Understanding headache in the context of macromastia: An observational pilot study of headache profiles and postoperative changes

Abstract

Background

Women with enlarged breast tissue (macromastia) experience many musculoskeletal and neurologic symptoms, including headaches, and may seek breast reduction. These headaches are frequently labeled “tension-type,” though headache features and diagnoses remain poorly defined.

Methods

This observational study aimed to characterize headache features and ICHD-3 diagnoses in women with macromastia undergoing reduction and assess headache pre- and postoperatively. Validated surveys included migraine screening (ID-Migraine), disability (Migraine Disability Assessment [MIDAS]), allodynia (Allodynia Symptoms Checklist [ASC-12]), and obstructive sleep apnea risk (OSA, Berlin).

Results

Inclusion criteria: age ≥18 and ≥4 headache-days/month. Exclusion criteria: brain/spine surgery, breast malignancy, or high-dose estrogen use. The primary outcome was migraine identification preoperatively; secondary outcomes included postoperative changes in headache and OSA risk. Among 34 participants (mean age 34.9 [standard deviation (SD) = 11.4] years, BMI 30.9 [4.1] kg/m², 62% White), baseline headaches were frequent and disabling (median 10 [interquartile range (IQR) = 7–19.5] days/month, mean pain intensity 6.2/10 [SD = 1.8], mean MIDAS 49.8 [SD = 42.7]). Allodynia was present in 40%; 56% screened high-risk for OSA. Migraine screening was positive in 91%, though 100% reported red flag features. Postoperatively, significant improvements in headache frequency (incidence rate ratio 0.23 [IQR = 0.18, 0.29]; p < 0.0001), pain intensity (mean −3.0; p < 0.0001), disability (mean −32.9; p < 0.0001), allodynia (mean −2.1; p = 0.0008), and OSA risk (OR = 0.19; p < 0.05) were observed and sustained through 19–28 months postoperatively.

Conclusion

This pilot study shows that most women with macromastia and headache pursuing reduction screened positive for migraine, challenging the assumption of tension-type headaches. Many exhibited red flag features, suggesting a need for further evaluation. Improvements in headache features and OSA risk were observed following a reduction up to 28 months postoperatively.

Keywords

breast size breast hypertrophy migraine idiopathic intracranial hypertension sleep apnea obesity

Introduction

Macromastia, or symptomatically enlarged breast tissue, is associated with a range of musculoskeletal and neurologic symptoms, including headache, neck pain, backache, cervicothoracic radicular pain, dyspnea, and sleep disturbances. Physical signs may include shoulder grooving from bra straps, thoracic kyphosis, and inframammary rash (Figure 1).^1–4 These symptoms may lead women to seek breast reduction surgery (reduction mammoplasty).

Figure 1.

Examples of macromastia. Macromastia (a and b) is characterized by excessive breast volume and weight, often resulting in breast ptosis, or drooping (blue arrow), with significant amounts of breast tissue falling inferior to the inframammary fold (IMF), demarcated by the red line. Women with macromastia may also develop infra-mammary rashes (c, red arrows) or hidradenitis suppurativa with boils and scarring (d, yellow arrows). Skin discoloration (e, green arrows) and shoulder grooving, or skin indentations (f, orange arrows) from bra straps and excessive breast weight may also occur.

Several factors influence our clinical understanding and management of macromastia, including breast size, composition, symptom intensity, and obesity.^4,5 In practice, bra size is often used for defining macromastia (e.g. cup sizes > D); however, such definitions are oversimplified, because symptoms vary with breast structure and composition. Furthermore, bra size is often inaccurate; up to 80% of women wear incorrectly sized bras, and annual bra fittings are recommended.^6,7 In the United States, the average bra cup size is a 34E-F, and sizes ranging from D to J are typical among women undergoing reduction mammoplasty.^5,8,9 Bra sizing systems vary internationally, with cup sizes remaining relatively consistent across regions, while band measurements exhibit more substantial differences due to varying units and sizing standards.¹⁰ Surgeons typically estimate breast volume using anatomical landmarks and clinical judgment. Intraoperatively, macromastia can be defined as breast tissue exceeding ∼500 g per breast, while a severe macromastia subtype—gigantomastia—is defined by volumes >1500 g per breast or more than 3% of total body weight during reduction procedures.¹¹

Obesity adds complexity to macromastia. Increased adipose tissue and estrogen levels in individuals with higher body mass index (BMI) may contribute to macromastia.⁴ Higher BMI is associated with an increased risk of tension-type headache (TTH), migraine, cervicogenic headache, and idiopathic intracranial hypertension (IIH).^12–19 Obesity influences the symptom patterns: obese individuals report more physical discomfort, while non-obese individuals more often report psychological distress.²⁰ Sex further shapes headache prevalence; women are more likely to have migraine, cervicogenic headache, and IIH.^12–15 Migraine affects 17%–19% of women in the United States, particularly those aged 20–50 years, a demographic that overlaps with women seeking reduction mammoplasty.^15,21

Despite these associations, plastic surgery journals publish 95% of research on macromastia-associated pain disorders, including research on headache.⁴ Little awareness exists of macromastia's impact on neurological conditions by the very clinicians caring for patients with the symptoms (i.e. neurologists, headache, and pain specialists). Studies reveal that up to 89% of women with macromastia report headache prior to reduction mammoplasty.⁴ The plastic surgery literature describes the headaches as “tension-type,” “myofascial,” or simply “headache” without reporting detailed symptom profiles or using the International Classification of Headache Disorders (ICHD-3).²² While most studies note headache improvement following reduction, they lack a systematic assessment of headache features or diagnostic criteria.⁴ No studies have rigorously evaluated ICHD-3 headache diagnoses in this population.

