Breast Cancer Res Treat (2013) 142:435–443 DOI 10.1007/s10549-013-2744-2

EPIDEMIOLOGY

Aromatase inhibitor therapy and hair loss among breast cancer survivors Lisa Gallicchio • Carla Calhoun • Kathy J. Helzlsouer

Received: 30 July 2013 / Accepted: 21 October 2013 / Published online: 7 November 2013 Ó Springer Science+Business Media New York 2013

Abstract The objective of this study was to examine the associations between aromatase inhibitor therapy and hair loss or hair thinning among female breast cancer survivors. Data were analyzed from 851 female breast cancer survivors who responded to a hospital registry-based survey. Data on hair loss, hair thinning, demographic characteristics, and health habits were based on self-report; data on aromatase inhibitor therapy were collected on the survey and verified using medical record review. Logistic regression was used to estimate the odds ratios (ORs) and 95 % confidence intervals (CIs) for the associations between aromatase inhibitor therapy and the hair outcome variables adjusted for potential confounders, including age and chemotherapy treatment. The results showed that 22.4 % of the breast cancer survivors reported hair loss and 31.8 % reported hair thinning. In the confounder-adjusted analyses, breast cancer survivors who were within 2 years of starting aromatase inhibitor treatment at the time of survey completion were approximately two and a half times more likely to report reporting hair loss (OR 2.55; 95 % CI 1.19–5.45) or hair thinning (OR 2.33; 95 % CI 1.10–4.93) within the past 4 weeks compared to those who were never treated with an aromatase inhibitor. Current aromatase L. Gallicchio (&)  C. Calhoun  K. J. Helzlsouer The Prevention and Research Center, The Weinberg Center for Women’s Health and Medicine, Mercy Medical Center, 227 St. Paul Place, Baltimore, MD 21202, USA e-mail: [email protected] L. Gallicchio  K. J. Helzlsouer Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA L. Gallicchio Department of Epidemiology and Public Health, University of Maryland, Baltimore, Baltimore, MD, USA

inhibitor use for two or more years at the time of the survey and prior use were significantly associated with hair thinning (current users, C2 years: OR 1.86; prior users: OR 1.62), but not hair loss. Findings from this study suggest that aromatase inhibitor use is associated with an increased risk of hair loss and hair thinning independent of chemotherapy and age; these side effects are likely due to the substantial decrease in estrogen concentrations resulting from treatment with this drug. Future research should focus on examining these associations in a prospective manner using more detailed and objective measures of hair loss and thinning. Keywords Aromatase inhibitors  Estrogen  Hair loss  Hair thinning  Side effects

Introduction Aromatase inhibitors are currently the adjuvant hormonal therapy of choice among postmenopausal women with early stage, estrogen receptor-positive breast cancer. Aromatase inhibitors work by preventing the formation of estrogen in the body by blocking the aromatization of testosterone to estradiol and androstenedione to estrone in fat tissue [1]. Large randomized clinical trials have shown that the use of aromatase inhibitors decreases a woman’s risk of breast cancer recurrence and death [2–5]. However, the positive effects of aromatase inhibitors on breast cancer recurrence and survival for a breast cancer patient are not without costs. Studies have shown that the use of aromatase inhibitors increases a woman’s risk of experiencing menopausal-type symptoms such as hot flashes and vaginal dryness [6–11]. These side effects not only impact a woman’s quality of life, but also create barriers to

