Does the use of vaginal estrogen counteract or interfere with systemic testosterone therapy in transgender males?

Topical/vaginal estrogen does not have significant systemic absorption, so it does not affect free testosterone levels or increase steroid hormone-binding globulin. Only systemic/oral estrogen would affect testosterone therapy via those mechanisms.

No, vaginal estrogen will not interact with testosterone. It has only a tiny bit of systemic absorption, and the effects of testosterone are much more powerful. I would not expect a patient to experience any side effects or reduced masculinization from starting vaginal estrogen.

”Front hole” irritation is a frequently used gender-free term used to describe the irritation and discomfort that many trans-male or non-binary trans-masc individuals treated with testosterone experience from vaginal atrophy. Low-dose topical estrogen, either in cream or vaginal-tablet form, has a local effect to help address the pain, itching, burning, urinary urgency, and discomfort from intercourse that many people experience as a result of vaginal atrophy. I typically prescribe 10 mcg vaginal tablets to be used twice weekly.

Robert Gotfried DO FAAFP DACD
The Ohio State University Wexner Medical Center
Transgender Primary Care