The mechanism of headache in women with macromastia remains unclear. Potential mechanisms include macromastia-induced head and neck structural changes (i.e. accelerated degenerative spondylosis), chronic traction on dorsal cervical nerves causing peripheral sensitization, inflammatory and metabolic changes driven by breast adipose and endocrine tissue, impaired chest wall compliance predisposing to disordered sleep, and increased psychological comorbidity.⁴

In the United States, some commercial insurers list headache as an indication for reduction mammoplasty, but this may not apply globally.^23,24 Clarifying the nature of headache in women with macromastia and the extent to which surgical intervention offers relief requires careful scrutiny, as many questions remain, including:

What are the clinical headache features and ICHD-3 diagnoses in women with macromastia?;

What mechanisms link macromastia and headache (e.g. mechanical, inflammatory, hormonal, etc.)? and

Should women with macromastia and headache be evaluated by neurologists prior to surgical intervention?

As a first step towards answering these questions, we conducted an observational study in women with headaches scheduled for reduction mammoplasty. We recruited participants from the Plastic Surgery Clinic to capture women exhibiting the most pronounced macromastia-related symptoms, thereby enhancing the likelihood of detecting meaningful clinical signals. Our aims were to: (1) understand the headache characteristics associated with macromastia by identifying the percentage of participants screening positive for migraine at baseline/preoperatively—the primary outcome; and (2) explore the link between headache and macromastia by assessing changes in headache following reduction. We did not endeavor to establish the benefits of reduction mammoplasty for headache, as this requires a randomized controlled trial with its own design challenges. Given the age and gender overlap with migraine and the proposed mechanisms underlying headache in women with macromastia, we hypothesized that some patients with headache seeking surgery would screen positive for migraine and that women with macromastia and migraine may experience severe headache features (e.g. high frequency, allodynia, and disability) with potential postoperative improvement in headache features.

Methods

Study design, setting, and participants

We conducted a single-center prospective cohort study at Atrium Health Wake Forest Baptist (AHWFB) Plastic Surgery Clinic and Comprehensive Headache Program in Winston-Salem, NC. The AHWFB IRB approved the study (IRB00092402). Funding was provided by the American Headache Society's International Headache Academy and the AHWFB Comprehensive Headache Program Inspire funds.

Between 16 March 2023 and 4 February 2024, patients scheduled for reduction mammoplasty with four plastic surgeons were contacted via the electronic medical record portal. Interested participants were screened and consented by phone, virtually, or in-person visit (for all encounter types, an electronic signature was obtained through research electronic data capture [REDCap]). Participants were included if they were English-speaking adults with regular headaches (≥4/month by self-report, a minimum frequency standard to migraine trials²⁵), had insurance approval for reduction mammoplasty, and met institutional requirements, including BMI <39 kg/m². Exclusion criteria included active/past breast malignancy, recent (<2 years) brain or cervical spine surgery, pregnant/breastfeeding, or use of high-dose (>50 mcg) exogenous estrogen (see Supplemental Material for justifications).

Evaluations

Participants completed three evaluations via REDCap (Figure 2), hosted at Wake Forest University School of Medicine.²⁶ They received $60 in gift cards for completing three surveys and were entered into a $500 raffle. The headache neurologist (KP) conducted the baseline (preoperative [“preop”]) evaluation 1 day to 3 months before surgery. Postoperative (“postop”) surveys 1 and 2 were completed independently at 12–16 weeks (standard in headache studies^25,27,28) and 19–28 months, respectively. Each evaluation included standard patient assessment tools (described below). Survey timing varied due to insurance authorization and surgeon-specific schedules.

Figure 2.

Participants completed three evaluations. A headache neurologist conducted the baseline (preoperative) evaluation 1 day to 3 months before surgery. Postoperative surveys 1 and 2 were completed independently at 12–16 weeks and 19–28 months, respectively.

The baseline evaluation included the ID-Migraine,²⁹ monthly Migraine Disability Assessment Scale³⁰ (mMIDAS, score 0–90; multiplied by three to align with validated MIDAS categories), Allodynia Symptoms Checklist³¹ (ASC-12, score 0–24, no allodynia = 0–2, mild = 3–5, moderate = 6–8, severe ≥9; ictal vs. interictal not specified), Berlin questionnaire (obstructive sleep apnea [OSA] risk),³² and sociodemographic data. We selected ID-Migraine for screening due to its ease of administration, validity, and reliability.²⁹ Semi-structured interview was used to further assess clinical features and ICHD-3 migraine diagnosis.²² We used the recall-based MIDAS questionnaire to estimate headache-day frequency.³⁰ A baseline/preoperative semi-structured interview captured headache features (e.g. duration and average intensity), prior headache evaluations/diagnoses, the presence of neck pain or occipital neuralgiform pain, family history of headache/migraine, and prior treatments. Medication overuse headache due to the use of over-the-counter medications was defined as the use of acute over-the-counter headache medication (e.g. acetaminophen, nonsteroidal anti-inflammatory agents [NSAIDs]) on ≥15 days/month.²² Red flag symptoms (e.g. pulsatile tinnitus, Valsalva-triggered or aggravated headache, vision dimming, etc.) prompted referral to our Comprehensive Headache Program. Participants reported bra sizes and timing of previous bra-fitting, or by assessing for current bra size. Additional questions included: plastic surgery referral origin (provider-initiated vs. patient-imitated), previously trialed therapies for macromastia-associated symptoms (and degree of benefit on a 4-point scale from “not at all helpful” to “greatly helpful”), and reasons for surgery (multiple choice with free text option). Postop surveys 1 and 2 used the same instruments with additional questions, including (1) complications and satisfaction with surgery; (2) unvalidated lifestyle questions querying changes in sleep/mood/exercise; and (3) the Perceived Global Impression of Change (PGI-C) (a 7-point scale with 1 = “no change” and 7 = “a great deal better and considerate improvement that has made all the difference”).³³ For additional details, see the Supplemental Material.

