For example, beta-estrogen receptor-selective ligands may have differing effects on cognition than estradiol given the relatively higher concentration of estrogen receptor beta than alpha in

the hippocampus.178,179 Additionally, selective androgen receptor modulators (Selleckchem TSA HDAC SARM’s),180 selective estrogen receptor modulators (SFIRMs),181 and selective progesterone receptor modulators (SPRM’s)182,183 may display a more acceptable profile of long-term Inhibitors,research,lifescience,medical side effects (eg, lack of activity of S ARMs at the prostate180) and permit their use on a more chronic basis. Inhibitors,research,lifescience,medical A potential advantage of reproductive hormonal therapies over conventional antidepressants is suggested by studies reporting the medical sequelae of depression including disorders of metabolism, the musculoskeletal system, and the cardiovascular system.184,185

Given the strong association of some of these disorders with deficient or abnormal reproductive endocrine activity,33,186-188 reproductive therapies of depression Inhibitors,research,lifescience,medical might prevent or reverse some of the medical sequelae in addition to improving mood. Finally, effects of reproductive therapies on the vascular endothelium and local blood flow may contribute to therapeutic effects of these compounds (eg, estradiol Inhibitors,research,lifescience,medical or DHEA) in certain conditions where deficits in the vascular system are thought to mediate the primary mood problem, such Inhibitors,research,lifescience,medical as in the vascular depressions described in the late-onset mood disorders.189 Conclusions Compared with studies performed in the 1800s and to some extent the 1940s and 1950s, recent trials of reproductive endocrine

therapies in mood disorders in women have employed more selective pharmacologic Adenylyl cyclase compounds, more rigorous study designs, and in some studies more homogeneous patient samples. Despite improved methodologies, the effects of gonadal steroids on mood regulation remain inconsistently demonstrated. However, there are compelling data supporting a role for gonadal steroids (and reproductive endocrine modulators) in the treatment of depression in women. Future studies should be directed to better identify both the clinical predictors and the physiological mechanisms of the psychotropic efficacy of reproductive therapies.