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Don’t forget the men !
Gynaecomastia
Professor Philip J Drew
Gynaecomastia
 “Man boobs” “Moobs”
 Increasing
 Actual
 Patient
 Male
Expectations
breast cancer
 1973
- 1998
 0.86 – 1.08 / 100,000 men
Giordano et al Cancer 2004
Gynaecomastia
Definition:
 Histologically:


Clinically:


Benign proliferation of glandular tissue of the male breast
Rubbery firm mass extending concentrically from the nipple
Pseudogynaecomastia:

Fat deposition without glandular proliferation “lipomastia”
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)
Gynaecomastia

Histology


Early “florid” phase
Oestrogen




Later inactive senescent phase



Ductal epithelial hyperplasia
Ductal elongation and branching
Proliferation periductal fibroblasts
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
Gynaecomastia

Aetiology








Persistent pubertal gynaecomastia
Drugs
Idiopathic
Cirrhosis or malnutrition
Primary hypogonadism
Testicular tumours
Secondary hypogonadism
Hyperthyroidism
25%
10-25%
25%
8%
8%
3%
2%
1.5%
Primary Gynaecomastia
Prevalence: “Trimodal”

Infants:
60% to 90%

Pubertal:
30% to 60%

Adults:
24% to 80%
Wise et al J Am Coll Surg 2005
Gynaecomastia

Pubertal gynaecomastia


Bilateral 50-60%
Midpuberty


Nydick et al
1855 boy scouts



Exact mechanism unknown


65% 14 yr olds
14% 16 yr olds
Oestrogen increases before testosterone
Most resolve spontaneously
Moore DC J Clin Endocrinol Metab 1984
Nydick et al J Am Med Soc 1961
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
Gynaecomastia

Age related “senescent” gynaecomastia

Increases in normal men after 44yrs (57%)

Histologically only 7% active phase
Bilateral >90%
 Peak 50-69yrs (72%)
 Decreases 70-89 yrs (47%)


>80% if BMI>25
Nuttal FQ J Clin Endocrinol Metab 1979
Gynaecomastia

Systemic Illness

Liver disease

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

Gynaecomastia

Chronic renal failure



HIV



Dialysis patients: 50%
Leydig cell dysfunction
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
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


26-35 yr olds


Precocious puberty
Testicular mass, impotence
20-30% have gynaecomastia at presentation
Gynaecomastia

Other tumours

Prolactinoma



8%
Hypogonadotrophic hypogonadism
Large cell calcifying Sertoli cell (sex-cord) tumours



Increased aromatase activity
Sporadic
Autosomal dominant



Feminising adrenocortical tumours




Peutz-Jehger’s syndrome
Carney complex
98% gynaecomastia
58% palpable adrenal tumour
50% testicular atrophy
Pituitary / Hypothalamic tumours
Braunstein GD Endocr Related Cancer 1999
Gynaecomastia

True hermaphroditism

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
Gynaecomastia

Primary hypogonadism

Congenital

Klinefelter’s syndrome



Acquired






Lobular strutures
16 fold increase in breast cancer
Trauma
Infection
Infiltration
Vascular insufficiency
Age
Decrease in testosterone


Increase in LH release
Increase in aromatisation of testosterone to estradiol
Gynaecomastia

Secondary hypogonadism

Prostate cancer treatment
Combined androgen blockade
 LH-RH analogue alone
 Orchidectomy alone
 Combined drug + orchidectomy

Dicker AP Lancet Oncol 2003
50%
25%
10%
1-24%
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
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
Gynaecomastia

Other causes

Diabetic mastopathy




Occupational


Not related to type of insulin
Mimics gynaecomastia clinically
Different histologically
Morticians
Very unusual causes

Drinking female urine
Vierhapper H Lancet 1999
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
Gynaecomastia

Assessment:

Clinical
Imaging - ? mammogram / ultrasound
Tissue ? Core biopsy



Not FNAC – C3 result
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
Gynaecomastia

Examination





Sinister findings


Eccentric, unilateral, nipple retraction, skin dimpling, lymphadenopathy, nipple
discharge
Pseudogynaecomastia


Swelling of the breast
Tender
Concentric
Mobile
No resistance to apposition of fingers
Abdominal / chest / ? testes examination
GYNAECOMASTIA –
CLASSIFICATION

Simons et al ( 1973 )
I. Minor breast enlargement
without skin redundancy
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

Gynaecomastia
hCG, LH,
Testosterone, Estrogen
Increased hCG
Testicular
ultrasound
NormalCXR /
abdominal CT
Increased LH
Decreased
Testosterone
Primary
hypogonadism
Increased LH and
Testosterone
Normal
Idiopathic
gynaecomastia
Check TSH
Normal –
Androgen
resistance
Gynaecomastia

Imaging / biopsy

Mammography

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
Gynaecomastia
Primary gonadal failure
“Hypogonadism”
 “Andropause”

Consider endocrinology referral
 Testosterone Replacement Therapy?


No mature data from large trials
Gynaecomastia

TRT

Potential benefits / drawbacks
Bone density
 Cognition
 Muscle mass / body composition
 Mood
 Erythropoiesis
 Libido

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
Treatment of Gynaecomastia

Indications




Pain
Tenderness
Embarrassment interfering with normal activity
Options

Medical

Surgical
Gynaecomastia

Non-surgical treatment

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
Gynaecomastia

Medical therapy
Clomiphene
 Danazol
 Tamoxifen
 Aromatase Inhibitors

Gynaecomastia

Clomiphene 50-100mg 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
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: 70-100%
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
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
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. 2007 52(1): 106-114
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
USS Guided Intervention

VABD

Initially diagnostic


Burbank, Parker, Fogarty Am J Surg 1996
Therapeutic

Zannis, Aliano Am J Surg 1998
VABD




Breast vacuum biopsy system
Hand held
Multiple sampling through a single incision
Introduction of 8-gauge probe
 Therapeutic procedures
Mammotome® Technique
Gynaecomastia - VABD


Hull Breast Unit
Patients
59 men
 Mean age 38 (range 21-80)


Grade
Grade 1/2
 14 unilateral

Gynaecomastia

Complications

Haematoma n=2
Spontaneously resolved
 (“Bruising” inevitable)


Recurrence n=2

Re-mammotome
Iwuagwu O et al Annals of Plastic Surgery 2004
Gynaecomastia

Operating time



50 min (range 20-60 min)
Patient satisfaction: 8-9/10
Cosmesis:
9-10/10
Gynaecomastia
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
SURGICAL TECHNIQUE

Pre-operative markings – standing

Operative patient position : semi-sitting

Infiltrate breast with adrenaline solution
( 1 litre Ringers, 1ml 1: 1000 adrenaline , LA )
GYNAECOMASTIA ASSESSMENT –
NIPPLE POSITION
B
A

A = ( 0.19 chest circumference ) + 2.192 cm

B = ( 0.12 height ) – 2.782 cm
•Shulman et al PRS 2001
CIRCUMAREOLAR
CONCENTRIC SKIN REDUCTION
CIRCUMAREOLAR
CONCENTRIC SKIN REDUCTION
CIRCUMAREOLAR
CONCENTRIC SKIN REDUCTION
CIRCUMAREOLAR CONCENTRIC SKIN
REDUCTION
CIRCUMAREOLAR
CONCENTRIC SKIN REDUCTION
CIRCUMAREOLAR
CONCENTRIC SKIN REDUCTION
CIRCUMAREOLAR CONCENTRIC SKIN
REDUCTION
Pseudo-gynaecomastia after massive
weight loss
VERTICAL SCAR REDUCTION TECHNIQUE
VERTICAL SCAR REDUCTION TECHNIQUE
VERTICAL SCAR TECHNIQUE
GYNAECOMASTIA SURGERY –
SKIN REDUCTION
GYNAECOMASTIA SURGERY –
SKIN REDUCTION
GYNAECOMASTIA SURGERY –
SKIN REDUCTION
GYNAECOMASTIA SURGERY –
SKIN REDUCTION
GYNAECOMASTIA SURGERY –
SKIN REDUCTION
Gusenoff et al
Plas. Recon. Surg. 122: p1301, 2008
Gynaecomastia

Surgical complications
Scarring and adherence to underlying muscle
 Excessive resection



Contour deformity
Solutions
Local dermoglandular flaps
 Lipomodelling


Autologous fat injections
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

Gynaecomastia

Summary

Treatment

Medical



Surgical



Do the least required to achieve patient’s desires
Not supported by PCT unless “exceptional”
Grade 1/2a


Little good data
Tamoxifen in adults only
Minimally invasive plus liposuction
Grade 2b/3

Aesthetic techniques
Gynaecomastia

Conclusion
Common benign condition
 ? Normal part of ageing
 No licensed effective medication
 Trial needed
 ?Minimally invasive surgery operation of choice if
appropriate
