Annals of Oncology 14:1689-1690, 2003
© 2003 European Society for Medical Oncology
Letters to the Editor |
Alopecia in a premenopausal breast cancer woman treated with letrozole and triptorelin
Division of Medical Oncology ‘A’, Regina Elena Cancer Institute, Rome, Italy
*E-mail: pcarlini@iol.it
A 37-year-old premenopausal woman with relapsed breast cancer (BC) in the right supraclavicular nodes, after failed treatment with the combination luteinizing hormone releasing hormone-a (LHRHa; triptorelin) plus tamoxifen, was started on triptorelin 3.75 mg every 28 days plus letrozole 2.5 mg daily. Approximately 6 months after starting this therapy, she complained of a daily scalp hair loss while combing and progressively developed a diffuse non-scarring alopecia on her crown. There were no signs of virilization. A gynecological examination showed a normal looking vagina and uterine cervix. The uterus was normal in size and there were no ovarian masses at ultrasonography. Her previous medical history was unremarkable. She was not taking any other drug. Hematological parameters were normal. Blood examination ruled out pituitary or thyroid problems. There were no other possible causes that could induce alopecia, such as lupus erythematosus, HIV infection, secondary syphilis, or deficiencies of protein, iron, biotin or zinc (Table 1). A dermatologist prescribed topical minoxidil 2%, two local applications (2 ml) daily. Approximately 6–8 weeks after initiating minoxidil, hair loss stopped and hair regrowth became apparent.
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Hormonal levels of premenopausal BC women treated with the association LHRHa plus an aromatase inhibitor (AI) are different from those of postmenopausal women treated with an AI alone [1]. Whether estradiol directly inhibits 5
-reductase or whether the effect of estrogens might be explained by an increased conversion of testosterone to the weaker androgens, thereby diminishing the amount of testosterone available for the conversion to dihydrotestosterone (DHT), remains to be shown [2]. Additionally, aromatase levels have been demonstrated to be decreased in balding scalp [3]. This is the first report of alopecia related to the combination of LHRHa (triptorelin) with a non-steroidal AI. AIs alone lead to thinning hair, rather than baldness, with an incidence of 2.5–6%. One report suggested that LHRHa can also induce hair loss [4]. Consistent with the role of aromatase in avoiding androgen-mediated effects on androgen-dependent hair follicles is the observation that women taking AIs for the treatment of BC often experience androgenetic alopecia-like hair loss, as a consequence of the hormonal imbalance towards androgenization of the hair follicles. We could speculate that the LHRHa caused a fall in estradiol concentrations, leading to a relative hyperandrogenism. Additionally, the reduction of aromatase activity driven by letrozole may have resulted in a further relative increase in systemic and pilosebaceous testosterone available for conversion to DHT. This synergic action may explain why our patient did not show alopecia while taking triptorelin with tamoxifen. Moreover, minoxidil lengthened and enlarged the small vellus hairs and decreased shedding, highlighting the hypothesis of a relative hyperandrogenism as the cause of alopecia. Female sex hormone-binding globulin (SHBG) levels are inversely correlated with the grade of alopecia [5]. In our patient, the SHBG levels were low, potentially due to the AI effect.
Considering the pivotal importance of pharmacological castration in premenopausal endocrine-responsive BC patients and the widespread use of AIs in the metastatic and, probably in the near future, adjuvant settings, potential alopecia should not be a determinant in making clinical decisions. However, oncologists must be aware of such atypical adverse events for treatment planning, in order to highlight its consequent distress and to provide psychological counseling, especially in young patients.
P. Carlini*, S. Di Cosimo, G. Ferretti, P. Papaldo, A. Fabi, E. M. Ruggeri, M. Milella & F. Cognetti
Division of Medical Oncology ‘A’, Regina Elena Cancer Institute, Rome, Italy (*E-mail: pcarlini@iol.it)
References
1. Dowsett M, Doody D, Miall S et al. Vorozole results in greater oestrogen suppression than formestane in postmenopausal women and when added to goserelin in premenopausal women with advanced breast cancer. Breast Cancer Res Treat 1999; 56: 25–34.[CrossRef][Web of Science][Medline]
2. Niiyama S, Happle R, Hoffmann R. Influence of estrogens on the androgen metabolism in different subunits of human hair follicle. Eur J Dermatol 2001; 11: 195–198.[Web of Science][Medline]
3. Sawaya ME, Price VH. Different levels of 5 -reductase type I and II, aromatase and androgen receptor in hair follicles of women and men with androgenic alopecia. J Invest Dermatol 1997; 109: 296–300.[CrossRef][Web of Science][Medline]
4. Gateley CA, Bundred NJ. Alopecia and breast disease. BMJ 1997; 314: 481.
5. Vexiau P, Chaspoux C, Boudou P et al. Role of androgens in female-pattern androgenetic alopecia, either alone or associated with other symptoms of hyperandrogenism. Arch Dermatol Res 2000; 292: 598–604.[CrossRef][Web of Science][Medline]
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