Research

Original Investigation

Cutaneous Findings and Systemic Associations in Women

With Polycystic Ovary Syndrome
Timothy H. Schmidt, MD, PhD; Keshav Khanijow, MD; Marcelle I. Cedars, MD; Heather Huddleston, MD; Lauri Pasch, PhD;
Erica T. Wang, MD, MAS; Julie Lee, BS; Lee T. Zane, MD, MAS; Kanade Shinkai, MD, PhD

Editorial page 377

IMPORTANCE Understanding of the associations among cutaneous findings, systemic Related article page 399
abnormalities, and fulfillment of the diagnostic criteria in women suspected of having
polycystic ovary syndrome (PCOS) is incomplete. CME Quiz at
jamanetworkcme.com and
CME Questions page 500
OBJECTIVE To identify cutaneous and systemic features of PCOS that help distinguish women
who do and do not meet the diagnostic criteria.

DESIGN, SETTING, AND PARTICIPANTS Retrospective cross-sectional study of a racially diverse

referred sample of women seen at the University of California, San Francisco, Polycystic
Ovary Syndrome Multidisciplinary Clinic over a 6-year period between May 18, 2006, and
October 25, 2012. Participants were 401 women referred for suspected PCOS. In total, 68.8%
(276 of 401) met the Rotterdam PCOS diagnostic criteria, while 12.0% (48 of 401) did not.
Overall, 11.5% (46 of 401) had insufficient data to render a diagnosis, 1.7% (7 of 401) were
excluded from the study, and 6.0% (24 of 401) refused to participate in the study.

EXPOSURE Comprehensive skin examination and transvaginal ultrasonography. All patients

were tested for levels of total testosterone, free testosterone, dehydroepiandrosterone
(DHEAS), androstenedione, luteinizing hormone, and follicle-stimulating hormone. Levels of
serum cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein
cholesterol (LDL-C), and triglycerides were obtained, in addition to 0-hour and 2-hour oral
glucose tolerance test (OGTT) results, with measurement of glucose and insulin levels.

MAIN OUTCOMES AND MEASURES Findings from comprehensive skin examination, laboratory
testing, and transvaginal ultrasonography.

RESULTS In total, 401 women with suspected PCOS were included in the study. The median
patient age was 28 years. Compared with women who did not meet the diagnostic criteria for
PCOS, women who met the criteria had higher rates of hirsutism (53.3% [144 of 270] vs 31.2% Author Affiliations: Department of
[15 of 48], P = .005) (with higher mean modified Ferriman-Gallwey scores of 8.6 vs 5.6, Dermatology, University of California,
P = .001), acne (61.2% [164 of 268] vs 40.4% [19 of 47], P = .004), and acanthosis nigricans San Francisco (Schmidt, Shinkai);
Division of General Internal Medicine,
(AN) (36.9% [89 of 241] vs 20.0% [9 of 45], P = .03). Cutaneous distributions also varied.
Department of Medicine, The Johns
Women who met the PCOS criteria demonstrated more severe truncal hirsutism and higher Hopkins University, Baltimore,
rates of axillary AN. Women who met the PCOS criteria had elevated total testosterone levels Maryland (Khanijow); Department of
(40.7% [105 of 258] vs 4.3% [2 of 47], P < .001). Among women with PCOS, the presence of Obstetrics, Gynecology, and
Reproductive Sciences, University of
hirsutism (43.9% [54 of 123] vs 30.9% [34 of 110], P = .04) or AN (53.3% [40 of 75] vs 27.0%
California, San Francisco (Cedars,
[40 of 148], P < .001) was associated with higher rates of elevated free testosterone levels as Huddleston); Department of
well as several metabolic abnormalities, including insulin resistance, dyslipidemia, and increased Psychiatry, University of California,
body mass index. Although the prevalence of acne was increased among women with PCOS, San Francisco (Pasch); Department of
Obstetrics and Gynecology,
there were minimal differences in acne types and distribution between the women meeting Cedars-Sinai Medical Center,
vs not meeting the PCOS criteria. Los Angeles, California (Wang);
medical student, School of Medicine,
University of California, San Diego
CONCLUSIONS AND RELEVANCE Hirsutism and AN are the most reliable cutaneous markers of
(Lee); Anacor Pharmaceuticals,
PCOS and require a comprehensive skin examination to diagnose. When present, hirsutism Palo Alto, California (Zane).
and AN should raise clinical concern that warrants further diagnostic evaluation for metabolic Corresponding Author: Kanade
comorbidities that may lead to long-term complications. Acne and androgenic alopecia are Shinkai, MD, PhD, Department of
prevalent but unreliable markers of biochemical hyperandrogenism among this population. Dermatology, University of California,
San Francisco, 1701 Divisadero St,
JAMA Dermatol. 2016;152(4):391-398. doi:10.1001/jamadermatol.2015.4498 Third Floor, San Francisco, CA 94115
Published online December 23, 2015. (kanade.shinkai@ucsf.edu).

(Reprinted) 391

Copyright 2016 American Medical Association. All rights reserved.

