Metabolic changes during treatment with two different progestogens

Refn, H; Kjær, Andreas; Lebech, A-M; Borggaard, Birgit; Schierup, L; Bremmelgaard, A.

doi:10.1016/0020-7292(91)90076-h

Cited by 3 publications

(3 citation statements)

References 9 publications

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“…In agreement with previous studies [9, 22–24], we found in the present study a clear effect of both combined oral contraceptives. In second generation oral contraceptives we observed a decrease in HDL, and an increase in LDL, triglycerides and total/HDL cholesterol ratio, whereas in third generation preparations opposite results were found for HDL, LDL and total/HDL cholesterol ratio.…”

Section: Discussionsupporting

confidence: 94%

Effect of second and third generation oral contraceptives on lipid metabolism in the absence or presence of the factor V Leiden mutation

Kemmeren

Algra

Grobbee

2001

Journal of Internal Medicine

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Abstract. Kemmeren JM, Algra A, Grobbee DE (University Medical Center Utrecht, Utrecht, The Netherlands). Effect of second and third generation oral contraceptives on lipid metabolism in the absence or presence of the factor V Leiden mutation. J Intern Med 2001; 250: 441±448.Objectives. The effect of a second and third generation oral contraceptive and of the progestagens used in these pills on lipid metabolism was studied in the absence or presence of the factor V Leiden mutation. Design. A single centre, double blind randomized trial. Setting. University Medical Centre. Subjects. A total of 51 women without and 35 women with the factor V Leiden mutation. Interventions. A second generation (30 lg ethinylestradiol/150 lg levonorgestrel) or a third generation (30 lg ethinylestradiol/150 lg desogestrel) oral contraceptive. After two cycles of use and a wash-out period of two cycles, the participants received the corresponding progestagen-only preparation containing 150 lg levonorgestrel or 150 lg desogestrel. Main outcome measures. Mean difference in changes between the treatment groups on total cholesterol, HDL, LDL, triglycerides and total/HDL cholesterol ratio.Results. Compared with levonorgestrel, desogestrelcontaining oral contraceptives caused in women without the factor V Leiden mutation signi®cant changes in HDL (0.43; 95% con®dence interval [CI] 0.25±0.61), LDL (±0.55; 95% CI ±0.90 to ±0.20), triglycerides (0.19; 95% CI 0.06±0.32) and total/ HDL cholesterol ratio (±0.87; 95% CI ±1.21 to ±0.53). When the progestagen-only preparations were used, differential changes were found for HDL (0.16; 95% CI 0.03±0.29), LDL (±0.31; 95% CI ± 0.56 to ±0.05) and total/HDL cholesterol ratio ()0.55; 95% CI ±0.84 to ±0.26). Desogestrel-only caused changes opposite to those of desogestrelcontaining oral contraceptives. For cholesterol and triglycerides, this effect was also found for levonorgestrel-only in comparison with levonorgestrelcombined oral contraceptives. Levonorgestrel appeared to induce the effect on HDL. Almost all results were similar for women with the factor V Leiden mutation. Conclusion. It appears that desogestrel counteracts the effects of oestrogens to a lesser extent than levonorgestrel. Desogestrel-containing oral contraceptives have therefore a more favourable in¯uence on cholesterol metabolism in comparison with levonorgestrel-containing oral contraceptives.

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Section: Discussionsupporting

confidence: 94%

Effect of second and third generation oral contraceptives on lipid metabolism in the absence or presence of the factor V Leiden mutation

Kemmeren

Algra

Grobbee

2001

Journal of Internal Medicine

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“…148 Antithrombin levels decrease more with gestodene-containing OCs than with levonorgestrelcontaining contraceptives. 149,150 In a randomized controlled trial both free and total protein S in plasma from users of desogestrel-containing OCs were more decreased than in plasma from users of levonorgestrel-containing OCs. 143…”

Section: Acquired Decreased Levels Of Protein S and Antithrombinmentioning

confidence: 99%

Venous and Arterial Thrombosis during Oral Contraceptive Use: Risks and Risk Factors

Tanis¹,

Rosendaal²

2003

Seminars in Vascular Medicine

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Since the introduction of oral contraceptives, their use has been associated with an increased risk of both venous and arterial thrombosis. Pulmonary embolism, myocardial infarction, and stroke are serious disorders with a considerable risk of mortality. Because worldwide over 100 million women use oral contraceptives, issues of drug safety are of great importance. The risk of venous thrombosis during low-dose oral contraceptive use is three- to sixfold increased compared with that of nonusers. The association is not only attributed to the estrogen component of the pill: the risk is twice as high for desogestrel and gestodene (third generation) containing oral contraceptives as for levonorgestrel (second generation) containing oral contraceptives. The risk of venous thrombosis is highest in the first year of use and in women with genetic or acquired risk factors for thrombosis. Both venous or arterial thrombosis are unrelated to duration of use or past use of combined oral contraceptives. The risk of myocardial infarction and stroke during low-dose oral contraceptive use is two- to fivefold increased relative to that of nonusers. The risk of arterial thrombosis induced by oral contraceptive use is more pronounced in smokers and women with hypertension, diabetes, and hypercholesterolemia. All types of thrombosis have strongly age-dependent incidences, and therefore in absolute figures the risks and effects of risk factors increase with age. The lowering of the estrogen dose in combined oral contraceptives from 50 microg to 20-30 microg in the last decade did not clearly reduce the risk of venous thrombosis, myocardial infarction, stroke, or peripheral arterial disease. For stroke and peripheral arterial disease no difference in risk was found between second and third generation oral contraceptives. For myocardial infarction study results are conflicting, and a small benefit of third- over second-generation oral contraceptives cannot be ruled out. However, this is unlikely to counterbalance the adverse effect of third generation contraceptives on venous thrombosis.

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“…There is no known biologically plausible mechanism which can explain the reported rate ratios of second and third generation OCs for VTE. Many randomized controlled studies have investigated the haematological effects of second and third generation OCs (Rakoczi et al, 1985;Bonnar etal, 1987;Gramolini et al, 1987;Kloosterboer et al, 1987;Machin et al, 1987;Rabe et al, 1987;Vekemans et al, 1987;Zichella, 1987;Cohen etal, 1988;Kjaer etal, 1989;Omsjo etal, 1989;Prasad etal, 1989;Ball etal, 1990;Refin etal, 1990;Sirtori etal, 1990;Melis etal, 1991). None of these have shown any difference that could be considered to be indicative of a higher (pro)thrombotic potential of third generation OCs.…”

Section: Missing Biological Plausibilitymentioning

confidence: 99%

The 1995 pill scare revisited: anatomy of a non-epidemic

Spitzer

1997

Human Reproduction

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Two years after the October 1995 pill scare that received worldwide attention, this synthesis of evidence goes back to the earliest research on risks of first generation oral contraceptives (OCs). It also covers epidemiological data published since, emphasising the 1995-1996 findings. Late breaking data are also examined. The key issue: are there differences in the risk profiles of second and third generation OCs. The ultimate question is: did any epidemics of venous thromboembolism (VTE) occur? This synthesis of evidence leads to the following conclusions and observations: (i) all OCs on the market are becoming progressively safer; (ii) relative risks of about 2 for VTE, even if real, are clinically unimportant and of no public health significance; (iii) the weak odds ratios contrasting third and second generation OCs, ranging from 1.5 to 2.3 in the 1995-1996 studies are more likely explained by bias than by a causal relationship; (iv) incidences of VTE among users of any OC have been declining over the past three decades; (v) absolute rates of VTE for third generation OC users reported in 1995-1996 are lower than those for users of second generation OCs in 1988 and 1991; (vi) there is no difference in risk of VTE between first starters on second generation OCs versus first starters on third generation OCs; (vii) users of third generation OCs are at much lower risk of acute myocardial infarction than users of second generation OCs; (viii) among users of any OC, the occurrence rates of stroke are low, they are declining, and no differences between second and third generation OCs are apparent; (ix) 2 years after the pill scare there are no epidemics of VTE; (x) there have been excessive rates of therapeutic abortions in some countries; and (xi) the benefit-risk ratio is favourable for users of any OC.

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Metabolic changes during treatment with two different progestogens

Cited by 3 publications

References 9 publications

Effect of second and third generation oral contraceptives on lipid metabolism in the absence or presence of the factor V Leiden mutation

Effect of second and third generation oral contraceptives on lipid metabolism in the absence or presence of the factor V Leiden mutation

Venous and Arterial Thrombosis during Oral Contraceptive Use: Risks and Risk Factors

The 1995 pill scare revisited: anatomy of a non-epidemic

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