REPORTS AND RECOMMENDATIONS Female Pattern Hair Loss and Androgen Excess: A Report From the Multidisciplinary Androgen Excess and Downloaded from https://academic.oup.com/jcem/article-abstract/104/7/2875/5342938 by Endocrine Society Member Access 2 user on 24 June 2019 PCOS Committee Enrico Carmina,1 Ricardo Azziz,2 Wilma Bergfeld,3,4 Héctor F. Escobar-Morreale,5,6,7 Walter Futterweit,8 Heather Huddleston,9 Rogerio Lobo,10 and Elise Olsen11,12 1Department of Health Sciences and Mother and Child Care, University of Palermo, 90121 Palermo, Italy; 2Department of Health Policy, Management, and Behavior, School of Public Health, University at Albany, State University of New York, Albany, New York 12144; 3Department of Dermatology, Cleveland Clinic, Cleveland, Ohio 44195; 4Department of Pathology, Cleveland Clinic, Cleveland, Ohio 44195; 5Department of Endocrinology and Nutrition, Hospital Universitario Ramon ´ y Cajal, Universidad de Alcala, ´ 28801 Madrid, Spain; 6Centro de Investigacion ´ Biomedica ´ en Red Diabetes y Enfermedades Metabolicas ´ Asociadas, 28029 Madrid Spain; 7Instituto Ramon ´ y Cajal de Investigacion ´ Sanitaria, 28034 Madrid, Spain; 8Mount Sinai School of Medicine, New York, New York 10029; 9Department of Obstetrics and Gynecology, University of California at San Francisco, San Francisco, California 94143; 10Department of Obstetrics and Gynecology, Columbia University, New York, New York 10032; 11Department of Dermatology, Duke University Medical Center, Durham, North Carolina 27710; and 12Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710 ORCiD numbers: 0000-0001-7336-7610 (E. Carmina); 0000-0002-6890-1644 (H. F. Escobar-Morreale). Objective: To determine the current state of knowledge and provide evidence-based recommendations that could be valid for all specialists taking care of female pattern hair loss (FPHL), a common form of hair loss in women that is characterized by the reduction of hair density in the central area of the scalp, whereas the frontal hairline is generally well conserved. Participants: An expert task force appointed by the Androgen Excess and PCOS Society, which included specialists from dermatology, endocrinology, and reproductive endocrinology. Design: Levels of evidence were assessed and graded from A to D. Peer-reviewed studies evaluating FPHL published through December 2017 were reviewed. Criteria for inclusion/exclusion of the published papers were agreed on by at least two reviewers in each area and arbitrated by a third when necessary. Conclusions: (i) The term “female pattern hair loss” should be used, avoiding the previous terms of alopecia or androgenetic alopecia. (ii) The two typical patterns of hair loss in FPHL are centrifugal expansion in the mid scalp, and a frontal accentuation or Christmas tree pattern. (iii) Isolated FPHL should not be considered a sign of hyperandrogenism when androgen levels are normal. (iv) The assessment of patients with FPHL is primarily clinical. (v) In all patients with FPHL, assessment of a possible androgen excess is mandatory. Measurement of vitamin D, iron, zinc, thyroid hormones, and prolactin are optional but recommended. (vi) Treatment of FPHL should start with minoxidil (5%), adding 5a-reductase inhibitors or antiandrogens when there is severe hair loss or hyperandrogenism. (J Clin Endocrinol Metab 104: 2875–2891, 2019) ISSN Print 0021-972X ISSN Online 1945-7197 Abbreviations: AE-PCOS Society, Androgen Excess and PCOS Society; AR, androgen Printed in USA receptor; CCCA, central centrifugal cicatricial alopecia; CTE, chronic telogen effluvium; Copyright © 2019 Endocrine Society DHEA, dehydroepiandrosterone; DHEAS, DHEA sulfate; FAPD, fibrosing alopecia in a Received 27 November 2018. Accepted 15 February 2019. pattern distribution; FFA, frontal fibrosing alopecia; FPHL, female pattern hair loss; LC/MS, First Published Online 20 February 2019 liquid chromatography/mass spectrometry; LLL, low-intensity light laser; MPHL, male pattern hair loss; PCOS, polycystic ovary syndrome; PRP, platelet-rich plasma; T, tes- tosterone; TMF, topical minoxidil foam; TMS, topical minoxidil solution. doi: 10.1210/jc.2018-02548 J Clin Endocrinol Metab, July 2019, 104(7):2875–2891 https://academic.oup.com/jcem 2875 2876 Carmina et al FPHL and Androgen Excess J Clin Endocrinol Metab, July 2019, 104(7):2875–2891 air loss in women is common and may have different excess, and to provide evidence-based recommendations. All causes. A specific and particularly common subtype members of the task force declared no conflicts of interest or H financial interests that might interfere with their objectivity and is characterized by reduction of hair density in the central duty. area of the scalp whereas the frontal hairline is generally