Advances in progesterone delivery systems: Still work in progress?

[Display omitted] Progesterone is a natural steroidal sex hormone in the human body, mainly secreted through the adrenal cortex, ovary, and placenta. In humans, progesterone is essential for endometrium transformation in the uterus at the time of ovulation and maintenance of pregnancy. When the body cannot produce enough progesterone for specific ailments, it is administered via different routes such as oral, vaginal, transdermal, topical, parental, and intranasal routes. Although progesterone is commercially available in multiple conventional formulations, low solubility, less permeability and extensive hepatic first-pass metabolism are the major constraints to its delivery. These challenges can be overcome substantially by formulating progesterone into novel delivery systems like lipid carriers, polymeric carriers, hydrogels, several nanocarriers, depot and controlled release systems. Various research papers and patents have been published in the last two decades on progesterone delivery systems; clinical studies were conducted to establish safety and efficacy. This review is focused on the pharmacodynamic and pharmacokinetic parameters of progesterone, its delivery constraints, and various advanced delivery systems of progesterone.