surg 1998; 176: 638 28. Appelbaum AH, Evans GF, Levy KR et al. Mammographic appearances of male breast disease. Radiographics 1999; 19(3): 559-68 29. Chantra PK, So GJ, Wollman JS et al. Mammography of the male breast. AJR Am J Roentgenol 1995;164(4): 853-58 30. Evans GF, Anthony T, Turnage RH et al. The diagnostic accuracy of mammography n the evaluation of male breast disease. Am J Surg 2001; 181(2): 96-100 31. Gupta RK, Naran S, Simpson J. The role of ne needle aspiration cytology (FNAC) in the diagnosis of breast masses in males. Eur J Surg Oncol 1988; 14(4): 317-20 32. Buckle R. Danazol therapy in gynaecomastia: recent experience and indications for therapy. Postgrad Med J 1979; 55(Suppl 5): 71-8 33. Jones DJ, Holt SD, Surtess P et al. A comparison of danazol and placebo in the treatment of adult idiopathic gynaecomastia: result of a prospective study in 55 patients. Ann R Coll Surg Engl 1990; 72:296-98 34. Khan HN, Blamey RW. Endocrine treatment of physiological gynaecomastia. BMJ 2003; 327(7410): 301-02 35. Parker LN, Gray DR, Lai MK et al. Treatment of gynaecomastia with tamoxifen: a double-blind crossover study. Metabolism 1986; 35(8): 705-08 36. McDermott MT, Hofeldt FD, Kidd GS. Tamoxifen therapy for painful idiopathic gynaecomastia. South Med J 1990; 83(11): 1283-85 37. Alagaratnam TT. Idiopathic gynaecomastia treated with tamoxifen: a preliminary report. Clin Ther 1987; 9(5): 483-87 38. Khan HN, Ramoaul R, Blamey RW. The use of tamoxifen for gynaecomastia at Nottingham Breast Unit. Br J Surg 2003; 90(s1):1 00 39. Parker LN, Gray DR, Lai MK et al. Treatment of gynaecomastia with tamoxifen: a double-blind crossover study. Metabolism 1986; 35(8):705-08
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40. Serels S, Melman A. Tamoxifen as treatment for gynaecomastia and mastodynia resulting from hormonal deprivation. J Urol 1998; 159(4): 1309. 41. Staiman VR, Lowe FC. Tamoxifen for utamide/ nasteride-induced gynaecomastia. Urology 1997; 50(6): 929-33 42. Dobs A, Darkes MJ. Incidence and management of gynaecomastia in men treated with prostate cancer. J Urol 2005; 174(5): 1731-42 43. Braunstein GD. Aromatase and gynaecomastia. Endocr Relat Cancer 1999; 6(2): 315-24 44. Boccardo F, Rubagotti A, Battaglia M et al. Evaluation of tamoxifen and anastrozole in the prevention of gynaecomastia and breast pain induced by bicalutamide monotherapy of prostate cancer. J Clin Oncol. 2005; 23(4): 808-15 45. Ting AC, Chow LW, Leung YF. Comparison of tamoxifen with danazol in the management of idiopathic gynaecomastia. Am Surg 2000; 66(1): 38-40 46. Moss ALH. The surgical approach to gynaecomastia. N Z Med J 1982; 95: 505-06 47. Colombo-Benkmann M, Buse B et al. Surgical therapy of gynaecomastia and its results. Langenbecks Arch Chir Suppl Kongress 1998; 11: 1282-84 48. Nicolis GL, Modlinger RS, Gabrilove JL. A study of the histopathology of human gynaecomastia. J Clin Endocrinol Metab 1971; 32(2): 173-78 49. Williams MJ. Gynaecomastia. Its incidence, recognition and host characterization in 447 autopsy cases. Am J Med1963; 34: 103-12 50. Webster JP. Mastectomy for gynaecomastia through a semicircular intra-areolar incision. Ann Surg 1946; 124: 557 51. Park AJ, Lamberty BG. Gynaecomastia: have Webster’s lessons been ignored? J R Coll Surg Edin 1998; 43(2): 89-92 52. Pitanguy I. Transareolar incision for gynaecomastia. Plast Reconstr Surg 1966; 38(5): 414-19 53. Letterman G, Schurter M. Surgical correction of massive gynaecomastia. Plast Reconstr Surg 1972; 49(3): 259-62 54. Melmed EP. Surgical treatment of grade III gynaecomastia. Ann R Coll Surg Engl 1990; 72(1): 68-9 55. Wray RC Jr, Hoopes JE, Davis GM. Correction of extreme gynaecomastia. Br J Plast Surg 1974; 27(1): 39-41 56. Rohrich RJ, Ha RY, Kenkel JM et al. Classication and management of gynaecomastia: dening the role of ultrasound-assisted liposuction. Plast Reconstr Surg 2003; 111(2): 909-25 57. Iwuagwu OC, Calvey TA, Ilsley D et al. Ultrasound guided minimally invasive breast surgery (UMIBS): a superior technique for gynaecomastia. Ann Plast Surg 2004; 52(2): 131-33 58. Hall-Craggs MA, Vaidya JS. Minimally invasive therapy for the treatment of breast tumours. Eur J Radiol 2002; 42(1): 52-57 59. Singletary SE. Minimally invasive techniques in breast cancer treatment.Semin Surg Oncol 2001; 20(3): 246-50
