Decreased bone mineral density and reproductive axis dysfunction: more than oestrogen

Decreased bone mineral density (BMD) in oestrogendeficient states has long been thought to be a direct outcome of the reduction in oestrogen. In physiologic and many pathologic hypo-oestrogenic states, oestrogen supplementation improves BMD. However, the relationship between oestrogen replacement and BMD is less clear in the case of reproductive axis dysfunction secondary to decreased caloric intake or increased energy expenditure, such as in female athletes or anorexia nervosa. This decrease in oestrogen is associated with decreased BMD, but oestrogen replacement in these states fails to conclusively improve BMD. This suggests that the decrease in BMD in these states is not driven solely by low oestrogen. Cortisol and other markers of inflammation may play a role in BMD reduction but further research is needed. What is clear is that increased caloric consumption and restoration of menses and the reproductive axis are essential to improving BMD, while pharmacologic therapy, including oestrogen replacement through hormone therapy or contraceptives, does not provide conclusive benefit.