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The role of triphasic levonorgestrel in oral contraception: a review of metabolic and hemostatic effects.
Gynecol Endocrinol. 1996 Jun; 10(3):207-18.GE

Abstract

Epidemiological studies suggesting a possible association between the use of combined oral contraceptives and an increased risk of cardiovascular disease have led to extensive investigations into the effect of oral contraceptives on lipid and carbohydrate metabolism, and on hemostasis. Since this association was originally suggested, the steroid dose in oral contraceptives has been significantly reduced and new progestogens have been developed. Also, triphasic formulations have been introduced which offer a well-balanced estrogen/progestogen ratio, allowing a further reduction in the progestogen dose per cycle, and thus helping to minimize unwanted metabolic and hemostatic effects. The metabolic interactions of triphasic levonorgestrel, the first triphasic formulation to be introduced, have received particular attention. Lipid metabolism appears to be largely unaffected by triphasic levonorgestrel, most studies reporting no significant change in high- (HDL-C) or low-density lipoprotein-cholesterol (LDL-C) levels. Several studies have reported a decrease in the lipoprotein subfraction HDL2-C levels, but in most cases measurements of the LDL-C/HDL-C and apolipoprotein A-1/B ratios reveal no clinically significant effects. Concerning lipids, most studies suggest that triphasic levonorgestrel has less metabolic impact than the monophasic formulation. In common with all currently available oral contraceptives, triphasic levonorgestrel appears to have some effect on carbohydrate metabolism. The study results vary, however; some investigators have found an impairment of glucose tolerance, whereas others have not detected any significant effect. Compared with lipid and carbohydrate metabolism, fewer studies have investigated the effect of triphasic levonorgestrel on hemostasis. In common with all estrogen-containing oral contraceptives, levonorgestrel appears to stimulate some procoagulant activity, elevating the levels of factors VII and X, and fibrinogen. However, the effect of triphasic levonorgestrel appears to be balanced, with most studies reporting a corresponding increase in anti-coagulant-fibrinolytic activity. Although most of the studies reviewed here reported some statistically significant metabolic interactions, many authors comment that the changes are probably not clinically relevant in terms of an altered risk of cardiovascular disease. The true risk of vascular disease associated with modern low-dose oral contraceptives remains to be confirmed when sufficient epidemiological data eventually become available.

Authors+Show Affiliations

Ernst Schering Research Foundation, Berlin, Germany.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

8862497

Citation

Lachnit-Fixson, U. "The Role of Triphasic Levonorgestrel in Oral Contraception: a Review of Metabolic and Hemostatic Effects." Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology, vol. 10, no. 3, 1996, pp. 207-18.
Lachnit-Fixson U. The role of triphasic levonorgestrel in oral contraception: a review of metabolic and hemostatic effects. Gynecol Endocrinol. 1996;10(3):207-18.
Lachnit-Fixson, U. (1996). The role of triphasic levonorgestrel in oral contraception: a review of metabolic and hemostatic effects. Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology, 10(3), 207-18.
Lachnit-Fixson U. The Role of Triphasic Levonorgestrel in Oral Contraception: a Review of Metabolic and Hemostatic Effects. Gynecol Endocrinol. 1996;10(3):207-18. PubMed PMID: 8862497.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The role of triphasic levonorgestrel in oral contraception: a review of metabolic and hemostatic effects. A1 - Lachnit-Fixson,U, PY - 1996/6/1/pubmed PY - 1996/6/1/medline PY - 1996/6/1/entrez KW - Biology KW - Carbohydrate Metabolic Effects KW - Cardiovascular Effects KW - Contraception KW - Contraceptive Agents KW - Contraceptive Agents, Female KW - Contraceptive Agents, Progestin KW - Contraceptive Methods--pharmacodynamics KW - Family Planning KW - Hematological Effects KW - Hemic System KW - Levonorgestrel KW - Lipid Metabolic Effects KW - Lipids KW - Literature Review KW - Metabolic Effects KW - Oral Contraceptives, Combined--pharmacodynamics KW - Oral Contraceptives, Phasic--pharmacodynamics KW - Oral Contraceptives--pharmacodynamics KW - Physiology SP - 207 EP - 18 JF - Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology JO - Gynecol Endocrinol VL - 10 IS - 3 N2 - Epidemiological studies suggesting a possible association between the use of combined oral contraceptives and an increased risk of cardiovascular disease have led to extensive investigations into the effect of oral contraceptives on lipid and carbohydrate metabolism, and on hemostasis. Since this association was originally suggested, the steroid dose in oral contraceptives has been significantly reduced and new progestogens have been developed. Also, triphasic formulations have been introduced which offer a well-balanced estrogen/progestogen ratio, allowing a further reduction in the progestogen dose per cycle, and thus helping to minimize unwanted metabolic and hemostatic effects. The metabolic interactions of triphasic levonorgestrel, the first triphasic formulation to be introduced, have received particular attention. Lipid metabolism appears to be largely unaffected by triphasic levonorgestrel, most studies reporting no significant change in high- (HDL-C) or low-density lipoprotein-cholesterol (LDL-C) levels. Several studies have reported a decrease in the lipoprotein subfraction HDL2-C levels, but in most cases measurements of the LDL-C/HDL-C and apolipoprotein A-1/B ratios reveal no clinically significant effects. Concerning lipids, most studies suggest that triphasic levonorgestrel has less metabolic impact than the monophasic formulation. In common with all currently available oral contraceptives, triphasic levonorgestrel appears to have some effect on carbohydrate metabolism. The study results vary, however; some investigators have found an impairment of glucose tolerance, whereas others have not detected any significant effect. Compared with lipid and carbohydrate metabolism, fewer studies have investigated the effect of triphasic levonorgestrel on hemostasis. In common with all estrogen-containing oral contraceptives, levonorgestrel appears to stimulate some procoagulant activity, elevating the levels of factors VII and X, and fibrinogen. However, the effect of triphasic levonorgestrel appears to be balanced, with most studies reporting a corresponding increase in anti-coagulant-fibrinolytic activity. Although most of the studies reviewed here reported some statistically significant metabolic interactions, many authors comment that the changes are probably not clinically relevant in terms of an altered risk of cardiovascular disease. The true risk of vascular disease associated with modern low-dose oral contraceptives remains to be confirmed when sufficient epidemiological data eventually become available. SN - 0951-3590 UR - https://www.unboundmedicine.com/medline/citation/8862497/The_role_of_triphasic_levonorgestrel_in_oral_contraception:_a_review_of_metabolic_and_hemostatic_effects_ L2 - https://www.tandfonline.com/doi/full/10.3109/09513599609027990 DB - PRIME DP - Unbound Medicine ER -