Progesterone is a compound that has high structural similarity to testosterone, and therefore can use the same enzymes (5 alpha – Reductase), and bind to the androgen receptor. Some progestins (synthetic progesterone) have inherent estrogenic as well as androgenic effects. Although progesterone binds to its own intracellular transcription receptor, it has affinity to the androgen receptor, which renders it able to act as an androgen or as an antiandrogen.
Progesterone is a potent inhibitor of 5 alpha – Reductase activity and androgen receptor binding. 5 alpha – Reductase is the enzyme responsible for the metabolism of testosterone to DHT. Compared to testosterone, DHT binds the androgen receptor with five times the tenacity of testosterone and is more potent in its ability to cause downstream activation.
Progesterone also inhibits the formation of 5 metabolites from androstenedione. Progesterone is rapidly metabolized in most tissues (including skin) to relatively nonandrogenic substances. One milliliter of a 2 percent solution applied topically twice daily appears to be well tolerated in women, but higher doses lead to menstrual irregularities.
Topical progesterone has been utilized widely, but has not been thoroughly tested in clinical studies. One study undertaken to ascertain the efficacy of the compound used topical progesterone (concentration and vehicle unnamed) for 10 to 48 months in 12 men, in the age group 18 to 39 years, with male pattern baldness. None of the subjects grew hair: 6 of them developed further thinning, and the other 6 had the same hair density.
A “positive” response was documented in 14 patients who were treated with topical 11alpha – hydroxyprogesterone, 15 mL of a 0.5 percent solution applied twice daily to the scalp for 2.4 to 4 years.
A 12-month study of 1% 11 alpha – hydroxyprogesterone lotions in 18 young men with androgenetic alopecia was performed. The 11 alpha – hydroxyprogesterone treated group had increased numbers of anagen hairs in the treated scalp, and 9 of 10 had improvement. There was a decrease in anagen hairs and worsening hair loss in 7 of the 8 controls.
Overall, topical progesterone has not been found to be of great value in treating androgenetic alopecia, but it can have a limited positive effect for some people.