Endocrine treatment of physiological gynaecomastia
BMJ 2003; 327 doi: https://doi.org/10.1136/bmj.327.7410.301 (Published 07 August 2003) Cite this as: BMJ 2003;327:301All rapid responses
Rapid responses are electronic comments to the editor. They enable our users to debate issues raised in articles published on bmj.com. A rapid response is first posted online. If you need the URL (web address) of an individual response, simply click on the response headline and copy the URL from the browser window. A proportion of responses will, after editing, be published online and in the print journal as letters, which are indexed in PubMed. Rapid responses are not indexed in PubMed and they are not journal articles. The BMJ reserves the right to remove responses which are being wilfully misrepresented as published articles or when it is brought to our attention that a response spreads misinformation.
From March 2022, the word limit for rapid responses will be 600 words not including references and author details. We will no longer post responses that exceed this limit.
The word limit for letters selected from posted responses remains 300 words.
Dear Sir - We read with interest Professor Blamey's article on the Treatment of
Gynaecomastia and were amazed at his suggestion that a drug which does not
have a product licence for the treatment of gynaecomastia should be
recommended as the first-line treatment of this condition. The evidence
base for his conclusion is small (135 patients) and is certainly not
derived from randomised controlled clinical trials. Gynaecomastia is most
common in pubertal boys in which the condition is usually self-limiting
(1) and we certainly do not have the sufficient data to show that
Tamoxifen is safe in this group of patients. There are still many
unanswered questions:
What effect does it have on bone growth?; Does the gynaecomastia come
back after stopping treatment?; What is the optimum duration of therapy?
We feel that this article is misleading and until we have more
evidence demonstrating that Tamoxifen is safe in this condition then we
should not be suggesting that this is used as first-line therapy
especially in pubertal boys.
Ref (1): Nydick M, Bustos J, Dale J H, Rawson R W. Gynaecomastia in
Adolescent Boys. Journal of the American Medical Association 1961;
178:449-557.
Competing interests:
None declared
Competing interests: No competing interests
EDITOR - Further to Hakim and Blamey’s timely editorial on the taboo subject
of gynaecomastia 1, we wish to clarify several points, which we address
below, but strongly concur that surgery should be reserved for recurrent
cases and those that do not respond to medical therapy (about 15% overall
2), for the reasons given in their article.
We recently published a large series of men with a breast “lump”. A
consecutive series of 175 men 2 presenting to a single surgeon was
investigated thoroughly including imaging, biochemical, hormonal and
testicular tumour marker tests and core biopsy where appropriate.
We noted that:
1) there are two types of gynaecomastia, true and pseudo, true being
enlargement of ductal and stromal tissue with varying degrees of
proliferation and pseudo being essentially adipose tissue with no increase
in ductal or stromal breast tissue. Both may coexist.
2) gynaecomastia can be primary (which is common in puberty and
senescence) and is often part of the spectrum of normal and varies with
incidence and significance. Secondary gynaecomastia is often related to
drugs but may be due to less common pathology (see 4 below). The
“physiological gynaecomastia” to which Hakim and Blamey refer 1 is
presumably true primary gynaecomastia.
3) fine needle biopsy in men is particularly painful and unrewarding
with a higher inadequate (C1) rate than in women due to the nature of the
histology.
4) the cause of gynaecomastia remains idiopathic in around a third
but in our series we discovered eight invasive breast cancers and four
testicular cancers 3 amongst other causations including five with
hyperprolactinaemia.
5) gynaecomastia is often transient so reassurance may be all that
is required and then no treatment is needed 2.
6) Danazol is effective in 80% and is licensed and we recommend a
short six week course of 100mg bd for a week, followed by 100mg tds for
the second to sixth weeks with assessment of response at the eighth week.
A repeat course may be prescribed in those cases responding notably with a
decrease in pain and/or size of the breast enlargement.
7) repeat imaging, both mammograms and ultrasound is useful to
objectively monitor the response to medical treatment.
8) surgical intervention should be reserved for refractory cases 4.
The evidence to recommend tamoxifen in preference to danazol is
sketchy. We advise caution on the use of tamoxifen, which at any dose or
for any length of time, is as yet unlicensed for the treatment of
gynaecomastia.
Competing interests: None declared
1 Khan HN, Blamey RW
Endocrine treatment of physiological gynaecomastia.
BMJ 2003;327:301-302 (9 August)
2 Daniels Ian R, Layer Graham T
How should gynaecomastia be managed?
Aust N Z J Surg 2003;73:213-216
3 Daniels IR, Layer GT
Testicular tumours presenting as gynaecomastia.
Eur J Surg Oncol 2003;29:437-439
4 Daniels IR, Layer GT
Gynaecomastia.
Eur J Surg 2001;167:885-892
Competing interests:
None declared
Competing interests: No competing interests
Treatment of gynaecomastia with raloxifene.
Sir,
We read with interest the Editorial on the treatment of gynaecomastia by
Khan & Blamey.1 They review the experience of several centres,
including their own, with the use of tamoxifen. We would like to comment
on our experience with another drug, raloxifene.