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THE MILLIN LECTURE 2009 The 32nd Millin Lecture will be delivered in November 2009. Fellows of the College are invited to nominate candidates. Completed applications must be received before Friday 8th May 2009. This is a prestigious award and open to all the Surgical specialties. Usually, the successful applicant will be well advanced in his/her surgical training or in their rst ve years in consultant practice. Preference will be given to candidates whose surgical research has been carried out wholly or in part in Ireland. The subject chosen should be of clinical interest embodying original research. Further particulars may be obtained from: Ms G Conroy Ofce of the Director of Surgical Affairs Royal College of Surgeons in Ireland 123 St Stephen’s Green Dublin 2. Tel: +353 1 4022187 email: [email protected] http://www.rcsi.ie
Professor W Arthur Tanner Director of Surgical Affairs
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Royal Surrey County Hospital NHS Trust and University of Surrey, Egerton Road, Guildford GU2 7XX 2 Postgraduate medical school, University of Surrey Correspondence to: Mr Haresh Devalia 35 Fairway, Raynes Park, London SW20 9DN Tel: +44(0)7789773974 Fax: +44(0)2085421897 Email: hareshdevalia@doctors. org.uk
CURRENT CONCEPTS IN GYNAECOMASTIA Gynaecomastia is a common breast condition. Each case merits a careful and complete history, with thorough examination and investigations being required in selected patients with progressive disease or suspected sinister pathology. Treatment is usually indicated for any underlying cause, associated symptoms and the gynaecomastia itself. Treatment may be either medical or surgical but must be individualised. Medical treatment may be especially advocated in the symptomatic group. The indications for surgery include failure of medical treatment, intolerable side-effects of necessary drugs, malignancy, small lesions which cause signicant distress and patients with large and ptotic gynaecomastia. A careful programme of counselling, pre-operatively in particular, may help to minimise litigation. keywords: gynaecomastia, tamoxifen, danazol Surgeon, 1 April 2009, pp. 114-19
Introduction Gynaecomastia is usually a benign enlargement of the male breast. The term is derived from the Greek words ‘gyne’ meaning woman and ‘mastos’ meaning breast.1 In some cases it may be due to an imbalance between circulating oestrogens and androgens in the blood, but the aetiology is broad and varied. It may be seen as either ‘true’ or ‘pseudo’ gynaecomastia or a combination of both. True gynaecomastia indicates enlargement of male breast glandular tissue, whilst pseudo-gynaecomastia represents excessive adipose tissue. Clinically it may be either unilateral or bilateral, giving an indication of local or systemic underlying pathology.
Prevalence Asymptomatic palpable gynaecomastia is a common entity. Nuttall examined 306 Air Force personnel and showed that 36% suffered with gynaecomastia.2 Its overall prevalence is about 32% in hospital patients.3 It can be as high as 64% in adolescent boys and 40% in autopsy studies.4,5 Niewoehner et al. reported a prevalence of 80% in males with a BMI of 25kg/m2 or greater.6 It is probable that many of these statistics will have included cases of pseudo-gynaecomastia. Many males may notice breast enlargement but do not report it.
