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Don’t forget the men ! Gynaecomastia Professor Philip J Drew.

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Presentation on theme: "Don’t forget the men ! Gynaecomastia Professor Philip J Drew."— Presentation transcript:

1 Don’t forget the men ! Gynaecomastia Professor Philip J Drew

2 Gynaecomastia “ Man boobs” “Moobs” “ Man boobs” “Moobs” Increasing Increasing Actual Actual Patient Expectations Patient Expectations Male breast cancer Male breast cancer – 1.08 / 100,000 men 0.86 – 1.08 / 100,000 men Giordano et al Cancer 2004

3 Gynaecomastia Definition: Histologically: Histologically: Benign proliferation of glandular tissue of the male breast Benign proliferation of glandular tissue of the male breast Clinically: Clinically: Rubbery firm mass extending concentrically from the nipple Rubbery firm mass extending concentrically from the nipple Pseudogynaecomastia: Pseudogynaecomastia: Fat deposition without glandular proliferation “lipomastia” Fat deposition without glandular proliferation “lipomastia”

4 Gynaecomastia Pathophysiology: due to oestrogen / androgen imbalance Pathophysiology: due to oestrogen / androgen imbalance Primary Primary Secondary Secondary Decrease in androgen Decrease in androgen Actual / relative Actual / relative Increased binding to SHBG Increased binding to SHBG Receptor blockade Receptor blockade Increase in oestrogen Increase in oestrogen Direct / indirect (precursors) Direct / indirect (precursors)

5 Gynaecomastia Histology Histology Early “florid” phase Early “florid” phase Oestrogen Oestrogen Ductal epithelial hyperplasia Ductal epithelial hyperplasia Ductal elongation and branching Ductal elongation and branching Proliferation periductal fibroblasts Proliferation periductal fibroblasts Later inactive senescent phase Later inactive senescent phase Dense fibrous tissue Dense fibrous tissue Breast enlargement may diminish Breast enlargement may diminish Male / Female breast tissue Male / Female breast tissue Similar responsiveness Similar responsiveness No acinar development in men (progesterone) No acinar development in men (progesterone) Wilson RL et al Adv Intern Med 1980

6 Gynaecomastia Aetiology Aetiology Persistent pubertal gynaecomastia25% Persistent pubertal gynaecomastia25% Drugs10-25% Drugs10-25% Idiopathic25% Idiopathic25% Cirrhosis or malnutrition8% Cirrhosis or malnutrition8% Primary hypogonadism8% Primary hypogonadism8% Testicular tumours3% Testicular tumours3% Secondary hypogonadism2% Secondary hypogonadism2% Hyperthyroidism1.5% Hyperthyroidism1.5%

7 Primary Gynaecomastia Prevalence: “Trimodal” Infants:60% to 90% Infants:60% to 90% Pubertal:30% to 60% Pubertal:30% to 60% Adults:24% to 80% Adults:24% to 80% Wise et al J Am Coll Surg 2005

8 Gynaecomastia Pubertal gynaecomastia Pubertal gynaecomastia Bilateral 50-60% Bilateral 50-60% Midpuberty Midpuberty Nydick et al Nydick et al 1855 boy scouts 1855 boy scouts 65% 14 yr olds 65% 14 yr olds 14% 16 yr olds 14% 16 yr olds Exact mechanism unknown Exact mechanism unknown Oestrogen increases before testosterone Oestrogen increases before testosterone Most resolve spontaneously Most resolve spontaneously Moore DC J Clin Endocrinol Metab 1984 Nydick et al J Am Med Soc 1961

9 Gynaecomastia Marked pubertal breast development Marked pubertal breast development 10% endocrine abnormality 10% endocrine abnormality Kleinfelter’s / XX maleness Kleinfelter’s / XX maleness Primary testicular failure Primary testicular failure Androgen insensitivity Androgen insensitivity Increase aromatase activity Increase aromatase activity Autosomal dominant gene Autosomal dominant gene Sher ES et al Clinical Paediatrics 1998

10 Gynaecomastia Age related “senescent” gynaecomastia Age related “senescent” gynaecomastia Increases in normal men after 44yrs (57%) Increases in normal men after 44yrs (57%) Histologically only 7% active phase Histologically only 7% active phase Bilateral >90% Bilateral >90% Peak 50-69yrs (72%) Peak 50-69yrs (72%) Decreases yrs (47%) Decreases yrs (47%) >80% if BMI>25 >80% if BMI>25 Nuttal FQ J Clin Endocrinol Metab 1979