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adherence, which ultimately could impact breast cancerassociated survival and recurrence [9, 12]. One of the less frequently investigated possible side effects impacting breast cancer survivors on aromatase inhibitor therapy is hair loss and thinning. Hair loss and thinning is considered to be a normal occurrence in older, post-menopausal women [13–15]. Throughout a women’s lifetime, her hair follicles (the portion of hair responsible for the production of the hair shaft or hair fiber) go through cycles of growth (anagen), resorption (catagen), and rest (telogen) [13]. Changes in hair are attributed to changes in the hair cycle, hair follicle, or hair shaft. Women with hair loss are most often diagnosed with one of three clinical conditions: hair follicle disorders such as female pattern hair loss (FPHL), hair shaft alterations caused by hair care, and telogen effluvium due to changes in the hair cycle [13–15]. FPHL is found to be the most common of these conditions impacting at least 55 % of women over 70 years of age [13, 15]. There is evidence that estrogens, and other sex hormones such as testosterone, have a role in the hair processes, particularly in the modulation of hair follicle biology [13–16]. Specifically, the increased prevalence in FPHL after the menopausal transition, when estrogen concentrations drop significantly, as well as hair composition changes observed during pregnancy, a time period of dramatically changing estrogen concentrations, suggest that low estrogen may lead to hair loss and thinning [13, 15, 17, 18]. Thus, it is biologically plausible that aromatase inhibitors, which reduce estrogen levels to near undetectable concentrations in most breast cancer patients, may cause hair loss and hair thinning. However, the associations between aromatase inhibitors and hair loss or thinning have only been examined in a few, primarily small, studies, most of which have noted this symptom only as a side effect or adverse outcome [10, 19, 20]. Thus, the purpose of this analysis was to examine the associations between aromatase inhibitor use and hair loss and thinning in a systematic fashion among a registry-based study of 851 female breast cancer survivors.

Methods Study sample Data were collected from a survey-based study of cancer survivors listed in the Mercy Medical Center cancer registry between January 1996 and July 2007. Detailed methods of data collection are published elsewhere [21]. Briefly, in June 2008, a self-administered questionnaire was sent to all cancer survivors in the Mercy Medical Center registry; a second mailing to non-respondents was

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conducted in November 2009. Consent was implied with the return of the questionnaire. The study was approved by the Institutional Review Board at Mercy Medical Center in Baltimore, Maryland, USA. A total of 2,513 breast cancer survivors were sent the questionnaire (57.1 % of all cancer survivors in the registry dataset); of these, 868 (34.5 %) returned the questionnaire. Respondents were significantly more likely to be of white race compared to non-respondents (83.7 vs. 67.4 %); however, the two groups did not differ in terms of sex, time since diagnosis, or tumor behavior (malignant versus in situ). Measures Information on cancer treatments was self-reported on the survey, and when treatment information was available in the medical records (approximately 95 % of patients who responded), this information was verified using a review of medical records. The primary reason that treatment information was not available for some patients was that they were treated at another institution and their treatment records were not transferred to Mercy Medical Center. For breast cancer patients whose treatment records were reviewed, the survey data were 100 % accurate in terms of whether the patient had been treated with chemotherapy and/or radiation (although survey data on type of chemotherapy was slightly less accurate at 94 %). Agreement of survey data on treatment with hormone therapy (tamoxifen and aromatase inhibitors) with medical record data was approximately 98 %. Among women indicating aromatase inhibitor use on the survey, medical record review was also used to determine whether the aromatase inhibitor was being taken at the time of or prior to survey completion and, if the information was available, the duration of aromatase inhibitor use. Hair loss and hair thinning was assessed by asking women ‘‘the extent to which you have been bothered by any of the following problems during the past 4 weeks.’’ Possible responses were: ‘‘not at all,’’ ‘‘slightly,’’ ‘‘moderately,’’ ‘‘quite a bit,’’ and ‘‘extremely.’’ For the analyses, the hair loss and hair thinning responses were categorized as ‘‘yes’’ and ‘‘no’’ by collapsing the categories indicating any experience of the symptom over the queried time period. A combined category of ‘‘hair loss or thinning’’ was also created and analyzed. Cancer survivors reported their race, date of birth, education, marital status, menopausal status, smoking status, and use of alcohol in response to survey questions. Body mass index (BMI) was calculated based on selfreported weight and height on the survey. With the exception of race and date of birth, these data reflect participant information at the time of the survey and not at the

