Summary
The newer progestogens desogestrel, norgestimate, gestodene, dienogest and nomegestrol share the common property of having weak or no androgenic effects, but there is great variation between agents in their pharmacokinetic properties and hormonal activities. Both desogestrel (acting as 3-keto-desogestrel) and norgestimate (acting mainly through levonorgestrel) are prodrugs. While nomegestrol is derived from 19-norprogesterone, the other compounds are 19-nortestosterone derivatives: desogestrel, norgestimate and gestodene belong to the subgroup of 13-ethyl-gonanes with an ethinyl group at C17α, and dienogest represents an estrane (13-methyl-gonane) with a cyanomethyl group at C17α
Both dienogest and nomegestrol have antiandrogenic properties. In proportion to the dose, the highest serum concentrations are observed after intake of gestodene. When combined with ethinylestradiol, gestodene and 3-keto-desogestrel accumulate in serum during daily treatment because of slowed-down elimination. This is probably caused both by binding to sex hormone-binding globulin (SHBG) and by inhibition of inactivating enzymes. Dienogest does not accumulate in serum, although at a dose of 2mg very high serum concentrations of dienogest are reached.
The most potent progestogens are gestodene and desogestrel, while the effect of dienogest and nomegestrol on endometrium and cervix is less, even though in a similar range. As the ovulation-inhibiting effect is brought about not only by receptor-mediated interactions but also by a direct inhibition of steroid biosynthesis, dienogest and nomegestrol are much less effective than gestodene, desogestrel and norgestimate. Ethinylated progestogens, particularly gestodene, have been demonstrated to inhibit cytochrome P450 enzymes. Both gestodene and desogestrel may moderately reduce SHBG levels and counteract the stimulating effect of ethinylestradiol on hepatic serum proteins, while dienogest and nomegestrol have no influence.
Compared with progestogens with androgenic properties which may restrict the stimulatory action of ethinylestradiol on haemostatic parameters, the newer progestogens do not seem to be superior with respect to haemostasis. There are no data on the direct effect of the compounds on the arterial and venous vessel wall. Due to the less pronounced antagonism on ethinylestradiol-induced changes in lipid metabolism, the newer progestogens appear to be beneficial rather than deleterious, although atherosclerosis was probably not promoted by the older formulations because of the direct effect of ethinylestradiol on the arterial wall. There is no evidence for a lesser impact of the newer progestogens on carbohydrate metabolism, which is mostly impaired by the estrogen component in oral contraceptives. Formulations containing the newer progestogens are, however, preferable in patients with hyperandrogenaemia, the symptoms of which may be improved by the suppression of total and free testosterone and an increase in SHBG; an additional beneficial effect of the antiandrogenic properties of dienogest or nomegestrol remains to be proven.
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References
Düsterberg B, Tack JW, Krause W, et al. Pharmacokinetics and biotransformation of gestodene in man. In: Elsein M, editor. Gestodene. Carnforth: Parthenon, 1987; 35–44
Viinikka L. Metabolism of a new synthetic progestagen, Org 2969, by human liver in vitro. J Steroid Biochem 1979; 10: 353–7
Madden S, Back DJ, Martin CA, et al. Metabolism of the contraceptive steroid desogestrel by the intestinal mucosa. Br J Clin Pharmacol 1989; 27: 295–9
