Hydroxyprogesterone caproate

Hydroxyprogesterone caproate (OHPC), sold under the brand names Proluton and Makena among others, is a progestin medication which is used to prevent preterm birth in pregnant women with a history of the condition and to treat gynecological disorders. It has also been formulated in combination with estrogens for various indications (brand names Gravibinon and Primosiston) and as a form of long-lasting injectable birth control (brand name Chinese Injectable No. 1). It is not used by mouth and is instead given by injection into muscle or fat, typically once per week to once per month depending on the indication.OPPTIMUM strongly suggests that the efficacy of progesterone in improving outcomes is either non-existent or weak. Given the heterogeneity of the preterm labour syndrome we cannot exclude benefit in specific phenotypic or genotypic subgroups of women at risk. However, the subgroups of women who might benefit do not appear to be easily identifiable by current selection strategies, including cervical length measurement and fibronectin testing. Hydroxyprogesterone caproate (OHPC), sold under the brand names Proluton and Makena among others, is a progestin medication which is used to prevent preterm birth in pregnant women with a history of the condition and to treat gynecological disorders. It has also been formulated in combination with estrogens for various indications (brand names Gravibinon and Primosiston) and as a form of long-lasting injectable birth control (brand name Chinese Injectable No. 1). It is not used by mouth and is instead given by injection into muscle or fat, typically once per week to once per month depending on the indication. OHPC is generally well-tolerated and produces few side effects. Injection site reactions such as pain and swelling are the most common side effect of OHPC. The medication may increase the risk of gestational diabetes when used in pregnant women. OHPC is a progestin, or a synthetic progestogen, and hence is an agonist of the progesterone receptor, the biological target of progestogens like progesterone. It has some antimineralocorticoid activity and no other important hormonal activity. The medication shows a number of differences from natural progesterone. OHPC was discovered in 1953 and was introduced for medical use in 1954 or 1955. It was marketed in the United States under the brand name Delalutin and throughout Europe under the brand name Proluton. The medication was discontinued in the United States in 1999. However, OHPC was subsequently reintroduced in the United States under the brand name Makena for the treatment of preterm birth in 2011. Due to a greatly increased price, a pricing controversy occurred in this country. OHPC was previously available at low cost from compounding pharmacies in the United States, but this became prohibited in 2016. The use of OHPC in pregnancy to prevent preterm birth in women with a history of preterm delivery between 20 weeks and 36 weeks and 6 days is supported by the Society of Maternal Fetal Medicine Clinic Guidelines put out in May 2012 as Level I and III evidence, Level A recommendation. Level I evidence refers to a properly powered randomized controlled trial, and level III evidence is support from expert opinion, while a Level A recommendation confers that the recommendation is made based on good and consistent scientific evidence. OHPC 250 mg IM weekly preferably starting at 16–20 weeks until 36 weeks is recommended. In these women, if the transvaginal ultrasound cervical length shortens to <25 mm at < 24 weeks, cervical cerclage may be offered. In the 2013 study the guideline recommendation is based on, there was also a significant decrease of neonatal morbidity including lower rates of necrotizing enterocolitis (0 in the treatment group vs 4 in the control), intraventricular hemorrhage (4 in the treatment group compared with 8 in the control for a relative risk of 0.25), and need for supplemental oxygen (14% in the treatment group vs 24% in the placebo for a relative risk of 0.42). Furthermore, this study contained 463 women, 310 of whom received injection. Of these women, 9 had infants with congenital malformations (2%), but there was no consistent pattern and none involved internal organs. OHPC is currently (as of June 2014) pregnancy category B, meaning there is no evidence of fetal risk with use of this medication during pregnancy. Although this is now the recommendation, this has not always been the case. A 2006 Cochrane Review concluded '...important maternal and infant outcomes have been poorly reported to date... information regarding the potential harms of progesterone therapy to prevent preterm birth is limited'. There was a similar conclusion from a review by Marc Keirse of Flinders University. Three clinical studies in singleton pregnancies of 250 mg/week of intramuscular OHPC have all shown a trend for an increase in pregnancy loss due to miscarriage compared to placebo. One of them, a large National Institutes of Health (NIH) study in 2003, looked at the effect of OHPC injections in women at risk for repeat premature birth and found that the treated group experienced premature birth in 37% versus 55% in the controls. A follow-up study of the offspring showed no evidence that OHPC affected the children in the first years of life. Based on these NIH data, OHPC was approved by the Food and Drug Administration (FDA) in 2011 as a medication to reduce the risk of premature birth in selected women at risk. (v.i.) The FDA expressed concern about miscarriage at the 2006 advisory committee meeting; the committee voted unanimously that further study was needed to evaluate the potential association of OHPC with increased risk of second trimester miscarriage and stillbirth. A toxicology study in rhesus monkeys resulted in the death of all rhesus fetuses exposed to 1 and 10 times the human dose equivalent of OHPC. As of 2008, OHPC was a category D progestin according to the FDA (that is, there is evidence of fetal harm). There is speculation that the castor oil in the OHPC formulation may not be beneficial for pregnancy. Of note, the above-mentioned NEJM study by Meirs et al. compares the effect of OHPC (with the castor oil component) to castor oil injection as the placebo. A study published in February 2016 in The Lancet stated the below, amongst other findings: The journal reviewer Richard Lehman, senior Research Fellow at the Department of Primary Health Care at the University of Oxford, made the following notable commentary on the OPPTIMUM study: 'That's it. This story is ended, and nobody need ever use vaginal progesterone again to prevent preterm birth.' OHPC is used in the treatment of threatened miscarriage, gynecological disorders such as dysmenorrhea, premenstrual syndrome, fibrocystic breast disease, adenosis, and breast pain. In addition, OHPC is used in the treatment of endometrial cancer and has been found to be significantly effective in extending life in both premenopausal and postmenopausal women with the disease. The medication was used widely in the 1950s through the 1970s for such indications, but OHPC more recently has received the most attention in the prevention of preterm birth.