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time of diagnosis. Further, respondents were queried as to whether they had ‘‘ever been told by a doctor or other health professional’’ that they had any of 49 medical conditions, including diabetes, high cholesterol, depression, and osteoporosis. Participants were also given the option of listing ‘‘other’’ medical conditions not present among the 49 conditions on the survey. Conditions were then grouped into the following 12 overarching categories: diabetes, heart, bone, thyroid, lung, autoimmune, gastrointestinal, kidney/bladder, neurological, gynecological, eye, and emotional. A variable was created that reflected the total number of co-morbid condition types. For analyses, the number of co-morbid condition types was categorized into quartiles. Respondents reported their history of all cancer diagnoses, including their breast cancer diagnosis, as well as the age at which each cancer was diagnosed. Self-reported information was supplemented with data from the cancer registry. Although estrogen receptor status was not part of the information collected from the registry or the survey, pathology reports were reviewed for a random sample of 100 breast cancer survivors who responded to the survey; this review showed that 69.8 % of the patients were estrogen receptor positive. Time since diagnosis of first breast cancer was calculated. The median time since breast cancer diagnosis for the breast cancer survivors who responded to the survey was 7 years (range 1–43 years). Data analysis

437 Table 1 Characteristics of the study sample at the time of survey completion (n = 851) n Demographics Age at survey (years), median (range)

62

(33, 95)

Race White

709

83.3

Black

116

13.6

Other

26

3.1

232

27.3

Marital status Single Married/living with partner

475

55.8

Widowed

141

16.6

3

0.3

Missing Educational level High school or less

269

31.6

College graduate

369

43.4

Graduate school

208

24.4

5

0.6

Missing Body mass index (kg/m2) \25.0

336

39.5

25.0 to B29.9

270

31.7

C30.0

243

28.6

2

0.2

Missing Smoking status Current

59

6.9

Former

355

41.7

Never

426

50.1

11

1.3

Missing

Male breast cancer survivors (n = 5) and respondents missing data on both hair symptom questions (n = 8) or aromatase inhibitor use (n = 4) were excluded from the analytic dataset. Thus, the final analytic was comprised of 851 female breast cancer survivors. Differences in the demographic and health characteristics at the time of survey completion between the breast cancer survivors reporting and not reporting each hair symptom were tested using Chi square tests. In addition, logistic regression was used to estimate the unadjusted and adjusted odds ratios (ORs) and 95 % confidence intervals (CI) for the association between aromatase inhibitor use and each hair outcome variable. Covariates included in the adjusted model were identified as variables significantly associated (p \ 0.05) with both aromatase inhibitor use and at least one of the hair outcome variables in the bivariate analyses (age, race, BMI, chemotherapy, and radiation). In addition, time since diagnosis was entered into the model as a surrogate for time since the completion of adjuvant therapy (chemotherapy and radiation). Stratified analyses were conducted by age (\60 years and C60 years), BMI (\25 kg/m2, 25 to \30 kg/m2, and C30 kg/m2), prior chemotherapy treatment (yes, no), and

%

Current alcohol drinker Yes

569

66.8

No

272

32.0

10

1.2

Yes

779

91.6

No

59

6.9

Missing

13

1.5

0–2

124

14.6

3–5

262

30.8

6 or 7 C8

275 188

32.3 22.1

2

0.2

Missing Postmenopausal

Number of co-morbid conditions

Missing Cancer diagnosis and treatments Age at diagnosis (years) median (range)

55

(26, 89)

Years since diagnosis \2 years

18

2.1

2–5 years

225

26.4

[5 years

608

71.5

212

24.9

Aromatase inhibitor therapy Current

123

438

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Table 1 continued n

%

Prior

110

12.9

Never

529

62.2

Duration of aromatase inhibitor usea C5 years

50

15.5

148

46.0

\2 years

83

25.8

Missing

41

12.7

Yes

342

40.2

No

509

59.8

367

43.1

484

56.9

Yes

523

61.5

No

328

38.5

Yes

191

22.4

No

646

75.9

14

1.7

Yes

269

31.6

No

577

67.8

5

0.6

Yes

289

34.0

No Missing

557 5

65.4 0.6

2 to \5 years

Tamoxifen

Chemotherapy Yes No Radiation

Hair symptoms Hair loss

Missing Hair thinning

Missing Hair loss or hair thinning

a

Among only women who reported current or prior aromatase inhibitor use

years since first breast cancer diagnosis (\5 years, C5 years); however, no evidence of effect modification was found, either in comparing the ORs across strata or by examining the statistical significance of an interaction term in the regression model. Thus, the results of these stratified analyses are not reported. All analyses were performed using SAS version 9.2. A two-sided p value \0.05 was considered statistically significant.

