Methods: In this review study, online English databases such as PubMed, Scopus, Web of Science, and Cochrane Library were systematically searched without a time limit until January 10, 2025.

Results: Tamoxifen and centchroman are both more effective than placebo in relieving breast pain. Centchroman can reduce the severity of mastalgia by 92-100%. Pain score significantly reduced in the centchroman group compared to the placebo group (P < 0.0001). Centchroman and tamoxifen similarly affected pain relief (P < 0.005). Tamoxifen was more effective than danzol in relieving breast pain (P < 0.001). The effects of tamoxifen were not dose dependent, as 10 mg and 20 mg did not follow a trend, but 10 mg produced significantly fewer side effects. There are inconsistent results when comparing the efficacy of danazol and centchroman at 12 weeks. However, tamoxifen outperformed danazol long-term AT 24 weeks. Four case series were included in the systematic review. Tamoxifen and raloxifene may be effective for the treatment of pubertal gynecomastia. In the first, reduction in breast nodule diameter was 86% in the tamoxifen group and 91%in the raloxifene group. However, a more significant improvement was observed in the tamoxifen group than in the raloxifene group (P = 0.03). In the second study, both groups had a statistically significant breast size reduction (tamoxifen group, P = 0.013; no treatment group, P = 0.038). In the third and fourth studies, the treatment success rate with tamoxifen was calculated to be 86 to 94%.

Conclusions: Mild cyclic mastalgia can be treated by making appropriate lifestyle changes. Moderate to severe mastalgia usually requires medical treatment. Ormeloxifene, tamoxifen, and danazol were all effective in relieving breast pain. Tamoxifen and raloxifene may be effective for the treatment of pubertal gynecomastia.