Samsioe and Mattsson
l~.
13.
14.
15. 16. 17.
Crona N, Enk L, Mattsson LA, Samsioe G, Silfverstolpe G. Progestogens and lipid metabolism. Maturitas 1986;8: 141-58. Crona N, Silfverstolpe G, Samsioe G. The effects of two gonane progestins alone and in combination with ethinylestradiol on serum lipoproteins. Eur] Obstet Gynecol 1985;19:365-74. Lindberg UB, Crona N, Enk L, Samsioe G, Silfverstolpe G. Effects of cyproterone acetate on serum lipoproteins when administered alone and in combination with ethinylestradiol. Horm Metab Res 1987;19:222-5. Porter ]B, Hershel]R, Walker AM. Mortality among oral contraceptive users. Obstet Gynecol 1987;70:29-32. Royal College of General Practitioners Oral Contraceptive Study. Further analysis of mortality in oral contraceptive users. Lancet 1981; I :541-3. Mann]I, Doll R, Thorogood M, Vessey MP, Waters WE.
July 1990 Am J Obstet Gynecol
18. 19. 20. 21.
22.
Risk factors for myocardial infarction in young women. Br] Prev Soc Med 1976;30:94-100. Adams MR, Clarksson TB, Koritnik DR, et al. Contraceptive steroids and coronary artery atherosclerosis in cynomolgus macaques. Fertil Steril 1987;47:1010-8. Hirvonen E. Thorogood M, Vessey MP. Silfverstolpe G, Johnson P, Samsioe G, Svanborg A, Gustafson A. Lipid metabolic studies in oophorectomized women. Effects induced by two different estrogens on serum individual phospholipids and serum lecithin fatty acid composition. Horm Metab Ret 1981;13:141-5. Mattsson LA, Cullberg C, Samsioe G. The relative fatty acid composition of lecithin and cholesterol ester: influence of an estrogen-progestogen combination. AM] OBSTET GYNECOL 1986;155:174-7.
Estrogenic effect of gestodene- or desogestrel-containing oral contraceptives on lipoprotein metabolism Jan A. Gevers Leuven, MD, PhD,. Marianne C. Dersjant-Roorda,b Frans M. Helmerhorst, MD, PhD/ Rinse de Boer, MD,c A. Neymeyer-Leloux, MD,c and Louis Havekes, PhD" Leiden and Hertogenbosch, The Netherlands In a randomized comparative study, changes in lipoprotein metabolism during the use of two low-dose oral contraceptives with similar doses of ethinyl estradiol but with different progestogenically active compounds were evaluated for their effective estrogen/androgen balance. Sixty-eight healthy women who did not take hormonally active drugs or were pregnant the previous 3 months took either 75 /1g of gestodene + 30 /1g of ethinyl estradiol or 150 /1g of desogestrel + 30 /1g ethinyl estradiol during 12 cycles. During the first three cycles serum levels of the following parameters increased: triglycerides, cholesterol in high-density lipoprotein, and apolipoproteins A" A2 , and B. Additional increase was observed in apolipoprotein B only after three and six cycles. The induced changes were not significantly different in the two groups, and the levels generally remained within normal limits. The changes seen with both pills reflect a mild estrogenic dominance. On the basis of current knowledge, moderately altered lipoprotein metabolism is not expected to impose an extra risk of atherosclerosis. (AM J OBSTET GVNECOL 1990;163:358-62.)
Key words: Gestodene, lipoproteins, oral contraceptives High plasma levels of low-density lipoprotein (LDL) cholesterol' and its apolipoprotein B2 and low levels of high-density lipoprotein (HDL) cholesterol" 4 and its apolipoproteins A, and A25 -7 are associated with an increased incidence of ischemic heart disease. LDL is a direct cause of atherogenesis, but the role of HDL in this process is still uncertain. Thus changing LDL levels by intervention will probably alter cardiovascular progFrom the Gaubius Institute: The Netherlands Organization for Applied Scientific Research, University Hospital Leiden,b and Groot lieken Gasthuis.' Supported fry Wyeth Laboratories, Hoofddorp, The Netherlands. Reprint requests: J. A. Gevers Leuven, MD, Gaubius Institute TNO, P_ O. Box 612, 2300 AP Leiden, The Netherlands.
6/0/20052
358
nosis, and changing HDL levels will possibly alter cardiovascular prognosis. Women have a sixfold lower incidence of myocardial infarctions than do men by age 50 years. 8 This advantage declines thereafter. It is conceivable that this advantage is due to the effects of estrogens on lipoprotein metabolism. Postmenopausal oral estrogen therapy is indeed associated with a reduced risk of myocardial infarction,9 and this therapy causes a decrease in LDL cholesterol'° and an increase in HDL cholesterol. II However, it is also conceivable that testosterone exerts a harmful effect on cardiovascular prognosis in men ("male disadvantage"). Androgens have an HDL cholesterol-lowering effect. 12 Thus HDL levels reflect the balance of estrogenic/androgenic effects (es-
Oral contraceptives and lipoproteins 359
Volume 163 Number I. Part 2
Table I. Effect of two low-dose OCs on serum triglyceride and lipoprotein lipid levels (range and median or mean ± SD, mmollL) GTD-EE
DSG-EE
Cycle (n)
12 (29)
TG (range) median
0(28)
0.33-2.00 0.47-2.23 0.43-2.75 0.60-1.87 0.73 0.95 1.11 1.24
l~.
