Faculty Bibliography

Androgens are produced throughout the body in steroid-producing organs, such as the adrenal glands and ovaries, as well as in other tissues, like the skin. Several androgens are found normally in women, including dehydroepiandrosterone (DHEA), dehydroepiandrosterone-sulfate (DHEA-S), testosterone, dihydrotestosterone (DHT), and androstenedione. These androgens are essential in the development of several common cutaneous conditions in women, including acne, hirsutism, and female pattern hair loss (FPHL) - androgen mediated cutaneous disorders (AMCDs). However, the role of androgens in the pathophysiology of these diseases is complicated and incompletely understood. In the first article in this Continuing Medical Education series, we discuss the role of the skin in androgen production as well as the impact of androgens on the skin in women. Specifically, we review the necessary, but insufficient role that androgens play in the development of acne, hirsutism, and FPHL in women. Dermatologists face the challenge of differentiating physiologic from pathologic presentations of AMCDs in women. There are currently no dermatology guidelines outlining the indications for endocrinologic evaluation in women presenting with acne, hirsutism, and/or FPHL. We review available evidence regarding when to consider an endocrinologic work-up in women presenting with AMCDs, including the appropriate type and timing of testing.

Androgen-mediated cutaneous disorders (AMCDs) in women including acne, hirsutism, and female pattern hair loss (FPHL) can be treated with hormone-modulating therapies. In the second part of this Continuing Medical Education series, we discuss the hormone-modulating therapies available to dermatologists for the treatment of AMCDs including combined oral contraceptives, spironolactone, finasteride, dutasteride, and flutamide. Available hormone-modulating treatments utilized for each AMCDs are reviewed, along with mechanisms of androgen modulation, safety profile, contraindications, monitoring parameters, and evidence of efficacy. Medications discussed include ones that are FDA-approved for certain AMCDs as well as some that are used off-label. Despite the ubiquity of hormone-modulating therapies used for AMCDs, this review highlights the need for more rigorous studies to evaluate these therapies for acne, hirsutism, and FPHL.

In dermatology, autologous platelet-rich plasma (PRP) therapy has been used in the treatment of chronic wounds and ulcers and scar tissue, and as a skin rejuvenation therapy. Recently, PRP has been used in the treatment of androgenetic alopecia and alopecia areata. Our aim was to determine the efficacy of PRP for hair growth promotion in patients with androgenetic alopecia in a randomized, double-blinded, placebo-controlled, pilot clinical trial (NCT02074943). We determined the efficacy of an 8-week, five-session PRP treatment course by measuring hair density and hair calibre changes in 10 patients with AGA. We quantified the presence of FGFb, EGF, HGF, VEGF, GDNF, PDGF-BB and TGF-beta in PRP to evaluate potential correlations between growth factor (GF) concentrations and hair growth measurements. At 16 weeks, 8 weeks after the last PRP injection, treated areas exhibited an increased mean hair density (+12.8%) over baseline compared with the placebotreated area (+0.99%). Unexpectedly, the mean hair calibre decreased in both treated and placebo regions (-16.2% and -19.5%, respectively). GF concentration in PRP was highly variable between individuals, and to a lesser extent within individuals over time. Multiple linear regression analysis did not identify significant correlation between GF concentration and hair growth. However, analysis of individual GF concentrations identified correlation between GDNF (glial cellderived neurotrophic factor) and hair density (P = 0.004). Trends, although not statistically significant, were also observed for FGFb and VEGF. This study suggests a potential beneficial effect for PRP treatment of AGA. The variable hair growth response, and the apparent reduction in hair calibre, suggest there is a significant opportunity to improve PRP therapy protocols for hair growth promotion. The variability in PRP GF concentration suggests that standardization of GFs postprocessing could improve hair growth responses. A larger cohort study may help with development of new and improved PRP protocols for patients with AGA

Cytotoxic chemotherapies, molecularly targeted therapies, immunotherapies, radiotherapy, stem cell transplants, and endocrine therapies may lead to hair disorders (including alopecia, hirsutism, hypertrichosis, pigmentary and textural hair changes). The mechanisms underlying these changes are varied and remain incompletely understood, hampering the development of preventive or therapeutic guidelines. The psychosocial impact of chemotherapy -induced alopecia has been well-documented mainly in the oncology literature, however the effect of other alterations such as radiation-induced alopecia, hirsutism, changes in hair color or texture on quality of life have not been described. This article reviews clinically significant therapy-related hair disorders in cancer patients, underlying pathophysiological mechanisms, severity grading scales, patient reported quality of life instruments, management strategies, and future translational research opportunities.

With increasing survival rates across all cancers, survivors represent a growing population that is frequently affected by persistent or permanent hair growth disorders as a result of systemic therapies, radiotherapy, surgical procedures, and therapeutic transplants. These hair disorders include persistent chemotherapy-induced alopecia, persistent radiotherapy-induced alopecia, endocrine therapy-induced alopecia and hirsutism, post-surgery alopecia and localized hypertrichosis, alopecia attributed to therapeutic transplants, and to novel anticancer therapies. The information contained in this continuing medical education article should facilitate a better understanding on hair disorders in cancer survivors, so that adequate support and therapies may be provided to cancer survivors.

The treatment of hair loss is a challenge for all dermatologists. New medications are needed due to lack of efficacy of many treatments or their side-effect profile. This article discusses the most recent literature updates on the use of retinoids in frontal fibrosing alopecia, platelet-rich plasma in androgenetic alopecia, and JAK inhibitors in alopecia areata.

PURPOSE/OBJECTIVE:To provide dermatologists and oncologists with a foundation for practical understanding and uses of 5α-reductase inhibitors and spironolactone for breast cancer patients and survivors receiving endocrine therapies (ETs), including the effect of these treatments on sex hormone levels, any reported drug interactions, and any risk of malignancy. METHODS:All published studies from January 1978 through April 2018 were considered, using databases such as PubMed, Google Scholar, and Science Direct. Forty-seven studies were included in this review. RESULTS:There is no evidence of interactions between 5α-reductase inhibitors and spironolactone with ETs used in breast cancer. Sex hormone alteration with 5α-reductase inhibitor or spironolactone use is variable. Three randomized controlled trials, 1 case-control study, and 6 retrospective cohort studies, including 284 female patients, studied the effects of 5α-reductase inhibitors on serum estrogen levels. Levels were increased in 97 of 284 (34%) patients, decreased in 15 of 284 (5.3%) patients, and unchanged in 162 of 284 (57%) patients. Four retrospective cohort studies, 1 case study, and 1 double-blinded crossover study, including 95 female patients, assessed the effect of spironolactone on estrogen levels. Levels were increased in 25 of 95 (26%) patients, decreased in 6 of 95 (6.3%) patients, and unchanged in 64 of 95 (67%) patients. Ultimately, most patients did not have a significant alteration in the level of estrogen when using 5α-reductase inhibitors or spironolactone. No consistent evidence of increased risk of female breast cancer while on spironolactone was reported in 3 studies including 49,298 patients; the risk of breast cancer with the use of 5α-reductase inhibitors has not been studied. CONCLUSIONS:Most patients did not show increased estrogen levels with spironolactone and there were no data suggesting increased risk of breast cancer. Based on hormonal and pharmacological activity, spironolactone may be considered for further research on alopecia and hirsutism in breast cancer patients.