Aetiology Gynaecomastia can coexist with many other disorders. Many surgeons accept a classification based on physiological, pharmacological, pathological and idiopathic causes. Three distinct peaks are recognised in the age distribution of patients with physiological gynaecomastia. The first peak occurs in the neonatal period in which 60-90% of all newborns develop transient breast enlargement due 114
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to the transplacental passage of oestrogens. This is usually a self-limiting process and treatment is rarely sought or indeed indicated. The second peak originates in puberty during the early teenage years. This usually resolves over several months or years. A relative excess of plasma oestradiol compared with testosterone has been implicated in the pathogenesis of peri-pubertal gynaecomastia.7,8 The last peak is found in the more mature population, with the highest prevalence among 60- to 80-year-olds. This probably relates to declining levels of testosterone and its peripheral aromatisation to oestrogen, resulting in an increased plasma oestrogen to androgen ratio and is known as senile gynaecomastia.9,10 Pathological gynaecomastia occurs as a result of various metabolic disorders (e.g. alcoholic cirrhosis), endocrine disorders (e.g. hyperthyroidism, Cushing’s disease), congenital or acquired hypogonadal states (e.g. Klinefelter’s syndrome, congenital anorchia, orchitis) and increased oestrogenic states as a result of testicular tumours or bronchogenic carcinoma. Pharmacological gynaecomastia may occur due to increased direct oestrogen activity, increased secretion of oestrogens, decreased testosterone synthesis and decreased androgen sensitivity. It can also occur from increased oestrogenic effects from metabolic conversion of exogenous androgens into oestrogenic compounds. Many pharmaceutical preparations, prescription medicines and recreational drugs have been implicated within this group. Idiopathic gynaecomastia is, however, the commonest cause of breast enlargement, accounting for up to a quarter of cases.11 Up to 20% of cases can also be attributed to physiological causes while drug-induced gynaecomastia accounts for about 1/5 © 2009 Surgeon 7; 2: 114-19
table 1. Simon’s classication
Diagnosis
I
Minor breast enlargement without skin redundancy
IIa
Moderate breast enlargement without skin redundancy
IIb
Moderate breast enlargement with skin redundancy
III
Gross breast enlargement with skin redundancy that simulates a pendulous female breast
Careful history taking involves symptoms related to the patient’s age, onset of breast enlargement, its duration, use of medication, testicular insufficiency and use of recreational drugs. The history should incorporate direct questioning of symptoms referable to hepatic dysfunction, renal dysfunction and hyperthyroidism. Rarely a prolactinoma may present with eye problems related to pressure on the optic chiasma. Common drugs that produce gynaecomastia include spironolactone, digoxin, histamine H2 receptor antagonists, antipsychotics, methyldopa, griseofulvin, and recreational drugs such as alcohol, cannabis and heroin. Historical use of anabolic steroids in bodybuilders is also important. New mediations which are in common use causing gynaecomastia are antihypertensive medications, such as captopril and analapril, and the proton pump inhibitors like omeprazole. Gynaecomastia may cause a fear of male breast cancer and sometimes denial. It can cause physical embarrassment or emotional discomfort interfering with the patient’s daily life. It is important to assess these issues whilst taking the history. It is essential to differentiate fatty enlargement (pseudo-gynaecomastia) from true gynaecomastia.21 Sometimes, it may be difficult to determine this clinically and additional investigations may be warranted. Carcinoma of the male breast is a rare cause of breast enlargement, accounting for about 0.2% of all cancer in male patients.3 Asymmetric and eccentric enlargement needs to be differentiated from breast carcinoma. In patients with Klinefelter’s syndrome, the risk of breast cancer is 60 times higher than other males and demands careful triple assessment. The incidence is approximately 1:400 to 1:1000.22 It is critical that male breast cancer is considered in all men presenting with a new mass over the age of 50. The peak incidence is in the 60s and 70s. Men tend to present late with male breast cancer. There may be skin puckering, nipple indrawing and nipple destruction, Paget’s disease of the nipple or simply a hard subareolar mass. The axilla must be examined for possible lymphadenopathy. Clinical testicular examination is vital and the likelihood of testicular tumour must be considered in any younger man presenting with gynaecomastia. The reported incidence of testicular neoplasm is around 3-4%.23-25 In patients with testicular tumours, gynaecomastia is reported as an initial symptom in 7-11%. Investigations include a complete biochemical assessment including liver function tests, gamma-GT and prolactin, together with an MCV, mammography and/or ultrasound.23-25 The direct measurement of oestrogen and testosterone levels is not usually useful. A high index of suspicion with biochemical assessment of testicular tumour markers (beta-HCG, alpha-fetoprotein) is essential.11,23-26 Scrotal ultrasound is also a useful tool in determining the nature of testicular or epididymal swellings.27 Elevated prolactin levels should raise the suspicion of a pituitary adenoma.23-25 Magnetic resonance imaging of the pituitary fossa is recommended to exclude a prolactinoma.