13.
14.
15. 16. 17.
Crona N, Enk L, Mattsson LA, Samsioe G, Silfverstolpe G. Progestogens and lipid metabolism. Maturitas 1986;8: 141-58. Crona N, Silfverstolpe G, Samsioe G. The effects of two gonane progestins alone and in combination with ethinylestradiol on serum lipoproteins. Eur] Obstet Gynecol 1985;19:365-74. Lindberg UB, Crona N, Enk L, Samsioe G, Silfverstolpe G. Effects of cyproterone acetate on serum lipoproteins when administered alone and in combination with ethinylestradiol. Horm Metab Res 1987;19:222-5. Porter ]B, Hershel]R, Walker AM. Mortality among oral contraceptive users. Obstet Gynecol 1987;70:29-32. Royal College of General Practitioners Oral Contraceptive Study. Further analysis of mortality in oral contraceptive users. Lancet 1981; I :541-3. Mann]I, Doll R, Thorogood M, Vessey MP, Waters WE.
July 1990 Am J Obstet Gynecol
18. 19. 20. 21.
22.
Risk factors for myocardial infarction in young women. Br] Prev Soc Med 1976;30:94-100. Adams MR, Clarksson TB, Koritnik DR, et al. Contraceptive steroids and coronary artery atherosclerosis in cynomolgus macaques. Fertil Steril 1987;47:1010-8. Hirvonen E. Thorogood M, Vessey MP. Silfverstolpe G, Johnson P, Samsioe G, Svanborg A, Gustafson A. Lipid metabolic studies in oophorectomized women. Effects induced by two different estrogens on serum individual phospholipids and serum lecithin fatty acid composition. Horm Metab Ret 1981;13:141-5. Mattsson LA, Cullberg C, Samsioe G. The relative fatty acid composition of lecithin and cholesterol ester: influence of an estrogen-progestogen combination. AM] OBSTET GYNECOL 1986;155:174-7.
Estrogenic effect of gestodene- or desogestrel-containing oral contraceptives on lipoprotein metabolism Jan A. Gevers Leuven, MD, PhD,. Marianne C. Dersjant-Roorda,b Frans M. Helmerhorst, MD, PhD/ Rinse de Boer, MD,c A. Neymeyer-Leloux, MD,c and Louis Havekes, PhD" Leiden and Hertogenbosch, The Netherlands In a randomized comparative study, changes in lipoprotein metabolism during the use of two low-dose oral contraceptives with similar doses of ethinyl estradiol but with different progestogenically active compounds were evaluated for their effective estrogen/androgen balance. Sixty-eight healthy women who did not take hormonally active drugs or were pregnant the previous 3 months took either 75 /1g of gestodene + 30 /1g of ethinyl estradiol or 150 /1g of desogestrel + 30 /1g ethinyl estradiol during 12 cycles. During the first three cycles serum levels of the following parameters increased: triglycerides, cholesterol in high-density lipoprotein, and apolipoproteins A" A2 , and B. Additional increase was observed in apolipoprotein B only after three and six cycles. The induced changes were not significantly different in the two groups, and the levels generally remained within normal limits. The changes seen with both pills reflect a mild estrogenic dominance. On the basis of current knowledge, moderately altered lipoprotein metabolism is not expected to impose an extra risk of atherosclerosis. (AM J OBSTET GVNECOL 1990;163:358-62.)
Key words: Gestodene, lipoproteins, oral contraceptives High plasma levels of low-density lipoprotein (LDL) cholesterol' and its apolipoprotein B2 and low levels of high-density lipoprotein (HDL) cholesterol" 4 and its apolipoproteins A, and A25 -7 are associated with an increased incidence of ischemic heart disease. LDL is a direct cause of atherogenesis, but the role of HDL in this process is still uncertain. Thus changing LDL levels by intervention will probably alter cardiovascular progFrom the Gaubius Institute: The Netherlands Organization for Applied Scientific Research, University Hospital Leiden,b and Groot lieken Gasthuis.' Supported fry Wyeth Laboratories, Hoofddorp, The Netherlands. Reprint requests: J. A. Gevers Leuven, MD, Gaubius Institute TNO, P_ O. Box 612, 2300 AP Leiden, The Netherlands.
6/0/20052
358
nosis, and changing HDL levels will possibly alter cardiovascular prognosis. Women have a sixfold lower incidence of myocardial infarctions than do men by age 50 years. 8 This advantage declines thereafter. It is conceivable that this advantage is due to the effects of estrogens on lipoprotein metabolism. Postmenopausal oral estrogen therapy is indeed associated with a reduced risk of myocardial infarction,9 and this therapy causes a decrease in LDL cholesterol'° and an increase in HDL cholesterol. II However, it is also conceivable that testosterone exerts a harmful effect on cardiovascular prognosis in men ("male disadvantage"). Androgens have an HDL cholesterol-lowering effect. 12 Thus HDL levels reflect the balance of estrogenic/androgenic effects (es-
Oral contraceptives and lipoproteins 359
Volume 163 Number I. Part 2
Table I. Effect of two low-dose OCs on serum triglyceride and lipoprotein lipid levels (range and median or mean ± SD, mmollL) GTD-EE
DSG-EE
Cycle (n)
12 (29)
TG (range) median
0(28)
0.33-2.00 0.47-2.23 0.43-2.75 0.60-1.87 0.73 0.95 1.11 1.24