Results Breast cancer survivors in the analytic study sample had a median age of 62 years at the time of the survey (range 33–95 years) and a median age of 55 years at the time of diagnosis (range 26–89 years) (Table 1). The breast cancer survivors were, on average, 7.4 years from their breast

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cancer diagnosis (range 1–43 years). The majority were white (83.3 %), married or living with partner (55.8 %), college graduates (67.8 %), never smokers (50.1 %), current alcohol drinkers (66.8 %), and postmenopausal (91.6 %). The mean BMI at the time of the survey was 27.7 kg/m2 (standard deviation (SD) 6.2), with 28.6 % of survivors categorized as being obese. Approximately 85.2 % reported three or more co-morbid conditions; 22.1 % of the survivors reported at least eight co-morbid conditions. Among the breast cancer survivors, 43.1 % reported being treated with chemotherapy (Table 1). The most common agents used for treatment among those who received chemotherapy were doxorubicin (80.1 %), cyclophosphamide (84.7 %), and a taxane (56.1 %). With the exception of 5-fluorouracil (7.1 %), all other agents were used for treatment by less than 5 % of participants receiving chemotherapy. Approximately 62 % of the sample was treated with radiation and 37.8 % with an aromatase inhibitor; most survivors who reported aromatase inhibitor use were taking the drug at the time of survey completion (65.8 %). The majority of women who took or were taking an aromatase inhibitor took the medication for 2–5 years (46.0 %). Hair loss in the past 4 weeks was reported by 22.4 % of the survivors; 31.6 % reported hair thinning within this same time period. Thirty-four percent (34.0 %) had at least one of the queried hair symptoms (hair loss or hair thinning) in the past 4 weeks. Hair loss among the breast cancer survivors was significantly associated with black and other races, higher BMI, fewer co-morbid conditions, as well as treatment with chemotherapy, radiation, and an aromatase inhibitor (Table 2). Similar statistically significant associations were observed for hair thinning and for the combined outcome of hair loss and/or hair thinning and these characteristics. In contrast, age, marital status, educational level, smoking status, current alcohol drinking, menopausal status, tamoxifen treatment, and years since breast cancer diagnosis were not associated with hair loss, hair thinning, or the combined outcome of hair loss, and/or hair thinning. Duration of aromatase inhibitor used among breast cancer survivors who reported being treated with an aromatase inhibitor was not associated with any of the hair outcomes. The confounder-adjusted ORs and 95 % CIs of aromatase inhibitor use and the hair outcome variables are shown in Table 3. After adjustment for potential confounders, the results showed that breast cancer survivors who were within 2 years of starting aromatase inhibitor treatment at the time of survey completion were approximately two and a half times more likely to report reporting hair loss within the past 4 weeks compared to those who never were treated with an aromatase inhibitor (OR 2.55; 95 % CI 1.19–5.45).

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439

Table 2 Bivariate associations between sample characteristics and hair-related outcome variables Hair loss

Hair thinning

Yes (n = 191)

No (n = 646)

n

n

%

p value

%

Yes (n = 269)

No (n = 577)

n

n

%

p value

%

Demographics Age, years, mean (SD)

62.5

10.7

Race White

147

77.0

Black

35

Other

9

62.1

11.3

0.6

62.7

10.8

62.0

11.3

0.02 551

85.3

18.3

79

4.7

16

0.001 205

76.2

12.2

52

2.5

12

Marital status

499

86.5

19.3

64

11.1

4.5

14

2.4

0.3

0.06

Single

60

31.4

169

26.1

86

32.0

142

24.6

Married/living with partner

99

51.8

370

57.3

136

50.6

338

58.6

Widowed

31

16.2

105

16.3

45

16.7

96

16.6

Educational level

0.5

0.7

High school or less

59

30.9

205

31.7

87

32.3

182

31.5

College graduate

89

46.6

276

42.7

118

43.9

247

42.8

Graduate school

41

21.5

162

25.1

61

22.7

146

25.3

BMI (kg/m2)