Selective oestrogen receptor modulators (SERMs) are a relatively new
family of drugs designed to act as oestrogens on some, but not all,
tissues.2 Tamoxifen is a first-generation SERM. Raloxifene, a second-generation SERM, has been extensively studied on postmenopausal women, and
is indicated for the treatment of postmenopausal osteoporosis.3 It is an
alternative to oestrogen replacement therapy in women with a history of
breast cancer.4, 5 Its anti-proliferative effect on mammary tissue is such
that prolonged use reduces the risk of breast cancer among osteoporotic
women.6
In a recent placebo-controlled short-term trial, the drug was
administered to 34 healthy males (mean age, 48 years) at the dose of 60
mg/day for one month; no subject developed gynaecomastia. Besides, serum
testosterone increased 20%, and serum estradiol decreased slightly.7
We decided to evaluate the effect of raloxifene in a series of patients
with gynaecomastia. Twelve patients aged 18-84 years were treated. Breast
enlargement was unilateral in 5 cases; its duration ranged from a few
weeks (7 cases) to several years (5 cases). Four patients were hypogonadal
by clinical criteria, and had low serum testosterone. In two patients
there was a possible drug effect (prasterone in one, ranitidine in the
other). The size of breast tissue ranged between 1.5 and 6.0 cm. All
patients had normal testes by palpation, and normal serum levels of
estradiol, LH, FSH, prolactin, and alpha-hCG. Liver function tests and serum
creatinine also were normal. The dose of raloxifene was 60 mg every other
day in 4 elderly patients (age 70 years or more), and 60 mg daily in the
remaining; the medication was given for 2-12 months. Hypogonadal patients
received, in addition, i.m. injections of testosterone enanthate, 100 mg
twice a month.
Raloxifene was well tolerated; only one young patient
reported a slight decrease in sexual potency. No subject complained of hot
flushes; there were no episodes of thrombophlebitis during follow-up. The
analgesic effect of treatment was fast (2-4 weeks) and sustained among 9
patients with pain and tenderness. The size of the gynaecomastia was
evaluated monthly by means of a caliper (all patients), and
ultrasonography (7 patients). All patients responded: there was an average
reduction in size of 61% (range: 34-100%); in 2 patients gynaecomastia
disappeared. Six of 8 eugonadal patients (75%) had a reduction in the size
of breast tissue of at least 50% (average, 73%). Among hypogonadal
patients (all of them followed with ultrasonography) gynaecomastia
disappeared in one, and size reduction in the remaining subjects ranged
between 46 and 67% (this is particularly noteworthy, since testosterone
replacement not infrequently causes or aggravates gynaecomastia due to
local aromatization to oestrogens by mammary tissue). Maximal effect was
observed during the first 2 months of treatment.
This open, observational study suggests that raloxifene may be a safe,
well tolerated and effective therapeutic alternative for drug-induced or
idiopathic gynaecomastia in men of all ages.
Zulema Man, MD.
TIEMPO, Buenos Aires, Argentina
Ariel S¨¢nchez, MD, PhD;
Hugo Carretto, MD;
Ricardo Parma, MD.
Centro de Endocrinolog¨ªa,
Rosario, Argentina
References
1. Khan HN, Blamey RW. Endocrine treatment of physiological gynaecomastia.
Br Med J 2003;327:301-2.
2. Compston JE. Selective oestrogen receptor modulators: potential
therapeutic implications. Clin Endocrinol 1998;48:389-91.
3. Agnusdei D, Iori N. Raloxifene: results from the MORE study. J
Musculoskel Neuron Interact 2000;1:127-32.
4. Cummings SR, Eckert S, Krueger KA, Grady D, Powles TJ, Cauley JA,
Norton L, Nickelsen T, Bjarnasson NH, Morrow M, Lippman ME, Black D,
Glusman JE, Costa A, Jordan VC. The effect of raloxifene on risk of breast
cancer in postmenopausal women. J Am Med Ass 1999;281:2189-97.
5. Mincey BA, Morahan TJ, Perez EA. Prevention and treatment of
osteoporosis in women with breast cancer. Mayo Clin Proc 2000;75:821-9.
6. Cauley JA, Norton L, Lippman ME, Eckert S, Krueger KA, Purdie DW,
Farrerons J, Karasik A, Mellstrom D, Ng KW, Stepan JJ, Powles TJ, Morrow
M, Costa A, Silfen SL, Walls EL, Schmitt H, Muchmore DM, Jordan VC.
Continued breast cancer risk reduction in postmenopausal women treated
with raloxifene: 4-year results from the MORE trial. Breast Cancer Res
Treatment 2001;65:125-34.
7. Uebelhart B, Bonjour JP, Draper MW, Pavo I, Basson R, Rizzoli R.
Effects of selective estrogen receptor modulator raloxifene on the
pituitary gonadal axis in healthy males (Abstract). J Bone Miner Res
2000;15(Suppl 1):S453.
Competing interests:
None declared
Competing interests: No competing interests