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Clinical Factors Affecting the Therapeutic Efficacy of Evening Primrose Oil on Mastalgia



Saturated fatty acid esters may cause mastalgia via hypersensitivity of breast epithelium to circulating hormones. Evening primrose oil (EPO) may restore the saturated/unsaturated fatty acid balance and decrease sensitivity to steroidal hormones or prolactin. Conflicting results exist regarding EPO treatment for mastalgia. The aim of this study was to determine the effectiveness of EPO and factors affecting its efficacy in treatment of mastalgia.


The study included 1015 patients, ages 14–82 (mean age 42.21 ± 10.8), admitted to Acibadem Breast Clinic between January 2015 and March 2018. The patients were divided into group I (n = 581) treated with EPO (1300 mg, twice a day) and group II (n = 434) treated with paracetamol (500 mg, twice a day). The visual analog scale was used to assess EPO’s therapeutic efficacy, compared with paracetamol, measured at admittance, 2 weeks, and 6 weeks. Clinical factors affecting the efficacy of EPO were analyzed.


The therapeutic efficacy of EPO on mastalgia was significantly higher than with paracetamol (p < 0.001). Factors significantly affecting the efficacy of EPO treatment were hormone replacement therapy (HRT), IUD-with-levonorgestrel, iron deficiency, overt hypothyroidism, and Hashimoto thyroiditis (p < 0.01). Replacement of iron or thyroid hormone efficiently treated mastalgia in patients that did not respond to EPO treatment. Side effects (allergy, anxiety, blurred vision, constipation, and nausea) were rare and not statistically significant (p = 0.88).


EPO can be used in the treatment of mastalgia without significant side effects. HRT, IUD-with-levonorgestrel, iron deficiency, overt hypothyroidism, and Hashimoto thyroiditis significantly affect the efficacy of EPO on mastalgia.

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  1. 1.

    Morrow M. The evaluation of common breast problems. Am Fam Phys. 2000;61(8):2371–8.

    CAS  PubMed  Google Scholar 

  2. 2.

    Pruthi S, Wahner-Roedler DL, Torkelson CJ, et al. Vitamin E and evening primrose oil for management of cyclical mastalgia: a randomized pilot study. Altern Med Rev. 2010;15(1):59–67.

    PubMed  Google Scholar 

  3. 3.

    Gateley CA, Maddox PR, Pritchard GA, et al. Plasma fatty acid profiles in benign breast disorders. Br J Surg. 1992;79(5):407–409.

    CAS  PubMed  Google Scholar 

  4. 4.

    Blommers J, de Lange-De Klerk ES, Kuik DJ, et al. Evening primrose oil and fish oil for severe chronic mastalgia: a randomized, double-blind, controlled trial. Am J Obstet Gynecol. 2002;187:1389–1394.

    CAS  PubMed  Google Scholar 

  5. 5.

    Srivastava A, Mansel RE, Arvind N, et al. Evidence-based management of mastalgia: a meta-analysis of randomised trials. Breast. 2007;16:503–512.

    CAS  PubMed  Google Scholar 

  6. 6.

    Ader DN, Browne MW. Prevalence and impact of cyclic mastalgia in a United States clinic-based sample. Am J Obstet Gynecol. 1997;177:126–132.

    CAS  PubMed  Google Scholar 

  7. 7.

    Colak T, Ipek T, Kanik A, et al. Efficacy of topical nonsteroidal anti-inflammatory drugs in mastalgia treatment. J Am Coll Surg. 2003;196 (4):525–530.

    PubMed  Google Scholar 

  8. 8.

    Irving AD, Morrison SL. Effectiveness of topical non-steroidal anti-inflammatory drugs in the management of breast pain. J R Coll Surg Edinb. 1998;43 (3):158–159.

    CAS  PubMed  Google Scholar 

  9. 9.

    Groen JW, Grosfeld S, Wilschut JA, et al. Cyclic and non-cyclic breast-pain: a systematic review on pain reduction, side effects, and quality of life for various treatments. Eur J Obstet Gynecol Reprod Biol. 2018;2017;219:74–93.