\0.0001

0.001

\25.0

59

30.9

274

42.4

76

28.3

259

44.9

25.0 to B29.9

58

30.4

203

31.4

95

35.3

173

30.0

C30.0 Smoking status

74

38.7

167

25.9

98

36.4

143

24.8

Current

11

5.8

47

7.3

20

7.4

39

6.8

Former

84

44.0

266

41.2

114

42.4

240

41.6

Never

94

49.2

325

50.3

134

49.8

289

50.1

0.7

Current alcohol drinker

0.9

0.6

0.2

Yes

124

64.9

437

67.3

173

64.3

395

68.5

No

63

33.0

203

31.4

93

34.6

176

30.5

Postmenopausal Yes

0.2

0.3

178

93.2

588

91.0

249

92.6

525

91.0

9

4.7

50

7.7

15

5.6

44

7.6

0–2

27

14.1

97

15.0

30

11.2

93

16.1

3–5

38

19.9

218

33.7

63

23.4

197

34.1

6 or 7

60

31.4

214

33.1

84

31.2

190

32.9

C8

65

34.0

116

18.0

91

33.8

97

16.8

4

2.1

14

2.2

4

1.5

14

2.4

No

\0.0001

Number of co-morbid conditions

Cancer diagnosis and treatments Years since diagnosis \2 years

\0.0001

0.7

0.3

2–5 years

46

24.1

175

27.1

63

23.4

160

27.7

[5 years

141

73.6

457

70.7

202

75.1

403

69.8

Aromatase inhibitor

0.02

0.0003

Current

50

26.2

157

24.3

78

29.0

132

22.9

Prior

35

18.3

73

11.3

48

17.8

60

10.4

Never

106

55.5

416

64.4

143

53.2

385

66.7

21

16.7

29

15.1

Duration of aromatase inhibitor usea C5 years

1.0 13

15.3

35

15.2

0.4

0.3

2 to \5 years

39

45.9

105

45.6

61

48.4

85

44.3

\2 years

21

24.7

61

26.5

26

20.6

55

28.6

123

440

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Table 2 continued Hair loss

Hair thinning

Yes (n = 191)

No (n = 646)

n

n

%

p value

%

Tamoxifen

Yes (n = 269)

No (n = 577)

n

n

%

p value

%

0.06

0.4

Yes

89

46.6

246

38.1

114

42.4

226

39.2

No

102

53.4

400

61.9

155

57.6

351

60.8

95

49.7

267

41.3

134

49.8

231

40.0

96

50.3

379

58.7

135

50.2

346

60.0

Chemotherapy Yes

0.04

No Radiation

0.008

0.04

0.04

Yes

129

67.5

385

59.6

178

66.2

340

58.9

No

62

32.5

261

40.4

91

33.8

237

41.1

Some percentages for certain categories may not add up to 100 % due to missing values a

Among only women who reported current or prior aromatase inhibitor use with data on the specific hair outcome

Table 3 Confounder-adjusted odds ratios (OR) and 95 % confidence intervals (CI) for the associations between aromatase inhibitor therapy and hair outcomes Characteristic

Hair loss

Hair thinning

Hair loss or thinning

OR

(95 % CI)

OR

(95 % CI)

OR

(95 % CI)

Never

1.00

Reference

1.00

Reference

1.00

Reference

Prior use

1.21

(0.80, 1.83)

1.62

(1.12, 2.35)

1.53

(1.06, 2.20)

Current use: \2 years

2.55

(1.19, 5.45)

2.33

(1.10, 4.93)

2.19

(1.05, 4.55)

Current use: C2 years Age, years (continuous)

1.28 1.00

(0.67, 2.46) (0.99, 1.02)

1.86 1.01

(1.03, 3.34) (0.99, 1.02)

1.90 1.00

(1.06, 3.39) (0.99, 1.02)

White

1.00

Reference

1.00

Reference

1.00

Reference

Black

1.51

(0.94, 2.43)

1.86

(1.21, 2.88)

1.63

(1.06, 2.52)

Other

2.54

(1.07, 6.01)

2.43

(1.06, 5.54)

2.52

(1.11, 5.73)

\ 25

1.00

Reference

1.00

Reference

1.00

Reference

25 to \30

1.11

(0.72, 1.69)

1.64

(1.13, 2.38)

1.51

(1.05, 2.17)

C30

1.85

(1.22, 2.81)

2.07

(1.41, 3.06)

2.01

(1.37, 2.93)

