madman
Super Moderator
Abstract
Hair loss and thinning are possible complications in those undergoing endocrine therapies with aromatase inhibitors. Alopecia in pediatric patients undergoing endocrine therapy has not been previously reported. We describe two adolescents, 14 and 16 years of age, who developed androgenetic alopecia following treatment with anastrozole for idiopathic short stature. Accordingly, the possible adverse event of alopecia should be considered in the pediatric population undergoing treatment with aromatase inhibitors.
1 | INTRODUCTION
Aromatase inhibitors are endocrine agents that inhibit the peripheral conversion of androgens into estrogens through inhibition of the aromatase enzyme. They were first introduced as a treatment for estrogen receptor-positive breast cancer, as well as other cancer types. These agents have since been used for various conditions in children and adolescents.1 Although aromatase inhibitors are FDA approved for treating estrogen-dependent breast cancer, they have been used off-label for conditions such as short stature, pubertal delay in adolescents, hypoestrogenism in aromatase excess syndrome, pubertal gynecomastia, Peutz-Jeghers syndrome, McCune-Albright syndrome, functional ovarian cysts, hyperandrogenism in testotoxicosis (familial male-limited precocious puberty), and congenital adrenal hyperplasia.1,2
Among the complications related to aromatase inhibitors in pediatrics, decreased bone mineral density (BMD) secondary to decreased estradiol, effects on spermatogenesis and sperm motility, reduced high-density lipoprotein cholesterol and decreased fat mass in boys have been reported. However, these data are limited by the dearth of long-term data regarding aromatase inhibitors in children and adolescents. As such, it is vital to assess the effects of the medication on bone health, reproductive function, lipid and carbohydrate metabolism, and adrenal function.3 Alopecia caused by aromatase inhibitors has been established in the adult population in women receiving aromatase inhibitors for breast cancer treatment. In a retrospective review by Moscetti et al,4 8% of 236 patients treated with aromatase inhibitors discontinued treatment due to alopecia. Further, a survey-based study of 851 female patients with breast cancer receiving aromatase inhibitors indicated that 34% of patients reported hair loss or hair thinning toward the end of treatment, independent of previous chemotherapy or age.5 Although alopecia is a well-known side effect of this medication in adult cancer patients, to our knowledge, the occurrence of alopecia following treatment with aromatase inhibitors has not yet been documented in the adolescent population.6
2 | CASE REPORTS
2.1 | Case 1
A 14-year-old boy with a strong paternal history of male pattern hair loss showed no evident hair loss on physical examination on January 28, 2019 (Figure 1A). He began treatment with anastrozole in May 2019 for idiopathic short stature. Ten months after initiation of treatment, on February 3, 2020, he developed trichoscopy-confirmed androgenetic alopecia (AGA) with a female Ludwig II pattern, primarily involving the top of the scalp (Figures 1B and 2). The patient was subsequently treated with topical minoxidil 2% daily.
2.2 | Case 2
A 16-year-old boy presented because of hair loss that had recently progressed very rapidly. Family history was significant for mild (Hamilton III) male pattern hair loss (MPHL) in his father. Clinical history showed that he had been treated with somatropin (beginning in 2016 for 2 years) and anastrozole (from April 2018 to March 2019) for idiopathic short stature. Dermatologic history revealed the patient was evaluated by a dermatologist in 2018, just after starting anastrozole treatment, and was diagnosed with early AGA and treated with ketoconazole shampoo. On physical examination, the patient was noted to have moderate androgenetic alopecia with the preservation of the frontotemporal hairline (female Ludwig II pattern). Trichoscopy confirmed the diagnosis, showing more than 20% variability in the hair shaft diameter. As such, the patient was placed on a treatment regimen of low-level laser therapy (CapillusPro™, 5 mW, 650 wavelengths, continuous output, 6 minutes daily) and oral minoxidil 2.5 mg daily.
3 | DISCUSSION
Aromatase, an enzyme chiefly found in the stromal cells of adipose tissue, catalyzes the rate-limiting step in the conversion of testosterone to estradiol, as well as androstenedione to estrone.1,7 Since estrogen is the principal regulator of epiphyseal fusion, aromatase inhibitors are primarily used for idiopathic short stature in children and adolescents.8 Estrogens and androgens are also critical hair growth modulators. When endocrine receptor activation and pathway signaling are blocked, such as with the use of aromatase inhibitors, dihydrotestosterone levels increase secondary to enhancement in the activity of 5α-reductase, contributing to the induction of alopecia in those receiving the medication.9
We implemented a treatment regimen of low-level laser therapy, a modality known to stimulate epidermal stem cells in the hair follicle bulge and shift the follicles into the anagen phase,17 as well as minoxidil, as it is the standard of care. By carefully identifying alopecia in adolescents on aromatase inhibitors, practitioners may mitigate the negative psychologic outcomes of childhood and adolescent hair loss.
Hair loss and thinning are possible complications in those undergoing endocrine therapies with aromatase inhibitors. Alopecia in pediatric patients undergoing endocrine therapy has not been previously reported. We describe two adolescents, 14 and 16 years of age, who developed androgenetic alopecia following treatment with anastrozole for idiopathic short stature. Accordingly, the possible adverse event of alopecia should be considered in the pediatric population undergoing treatment with aromatase inhibitors.
1 | INTRODUCTION
Aromatase inhibitors are endocrine agents that inhibit the peripheral conversion of androgens into estrogens through inhibition of the aromatase enzyme. They were first introduced as a treatment for estrogen receptor-positive breast cancer, as well as other cancer types. These agents have since been used for various conditions in children and adolescents.1 Although aromatase inhibitors are FDA approved for treating estrogen-dependent breast cancer, they have been used off-label for conditions such as short stature, pubertal delay in adolescents, hypoestrogenism in aromatase excess syndrome, pubertal gynecomastia, Peutz-Jeghers syndrome, McCune-Albright syndrome, functional ovarian cysts, hyperandrogenism in testotoxicosis (familial male-limited precocious puberty), and congenital adrenal hyperplasia.1,2
Among the complications related to aromatase inhibitors in pediatrics, decreased bone mineral density (BMD) secondary to decreased estradiol, effects on spermatogenesis and sperm motility, reduced high-density lipoprotein cholesterol and decreased fat mass in boys have been reported. However, these data are limited by the dearth of long-term data regarding aromatase inhibitors in children and adolescents. As such, it is vital to assess the effects of the medication on bone health, reproductive function, lipid and carbohydrate metabolism, and adrenal function.3 Alopecia caused by aromatase inhibitors has been established in the adult population in women receiving aromatase inhibitors for breast cancer treatment. In a retrospective review by Moscetti et al,4 8% of 236 patients treated with aromatase inhibitors discontinued treatment due to alopecia. Further, a survey-based study of 851 female patients with breast cancer receiving aromatase inhibitors indicated that 34% of patients reported hair loss or hair thinning toward the end of treatment, independent of previous chemotherapy or age.5 Although alopecia is a well-known side effect of this medication in adult cancer patients, to our knowledge, the occurrence of alopecia following treatment with aromatase inhibitors has not yet been documented in the adolescent population.6
2 | CASE REPORTS
2.1 | Case 1
A 14-year-old boy with a strong paternal history of male pattern hair loss showed no evident hair loss on physical examination on January 28, 2019 (Figure 1A). He began treatment with anastrozole in May 2019 for idiopathic short stature. Ten months after initiation of treatment, on February 3, 2020, he developed trichoscopy-confirmed androgenetic alopecia (AGA) with a female Ludwig II pattern, primarily involving the top of the scalp (Figures 1B and 2). The patient was subsequently treated with topical minoxidil 2% daily.
2.2 | Case 2
A 16-year-old boy presented because of hair loss that had recently progressed very rapidly. Family history was significant for mild (Hamilton III) male pattern hair loss (MPHL) in his father. Clinical history showed that he had been treated with somatropin (beginning in 2016 for 2 years) and anastrozole (from April 2018 to March 2019) for idiopathic short stature. Dermatologic history revealed the patient was evaluated by a dermatologist in 2018, just after starting anastrozole treatment, and was diagnosed with early AGA and treated with ketoconazole shampoo. On physical examination, the patient was noted to have moderate androgenetic alopecia with the preservation of the frontotemporal hairline (female Ludwig II pattern). Trichoscopy confirmed the diagnosis, showing more than 20% variability in the hair shaft diameter. As such, the patient was placed on a treatment regimen of low-level laser therapy (CapillusPro™, 5 mW, 650 wavelengths, continuous output, 6 minutes daily) and oral minoxidil 2.5 mg daily.
3 | DISCUSSION
Aromatase, an enzyme chiefly found in the stromal cells of adipose tissue, catalyzes the rate-limiting step in the conversion of testosterone to estradiol, as well as androstenedione to estrone.1,7 Since estrogen is the principal regulator of epiphyseal fusion, aromatase inhibitors are primarily used for idiopathic short stature in children and adolescents.8 Estrogens and androgens are also critical hair growth modulators. When endocrine receptor activation and pathway signaling are blocked, such as with the use of aromatase inhibitors, dihydrotestosterone levels increase secondary to enhancement in the activity of 5α-reductase, contributing to the induction of alopecia in those receiving the medication.9
We implemented a treatment regimen of low-level laser therapy, a modality known to stimulate epidermal stem cells in the hair follicle bulge and shift the follicles into the anagen phase,17 as well as minoxidil, as it is the standard of care. By carefully identifying alopecia in adolescents on aromatase inhibitors, practitioners may mitigate the negative psychologic outcomes of childhood and adolescent hair loss.