of the cases. Important pathological causes are hepatic disease (8%), primary hypogonadism (8%), secondary hypogonadism (2%), testicular tumours (3%), hyperthyroidism (2%) and renal disease (1%). A classification of the physical aspects of gynaecomastia has been described by Simon et al. and is more applicable to modern surgical practice as it is based on the amount of breast enlargement with or without skin redundancy (Table 1).12
Pathophysiology Oestrogenism Normally, the adult testes secrete 15% of the oestradiol and less than 5% of oestrone in the circulation. Eighty five percent of oestradiol and 95% of oestrone are produced in extragonadal sites through the aromatisation of precursor compounds, which are produced either from the testes or adrenal glands. Testicular Leydig cell tumours and the rare feminising adrenocortical neoplasms can synthesise and secrete increased quantities of oestrogen which may lead to gynaecomastia.13,14 Increased aromatisation is found to occur physiologically because of ageing as well as in patients with Sertoli cell or sex cord tumour of the testes, trophoblastic and non-trophoblastic germ cell tumours, testicular disease, hyperthyroidism or Klinefelter’s syndrome and in those receiving spironolactone.15 Pharmacological gynaecomastia also includes increased oestrogenic effects from metabolic conversion of exogenous androgens into oestrogenic compounds. Imbalance of hormones The pubertal state is associated with a thirty-fold rise in testosterone concentration with only a threefold increase in the oestrogen level.16 This relative imbalance or altered ratio may lead to true gynaecomastia. Diminished androgen concentration This is commonly encountered in older men as a part of a normal ageing process and in patients with primary and secondary hypogonadism. Spironolactone and ketoconazole inhibit the biosynthesis of testosterone and can result in significant gynaecomastia.17,18 Receptor mediated pathogenesis Displacement of androgen from breast androgen receptors can occur with drugs such as spironolactone, cyproterone acetate, flutamide and cimetidine. This leads to unopposed oestrogenic effects on the breast tissue. Drugs such as digoxin, which have a structural homology to oestrogen, can lead to an activation of oestrogen receptors in the breast tissue.19 Enhanced oestrogen receptor sensitivity (hypersensitive breast tissue) has also been implicated in the cause of idiopathic gynaecomastia and the increased aromatisation of androgen to oestrogen within breast tissue may also be responsible.20 © 2009 Surgeon 7; 2: 114-19
Mammography Most patients with gynaecomastia have subareolar density of various degrees on mammography. Three mammographic patterns have been recognised: early nodular phase, later fibrous phase and a diffuse glandular pattern.28,29 Radiolucent fat is revealed on mammograms in patients with pseudo-gynaecomastia. An overall accuracy of 90% is reported for both benign and malignant conditions.30 Male breast cancer may manifest as a spiculated or circumscribed mass.
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Calcifications are uncommon in male breast cancer compared to females.29 However, a biopsy is warranted if there is an eccentric mass clustered microcalcifications or if there is an overlying skin thickening.
week course of 100mg twice a day for a week followed by 100mg three times a day for two to six weeks. The dose can also be repeated for responders very satisfactorily.34 The drug is licensed for treatment of gynaecomastia in the UK.
Breast ultrasound The majority of benign and malignant lesions can be accurately differentiated with ultrasound. It is sometimes difficult to obtain mammograms in men. Ultrasound is easy to use and can be effectively carried in an outpatient one stop breast clinic. The use of both modalities can improve the diagnostic accuracy. Perpendicular measurements of the gynaecomastia and also its depth can be estimated objectively by ultrasound imaging to allow the observation of the results of medical therapies.
