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

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

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

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

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

6. Gynaecomastia Aetiology Persistent pubertal gynaecomastia 25%
Drugs %
Idiopathic %
Cirrhosis or malnutrition 8%
Primary hypogonadism 8%
Testicular tumours 3%
Secondary hypogonadism 2%
Hyperthyroidism %

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

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

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

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

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

12. Gynaecomastia Chronic renal failure HIV Malnutrition
Dialysis patients: 50%
Leydig cell dysfunction
HIV
Antiretroviral therapy
Inhibition of cytochrome P450 enzyme
Malnutrition
“Refeeding” gynaecomastia
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
2.5-6% gynaecomastia at presentation
hCG
Leydig cell dysfunction
Inhibition of 17 alpha hydoxylase / 17,20 lyase enzymes
Increased CYP450 aromatase activity
Poor prognostic sign
Same mechanism for other hCG producing tumours
Leydig cell tumour
2% testicular neoplasms
Testosterone and oestrodiol
6-10 yr olds
Precocious puberty
26-35 yr olds
Testicular mass, impotence
20-30% have gynaecomastia at presentation

14. Gynaecomastia Other tumours Prolactinoma8%
Hypogonadotrophic hypogonadism
Large cell calcifying Sertoli cell (sex-cord) tumours
Increased aromatase activity
Sporadic
Autosomal dominant
Peutz-Jehger’s syndrome
Carney complex
Feminising adrenocortical tumours
98% gynaecomastia
58% palpable adrenal tumour
50% testicular atrophy
Pituitary / Hypothalamic tumours
Braunstein GD Endocr Related Cancer 1999

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

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

17. Gynaecomastia Secondary hypogonadism Prostate cancer treatment
Combined androgen blockade 50%
LH-RH analogue alone 25%
Orchidectomy alone 10%
Combined drug + orchidectomy 1-24%
Dicker AP Lancet Oncol 2003

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

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

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

21. Gynaecomastia Drug therapy Large number implicated
Obvious association with hormonal agents
Difficult to confirm for other agents
Thompson & Carter
Probable
Ca channel blockers, chemotherapy, H2 blockers, ketoconazole, spirinolactone
Inconclusive
Digitalis, neuroleptic agents and marijuana
Thompson DF & Carter JR Pharmacotherapy 1993

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

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

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

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

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

27. Gynaecomastia

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

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

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

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

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

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

34. Gynaecomastia Medical therapy Clomiphene Danazol Tamoxifen
Aromatase Inhibitors

35. Gynaecomastia Clomiphene 50-100mg day Danazol 400mg day
Evaluated in adolescents
Unproven efficacy especially at 50mg
May achieve up to 64% resolution
Adverse effects rare
Danazol 400mg day
Evaluated in adolescents (200mg day)
Objective response 20-76%
Side effects common
Weight gain, acne, abnormal LFT’s
LeeRoith et al Acta Endocrinol 1980
Jones DJ et al Ann RCS Eng 1990

36. Gynaecomastia Tamoxifen Not evaluated in adolescents
Generally poorly designed trials and audits
Total of 136 patients in 5 trials
Only 113 studied prospectively
No randomised controlled studies
Doses of 10, 20 & 40mg used
From this “evidence” in adults
Reduces pain: %
May decrease lump: 50-80%
Amoxifene
4-OH Tam gel
No significant systemic level
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 One RCT in adolescents
Pain reduced
No effect on lump
Theoretical risks
Bone health
LH increases leading to peripheral aromatisation
Not use AI’s for male breast cancer

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

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

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

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

42. Mammotome® Technique

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

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

45. Gynaecomastia Operating time Patient satisfaction: 8-9/10
50 min (range min)
Patient satisfaction: 8-9/10
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 POSITIONB A
A = ( 0.19 chest circumference ) cm
B = ( 0.12 height ) – cm
Shulman et al PRS 2001

50. CIRCUMAREOLAR CONCENTRIC SKIN REDUCTION

51. CIRCUMAREOLAR CONCENTRIC SKIN REDUCTION

52. CIRCUMAREOLAR CONCENTRIC SKIN REDUCTION

53. CIRCUMAREOLAR CONCENTRIC SKIN REDUCTION

54. CIRCUMAREOLAR CONCENTRIC SKIN REDUCTION

55. CIRCUMAREOLAR CONCENTRIC SKIN REDUCTION

56. CIRCUMAREOLAR CONCENTRIC SKIN REDUCTION

57. Pseudo-gynaecomastia after massive weight loss

58. VERTICAL SCAR REDUCTION TECHNIQUE

59. VERTICAL SCAR REDUCTION TECHNIQUE

60. VERTICAL SCAR TECHNIQUE

61. GYNAECOMASTIA SURGERY – SKIN REDUCTION

62. GYNAECOMASTIA SURGERY – SKIN REDUCTION

63. GYNAECOMASTIA SURGERY – SKIN REDUCTION

64. GYNAECOMASTIA SURGERY – SKIN REDUCTION

65. GYNAECOMASTIA SURGERY – SKIN REDUCTION
Gusenoff et al Plas. Recon. Surg. 122: p1301, 2008

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

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

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

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