11 Gynaecomastia Systemic Illness Systemic Illness Liver disease Liver disease Alcoholic cirrhosis Alcoholic cirrhosis Direct effect on hypothalamic-pituitary-testicular system Direct effect on hypothalamic-pituitary-testicular system SHBG increased – decreases free testosterone SHBG increased – decreases free testosterone Thyrotoxicosis Thyrotoxicosis SHBG increased SHBG increased Increased peripheral aromatisation Increased peripheral aromatisation 25-40% men with Grave’s disease 25-40% men with Grave’s disease

12 Gynaecomastia Chronic renal failure Chronic renal failure Dialysis patients: 50% Dialysis patients: 50% Leydig cell dysfunction Leydig cell dysfunction HIV HIV Antiretroviral therapy Antiretroviral therapy Inhibition of cytochrome P450 enzyme Inhibition of cytochrome P450 enzyme Malnutrition Malnutrition “Refeeding” gynaecomastia “Refeeding” gynaecomastia Second puberty Second puberty Biglia A et al Clin Infect Diseases 2004 Holdsworth et al N Engl J Med 1977 Smith SR J Clin Endocrinol Metab 1975

13 Gynaecomastia Testicular neoplasms Germ cell tumours Germ cell tumours 2.5-6% gynaecomastia at presentation 2.5-6% gynaecomastia at presentation hCG hCG Leydig cell dysfunction Leydig cell dysfunction Inhibition of 17 alpha hydoxylase / 17,20 lyase enzymes Inhibition of 17 alpha hydoxylase / 17,20 lyase enzymes Increased CYP450 aromatase activity Increased CYP450 aromatase activity Poor prognostic sign Poor prognostic sign Same mechanism for other hCG producing tumours Same mechanism for other hCG producing tumours Leydig cell tumour Leydig cell tumour 2% testicular neoplasms 2% testicular neoplasms Testosterone and oestrodiol Testosterone and oestrodiol 6-10 yr olds 6-10 yr olds Precocious puberty Precocious puberty yr olds yr olds Testicular mass, impotence Testicular mass, impotence 20-30% have gynaecomastia at presentation 20-30% have gynaecomastia at presentation

14 Gynaecomastia Other tumours Other tumours Prolactinoma Prolactinoma 8% 8% Hypogonadotrophic hypogonadism Hypogonadotrophic hypogonadism Large cell calcifying Sertoli cell (sex-cord) tumours Large cell calcifying Sertoli cell (sex-cord) tumours Increased aromatase activity Increased aromatase activity Sporadic Sporadic Autosomal dominant Autosomal dominant Peutz-Jehger’s syndrome Peutz-Jehger’s syndrome Carney complex Carney complex Feminising adrenocortical tumours Feminising adrenocortical tumours 98% gynaecomastia 98% gynaecomastia 58% palpable adrenal tumour 58% palpable adrenal tumour 50% testicular atrophy 50% testicular atrophy Pituitary / Hypothalamic tumours Pituitary / Hypothalamic tumours Braunstein GD Endocr Related Cancer 1999

15 Gynaecomastia True hermaphroditism True hermaphroditism Testicular and ovarian tissue Testicular and ovarian tissue Excessive oestrogen production Excessive oestrogen production Direct affect Direct affect Suppression of intratesticular cytochrome P450 Suppression of intratesticular cytochrome P450 Androgen insensitivity syndromes Androgen insensitivity syndromes Defect or absence intracellular androgen receptor Defect or absence intracellular androgen receptor Spectrum Spectrum Complete absence “testicular feminisation” Complete absence “testicular feminisation” Phenotypic females Phenotypic females Complete / partial insensitivity Complete / partial insensitivity Phenotypic males Phenotypic males Quigley CA et al Endocr Rev 1995

16 Gynaecomastia Primary hypogonadism Primary hypogonadism Congenital Congenital Klinefelter’s syndrome Klinefelter’s syndrome Lobular strutures Lobular strutures 16 fold increase in breast cancer 16 fold increase in breast cancer Acquired Acquired Trauma Trauma Infection Infection Infiltration Infiltration Vascular insufficiency Vascular insufficiency Age Age Decrease in testosterone Decrease in testosterone Increase in LH release Increase in LH release Increase in aromatisation of testosterone to estradiol Increase in aromatisation of testosterone to estradiol

17 Gynaecomastia Secondary hypogonadism Secondary hypogonadism Prostate cancer treatment Prostate cancer treatment Combined androgen blockade50% Combined androgen blockade50% LH-RH analogue alone25% LH-RH analogue alone25% Orchidectomy alone10% Orchidectomy alone10% Combined drug + orchidectomy1-24% Combined drug + orchidectomy1-24% Dicker AP Lancet Oncol 2003

