Breast pain is increased in some individuals who have elevated prolactin (PRL) levels induced by thyrotropin-releasing hormone (TRH) (116). Bromocriptine is a dopamine antagonist that inhibits the release of PRL. Bromocriptine (2.5 mg twice daily) given for 3 to 6 months is effective in reducing mastalgia in women who have TRH-induced elevation of PRL (123). Patients who have normal TRH levels, are resistant to bromocriptine, or do not tolerate the side effects of nausea, vomiting, and headache respond favorably to progesterone and systemic nonsteroidal anti-inﬂammatory drugs (NSAIDs).
Prolactin induces active transport of iodine in breast tissue (126,127). Iodine deficiency in rats causes hyperplasia and atypia (128). Iodine replacement is associated with improvement in subjective pain (129). A randomized, double-blind study with supraphysiologic levels of iodine in women with documented cyclic mastalgia demonstrated dose-dependent reduction in physician-assessed and self-reported pain at 3 and 6 months of treatment (130).
Goserelin is a potent synthetic analogue of luteinizing hormone-releasing hormone (LHRH) that causes reversible reduction in serum estrogen level and decrease in breast pain (131). Side effects of goserelin include vaginal dryness, hot ﬂushes, decreased libido, oily skin and hair, and decreased breast size. A recent clinical trial randomized 147 women into goserelin versus placebo groups. The study had a 49% drop-out rate. The mean breast pain score decreased by 67% in the goserelin arm and 35% in the placebo arm. The authors concluded that goserelin is an effective treatment for mastalgia with significant side effects and should be kept as second-line therapy. Hormonal blockade of the estrogen receptor is another approach to minimizing the effects of circulating estrogen on breast pain. Treatment with the selective estrogen receptor modulator tamoxifen demonstrated reduction in breast pain at 10 and 20 mg per day, with equivalent effects compared with danazol and bromocriptine in most studies (124,132–134). Topical nonsteroidal therapy is another option for women with mastalgia (135). Gel forms of NSAIDs often are used for relief of pain. Patients were stratified by cyclic versus noncyclic pain and then randomized to treatment with NSAIDs versus placebo. There was a significant reduction in cyclic and noncyclic pain in all groups, but the magnitude of change was greater in the treatment arms and similar for cyclic and noncyclic pain. Use of NSAIDs appears to be a less toxic treatment and may be considered as an option for both cyclic and noncyclic breast pain.