Description

Hydroxyprogesterone caproate, also named 17α-Hydroxyprogesterone hexanoate, is a synthetic progestogen.  As a synthetic steroid hormone, that is similar to medroxyprogesterone acetate and megestrol acetate. It is an Off-White solid that is slightly soluble in chloroform and methanol. 

Synthetic routes

17a-hydroxyprogesterone (33 g) is added to chloroform (264 g), and then dropwise n-hexanoyl chloride (17.5 g) at 8-10°C. After that, the temperature is raised to 30-40°C and the reaction is kept at 30-40°C for 5 hours. HPLC detection 17a - hydroxyprogesterone content less than 0.5%, the acylation reaction is terminated. After the acylation reaction is over, the reaction solution is cooled to room temperature, and a 5% sodium carbonate aqueous solution is added dropwise to neutralize the reaction to generate hydrogen chloride and excess n-hexanoyl chloride until the pH=7 to complete the reaction. The mixture was filtered, washed with water, and dried in a vacuum to obtain crude progesterone caproate. Finally, the crude progesterone caproate was recrystallized with ethanol to obtain hydroxyprogesterone caproate. 

Uses

 Hydroxyprogesterone Caproate is a synthetic pregnancy agent. As a powerful, long-acting progestogen steroid ester, it converts the proliferative endothelium into a secretory endothelium and induces the development of breast ducts. It also exhibits mild estrogenic, androgenic, or corticosteroid effects. The drug 17-alpha hydroxyprogesterone caproate is an injectable synthetic progestin, which can prevent or delay preterm birth for women who have previously experienced preterm birth. It used to be an inexpensive combination drug, but now it's about 100 times more expensive. 

Although it is a relatively safe drug, it has some side effects. For example, pain, swelling, or itching at the injection site. Even hives, itching, nausea, or diarrhea in severe cases.

References

[1] Fried I, et al. Utilization, Cost, and Outcome of Branded vs Compounded 17-Alpha Hydroxyprogesterone Caproate in Prevention of Preterm Birth. JAMA Internal Medicine, 2017; 177: 1689-1690.

[2] Sibai B, et al. Safety review of hydroxyprogesterone caproate in women with a history of spontaneous preterm birth. Journal of Perinatology, 2020; 41: 718–725.

[3] Blackwell  S, et al. PROLONG Clinical Study Protocol: Hydroxyprogesterone Caproate to Reduce Recurrent Preterm Birth. American Journal of Perinatology, 2018; 35: 1228-1234.

[4] Hauspurg  A, et al. Evaluation of 17-alpha hydroxyprogesterone caproate efficacy. American Journal of Obstetrics and Gynecology, 2017; 218.