No

1.00

Reference

1.00

Reference

1.00

Reference

Yes

1.32

(0.91, 1.92)

1.32

(0.94, 1.85)

1.32

(0.95, 1.84)

1.00

Reference

1.00

Reference

1.00

Reference

1.30 1.25

(0.90, 1.86) (0.94, 1.65)

1.18 1.28

(0.86, 1.63) (1.00, 1.65)

1.22 1.26

(0.89, 1.68) (0.98, 1.61)

Aromatase inhibitor therapy

Race

BMI (kg/m2)

Chemotherapy

Radiation therapy No Yes Time since diagnosis, years (continuous)

Current users who had been treated for two or more years did not have significantly increased odds of hair loss (OR 1.28; 95 % CI 0.67–2.46), nor did prior users regardless of duration of use (OR 1.21; 95 % CI 0.80–1.83).

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All breast cancer survivors who were being treated with an aromatase inhibitor at the time of survey completion or had previously been treated with an aromatase inhibitor had significantly greater odds of reporting hair thinning

Breast Cancer Res Treat (2013) 142:435–443

compared to those who never were treated with an aromatase inhibitor, independent of age, race, BMI, chemotherapy treatment, radiation, and time since diagnosis. The association was strongest among women who were within 2 years of starting aromatase inhibitor treatment (OR 2.33; 95 % CI 1.10–4.93). ORs for the combined hair outcome variable were similar to those reported for hair thinning. The other characteristics associated with hair loss in the confounder-adjusted analyses were obesity (OR 1.85; 95 % CI 1.22–2.81) and being of a race other than white or black (OR 2.54; 95 % CI 1.07–6.01). The odds of hair thinning were significantly elevated for women of black (OR 1.86; 95 % CI 1.21–2.88) or other races (OR 2.43; 95 % CI 1.06–5.54) compared to white women and for women categorized as overweight (OR 1.64; 95 % CI 1.13–2.38) or obese (OR 2.07; 95 % CI 1.41–3.06) compared to women of normal BMI. As with the estimates for the aromatase inhibitor variables, ORs for the potential confounders and the combined hair outcome variable were similar to those reported for hair thinning.

Discussion The findings from this cross-sectional study suggest that aromatase inhibitor therapy is associated with both hair loss and thinning among breast cancer survivors. The odds of experiencing hair loss and hair thinning were greatest among current users who had taken their aromatase inhibitor for less than 2 years at the time of survey completion; however, increased odds of hair thinning were also observed among current users who had been taking the aromatase inhibitor for a longer period of time as well as former users compared to survivors who reported never been treated with an aromatase inhibitor. It is likely that the observation of higher odds of both hair loss and thinning among women who had begun aromatase inhibitor therapy more recently is due to the fact that women were asked about symptoms during the past 4 weeks and, if aromatase inhibitor therapy causes hair changes, these changes would occur soon after the initiation of treatment and the associated decline of estrogen levels. Thinning, but not hair loss, may continue to occur over the course of aromatase inhibitor treatment. Importantly, in this study, hair loss and hair thinning associated with aromatase inhibitor therapy was found to be independent of other treatments known to be associated with hair loss, including chemotherapy and radiation. Although this is the first study, to our knowledge, to systematically examine the associations between aromatase inhibitors and hair loss or thinning in large sample of breast cancer patients, reports of hair loss have been noted in studies of breast cancer patients treated with this drug [7, 10, 19, 20]. Recently, Rossi et al. [19] reported findings