Downloaded From: https://jamanetwork.com/ on 04/06/2022

 Research Original Investigation
P
olycystic ovary syndrome (PCOS) affects 2% to 7% of
women in the general population.1 The diagnostic cri-
teria for PCOS continue to evolve, but the 2003 Rotter-
dam consensus criteria remain widely used.2 In addition to the
exclusion of other disorders, these criteria require at least 2 of
the following findings for diagnosis: oligoanovulation, poly-
cystic ovaries on transvaginal ultrasonography, and clinical
signs or biochemical evidence of hyperandrogenism (HA). The
pathogenesis underlying these clinical features is poorly un-
derstood. Gonadotropic dysregulation, genetics, and environ-
mental factors have been implicated.3
It is estimated that 72% to 82% of women with PCOS are
seen with cutaneous signs classically associated with HA such
as acne, hirsutism, and androgenic alopecia (AGA).1,4,5 Hy-
perandrogenism may also manifest as acanthosis nigricans (AN)
or seborrheic dermatitis.6,7 Patients with PCOS are frequently
first seen by a dermatologist.8
Polycystic ovary syndrome is associated with cardiovas-
cular risk factors as well as long-term complications, includ-
ing obesity, infertility, malignancy, and insulin resistance.2,9-13
Other associations include obstructive sleep apnea, nonalco-
holic steatohepatitis, and psychiatric illnesses, such as depres-
sion, anxiety, and eating disorders.13 However, understand-
ing regarding the cutaneous features seen in PCOS and their
associations with clinically measurable endocrine and meta-
bolic abnormalities requires further development.4,14-17 In-
complete cutaneous examinations, few patients, racially ho-
mogeneous cross-sections, and an absence of comparison
groups have limited the generalizability of these findings.
In addition, it is difficult for physicians to identify women
with PCOS among those with similar features, such as acne, AGA,
or hirsutism. This study aimed to identify the cutaneous, re-
productive, and metabolic characteristics that distinguished pa-
tients meeting the diagnostic criteria for PCOS vs those not meet-
ing the criteria among a high-risk population of women referred
to a multidisciplinary PCOS clinic. To achieve this aim, this study
systematically characterized the cutaneous, reproductive, and
metabolic characteristics in a large, racially diverse cross-
section of patients referred for suspected PCOS.
Methods
Study Design
This UCSF Committee for Human Research–approved, retro-
spective study consecutively recruited women suspected of hav-
ing PCOS who were referred to the University of California, San
Francisco, Polycystic Ovary Syndrome Multidisciplinary Clinic
between May 18, 2006, and October 25, 2012. Any patient able
to provide written informed consent who had discontinued hor-
monal contraception for at least 4 weeks was eligible for study
inclusion. The Rotterdam consensus criteria were used to ren-
der diagnoses of PCOS.2 In defining the Rotterdam criteria for
the purposes of this study, clinical HA was defined as the pres-
ence of the cutaneous features of HA, and biochemical HA was
defined as the presence of at least 1 serum androgen. Oligoan-
ovulation was defined as fewer than 8 menstrual cycles per year.
Referred women who did not meet the criteria for PCOS were
392 JAMA Dermatology April 2016 Volume 152, Number 4 (Reprinted)
Copyright 2016 American Medical Association. All rights reserved.
Downloaded From: https://jamanetwork.com/ on 04/06/2022
Cutaneous Findings Associated With Polycystic Ovary Syndrome
assessed as well and served as a comparison group. Women hav-
ing another endocrinopathy or taking combined oral contra-
ceptives at the time of testing or evaluation were excluded from
the study. Women with prior or current treatments for acne (topi-
cal or systemic medications, including isotretinoin), hirsutism
(laser, electrolysis, or eflornithine hydrochloride), or AGA (topi-
cal minoxidil) were included in the study. Scoring of their cu-
taneous findings was not adjusted for their treatment histo-
ries. Patients were instructed not to perform any type of hair
removal for 1 week before clinical evaluation.
A reproductive endocrinologist (M.I.C. or H.H.) and derma-
tologist (L.T.Z. or K.S.) evaluated patients on the same day. Demo-
graphic information and detailed medical histories were ob-
tained. Transvaginal ultrasonography was performed in all pa-
tients for assessment of antral follicle count and ovarian volume.
A comprehensive dermatologic examination was performed on
each patient, including evaluation for acne, hirsutism, AN, AGA,
and seborrheic dermatitis. Acne lesions were counted and re-
corded as comedones, papulopustules, nodules, and postlesional
erythematous macules or postinflammatory pigment alterations
in each segment of the face (forehead, left cheek, right cheek,
perioral or jawline region, and submental area). The Leeds
technique18 was used to grade acne burden on the back and chest.
Hirsutism was evaluated by the modified Ferriman-Gallwey
(MFG) score.19-21 A total MFG score of at least 8 was denoted as
hirsutism. The axillae, central chest, inframammary region, in-
guinal creases, knuckles, and neck were examined for AN.
Androgenic alopecia was graded by the degree and distribution
of hair loss based on the scales by Ludwig22 and Olsen.23
All patients were tested for levels of total testosterone, free
testosterone, dehydroepiandrosterone (DHEAS), androstene-
dione, luteinizing hormone, and follicle-stimulating hor-
mone. Rarely, Cushing syndrome needed to be ruled out with
cortisol testing based on the clinical presentation. However, be-
cause of the challenging logistics of testing for Cushing syn-
drome, only women with suspicious presentations were tested.
Levels of thyroid-stimulating hormone, prolactin, and 17-
hydroxyprogesterone were evaluated to rule out alternative en-
docrine disorders. Laboratory values were obtained at the study
clinic or from referring health care professionals. Normative val-
ues from each test’s laboratory were used to determine whether
levels were normal or abnormal. Levels of serum cholesterol,
high-density lipoprotein cholesterol (HDL-C), low-density li-
poprotein cholesterol (LDL-C), and triglycerides were ob-
tained, in addition to 0-hour and 2-hour oral glucose tolerance
test (OGTT) results, with measurement of glucose and insulin
levels. The homeostatic model of insulin resistance (HOMA-IR)24
was used to calculate insulin resistance for each participant with
the following equation: (Glucose Level × Insulin Level) / 405,
where the glucose level is expressed in milligrams per decili-
ter, and the insulin level is expressed in milliunits per liter.
Data Reporting and Statistical Analysis
Levels of DHEAS, total testosterone, and free testosterone, in ad-
dition to 2-hour OGTT results and findings of polycystic ovaries
by ultrasonography, acne, AGA, and AN, were dichotomously re-
ported as normal or abnormal or as present or absent. The mean
values were used to compare levels of serum cholesterol, HDL-C,
jamadermatology.com
 Cutaneous Findings Associated With Polycystic Ovary Syndrome
LDL-C, and triglycerides, as well as continuous clinical scores.
Statistical analyses were performed with the Mann-Whitney test
or the Kruskal-Wallis test to compare continuous or ordinal vari-
ables, as well as the χ2 test to compare proportions. Analyses were
performed with statistical software (SAS, version 9.2; SAS Insti-
tute Inc and Prism, version 5.0; GraphPad Software, Inc). Two-
sided P < .05 was considered statistically significant.
Results
Demographics
In total, 401 women suspected of having PCOS were referred
to our clinic during a 6-year period (May 18, 2006, to October
25, 2012). The median patient age was 28 years. Overall, 68.8%
(276 of 401) met the Rotterdam PCOS diagnostic criteria, while
12.0% (48 of 401) did not. A total of 11.5% (46 of 401) had in-
sufficient data to render a diagnosis, 1.7% (7 of 401) were ex-
cluded from the study, and 6.0% (24 of 401) refused to partici-
pate in the study. Women with missing information about
menstrual patterns (n = 9), biochemical and clinical HA (n = 1),
transvaginal ultrasonography (n = 24), or other dermatologic
and biochemical evaluations were included in the study if they
were able to meet the PCOS criteria but were excluded from the
relevant subanalyses. Women meeting the criteria for PCOS had
a younger mean age than women not meeting the criteria (28.1
vs 33.0 years, P = .002). There were no significant differences
with respect to race, marital status, parity, level of education,
household income, and the use of alcohol or tobacco between
women who met the PCOS criteria and those who did not.
Overall Burden of Cutaneous Findings
Most women (91.7% [253 of 276]) meeting the criteria for PCOS
had at least 1 skin finding. Those who met the criteria were
found to have a higher burden of acne, hirsutism, and AN than
women who did not meet the criteria (Table 1). On average, pa-
tients meeting the criteria for PCOS had more cutaneous find-
ings (mean [SD], 1.97 [1.18] vs 1.25 [1.14], P < .001). Among
women meeting the PCOS criteria, hirsutism was signifi-
cantly associated with the presence of AN (P < .001), with one-
quarter (25.0% [67 of 268]) of patients with either cutaneous
manifestation having both.
Acne
Women who met the criteria for PCOS were more likely to have
acne than women who did not meet the criteria (61.2% [164 of
268] vs 40.4% [19 of 47], P = .004) (Table 1). The mean Leeds
scores for the back and chest were not significantly different.
Analysis by acne lesion counts and types revealed minimal dif-
ferences between the 2 groups. Women meeting the PCOS cri-
teria had slightly increased mean numbers of comedones on the
forehead (5.15 vs 3.84, P = .006) and the perioral or jawline re-
gions (2.92 vs 2.62, P = .04). Comparison of regional burdens of
other acne lesion types did not reveal significant differences.
Among women meeting the criteria for PCOS, acne when present
was associated with younger age (27.3 vs 29.2 years, P = .03) and
with a slightly lower prevalence of biochemical androgen eleva-
tion (57.6% [87 of 151] vs 70.3% [64 of 91], P = .05) (Table 2).
jamadermatology.com
Copyright 2016 American Medical Association. All rights reserved.
Downloaded From: https://jamanetwork.com/ on 04/06/2022
Original Investigation Research
Table 1. Prevalence of Cutaneous Findings Among Women Clinically
Suspected of Having PCOS Who Did or Did Not Meet the PCOS Criteria
No./Total No. (%)
Did Not Meet Met the
Cutaneous Finding the Criteria PCOS Criteria P Valuea
Acne 19/47 (40.4) 164/268 (61.2) .004
Hirsutism 15/48 (31.2) 144/270 (53.3) .005
Acanthosis nigricans 9/45 (20.0) 89/241 (36.9) .03
Androgenic alopecia 5/44 (11.4) 53/237 (22.4) .10
Seborrheic dermatitis 8/45 (17.8) 73/240 (30.4) .08
Abbreviation: PCOS, polycystic ovary syndrome.
a
χ2 Test.
Hirsutism
Women who met the criteria for PCOS were more likely to have
hirsutism than women who did not meet the criteria (53.3% [144
of 270] vs 31.2% [15 of 48], P = .005) (Table 1). Women meeting
the criteria had a higher mean total MFG score (8.6 vs 5.6, P =
.001) (Table 3). Increased hair was noted on the chin, with a site-
specific MFG score (range, 0-4) of 1.3 for women who met the
PCOS criteria vs 0.9 for women who did not (P = .05). Most im-
portant, higher mean truncal MFG scores were noted in wom-
en with PCOS, including the chest (0.4 vs 0.1, P = .01), upper ab-
domen (0.7 vs 0.3, P = .01), lower abdomen (1.7 vs 1.0, P < .001),
upper back (0.5 vs 0.2, P = .01), and lower back (0.9 vs 0.6, P =
.03). No significant differences were noted for the upper lip, up-
per arms, and thighs. In patients meeting the criteria for PCOS,
hirsutism when present was associated with a higher prevalence
of elevated free testosterone (43.9% [54 of 123] vs 30.9% [34 of
110], P = .04) but not other androgen measurements. The
presence of hirsutism was also associated with a higher mean
HOMA-IR (4.18 vs 3.38, P = .002), body mass index (BMI, cal-
culated as weight in kilograms divided by height in meters
squared) (32.3 vs 28.0, P < .001), and triglycerides level (114 vs
104 mg/dL, P = .04), as well as a lower HDL-C level (52 vs
59 mg/dL, P < .001) (Table 2).
Acanthosis Nigricans
Women who met the criteria for PCOS were more likely to have
AN than women who did not meet the criteria (36.9% [89 of 241]
vs 20.0% [9 of 45], P = .03) (Table 1), particularly in the axillae
(32.4% [78 of 241] vs 13.3% [6 of 45], P = .01) (Table 4). Among
women with PCOS, AN when present was associated with an
increased prevalence of free testosterone elevation (53.3% [40
of 75] vs 27.0% [40 of 148], P < .001) but not other androgen
measurements and with abnormal 2-hour OGTT results (31.7%
[20 of 63] vs 9.1% [12 of 132], P < .001) (Table 2). Acanthosis ni-
gricans in PCOS was also associated with an increased mean
HOMA-IR (7.13 vs 2.05, P < .001) and BMI (36.4 vs 27.6, P < .001)
and with higher levels of total cholesterol (197 vs 182 mg/dL, P =
.02), LDL-C (115 vs 105 mg/dL, P = .02), and triglycerides (147
vs 91 mg/dL, P < .001), as well as a lower mean HDL-C level (49
vs 58, P < .001) (Table 2). Among women without PCOS, AN was
associated with an increased BMI (29.0 vs 34.3, P = .04) and a
higher prevalence of abnormal 2-hour OGTT results (8.3% [2 of
24] vs 50.0% [3 of 6], P = .02).
(Reprinted) JAMA Dermatology April 2016 Volume 152, Number 4 393
 394
Table 2. Reproductive and Metabolic Characteristics of Women Clinically Suspected of Having PCOS Who Did or Did Not Meet the PCOS Criteria