Fine needle aspiration cytology (FNAC) and core biopsy The diagnosis of gynaecomastia is made clinically and radiologically. Classically FNAC shows cohesive clusters of epithelial cells of ductal origin with superimposed myoepithelial cells.23-25 However, FNAC is associated with a high number of reports as ‘inadequate’ or ‘insufficient for diagnosis’ due to failure to sample epithelial cells. Frequently it leads to unsatisfactory and repetitive investigations. Moreover, it is a more painful procedure in men and is best avoided. Clinical distinction between male breast carcinoma and gynaecomastia can often be difficult. Core biopsy is the most appropriate procedure for histological confirmation.31 If a freehand sample is non-diagnostic, an ultrasound guided core should be requested. Core biopsy is associated with a lower false negative and false positive rate and is the investigation of choice for suspicious lesions.
Treatment After the diagnosis is made, the overall aim is to treat the underlying cause to prevent further breast enlargement and treat the patient’s symptom (e.g. pain, tenderness, swelling). Physiological gynaecomastia is often transient and patients only require reassurance. Obviously, withdrawal of the drug or change to an alternative should be considered in pharmacological gynaecomastia. An underlying cause needs to be treated in patients with pathological gynaecomastia (e.g. chronic liver disease, testicular tumour). Medical management benefits from a high success rate and avoidance of an operation. Imaging and clinical photography can be used to assess the response and to evaluate the success of the treatment objectively.
Danazol The first reported controlled trial investigating the efficacy of danazol was published in 1979 and showed marked to moderate regression in patients with gynaecomastia.32 Jones et al. were the first to investigate the efficacy of danazol in adult idiopathic gynaecomastia. In this double-blind, randomised, two centre study, 55 patients were enrolled and danazol was randomly allocated to 27 patients and placebo to 28 patients. There was a significant decrease in the mean diameter of the lump in patients with danazol treatment compared to that of placebo.33 Thus, it may obviate the need for surgery. Danazol is particularly effective in reducing tenderness. Weight gain seems to be the most significant side effect, but is rarely reported. It is effective in about 80% of the patients. The recommended dose is a short six 116
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Tamoxifen There are two randomised double blind controlled trials examining the efficacy of tamoxifen. These trials have shown that tamoxifen leads to a statistically significant reduction in breast size and breast pain without any major side effects.35,36 Complete regression was not noted in either of the studies. However, in an uncontrolled study, Alagaratnam (1987) reported a good response in 80% of patients.37 Similarly, a study from the Nottingham Unit involving 36 consecutive patients confirmed the resolution of gynaecomastia in 83% of them. A single dose of 20mg of tamoxifen for 6 to 12 weeks alleviated tenderness in 84% of cases. ‘Lump’ gynaecomastia (true) was more responsive to tamoxifen than the ‘fatty’ (pseudo) type of gynaecomastia (100% vs 62.5%). It was concluded that oral tamoxifen is an effective treatment for physiological gynaecomastia especially of the ‘lump’ type.38 In a double blind crossover study, Parker et al. reported no toxicity.39 They proposed that tamoxifen may represent a safe and effective treatment for selected cases of cosmetically disfiguring or symptomatic gynaecomastia in adults, although the drug is not licensed for use in this condition. Preliminary efficacy data from two crossover studies and a case series indicated that tamoxifen was associated with a reduction of breast size and decreased breast pain.36,39-41 No studies have yet correlated response with oestrogen and progesterone status although this is under way in our unit. Gynaecomastia may occur in men undergoing hormonal therapy for prostate cancer. Tamoxifen has been advocated as a prophylactic drug for its prevention.42 Tamoxifen is also being tested against anastrozole, a selective aromatase inhibitor, for prophylactic use in patients receiving anti-androgen hormone therapy for prostate cancer.43 Relative to placebo, and anastrozole, tamoxifen is associated with the lowest incidence of gynaecomastia and breast pain.44 Ting et al. compared the efficacy of tamoxifen and danazol in the treatment of idiopathic gynaecomastia.45 Seventy-eight percent of patients treated with tamoxifen showed complete resolution of idiopathic gynaecomastia, whereas only 40% in the danazol group had a complete response. Although tamoxifen showed promising initial responses, it is associated with trends towards a higher relapse rate than danazol. Despite these reports, there is no consensus as to the drug of choice or the optimal duration of treatment and danazol remains the only drug licensed for the treatment of gynaecomastia in the UK, although clomiphene and others have also been used with varying degrees of success.23-25