Primary outcome

The primary outcome was the percentage of patients screening positive for migraine on the ID-Migraine survey at baseline/preoperatively.

Secondary outcomes

Headache-related outcomes

Secondary headache outcomes included group mean pre- to postoperative changes for all patients in monthly self-reported headache-days, headache intensity, disability (mMIDAS), cutaneous allodynia score (ASC-12), OSA risk score (Berlin), and proportion of “headache responders” (those with ≥50% reduction in headache-days) at postop 1 and 2.

Plastic surgery outcomes

Secondary plastic surgery outcomes included satisfaction with surgery by asking “Are you happy you had the breast reduction surgery performed?” (Yes/No) and “If given the change to undergo breast reduction surgery again, would you make the same decision?” (Yes/No/I Don’t Know).

Exploratory outcomes

Unvalidated wellness outcomes included perceived postoperative changes in sleep/exercise/mood.

Sample size and statistical analysis

For the primary outcome of migraine frequency (binary “yes/no” on ID-Migraine), the sample size was planned a priori around a margin of error for the binomial proportion of patients with migraine at baseline.³⁴ For a binomial proportion, the margin of error for a 95% confidence interval is at most approximately $2 * \sqrt (0.5 * 1 - 0.5) / n = 1 \sqrt n$ . A sample size of n = 34 yields a margin of error of 0.17, which we deemed as acceptable for this pilot study.

We used descriptive statistics to summarize the overall study sample, with means/standard deviations or median/interquartile range (IQR) for continuous or count variables, respectively, and frequencies/percentages for categorical variables. We estimated the primary outcome of the proportion with migraine using a binomial proportion and 95% confidence interval. Once identified as migraine, baseline headache frequency was used to categorize as episodic versus chronic migraine as per ICHD-3 criteria.³⁵ Over-the-counter medication use frequency informed medication overuse diagnosis.²² Secondary outcomes involving pre- to postoperative changes (headache days, intensity, disability, allodynia, and OSA) were analyzed descriptively. Data from post-op visits 1 and 2 were compared to baseline data. We performed statistical inferences about changes using generalized linear mixed effects models³⁶ with a fixed effect for time point (pre-op, post-op 12–16 weeks, and post-op 19–28 months) and a random effect for study participant.³⁷ 95% confidence intervals were reported for primary and secondary outcomes with Kenward-Roger denominator degrees of freedom.³⁷ A Poisson mixed effects model was run for monthly headache days, a count outcome. A linear mixed effects model was run for pain intensity, MIDAS, and ASC-12 scores, continuous outcomes. A logistic mixed effects model was run for the Berlin OSA high-risk score, a binary outcome. Subgroup analysis of referral origin and race, migraine subtype (episodic vs. chronic), and obesity was performed post hoc using Fisher's exact test.

Responders were defined as those with a ≥ 50% improvement in monthly headache-days, and correlates of response were explored using univariate statistical tests. To measure the benefit of surgery on allodynia, we restricted the analysis to those who had allodynia at baseline. Note that this is analogous to measuring the benefits of acute pain treatment or preventive treatment on monthly headache days to individuals who have the feature. All statistical tests were two-sided and used a significance level of 0.05. Statistical analyses were performed using R version 4.3.2.³⁸ Given the hypothesis-generating nature of this first study investigating headaches in patients with macromastia, no adjustments were made for multiple comparisons.

Missing data, sensitivity analysis, and potential confounders

There was no missing data at baseline. Given minimal missing data at postop 1 (<3%), missing data sensitivity analyses were not conducted. Three patients started preventive migraine medications between postop 1 and 2 (details in the Supplemental Material).

Data availability and use of artificial intelligence (AI) tools

The data that support the findings of this study are not openly available due to reasons of sensitivity and are available from the corresponding author upon reasonable request. Data are located in controlled access data storage in research electronic data capture (REDCap), hosted at Wake Forest University School of Medicine. We used generative AI (Microsoft Copilot, GPT-4-turbo model) to edit for clarity and improve readability. All intellectual content, interpretations, and conclusions are the author's sole work.

Results

Participant characteristics

Of the 63 patients screened, 34 were consented and enrolled (Figure 3); reasons for nonparticipation are summarized in Figure 3. Completion rate for the baseline survey was 100%; 97% (33/34) completed postop survey 1, and 82% (28/34) completed postop survey 2 (Figure 3). Participants had a mean (SD) age of 34.9 (11.4) years and mean BMI of 30.9 (3.7) kg/m² (the mildest class of obesity [1 of 3] with a BMI range of 30.0–34.9 kg/m²) (Table 1).³⁹ Patients were White (62%, 21/34), Black (32%, 11/34), Hispanic (2/34, 3%), or declined to answer (2/34, 3%). All reported bra cup sizes ranging from cup C-J. Only 25% (7/28) reported formal bra fitting within the last year, while 43% (12/28) had not had a fitting for >5 years.

Figure 3.

Flow diagram.

Table 1.

Demographic characteristics of participants.

	All, n (%) or Mean (SD) n = 34
Age (years)	34.9 (11.4)
Female sex assigned at birth	34 (100)
Female gender identity	34 (100)
Race/ethnicity^a
White or Caucasian	21 (62)
Black or African American	11 (32)
Hispanic or Latino	1 (3)
BMI (kg/m²)	30.9 (4.1)
BMI category
<25 (normal)	2 (6)
25.0–29.9 (overweight)	12 (35)
≥30–34.9 (obesity class 1)	14 (41)
>35.0–39.9 (obesity class 2)	6 (18)
> 40 (extreme obesity, obesity class 3)	0 (0)
Bra size	Band (32–44 in), Cup (C-J)
Band size (inches)
L-XL	2 (3)
32–36	11 (32)
38	13 (38)
40–44	8 (24)
Cup size^c
A-B	0 (0)
C-E	10 (29)
F	10 (29)
G-J	14 (41)
Marital status^a
Single or never married	16 (47)
Married	13 (38)
Other	4 (12)
Income category^b
≤ $49,999	16 (47)
$50–99,999	8 (24)
≥ $100,000	8 (24)
Employment status
Full-time	26 (77)
Other (e.g. part-time, student, and disabled)	8 (24)
Highest level of education
Bachelor's degree or higher	13 (38)
Some college, associate's degree, high school diploma, or GED	21 (62)

One patient declined to answer.

Two patients declined to answer.

Bra cup size E is equivalent to DD, F to DDD, G to DDDD, and so on.

We list reasons for surgery and referral origins in Figure 4. Most (26/34, 76%) referrals were from primary care. Five participants (5/24, 15%) were referred by specialists (1/5 [20%] neurology, 1/5 [20%] bariatrics, 1/5 [20%] OB/GYN, 1/5 [20%] breast oncology [non-cancer patient]). Three (3/34, 9%) were referred by chiropractors. Two (2/34, 6%) were self-referrals. Many reported personally requesting referrals from their providers (23/34, 68%), with more Black women requesting it than White women (91% vs. 67%, p = 0.21).

Figure 4.

(a) Reasons for reduction mammoplasty. Participants could select more than one reason for pursuing reduction mammoplasty, with shoulder grooving, headache, back pain, and shoulder pain being the most common reasons for surgery. (b) Source of referral for reduction mammoplasty and who initiated the referral (provider or patient). Most patients (77%) were referred by primary care and initiated the surgical referral.

At baseline, participants had a mean (standard deviation) headache frequency of 13.4 (8.9) days per month, a mean headache pain intensity score of 6.1 (1.8), and a mean MIDAS score of 48.2 (42.4) (severe disability). Many (44%, 15/34) had previously been diagnosed with migraine, some (18%, 6/34) with TTH, and 38% (13/34) had been previously evaluated by a neurologist or other provider for headache. Family history of headache was reported by 65% (22/34), of whom 64% (14/22) had a family history of migraine. Two patients were already established with our headache clinic.

At baseline, 38% (13/34) had occipital neuralgiform pain, and 41% (14/34) had cutaneous allodynia (of those, 7/14 mild, 6/14 moderate, and 1/14 severe allodynia, with an average ASC-12 score of 3.4 (3.4) [mild]). Twenty-six (26/34, 77%) screened positive for any degree of OSA risk (low or high) at baseline, with 73% (19/26) high risk.

Patients trialed several medications, alternative/complementary therapies, and procedural interventions prior to resorting to surgery, with few participants (n = 3–10) finding any such treatments “greatly helpful” (Table 2). Five participants (15%, 5/34) reported using over-the-counter medications daily, and 15/34 (44%) reported use 2 to 3 days/week.

Table 2.

Previously trialed interventions for macromastia-related symptoms.

Intervention	Percent of participants who reported use,n (%)	Not at all helpful,n	A little helpful,n	Somewhat helpful,n	Greatly helpful,n
Medications
NSAIDs	32 (94)	10	6	12	4
Muscle relaxants	20 (59)	7	4	7	2
Triptans	13 (38)	5	0	4	4
Other (oral steroids, neuropathic pain agents, opioids, and topiramate)	20 (59)	8	4	8	0
Complementary/alternative therapy
Supportive bras	31 (91)	7	9	12	3
Massage	20 (59)	3	6	9	2
Physical therapy	10 (29)	6	3	1	0
Chiropractic, acupuncture	24 (71)	6	3	12	3
Consultations and procedures
Spine/pain consultation, nerve block or ablation, and onabotulinumtoxinA	7 (21)	2	0	2	3

Primary outcome

Most patients (91%, 31/34) screened positive for migraine (via ID-Migraine) (Figure 5). Of these, all met ICHD-3 criteria for migraine with the exception of criterion E (“[headache] not better accounted for by another ICHD-3 diagnosis”). Red flags atypical for migraine, suggesting the possibility of alternative diagnoses included pulsatile tinnitus (81%, 25/31), headaches triggered by Valsalva (25%, 8/31), headaches aggravated by Valsalva (52%, 16/31), and visual dimming/darkening (32%, 11/31) (Figure 5). Most participants (58%, 18/31) were classified as episodic migraine, and 42% (13/31) as chronic migraine. Medication overuse of over-the-counter medications was identified in 38% (5/13) of those with chronic migraine.

Figure 5.

Primary outcome: Proportion of patients screening positive for migraine based on ID-Migraine among women undergoing reduction mammoplasty. The same patients screening positive on ID-Migraine also met ICHD-3 criteria for migraine (excluding criterion E) based on a semi-structured diagnostic interview. Most surgical studies classify headaches in women undergoing reduction mammoplasty as tension-type, so the historical estimate of migraine is 0. In this study, 91% (31/34) screened positive for migraine on ID-Migraine, and the same patients met ICHD-3 criteria based on a semi-structured diagnostic interview (a). Common red flag features observed in this population included transient visual obscurations, Valsalva-aggravated headaches, and pulsatile tinnitus (b).

Secondary outcomes

Pre- to postoperative survey headache-related outcomes

Participants had statistically significant improvements from baseline at both follow-up time points in headache frequency, intensity, disability, allodynia, and OSA risk (Table 3). Most (79% [26/33], CI [60.6%, 90.4%]) reported a ≥ 50% improvement in monthly headache-days at postop 1, which increased to 89% (77% and 100%) at postop 2.

Table 3.

Secondary headache outcomes and postoperative change estimates. Descriptive statistics and change estimates (vs. baseline) over time are presented. Median (interquartile range [IQR]) is presented for the count outcome of mean monthly headache days. Mean (± standard deviation [SD]) is presented for continuous outcomes of pain intensity, Migraine Disability Assessment Scale (MIDAS) scores, and Allodynia Symptoms Checklist (ASC-12) scores. Frequency (percentage) is presented for the binary outcome of the Berlin obstructive sleep apnea (OSA) high-risk score. Estimates, (95% confidence) intervals, and p-values are reported from generalized linear mixed effects models with fixed effects for time and random effects for study participants. Incidence rate ratios (Poisson regression) are presented for headache days, beta coefficients (linear regression) for pain intensity, MIDAS scores, and ASC-12 scores. Odds ratios (linear regression) are presented for OSA high-risk scores.

	Baseline,n = 34	Postop12–16 weeks,n = 33	Change at 12–16 weeks, estimate (95% CI); p-value	Postop19–28 months,n = 28	Change at 19–28 months, estimate (95% CI); p-value
Mean monthly headache-days^a	10 (7–19.5)	0 (0–3)	0.27 (0.22, 0.32); <0.0001	0 (0.5–3)	0.23 (0.18, 0.29); <0.0001
Mean headache intensity	6.2 (±1.8)	2.5 (±2.6)	−3.7 (−4.8, −2.5); <0.0001	3.2 (±3.0)	−3.0 (−4.2, −1.8); <0.0001
Mean Migraine Disability Assessment Scale (mMIDAS x3) score^b	49.8 (±42.7)	15.6 (±41.6)	−33.2 (−46.2, −20.1); <0.0001	16.2 (±40.1)	−32.9 (−46.7, −19.1); <0.0001
Mean Allodynia Symptoms Checklist (ASC-12) score^c	3.3 (±3.4)	1.3 (±2.4)	−2.0 (−3.1, −0.9); 0.0006	1.2 (±2.5)	−2.1 (−3.2, −0.9); 0.0008
Proportion with high-risk Berlin obstructive sleep apnea score	19 (55.9%)	9 (27.3%)	0.09 (0.01, 0.42); 0.0071	10 (35.7%)	0.19 (0.03, 0.83); 0.0427

Derived from the mMIDAS questionnaire.

MIDAS scores: 0–5 = little or no disability, 6–10 = mild disability, 11–20 = moderate disability, 21+ = severe disability.

ASC Scores: 0–2 = no cutaneous allodynia (CA), 3–5 = mild CA, 6–8 = moderate CA, ≥ 9 = severe CA.

Mean BMI decreased from 30.9 (4.1) kg/m² at baseline to 30.3 (4.3) kg/m² at postop 1 (–0.7 [–1.5, 0.2]; p = 0.130), and 28.7 (4.6) kg/m² at postop 2 (change −2.3 [–3.2, −1.4]; p < 0.001). Of those with chronic migraine, 31% (4/13) were obese at baseline. Of those with episodic migraine, 78% (14/18) were obese (p = 0.013). Neck pain was present at baseline in all participants (100%, 34/34), with 88% (29/33) reporting improvement and 12% (4/33) reporting stability at postop 1, and 25/28 (89%) reporting improvement and 3/28 (11%) stability at postop 2. Of those with allodynia at baseline (14/34), 86% (12/14) had a categorial improvement in ASC-12 score (i.e. improved between categories “absent,” “mild,” “moderate,” “severe”) at postop 1 and 71% (10/14) at postop 2. Of these, 80%–92% (92% [11/12] at postop 1; 80% [8/10] at postop 2) reported improvement in neck pain. Of those without allodynia at baseline (59%, 20/34), most also reported neck pain improvement (90% [18/20] at postop 1; 80% [16/20]) at postop 2).

Post hoc analysis of associations between demographics and headache responder status at postop 1 revealed that mean BMI was higher in responders (31.7 kg/m²) compared to nonresponders (27.9 kg/m²) (p = 0.028) (Table 4). At postop 2, the mean BMI of responders was 31.9 kg/m² and 27.9 kg/m² in nonresponders (p = 0.056). At postop 1, the mean weight change among responders was −1.7 (1.5) kg and −1.8 (4.7) kg for nonresponders (p = 0.93). At postop 2, the mean weight change among responders was −7.1 (10.2) kg and −6.5 (6.9) kg for nonresponders (p = 0.88).

Table 4.

Associations between demographic factors and headache responder status. Responders were defined as those who experienced a ≥ 50% improvement in monthly headache-days postoperatively (weeks 12–16). Participants without survey responses were excluded from analysis (one study participant at postop 1 and five participants at postop 2).^a

	Non-responder	Responder	p-value
Postop 1
	n (%) or Mean (SD)n = 7	n (%) or Mean (SD)n = 26