Back DJ, Grimmer SFM, Shenoy N, et al. Plasma concentrations of 3-keto-desogestrel after oral administration of desogestrel and intravenous administration of 3-keto-desogestrel. Contraception 1987; 35: 619–26
Viinikka L. Metabolism of a new synthetic progestagen, Org 2969, by human liver in vitro. J Steroid Biochem 1979; 10: 353–7
Madden S, Back DJ, Orme MLE. Metabolism of the contraceptive steroid desogestrel by human liver in vitro. J Steroid Biochem 1990; 35: 281–8
Madden S, Back DJ. Metabolism of norgestimate by human gastrointestinal mucosa and liver microsomes in vitro. J Steroid Biochem Mol Biol 1991; 38: 497–503
Alton KB, Hetyei NS, Shaw C, et al. Biotransformation of norgestimate in women. Contraception 1984; 29: 19–29
Hobe G, Schön R, Schade W, et al. Zur Biotransformation von Dienogest beim Menschen. In: Teichmann AT, editor. Dienog-est — Präklinik und Klinik eines neuen Gestagens. Berlin: Walter de Gruyter Verlag, 1995: 105–17
Oettel M, Kaufmann G, Kurischko A. Das endokrinologische Profil von Metaboliten des Gestagens Dienogest. Pharmazie 1993: 48: 541–5
Cooper JM, Kellie AE. The metabolism of megestrol acetate (17α-acetoxy-6-methylpregna-4,6-diene-3,20-dione) in women. Steroids 1968; 11: 133–49
Kühl H, Jung-Hoffmann C, Heidt F. Alteration in the serum levels of gestodene and SHBG during 12 cycles of treatment with 30 μg ethinylestradiol and 75 μg gestodene. Contraception 1988; 38: 477–86
Höbe G, Klinger G, Reddersen G, et al. Radioimmunologische Bestimmung des Progestagens Dienogest im Plasma und Speichel. Pharmazie 1986; 41: 772–4
Steingold KA, Cefalu W, Pardridge W, et al. Enhanced hepatic extraction of estrogens used for replacement therapy. J Clin Endocrinol Metab 1986; 62: 761–6
Hammond GL, Bocchinfuso WP, Orava M, et al. Serum distribution of two contraceptive progestins: 3-ketodesogestrel and gestodene. Contraception 1994; 50: 301–18
Kuhnz W, Gansau C, Fuhrmeister A. Pharmacokinetics of gestodene in 12 women who received a single oral dose of 0.075 mg gestodene and after a wash-out phase, the same dose during one treatment cycle. Contraception 1992; 46: 29–40
Kuhnz W, Baumann A, Staks T, et al. Pharmacokinetics of gestodene and ethinylestradiol in 14 women during three months of treatment with a new tri-step combination oral contraceptive: serum protein binding of gestodene and influence of treatment on free and total testosterone levels in the serum. Contraception 1993; 48: 303–22
Pollow K, Juchem M, Grill HJ, et al. Gestodene: a novel synthetic progestin — characterization of binding to receptor and serum proteins. Contraception 1989; 40: 325–41
Jung-Hoffmann C, Kühl H. Intra- and interindividual variations in contraceptive steroid levels during 12 treatment cycles: no relation to irregular bleeding. Contraception 1990; 42: 423–38
Guengerich FP. Mechanism-based inactivation of human liver microsomal cytochrome P-450 IIIA4 by gestodene. Chem Res Toxicol 1990; 3: 363–71
Kuhl H, Jung-Hoffmann C, Storch A, et al. New aspects on the mechanism of action of contraceptive steroids — recent phar-macokinetic studies of low dose formulations. Adv Con-tracept 1991; 7 Suppl. 3: 149–63
Viinikka L. Radioimmunoassay of a new progestagen, ORG 2969, and its metabolite. J Steroid Biochem 1978; 9: 979–82
Hasenack HG, Bosch AMG, Käär K. Serum levels of 3-keto-desogestrel after oral administration of desogestrel and 3-keto-desogestrel. Contraception 1986; 33: 591–6
Kuhl H, Jung-Hoffmann C, Heidt F. Serum levels of 3-keto-desogestrel and SHBG during 12 cycles of treatment with 30 μg ethinylestradiol and 150 μg desogestrel. Contraception 1988; 38: 381–90
Kuhl H, Jung-Hoffmann C, Fitzner M. Prodrug versus drug effects of 150 μg desogestrel or 3-keto-desogestrel in combination with 30 μg ethinylestradiol on hormonal parameters: relevance of the peak serum level of 3 keto-desogestrel. Horm Res 1995; 44: 126–32
