Here's a peer-reviewed article... not sure you will be able to click it, so I copy/pasted below.
http://onlinelibrary.wiley.com.ezproxy.library.ubc.ca/doi/10.1111/j.1365-2133.2011.10273.x/pdf
Melanotan-associated melanoma
DOI: 10.1111/j.1365-2133.2011.10273.x
MADAM,
Melanotan (Ac-Nle-Asp-His-D-Phe-Arg-Trp-Lys-NH2,
C50H69N15O9), an a-melanocyte stimulating hormone analogue,
stimulates melanogenesis.1–3 These synthetic analogues
target the melanocortin type 1 receptor (MC1R), overexpressed
in melanoma.4 Currently, the uncontrolled and unlicensed
use of melanotan is ever expanding.5 It can be purchased as
subcutaneous injection or nasal spray without medical
prescription from the internet and is often sold in gyms, spas,
fitness studios and tanning parlours.
Recently, serious concerns have been raised in respect to
the safety of melanotan, in particular the effects on melanocytic
naevi. The appearance of atypical pigmented naevi and
the change of pre-existing pigmentary lesions into dysplasticlike
naevi have been reported.6–8 A melanoma was reported in
a melanotan I user, but without a clear incrimination of afamelanotide
use.9
We present a 42-year-old white woman with a suspicious
enlargement and a change of colour of a pigmentary naevus on
the abdomen (Fig. 1a). She presented numerous naevi and was
examined yearly by her dermatologist. Previous follow-ups
were always unremarkable. The changes appeared progressively
over a 3-month period after subcutaneous injections of melanotan
II (100 mg daily for 2 days, followed by 50 mg daily
for 5 days) into the abdominal region. She also noted significant
tanning. New naevi had appeared and other pre-existing
naevi presented enlargement and ⁄or darkening. Due to nausea,
a melanotan-related adverse effect, she did not pursue further
injections. No other medication apart from oral hormonal contraception
was taken. She had a phototype III skin complexion
and visited the tanning parlour occasionally. There was no
hereditary history of melanoma or other cancers. She had experienced
sunburns in her youth. Clinical examination suggested
melanoma (Fig. 1a) and dermoscopy was highly suspicious for
melanoma (Fig. 1b). The lesion was excised and histology
revealed a melanoma (Breslow thickness 0Æ30 mm, Clark level
II). Immunohistochemical staining showed positive S100a,
HMB45, Melan-A, NKIC3 and tyrosinase expression, confirming
melanoma. The proliferation marker Ki-67 was estimated
at 10%. There were no local micrometastases or superficial
ulceration. Further clinical examination was normal and no
lymphadenopathies were evidenced. The area was re-excised
with the recommended surgical margin of 0Æ5 cm.
This case report raises alarm concerning the safety of melanotan,
in particular with respect to melanocytic lesions. Two
young women with skin phototype I ⁄II presented changes in
the appearance of their naevi following the use of self-injected
afamelanotide.6 Histology presented atypical melanocytic
nests.6 After the autoinjection of melanotan, a 40-year-old
man with a previous history of melanoma developed new
atypical naevi and a darkening of existing naevi. Histology also
revealed atypical melanocytic features.7 Interestingly, these
changes were partially reversible on cessation of afamelanotide
use. A young woman developed a multitude of pigmentary
naevi subsequent to afamelanotide injections.8 Whether malignant
transformation may occur remains unclear. One patient
using melanotan developed a melanoma.9 There was no clear
relationship between the development of the melanoma and
the use of melanotan.
Our patient presented other risk factors for developing melanoma,
such as sun-seeking behaviour, repeated sunburns in
her youth, a high number of naevi and occasional visits to the
tanning parlour. None the less, the rapid changes of a documented
pre-existing naevus in a 3-month period after melanotan
injections suggest a link between the injections and the
development of the melanoma. In vitro and in vivo experiments
suggested no carcinogenic potential of melanotan.3 Whether
afamelanotide potentially affects the initiation, promotion or
metastatic potential of melanoma cells in humans merits
absolute attention. Another danger may come from the longlasting
stimulating potential of afamelanotide, related to its
resistance to enzymatic breakdown.10
In conclusion, as long as the question of carcinogenesis has
not been adequately addressed, the harmlessness of melanotan
should not be promoted. Patients should be warned about the
potential risks. Dermatologists should be aware of this
phenomenon and be especially vigilant during skin examination
for skin cancer. Patients should be thoroughly questioned
as they are often reluctant to confess the use of these ‘Barbietanning’
drugs.
D. PAUROBALLY
F. JASON
B. DEZFOULIAN
A.F. NIKKELS
Department of Dermatology, CHU du Sart Tilman,
University of Lie`ge,
B-4000 Lie`ge, Belgium
Correspondence: Arjen Nikkels.
E-mail:
[email protected]
References
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and decreased UV damage in fair-skinned caucasian volunteers.
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[Nle(4), D-Phe(7)]-alpha-MSH, on melanin synthesis in
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Funding sources: none.
Conflicts of interest: none declared.