    Google Scholar 

  10. 10.

    Srivastava A, Mansel RE, Arvind N, et al. Evidence-based management of mastalgia: a meta-analysis of randomised trials. Breast. 2007;16(5):503–512.

    CAS  PubMed  Google Scholar 

  11. 11.

    Iddon J, Dixon JM. Mastalgia. BMJ. 2013;347:f3288.

    PubMed  Google Scholar 

  12. 12.

    Gately CA, Miers M, Mansel RE, Hughes LE. Drug treatments for mastalgia: 17 years experience in the Cardiff Mastalgia Clinic. J R Soc Med. 1992;85: 12–15.

    Google Scholar 

  13. 13.

    Horrobin DF, Manku MS. Premenstrual syndrome and premenstrual breast pain (cyclical mastalgia): disorders of essential fatty acid (EFA) metabolism. Prostaglandins Leukot Essent Fatty Acids Rev. 1989;37: 255–261.

    CAS  Google Scholar 

  14. 14.

    Pye JK, Mansel RE, Hughes LE. Clinical experience of drug treatments for mastalgia. Lancet. 1985;2(8451):373–377.

    CAS  PubMed  Google Scholar 

  15. 15.

    Ingram DM, Hickling C, West L, Mahe LJ, Dunbar PM. A double-blind randomized controlled trial of isoflavones in the treatment of cyclical mastalgia. Breast. 2002;11:170–174.

    CAS  PubMed  Google Scholar 

  16. 16.

    Pashby NL, Mansel RE, Hughes LE, et al. A clinical trial of evening primrose oil in mastalgia. Br J Surg. 1981;68:801.

    Google Scholar 

  17. 17.

    Preece PE, Baum M, Mansel RE, et al. Importance of mastalgia in operable breast cancer. Br Med J (Clin Res Ed). 1982;284:1299-1300.

    CAS  PubMed Central  Google Scholar 

  18. 18.

    Melzack R. The short-form McGill Pain Questionnaire. Pain. 1987;30:191–197.

    CAS  Google Scholar 

  19. 19.

    Pye JK, Mansel RE, Hughes LE. Clinical experience of drug treatments for mastalgia. Lancet. 1985;2:373–377.

    CAS  PubMed  Google Scholar 

  20. 20.

    McFayden IJ, Forrest AP, Chetty U, Raab G. Cyclical breast pain—some observations and the difficulties in treatment. Br J Clin Pract 1992;46:161–164.

    CAS  PubMed  Google Scholar 

  21. 21.

    Cheung AN, Shen DH, Khoo US, et al. Immunohistochemical and mutational analysis of p53 tumor suppressor gene in gestational trophoblastic disease: correlation with mdm2, proliferation index, and clinicopathologic parameters. Int J Gynecol Cancer. 1999;9:123–130.

    PubMed  Google Scholar 

  22. 22.

    Goyal A, Mansel RE, Efamast Study Group. A randomized multicenter study of gamolenic acid (Efamast) with and without antioxidant vitamins and minerals in the management of mastalgia. Breast J. 2005;11:41-47.

    CAS  PubMed  Google Scholar 

  23. 23.

    Goyal A. Breast pain. BMJ Clin Evid. 2011;2011:0812.

    PubMed  PubMed Central  Google Scholar 

  24. 24.

    Pearlman M, Griffin J, Swain M, Chelmow D. American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins—Gynecology. Practice bulletin no. 164: Diagnosis and management of benign breast disorders. Obstet Gynecol. 2016;127(6):e141–e156.

    Google Scholar 

  25. 25.

    Goyal A. Breast pain. BMJ Clin Evid. 2014;2014:0812.

    PubMed Central  Google Scholar 

  26. 26.

    Parveen S, Sarwar G, Ali M, Channa GA. Danazol versus oil of evening primrose in the treatment of mastalgia. Pak J Surg. 2007;23:10-13.

    Google Scholar 

  27. 27.

    Sharma N, Gupta A, Jha PK, Rajput P. Mastalgia cured! Randomized trial comparing centchroman to evening primrose oil. Breast J. 2012;18:509-510.

    PubMed  Google Scholar 

  28. 28.

    Adamopoulos DA, Vassilaros S, Kapolla N, et al. Thyroid disease in patients with benign and malignant mastopathy. Cancer. 1986;57:125–128.

    CAS  PubMed  Google Scholar 

  29. 29.

    Giustarini E, Pinchera A, Fierabracci P, et al. Thyroid autoimmunity in patients with malignant and benign breast diseases before surgery. Eur J Endocrinol. 2006;154:645–649.

    CAS  PubMed  Google Scholar 

  30. 30.

    Venturi S. Is there a role for iodine in breast diseases? Breast. 2001;10:379–382.

    CAS  PubMed  Google Scholar 

  31. 31.

    Ghent WR, Eskin BA, Low DA et al. Iodine replacement in fibrocystic disease of the breast. Can J Surg. 1993;36:453–460.

    CAS  PubMed  Google Scholar 

  32. 32.

    Estes NC. Mastodynia due to fibrocystic disease of the breast controlled with thyroid hormone. Am J Surg. 1982;42:764–766.

    Google Scholar 

  33. 33.

    Bhargav PR, Mishra A, Agarwal G, et al. Prevalence of hypothyroidism in benign breast disorders and effect of thyroxine replacement on the clinical outcome. World J Surg. 2009;33(10):2087–2093.

    PubMed  Google Scholar 

  34. 34.

    Surks MI, Ortiz E, Daniels GH, et al. Subclinical thyroid disease: scientific review and guidelines for diagnosis and management. JAMA 2004;291:228–238.

    CAS  PubMed  Google Scholar 

  35. 35.

    Vanderpump MP, Tunbridge WH, French JM. The incidence of thyroid disorders in the community: a twenty-year follow-up of the Whickham survey. Clin Endocrinol (Oxf). 1995;43:55–68.

    CAS  PubMed  Google Scholar 

  36. 36.

    Wilson GR, Curry RW. Subclinical thyroid disease. Am Fam Phys. 2005;72:1517–1524.

    PubMed  Google Scholar 

  37. 37.

    Arrigo T, Wasniewska M, Crisafulli G, et al. Subclinical hypothyroidism: the state of the art. J Endocrinol Invest. 2009;31:79– 84.

    Google Scholar 

  38. 38.

    Bianco LE, Wiesinger J, Earley CJ, et al. Iron deficiency alters dopamine uptake and response to L-DOPA injection in Sprague–Dawley rats. J Neurochem. 2008;106(1):205–215.

    CAS  PubMed  Google Scholar 

  39. 39.

    Erikson KM, Jones BC, Hess EJ, et al. Iron deficiency decreases dopamine D1 and D2 receptors in rat brain. Pharmacol Biochem Behav. 2001;69(3–4):409–418.

    CAS  PubMed  Google Scholar 

  40. 40.

    Sen M, Kilic MO, Cemeroglu O, Icen D. Can mastalgia be another somatic symptom in fibromyalgia syndrome? Clinics (Sao Paulo). 2015;70(11):733–737.

    PubMed Central  Google Scholar 

  41. 41.

    Colegrave S, Holcombe C, Salmon P. Psychological characteristics of women presenting with breast pain. J Psychosom Res. 2001;50:303–307.

    CAS  PubMed  Google Scholar 

  42. 42.

    Jenkins PL, Jamil N, Gateley C, Mansel RE. Psychiatric illness in patients with severe treatment-resistant mastalgia. Gen Hosp Psychiatry. 1993;15:55–57.

    CAS  PubMed  Google Scholar 

  43. 43.

    Preece PE, Mansel RE, Hughes LE. Mastalgia: psychoneurosis or organic disease? Br Med J. 1978;1:29–30.

    CAS  PubMed  PubMed Central  Google Scholar 

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Correspondence to Fatih Levent Balci MD.

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Balci, F.L., Uras, C. & Feldman, S. Clinical Factors Affecting the Therapeutic Efficacy of Evening Primrose Oil on Mastalgia. Ann Surg Oncol 27, 4844–4852 (2020).

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