Effect of isosorbide dinitrate, verapamil, and labetalol on portal pressure in cirrhosis
BMJ (Clinical Research Edition)
BRITISH MEDICAL JOURNAL VOLUME 291 31 AUGUST 1985 561 phase" there were no method failures, but a progestogen was given with or without an oestrogen every two to three months to induce vaginal bleeding. Galactorrhoea was induced in all but four of the women, and drowsiness and sedation were common. In this study we found that the combination of a progestogen with a dopamine receptor blocker was more effective than either drug given alone. This may be because sulpiride, by sensitising the
... lamicpituitary axis, rendered the action of norethisterone more effective. This combination may offer a new approach to contraception, and it may be possible to reduce the doses of both the dopamine antagonist and the progestogen considerably while still retaining a satisfactory contraceptive effect. It must be remembered that the progestogen only pill contains less progestogen than the combined pill, and a further reduction in progestogen content would be desirable after the doubts raised about its safety.'4 Thus it may be possible to overcome the traditional problems of poor control of cycles and reduced effectiveness associated with progestogen only contraception. Reduction in dosage may reduce or eliminate the side effects associated with this combination, although the drugs were on the whole well tolerated. Another potential use of this approach of combining the progestogen only pill with a dopamine antagonist would be its use during lactation. Badraoui and Hefnawi used sulpiride as a contraceptive with some apparent success during lactation. 15 An improved supply of milk during lactation has been reported with administration of sulpiride,'6 and a treatment regimen that acted as both a galactagogue and a contraceptive would be highly attractive. Because sulpiride is transferred in the breast milk its widespread use in lactating women cannot be recommended until more is known about its effects on the nursing infant. Further studies are required to determine the optimum dosage regimen and the possible side effects of this potentially promising new approach to contraception. References 1 Graham S, Fraser IS. The progestogen-only mini-pill. Contraception 1982;26:373-88. 2 Baird DT, McNeilly AS, Sawers RS, Sharpe RM. Failure of estrogen induced discharge of luteinizing hormone in lactating women. 3'ournal of Clinical Endocrinology and Metabolism 1979;49:500-90. 3 Delvoye P, Taubert H-D, Jurgensen 0, et al. Evolution des gonadtrophines et de la progesterone seriques au cours d'une hyperprolactinemie induite par le sulpride (Dogtnatil) pendant la phase luteale du cycle menstruel. Compies Rendus Hebdomadaires des Seances de l'Academie des Sciences 1974;279, serie D: 1463-6. 4 Buvat J, Decroix-Blacker C, Legal F, Gasnault JP. Mille mois de contraception par le sulpride. Revue Fran,aise de Gynecologie et d'Obstetrique 1976;71:53-61. 5 McNeilly AS, Hagen C. The prolactin, LH, FSH and TSH response to a combined LHRH/TRH test in normal male subjects and during the menstrual cycle. Clin Endocrinol 1974;3:426-35. 6 Baker ST, Jennison KM, Kellie. AE. The direct radioimmunoassay of oestrogen glucuronides in human female urine. Biochemn 1979;177:729-38. 7 Samarajeewa P, Cooley G, Kellie AE. The radioimmunoassay of pregnanediol-3a-glucuronide. 7 SteroidBiochem 1979;111:1165-71. 8 Wright K, Collins DC, Preedy JRK. Urinary excretion of oestrone glucosiduronate, 17j3estradiol-17-glucosiduronate and estriol-16a-glucosiduronate. Significance of proportionate differences during the menstrual cycle. Steroids 1979;34:445-57. 9 Collins WP, Collins PO, Kilpatrick MJ, Manning PA, Pike JM, Tyler JPP. The concentrations of urinary oestrone-3-glucuronide, LH and pregnanediol-3a-glucuronide as indices of ovarian function. Acta Endocrinol 1979;90:336-48. 10 Howie PW, McNeilly AS. Effect of breast-feeding pattems on human birth intervals. J Reprod Fertil 1982;65:545-57. 11 Landgren B-M, Diczfalusy E. Hormonal effects of the 300 ug norethisterone (NET) minipill. Contraception 1974;21:87-113. 12 Elstein M, Briston PG, Hewitt KJ, Kirk D, Miller H. The effect ofdaily norethisterone (035 mg) on cervical mucus and on urinary LH, pregnanediol and oestrogen levels. BrJ3 Obstet Gynaecol 1976;83: 165-8. 13 Toyob Y, Adams J, Jacobs HS, Guillebaud J. Ultrasonographic demonstration of increased frequency of functional ovarian cysts in progestogen-only pill users. BrJ Obstet Gynaecol (in press). 14 Pike MC, Krailo MD, Henderson BE, Duke A, Roy S. Breast cancer in young women and the use of oral contraceptives: possible modifying effect of formulation and age at use. Lancet Abstract The effects on portal pressure of the vasodilatory drugs isosorbide dinitrate and verapamil and of an a and ji blocking agent, labetalol, were assessed in 21 patients with cirrhosis and portal hypertension. The wedged hepatic venous pressure gradient (wedged minus free hepatic venous pressures) was used as an index of portal pressure and was not significantly changed by treatment with labetalol (n==5) but was significantly decreased by verapamil (n= 6; p <0 05) and isosorbide dinitrate (n= 10; p <0-01). Long term administration of isosorbide dinitrate also had a significant effect (p <0 01).