SS Clinical Evaluation of Mastalgia Houman Tavaf-Motamen, MD; Deborah N. Ader, PhD; Matrice W. Browne, MD; Craig D. Shriver, MD Objectives To describe an accurate and reproducible method to quantify a patient's subjective experience of breast pain. Design: Prospective diary study Setting: Military tertiary care hospital. Patients: Thirty female military health care beneficia- ries from the Walter Reed Army Medical Center, Wash- ington, DC, gynecology and general surgery clinies, Main Outcome Measures: Daily mastalgia was re- corded using a visual analog scale and menstrual symmp- toms were measured using a daily questionnaire. These measures were correlated with results ofa screening ques- tionnaire completed prior to study entry Results: Patients identified as having cyclical mastalgia based on the screening questionnaire (n=15) were found to have higher peak perimenstrual mastalgia according to their daily diaries than patients who did not meet di- agnostic criteria (n=15) (5.340.7 vs 3.5405, P<.001). Applying the same eriteria used in the screening ques- onnaire to the diary data, 17 of 30 patients met diag- nostic eriteria for cyclical mastalgia. The ability of the screening questionnaire to predict the results of the pro- spective diaty data was calculated, and positive and negs- ive predictive values were 73% and 60%, respectively ‘Most patients with cyclical mastalgia also have other peri- menstrual psychological and somatic complaints, al- though a subset of patients has high levels of mastalgia with minimal associated symptoms. Conelustons: Accurate assessment of mastalgia cannot be done with a retrospective questionnaire and requires prospective diary evaluation, owing to the variable and subjective nature of symptoms and recall bias. A daily visual analog scale provides reproducible results and is easy for patients to use Arch Surg, 1998:135:211-213 From the Departments of Surgery (Dr3 TavafMotamen ‘and Shrive), Psychology (Dr Ader), and Obstetrics and Gynecology (Dr Browne), Walter Reed Army Medical Genter, Washington, DC Downloaded From: on 03/20/2018 ASTALGIA IS the most ‘common breast-re- lated complaint of pa- tients seeking care at both primary care clin- fceand breast referral centers. Two thirds of screened patients in most series com- plain of breast pain, of which more than 50% cyclical in nature."* While most p- tients only require reassurance of the be- nigh nature of their complaint, up to 15% wil require further therapy.’ Despite the pervasive nature of this condition, it has received little attention clinically of in the US medical literature, with the majority of references originating in Great Britain and. western Europe. This relative inattention may be due to the misconception that breast pain is a normal part of the peri- menstrual symptom complex and that there is no acceptable treatment avail- able. To study and treat mastalgia effec- tively, an accurate and reproducible method to record a patient's subjective ex- perience of breast pain is needed. (©1908 American Med es Patients identified as having cyclical rmastalgia based on the screening que Lonnaire were found to have higher peal perimensttual breast pain noted in their daily mastalgia diaries than those who did not meet screening questionnaire diagnostic criteria (5340.7 vs 3.540.5, P<.001). Applying the same criteria used to make a diagnosis of eyelical mas- talgia on the screening questionnaire (le, duration =5 days and peak intensity >4), 17 of 30 patients met diagnostic criteria for cyclical mastalgia using the diary data, The positive predictive value, negative predictive value, sensitivity, and specificity of the screening questionnat were calculated using the prospective This article is also available on our Web site: www.ama-assn.org/surgery. Association, All rights reserved.SUBJECTS AND METHODS Allhuma studies were performed in accordance with theprotacol approved by an institutional review board fand informed consent was obtained from all sub Jetspriorto sty enrolment. Patentsecking cre the Walter Reed Army Hospital, Washington: DC fynccology and general surgery breast clinics were Sted completes nrecning stionnaieregaed- ing the intensity and duration of their perimen- situa breast pain. Intensity of mastalgia was mea- fed witha visual anlog sal, Responses were “quand by measuring the distance marked in cen- timeters, from 0 (no bres pin) to 1 (exteme breast pal) A dignosis of yl masa, using a modi- Rtn of enters roposed by the masta clinic a Cardi, Wales? was made fa patient claimed per- treasures pein for $ dae or ate per je wieaynptom sever eons gre taco the visual analog sale Thirty pact wee gen dni inwhich ap tom of mating were ecored daly an averages 1 days using the same visual analog sale Half of these 30 patients met the screening questionnaire di- gnostic eritera fr cyclical masala, we the r= Tisning 13 had esse and nondagnostc breast pain Darnton ofmastalgia and peak mstalgiavasdcter- mined foreach menstrual cycle andaveraged foreach patient “The same diagnostic criteria used inthe screen ing qstonnaie namely, ncan dation af at st S dope per el sid mean peak print mas alin greater than 4 em on the Vistal analog scale, twereappied tothe prospectively gathered dnt dat The positive predictive value, negative predictive value sensitiv, and speci of thescreching ques tlomire were called tng the pronpecie i= data a the dagnosticitefonstandird Patients completing the masala dary were also cvaluted regarding 33 other psychological and so- matic complains (Rable) using «standard Men ‘tru Symptom Severity List” Each symptom was Scored from (absent to (extreme) daly. The scones for opmpton tsetse feracunabtve daly syspion score, Peak ptncnsron sjptom score ‘vas determined for each mensirul cycle and aver- ged foreach patent. 68 elise repored as meanaSEM. Parson cor relations wert computed wl comparisons beeen fsroups ere made withthe Student test The int fvasset at P05, 2 tailed, forall tests diary data as the diagnostic criterion standard, and were 73%, 60%, 65%, and 69%, respectively. ‘Overall, prospectively measured breast pain was sig- nificantly correlated with other menstrual complaints with a correlation coefficient of 0.54 (P<.001). Most pa- tients experience mastalgia in association with high lev- cls of other menstrual complaints, although a subset of patients (12% of patients with cyclical mastalgia) has high levels of mastalgia but relatively minimal associated symp- toms, Figure 1 demonstrates the experience of @ pa- Table 1. Menstrual Symptom Severity List ‘dominal ung Tot tatavestng ‘Admin Handa suaing Anger ote Backache Breast paint Cant gatos Lonely Decresee appetite Mood svings Decree cnceniation Night aang Decrseed dcveneet (ut of conta ed ol es ash eta be lone Sad Ely awakening Sensi to colt Feo eraving Tear uit Tension Headache Weigh oan Hosilty ~Breas gan was omted when calculating the pernenstual symptom sere and when calling coretton to vsual analog sale masta love ‘ient in whom catamenial symptoms mirror mastalgia ine couse. In contrast, Figure 2 represents a patient Who has significant eyelical breast pain but minimal associ- ated symptoms a Cyclical mastalgia isan under-recognized and poorly un- derstood disorder that is common among patients in the primary care setting and those referred for surgical con- sultation, Studies have shown that in a standard breast clinic oF general surgery practice setting, 15% of p menopausal women will have clinically significant cy- clical mastalgia. However, this disorder will not be ap- propriately diagnosed unless patients are properly evaluated for it. Our own data at the Walter Reed breast clinic demonstrates that, of those women diagnosed with cyclical mastalga, the disorder significantly interferes with social, physical, and sexual activites in 13%, 35%, and 45% of patients, respectively. Moreover, we have shown that there is a significant increased wilization of health care resources, specifically mammography, in women younger than 35 years who reported a history of eyelical rmastalgia.” See Invited Commentary at end of article Study of eyclical mastalgia is confounded by the vari- able and subjective nature of symptoms as well as recall bias, prompting some authors to mandate the use of pro- spective studies in the evaluation of mastalgia.? Out re sults corroborate this sentiment. When patients were as- signed to a diagnostic group based on their answers (o a mastalgia screening questionnaire, the agreement with the prospectively gathered diary data was only moder- ate, witha positive and negative predictive value of 73% and 60%, respectively. These figures will vary with the prevalence of mastalgia in the study population and with (©1908 American Med Downloaded From: on 03/20/2018 Association, All rights reserved.0 10 ‘ i jog : z as of gs 5 2 joe 2 a 2 od : . as figure +. Tele (146 dy) of pat with yccal masala (shed li) associated wit igh velo fer menstrual camps (so ine). Astesks idea begining of mental ec. Masta was mead ‘uth aviv analog scale other