Transgender

not all HRT, just progesterone, and because other routes of administration don't make sense. See: Oral Progesterone Achieves Very Low Levels of Progesterone and Has Only Weak Progestogenic Effects

Abstract / TL;DR

Oral progesterone is the most widely used form of progesterone in transfeminine hormone therapy. Because of previous studies using inaccurate blood tests (immunoassays without adequate chromatographic purification), it was thought that typical therapeutic dosages of oral progesterone produced progesterone levels that reached typical luteal-phase levels in cisgender women (which range from about 7 to 22 ng/mL). However, newer studies using more accurate blood tests (immunoassays with adequate purification and mass spectrometry-based assays) have shown that 100 mg/day progesterone—with or without food—achieves very low peak progesterone levels of only about 2 to 3 ng/mL and average progesterone levels over 24 hours of only about 0.1 to 0.6 ng/mL. In accordance, oral progesterone has often shown only weak progestogenic effects in clinical studies. Higher doses of oral progesterone that might achieve better levels are limited by persistingly low progesterone levels, pronounced neurosteroid side effects caused by the first pass of progesterone through the liver, and substantial variability between individuals. While the progesterone levels with oral progesterone are apparently sufficient for endometrial protection in cisgender women, they are unlikely to be adequate for desired effects in transfeminine people. For these reasons, transfeminine people and their clinicians may wish to avoid oral progesterone if the aim is therapeutic progestogenic effects. Instead, non-oral forms of progesterone with greater bioavailability like rectal or injectable progesterone can be used. Alternatively, progestins, which are likewise fully effective progestogens, can be employed.