Tamoxifen is a selective estrogen receptor modulator (SERM) with agonist-antagonist properties used as adjuvant treatment of hormone sensitive breast cancer.  Rodent studies have shown ovarian protection with tamoxifen administered prior to cyclophosphamide [31].   Tamoxifen has also been shown to be protective when given prior to radiation treatment in rats with a reduction in loss of primordial follicles and increase in AMH [32].  Human studies with tamoxifen given post-chemotherapy have shown no protection [33].  Human studies evaluating the effects of tamoxifen as an ovarian protective agent have been conflicting due to study design and use of different endpoints [34].  The postulated mechanism of action remains unclear.  It is postulated that the protective effects of tamoxifen may be due to its anti-apoptotic and antioxidant effects from its estrogen-agonist properties [35, 36].
Protection may also result from increased transcription and translation of IGF-1 which has been shown to augment granulosa cell FSH receptor expression in the ovary and potentiate FSH action.  Lastly, antagonist effects of tamoxifen are similar to GnRHa with down-regulation of the H-P-O axis and ovarian quiescence which may also have a protective role.  Well-designed human studies are warranted to assess the protective effect of tamoxifen on ovarian function during chemotherapy and radiation.