Endocrine treatment of physiological gynaecomastia

Gynecomastia is a common condition among normal healthy men of varying ages. Tenderness may be one of its symptoms, but the usual reason for presentation is that young men don't like having breasts and older men are worried about the possibility of cancer. Diagnosis is primarily by clinical examination and where necessary ultrasound and needle biopsy. Traditional methods of management of gynaecomastia have included simple analgesia for pain, and surgery. The most common reason for the patient to request surgery is cosmetic. However, although surgery in experienced hands is safe and effective, with minimal stay in hospital, the cosmetic results cannot always be guaranteed—noticeable scars, permanent pigment changes in the breast area, and mismatched breasts or nipples have been reported.¹ An uncommon but particularly ugly effect is tether of the subareolar area to the chest wall. These possible complications are balanced by the immediate therapeutic effect of surgery on gynaecomastia, especially in adolescents, for whom any form of prolonged treatment may not be appropriate.

At our hospital we recognise two forms of gynaecomastia; “lump” and “fatty” types. The former is a single firm retro-areolar lump, often tender, whereas the latter is a diffuse fatty lesion in the whole breast area. Adolescents usually have the lump form, and elderly people often have the fatty type.

Most cases of gynaecomastia have no known cause, especially in patients presenting in adolescence. Gynaecomastia secondary to underlying pathologies such as testicular tumours (very rare), liver dysfunction, or to a broad spectrum of drugs (notably oestrogens, cimetidine, and spironolactone) tends to be bilateral (by no means always) and is of the more diffuse fatty type.²

Primary breast cancer, although rare, is an important differential diagnosis. It usually presents as a lump—not centrally placed—and in male patients often shows skin tether. Ultrasound examination and core biopsies confirm the diagnosis.³

An altered ratio between serum free oestradiol (which stimulates mammary epithelium) and testosterone (which inhibits it) is believed to underlie the pathophysiology of physiological gynaecomastia.² Antioestrogens such as tamoxifen have therefore been suggested in the non-surgical treatment of this condition. Other suggested endocrine treatments have included clomiphene⁴ and danazol,⁵ both given for one to three months. Clomiphene is a non-steroidal agent with a weak oestrogenic activity. It acts on the hypothalamic-pituitary axis to increase gonadotrophin releasing hormone and therefore luteinising hormone releasing hormone and follicle stimulating hormone release. Its efficacy as a satisfactory medical treatment for gynaecomastia has not been proved. Danazol inhibits the production of oestrogen by suppressing the pituitary-ovarian axis due to the inhibition of the output of both follicle stimulating hormone and luteinising hormone from the pituitary gland. It also has androgenic side effects. It has proved effective in the management of gynaecomastia compared with placebo,⁵ but adverse effects such as weight gain limit its application in general use.

Table 1.

Previous studies of tamoxifen on physiological gynaecomastia

	Tamoxifen dose (daily dose in mg)	Duration (months)	No of patients	Success No/total (%)
Ting6	20	3	23	Lump: 18/23 (78) Pain: 19/23 (82)
Parker7	10	2	10	Lump: 7/10 (70) Pain: 4/4 (100)
McDermott8	20	2-4	6	Lump: 3/6 (50) Pain: 5/6 (83)
Alagaratnam9	40	2	61	Lump: 49/61 (80) Pain: 49/61 (80)

The use of tamoxifen for gynaecomastia has been studied previously in several centres. The table shows the various published studies on the use and efficacy of tamoxifen for physiological gynaecomastia in the English literature.^6-9 Only two of these studies⁶,⁹ have more than 10 patients and both showed resolution of lump and pain in 80% of cases. A recent study from our own unit in 36 cases confirms this figure (83% resolution of lump).¹⁰ Ting et al also found tamoxifen to be more efficacious than danazol.⁶ Importantly only minor and reversible side effects were reported. This confirms findings that tamoxifen used in male breast cancer appears to have no serious side effects.¹¹ Tamoxifen appears to be successful, safe, and avoids operation and on present evidence should be regarded as the first line treatment of gynecomastia.