White	5 (71)	16 (62)	1.0
Black	2 (29)	8 (31)
Hispanic or Latino	0 (0)	1 (4)
Decline to answer	0 (0)	1 (4)
BMI (kg/m²)	27.9 (3.6)	31.7 (3.9)	0.028
Weight change (kg)	−1.7 (1.5)	−1.8 (4.7)	0.93
Marital status
Married or partner	4 (57)	9 (35)	0.67
Single or never married	3 (43)	13 (50)
Other	0 (0)	3 (12)
Decline to answer	0 (0)	1 (4)
Income category
< 50k	4 (57)	12 (46)	1.00
50–99k	2 (29)	6 (23)
> 100k	1 (14)	6 (23)
Decline to answer	0 (0)	2 (8)
Employment status
Full time	4 (57)	21 (81)	0.32
Other	3 (43)	5 (19)
Highest level of education
Associate's, GED, HS diploma	3 (43)	10 (39)	1.0
Bachelor's or higher	4 (57)	16 (62)

Postop 2
	n = 5	n = 23
Age (years)	33.6 (12.6)	35.3 (11.9)	0.78
Race/ethnicity
White	4 (80)	12 (52)	0.74
Black	1 (20)	9 (39)
Hispanic or Latino	0 (0)	1 (4)
Decline to answer	0 (0)	1 (4)
BMI (kg/m²)	27.9 (4.2)	31.9 (4.0)	0.06
Weight change (kg)	−7.1 (10.2)	−6.5 (6.9)	0.88
Marital status
Married or partner	2 (40)	10 (44)	1.00
Single or never married	3 (60)	11 (48)
Other	0 (0)	1 (4)
Decline to answer	0 (0)	1 (4)
Income category
< 50k	3 (60)	10 (44)	0.63
50–99k	2 (40)	5 (22)
> 100k	0 (0)	6 (26)
Decline to answer	0 (0)	2 (9)
Employment status
Full time	2 (40)	18 (78)	0.12
Other	3 (60)	5 (22)
Highest level of education
Associate's, GED, HS diploma	4 (80)	7 (30)	0.06
Bachelor's or higher	1 (20)	16 (70)

Post hoc analysis does not control for the number of analyses conducted.

Regarding headache, most participants (71%, 20/28) reported feeling “a great deal better” (43%, 12/20) or “better, with definite improvement” (29%, 8/20) on the Perceived Global Impression of Change, with 79% (22/28) scoring ≥5 points.

Plastic surgery outcomes

Most (91%, 31/34) reported satisfaction with surgery at postop 1 and all (100%) at postop 2.

Exploratory outcomes

Subjective changes in sleep, mood, and exercise

At baseline, 65% (22/34) reported impaired sleep; 70% (23/33) improved at postop 1 (69.7% [51.5, 83.8]), rising to 75% (21/28) at postop 2 (56.6, 87.3). Impaired mood was reported by 62% (21/34); improvement was seen in 76% (25/33) at postop 1 (75.8% [57.4, 88.3]) and 86% (24/28) at postop 2 (85.7% [68.5, 94.3]). Exercise difficulty due to macromastia was reported by 88% (30/34); increased activity was noted in 76% (25/33) at postop 1 and 86% (24/28) at postop 2. Some without baseline issues also reported postoperative improvements.

Adverse events

Eight patients (24%) reported mild surgical complications (rash, skin dimpling, excessive pain, and stitches not dissolving).

Discussion

This small prospective pilot study characterizes headache features in 34 women with macromastia and headache before and after reduction mammoplasty. Most patients (91%) screened positive for migraine—a finding challenging the prevailing assumption that the headache of women with macromastia has a TTH or myofascial pain phenotype.⁴ However, a migraine diagnosis could not definitively be made as 100% of patients had red flag features uncommon in migraine.⁴⁰ Headache frequency and disability were moderately severe at baseline. Postoperatively, patients reported improvements in headache frequency, intensity, disability, cutaneous allodynia, and OSA risk with benefits persisting up to 28 months after surgery.

Taken together, the results suggest several hypotheses. First, headache associated with macromastia may represent a previously unrecognized secondary headache disorder (“headache attributed to macromastia”) with a migraine phenotype, analogous to post-traumatic headache.³² Second, macromastia may exacerbate underlying migraine, which could explain postoperative improvement but not the red flag features. Third, the association may reflect an undiagnosed secondary headache disorder, such as IIH, particularly in young women with elevated BMIs, pulsatile tinnitus, and possible visual obscurations. Finally, multiple mechanisms may contribute, analogous to medication overuse headache, which can worsen migraine and act as a secondary cause.³³

Given that 45% of participants with migraine phenotypes reported a family history of migraine, a primary migraine disorder may be present in many cases.³⁴ However, in this cohort, while most exhibited phenotypic migraine, the semi-structured interview also revealed symptoms that may align with other ICHD-3 diagnoses, including headache attributed to cervical myofascial pain, occipital neuralgia, cervicogenic headache, and IIH. The average BMI of our cohort (30.9 kg/m²) was lower than that reported in IIH populations (36–47 kg/m²), although study participants were limited to those with a BMI <39 kg/m² (our institution limits surgical treatment by BMI, implemented due to increased complication rates for obese patients).³⁵ Whether macromastia independently contributes to IIH risk remains unknown and warrants further investigation. We did not expect the high rate of red flag features and did not include neurological examinations or information on prior neuroimaging as part of the baseline evaluation, a limitation given this high rate of red flags. However, it should be noted that some of the red flag features can also occur in up to 85% of patients with primary headache disorders.^41,42 Semi-structured interviews were only conducted at baseline, so it is unclear if these red flags resolved postoperatively. We offered all patients with red flag features not already established with the clinic (n = 30) referrals to our Comprehensive Headache Program (see the Supplemental Material for details). Future research should aim to clarify diagnoses and mechanisms through neurologic evaluation, including assessment for papilledema, neuroimaging in patients with Valsalva-associated headache, and migraine polygenic risk scoring.

