However, subcutaneous pellet implants of progesterone were later studied as a form of birth control in women in the 1980s and early 1990s, though no preparations were ultimately marketed.Aqueous suspensions of progesterone crystals for intramuscular injection were first described in 1944. These preparations were on the market in the 1950s under a variety of brand names including Flavolutan, Luteosan, Lutocyclin M, and Lutren, among others. Aqueous suspensions of steroids were developed because they showed much longer durations than intramuscular injection of steroids in oil solution. However, local injection site reactions, which do not occur with oil solutions, have limited the clinical use of aqueous suspensions of progesterone and other steroids. Today, a preparation with the brand name Agolutin Depot remains on the market in the Czech Republic and Slovakia. A combined preparation of progesterone, estradiol benzoate, and lidocaine remains available with the brand name Clinomin Forte in Paraguay as well. In addition to aqueous suspensions, water-in-oil emulsions of steroids were studied by 1949, and long-acting emulsions of progesterone were introduced for use by intramuscular injection under the brand names Progestin and Di-Pro-Emulsion (with estradiol benzoate) by the 1950s. Due to lack of standardization of crystal sizes, crystalline suspensions of steroids had marked variations in effect.
The preparation was originally developed in 1986 by a compounding pharmacy called Madison Pharmacy Associates in Madison, Wisconsin in the United States. Vaginal, rectal, and uterine
Vaginal progesterone suppositories were first studied in women by Robert Greenblatt in 1954. Shortly thereafter, vaginal progesterone suppositories were introduced for medical use under the brand name Colprosterone in 1955. Rectal progesterone suppositories were first studied in men and women by Christian Hamburger in 1965. Vaginal and rectal progesterone suppositories were introduced for use under the brand name Cyclogest by 1976. Vaginal micronized progesterone gels and capsules were introduced for medical use under brand names such as Utrogestan and Crinone in the early 1990s. Progesterone was approved in the United States as a vaginal gel in 1997 and as a vaginal insert in 2007. A progesterone contraceptive vaginal ring known as Progering was first studied in women in 1985 and continued to be researched through the 1990s. It was approved for use as a contraceptive in lactating mothers in Latin America by 2004. A second progesterone vaginal ring known as Fertiring was developed as a progesterone supplement for use during assisted reproduction and was approved in Latin America by 2007.Development of a progesterone-containing intrauterine device (IUD) for contraception began in the 1960s. Incorporation of progesterone into IUDs was initially studied to help reduce the risk of IUD expulsion. However, while addition of progesterone to IUDs showed no benefit on expulsion rates, it was unexpectedly found to induce endometrial atrophy.