well conserved. In the 1950s, Hamilton (1) noted that this Downloaded from https://academic.oup.com/jcem/article-abstract/104/7/2875/5342938 by Endocrine Society Member Access 2 user on 24 June 2019 form of hair loss shares certain characteristics with male Process pattern baldness [also called male pattern hair loss Each section of this review was prepared by at least two investigators and then reviewed by all members of the task (MPHL)] and considered it androgen-dependent. Further force. Analyzed papers included individual studies, systematic studies specifically related MPHL to increased DHT reviews, and abstracts published in the English scientific liter- production in skin (2). However, similar evidence for ature. Criteria for inclusion/exclusion of the published papers a relationship between DHT overproduction and this relating to each section were agreed on by at least two reviewers pattern of hair loss in women has not been produced. in each area and arbitrated by a third when necessary. Levels of evidence were assessed and graded from A to D (16, 17). This phenotype of hair loss in women has been given The final manuscript was reviewed and approved by the AE- various names, although in the endocrine and gyneco- PCOS Society Board of Directors. Institutional Review Board logic literature it is most frequently referred to as an- approval was not obtained because the study reviewed publicly drogenetic alopecia, under the assumption that is available medical literature. androgen related (3). Recent guidelines on the diagnosis of polycystic ovary syndrome (PCOS) continue using the Systematic review of the literature more general term “alopecia” and consider the finding and meta-analysis diagnostic for the presence of hyperandrogenism (4–7). Peer-reviewed studies evaluating FPHL published through Overall, the relationship of hair loss and androgen December 2017 were reviewed. Multiple databases were excess in women is neither consistent nor clear. Most searched, including MEDLINE, Embase, Cochrane, ERIC, affected women with the frontal–central pattern of hair EBSCO, Dissertation Abstracts International, and Current Contents. This review focuses on the epidemiology, patho- loss have normal circulating androgen concentrations (8, physiology, diagnosis, and treatment of the disorder. Some 9) and an absence of other androgen-related signs or studies were eliminated because the data were either not related symptoms, such as hirsutism or irregular periods/ovulation to the focus of the systematic review, insufficient for epide- (10). The presence of this phenotype of hair loss has been miological analysis, or reported in previous publications. All reported also in women with total absence of circulating data sources were analyzed while recognizing positive publi- cation bias. androgens, deficiency of postpubertal androgenization A meta-analysis was also performed to obtain pooled (11), or lacking an androgen receptor (AR) (12). Because prevalence estimates on FPHL in subjects with PCOS. The terms of this, the term female pattern hair loss (FPHL) has of the MEDLINE search for this meta-analysis were: (alopecia become the most common name used in the dermatologic OR androgenetic OR female pattern hair loss OR mid scalp OR literature for this common condition in women (10, Ludwig OR frontal accentuation OR Olsen OR male pattern 13–15), without immediately stressing a link to androgen OR Hamilton) AND prevalence AND (PCOS OR polycystic ovary OR polycystic ovarian OR polycystic ovaries). The excess. Consequently, we use the term FPHL in the search was completed by examining the references listed in the present publication. articles identified. As many women with hyperandrogenism also exhibit After study identification, screening, selection, and in- or complain of scalp hair loss, the Androgen Excess and clusion, a quality-effects model was applied considering the PCOS (AE-PCOS) Society appointed an expert task force heterogeneity of the studies in terms of age, race, and ethnicity of the populations being described. Double arcsine trans- to determine the current state of knowledge concerning formations were applied to stabilize the variance (18). Pub- the relationship of these two conditions. This publication lication bias was assessed by a funnel plot representing the provides evidence-based recommendations for the eval- double arcsine transformation of the prevalence against the uation, diagnosis, and treatment of FPHL, as well as its SE (19). MetaXL 3.0 software was used for the meta- association with hyperandrogenism for use by the many analysis (18). different specialties of health professionals that are called upon to evaluate and treat these women. Results and Discussion Clinical presentation of FPHL