We cannot fully interpret cutaneous allodynia frequency (42%) since we did not specify ictal versus interictal, although this falls within the range of what is typically seen in migraine populations.³⁷ The average allodynia score was mild in intensity, with postoperative allodynia resolution in 86%. All participants reported neck pain at baseline (100%), exceeding the 77% frequency in the general migraine population.³⁸ Forty-two percent of participants scheduled for reduction had a headache frequency in the chronic migraine range. In the US migraine population, chronic migraine comprises 8.8% of all migraine.⁴³ Known risk factors for migraine chronification include obesity, medication overuse, stress, caffeine, depression, and anxiety.^16,44 However, only 31% of patients with chronic migraine in our cohort were obese, whereas 78% of participants with episodic migraine were obese, raising the question of whether macromastia may contribute to migraine progression independent of generalized adiposity. Medication overuse was identified in 38% of those with chronic migraine, a proportion similar to that previously reported.⁴⁵

Patient-reported improvement in headache postoperatively may reflect various contributing factors, including biomechanical and systemic changes, placebo effects, anesthesia, and expectation bias. Potential effect modifiers such as improved mood, sleep, or exercise could also influence symptom perception.⁴⁶ BMI may also impact headache improvement, as average BMI was significantly higher in headache responders versus nonresponders (32.5 kg/m² vs. 29.0 kg/m²; p = 0.028). Migraine prevalence, intensity, chronification, and disability increase with obesity.^16,17 Obesity contributes to macromastia through adipose accumulation in the breasts and estrogen modulation, which promotes breast growth; however, breast adipose tissue accounts for an average of only 61% of breast tissue in women with macromastia.⁴⁷ Obesity's confounding effects in this cohort were somewhat mitigated by institutional BMI requirements for surgery.⁴⁸ Reduction mammoplasty unlikely exerts its positive headache effects through obesity treatment as the average total breast volume resected ranges from only 1.0–2.1 kg.⁴ Moreover, there were no significant weight loss changes between responders and nonresponders at either postoperative time point in our cohort. This raises the speculative hypothesis that localized (i.e. breast tissue-mediated) anatomical or molecular changes may play a role, rather than systemic weight reduction. Clinically, this points to the need for personalized predictors of response to refine surgical decision-making.

Black women constituted 32% of our cohort—more than double the typical migraine study representation (10%–15%), suggestive of racial differences in adipose distribution, cultural factors influencing pain perceptions, or biases/stigma in symptom recognition, surgical referral patterns, and/or acceptance of surgical treatment.^25,27,28 Moreover, most women requested surgery referrals from their providers and self-initiated the process (vs. provider recommendation), potentially reflecting the under-recognition of macromastia-related symptoms, lack of standardized screening, perception of reduction mammoplasty as cosmetic, bias toward conservative management, and/or disparities in medical attention to women's health concerns.

This study was not designed to evaluate reduction mammoplasty as a headache treatment, which requires a randomized controlled trial. Therefore, these results do not support its use for that purpose. Our study's value lies in characterizing headache phenotypes in women with macromastia before and after surgery. The observed reduction in attack frequency, pain, and disability suggests—but does not confirm—a link to macromastia.

Strengths and limitations

Study strengths include the integration of plastic surgeons and headache neurologists to evaluate headache type in women undergoing reduction mammoplasty. Study participants were highly engaged, with 98% (33/34) and 82% (28/34) completing surveys at 12–16 weeks and up to 28 months later, respectively. Data collection at pre- and postoperative timepoints enabled the assessment of baseline headache characteristics and comparisons of pre- and postoperative changes. Systematically collected data ascertained ID-Migraine criteria and ICHD-3 criteria A-D for migraine.

Study weaknesses include the inability to exclude the presence of other disorders (based on criterion E), small sample size, non-randomized design, lack of a control group, and placebo effects. This was a pilot study with limited resources, and we did not have the funding to compensate participants or provide smartphone-based tools for prospective headache-day tracking. For this reason, we relied on the recall-based MIDAS questionnaire, and recall bias may influence results. We acknowledge that current guidelines recommend diary-based assessments⁴⁹; however, our approach was driven by feasibility constraints rather than methodological preference. Recruitment was limited to surgical candidates, which selected individuals with more pronounced macromastia phenotypes and stronger motivation for symptom relief, limiting generalizability to the broader population with macromastia who do not pursue surgery. Additionally, participants received both surgical intervention and monetary incentives, factors that may have amplified perceived improvement in headache or other symptoms through expectancy effects or reporting bias. Using ID-Migraine to identify those with migraine is limited by its imperfect diagnostic accuracy,²⁹ as it can yield false positives and may not fully capture the complexity of the migraine diagnosis. Designing assessments to avoid in-person visits may introduce bias due to reliance on self-reported or remote data, potential inaccuracies compared to direct observation, and selection effects favoring participants comfortable with remote methods. Post hoc analyses of BMI and demographic factors related to headache response were not controlled for multiple comparisons and should be considered in future studies.

Acute postoperative pain management may include opioid use for 2–4 weeks, which may confound short-term assessments of headache frequency and intensity. Incorporating long-term follow-up data was essential to distinguish sustained symptom improvement from transient effects related to analgesic use.

Finally, our study cannot establish causality. It was not designed to separate natural symptom changes from surgical effects. Additionally, three participants began preventive migraine medications postoperatively, potentially confounding results. Future clinical trials could include sensitivity analyses to exclude such participants from analyses.

Future directions

Further research is needed to clarify links between breast tissue and craniocervical pain, investigate underlying mechanisms, and establish evidence-based treatment. Due to study limitations, the present findings cannot be extrapolated to clinical care. Preliminary results do not support reduction mammoplasty as a headache treatment and highlight the need for randomized controlled, longitudinal studies.