Kuhl H, Jung-Hoffmann C, Fitzner M, et al. Short- and long-term effects on lipid metabolism of oral contraceptives con-taing 30μg ethinylestradiol and 150μg desogestrel on 3-keto-desogestrel. Horm Res 1995; 44: 121–5
Jung-Hoffmann C, Fitzner M, Kuhl H. Oral contraceptives containing 20 or 30 μg ethinylestradiol and 150 μg desogestrel: pharmacokinetics and pharmacodynamic parameters. Horm Res 1991; 36: 238–46
McGuire JL, Phillips A, Hahn DW, et al. Pharmacologic and pharmacokinetic characteristics of norgestimate and its metabolites. Am J Obstet Gynecol 1990; 163: 2127–31
Kuhnz W, Blöde H, Mahler M. Systemic availability of levo-norgestrel after single oral administration of a norgestimate-containing combination oral contraceptive to 12 young women. Contraception 1994; 49: 255–63
Rühl E, Kühl H. Mechanism-based inhibition of reductase activity in rat liver microsomes by synthetic progestogens. Acta Endocrinol 1992; 126 Suppl. 4: 113
Böcker R, Kleingeist B, Eichhorn M, et al. In vitro interaction of contraceptive steroids with human liver cytochrome P-450 enzymes. Adv Contracept 1991; 7 Suppl. 3: 140–8
Böcker R, Kleingeist B. Der Einfluss von Dienogest auf das humane Cytochrom P-450 Enzymsystem in vitro. In: Teichmann AT, editor. Dienogest — Präklinik und Klinik eines neuen Gestagens. Berlin: Walter de Gruyter Verlag, 1995: 141–7
Juchem M, Schaffrath M, Pollow K, et al. Dienogest: Bindungsstudien an verschiedenen Rezeptor- und Serumproteinen. In: Teichmann AT, editor. Dienogest — Präklinik und Klinik eines neuen Gestagens. Berlin: Walter de Gruyter Verlag, 1995: 119–33
Ezan E, Benech H, Bucourt R, et al. Enzyme immunoassay for nomegestrol acetate in human plasma. J Steroid Biochem Mol Biol 1993; 46: 507–14
Neumann F. Grundlagen der hormonalen Kontrazeption. In: Hammerstein J, editor. 25 Jahre hormonale Kontrazeptiva aus Berlin. Amsterdam: Excerpta Medica, 1986: 36–42
Elger W, Steinbeck H, Schillinger E, et al. Endocrine-phar-amcological profile of gestodene. In: Elstein M, editor. Gesto-dene — development of a new gestodene-containing low-dose oral contraceptive. Carnforth: Parthenon, 1987: 19–33
Eyong E, Elstein M. Comparison of the effects of levonorgestrel and gestodene on pituitary gonadotropins, follicular development and cervical mucus. In: Elstein M, editor. Gestodene — development of a new gestodene-containing low-dose oral contraceptive. Carnforth: Parthenon, 1987: 55–65
Haboubi NY, Eyong E, Chantier EN, et al. Comparative histology of the endometrium under treatment with levonorgestrel and gestodene. In: Elstein M, editor. Gestodene — development of a new gestodene-containing low-dose oral contraceptive. Carnforth: Parthenon, 1987: 73–9
Cullberg G, Lindstedt G, Lundberg PA, et al. Central and peripheral effects of desogestrel 15-60 μg daily for 21 days in healthy female volunteers. Acta Obstet Gynecol Scand 1982; Suppl. 111: 21–8
Cullberg G. Androgenic, anabolic, estrogenic and antiestroge-nic effects of desogestrel and lynestrenol: effects on serum proteins and vaginal cytology. Contraception 1984; 30: 73–9
Cullberg G, Erikson O, Knutsson F, et al. Desogestrel, a new progestational compound. Acta Obstet Gynecol Scand 1982; Suppl. 111: 13–9
Killinger J, Hahn DW, Phillips A, et al. The affinity of norgesti-mate for uterine progestogen receptors and its direct action on the uterus. Contraception 1985; 32: 311–9
Phillips A, Demarest K, Hahn DW, et al. Progestational and androgenic receptor binding affinities and in vivo activities of norgestimate and other progestins. Contraception 1990; 41: 399–409