441

from a series of 15 breast cancer patients receiving aromatase inhibitors showing recession of the frontal and parietal hairlines as well as miniaturization of follicles in the fronto-temporal area after 1 year of aromatase inhibitor treatment. These patients had not been treated with any other modalities such as chemotherapy or radiation; therefore, hair loss was attributed to the aromatase inhibitors. Neither detailed data on the prevalence of hair loss among the 15 patients nor detailed analyses were presented in this small study. Similarly, Gallicchio et al. [7] showed that breast cancer patients (n = 95) had significantly increased odds of reporting hair loss over the first 6 months of aromatase inhibitor therapy compared to women of the same age without a history of cancer followed over the same time period (n = 195). The significant increase in odds remained when the breast cancer sample was limited to women not treated with chemotherapy. Hair loss has also been reported as a side effect of aromatase inhibitors in clinical trials and other clinic-based studies [10, 20]; however detailed data were not collected on this symptom in these investigations. Aromatase inhibitors work by blocking the production of the aromatase enzyme, which is responsible for the conversion of androgens to estrogens in fat tissue [1]. In addition to this enzyme playing an essential role in the conversion of androgens to estrogens in fat tissue, it also regulates the concentrations of androgens, particularly testosterone and dihydrotestosterone, and estrogens in the scalp [14, 17, 22]. Several studies indicate that concentrations of these sex hormones in the scalp regulate the hair loss process [19]. Specifically, estrogens have been shown to operate as hair growth modulators and hair protective factors [19]; further, female androgenetic alopecia is known to be caused by androgens in genetically susceptible women [19, 22, 23]. Thus, the low concentrations of estrogens, and potentially higher concentrations of androgens, resulting from the use of aromatase inhibitors could theoretically accelerate hair loss in breast cancer patients treated with this drug. Interestingly, in the present study, the ORs for hair loss and hair thinning were highest among current aromatase inhibitor users with recent onset of use, suggesting hair loss and thinning may be more accelerated at the beginning of treatment, when estrogen concentrations abruptly decline. Potentially, hair loss and thinning may stop after discontinuation of therapy. However, the present study was cross sectional in nature, and detailed data on hair loss and thinning were not collected over time; thus, this difference in ORs and potential reversibility of hair loss, as well as the biological mechanism behind the observed association between aromatase inhibitors and hair loss or thinning, should be investigated in future studies. In addition to aromatase inhibitor therapy, BMI was positively associated with hair loss and hair thinning

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independent of other covariates and cancer therapies. Overweight and obese postmenopausal women have, in general, higher concentrations of circulating estrogens compared to normal weight women due to the conversion of androgens to estrogens by the aromatase enzyme in fat tissue [24]. However, aromatase inhibitors block this conversion and, therefore, differences in circulating estrogens by BMI likely do not account for the statistically significant associations between BMI and the hair outcomes observed in this study. It is possible that higher androgens among overweight and obese women compared to normal weight women [24] are the mediating factors of these relationships, although the role of androgens in hair loss and hair thinning among women has not been clearly established [15]. Further, there are other biological and health differences between high and low BMI groups that could potentially explain the increased odds of hair thinning and hair loss among overweight and obese women compared to their counterparts. Future studies should be conducted to examine this issue. While the present study provides novel insight on the associations between aromatase inhibitors and hair loss and thinning, several limitations of the study should be noted. First, this study was cross sectional and, therefore, statements pertaining to the causality of the associations between hair loss and thinning cannot be made. Second, the response rate overall was relatively low (34.3 %), and, as with any survey study, breast cancer survivors who completed the questionnaire may differ from those who did not complete the questionnaire, limiting the generalizability of the results. In addition, the study sample included breast cancer survivors primarily from single institution (Mercy Medical Center), and the population that seeks services at this institution may not reflect the population in other parts of the country. Finally, the results were based on self-report and the outcomes were based on only two questions of hair loss and hair thinning; a more detailed, longitudinal assessment of hair loss prior to the initiation of treatment, through treatment, and after the completion of treatment should be conducted and may include a physician or nurse objective measurement of hair constitution. The findings from this study indicate that hair loss and thinning are prevalent and significant side effects of aromatase inhibitors. The results provide an impetus to further investigate the connection between aromatase inhibitors and hair loss and thinning and, if a true association exists, to examine the biological mechanism by which aromatase inhibitors cause hair loss or thinning. This work would help in developing treatments for those women on aromatase inhibitors who experience hair loss as well as preventive measures for those initiating aromatase inhibitor therapy who are the most likely to develop hair loss and thinning.

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Breast Cancer Res Treat (2013) 142:435–443 Acknowledgments Dr. Gallicchio is a recipient of a Health Disparities Career Catalyst Grant from Susan G. Komen for the Cure (KG110356).

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Aromatase inhibitor therapy and hair loss among breast cancer survivors.

The objective of this study was to examine the associations between aromatase inhibitor therapy and hair loss or hair thinning among female breast can...
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