Pharmacodynamics of combined estrogen-progestin oral contraceptives: 1. Effects on metabolism

References

• Geampana A. Pregnancy is more dangerous than the pill: a critical analysis of professional responses to the Yaz/Yasmin controversy. Soc Sci Med. 2016;166:9–16.
   PubMed Web of Science ®Google Scholar
• WHO, UNICEF, UNFPA, World Bank Group and the United Nations Population Division. Trends in maternal mortality: 1990 to 2015. Geneva: World health Organization; 2015. ISBN 978 92 4 156514 1.
   Google Scholar
• Briozzo L, Vidiella G, Rodríguez F, et al. A risk reduction strategy to prevent maternal deaths associated with unsafe abortion. Int J Gynecol Obstet. 2006;95:221–226.
   PubMed Web of Science ®Google Scholar
• Benagiano G, Primiero FM. Cycloprovera. In: Zatuchni GI, Goldsmith A, Shelton JD, Sciarra JJ, editors. Long-acting contraceptive delivery systems. Philadelphia (PA): Harper and Row; 1984. p. 523–536 (PARFR Series on Fertility Regulation).
   Google Scholar
• G H S, Meador ML, Lenihan JP Jr, et al. For the ORTHO EVRAEVRA 002 Study Group. Efficacy and safety of a transdermal contraceptive system. Obst Gynecol. 2001;98:799–805.
   PubMed Web of Science ®Google Scholar
• Watkins ES. On the pill: a social history of oral contraceptives, 1950–1970. Baltimore: Johns Hopkins University Press; 1998.
   Google Scholar
• Badaracco M, Vessey MP; the Medical Research Council Working Group. Risk of thromboembolicdisease in women taking oral contraceptives. Brit Med J. 1967;2:355–359.
   PubMedGoogle Scholar
• Benagiano G, Bastianelli C, Farris M. Contraception Today. Ann NY Acad Sci. 2006;1092:1–32.
   PubMed Web of Science ®Google Scholar
• Benagiano G, Bastianelli C, Farris M. Oral contraceptives, an update on clinical issues and perspectives. In: Kohli K, Gupta M, Tejwani S, editors. Contemporary perspectives on clinical pharmacotherapeutics. Delhi: Elsevier; 2006. p. 482–500.
   Google Scholar
• Ågren UM, Anttila M, Mäenpää-Liukko K, et al. Effects of a monophasic combined oral contraceptive containing nomegestrol acetate and 17β-oestradiol compared with one containing levonorgestrel and ethinylestradiol on haemostasis, lipids and carbohydrate metabolism. Eur J Contracept Reprod Health Care. 2011;16:444–457.
   PubMed Web of Science ®Google Scholar
• Ahrendt HJ, Makalová D, Parke S, et al. Bleeding pattern and cycle control with an estradiol-based oral contraceptive: a seven-cycle, randomized comparative trial of estradiol valerate/dienogest and ethinyl estradiol/levonorgestrel. Contraception. 2009;80:436–444.
   PubMed Web of Science ®Google Scholar
• Apter D, Zimmerman Y, Beekman L, et al. Bleeding pattern and cycle control with estetrol-containing combined oral contraceptives: results from a phase II, randomised, dose-finding study (FIESTA). Contraception. 2016. [Epub ahead of print: May 3. pii: S0010-7824(16)30050-6. DOI:10.1016/j]
   Web of Science ®Google Scholar
• Krattenmacher R. Drospirenone: pharmacology and pharmacokinetics of a unique progestogen. Contraception. 2000;62:29–38.
   PubMed Web of Science ®Google Scholar
• Bachmann G, Kopacz S. Drospirenone/ethinyl estradiol 3 mg/20 μg (24/4 day regimen): hormonal contraceptive choices – use of a fourth-generation progestin. Patient Prefer Adherence. 2009;3:259–264.
   PubMed Web of Science ®Google Scholar
• Pérez-Campos EF. Ethinylestradiol/dienogest in oral contraception. Drugs. 2010;70:681–689.
   PubMed Web of Science ®Google Scholar
• Kiley JW, Shulman LP. Estradiol valerate and dienogest: a new approach to oral contraception. Int J Womens Health. 2011;3:281–286.
   PubMedGoogle Scholar
• Owen LN, Briggs MH. Contraceptive steroid toxicology in the Beagle dog and its relevance to human carcinogenicity. Curr Med Res Opin. 1976;4(5):309–329.
   PubMedGoogle Scholar
• Echt CR, Berner HW Jr, Dersch DM. Evaluation of megestrol acetate and ethinyl estradiol as an oral contraceptive. Fertil Steril. 1967;18:840–844.
   PubMed Web of Science ®Google Scholar
• Zahradnik HP. Belara® – A reliable oral contraceptive with additional benefits for health and efficacy in dysmenorrhea. Eur J Contracept Reprod Health Care. 2005;10(Suppl 1):12–18.
   PubMed Web of Science ®Google Scholar
• Mueck AO, Sitruk-Ware R. Nomegestrol acetate, a novel progestogen for oral contraception. Steroids. 2011;76:531–539.
   PubMed Web of Science ®Google Scholar
• De Leo V, Musacchio MC, Cappelli V, et al. Hormonal contraceptives: pharmacology tailored to women’s health. Hum Reprod Update. 2016;22:634–646.
   PubMed Web of Science ®Google Scholar
• Hirvonen E, Mälkönen M, Manninen V. Effects of different progestogens on lipoproteins during postmenopausal replacement therapy. N Engl J Med. 1981;304:560–563.
   PubMed Web of Science ®Google Scholar
• Sitruk-Ware R. New progestagens for contraceptive use. Human Reproduction Update. 2006;12:169–178.
   PubMed Web of Science ®Google Scholar
• Schwers J, Eriksson G, Wiqvist N, et al. 15a-hydroxylation: A new pathway of estrogen metabolism in the human fetus and newborn. Biochim Biophys Acta. 1965;100:313–316.
   PubMed Web of Science ®Google Scholar
• Helgason S, Damber MG, Von Schoultz B, et al. Estrogenic potency of oral replacement therapy estimated by the induction of pregnancy zone protein. Acta Obstet Gynecol Scand. 1982;61:75–79.
   PubMed Web of Science ®Google Scholar
• Crook D, Godsland I. Safety evaluation of modern oral contraceptives. Effects on lipoprotein and carbohydrate metabolism. Contraception. 1998;57:189–201.
   PubMed Web of Science ®Google Scholar
• Sitruk-Ware R, Nath A. Characteristics and metabolic effectsof estrogen and progestins containedin oral contraceptive pills. Pract Res Clin Endocrinol Metab. 2013;27:13–24.
   PubMed Web of Science ®Google Scholar
• Grandi G, Napolitano A, Cagnacci A. Metabolic impact of combined hormonal contraceptives containing estradiol. Expert Opin Drug Metab Toxicol. 2016;12:779–787.
   PubMed Web of Science ®Google Scholar
• Lopez LM, Grimes DA, Schulz KF. Steroidal contraceptives: effect on carbohydrate metabolism in women without diabetes mellitus. Cochrane Database System Rev. 2014;4:CD006133.
   PubMed Web of Science ®Google Scholar
• Liukko P, Erkkola R, Lammintausta R, et al. Blood glucose, serum insulin, serum growth hormone and serum glycosylated proteins during two years’ oral contraception with low-estrogen combinations. Ann Chir Gynaecol Suppl. 1987;202:45–49.
   PubMedGoogle Scholar
• Prasad RN, Liew D, Ratnam SS. Comparative metabolic effects of three types of combined oral contraceptive pills in Chinese women. Contraception. 1989;39:21–35.
   PubMed Web of Science ®Google Scholar
• Luyckx AS, Gaspard UJ, Romus MA, et al. Carbohydrate metabolism in women who used oral contraceptives containing levonorgestrel or desogestrel: a 6-month prospective study. Fertil Steril. 1986;45:635–642.
   PubMed Web of Science ®Google Scholar
• Knopp RH, Broyles FE, Cheung M, et al. Comparison of the lipoprotein, carbohydrate, and hemostatic effects of phasic oral contraceptives containing desogestrel or levonorgestrel. Contraception. 2001;63:1–11.
   PubMed Web of Science ®Google Scholar
• Van Der Mooren MJ, Klipping C, Van Aken B, et al. A comparative study of the effects of gestodene 60 microg/ethinylestradiol 15 microg and desogestrel 150 microg/ethinylestradiol 20 microg on hemostatic balance, blood lipid levels and carbohydrate metabolism. Eur J Contracept Reprod Health Care. 1999 Nov;4(Suppl 2):27–35.
   PubMed Web of Science ®Google Scholar
• Lüdicke F, Gaspard UJ, Demeyer F, et al. Randomized controlled study of the influence of two low estrogen dose oral contraceptives containing gestodene or desogestrel on carbohydrate metabolism. Contraception. 2002;66:411–415.
