Tibolone has tissue -selective estrogenic effects, with desirable effects in bone , the brain , and the vagina , and lack of undesirable action in the endometrium and breasts .  Its tissue selectivity is the result of metabolism , enzyme modulation (., of estrogen sulfatase and estrogen sulfotransferase ), and receptor modulation that vary in different target tissues, and differs mechanistically from that of selective estrogen receptor modulators (SERMs) such as tamoxifen , which produce their tissue selectivity via means of modulation of the ER.   As such, to distinguish it from SERMs, tibolone has been described as a "selective tissue estrogenic activity regulator" (STEAR),  and also as a "selective estrogen enzyme modulator" (SEEM). 
In one small scale clinical trial of depressed patients, an improvement of symptoms which included anxiety, lack of drive and desire was observed.  In patients with dysthymia , unipolar , and bipolar depression significant improvement was observed.  In this series of studies, mesterolone lead to a significant decrease in luteinizing hormone and testosterone levels.  In another study, 100 mg mesterolone cipionate was administered twice monthly.  With regards to plasma testosterone levels, there was no difference between the treated versus untreated group, and baseline luteinizing hormone levels were minimally affected. 
A psychopharmacological profile of mesterolone, an androgen and potential antidepressant drug, was tested in mice and rats. Given in a dose of 80 mg/kg ip, mesterolone potentiated the action of L-DOPA in mice and in doses 40 and 80 mg/kg ip potentiated the amphetamine stereotypy in rats. On the other hand, in doses of 20--80 mg/kg ip mesterolone did not affect the reserpine induced hypothermia and ptosis, did not antagonize the apomorphine induced hypothermia in mice, did not change the motor stimulation produced by amphetamine and did not affect the spiperone induced catalepsy in rats. Mesterolone did not affect the head twitch response after 5-hydroxytryptophan in mice and was inactive in the behavioral despair test in rats. The results indicate that the psychopharmacological profile of mesterolone only slightly resembles the profile of classical imipramine-like anti-depressants.