Abstract
Introduction:
Gestational hypertension remains one of the main causes of maternal deaths all over the world. Attempts to reduce/prevent the incidence had failed due to lack of understanding of the disease’s aetiology. One of the early roles of natural progesterone in the first trimester of pregnancy is to promote formation of wide-calibre spiral vessels that invade into the myometrial layer of the gravid uterus. Theoretically, this will prevent or reduce the incidence of gestational hypertension in the latter half of the pregnancy.
Review:
The progestogen, dydrogesterone, has similar molecular structure and properties to natural progesterone. A pilot study was undertaken on primigravidae, who have higher risk of developing gestational hypertension. They were supplemented with dydrogesterone in the first trimester (Study Group) and compared with a similar number of primigravidae (Control Group) without supplementation with the progestogen. The incidence of gestational hypertension was significantly lower in the Study Group as compared to the Control Group (1.7% vs. 12.9%, respectively, p<0.001). The incidence of foetal distress was also significantly lower in the Study Group compared to the Control Group (4.3% vs. 18.1%, respectively, p<0.001).
Conclusion:
Supplementation of the progestogen, dydrogesterone, in the first trimester to primigravidae has shown great potential in reducing or preventing the incidence of gestational hypertension.
References
1. Draycott T, Lewis G, Stephens I. Executive summary, Centre for Maternal and Child Enquiries (CMACE). Br J Obstet Gynaecol 2011;118(Suppl 1):e12–21.Search in Google Scholar
2. Khan KS, Wojdyla D, Say L, Gulmezoglu M, Van Look PF. WHO analysis of causes of maternal deaths: a systematic review. Lancet 2006;367:1066–74.10.1016/S0140-6736(06)68397-9Search in Google Scholar
3. Repke JT, Robinson JN. The prevention and management of pre-eclampsia and eclampsia. Int J Gynaecol Obstet 1998;62:1–9.10.1016/S0020-7292(98)00082-4Search in Google Scholar
4. Hofmeyr GJ, Atallah AN, Duley L. Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems. Cochrane Database of Systematic Reviews 2006; Issue 3. Art No. CD; DOI: 10.1002/14651858. CD 001059.pub2.10.1002/14651858Search in Google Scholar
5. Zainul Rashid MR, Lim JF, Nawawi NH, Luqman M, Zolkeplai MF, Rangkuty HS, Mohamad Nor NA, Tamil A, Shah SA, Tham SW, Schindler AE. A pilot study to determine whether progestogen supplementation during the first trimester will reduce the incidence of gestational hypertension in primigravidae. Gynecol Endocrinol 2014;30:217–20.10.3109/09513590.2013.860960Search in Google Scholar PubMed
6. Zhou Y, Damsky CH, Fisher SJ. Preeclampsia is associated with failure of human cytotrophoblasts to mimic a vascular adhesions phenotype. One cause of defective endovascular invasion in this syndrome? J Clin Invest 1997;99:2152–64.10.1172/JCI119388Search in Google Scholar PubMed PubMed Central
7. Meekins JW, Pijnenborg R, Hanssens M, McFadyen IR, Vanasshe A. A study of placental bed spiral arteries and trophoblast invasion in normal and severe pre-eclamptic pregnancies. Br J Obstet Gynaecol 1994;101:669–74.10.1111/j.1471-0528.1994.tb13182.xSearch in Google Scholar PubMed
8. Orange SJ, Painter D, Horvath J, Yu B, Trent R, Hennessy A. Placental endothelial nitric oxide synthase localization and expression in normal human pregnancy and pre-eclampsia. Clin Exp Pharmacol Physiol 2003;30:376–81.10.1046/j.1440-1681.2003.03844.xSearch in Google Scholar PubMed
9. Schindler AE. Immunology and progestins in pregnancy. Gynecol Endocrinol 1999;13:47–50.10.1080/gye.13.s4.47.50Search in Google Scholar PubMed
10. Schindler AE. Endocrinology of pregnancy: consequences for the diagnosis and treatment of pregnancy disorders. J Steroid Biochem Mol Biol 2005;97:386–8.10.1016/j.jsbmb.2005.08.006Search in Google Scholar PubMed
11. Wardell SE, Edwards DP. Mechanisms controlling agonist and antagonist potential of selective progesterone receptor modulators (SPRMs). Semin Reprod Med 2005;23:9–21.10.1055/s-2005-864030Search in Google Scholar PubMed
12. Goldman-Wohl D, Yagel S. NK cells and pre-eclampsia. Reprod Biomed Online 2008;16:227–31.10.1016/S1472-6483(10)60578-0Search in Google Scholar
13. Roberts JM, Cooper DW. Pathogenesis and genetics of pre-eclampsia. Lancet 2001;357:53–6.10.1016/S0140-6736(00)03577-7Search in Google Scholar
14. Waught JS, Smith MC. Hypertensive disorders. In: Edmonds DK, editor, Dewhurst textbook of obstetrics & gynaecology – 8th ed. West Sussex, UK: John Wiley & Sons Ltd., 2012:101–10.10.1002/9781119979449.ch11Search in Google Scholar
15. Huppertz B. Placental origins of pre-eclampsia: challenging the current hypothesis. Hypertension 2008;51:970–5.10.1161/HYPERTENSIONAHA.107.107607Search in Google Scholar
16. Pijnenborg R, Vercruysse L, Hanssens M. The uterine spiral arteries in human pregnancy: facts and controversies. Placenta 2006;27:939–58.10.1016/j.placenta.2005.12.006Search in Google Scholar
17. Sammour MB, el-Kabarity H, Fawzy MM, Schindler AE. Prevention and treatment of pregnancy-induced hypertension (preeclampsia) with progestogens. J Steroid Biochem Mol Biol 2005;97:439–40.10.1016/j.jsbmb.2005.08.014Search in Google Scholar
18. Sibai BM. Diagnosis and management of gestational hypertension and preeclampsia. Obstet Gynecol 2003;102:181–92.10.1016/S0029-7844(03)00475-7Search in Google Scholar
19. Colombo D, Ferraboschi P, Prestileo P, Toma L. A comparative molecular modeling study of dydrogesterone with other progestational agents through theoretical calculations and nuclear magnetic resonance spectroscopy. J Steroid Biochem Mol Biol 2006;98:56–62.10.1016/j.jsbmb.2005.07.009Search in Google Scholar
20. Schindler AE. Progestational effects of dydrogesterone in vitro, in vivo and on the human endometrium. Maturitas 2009;65:S3–11.10.1016/j.maturitas.2009.10.011Search in Google Scholar
21. Daya S. Luteal Support: progestogens for pregnancy protection. Maturitas 2009;65:S29–34.10.1016/j.maturitas.2009.09.012Search in Google Scholar
22. Young BC, Levine RJ, Karumanchi SA. Pathogenesis of preeclampsia. Annu Rev Pathol Mech Dis 2010;5:173–92.10.1146/annurev-pathol-121808-102149Search in Google Scholar
23. Lee CJ, Hsieh TT, Chiu TH, Chen KC, Lo LM, Hung TH. Risk factors for pre-eclampsia in an Asian population. Int J Gynecol Obstet 2000;70:327–33.10.1016/S0020-7292(00)00240-XSearch in Google Scholar
©2016 Walter de Gruyter GmbH, Berlin/Boston