Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1993 Jul;92(1):456–461. doi: 10.1172/JCI116588

Effects of low dosage progestin-only administration upon plasma triglycerides and lipoprotein metabolism in postmenopausal women.

B M Wolfe 1, M W Huff 1
PMCID: PMC293632  PMID: 8326011

Abstract

Oral administration to five postmenopausal women of dl-norgestrel (0.075 mg/d for 7 wk) reduced mean fasting plasma levels of triglycerides by 29% (P < 0.001), VLDL triglycerides by 39% (P < 0.01), and VLDL apo B by 26% (P < 0.05), while lowering mean total cholesterol by 7% (P < 0.06). To explain these observations the kinetics of VLDL and LDL apo B turnover were studied by injecting autologous 125I-labeled VLDL and 131I-labeled LDL under control conditions and again in the fourth week of a 7-wk course of dl-norgestrel. VLDL apo B pool size fell by an average of 27% (1.2 vs 1.7 mg/kg, P < 0.06) and production of apo B by 18% (18 vs 22 mg/kg per d, P < 0.05) with unchanged fractional catabolic rate. Production of LDL apo B increased 36% with dl-norgestrel (12 vs 9.4 mg/kg per d, P < 0.05), but this was compensated by a 36% increase in fractional catabolic rate of LDL apo B (0.33 vs 0.25 pools/d, P < 0.005), thereby maintaining pool size. Lipoprotein (a) fell by an average of 12% (16 vs 18 mg/dl, P < 0.06). dl-Norgestrel reduced VLDL triglycerides (40 vs 64 mg/dl, P < 0.05), intermediate density lipoprotein cholesterol (14 vs 19 mg/dl, P < 0.02), IDL apo B (5.3 vs 7.2 mg/dl, P < 0.05), and VLDL cholesterol (3.1 vs 5.1 mg/dl, 0.10 > P > 0.05), in parallel with the reductions in VLDL apo B production and pool size. dl-Norgestrel significantly lowered the production rate of VLDL apo B, thereby decreasing plasma VLDL and intermediate density lipoprotein concentrations.

Full text

PDF
456

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Albers J. J., Taggart H. M., Applebaum-Bowden D., Haffner S., Chesnut C. H., 3rd, Hazzard W. R. Reduction of lecithin-cholesterol acyltransferase, apolipoprotein D and the Lp(a) lipoprotein with the anabolic steroid stanozolol. Biochim Biophys Acta. 1984 Sep 12;795(2):293–296. doi: 10.1016/0005-2760(84)90078-x. [DOI] [PubMed] [Google Scholar]
  2. Bank S., Marks I. N. Case reports. Hyperlipaemic pancreatitis and the pill. Postgrad Med J. 1970 Sep;46(539):576–578. doi: 10.1136/pgmj.46.539.576. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Eriksson M., Berglund L., Rudling M., Henriksson P., Angelin B. Effects of estrogen on low density lipoprotein metabolism in males. Short-term and long-term studies during hormonal treatment of prostatic carcinoma. J Clin Invest. 1989 Sep;84(3):802–810. doi: 10.1172/JCI114239. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Foegh M., Damgaard-Pedersen F., Gormsen J., Knudsen J. B., Schou G. Oral levo-norgestrel - testosterone effects on spermatogenesis, hormone levels, coagulation factors and lipoproteins in normal men. Contraception. 1980 Apr;21(4):381–391. doi: 10.1016/s0010-7824(80)80016-3. [DOI] [PubMed] [Google Scholar]
  5. GURPIDE E., MANN J., SANDBERG E. DETERMINATION OF KINETIC PARAMETERS INA TWO-POOL SYSTEM BY ADMINISTRATION OF ONE OR MORE TRACERS. Biochemistry. 1964 Sep;3:1250–1255. doi: 10.1021/bi00897a012. [DOI] [PubMed] [Google Scholar]
  6. Glueck C. J., Scheel D., Fishback J., Steiner P. Estrogen-induced pancreatitis in patients with previously covert familial type V hyperlipoproteinemia. Metabolism. 1972 Jul;21(7):657–666. doi: 10.1016/0026-0495(72)90089-3. [DOI] [PubMed] [Google Scholar]
  7. Goldberg I. J., Le N. A., Ginsberg H. N., Paterniti J. R., Jr, Brown W. V. Metabolism of apoprotein B in cynomolgus monkey: evidence for independent production of low-density lipoprotein apoprotein B. Am J Physiol. 1983 Feb;244(2):E196–E201. doi: 10.1152/ajpendo.1983.244.2.E196. [DOI] [PubMed] [Google Scholar]
  8. Goldzieher J. W. Pharmacology of contraceptive steroids: a brief review. Am J Obstet Gynecol. 1989 May;160(5 Pt 2):1260–1264. doi: 10.1016/s0002-9378(89)80010-9. [DOI] [PubMed] [Google Scholar]
  9. Goodman D. S., Noble R. P., Dell R. B. Three-pool model of the long-term turnover of plasma cholesterol in man. J Lipid Res. 1973 Mar;14(2):178–188. [PubMed] [Google Scholar]
  10. Goodman D. S., Noble R. P. Turnover of plasma cholesterol in man. J Clin Invest. 1968 Feb;47(2):231–241. doi: 10.1172/JCI105719. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. HAVEL R. J., EDER H. A., BRAGDON J. H. The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum. J Clin Invest. 1955 Sep;34(9):1345–1353. doi: 10.1172/JCI103182. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Henderson B. E., Paganini-Hill A., Ross R. K. Decreased mortality in users of estrogen replacement therapy. Arch Intern Med. 1991 Jan;151(1):75–78. [PubMed] [Google Scholar]
  13. Huff M. W., Breckenridge W. C., Strong W. L., Wolfe B. M. Metabolism of apolipoproteins C-II, C-III, and B in hypertriglyceridemic men. Changes after heparin-induced lipolysis. Arteriosclerosis. 1988 Sep-Oct;8(5):471–479. doi: 10.1161/01.atv.8.5.471. [DOI] [PubMed] [Google Scholar]
  14. Huff M. W., Giovannetti P. M., Wolfe B. M. Turnover of very low-density lipoprotein-apoprotein B is increased by substitution of soybean protein for meat and dairy protein in the diets of hypercholesterolemic men. Am J Clin Nutr. 1984 Jun;39(6):888–897. doi: 10.1093/ajcn/39.6.888. [DOI] [PubMed] [Google Scholar]
  15. Huff M. W., Telford D. E., Woodcroft K., Strong W. L. Mevinolin and cholestyramine inhibit the direct synthesis of low density lipoprotein apolipoprotein B in miniature pigs. J Lipid Res. 1985 Oct;26(10):1175–1186. [PubMed] [Google Scholar]
  16. Johansson S., Bondjers G., Fager G., Wedel H., Tsipogianni A., Olofsson S. O., Vedin A., Wiklund O., Wilhelmsson C. Serum lipids and apolipoprotein levels in women with acute myocardial infarction. Arteriosclerosis. 1988 Nov-Dec;8(6):742–749. doi: 10.1161/01.atv.8.6.742. [DOI] [PubMed] [Google Scholar]
  17. Khokha R., Huff M. W., Wolfe B. M. Divergent effects of d-norgestrel on the metabolism of rat very low density and low density apolipoprotein B. J Lipid Res. 1986 Jul;27(7):699–705. [PubMed] [Google Scholar]
  18. Khokha R., Walton P. A., Possmayer F., Wolfe B. Effects of levonorgestrel on enzymes responsible for synthesis of triacylglycerols in rat liver. Biochim Biophys Acta. 1987 Apr 3;918(2):120–125. doi: 10.1016/0005-2760(87)90186-x. [DOI] [PubMed] [Google Scholar]
  19. Khokha R., Wolfe B. M. Hypotriglyceridemic effects of levonorgestrel in rats. Atherosclerosis. 1984 Sep;52(3):329–338. doi: 10.1016/0021-9150(84)90063-7. [DOI] [PubMed] [Google Scholar]
  20. Kushwaha R. S., Foster D. M., Barrett P. H., Carey K. D. Effect of estrogen and progesterone on metabolism of apoprotein B in baboons. Am J Physiol. 1990 Jan;258(1 Pt 1):E172–E183. doi: 10.1152/ajpendo.1990.258.1.E172. [DOI] [PubMed] [Google Scholar]