Met the PCOS Criteria

Did Not Met the Acanthosis Acanthosis Androgenic Androgenic
Meet the PCOS Acne Acne Hirsutism Hirsutism Nigricans Nigricans Alopecia Alopecia
Cutaneous Findings Criteria Criteria P Value Absent Present P Value Absent Present P Value Absent Present P Value Absent Present P Value
Age, mean (SD), y 33.0 28.1 .002a 29.2 27.3 .03a 27.8 28.2 .55a 28.1 28.0 .98a 27.8 28.8 .19a
(9.6) (6.1) (6.3) (5.7) (5.4) (6.6) (5.8) (6.6) (6.1) (5.6)
(n = 48) (n = 274) (n = 96) (n = 164) (n = 126) (n = 144) (n = 173) (n = 83) (n = 197) (n = 56)
Reproductive Findings, No./Total No. (%)
Research Original Investigation

Elevation of ≥1 9/43 157/251 <.001a 64/91 87/151 .05b 70/118 87/129 .19b 93/160 55/76 .03b 104/164 30/50 .66b
biochemical (20.9) (62.5) (70.3) (57.6) (59.3) (67.4) (58.1) (72.4) (63.4) (60.0)
androgen level
Elevated total 2/47 105/258 <.001a 40/92 58/153 .30b 43/118 61/134 .14b 62/162 34/73 .43b 75/170 17/51 .17b
testosterone level (4.3) (40.7) (43.5) (37.9) (36.4) (45.5) (38.3) (46.6) (44.1) (33.3)
Elevated free 3/46 88/238 <.001a 35/89 49/139 .53b 34/110 54/123 .04b 40/148 40/75 <.001b 56/157 18/46 .67b

