Letter to the Editor: Topical Anti-Estrogen Therapy To Treat Melasma

by Philip R. Cohen, MD

Dear Editor:
I read with interest the recent report by Snyder et al[1] describing melasma associated with the application of a topical estrogen cream. The development of melasma is multifactorial and female sex hormones have been implicated in the pathogenesis of this condition.[2] Estrogen receptor expression is increased in melasma lesions.[3] Also, melanogenesis of cultured human melanocytes can be stimulated by estrogens and inhibited by estrogen antagonists.[4]

The induction of melasma with a topical estrogen raises the possibility that the treatment of this condition could be facilitated by the use of a topical anti-estrogen. I recently proposed a novel topical approach for the treatment of melasma that utilized an anti-estrogen, such as a selective estrogen receptor modulator (tamoxifen or raloxifene) or an aromatase inhibitor (anastrozole or tetrozole or exemestane).[5] The topical agent would also include a vascular endothelial growth factor inhibitor (bevacizumab) that would be directed toward blocking the angiogenesis component of melasma pathogenesis.[5] Investigation of this novel—topically administered—therapy for melasma is warranted.

Philip R. Cohen, MD
Department of Dermatology, University of California San Diego, La Jolla, California

Disclosure: The author reports no relevant conflicts of interest.

1. Snyder A, Schiechert RA, Zaiac MN. Melasma associated with topical estrogen cream. J Clin Aesthet Dermatol. 2017;10(2):57–58.
2. Lee A-Y. Recent progress in melasma pathogenesis. Pigm Cell Melanoma Res. 2015;28:648–660.
3. Jang YH, Lee JY, Kang HY, et al. Oestrogen and progesterone receptor expression in melasma: an immunohistochemical analysis. J Eur Acad Dermatol Venereol. 2010;24:1312–1316.
4. Kim NH, Cheong KA, Lee TR, Lee AY. PDZK1 upregulation in estrogen-related hyperpigmentation in melasma. J Invest Dermatol. 2012;132:2622–2631.
5. Cohen PR. Melasma treatment: a novel approach using a topical agent that contains an anti-estrogen and a vascular endothelial growth factor inhibitor. Med Hypotheses. 2017;101:1–5.