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.
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
24 September 2003
Ariel S¨¢nchez
Director
Centro de Endocrinolog¨ªa, San Lorenzo 876, (2000) Rosario, SF, Argentina
Rapid Response:
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