Downloaded From: https://jamanetwork.com/ on 04/06/2022

testosterone level (6.5) (37.0) (39.3) (35.3) (30.9) (43.9) (27.0) (53.3) (35.7) (39.1)
Elevated DHEAS level 6/45 43/254 .55a 19/92 24/152 .33b 17/116 26/133 .31b 26/160 16/76 .37b 29/167 4/51 .10b
(13.3) (16.9) (20.7) (15.8) (14.7) (19.5) (16.3) (21.1) (17.4) (7.8)
Oligoanovulation 13/44 240/267 <.001a 86/92 140/161 .11b 113/123 121/138 .27b 147/168 74/80 .24b 159/178 47/50 .32b
(29.5) (89.9) (93.5) (87.0) (91.9) (87.7) (87.5) (92.5) (89.3) (94.0)
Polycystic ovaries 12/36 226/252 <.001a 78/88 135/151 .85b 103/118 118/129 .28b 140/155 64/73 .57b 158/171 38/44 .05b

JAMA Dermatology April 2016 Volume 152, Number 4 (Reprinted)

(33.3) (89.7) (88.6) (89.4) (87.3) (91.5) (90.3) (87.7) (92.4) (86.4)
Metabolic Findings
HOMA-IR, mean (SD) 1.94 3.75 .06b 4.21 3.55 .66a 3.38 4.18 .002a 2.05 7.13 <.001a 3.46 5.17 .57a
(1.91) (6.82) (9.28) (4.80) (8.41) (5.23) (2.26) (10.70) (4.30) (12.40)
(n = 34) (n = 225) (n = 87) (n = 129) (n = 102) (n = 118) (n = 136) (n = 75) (n = 165) (n = 48)
Abnormal 2-h 2/36 35/213 .091a 12/75 21/126 .90b 13/97 20/112 .38b 12/132 20/63 <.001b 18/144 9/39 .10b
OGTT result, (5.6) (16.4) (16.0) (16.7) (13.4) (17.9) (9.1) (31.7) (12.5) (23.1)
No./total No. (%)
BMI, mean (SD) 28.9 30.3 .21b 30.5 30.1 .56a 28.0 32.3 <.001a 27.6 36.4 <.001a 29.9 31.5 .19a
(8.4) (8.2) (8.0) (8.3) (7.6) (8.2) (6.8) (8.0) (8.1) (8.4)
(n = 48) (n = 274) (n = 95) (n = 163) (n = 126) (n = 142) (n = 172) (n = 82) (n = 182) (n = 53)
Cholesterol level, 186 187 .98b 187 188 .39a 186 188 .71a 182 197 .02a 188 189 .92a
mean (SD), mg/dL (38) (41) (30) (47) (43) (41) (37) (50) (41) (50)
(n = 44) (n = 255) (n = 93) (n = 150) (n = 115) (n = 134) (n = 159) (n = 79) (n = 169) (n = 50)
LDL-C level, 109 108 .99b 108 109 .64a 106 111 .23a 105 115 .02a 106 112 .19a
mean (SD), mg/dL (35) (33) (31) (34) (32) (34) (32) (34) (33) (32)

Copyright 2016 American Medical Association. All rights reserved.

(n = 44) (n = 252) (n = 91) (n = 149) (n = 117) (n = 130) (n = 162) (n = 75) (n = 182) (n = 53)
HDL-C level, 62 56 .03b 57 55 .19a 59 52 <.001a 58 49 <.001a 56 51 .07a
mean (SD), mg/dL (18) (16) (15) (17) (16) (16) (16) (14) (17) (12)
(n = 42) (n = 251) (n = 93) (n = 147) (n = 115) (n = 131) (n = 159) (n = 78) (n = 181) (n = 54)
Triglycerides level, 85 109 .10b 111 108 .38a 104 114 .04a 91 147 <.001a 99 132 .17a
mean (SD), mg/dL (40) (102) (73) (119) (128) (72) (55) (157) (58) (183)
(n = 44) (n = 249) (n = 93) (n = 145) (n = 114) (n = 129) (n = 158) (n = 76) (n = 165) (n = 50)
Abbreviations: BMI, body mass index (calculated as weight in kilograms divided by height in meters squared); triglycerides level to millimoles per liter, multiply by 0.0113.
DHEAS, dehydroepiandrosterone; HDL-C, high-density lipoprotein cholesterol; HOMA-IR, homeostatic model of a
Mann-Whitney test.
insulin resistance; LDL-C, low-density lipoprotein cholesterol; OGTT, oral glucose tolerance test; PCOS, polycystic b
χ2 Test.
ovary syndrome.
SI conversion factors: To convert cholesterol level to millimoles per liter, multiply by 0.0259, and to convert

jamadermatology.com
Cutaneous Findings Associated With Polycystic Ovary Syndrome
 Cutaneous Findings Associated With Polycystic Ovary Syndrome Original Investigation Research

Androgenic Alopecia to multiple findings, mirroring previously recognized clinical

There was a suggestion of an increased prevalence of AGA heterogeneity of PCOS subtypes defined by the Rotterdam
among women who met the criteria for PCOS relative to those criteria.2,25 Herein, 8.3% [23 of 276] of women meeting the PCOS
who did not, but this difference was not statistically signifi- criteria had none of the skin manifestations examined. Each
cant (22.4% [53 of 237] vs 11.4% [5 of 44], P = .10) (Table 1). Of finding has a characteristic distribution and is associated with
women with AGA meeting the PCOS criteria, 43.7% (31 of 71) systemic abnormalities, which are summarized in Table 5.
demonstrated a diffuse pattern, with Ludwig grades of 1 (38.1%
[16 of 42]), 2 (11.9% [5 of 42]), and 3 (7.1% [3 of 42]). Of women Table 3. Hirsutism Burden by Body Area Among Women Who Did
or Did Not Meet the PCOS Criteria
with AGA meeting the PCOS criteria, 56.3% (40 of 71) demon-
strated frontal accentuation, with Olsen grades of 1 (81.1% [30 MFG Score, Mean (SD)
of 37]) and 2 (10.8% [4 of 37]). Among women meeting the cri- Did Not Meet Met the
the Criteria PCOS Criteria
teria, AGA when present was inversely related to the preva- Body Area (n = 45) (n = 242) P Valuea
lence of polycystic ovaries (86.4% [38 of 44] vs 92.4% [158 of Total MFG scoreb 5.6 (5.1) 8.6 (6.3) (n = 240) .001
171], P = .05) (Table 2). Upper lip 1.0 (1.0) 1.1 (1.0) .53
Chin 0.9 (1.0) 1.3 (1.3) .05
Reproductive and Metabolic Findings Chest 0.1 (0.4) 0.4 (0.8) (n = 240) .01
Women meeting the PCOS criteria had a higher prevalence of Upper arm 0.3 (0.7) 0.4 (0.8) (n = 241) .20
at least 1 elevated biochemical androgen (total testosterone, Upper abdomen 0.3 (0.5) 0.7 (0.9) .01
free testosterone, or DHEAS) (62.5% [157 of 251] vs 20.9% [9 Lower abdomen 1.0 (1.2) 1.7 (1.2) <.001