Surgery Traditionally, surgery has been the treatment of choice for gynaecomastia. The main objective of surgical treatment is to restore the normal male contour and leave an inconspicuous scar.46 Surgery is associated with complications such as doughnut deformity and scalloping, asymmetry, nipple necrosis, nipple flattening and loss of sensation. Cosmetically unsatisfactory results are reported to occur in as much as 50% of all patients.47 An unpleasant complication of surgery for gynaecomastia is tethering of the subareolar area to the chest wall (saucer deformity). Surgery should be carried out only by a specialist
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breast surgeon familiar with male breast reduction for gynaecomastia, to reduce the risk of unsatisfactory cosmesis. Special techniques are available to produce the best outcomes. If this is not available at the hospital where a patient is seen, a tertiary referral may be appropriate. Pre-operative photography is recommended. Surgery should only be undertaken in the following circumstances. • Patients with large ‘lumps’ (Simon’s grade IIb, III). • Even small lumps which significantly interfere with quality of life (e.g. persistent enlargement of the male breast) can be a source of embarrassment and/or distress. • Failure of medical therapy – persistent gynaecomastia for more than a year is considered a medical failure. It may be due to stromal hyalinisation and irreversible dense fibrosis48,49 • Patients on prolonged treatment with medical therapy. Drug treatment may not be appropriate due to the subsequent side effects of the medication. The following principles underlie the surgical treatment of gynaecomastia: • cosmetic scar • excision of the lump and restoration of the male chest shape • avoidance of saucer deformity by leaving adequate tissue between the nipple-areola complex and the pectoral fascia, to prevent adhesions and subsequent dimpling • skin flaps are kept thick to prevent the deformity and skin necrosis. The type of surgical treatment varies from minimally invasive surgery to traditional subcutaneous mastectomy. It is principally dependent on the amount and character of breast hypertrophy, the degree of skin redundancy, the relative enlargement of the nipple areola complex and the degree of breast ptosis. Paulus Aegineta (625-690 A.D.) was apparently the first to report surgical excision of enlarged male breast tissue. Semicircular circumareolar incisions have gained wide acceptance. Although a semicircular infra-areolar incision is attributed to Webster in 1946, it was first described by Dufourmental in 1928.1,50-52 Some authors believe that a complete circumareolar technique with purse string sutures produces a better aesthetic result with fewer complications.1 This technique is particularly effective in those breast enlargements that have skin redundancy.1 This is often useful in unilateral cases as it reduces inequality. In principle, it involves the preservation of vascularity to the nipple-areola complex and may avoid necrosis. In patients with moderate and large gynaecomastia associated with skin redundancy (Simon’s grade IIb and III) the excess skin needs to be excised. These patients may require a procedure similar to reduction mammoplasty or mastopexy.12,46,53 An alternative technique is to perform a ‘round block excision’ which renders an almost invisible scar and allows performance of an internal mastopexy.54 Free nipple grafting can also be performed after the excision of a large amount of breast tissue.55 Scaphoid deformity as a resultant of traditional subcutaneous mastectomy may be unacceptable to many patients and surgeons. Over the last thirty years, there has been an increase in the use of minimally invasive techniques in the surgical treatment of gynaecomastia. The mammotome is a newly emerging minimally invasive device, which is safe and is associated with a high patient satisfaction rate. The mammotome is inserted through a cosmetically placed small © 2009 Surgeon 7; 2: 114-19
scar under ultrasound guidance. It sequentially resects the breast tissue using suction.56,57 The entire procedure can be performed under local anaesthetic. Other minimally invasive techniques are laser therapy, radiofrequency ablation, and cryosurgery and focused ultrasound waves.58,59 All of them are unsuitable for large volume reduction. As with all minimally invasive surgery, a learning curve exists with the mammotome. Furthermore, there are theoretical risks of skin injury and haemorrhage. Use of liposuction has been advocated since the early 1980s. This is particularly useful in the management of pseudo-gynaecomastia. Ultrasound assisted liposuction has recently emerged as a safe and effective method. It is particularly efficient in the removal of dense and fibrous male breast tissue rather than simply fatty tissue, while offering advantages with minimal skin scarring. It seems to be effective in treating most grades of gynaecomastia. Considerable skin retraction is known to occur depending on patient age and skin elasticity. Rohrich et al. demonstrated that more than 85% of patients treated with this technique did not require an extensive skin incision for removal of remaining breast tissue.56 However, patients with firm and fibrous discs still probably require open surgery. Thermal injury to the overlying skin is a specific complication with this technique.
Summary and conclusions with recommendations Gynaecomastia is the most common benign breast condition in men. There are two types of gynaecomastia, true and pseudo, which may coexist as mixed pattern. A detailed history and thorough clinical examination with a diagnostic protocol is recommended in most patients. Fine needle biopsy in men is particularly painful and unrewarding. Radiographic investigation using mammography or ultrasound is recommended to confirm the diagnosis. After the diagnosis is made, the overall aim is to treat the underlying cause to prevent further breast enlargement and treat the patient’s symptoms (e.g. pain, tenderness, swelling). Gynaecomastia is often transient so reassurance may be all that is required. Danazol therapy is effective in 80% and can be repeated for the non-responders. Tamoxifen may represent a safe and effective treatment method of therapy, although the drug is not licensed in the UK for this condition. Also, it is associated with a high relapse rate. The indications for surgery are failure of medical treatment, intolerable side-effects of drugs and patients with large gynaecomastia. The spectrum of surgical treatment varies from simple liposuction to subcutaneous mastectomy. Use of a mammotome is a newly emerging minimally invasive technique. All patients should be thoroughly counselled before surgery and cautioned about potential complications to minimise litigation.
Copyright © 5 September 2008
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20. Bulard J, Mowszowicz I, Schaison G. Increased aromatase activity in pubic skin broblasts from patients with isolated gynaecomastia. J Clin Endocrinol Metab 1987; 64(3): 618-23 21. Webster JP. Mastectomy for gynaecomastia through a semicircular intra-areolar incision. Ann Surg 1946; 124: 557 22. Jackson AW, Muldal S, Ockey CH et al. Carcinoma of male breast in association with the Kinefelter syndrome. Br Med J. 1965; 1(5429): 223-25 23. Daniels IR, Layer GT. Testicular tumours presenting as gynaecomastia. Eur J Surg Oncol 2003; 29(5): 437-39 24. Daniels IR, Layer GT. How should gynaecomastia be managed? ANZ J Surg 2003; 73(4): 213-6 25. Daniels IR, Layer GT. Gynaecomastia. Eur J Surg 2001;167(12):885-92. 26. Harris M, Rizvi S, Hindmarsh J, Bryan R. Testicular tumour presenting as gynaecomastia. BMJ 2006; 332(7545): 837 27. Bowers SP, Pearlman NW, McIntyre RC Jr. Et al. Cost- effective management of gynaecomastia. Am J Surg 1998; 176: 638 28. Appelbaum AH, Evans GF, Levy KR et al. Mammographic appearances of male breast disease. Radiographics 1999; 19(3): 559-68 29. Chantra PK, So GJ, Wollman JS et al. Mammography of the male breast. AJR Am J Roentgenol 1995;164(4): 853-58 30. Evans GF, Anthony T, Turnage RH et al. The diagnostic accuracy of mammography n the evaluation of male breast disease. Am J Surg 2001; 181(2): 96-100 31. Gupta RK, Naran S, Simpson J. The role of ne needle aspiration cytology (FNAC) in the diagnosis of breast masses in males. Eur J Surg Oncol 1988; 14(4): 317-20 32. Buckle R. Danazol therapy in gynaecomastia: recent experience and indications for therapy. Postgrad Med J 1979; 55(Suppl 5): 71-8 33. Jones DJ, Holt SD, Surtess P et al. A comparison of danazol and placebo in the treatment of adult idiopathic gynaecomastia: result of a prospective study in 55 patients. Ann R Coll Surg Engl 1990; 72:296-98 34. Khan HN, Blamey RW. Endocrine treatment of physiological gynaecomastia. BMJ 2003; 327(7410): 301-02 35. Parker LN, Gray DR, Lai MK et al. Treatment of gynaecomastia with tamoxifen: a double-blind crossover study. Metabolism 1986; 35(8): 705-08 36. McDermott MT, Hofeldt FD, Kidd GS. Tamoxifen therapy for painful idiopathic gynaecomastia. South Med J 1990; 83(11): 1283-85 37. Alagaratnam TT. Idiopathic gynaecomastia treated with tamoxifen: a preliminary report. Clin Ther 1987; 9(5): 483-87 38. Khan HN, Ramoaul R, Blamey RW. The use of tamoxifen for gynaecomastia at Nottingham Breast Unit. Br J Surg 2003; 90(s1):1 00 39. Parker LN, Gray DR, Lai MK et al. Treatment of gynaecomastia with tamoxifen: a double-blind crossover study. Metabolism 1986; 35(8):705-08
