Background
Transgender people experience an incongruence between their sex assigned at birth and their gender identity. In the Netherlands, it is estimated that 1:2,800 birth-assigned males and 1:5,200 birth-assigned females undergo or have undergone gender-affirming treatment [Progesterone is the natural ligand of the progesterone receptor (PR). In both cisgender (alignment of sex as-signed at birth and gender identity) men and women progesterone is synthesized in the adrenal glands and in pre-menopausal cisgender women the primary source is in the ovaries. The estrogen receptors and progesterone receptor (PR) are expressed in many tissues in the human body and regulate gene expression and cell differentiation. In addition to estradiol, progesterone has an important role in mammary and breast development during female puberty: Estradiol stimulates the expansion of breast tissue and progesterone stimulates differentiation of the mammary tissue [Only few studies have addressed the effect of addition of the progestin medroxyprogesterone acetate (MPA) to estradiol (and anti-androgen) treatment in transgender women: In a small group of transgender women, no differences in breast size were observed relative to transgender women receiving estrogens only [This study aims to explore the effects of addition of progesterone to estradiol treatment and increasing estradiol doses on breast volume with regard to breast size in transgender women. Secondary objectives include assessment of the effects of progesterone combined with estradiol on satisfaction with breast volume, mood and sleep quality, sexual pleasure, side effects of the treatment regimen, as well as serum progesterone concentrations.