of 43], P < .001), oligoanovulation (89.9% [240 of 267] vs 29.5% Upper back 0.2 (0.5) 0.5 (0.8) .01
Lower back 0.6 (1.0) 0.9 (1.0) .03
[13 of 44], P < .001), and polycystic ovaries (89.7% [226 of 252]
Thigh 1.3 (1.2) 1.7 (1.1) (n = 241) .05
vs 33.3% [12 of 36], P < .001), along with lower HDL-C levels
(55.6 vs 61.9 mg/dL, P = .03) (Table 2). Among biochemical an- Abbreviations: MFG, modified Ferriman-Gallwey; PCOS, polycystic ovary
drogens, only the prevalence of elevated DHEAS level was simi- syndrome.
a
lar between the 2 groups. There were also no significant dif- Mann-Whitney test.
b
ferences in the HOMA-IR and the prevalence of abnormal The sum of physician-determined scores at 9 sites. Hirsutism was defined by
scores of at least 8.
2-hour OGTT results, as well as levels of total cholesterol,
LDL-C, and triglycerides. However, a suggestion toward greater
insulin resistance among women meeting the PCOS criteria Table 4. Acanthosis Nigricans Burden by Body Area Among Women
(mean HOMA-IR, 3.75 vs 1.94, P = .06) was notable. There was Who Did or Did Not Meet the PCOS Criteria

no difference in the rates of obesity (BMI, >30.0) between No./Total No. (%)
women who met the criteria for PCOS vs women who did not Did Not Meet Met the
Body Area the Criteria PCOS Criteria P Valuea
(44.5% [122 of 274] vs 43.8% [21 of 48], P > .99). The associa-
Neck 7/45 (15.6) 64/241 (26.6) .12
tions among cutaneous, reproductive, and metabolic find-
Central chest 4/44 (9.1) 41/237 (17.3) .17
ings are summarized in Table 2. Inframammary 3/45 (6.7) 37/240 (15.4) .12
Axillary 6/45 (13.3) 78/241 (32.4) .01
Knuckle 3/45 (6.7) 44/240 (18.3) .05
Inguinal crease 3/45 (6.7) 42/241 (17.4) .07
Discussion
Abbreviation: PCOS, polycystic ovary syndrome.
This study demonstrates that cutaneous evidence of PCOS when a
χ2 Test.
present manifests across a clinical spectrum ranging from none

Table 5. Summary of Key Cutaneous Findings of PCOS Among a High-Risk Population

Cutaneous Finding Key Distribution Systemic Association Comment

Acne Face (forehead) None Increased prevalence among patients who meet
PCOS diagnosis but no significant difference in
distribution or lesional counts, not associated
with biochemical hyperandrogenism, not a
reliable marker of hyperandrogenism in PCOS
Hirsutism Truncal is most specific (chest, Elevated free testosterone level, increased Excellent marker for PCOS and warrants selective
abdomen, or back), less specific insulin resistance, increased BMI, dyslipidemia endocrine and metabolic diagnostic evaluation,
are chin and thigh, nonspecific are (HDL-C, triglycerides) requires a comprehensive skin examination
upper lip and upper arm
Acanthosis Axillae Elevated free testosterone level, increased Excellent marker for PCOS and warrants selective
nigricans insulin resistance, increased glucose intolerance, endocrine and metabolic diagnostic evaluation,
increased BMI, dyslipidemia (total cholesterol, requires a comprehensive skin examination
LDL-C, HDL-C, or triglycerides)
Androgenic Scalp Lower prevalence of polycystic ovaries, Not a reliable marker for PCOS
alopecia associated with clinical but not biochemical
hyperandrogenism

Abbreviations: BMI, body mass index; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; PCOS, polycystic ovary syndrome.

jamadermatology.com (Reprinted) JAMA Dermatology April 2016 Volume 152, Number 4 395

Copyright 2016 American Medical Association. All rights reserved.

Downloaded From: https://jamanetwork.com/ on 04/06/2022

 Research Original Investigation
As expected for the diagnostic criteria used, women who met
the PCOS criteria had a higher prevalence of skin findings, el-
evated androgens, oligoanovulation, and polycystic ovaries.
Physical examination and studies that investigate these features
help determine if a patient meets the Rotterdam criteria. Acne,
hirsutism, and AN were the most common skin manifestations,
while hirsutism and AN were the most sensitive and informa-
tive for PCOS diagnosis. In particular, findings of axillary AN and
low HDL-C levels in combination may distinguish women most
at risk for meeting the PCOS criteria among a suspected popu-
lation and may help identify patients most in need of further di-
agnostic evaluation. Although not classically considered a sign
of HA, AN was strongly associated with biochemical HA and a
diagnosis of PCOS among the referral population (women
suspected of having PCOS).
This study was intended to identify cutaneous and systemic
features that distinguish women most at risk for having PCOS
among a racially diverse, high-risk population. It has several im-
portant limitations. All women in this study were referred for
clinically suspected PCOS, likely increasing the overall prevalence
of cutaneous findings.16 In addition, the comparison group did
not comprise a healthy control population but was composed of
women with clinical suspicion of PCOS but ultimately found not
to meet the diagnostic criteria. Therefore, this study was not de-
signed to detect features that set women who meet the PCOS di-
agnostic criteria apart from healthy women. In addition, this
study was likely underpowered to detect clinically relevant dif-
ferences in insulin sensitivity between women meeting and those
not meeting the criteria. Another limitation is that women con-
tinuing treatments for cutaneous manifestations of PCOS were
not excluded. However, this study design may better mirror the
common clinical scenario in which a dermatologist must, from
a high-risk population, identify women who will likely meet the
PCOS criteria. Finally, because some androgen measurements
were derived from many different testing laboratories and be-
cause normal ranges vary between laboratories, only dichoto-
mous (normal or abnormal) biochemical androgen results could
be used, limiting the power of the study.
Acne
The prevalence of acne among women who did not meet the
PCOS criteria in this study (40.4% [19 of 47]) was consistent
with previously reported estimates of acne prevalence among
adult women (6%-55%).26,27 In this study, women with PCOS
had a prevalence of acne (61.2% [164 of 268]) in the range of
previous reports (15%-95%).4,10,14-17,25 This result may reflect
the study population’s broad racial distribution because race
may affect acne prevalence.25,26,28-30
Among women with PCOS, acne when present was not as-
sociated with metabolic dysregulation or increased serum an-
drogens, corroborating the results of other studies25,31-35 and
suggesting that the acne-androgen association is complex. Most
important, acne does not uniformly indicate biochemical HA.36
Hirsutism
Although hirsutism affects 5% to 15% of women in the gen-
eral population,37 previous studies have reported a higher bur-
den of hirsutism among women with PCOS, estimating its
396 JAMA Dermatology April 2016 Volume 152, Number 4 (Reprinted)
Copyright 2016 American Medical Association. All rights reserved.
Downloaded From: https://jamanetwork.com/ on 04/06/2022
Cutaneous Findings Associated With Polycystic Ovary Syndrome
prevalence between 8.1% in one study17 and 77.5% in another
study.15 The prevalence of hirsutism among women with PCOS
in this study was 53.3% (144 of 270). A comprehensive skin ex-
amination was necessary to detect pronounced truncal hir-
sutism among women affected by PCOS (Table 3). Facial hir-
sutism may potentially not be a reliable marker of hirsutism
in PCOS because of hair removal practices.
In patients with PCOS, hirsutism when present was asso-
ciated with important reproductive and metabolic abnormali-
ties, including elevated free testosterone levels, increased in-
sulin resistance, lower HDL-C levels, and higher triglycerides
levels. Therefore, hirsutism is a cogent indication for a repro-
ductive and metabolic workup in women with PCOS.
Acanthosis Nigricans
Acanthosis nigricans is estimated to affect 20% of the US
population.38 Previous studies have shown a broad range in the
prevalence of AN among women with PCOS (2.5% in the United
Kingdom,39 5.2% in Turkey,16 and 17.2% in China40). A compre-
hensive skin examination is necessary to detect AN in the ax-
illa, where it is most frequently affected. The high rate seen in
this study (36.9% [89 of 241]) may result from the inclusion of
more body sites for evaluation, demographic differences, and
the high prevalence of obesity and metabolic dysfunction in the
United States.41
Among women with PCOS, the finding that AN when present
was associated with higher free testosterone levels may be ex-
plained by the association of AN with hyperinsulinemia, which
can promote ovarian thecal androgen secretion and inhibit he-
patic synthesis of sex hormone–binding globulin.42 In addition,
among women with PCOS, AN was associated with substantial
metabolic dysfunction (increased insulin resistance, glucose in-
tolerance, BMI, and dyslipidemia), consistent with the observa-
tions that AN is a marker of metabolic derangement.6,38,43 There-
fore, the presence of AN should raise clinical concern regarding
a patient’s potential metabolic risk factors.
Androgenic Alopecia
The 22.4% (53 of 237) prevalence of AGA among women meet-
ing the PCOS criteria in this study (and that of a recently published
study44 based on the same cross-section) is elevated relative to
measurements in unselected populations of similar age45,46 but
is less than the 35% prevalence reported in a Turkish study16 of
women with PCOS. Among women meeting the criteria in this
study, AGA was not associated with biochemical HA. These data
support previous observations that AGA in PCOS is more tightly
associated with clinical HA but not biochemical HA.25,44,47,48
Conclusions
Cutaneous findings of PCOS when present manifest across a
clinical spectrum ranging from complete absence to multiple
skin findings. Although acne is a common cutaneous feature in
women with PCOS, it did not distinguish between women sus-
pected of having PCOS and those actually meeting the diagnos-
tic criteria. Acne was also not associated with increased andro-
gen levels, suggesting a complex acne-androgen association.
jamadermatology.com
 Cutaneous Findings Associated With Polycystic Ovary Syndrome Original Investigation Research

This study demonstrates that hirsutism and AN are the most use-
ful cutaneous indicators of PCOS to distinguish patients most
at risk for having PCOS among a suspected population. Most im-
portant, these cutaneous features manifest a characteristic dis-
tribution and systemic associations (Table 5). With regard to dis-
tribution, truncal hirsutism was found to be a better indicator
of PCOS than facial hirsutism. Acanthosis nigricans, with more
axillary involvement than neck involvement, was common in
PCOS. Therefore, a comprehensive skin examination may be
necessary to detect cutaneous evidence of PCOS.
This study found significant overlap among the reproduc-
tive and metabolic abnormalities associated with hirsutism and
AN in women meeting the criteria for PCOS. The significant
coincidence between hirsutism and AN may have contrib-
uted to the similarities in systemic findings. Alternatively, hir-
sutism and AN may be linked by an underlying mechanism that
is distinct from the pathogenesis underlying acne and AGA,
which are less likely to be associated with systemic abnormali-
ties in PCOS. This study lends support to the concept that hy-
perinsulinemia, a likely driver of AN, is also an important ele-
ment of PCOS-related pathogenesis, although it is not part of
the current criteria.49 Most important, in the setting of sus-
pected PCOS (with or without meeting the diagnostic crite-
ria), hirsutism and AN warrant additional diagnostic evalua-
tion because they are associated with increased glucose
intolerance, BMI, free testosterone levels, and dyslipidemia.

ARTICLE INFORMATION REFERENCES and manifestations. J Am Acad Dermatol. 2014;71(5):

Accepted for Publication: October 1, 2015. 1. Schmidt TH, Shinkai K. Evidence-based approach 847.e1-847.e10. doi:10.1016/j.jaad.2014.05.007.

