Breast cancer is the most commonly diagnosed cancer and the most common cause of cancer death among women. Hormones have been shown to have a key role in breast development and carcinogenesis. Repeated activation of progesterone receptor (PR) signaling as it occurs during menstrual cycles is important in cancer risk. Through hormonal contraception many women are exposed to synthetic PR agonists, progestins, either on their own or in combination with the synthetic estrogen receptor (ER) agonist, ethinyl estradiol (EE). Progestins vary in their chemical structures and biological activities. Epidemiological studies show that hormonal contraceptions increase the risk of breast cancer but to date there have been few studies that analyze specific progestins regarding the breast cancer risk they confer. We hypothesized that different progestins have distinct abilities to induce cell proliferation and to modulate gene expression in the breast epithelium and this may ultimately have different effects on breast cancer risk. To test the hypothesis that different progestins currently used in hormonal contraceptions in Switzerland have distinct abilities to induce the expression of important mediators of PR action, receptor activator of NF-κB ligand (RANKL) and Wnt4, we employed mouse mammary gland organoids and human breast tissue microstructures. We find that androgenic progestins strongly induce RANKL and Wnt4 whereas anti-androgenic progestins fail to do so. To test the ability of different progestins currently used in hormonal contraceptions in Switzerland to induce cell proliferation in human breast epithelium, we humanized mouse mammary gland using intraductal injection of human breast epithelial cells obtained from reduction mammoplasty surgery. We show that breast epithelial cells maintain hormone receptor expression and remain hormone responsive in this approach. We find that the androgenic progestins, Gestodene and Levonorgestrel, promote cell proliferation over two months more than progesterone. Furthermore, we show that Androgen receptor (AR) inhibition abrogates promegestone-induced RANKL induction and reduces cell proliferation induced by androgenic progestin, LNG. We also show that activation of AR signaling through DHT exposure is sufficient to induce proliferation of human breast epithelial cells. Thus, different progestins have different biological effects on the breast epithelium that appear to be related to their androgenic activities.