Injections of estradiol alone yield high enough levels of E so that gonads are arrested and stop producing androgen. Hence, there should, theoretically, be no need for any anti-androgen while taking E parenterally. It appears that in the case of estradiol valerate, 2 weeks might too long of an interval so that one may experience lows, similar to PMS. Most do well on 5-10 day schedule.
LhRH agonists are preferred in the UK due to better side-effect profile while Spiro is used in the US because CPA (cyproterone acetate) is banned there. CPA can stimulate prolactin far too much and potentially lead to a prolactinoma (also meningioma, at higher doses), lead to depression/fatigue in some, interfere with adrenal function, and cause liver problems at very high doses. Spironolactone, on the other hand, can result in electrolyte imbalance and all the effects from that.
Regarding bicalutamide:
Expert Opin. Drug Saf. (2014) 13(11)
"Diarrhea has been reported in only 2 - 6% of patients in
Bicalutamide monotherapy studies [29-31,43,44] and only isolated
cases of elevated liver enzymes were observed [67]. To
date, only one case of Bicalutamide-induced hepatic failure
has been reported in the literature [68]. This hepatic failure
was attributed to Bicalutamide because of the absence of other
etiologic factors, the temporal relation with drug administration
and the resolution of hepatitis following drug discontinuation
[68]. However, the authors note that the patient was
previously treated with Cyproterone and Flutamide and
hypothesize that these drugs might have sensitized the patient
to Bicalutamide toxicity [68]."
"Interstitial pneumonitis induced by Bicalutamide is an
extremely rare event [69]."
"Finally, caution is required when Bicalutamide is used
together with other medications that depend on CYP3A4
and, to a lesser extent, CYP2C9, 2C19 and 2D6 metabolization
[70]. Moreover, the use of Bicalutamide as well as of
Nilutamide or Flutamide in patients taking drugs with high
plasma protein binding such as warfarin, phenytoin or theophylline,
will increase the free-drug serum concentration of
these compounds, which might result either in increased
efficacy or in increased toxicity of these drugs [71]."
It should be noted that these effects are reported in men who typically take higher doses than those typically prescribed to transsexual women.