Published Online: December 23, 2015.
doi:10.1001/jamadermatol.2015.4498.
Author Contributions: Drs Schmidt and Shinkai
had full access to all the data in the study and take
responsibility for the integrity of the data and the
accuracy of the data analysis.
Study concept and design: Cedars, Huddleston,
Pasch, Zane, Shinkai.
Acquisition, analysis, or interpretation of data: All
authors.
Drafting of the manuscript: Schmidt, Khanijow,
Shinkai.
Critical revision of the manuscript for important
intellectual content: All authors.
Statistical analysis: Schmidt.
Study supervision: Cedars, Huddleston, Shinkai.
Conflict of Interest Disclosures: Dr Schmidt
reported being supported by the University of
California, San Francisco, Medical Scientist Training
Program and California Pacific Medical Center
residency program. Dr Cedars reported being an
investigator for and a recipient of grants from
Ferring and Nova Therapeutics. Dr Zane reported
being an employee and stockholder of Anacor
Pharmaceuticals. Dr Shinkai reported being
supported (2010-2013) by a Medical Dermatology
Career Development Award. No other disclosures
were reported.
Funding/Support: This study was funded in part by
University of California, San Francisco–Clinical and
Translational Science Institute grant UL1
TR000004 from the National Center for
Advancing Translational Sciences, National
Institutes of Health.
Role of the Funder/Sponsor: The funding sources
had no role in the design and conduct of the study;
collection, management, analysis, and
interpretation of data; preparation, review, or
approval of the manuscript; or decision to submit
the manuscript for publication.
Disclaimer: The contents are solely the
responsibility of the authors and do not necessarily
represent the official views of the National
Institutes of Health.
Additional Contributions: I. Elaine Allen, PhD,
Chengshi Jin, PhD, and David Glidden, PhD (all
affiliated with the University of California,
San Francisco) provided research support. No
financial compensation was provided.
to cutaneous hyperandrogenism in women. J Am
Acad Dermatol. 2015;73(4):672-690.
2. Rotterdam ESHRE/ASRM-Sponsored PCOS
Consensus Workshop Group. Revised 2003
consensus on diagnostic criteria and long-term
health risks related to polycystic ovary syndrome
(PCOS). Hum Reprod. 2004;19(1):41-47.
3. Norman RJ, Dewailly D, Legro RS, Hickey TE.
Polycystic ovary syndrome. Lancet. 2007;370
(9588):685-697.
4. Azziz R, Sanchez LA, Knochenhauer ES, et al.
Androgen excess in women: experience with over
1000 consecutive patients. J Clin Endocrinol Metab.
2004;89(2):453-462.
5. Carmina E, Rosato F, Jannì A, Rizzo M, Longo RA.
Extensive clinical experience: relative prevalence of
different androgen excess disorders in 950 women
referred because of clinical hyperandrogenism.
J Clin Endocrinol Metab. 2006;91(1):2-6.
6. Lee AT, Zane LT. Dermatologic manifestations of
polycystic ovary syndrome. Am J Clin Dermatol.
2007;8(4):201-219.
7. Lowenstein EJ. Diagnosis and management of
the dermatologic manifestations of the polycystic
ovary syndrome. Dermatol Ther. 2006;19(4):210-223.
8. Sivayoganathan D, Maruthini D, Glanville JM,
Balen AH. Full investigation of patients with
polycystic ovary syndrome (PCOS) presenting to
four different clinical specialties reveals significant
differences and undiagnosed morbidity. Hum Fertil
(Camb). 2011;14(4):261-265.
9. Livadas S, Diamanti-Kandarakis E. Polycystic
ovary syndrome: definitions, phenotypes and
diagnostic approach. Front Horm Res. 2013;40:1-21.
10. Balen A, Michelmore K. What is polycystic
ovary syndrome? are national views important?
Hum Reprod. 2002;17(9):2219-2227.
11. de Groot PC, Dekkers OM, Romijn JA, Dieben
SW, Helmerhorst FM. PCOS, coronary heart
disease, stroke and the influence of obesity:
a systematic review and meta-analysis. Hum Reprod
Update. 2011;17(4):495-500.
12. Chittenden BG, Fullerton G, Maheshwari A,
Bhattacharya S. Polycystic ovary syndrome and the
risk of gynaecological cancer: a systematic review.
Reprod Biomed Online. 2009;19(3):398-405.
13. Housman E, Reynolds RV. Polycystic ovary syn-
drome: a review for dermatologists: Part I. Diagnosis
14. Jones GL, Benes K, Clark TL, et al. The
Polycystic Ovary Syndrome Health-Related Quality
of Life Questionnaire (PCOSQ): a validation. Hum
Reprod. 2004;19(2):371-377.
15. Chang WY, Knochenhauer ES, Bartolucci AA,
Azziz R. Phenotypic spectrum of polycystic ovary
syndrome: clinical and biochemical characterization
of the three major clinical subgroups. Fertil Steril.
2005;83(6):1717-1723.
16. Ozdemir S, Ozdemir M, Görkemli H, Kiyici A,
Bodur S. Specific dermatologic features of the
polycystic ovary syndrome and its association with
biochemical markers of the metabolic syndrome
and hyperandrogenism. Acta Obstet Gynecol Scand.
2010;89(2):199-204.
17. Zhang HY, Guo CX, Zhu FF, Qu PP, Lin WJ, Xiong
J. Clinical characteristics, metabolic features, and
phenotype of Chinese women with polycystic ovary
syndrome: a large-scale case-control study. Arch
Gynecol Obstet. 2013;287(3):525-531.
18. Burke BM, Cunliffe WJ. The assessment of acne
vulgaris: the Leeds technique. Br J Dermatol. 1984;
111(1):83-92.
19. Ferriman D, Gallwey JD. Clinical assessment of
body hair growth in women. J Clin Endocrinol Metab.
1961;21:1440-1447.
20. Hatch R, Rosenfield RL, Kim MH, Tredway D.
Hirsutism: implications, etiology, and management.
Am J Obstet Gynecol. 1981;140(7):815-830.
21. Yildiz BO. Assessment, diagnosis and treatment
of a patient with hirsutism. Nat Clin Pract Endocrinol
Metab. 2008;4(5):294-300.
22. Ludwig E. Classification of the types of
androgenetic alopecia (common baldness)
occurring in the female sex. Br J Dermatol. 1977;97
(3):247-254.
23. Olsen EA. Current and novel methods for
assessing efficacy of hair growth promoters in
pattern hair loss. J Am Acad Dermatol. 2003;48(2):
253-262.
24. Matthews DR, Hosker JP, Rudenski AS, Naylor
BA, Treacher DF, Turner RC. Homeostasis model
assessment: insulin resistance and beta-cell
function from fasting plasma glucose and insulin
concentrations in man. Diabetologia. 1985;28(7):
412-419.
25. Hong JS, Kwon HH, Park SY, et al. Cutaneous
manifestations of the subtypes of polycystic ovary

jamadermatology.com (Reprinted) JAMA Dermatology April 2016 Volume 152, Number 4 397

Copyright 2016 American Medical Association. All rights reserved.

Downloaded From: https://jamanetwork.com/ on 04/06/2022

 Research Original Investigation Cutaneous Findings Associated With Polycystic Ovary Syndrome

