Nonhormonal therapies such as dietary restrictions, vitamins and supplements, and restriction of methylxantines were investigated as possible treatments for mastalgia because they are less likely to be associated with adverse drug-related side effects (116). Because mastalgia is one of the symptoms associated with fibrocystic disease, the treatments described for fibrocystic disease are relevant to mastalgia. A low-fat diet was effective in one randomized trial (136). Ninety percent of patients taking in 15% dietary fat experienced resolution of pain symptoms after 6 months compared with only 22% of those on a diet containing 36% fat (p = .0023). Evening primrose oil containing essential fatty acids (γ -linolenic acid [GLA]) was studied because of its affect on prostaglandin synthesis (137). It was used as first-line therapy, reserving danazol and bromocriptine for treatment of more severe symptoms (112). In a small prospective mastalgia trial, women were given eight capsules of evening primrose oil daily for 4 months (320 mg GLA) (138). Those who responded had a lower level of essential fatty acids at the time of initiation when compared with poor responders, suggesting that evening primrose oil increases essential fatty acids and that this increase may be associated with the improvement in symptoms in the responders. Two other trials failed to demonstrate efficacy of evening primrose oil capsules over placebo (139,140). In a Dutch trial, 124 women with cyclic or noncyclic pain lasting on average 7 or more days (minimum 5 days) were randomized to receive the following regimens: (i) fish oil and control oil, (ii) evening primrose oil and control oil, (iii) fish and evening primrose oil, or (iv) both control oils for 6 months (139). There was a statistically significant reduction in the number of days per month with pain but not in the pain score in the entire study population. There was a greater reduction in cyclic than noncyclic pain symptoms, and this finding was true for both the test oils and for the control oils. The authors concluded that neither fish oil nor evening primrose oil had a better effect than the less expensive wheat germ and corn oils. A second large double-blind randomized prospective trial was conducted in 555 women with cyclic mastalgia of moderate to severe degree present for at least 7 days of a menstrual cycle (140). The four groups were (i) GLA and placebo antioxidants, (ii) placebo fatty acids and antioxidants, (iii) GLA and placebo antioxidants, and (iv) placebo fatty acids and placebo antioxidants. The treatments were given in a blinded fashion for 4 months. All groups had a similar 35% reduction in symptoms. This treatment was followed by open treatment with GLA in all groups and blinded treatment with antioxidants. There was continued improvement of symptoms in all groups with a reduction in mastalgia by 50% over the next 12 months. This is the largest and best-controlled study to date evaluating GLA for relief of mastalgia, and GLA was not found to be superior to placebo. The results of this study were not consistent with those from previous smaller studies. The authors cannot exclude a significant psychologic impact that may confound the effect of GLA. GLA use was found to be safe, without any significant side effects, and was prescribed as therapy for mastalgia because of its lack of side effects. The randomized trials, however, bring into serious question the efficacy of these options.