There is considerable controversy over the earliest age at which it is clinically, morally, and legally safe to use GnRH analogues, and for how long. The sixth edition of the World Professional Association for Transgender Health 's Standards of Care permit it from Tanner stage 2 but do not allow the addition of hormones until age 16, which could be five or more years later. Sex steroids have important functions in addition to their role in puberty, and some skeletal changes (such as increased height) that may be considered masculine are not hindered by GnRH analogues.
A 2007 study investigated the interaction between bisphenol A's and estrogen-related receptor γ (ERR-γ). This orphan receptor (endogenous ligand unknown) behaves as a constitutive activator of transcription. BPA seems to bind strongly to ERR-γ ( dissociation constant = nM), but only weakly to the ER.  BPA binding to ERR-γ preserves its basal constitutive activity.  It can also protect it from deactivation from the SERM 4-hydroxytamoxifen (afimoxifene).  This may be the mechanism by which BPA acts as a xenoestrogen .  Different expression of ERR-γ in different parts of the body may account for variations in bisphenol A effects. For instance, ERR-γ has been found in high concentration in the placenta , explaining reports of high bisphenol accumulation in this tissue.  BPA has also been found to act as an agonist of the GPER (GPR30).