syndrome in Korean patients. J Eur Acad Dermatol
Venereol. 2015;29(1):42-47.
26. Shen Y, Wang T, Zhou C, et al. Prevalence of
acne vulgaris in Chinese adolescents and adults:
a community-based study of 17,345 subjects in six
cities. Acta Derm Venereol. 2012;92(1):40-44.
27. Perkins AC, Maglione J, Hillebrand GG,
Miyamoto K, Kimball AB. Acne vulgaris in women:
prevalence across the life span. J Womens Health
(Larchmt). 2012;21(2):223-230.
28. Williamson K, Gunn AJ, Johnson N, Milsom SR.
The impact of ethnicity on the presentation of
polycystic ovarian syndrome. Aust N Z J Obstet
Gynaecol. 2001;41(2):202-206.
29. Bhate K, Williams HC. Epidemiology of acne
vulgaris. Br J Dermatol. 2013;168(3):474-485.
30. Wang ET, Kao CN, Shinkai K, Pasch L, Cedars
MI, Huddleston HG. Phenotypic comparison of
Caucasian and Asian women with polycystic ovary
syndrome: a cross-sectional study. Fertil Steril.
2013;100(1):214-218.
31. Cibula D, Hill M, Vohradnikova O, Kuzel D, Fanta
M, Zivny J. The role of androgens in determining
acne severity in adult women. Br J Dermatol. 2000;
143(2):399-404.
32. Thiboutot D, Gilliland K, Light J, Lookingbill D.
Androgen metabolism in sebaceous glands from
subjects with and without acne. Arch Dermatol.
1999;135(9):1041-1045.
33. Harper JC. Antiandrogen therapy for skin and
hair disease. Dermatol Clin. 2006;24(2):137-143, v.
34. Walton S, Cunliffe WJ, Keczkes K, et al. Clinical,
ultrasound and hormonal markers of androgenicity
in acne vulgaris. Br J Dermatol. 1995;133(2):249-253.
35. Slayden SM, Moran C, Sams WM Jr, Boots LR,
Azziz R. Hyperandrogenemia in patients presenting
with acne. Fertil Steril. 2001;75(5):889-892.
36. Reingold SB, Rosenfield RL. The relationship of
mild hirsutism or acne in women to androgens. Arch
Dermatol. 1987;123(2):209-212.
37. Azziz R. The evaluation and management of
hirsutism. Obstet Gynecol. 2003;101(5, pt 1):995-1007.
38. Kong AS, Williams RL, Rhyne R, et al; PRIME
Net Clinicians. Acanthosis nigricans: high
prevalence and association with diabetes in a
practice-based research network consortium:
a Primary Care Multi-Ethnic Network (PRIME Net)
study. J Am Board Fam Med. 2010;23(4):476-485.
39. Balen AH, Conway GS, Kaltsas G, et al. Polycystic
ovary syndrome: the spectrum of the disorder in 1741
patients. Hum Reprod. 1995;10(8):2107-2111.
40. Li X, Lin JF. Clinical features, hormonal profile,
and metabolic abnormalities of obese women with
obese polycystic ovary syndrome [in Chinese].
Zhonghua Yi Xue Za Zhi. 2005;85(46):3266-3271.
41. Cameron AJ, Shaw JE, Zimmet PZ. The
metabolic syndrome: prevalence in worldwide
populations. Endocrinol Metab Clin North Am.
2004;33(2):351-375.
42. Poretsky L, Cataldo NA, Rosenwaks Z, Giudice
LC. The insulin-related ovarian regulatory system in
health and disease. Endocr Rev. 1999;20(4):535-582.
43. Higgins SP, Freemark M, Prose NS. Acanthosis
nigricans: a practical approach to evaluation and
management. Dermatol Online J. 2008;14(9):2.
44. Quinn M, Shinkai K, Pasch L, Kuzmich L, Cedars
M, Huddleston H. Prevalence of androgenic
alopecia in patients with polycystic ovary syndrome
and characterization of associated clinical and
biochemical features. Fertil Steril. 2014;101(4):
1129-1134.
45. Birch MP, Messenger JF, Messenger AG. Hair
density, hair diameter and the prevalence of female
pattern hair loss. Br J Dermatol. 2001;144(2):297-304.
46. Norwood OT. Incidence of female
androgenetic alopecia (female pattern alopecia).
Dermatol Surg. 2001;27(1):53-54.
47. Futterweit W, Dunaif A, Yeh HC, Kingsley P. The
prevalence of hyperandrogenism in 109
consecutive female patients with diffuse alopecia.
J Am Acad Dermatol. 1988;19(5 pt 1):831-836.
48. Schmidt JB, Lindmaier A, Trenz A, Schurz B,
Spona J. Hormone studies in females with
androgenic hairloss. Gynecol Obstet Invest. 1991;31
(4):235-239.
49. Azziz R, Carmina E, Dewailly D, et al; Task Force
on the Phenotype of the Polycystic Ovary
Syndrome of The Androgen Excess and PCOS
Society. The Androgen Excess and PCOS Society
criteria for the polycystic ovary syndrome: the
complete task force report. Fertil Steril. 2009;91(2):
456-488.

NOTABLE NOTES

Dermatologic Ailments in the White House

Stephanie Mlacker, BS; Adam S. Aldahan, BS; Vidhi V. Shah, BA; Keyvan Nouri, MD

American history encompasses a wide spectrum of dermatologic
disease that has affected past presidents of the United States and their
families. America’s founding father, George Washington, developed a
carbuncle on his left hip during his first year as president. After several
weeks, during which he was very ill, he underwent incision and drainage,
with his symptoms improving immediately. James Madison developed
frostbite on his nose after campaigning for the First Congress in 1788.
A few days after delivering the Gettysburg Address, Abraham
Lincoln developed “dusky red spots about the forehead,”1(pp185-186)
which after spreading to his face and extremities, evolved into an
acneiform appearance. Although Lincoln recovered uneventfully a few
weeks later, a smallpox epidemic had undoubtedly taken over
Washington during the winter of 1863.1 One of America’s Civil War
heroes, Ulysses S. Grant, developed a cancerous growth at the base of
his tongue in 1884; this occurred after many years of heavy drinking
and smoking, inevitably leading to his death. Similarly, Grover
Cleveland developed a malignant neoplasm on the left side of his jaw,
involving the soft palate, and underwent a secret operation for its
removal in 1893.1
In 1892, Rutherford B. Hayes developed dermatitis, involving his
hands and face, secondary to his exposure to poison ivy while pruning
trees. Franklin D. Roosevelt’s pigmented nevus, located above his left
eyebrow, no longer appeared in photographs after 1943, leading people
to believe that it had been removed. The importance of this subtlety was
noted after the president’s fatal seizure in 1945, raising questions
regarding melanoma as the possible culprit.1,2
John F. Kennedy was diagnosed as having Addison disease in 1947,
years before serving as president. Although Kennedy exuded vitality with
his youthful, tanned-like appearance, the hyperpigmentation of his face
was actually a manifestation of his autoimmune condition. Lyndon B.
Johnson underwent a clandestine procedure in 1967 to remove a basal
cell carcinoma from his left ankle. Similarly, Ronald Reagan had basal cell
carcinomas removed both during and in the years following his presi-
dency; moreover, his daughter, Maureen Reagan, subsequently died as
a result of melanoma metastases, affecting the brain.3
As revealed throughout American history, dermatology
can indeed have an impact on anyone’s life, including the lives of
prominent political leaders.
Author Affiliations: Department of Dermatology and Cutaneous Surgery,
University of Miami Miller School of Medicine, Miami, Florida.
Corresponding Author: Stephanie Mlacker, BS, Department of Dermatology
and Cutaneous Surgery, University of Miami Miller School of Medicine, 1475 NW
12th Ave, Miami, FL 33136 (mlackerstephanie@gmail.com).
1. Marx R. The Health of the Presidents. New York, NY: Putnam; 1961.
2. Etang H. The Pathology of Leadership. New York, NY: Hawthorn Books; 1970.
3. Bumgarner J. The Health of the Presidents: The 41 United States Presidents
Through 1993 From a Physician’s Point of View. Jefferson, NC: McFarland & Co;
1994.

398 JAMA Dermatology April 2016 Volume 152, Number 4 (Reprinted) jamadermatology.com

Copyright 2016 American Medical Association. All rights reserved.

Downloaded From: https://jamanetwork.com/ on 04/06/2022