Juchem M, Pollow K, Elger W, et al. Receptor binding of norgestimate — a new orally active synthetic progestational compound. Contraception 1993; 47: 283–94
Kuhnz W, Fritzemeier KH, Hegele-Hartung C, et al. Comparative progestational activity of norgestimate, levonorgestrel-oxime and levonorgestrel in the rat and binding of these compounds to the progesterone receptor. Contraception 1995; 51: 131–9
Phillips A. The selectivity of a new progestin. Acta Obstet Gynecol Scand 1990; Suppl. 152: 21–4
Phillips A, Hahn DW, Klimek S, et al. A comparison of the potencies and activities of progestogens used in contraceptives. Contraception 1987; 36: 181–92
Hahn DW, Allen GO, McGuire JL. The pharmacological profile of norgestimate, a new orally active progestin. Contraception 1977; 16: 541–53
Kuhnz W, Beier S. Comparative progestational and androgenic activity of norgestimate and levonorgestrel in the rat. Contraception 1994; 49: 275–89
Eyong E, Buchi K, Elstein M. Effects of 180 μg and 250 μg norgestimate on pituitary ovarian function and cervical mucus. Fertil Steril 1988; 50: 756–60
Mohsenian M, Moghissi KS, Borin K. Effects of norgestimate in combination with ethinyl estradiol on cervical mucus. Contraception 1981; 24: 173–81
Seliger E, Kaltwasser P, Schneider F, et al. Behandlung der Endometriose mit Dienogest — Einfluss auf den Rezeptorstatus im Endometrium und vergleichende Bindungsstudien. In: Teichmann AT, editor. Dienogest — Präklinik und Klinik eines neuen Gestagens. Berlin: Walter de Gruyter Verlag, 1995: 231–41
Moore C, Walter F, Klinger G, et al. Der Einfluss von Dienogest auf die Ovulation junger Frauen und auf ausgewählte en-dokrinologische Parameter. In: Teichmann AT, editor. Dienogest — Präklinik und Klinik eines neuen Gestagens. Berlin: Walter de Gruyter Verlag, 1995: 161–9
Oettel M, Elger W, Ernst M, et al. Experimentelle Endokrinpharmakologie von Dienogest. In: Teichmann AT, editor. Dienogest — Präklinik und Klinik eines neuen Gestagens. Berlin: Walter de Gruyter Verlag, 1995: 11–21
Botella J, Paris J, Lahlou B. The cellular mechanism of the antiandrogenic action of nomegestrol acetate, a new 19-nor-progestagen, on the rat prostate. Acta Endocrinol 1987; 115: 544–50
Duc I, Botella J, Delansorne R, et al. Interaction of [3H]nome-gestrol acetate with cytosolic progesterone receptors from the rat uterus. Steroids 1991; 56: 325–8
Fraser DI, Padwick ML, Whitehead MI, et al. The effects of the addition of nomegestrol acetate to post-menopausal oestrogen therapy. Maturitas 1989; 11: 21–34
Botella J, Duc I, Delansorne R, et al. Regulation of rat uterine steroid receptors by nomegestrol acetate, a new 19-nor-pro-gesterone derivative. J Pharm Exp Ther 1989; 248: 758–61
Chretien FC, Dubois R. Effect of nomegestrol acetate on spinability, ferning and mesh dimension of midcycle cervical mucus. Contraception 1991; 43: 55–65
Paris J, Botella J, Fournau P, et al. Extinction of mineralocorti-coid effects in 19-norprogesterone derivatives: structure-activity relationships. J Pharm Exp Ther 1987; 243: 288–91
Botella J, Porthe-Nibelle J, Paris J, et al. Interaction of new 19-nor-progesterone derivatives with progestagen, mineralo-corticoid and glucocorticoid receptors. J Pharmacol 1986; 17: 699–706
Paris J, Thevenot R, Bonnet P, et al. The pharmacological profile of TX 066 (17α-acetoxy-6-methyl-19-nor-4,6-pregna-diene-3,20-dione), a new oral progestative. Drug Res 1983; 33: 710–5
Bazin B, Thevenot R, Bursaux C, et al. Effect of nomegestrol acetate, a new 19-nor-progesterone derivative, on pituitaryovarian function in women. Br J Obstet Gynaecol 1987; 94: 1199–204
Fotherby K. Potency and pharmacokinetics of gestagens. Contraception 1990; 41: 533–50
Balogh A, Lautenschlager MT, Splinter FK, et al. Vergleichende Untersuchungen zum Einfluss von Ethinylestradiol-haltigen Kontrazeptiva mit Dienogest- oder Levonorgestrel-Kom-ponente auf die Cytochrom P-450-Funktion in vivo. In: Teichmann AT, editor. Dienogest — Präklinik und Klinik eines neuen Gestagens. Berlin: Walter de Gruyter Verlag, 1995: 149–59
Ortiz de Montellano PR. Suicide substrates for drug metabolizing enzymes: mechanisms and biological consequences. In: Gibson GG, editor. Progress in drug metabolism. London: Taylor & Francis, 1988: 99–148
Kuhl H, Jung-Hoffmann C. Pharmacokinetics of hormonal contraceptives. In: Moeloek FA, Affandi B, Trounson AO, editors. Advances in human reproduction. New York: Parthenon Publications, 1995: 133–41
Fern M, Rose DP, Fern EB. Effect of oral contraceptives on plasma androgenic steroids and their precursors. Obstet Gynecol 1978; 51: 541–4
Van der Vange N. Seven low dose oral contraceptives and their influence on metabolic pathways and ovarian activity [thesis]. Utrecht: Univ. of Utrecht, 1986: chap. 4, 71–84
Kim-Björklund T, Landgren BM, Hamberger L. Is the contraceptive effect of 300 μg norethisterone mainly peripheral or central? Contraception 1992; 45: 57–66
Schürenkämper P, Lisse K. Effects of the new progestagen STS 557 on the biosynthesis of steroids in tissue slices of the human ovary. Exp Clin Endocrinol 1985; 86: 185–9
Elger W, Steinbeck H, Schilllinger E, et al. Endocrine-pharmacological profile of gestodene. Adv Contracept Deliv Syst 1986; 2: 182–97
Phillips A, Demarest K, Hahn DW, et al. Progestational and androgenic receptor binding affinities and in vivo activities of norgestimate and other progestins. Contraception 1990; 41: 399–410
Jung-Hoffmann C, Kuhl H. Divergent effects of two low-dose oral contraceptives on sex hormone-binding globulin and free testosterone. Am J Obstet Gynecol 1987; 156: 199–203
van der Vange N, Blankenstein MA, Kloosterboer HJ, et al. Effects of seven low-dose combined oral contraceptives on sex hormone binding globulin, corticosteroid binding globulin, total and free testosterone. Contraception 1990; 41: 345–52
Ain KB, Mori Y, Refetoff S. Reduced clearance rate of thyrox-ine-binding globulin (TBG) with increased sialylation: a mechanism for estrogen-induced elevation of serum TBG concentration. J Clin Endocrinol Metab 1987; 65: 689–96
Kauppinen-Mäkelin R, Kuusi T, Ylikorkala O et al. Contraceptives containing desogestrel or levonorgestrel have different effects on serum lipoproteins and post-heparin plasma lipase activities. Clin Endocrinol 1992; 36: 203–9
Jung-Hoffmann C, Heidt F, Kuhl H. Effect of two oral contraceptives containing 30 μg ethinylestradiol and 75 μg gestodene or 150 μg desogestrel upon various hormonal parameters. Contraception 1988; 38: 593–603
Wiegratz I, Jung-Hoffmann C, Kuhl H. Effect of two oral contraceptives containing ethinylestradiol and gestodene or norgestimate upon androgen parameters and serum binding proteins. Contraception 1995; 51: 341–6
Moore C, Walter F, Klinger G et al. Der Einfluss von Dienogest auf die Ovulation junger Frauen und auf ausgewählte endo-krinologische Parameter. In: Teichmann AT, editor. Dienogest — Präklinik und Klinik eines neuen Gestagens. Berlin: Walter de Gruyter Verlag, 1995: 161–9
Basdevant A, Pelissier C, Conard J, et al. Effects of nomegestrol acetate (5 mg/d) on hormonal, metabolic and hemostatic parameters in premenopausal women. Contraception 1991; 44: 599–605
Kuhl H. Pharmacokinetics of oestrogens and progestogens. Maturitas 1990; 12: 171–97
Prasad RNV, Koh S, Ratnam SS. Effects of three types of combined O.C. pills on blood coagulation, fibrinolysis and platelet function. Contraception 1989; 39: 369–83
Cohen H, Mackie IJ, Walshe K, et al. A comparison of the effects of two triphasic oral contraceptives on haemostasis. Br J Haematol 1988; 69: 259–63
Omsjo IH, Oian P, Maltau JM, et al. Effects of two triphasic oral contraceptives containing ethinylestradiol plus levonorgestrel or gestodene on blood coagulation and fibrinolysis. Acta Ob-stet Gynecol Scand 1989; 68: 27–30
Refn H, Kjaer A, Lebech AM, et al. Metabolic changes during tratment with two different progestogens. Am J Obstet Gynecol 1990; 163: 374–7
Ball MJ, Ashwell E, Jackson M, et al. Comparison of two triphasic contraceptives with different progestogens: effects on metabolism and coagulation proteins. Contraception 1990; 41: 363–76
Bonnar J. Coagulation effects of oral contraception. Am J Obstet Gynecol 1987; 157: 1042–8
Hillard TC, Bourne TH, Whitehead MI, et al. Differential effects of transdermal estradiol and sequential progestogens on impedance to flow within the uterine arteries of post-menopausal women. Fertil Steril 1992; 58: 959–63
Sarrel P. Effects of ovarian steroids on the cardiovascular system. In: Ginsberg J, editor. The circulation in the female. Car-nforth: Parthenon, 1989: 117–41
Goodrich SM, Wood JE. Peripheral venous distensibility and velocity of venous blood flow during pregnancy or during oral contraceptive therapy. Am J Obstet Gynecol 1964; 90: 740–4
Fawer R, Dettling A, Weihs D, et al. Effect of the menstrual cycle, oral contraception and pregnancy on forearm blood flow, venous distensibility and clotting factors. Eur J Clin Pharmacol 1978; 13: 251–7
Bonnar J. Changes in coagulation and fibrinolysis with low dose oral contraceptives. Adv Contracept 1991; 7 Suppl. 3: 285–91
Thomson JM, Poller L, Bocaz JA, et al. A multicentre study of coagulation and haemostatic variables during oral contraception: variations with four formulations. Br J Obstet Gynaecol 1991; 98: 1117–28
Winkler UH, Koslowski S, Oberhoff C, et al. Changes of the dynamic equilibrium of hemostasis associated with the use of low-dose oral contraceptives: a controlled study of cyproter-one acetate containing oral contraceptives combined with either 35 or 50 μg ethinyl estradiol. Adv Contracept 1991; 7 Suppl. 3: 273–84
Winkler UH, Bühler K, Oberhoff C, et al. The dynamic balance of hemostasis: a key for understanding thromboembolism in oral contraceptive users. In: Genazzani AR, Petraglia F, Boselli F, et al., editors. Current research in gynecology and obstetrics. Carnforth: Parthenon, 1991: 389–94
Briel RC, Schindler AE, Zwirner M et al. Veränderungen gerinnungsphysiologischer Parameter durch orale Kontrazeption mit einem Desogestrel-haltigen Zweiphasenpräparat bei Rauchern und Nichtrauchern. Hamostaseologie 1988; 8/3: 1–11
Melis GB, Fruzzetti F, Nicoletti I et al. A comparative study on the effects of a monophasic pill containing desogestrel plus 20 μg ethinylestradiol, a triphasic combination containing levonorgestrel and a monophasic combination containing gestodene on coagulatory factors. Contraception 1991; 43: 23–31
Inauen W, Baumgartner HR, Haeberli A, et al. Excessive deposition of fibrin, platelets and platelet thrombi on vascular sub-endothelium during contraceptive drug treatment. Thromb Haemostas 1987; 57: 306–9
Gram J, Munkvad S, Jespersen J. Enhanced generation and resolution of fibrin in women above the age of 30 years using oral contraceptives low in estrogen. Am J Obstet Gynecol 1990; 163: 438–42
Petersen K, Sidelmann J, Skouby O, et al. Effects of monphasic low-dose oral contraceptives on fibrin formation and resolution in young women. Am J Obstet Gynecol 1993; 168: 32–8
Kuusi T, Nikkilä EA, Tikkanen MJ, et al. Effects of two pro-gestins with different androgenic properties on hepatic endo-thelial lipase and high density lipoprotein2. Atherosclerosis 1985; 54: 251–62
Tikkanen MJ, Kuusi T, Nikkilä EA, et al. Post-menopausal hormone replacement therapy: effects of progestogens on serum lipids and lipoproteins: a review. Maturitas 1986; 8: 7–17
Kuhl H, März W, Jung-Hoffmann C, et al. Time-dependent alterations in lipid metabolism during treatment with low-dose oral contraceptives. Am J Obstet Gynecol 1990; 163: 363–9
Speroff L, DeCherney A. Evaluation of a new generation of oral contraceptives. Obstet Gynecol 1993; 81: 1034–47
Janaud AJ, Rouffy J, Upmalis D, et al. A comparison study of lipid and androgen metabolism with a triphasic oral contraceptive formulation containing norgestimate or levonorgestrel. Acta Obstet Gynecol Scand 1992; 71: 33–8
Silfverstolpe G, Johnson P, Samsioe G, et al. Lipid metabolic studies in oophorectomized women: effects induced by the addition of norethisterone acetate to two different oestrogens on serum individual phospholipids and serum lecithin fatty acid composition. Acta Endocrinol 1981; 96: 527–33
Kuhl H, März W, Jung-Hoffmann C, et al. Effect on lipid metabolism of a biphasic desogestrel-containing oral contraceptive: divergent changes in apolipoprotein B and E and transitory decrease in Lp(a) levels. Contraception 1993; 47: 69–83
Spellacy WN. Carbohydrate metabolism during treatment with estrogen, progestogen and low-dose oral contraceptives. Am J Obstet Gynecol 1982; 142: 732–4
van den Ende A, Liitlens A, van Wayjen RGA, et al. Effects of the oral contraceptive combination 0.150 mg desogestrel plus 0.020 mg ethinylestradiol on carbohydrate metabolism in healthy female volunteers. Acta Obstet Gynecol Scand 1987; Suppl. 144: 29–32
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: 1375–81
Kuhl H, Jung-Hoffmann C, Weber J, et al. The effect of a biphasic desogestrel-containing oral contraceptive on carbohydrate metabolism and various hormonal parameters. Contraception 1993; 47: 55–68
Miccoli R, Orlandi MC, Fruzzetti O, et al. Metabolic effects of three new low-dose pills: a six-month experience. Contraception 1989; 39: 643–52
Spellacy WN, Tsibris JCM, Hunter-Bonner DL, et al. Six month carbohydrate metabolism studies in women using oral contraceptives containing gestodene and ethinylestradiol. Contraception 1992; 45: 533–9
Spellacy WN, Tsibris AMN, Tsibris JCM, et al. Carbohydrate metabolism studies after one year of using an oral contraceptive containing gestodene and ethinyl estradiol. Contraception 1994; 49: 125–30
Godsland IF, Walton C, Felton C, et al. Insulin resistance, secretion, and metabolism in users of oral contraceptives. J Clin Endocrinol Metab 1991; 74: 64–70
Crook D, Gosland I, Worthington M, et al. A comparative metabolic study of two low-dose oral contraceptives containing gestodene and desogestrel progestins. Am J Obstet Gynecol 1993; 169: 1183–9
Godsland IF, Crook D. Update on the metabolic effects of ste-roidal contraceptives and their relationship to cardiovascular disease risk. Am J Obstet Gynecol 1994; 170: 1528–36
van der Vange N, Kloosterboer HJ, Haspels AA. Effect of seven low-dose combined oral contraceptive preparations on carbohydrate metabolism. Am J Obstet Gynecol 1987; 156: 918–22
Dorangeon P, Thomas JL, Choisy H, et al. Effects of nomegestrol acetate on carbohydrate metabolism. Diabete Metab 1993; 19: 441–5
Tsibris JCM, Hunt LT, Ballejo G, et al. Selective inhibition of protein disulfide isomerase by estrogens. J Biol Chem 1989; 264: 13967–70
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Kuhl, H. Comparative Pharmacology of Newer Progestogens. Drugs 51, 188–215 (1996). https://doi.org/10.2165/00003495-199651020-00002
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DOI: https://doi.org/10.2165/00003495-199651020-00002