18 Gynaecomastia BPH BPH Finesteride Finesteride Type II 5 alpha – reductase inhibitor Type II 5 alpha – reductase inhibitor Blocks testosterone to DHT conversion Blocks testosterone to DHT conversion Increase tesosterone – precursor to oestrodiol Increase tesosterone – precursor to oestrodiol Oestrodiol increase leads to gynaecomastia Oestrodiol increase leads to gynaecomastia But...increased risk of male (and female) breast cancer cannot be excluded But...increased risk of male (and female) breast cancer cannot be excluded Total data (MHRA Dec 2009): Total data (MHRA Dec 2009): 90,000 pt/yr exposure, rate7.82 per 100,000 PYR 90,000 pt/yr exposure, rate7.82 per 100,000 PYR 80,000 placebo / yr exposure, rate 3.84 per 100,000 PYR 80,000 placebo / yr exposure, rate 3.84 per 100,000 PYR P=0.328 P=0.328

19 Gynaecomastia Anabolic steroids 52% gynaecomastia 52% gynaecomastia 57% testicular atrophy 57% testicular atrophy Self medicate with Tam or AI for gynaecomastia Self medicate with Tam or AI for gynaecomastia hCG for testicular atrophy hCG for testicular atrophy Clomiphene / Nolvadex Clomiphene / Nolvadex “PCT” “PCT” Post cycle therapy Post cycle therapy

20 Gynaecomastia Other causes Other causes Diabetic mastopathy Diabetic mastopathy Not related to type of insulin Not related to type of insulin Mimics gynaecomastia clinically Mimics gynaecomastia clinically Different histologically Different histologically Occupational Occupational Morticians Morticians Very unusual causes Very unusual causes Drinking female urine Drinking female urine Vierhapper H Lancet 1999

21 Gynaecomastia Drug therapy Drug therapy Large number implicated Large number implicated Obvious association with hormonal agents Obvious association with hormonal agents Difficult to confirm for other agents Difficult to confirm for other agents Thompson & Carter Thompson & Carter Probable Probable Ca channel blockers, chemotherapy, H 2 blockers, ketoconazole, spirinolactone Ca channel blockers, chemotherapy, H 2 blockers, ketoconazole, spirinolactone Inconclusive Inconclusive Digitalis, neuroleptic agents and marijuana Digitalis, neuroleptic agents and marijuana Thompson DF & Carter JR Pharmacotherapy 1993

22 Gynaecomastia Assessment: Assessment: Clinical Clinical Imaging - ? mammogram / ultrasound Imaging - ? mammogram / ultrasound Tissue ? Core biopsy Tissue ? Core biopsy Not FNAC – C3 result Not FNAC – C3 result

23 Gynaecomastia Clinical assessment Clinical assessment History History Age of onset Age of onset Duration Duration Family history Family history Aromatase excesss syndrome Aromatase excesss syndrome Auto dominant Auto dominant Chromosome 15 Chromosome 15 Underlying disorders Underlying disorders Hyperthyroidism Hyperthyroidism Hepatic / Renal disease Hepatic / Renal disease Loss of libido / impotence Loss of libido / impotence Drug history Drug history

24 Gynaecomastia Examination Examination Swelling of the breast Swelling of the breast Tender Tender Concentric Concentric Mobile Mobile Sinister findings Sinister findings Eccentric, unilateral, nipple retraction, skin dimpling, lymphadenopathy, nipple discharge Eccentric, unilateral, nipple retraction, skin dimpling, lymphadenopathy, nipple discharge Pseudogynaecomastia Pseudogynaecomastia No resistance to apposition of fingers No resistance to apposition of fingers Abdominal / chest / ? testes examination Abdominal / chest / ? testes examination

25 GYNAECOMASTIA – CLASSIFICATION Simons et al ( 1973 ) Simons et al ( 1973 ) I.Minor breast enlargement without skin redundancy

26 Gynaecomastia Investigation Investigation Teenager with otherwise normal examination Teenager with otherwise normal examination Re-examine to establish whether persistent Re-examine to establish whether persistent Adult or persistent/marked pubertal gynaecomastia Adult or persistent/marked pubertal gynaecomastia BCP, Prolactin, LH, Oestrogen, Testosterone, hCG BCP, Prolactin, LH, Oestrogen, Testosterone, hCG Consider genetic causes Consider genetic causes