  21. Nestel P. J., Reardon M. F., Fidge N. H. Very low density lipoprotein B-apoprotein kinetics in human subjects. relationships between pool size, flux, and removal rate. Circ Res. 1979 Jul;45(1):35–41. doi: 10.1161/01.res.45.1.35. [DOI] [PubMed] [Google Scholar]
  22. Nielsen F. H., Honoré E., Kristoffersen K., Secher N. J., Pedersen G. T. Changes in serum lipids during treatment with norgestrel, oestradiol-valerate and cycloprogynon. Acta Obstet Gynecol Scand. 1977;56(4):367–370. doi: 10.3109/00016347709154994. [DOI] [PubMed] [Google Scholar]
  23. Pavlik E. J., Coulson P. B. Modulation of estrogen receptors in four different target tissues: differential effects of estrogen vs progesterone. J Steroid Biochem. 1976 May;7(5):369–376. doi: 10.1016/0022-4731(76)90096-0. [DOI] [PubMed] [Google Scholar]
  24. Plunkett E. R., Wolfe B. M. Prolonged effects of a novel, low-dosage continuous progestin-cyclic estrogen replacement program in postmenopausal women. Am J Obstet Gynecol. 1992 Jan;166(1 Pt 1):117–121. doi: 10.1016/0002-9378(92)91842-x. [DOI] [PubMed] [Google Scholar]
  25. Reardon M. F., Fidge N. H., Nestel P. J. Catabolism of very low density lipoprotein B apoprotein in man. J Clin Invest. 1978 Mar;61(3):850–860. doi: 10.1172/JCI108999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Robertson D. N., Alvarez F., Sivin I., Brache V., Stern J., Leon P., Faundes A. Lipoprotein patterns in women in Santo Domingo using a levonorgestrel/estradiol contraceptive ring. Contraception. 1981 Oct;24(4):469–480. doi: 10.1016/0010-7824(81)90010-x. [DOI] [PubMed] [Google Scholar]
  27. SKINNER S. M., CLARK R. E., BAKER N., SHIPLEY R. A. Complete solution of the three-compartment model in steady state after single injection of radioactive tracer. Am J Physiol. 1959 Feb;196(2):238–244. doi: 10.1152/ajplegacy.1959.196.2.238. [DOI] [PubMed] [Google Scholar]
  28. Shames D. M., Havel R. J. De novo production of low density lipoproteins: fact or fancy. J Lipid Res. 1991 Jul;32(7):1099–1112. [PubMed] [Google Scholar]
  29. Silfverstolpe G., Gustafson A., Samsioe G., Svanborg A. Lipid metabolic studies in oophorectomized women. Effects of three different progestogens. Acta Obstet Gynecol Scand Suppl. 1979;88:89–95. doi: 10.3109/00016347909157235. [DOI] [PubMed] [Google Scholar]
  30. Stampfer M. J., Colditz G. A., Willett W. C., Manson J. E., Rosner B., Speizer F. E., Hennekens C. H. Postmenopausal estrogen therapy and cardiovascular disease. Ten-year follow-up from the nurses' health study. N Engl J Med. 1991 Sep 12;325(11):756–762. doi: 10.1056/NEJM199109123251102. [DOI] [PubMed] [Google Scholar]
  31. Taves E. H., Wolfe B. M. Estradiol is a potent inhibitor of the hypotriglyceridemic effect of levonorgestrel in female rats. Lipids. 1989 Jul;24(7):669–672. doi: 10.1007/BF02535088. [DOI] [PubMed] [Google Scholar]
  32. Tikkanen M. J., Nikkilä E. A., Kuusi T., Sipinen S. Different effects of two progestins on plasma high density lipoprotein (HDL2) and postheparin plasma hepatic lipase activity. Atherosclerosis. 1981 Nov-Dec;40(3-4):365–369. doi: 10.1016/0021-9150(81)90147-7. [DOI] [PubMed] [Google Scholar]
  33. Walsh B. W., Schiff I., Rosner B., Greenberg L., Ravnikar V., Sacks F. M. Effects of postmenopausal estrogen replacement on the concentrations and metabolism of plasma lipoproteins. N Engl J Med. 1991 Oct 24;325(17):1196–1204. doi: 10.1056/NEJM199110243251702. [DOI] [PubMed] [Google Scholar]
  34. Warnick G. R., Albers J. J. A comprehensive evaluation of the heparin-manganese precipitation procedure for estimating high density lipoprotein cholesterol. J Lipid Res. 1978 Jan;19(1):65–76. [PubMed] [Google Scholar]
  35. Williams J. K., Adams M. R., Klopfenstein H. S. Estrogen modulates responses of atherosclerotic coronary arteries. Circulation. 1990 May;81(5):1680–1687. doi: 10.1161/01.cir.81.5.1680. [DOI] [PubMed] [Google Scholar]
  36. Wolfe B. M., Ahuja S. P. Effects of intravenously administered fructose and glucose on splanchnic secretion of plasma triglycerides in hypertriglyceridemic men. Metabolism. 1977 Sep;26(9):963–978. doi: 10.1016/0026-0495(77)90014-2. [DOI] [PubMed] [Google Scholar]
  37. Wolfe B. M., Huff M. W. Effects of combined estrogen and progestin administration on plasma lipoprotein metabolism in postmenopausal women. J Clin Invest. 1989 Jan;83(1):40–45. doi: 10.1172/JCI113882. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Xu X. F., Hoebeke J., Björntorp P. Progestin binds to the glucocorticoid receptor and mediates antiglucocorticoid effect in rat adipose precursor cells. J Steroid Biochem. 1990 Aug 14;36(5):465–471. doi: 10.1016/0022-4731(90)90089-b. [DOI] [PubMed] [Google Scholar]
  39. ZILVERSMIT D. B. The design and analysis of isotope experiments. Am J Med. 1960 Nov;29:832–848. doi: 10.1016/0002-9343(60)90117-0. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES