The first birth control pills to be introduced were a noretynodrel-containing product in 1957 and a norethisterone-containing product in 1963, followed by numerous others containing a diversity of progestins. Progesterone itself has never been introduced for use in birth control pills.More modern clinical studies of oral progesterone demonstrating elevated levels of progesterone and end-organ responses in women, specifically progestational endometrial changes, were published between 1980 and 1983. Up to this point, many clinicians and researchers apparently still thought that oral progesterone was inactive. It was not until almost half a century after the introduction of progesterone in medicine that a reasonably effective oral formulation of progesterone was marketed. Micronization of progesterone and suspension in oil-filled capsules, which allowed progesterone to be absorbed several-fold more efficiently by the oral route, was first studied in the late 1970s and described in the literature in 1982. This formulation, known as oral micronized progesterone (OMP), was then introduced for medical use under the brand name Utrogestan in France in 1982. Subsequently, oral micronized progesterone was introduced under the brand name Prometrium in the United States in 1998. By 1999, oral micronized progesterone had been marketed in more than 35 countries. In 2019, the first combination of oral estradiol and progesterone was introduced under the brand name Bijuva in the United States.A sustained-release (SR) formulation of oral micronized progesterone, also known as "oral natural micronized progesterone sustained release" or "oral NMP SR", was marketed in India in 2012 under the brand name Gestofit SR. Many additional brand names followed.
This led in 1976 to the development and introduction of Progestasert, a progesterone-containing product and the first progestogen-containing IUD. Unfortunately, the product had various problems that limited its use. These included a short duration of efficacy of only one year, a high cost, a relatively high 2.9% failure rate, a lack of protection against ectopic pregnancy, and difficult and sometimes painful insertions that could necessitate use of a local anesthetic or analgesic. As a result of these issues, Progestasert never became widely used, and was discontinued in 2001. It was used mostly in the United States and France while it was marketed. Transdermal and topical
A topical gel formulation of progesterone, for direct application to the breasts as a local therapy for breast disorders such as breast pain, was introduced under the brand name Progestogel in Europe by 1972. No transdermal formulations of progesterone for systemic use have been successfully marketed, in spite of efforts of pharmaceutical companies towards this goal. The low potency of transdermal progesterone has thus far precluded it as a possibility. Although no formulations of transdermal progesterone are approved for systemic use, transdermal progesterone is available in the form of creams and gels from custom compounding pharmacies in some countries, and is also available over-the-counter without a prescription in the United States. However, these preparations are unregulated and have not been adequately characterized, with low and unsubstantiated effectiveness.