27 Gynaecomastia

28 Gynaecomastia Imaging / biopsy Imaging / biopsy Mammography Mammography Negative predictive value for malignancy: 99% Negative predictive value for malignancy: 99% Ultrasound +/- core biopsy Ultrasound +/- core biopsy Imaging for clinical gynaecomastia no longer supported by RCR Imaging for clinical gynaecomastia no longer supported by RCR Evans et al Am J Surg 2001

29 Gynaecomastia Primary gonadal failure “Hypogonadism” “Hypogonadism” “Andropause” “Andropause” Consider endocrinology referral Consider endocrinology referral Testosterone Replacement Therapy? Testosterone Replacement Therapy? No mature data from large trials No mature data from large trials

30 Gynaecomastia TRT TRT Potential benefits / drawbacks Potential benefits / drawbacks Bone density Bone density Cognition Cognition Muscle mass / body composition Muscle mass / body composition Mood Mood Erythropoiesis Erythropoiesis Libido Libido

31 Gynaecomastia TRT TRT Potential harm Potential harm ?Cardiovascular disease ?Cardiovascular disease Putative relationship Putative relationship Studies actually show favourable effect Studies actually show favourable effect Prostate risks Prostate risks Mild increase in volume Mild increase in volume Theoretical cancer risk Theoretical cancer risk Snyder PJ J Clin Endocrinol Metab 2000

32 Treatment of Gynaecomastia Indications Indications Pain Pain Tenderness Tenderness Embarrassment interfering with normal activity Embarrassment interfering with normal activity Options Options Medical Medical Surgical Surgical

33 Gynaecomastia Non-surgical treatment Non-surgical treatment Reassure and observe Reassure and observe Painful for 6-12 months during florid phase Painful for 6-12 months during florid phase Revue medication Revue medication Correct obesity / lifestyle Correct obesity / lifestyle Medication Medication Little good data Little good data End points difficult to assess End points difficult to assess Tends to resolve anyway Tends to resolve anyway Pain is self limiting Pain is self limiting

34 Gynaecomastia Medical therapy Medical therapy Clomiphene Clomiphene Danazol Danazol Tamoxifen Tamoxifen Aromatase Inhibitors Aromatase Inhibitors

35 Gynaecomastia Clomiphene mg day Clomiphene mg day Evaluated in adolescents Evaluated in adolescents Unproven efficacy especially at 50mg Unproven efficacy especially at 50mg May achieve up to 64% resolution May achieve up to 64% resolution Adverse effects rare Adverse effects rare Danazol 400mg day Danazol 400mg day Evaluated in adolescents (200mg day) Evaluated in adolescents (200mg day) Objective response 20-76% Objective response 20-76% Side effects common Side effects common Weight gain, acne, abnormal LFT’s Weight gain, acne, abnormal LFT’s LeeRoith et al Acta Endocrinol 1980 Jones DJ et al Ann RCS Eng 1990

36 Gynaecomastia Tamoxifen Tamoxifen Not evaluated in adolescents Not evaluated in adolescents Generally poorly designed trials and audits Generally poorly designed trials and audits Total of 136 patients in 5 trials Total of 136 patients in 5 trials Only 113 studied prospectively Only 113 studied prospectively No randomised controlled studies No randomised controlled studies Doses of 10, 20 & 40mg used Doses of 10, 20 & 40mg used From this “evidence” in adults From this “evidence” in adults Reduces pain:70-100% Reduces pain:70-100% May decrease lump:50-80% May decrease lump:50-80% Amoxifene Amoxifene 4-OH Tam gel 4-OH Tam gel No significant systemic level No significant systemic level Trial in design stage (Hull / Cardiff) Trial in design stage (Hull / Cardiff) Plourde PV et al J Clin Endocrinol Metab 2004 Kahn HN, Blamey RW BMJ 2003

37 Gynaecomastia Aromatase Inhibitors Aromatase Inhibitors One RCT in adolescents One RCT in adolescents Pain reduced Pain reduced No effect on lump No effect on lump Theoretical risks Theoretical risks Bone health Bone health LH increases leading to peripheral aromatisation LH increases leading to peripheral aromatisation Not use AI’s for male breast cancer Not use AI’s for male breast cancer

38 Gynaecomastia Prostate cancer therapy Prostate cancer therapy Bicalutamide Bicalutamide Dose dependent response to Tamoxifen prohylaxis Dose dependent response to Tamoxifen prohylaxis 8.8% on 20mg/day 8.8% on 20mg/day 96.7% placebo 96.7% placebo No increase in PSA No increase in PSA Alternatives Alternatives Low dose irradiation Low dose irradiation Fradet, Yves, Egerdie et al Europ Urol (1):