Conclusions

In our observational pilot study of 34 women with macromastia and headaches seeking reduction, 91% screened positive for migraine, suggesting headache in this population may extend beyond tension-type presentations. The presence of red flag features prevented satisfying the ICHD-3 migraine diagnostic criterion E, with more research needed to understand factors driving the red flags. After reduction, participants reported improvement in headache burden, allodynia, and OSA risk through 28 months postoperatively, potentially linked to changes in weight, mood, sleep, and/or physical activity, though individual contributions remain unclear. While not designed to assess IIH prevalence or causality, red flags raise concern for secondary headache disorders and highlight the need for careful neurologic evaluation. Future studies should explore whether macromastia influences migraine pathogenesis and its role in migraine's disproportionate impact on women, informing debates on peripheral versus central mechanisms.

Clinical implications

Headaches in women with macromastia are often misclassified as tension-type; most actually screen positive for migraine, though all women had “red flag” features.

Breast reduction surgery was associated with significant reductions in headache frequency, severity, disability, and cutaneous allodynia, as well as improved obstructive sleep apnea risk.

These findings suggest clinicians should screen for migraine and red flag features in patients with macromastia before attributing symptoms to musculoskeletal strain.

Despite promising pilot data, breast reduction should not be considered as a headache treatment until validated by larger, controlled studies.

Supplemental Material

sj-docx-1-rep-10.1177_25158163261416853 - Supplemental material for Understanding headache in the context of macromastia: An observational pilot study of headache profiles and postoperative changes

Supplemental material, sj-docx-1-rep-10.1177_25158163261416853 for Understanding headache in the context of macromastia: An observational pilot study of headache profiles and postoperative changes by Kristyn Spera Pocock, Joseph Rigdon, Elizabeth Laikhter, Alexa Hirshman, Aubrey Heath, Lauren Doyle Strauss, Liza Smirnoff, Sandhya Kumar, Jamy D Ard, Adam J Katz, Ivo Pestana, Bennett Calder, Barbara L Nye, Lisa R David, Richard B Lipton and Rebecca Erwin Wells in Cephalalgia Reports

Footnotes

Abbreviations

Acknowledgments

We thank all the participants who are a part of this study. We sincerely thank the American Headache Society and the International Headache Academy for their support of our research. We also extend our appreciation to Stephanie Ausborn and Laura Granetzke for their invaluable encouragement throughout the headache fellowship and beyond. We are grateful to Meghan Cassell, Kelly Walker, Renea Jennings, Caleb Suggs, Oddulia Santamaria, Cassandra Cass, and Erin Carrera for their assistance in patient recruitment for this study. Our appreciation also goes to Mark McKone for his expertise in EndNote manuscript preparation and to Breanna Stowe for medical photography. Additionally, we acknowledge the CTSI study coordinator pool of the Wake Forest Clinical and Translational Science Institute, supported by the National Center for Advancing Translational Sciences at the National Institutes of Health, CTSI support: NCATS: UL1TR001420.

ORCID iDs

Kristyn Spera Pocock

Liza Smirnoff

Richard B Lipton

Ethical considerations

The AHWFB IRB approved the study (IRB00092402).

Consent to participate

An electronic signature was obtained through research electronic data capture [REDCap]).

Consent for publishing

All authors agree to the publishing of this article.

Author contributions

Kristyn Spera Pocock—conceptualization, data curation, formal analysis, funding acquisition, investigation, methodology, resources, software, validation, visualization, writing–original draft, and writing–review and editing. Joseph Rigdon—data curation, formal analysis, validation, visualization, writing–original draft, and writing–review and editing. Elizabeth Laikhter—conceptualization, project administration, data curation, and writing–review and editing. Alexa Hirshman—investigation, data curation, and writing–review and editing. Aubrey Heath—investigation, data curation, and writing–review and editing. Lauren Doyle Strauss—writing–review and editing. Liza Smirnoff—writing–review and editing. Sandya Kumar—writing–review and editing. Jamy D Ard—conceptualization and writing–review and editing. Adam J Katz—writing–review and editing. Ivo Pestana—writing–review and editing. Bennett Calder—writing–review and editing. Barbara L Nye—writing–review and editing. Lisa R David—conceptualization and writing–review and editing. Richard B Lipton—conceptualization, formal analysis, validation, and writing–review and editing. Rebecca Erwin Wells—conceptualization, supervision, resources, validation, and writing–review and editing.

Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The authors received financial support for the research, authorship, and/or publication from the International Headache Academy. Funding was provided by the American Headache Society's International Headache Academy and the AHWFB Comprehensive Headache Program Inspire funds (grant number 11000001844).

Declaration of conflicting interests

The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: KP, JR, EL, AH, AH, LDS, AJK, SK, JA, IP, BC, LD, BN, and REW declare no conflicts. LS has received indirect funding for clinical trials from Ipsen and AbbVie. RBL serves on the editorial board of Neurology and as senior advisor to Headache but is not paid for his roles at these journals. He has received research support from the NIH, FDA, and the Sylvia and Leonard Marx Foundation. He receives research grants from Allergan/AbbVie, Amgen, Axsome, Dr Reddy's. He serves as a consultant, advisory board member, or has received honoraria from Allergan/AbbVie, Amgen, Axsome, Biohaven, Eli Lilly, GlaxoSmithKline, Merck, Novartis, Teva, and Vedanta. He receives royalties from Wolff's Headache (8th Edition, Oxford University Press, 2009) and Informa. He holds stock or options in Biohaven Pharmaceuticals, CoolTech, Manistee, and NuVie Bio.

Data availability statement

The data used for this article may be obtained from the authors with a reasonable request.

Open practices

Not applicable.

Supplemental material

Supplemental material for this article is available online.

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Supplementary Material

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