17-Hydroxyprogesterone
From Wikipedia, the free encyclopedia
 17-hydroxyprogesterone |
|
| pregn-4-ene-3,20-dione,17hydroxy | |
| CAS number [68-96-2] |
|
| Empirical formula | C21H30O3 |
| Molecular weight | 330.22 |
| Bioavailability | |
| Metabolism | Liver |
| Elimination half life | |
| Excretion | |
| Pregnancy category | (USA), |
| Physical properties | |
| Melting point | 219-220°C |
| Specific rotation [α]D | |
17-Hydroxyprogesterone (17-OH progesterone or 17OHP) is a C-21 steroid hormone produced in the synthesis of glucocorticoids and sex steroids. It is derived from progesterone via 17-hydroxylase, a P450c17 enzyme, or from 17-hydroxypregnenolone via 3β-hydroxysteroid dehydrogenase/Δ5-4 isomerase. As a hormone, 17OHP also interacts with the progesterone receptor. 17-Hydroxyprogesterone is not the same compound as 17-hydroxyprogesterone caproate. 17-hydroxyprogesterone is a natural progestin and in pregnancy increases in the third trimester primarily due to fetal adrenal production. 17-hydroxyprogesterone caproate is a synthetic (artificial) hormone that is similar in structure to medroxyprogesterone acetate and megestrol acetate. The terminology is confusing because 17P is used both to refer to the natural hormone and the artificial/synthetic hormone. It is preferable to refer to the synthetic hormone as 17-OHPC.
This hormone is primarily produced in the adrenal glands and to some degree in the gonads, specifically the corpus luteum of the ovary. Normal levels are 3-90 ng/dl in children, and in women, 15-70 ng/dl prior to ovulation, and 35-290 ng/dl during the luteal phase.
[edit] Clinical use
Measurements of levels of 17-hydroxyprogesterone are useful in the evaluation of patients with suspected congenital adrenal hyperplasia as the typical enzymes that are defective, namely 21-hydroxylase and 11β-hydroxylase, lead to a build-up of 17OHP. In contrast, the rare patient with 17α-hydroxylase deficiency will have very low or undetectable levels of 17OHP. 17OHP levels can also be used to measure contribution of progestational activity of the corpus luteum during pregnancy as progesterone but not 17OHP is also contributed by the placenta.
The application of 17OHP has been shown to be useful to delay premature labor in pregnancy.[1] [2]
The use of 17-hydroxyprogesterone caproate in pregnancy to prevent preterm birth is not recommended without further study according to two authorities. 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" [reference 3: The Cochrane Database of Systematic Reviews 2006 Issue 1]. There was a similar conclusion from a review by Marc Keirse [reference 6: Keirse MJNC, Progesterone and Preterm; Birth, 2004, vol 31]. Three clinical studies of 250mg/week of i.m. 17-hydroxyprogesterone caproate have all shown a trend for an increase in pregnancy loss due to miscarriage compared to placebo [reference 4: Johnson 1975 New England Journal of Medicine, vol 293 (14) - reference 1: Yemini 1985 American Journal of Obstetrics and Gynecology, 151 - reference 2: Meis 2003 New England Journal of Medicine, vol 348 (24)]. A meta-analysis by Keirse [reference 5: 1990 British Journal of Obstetrics and Gynaecology, vol 97] showed a trend for an increase in miscarriage with 17-hydroxyprogesterone caproate compared to placebo. There has also been a study in rhesus monkeys [reference 7: Hendrickx 1987 Teratology vol 35] where all rhesus fetuses exposed to 1 and 10 times the human dose equivalent of 17-hydroxyprogesterone caproate died in utero. Currently (2006), 17-hydroxyprogesterone caproate is a category D progestin according to the FDA (evidence of fetal harm). There is speculation that the castor oil in the 17-hydroxyprogesterone caproate formulation may not be beneficial for pregnancy [references 8: 2003, Duke University Medical Center, New England Journal of Medicine, correspondence, vol 349 and reference 9: Hauth 1983, Amercican Journal of Obstetrics and Gynecology, vol 146(2)].
[edit] References
- ^ Yemini M, Borenstein R, Dreazen, et al. Prevention of premature labor by 17 alpha-hydroxyprogesterone caproate. Am J Obstet Gynecol. 1985;151(5):574-7.PMID 3976757.
- ^ Meis PJ; Society for Maternal-Fetal Medicine. 17 hydroxyprogesterone for the prevention of preterm delivery. Obstet Gynecol. 2005;105:1128-35.PMID 15863556.
3. Dodd JM, Flenady V, Cincotta R, Crowther CA; The Cochrane Database of Systematic Reviews 2006 Issue 1
4. Johnson JWC, Austin KL, Jones GS, Davis GH, King TM. Efficacy of 17 alpha-hydroxyprogesterone caproate in the prevention of premature labor. NEJM 1975 October. 293(14):675.
5. Keirse MJNC, Progestogen administration in pregnancy may prevent preterm delivery. Br J Obstet Gynecol 1990 February; 97:149.
6. Keirse MJNC. Progesterone and Preterm: Seventy Years of "Deja vu" or "Still tTo Be Seen"?. Birth, 2004 September; 31:3.
7. Hendrixckx AG, et al. Embriotoxicity of sex steroidal hormones in nonhuman primates: II. Hydroxyprogesterone caproate, estradiol valerate. Teratology 1987 February. 35 (1): 129.
8. Duke University Medical Center, New England Journal of Medicine, correspondence, vol 349
9. Hauth JC, Gilstrap LC, Brekken AL, Hauth JM. The effect of 17 alpha-hydroxyprogesterone caproate on pregnancy outcome in an active-duty military population. Am J Obstet Gynecol. 1983 May; 146(2): 187.