mens Symptoms were measured wih the ens Symptom Seveny List the threshold at which the diagnosis of mastalgia is ar- rived. We believe thatthe standard of eare for the study, diagnosis, and treatment of eyelical mastalga isto per form a diary study for a minimum of 2 eyeles before and after an intervention. We have found a daily mas- talgia visual analog seale to provide reproducible results and to be intuitive and easy for patients to use. In our ‘experience, a questionnaire relying on patient recall is useful for sereening, but is not adequately sensitive or specific o determine who isan appropriate candidate for ‘As more rescarch is completed on this topic, com- mon clinical practices are being called into question and new treatments for eyelical mastalgia are gaining aceep- tance. Despite multiple studies showing no advantage to treatments including diuretic use, abstinence from meth- ylxanthines (such as coffee, chocolate, and other deriva- tives), oF vitamin supplementation, these modalities are still being advocated in the United States." Research has shown that for most patients, reassurance that mastal- gia is not associated with a malignant neoplasm i all that isrequired.'* For patients with refractory symptoms, rwule tiple hormonal agents such as gestrinone," danazol,” bro- rmocriptine,” and tamoxifen’ have been shown to be ef- ficacious when compared with placebo. Unfortunately, these medications are associated with high degrees of adverse reactions, including hirsutism, hot flashes, and dysfunctional uterine bleeding, among many others. ‘y-linolenic acid (GLA), found in evening primrose oil, is an over-the-counter nonhormonal agent with mini- imal adverse effects that has proven efficacy in European placebo-controlled trials,” but is not approved by the US Food and Drug Administration for treatment of mastal- gia. ILis thought that GLA works by inereasing the ratio of essential unsaturated fatty acids to saturated fatty ae- ids in the body. Our center is embarking on a prospec- tive, double-blind, placebo-controlled tral of GLA for the treatment of eyclical mastalgia, Diary data show a correlation between mastalgia and. ‘other eyelical somatic and psychological complaints; how- ever, there seems to be a subset of patients (12% with ‘yelical mastalgia in our study population) with signifi ‘cant mastalgia but minimal associated symptoms. This Figure 2. Tine (168 dys) ofa patent wih cea! masala who bas sient reas pan (asted ie), ut minal associated menstual aman sok ine) Astrists deat begining of ment eee ‘Masala was measured wih a vu aatog sete oter mens ‘Symons were measured with te Mensta Sjmotom Seer) List* divergence of symptom complexes suggests that, atleast for some patients, maslalgia is distinct from other men- strual complaints, Itwill be interesting to note whether this subset of patients differs in response to mastalgia- specific treatments stich as GLA. Funds for this study were obtained from an Uniformed Ser- vices University of the Health Sciences intramural grant (cossBc), The opinions or assertions herein are those ofthe au- thors and do not necessarily represent the views of the US “Army or the US Department of Defense. Reprints: Houman Tavaf-Motamen, MD, 28 Hickory ‘Ave, Takoma Park, MD 20912 (e-mail: tavafh@aol.com). EES] Baliu RI. Mesto. bse Gaz Cn Wath Am 1994216167 2 Hold PA, Gate CA Ought masala what athe apn? Drags. ont8 70076, 8 Lenser 8, Whashouse GH, Wal PV. Oye! masta: clan man ‘mograpi observations ina sone population. BJ Sug 188774220 mB 4 Maiox PR, Manel RE Haron Lal. Aandi onl lof me Saxprogesrons asta masala Ano Cal Sug Eng 100727176 5 Gatley CA, Mir M, Manoel E, Hughes LE Drogen for masa: 17 Yous exganee inte Cri mas ci Sar Med 109285121 6 Woo Mehl 5, Lane ML. Soc pata he premarsal yn toms. rs Hoth 10518226297 1 Ader ON, Bowne Mel masa: ralenceanimpactin aUSclie- based sample A J Onset Gna 189717125132 8 Sinabood J Ave 0, Ter Viamin Sin he eaknet of promensual rasulga Jon Pact 1086405025, 0. Alen $5, robe D The afro decreased cat consumption on bain Prorat bent sea andomnd lia tl. Surge 187101. 720- a Prose, Richards AR, Oven GM, Hughes LE Masti an eal bay wat. BU 1975-408 500 Pats Mice sy of getinen nee beet pin, ant, 192; sa0205-208 Hare Mon, Manel RE Minteance therapy oye masa sing low-ose dara J Cal Sur Eg 1985 3470-1 18 Mansel e, Dogo L Euopaan mute al of romacptie nee rasta. Lane 100385 10-13. 14. Famtinan 8, Cal Bane K Chau MA Hayward JL Double incon ‘ol lf anon tera fr masa are 10861287288, Pashy Masel RE Hughes LE.Acnalval teeing pias alin as- tig B.jSu. 181 801-308 (©1908 American Med Downloaded From: on 03/20/2018 Association, All rights reserved.«rr 1 this isue ofthe ARCHIVES, Taval-Motamen and asocats give a wake-up call o physicians who study of treat mas- todynia. They compared the recall questionnaires of 30 women with breast pain with each patients dll vista analog scale fr breast pain and found poor agreement. Only 73% of those denied as having cyelic mastalgia based onthe {questionnaire met thesame criteria based on thet daly dares, Furthermore, the intensity of oer somalictnensrual com lsints was not alvays in accord with the severity of breast pain on the analog scales. Ther dala emphasize the complexity btthis problem and the necessity for objective means of evaluating ts course and treatment. Inthe Une states, breast pa is almost the norm. n my sugial practice, only 2.5% of patients referred for breas-elated problems are seen primar breast pin, but on questioning, tht majority report some degree of masiodynia. Only when the pa esevere or debiliaing doesit become the facts ofatention In postmenopausal women the problem ts often elated to hormone replacement therapy ifthe cause not obvious, the tendency ist recommend relatively harmales remedies and reserve danacrne for resistant cases, The former include caffeine and tyramine restriction, vlamin E, and evening primrose ol cach witha tenuous raio- tale. The subjectivity and variable courte of symptoms often preclude an accurate aseesment of resus, The authors pro ‘ide few clues about ther enrollment questionnaire, and the periods evaluated with the questionnaire andthe daly diary ‘were not coincident, surely a problem when the course ofa cinta! problem is uneven. While it comes ax no surprise that Pullen histories are not slvays accurate, the message is clear tha understanding mastodynia and its reatment requires tore than heats. William L. Donegan, MD Milwaukee, Wis a ARCHIVES OF INTERNAL MEDICINE ‘A Comparison of Estrogen Replacement, Pravastatin, and Combined Treatment for the Management ‘of Hypercholesterolemia in Postmenopatsal Women Michael H. Davidson, MD; Lisa M. Testolin, RD, CNSD; Kevin C. Maki, MS: Serge von Duvillard, PRD; Kathleen B. Drennan. Objectives: To evaluate and compare the lipid-altering elfects of conjugated estrogens and pravastatin, alone and in com bination, in postmenopausal women with hypercholesterolemia. ‘Methods: This wasa double-blind, randomized, placcho-contrlled clinical ral with parallel groups. Participants (N=76) ‘were randomly assigned to receive conjugated estrogens, 0.625 mg/d pravastatin sodium, 20 mg/d; conjugated estrogens plus pravastatin; ora placeho for 16 weeks. Results: Primary end points were changes in serum lipid parameters. Among participants teated with conjugated estro- gens, levels of non-high density lipoprotein cholesterol (non-HDL-C) (13.0%) and calculated low density lipoprotein cho- lesterol (LDL-C) (13.5%) decreased, while levels of HDL-C (22.5%) and triglycerides (4.2%) increased. Participants in the pravastatin group achieved reductions of 23.7% and 25.4% in non-HDL-C and calculated LDL-C levels, respectively Levels ‘of HDL-C increased slightly (3.7%) and triglycerides decreased by 12.1%, Among participants treated witha combination of conjugated estrogens plus pravastatin, the non-HDL-C (-25.2%) and calculated LDL-C (-28.7%) esponses were similar to those ofthe pravastatin group, and the HDL-C response (21.2%) was similar to that observed in the conjugated estrogens ‘group. Triglyceride levels remained similar to baseline (-0.9%) in the combined treatment group. Conelusions: Administration of conjugated estrogens resulted in potentially antiatherogenic changes in levels of non HDL-C, HDL-C, and calculated LDL-C. The HDL-C response to combined treatment was similar to that observed in women taking conjugated estrogens alone, while the non-HDL-C and LDL-C responses to combined treatment were similar to those prodiiced by pravastatin therapy slone. These findings support the position ofthe National Cholesterol Education Program that estrogen replacement, with a progestin where indicated, should be given consideration as a therapeutic option for the ‘management of hypercholesterolemia in postmenopausal women. Arch Intern Med. 1997:137-1186-1192 Reprints: Michael H. Davidson, MD, Chicago Cente fr Clinical Research, 515 N State St, Suite 2700, Chicago, IL 60610. (©1908 American Med Association, All rights reserved. Downloaded From: on 03/20/2018