Estradiol's efficacy seems to vary widely with the person and the particular vehicle: I was on transdermal patches for two years ( , 2 patches changed twice weekly – considered a "high" dose of 17-beta estradiol), and my levels mostly stayed around 100 pg/mL, and I needed 100mg spironolactone daily to keep my testosterone down. When I switched to injections of Estradiol Valerate, as I was "titrating up" my testosterone was unmeasurably low at the same E2 level my patches were delivering. (I had decided to drop spiro at the same time due to it's side effects: for me it seemed to be fogging my brain and inducing suicidal ideation.) Increasing the dosage had the effect of adding a cup-size to my breasts after about two months of injections, after two years of HRT, at age 53 and with b-cup breasts already. This story is not unusual in the community, and it led me to try this form of HRT.
More recently, androgen receptors have been shown to have a second mode of action. As has been also found for other steroid hormone receptors such as estrogen receptors , androgen receptors can have actions that are independent of their interactions with DNA.   Androgen receptors interact with certain signal transduction proteins in the cytoplasm. Androgen binding to cytoplasmic androgen receptors can cause rapid changes in cell function independent of changes in gene transcription, such as changes in ion transport . Regulation of signal transduction pathways by cytoplasmic androgen receptors can indirectly lead to changes in gene transcription, for example, by leading to phosphorylation of other transcription factors.