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40. Serels S, Melman A. Tamoxifen as treatment for gynaecomastia and mastodynia resulting from hormonal deprivation. J Urol 1998; 159(4): 1309. 41. Staiman VR, Lowe FC. Tamoxifen for utamide/ nasteride-induced gynaecomastia. Urology 1997; 50(6): 929-33 42. Dobs A, Darkes MJ. Incidence and management of gynaecomastia in men treated with prostate cancer. J Urol 2005; 174(5): 1731-42 43. Braunstein GD. Aromatase and gynaecomastia. Endocr Relat Cancer 1999; 6(2): 315-24 44. Boccardo F, Rubagotti A, Battaglia M et al. Evaluation of tamoxifen and anastrozole in the prevention of gynaecomastia and breast pain induced by bicalutamide monotherapy of prostate cancer. J Clin Oncol. 2005; 23(4): 808-15 45. Ting AC, Chow LW, Leung YF. Comparison of tamoxifen with danazol in the management of idiopathic gynaecomastia. Am Surg 2000; 66(1): 38-40 46. Moss ALH. The surgical approach to gynaecomastia. N Z Med J 1982; 95: 505-06 47. Colombo-Benkmann M, Buse B et al. Surgical therapy of gynaecomastia and its results. Langenbecks Arch Chir Suppl Kongress 1998; 11: 1282-84 48. Nicolis GL, Modlinger RS, Gabrilove JL. A study of the histopathology of human gynaecomastia. J Clin Endocrinol Metab 1971; 32(2): 173-78 49. Williams MJ. Gynaecomastia. Its incidence, recognition and host characterization in 447 autopsy cases. Am J Med1963; 34: 103-12 50. Webster JP. Mastectomy for gynaecomastia through a semicircular intra-areolar incision. Ann Surg 1946; 124: 557 51. Park AJ, Lamberty BG. Gynaecomastia: have Webster’s lessons been ignored? J R Coll Surg Edin 1998; 43(2): 89-92 52. Pitanguy I. Transareolar incision for gynaecomastia. Plast Reconstr Surg 1966; 38(5): 414-19 53. Letterman G, Schurter M. Surgical correction of massive gynaecomastia. Plast Reconstr Surg 1972; 49(3): 259-62 54. Melmed EP. Surgical treatment of grade III gynaecomastia. Ann R Coll Surg Engl 1990; 72(1): 68-9 55. Wray RC Jr, Hoopes JE, Davis GM. Correction of extreme gynaecomastia. Br J Plast Surg 1974; 27(1): 39-41 56. Rohrich RJ, Ha RY, Kenkel JM et al. Classication and management of gynaecomastia: dening the role of ultrasound-assisted liposuction. Plast Reconstr Surg 2003; 111(2): 909-25 57. Iwuagwu OC, Calvey TA, Ilsley D et al. Ultrasound guided minimally invasive breast surgery (UMIBS): a superior technique for gynaecomastia. Ann Plast Surg 2004; 52(2): 131-33 58. Hall-Craggs MA, Vaidya JS. Minimally invasive therapy for the treatment of breast tumours. Eur J Radiol 2002; 42(1): 52-57 59. Singletary SE. Minimally invasive techniques in breast cancer treatment.Semin Surg Oncol 2001; 20(3): 246-50
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THE MILLIN LECTURE 2009 The 32nd Millin Lecture will be delivered in November 2009. Fellows of the College are invited to nominate candidates. Completed applications must be received before Friday 8th May 2009. This is a prestigious award and open to all the Surgical specialties. Usually, the successful applicant will be well advanced in his/her surgical training or in their rst ve years in consultant practice. Preference will be given to candidates whose surgical research has been carried out wholly or in part in Ireland. The subject chosen should be of clinical interest embodying original research. Further particulars may be obtained from: Ms G Conroy Ofce of the Director of Surgical Affairs Royal College of Surgeons in Ireland 123 St Stephen’s Green Dublin 2. Tel: +353 1 4022187 email: [email protected] http://www.rcsi.ie
Professor W Arthur Tanner Director of Surgical Affairs
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