39 Gynaecomastia - Surgery Glandular enlargement with no/little excess skin Glandular enlargement with no/little excess skin ?liposuction alone – will not remove glandular element ?liposuction alone – will not remove glandular element Ultrasound assisted Ultrasound assisted Risk of thermal damage Risk of thermal damage Minimally invasive gland excision +/- liposuction Minimally invasive gland excision +/- liposuction

40 USS Guided Intervention VABD VABD Initially diagnostic Initially diagnostic Burbank, Parker, Fogarty Am J Surg 1996 Burbank, Parker, Fogarty Am J Surg 1996 Therapeutic Therapeutic Zannis, Aliano Am J Surg 1998 Zannis, Aliano Am J Surg 1998

41 VABD Breast vacuum biopsy system Breast vacuum biopsy system Hand held Hand held Multiple sampling through a single incision Multiple sampling through a single incision Introduction of 8-gauge probe Introduction of 8-gauge probe Therapeutic procedures Therapeutic procedures

42 Mammotome ® Technique

43 Gynaecomastia - VABD Hull Breast Unit Hull Breast Unit Patients Patients 59 men 59 men Mean age 38 (range 21-80) Mean age 38 (range 21-80) Grade Grade Grade 1/2 Grade 1/2 14 unilateral 14 unilateral

44 Gynaecomastia Complications Complications Haematoma n=2 Haematoma n=2 Spontaneously resolved Spontaneously resolved (“Bruising” inevitable) (“Bruising” inevitable) Recurrence n=2 Recurrence n=2 Re-mammotome Re-mammotome Iwuagwu O et al Annals of Plastic Surgery 2004

45 Gynaecomastia Operating time Operating time 50 min (range min) 50 min (range min) Patient satisfaction:8-9/10 Patient satisfaction:8-9/10 Cosmesis:9-10/10 Cosmesis:9-10/10

46 Gynaecomastia

47 Gynaecomastia - Surgery  Excess skin +  Consider staged operation  Liposuction  +/- skin excision  Periareolar breast reduction  Excess skin +++  Consider Wise pattern, vertical scar etc.  Beware hypertrophic scars  Repeated periareolar operations

48 SURGICAL TECHNIQUE Pre-operative markings – standing Operative patient position : semi-sitting Infiltrate breast with adrenaline solution ( 1 litre Ringers, 1ml 1: 1000 adrenaline, LA )

49 GYNAECOMASTIA ASSESSMENT – NIPPLE POSITION A = ( 0.19 chest circumference ) cm B = ( 0.12 height ) – cm A B Shulman et al PRS 2001

50 CIRCUMAREOLAR CONCENTRIC SKIN REDUCTION

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57 Pseudo-gynaecomastia after massive weight loss

58 VERTICAL SCAR REDUCTION TECHNIQUE

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60 VERTICAL SCAR TECHNIQUE

61 GYNAECOMASTIA SURGERY – SKIN REDUCTION

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65 Gusenoff et alPlas. Recon. Surg. 122: p1301, 2008

66 Gynaecomastia Surgical complications Surgical complications Scarring and adherence to underlying muscle Scarring and adherence to underlying muscle Excessive resection Excessive resection Contour deformity Contour deformity Solutions Solutions Local dermoglandular flaps Local dermoglandular flaps Lipomodelling Lipomodelling Autologous fat injections Autologous fat injections

67 Gynaecomastia Summary Summary Usually “normal” or iatrogenic Usually “normal” or iatrogenic Occasional underlying disease Occasional underlying disease Consider primary gonadal failure in the mature male Consider primary gonadal failure in the mature male Investigate Investigate Persistent or extreme cases in adolescents Persistent or extreme cases in adolescents Adults Adults

68 Gynaecomastia Summary Summary Treatment Treatment Medical Medical Little good data Little good data Tamoxifen in adults only Tamoxifen in adults only Surgical Surgical Do the least required to achieve patient’s desires Do the least required to achieve patient’s desires Not supported by PCT unless “exceptional” Not supported by PCT unless “exceptional” Grade 1/2a Grade 1/2a Minimally invasive plus liposuction Minimally invasive plus liposuction Grade 2b/3 Grade 2b/3 Aesthetic techniques Aesthetic techniques

69 Gynaecomastia Conclusion Conclusion Common benign condition Common benign condition ? Normal part of ageing ? Normal part of ageing No licensed effective medication No licensed effective medication Trial needed Trial needed ?Minimally invasive surgery operation of choice if appropriate ?Minimally invasive surgery operation of choice if appropriate


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