Great question Tada. That paper I cited throughly explored this topic of sexual dimorphism in hepatic FMO3 mRNA and plasma TMAO levels in mice, but also did a few human analyses too. In mice, there is a HUGE sexual dimorphic difference in hepatic FMO3 mRNA levels. Female mice have 100 to 500 times higher expression of the FMO3 mRNA in liver than male mice. Differences in mRNA levels don't always correlate with differences in protein levels/enzyme activity. Indeed, despite the HUGE liver FMO3 mRNA difference between female and male mice, the total measured FMO enzyme activity in a liver homogenate was only about 5-fold higher in female mice than in male mice. Similarly, the plasma TMAO levels were only about 5-fold higher in female mice than in male mice. They further explored this sexual dimorphism in mice by removing the gonads (ovaries in females, testes in males) and showed clear, convincing evidence that androgens (i.e. testosterone) strongly suppress FMO3 mRNA levels and that estrogen modestly increases FMO3 mRNA levels. They also clearly show that FXR activation by bile acids increases FMO3 mRNA levels. So there seem to be both hormonal (sex hormones) and metabolite (bile acids) control mechanisms for hepatic FMO3 expression. However, in the human samples they analyzed, female liver FMO3 mRNA levels were only 2 to 3 times higher than levels in males. They didn't measure FMO activity in human liver, but they did measure plasma TMAO levels in humans and there was no difference between the male and female human samples they tested.

Now, it is easy to control for genetics and diet in mice. Most labs use inbred mice that have no genetic variability and the mice all eat the same diet (whatever the investigator chooses to feed them). It is not so easy to control for genetics and diet in humans. Nonetheless, the modest difference in humans between males and females for hepatic FMO3 mRNA, combined with the lack of evidence for circulating TMAO levels being different between human males and females, suggests that there isn't too much of a physiologically relevant sexual dimorphism for FMO3/TMAO in humans. 

Long story short.....there is no evidence at this time that apabetalone works better in one sex versus another, in my opinion.

BearDownAZ