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The effects of different formulations of oral contraceptive agents on lipid and carbohydrate metabolism.
N Engl J Med. 1990 Nov 15; 323(20):1375-81.NEJM

Abstract

BACKGROUND

Oral contraceptives can induce changes in lipid and carbohydrate metabolism similar to those associated with an increased risk of coronary heart disease, including increased serum triglyceride, low-density lipoprotein (LDL) cholesterol, and insulin levels and decreased high-density lipoprotein (HDL) cholesterol levels. In this study, we examined whether modification of the type or dose of progestin in oral-contraceptive preparations diminishes these changes.

METHODS

We measured plasma lipoprotein levels and performed oral glucose-tolerance tests in a cross section of 1060 women who took one of nine types of oral contraceptives for at least three months and 418 women who took none. Seven of the contraceptive formulations contained various doses and types of progestin: levonorgestrel in low (150 micrograms), high (250 micrograms), and triphasic (50 to 125 micrograms) doses; norethindrone in low (500 micrograms), high (1000 micrograms), and triphasic (500 to 1000 micrograms) doses; and a new progestin, desogestrel, in one dose (150 micrograms). All seven contained 30 to 40 micrograms of ethinyl estradiol. Two additional formulations contained progestin alone.

RESULTS

As compared with controls, women taking combination drugs did not have increased serum total cholesterol levels but did have increases of 13 to 75 percent in fasting triglyceride levels. Levels of LDL cholesterol were reduced by 14 percent in women taking the combination containing desogestrel and by 12 percent in those taking low-dose norethindrone. Levels of HDL cholesterol were lowered by 5 percent and 16 percent by the combinations containing low-dose and high-dose levonorgestrel, respectively; these decreases were due to reductions of 29 percent and 43 percent, respectively, in the levels of HDL subclass 2. The combination pill containing high-dose norethindrone did not affect HDL cholesterol levels, whereas that containing low-dose norethindrone increased HDL cholesterol levels by 10 percent. The desogestrel combination increased HDL cholesterol levels by 12 percent. Levels of apolipoproteins A-I, A-II, and B were generally increased by combination drugs. Depending on the dose and type of progestin, combination drugs were associated with plasma glucose levels on the glucose-tolerance test that were 43 to 61 percent higher than in controls, insulin responses 12 to 40 percent higher, and C-peptide responses 18 to 45 percent higher. Progestin-only formulations had only minor metabolic effects.

CONCLUSIONS

The appropriate dose and type of progestin may reduce the adverse effects of oral contraceptives on many metabolic markers of risk for coronary heart disease. Progestin-only formulations or combinations containing desogestrel or low-dose norethindrone were associated wtih the most favorable profiles.

Authors+Show Affiliations

Wynn Institute for Metabolic Research, St. John's Wood, London, England.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

2146499

Citation

Godsland, I F., et al. "The Effects of Different Formulations of Oral Contraceptive Agents On Lipid and Carbohydrate Metabolism." The New England Journal of Medicine, vol. 323, no. 20, 1990, pp. 1375-81.
Godsland IF, Crook D, Simpson R, et al. The effects of different formulations of oral contraceptive agents on lipid and carbohydrate metabolism. N Engl J Med. 1990;323(20):1375-81.
Godsland, I. F., Crook, D., Simpson, R., Proudler, T., Felton, C., Lees, B., Anyaoku, V., Devenport, M., & Wynn, V. (1990). The effects of different formulations of oral contraceptive agents on lipid and carbohydrate metabolism. The New England Journal of Medicine, 323(20), 1375-81.
Godsland IF, et al. The Effects of Different Formulations of Oral Contraceptive Agents On Lipid and Carbohydrate Metabolism. N Engl J Med. 1990 Nov 15;323(20):1375-81. PubMed PMID: 2146499.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The effects of different formulations of oral contraceptive agents on lipid and carbohydrate metabolism. AU - Godsland,I F, AU - Crook,D, AU - Simpson,R, AU - Proudler,T, AU - Felton,C, AU - Lees,B, AU - Anyaoku,V, AU - Devenport,M, AU - Wynn,V, PY - 1990/11/15/pubmed PY - 1990/11/15/medline PY - 1990/11/15/entrez KW - Biology KW - Carbohydrate Metabolic Effects--analysis KW - Cardiovascular Effects KW - Comparative Studies KW - Contraception KW - Contraceptive Agents, Female--side effects KW - Contraceptive Agents, Progestin--side effects KW - Contraceptive Agents--side effects KW - Contraceptive Methods KW - Desogestrel KW - Developed Countries KW - England KW - Ethynodiol Diacetate--side effects KW - Europe KW - Examinations And Diagnoses KW - Family Planning KW - Glucose Tolerance Test KW - Laboratory Examinations And Diagnoses KW - Laboratory Procedures KW - Levonorgestrel--side effects KW - Lipid Metabolic Effects--analysis KW - Lipids KW - Metabolic Effects KW - Norethindrone--side effects KW - Northern Europe KW - Oral Contraceptives KW - Oral Contraceptives, Combined KW - Physiology KW - Research Methodology KW - Risk Factors KW - Studies KW - United Kingdom SP - 1375 EP - 81 JF - The New England journal of medicine JO - N Engl J Med VL - 323 IS - 20 N2 - BACKGROUND: Oral contraceptives can induce changes in lipid and carbohydrate metabolism similar to those associated with an increased risk of coronary heart disease, including increased serum triglyceride, low-density lipoprotein (LDL) cholesterol, and insulin levels and decreased high-density lipoprotein (HDL) cholesterol levels. In this study, we examined whether modification of the type or dose of progestin in oral-contraceptive preparations diminishes these changes. METHODS: We measured plasma lipoprotein levels and performed oral glucose-tolerance tests in a cross section of 1060 women who took one of nine types of oral contraceptives for at least three months and 418 women who took none. Seven of the contraceptive formulations contained various doses and types of progestin: levonorgestrel in low (150 micrograms), high (250 micrograms), and triphasic (50 to 125 micrograms) doses; norethindrone in low (500 micrograms), high (1000 micrograms), and triphasic (500 to 1000 micrograms) doses; and a new progestin, desogestrel, in one dose (150 micrograms). All seven contained 30 to 40 micrograms of ethinyl estradiol. Two additional formulations contained progestin alone. RESULTS: As compared with controls, women taking combination drugs did not have increased serum total cholesterol levels but did have increases of 13 to 75 percent in fasting triglyceride levels. Levels of LDL cholesterol were reduced by 14 percent in women taking the combination containing desogestrel and by 12 percent in those taking low-dose norethindrone. Levels of HDL cholesterol were lowered by 5 percent and 16 percent by the combinations containing low-dose and high-dose levonorgestrel, respectively; these decreases were due to reductions of 29 percent and 43 percent, respectively, in the levels of HDL subclass 2. The combination pill containing high-dose norethindrone did not affect HDL cholesterol levels, whereas that containing low-dose norethindrone increased HDL cholesterol levels by 10 percent. The desogestrel combination increased HDL cholesterol levels by 12 percent. Levels of apolipoproteins A-I, A-II, and B were generally increased by combination drugs. Depending on the dose and type of progestin, combination drugs were associated with plasma glucose levels on the glucose-tolerance test that were 43 to 61 percent higher than in controls, insulin responses 12 to 40 percent higher, and C-peptide responses 18 to 45 percent higher. Progestin-only formulations had only minor metabolic effects. CONCLUSIONS: The appropriate dose and type of progestin may reduce the adverse effects of oral contraceptives on many metabolic markers of risk for coronary heart disease. Progestin-only formulations or combinations containing desogestrel or low-dose norethindrone were associated wtih the most favorable profiles. SN - 0028-4793 UR - https://www.unboundmedicine.com/medline/citation/2146499/The_effects_of_different_formulations_of_oral_contraceptive_agents_on_lipid_and_carbohydrate_metabolism_ L2 - https://www.nejm.org/doi/10.1056/NEJM199011153232003?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -