Effectiveness of melatonin adjuvant treatment in cisplatin to prevent depletion of ovarian follicles in mice: systematic review

Introduction: Cisplatin-based chemotherapy is the standard cancer therapy; however, this treatment causes depletion of ovarian follicles in women of reproductive age. Adjuvant treatment with melatonin can protect the ovaries from oxidative stress, reducing the side effects of chemotherapy. The objective was to evaluate the effects of the use of melatonin on the ovarian follicles of mice treated with cisplatin. Methodology: A systematic review was performed. The search strategy used the terms: “cisplatin”, “melatonin,” and “ovarian”. MEDLINE EMBASE, Cochrane Library, and gray literature (Google Scholar) were used as databases. The search was limited to experimental studies, performed on animals, with no language restrictions. Results: The search identified 30 studies and 5 primary studies, published between 2016 and 2021, and met the inclusion criteria, with a total of 115 mice. For the p-FOX3a/FOXO3a pathway, the meta-analysis showed a standard mean difference (SMD) of –4.79 (95% CI –6.16 to –3.42; P < 0.00001, two studies, 38 mice; I2 = 0%). For the p-PTEN pathway, the meta-analysis showed an SMD of –1.65 (95% CI –2.71 to –0.59; P = 0.002, two studies, 38 mice; I2 = 47%). Conclusion: Melatonin variation in efficacy varies according to the dose used in mice previously exposed to cisplatin. However, melatonin was able to alter the p-PTEN and p-FOX3a/FOXO3a pathways. Summary Sentence Melatonin interfered with the p-PTEN and p-FOX3a/FOXO3a pathways and Cisplatin associated with melatonin showed a reduction in ovarian follicles loss.