   PubMed Web of Science ®Google Scholar
• Steppan CM, Bailey ST, Bhat S, et al. The hormone resistin links obesity to diabetes. Nature. 2001;409:307–312.
   PubMed Web of Science ®Google Scholar
• Rechberger T, Tomaszewski J, Pieprzowska-Białek A, et al. Serum resistin levels in women taking combined oral contraceptives containing desogestrel or gestodene. Contraception. 2004;69:477–480.
   PubMed Web of Science ®Google Scholar
• Cagnacci A, Ferrari S, Tirelli A, et al. Route of administration of contraceptives containing desogestrel/etonogestrel and insulin sensitivity. A prospective randomized study. Contraception. 2009;80:34–39.
   PubMed Web of Science ®Google Scholar
• Cagnacci A, Ferrari S, Tirelli A, et al. Insulin sensitivity and lipid metabolism with oral contraceptives containing chlormadinone acetate or desogestrel: a randomized trial. Contraception. 2009;79:111–116.
   PubMed Web of Science ®Google Scholar
• Oelkers W, Foidart JM, Dombrovicz N, et al. Effects of a new oral contraceptive containing an antimineralocorticoid progestogen, drospirenone, on the renin-aldosterone system, body weight, blood pressure, glucose tolerance, and lipid metabolism. J Clin Endocrinol Metab. 1995;80:1816–1821.
   PubMed Web of Science ®Google Scholar
• Gaspard U, Scheen A, Endrikat J, et al. A randomized study over 13 cycles to assess the influence of oral contraceptives containing ethinylestradiol combined with drospirenone or desogestrel on carbohydrate metabolism. Contraception. 2003;67:423–429.
   PubMed Web of Science ®Google Scholar
• Klipping C, Marr J. Effects of two combined oral contraceptives containing ethinyl estradiol 20 μg combined with either drospirenone or desogestrel on lipids, hemostatic parameters and carbohydrate metabolism. Contraception. 2005;71:409–416.
   PubMed Web of Science ®Google Scholar
• Benagiano G, Carrara S, Filippi V. Safety, efficacy and patient satisfaction with continuous daily administration of levonorgestrel/ethinylestradiol oral contraceptives. Patient Prefer Adherence. 2009;3:131–143.
   PubMed Web of Science ®Google Scholar
• Machado RB, De Melo NR, Maia H Jr, et al. Effect of a continuous regimen of contraceptive combination of ethinylestradiol and drospirenone on lipid, carbohydrate and coagulation profiles. Contraception. 2010;81:102–106.
   PubMed Web of Science ®Google Scholar
• Wiegratz I, Stahlberg S, Manthey T, et al. Effects of combined oral contraceptive ethinylestradiol (30 microg) and dienogest (2 mg) on carbohydrate metabolism during 1 year of conventional or extended-cycle use. Horm Metab Res. 2010;42:358–363.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Junge W, Mellinger U, Parke S, et al. Metabolic and haemostatic effects of estradiol valerate/dienogest, a novel oral contraceptive: a randomized, open-label, single-centre study. Clin Drug Investig. 2011;31:573–584.
   PubMed Web of Science ®Google Scholar
• Grandi G, Piacenti I, Volpe A, et al. Modification of body composition and metabolism during oral contraceptives containing non-androgenic progestins in association with estradiol or ethinyl estradiol. Gynecol Endocrinol. 2014;30:676–680.
   PubMed Web of Science ®Google Scholar
• Mawet M, Maillard C, Klipping C, et al. Unique effects on hepatic function, lipid metabolism, bone and growth endocrine parameters of estetrol in combined oral contraceptives. Eur J Contracept Reprod Health Care. 2015;20:463–475.
   PubMed Web of Science ®Google Scholar
• Machado RB, Bernardes CR, De Souza IM, et al. Is lipid profile determination necessary in women wishing to use oral contraceptives? Contraception. 2013;87:801–805.
   PubMed Web of Science ®Google Scholar
• Oster P, Arab L, Kohlmeier M, et al. Effects of estrogens and progestogens on lipid metabolism. Am J Obstet Gynecol. 1982;142:773–775.
   PubMed Web of Science ®Google Scholar
• Ottosson UB. Oral progesterone and estrogen/progestogen therapy: effects of natural and synthetic hormones on subfractions of HDL cholesterol and liver proteins. Acta Obstet Gynecol Scand. 1984;127(Suppl):1–37.
   Google Scholar
• Van Rooijen M, Von Schoultz B, Silveira A, et al. Different effects of oral contraceptives containing levonorgestrel or desogestrel on plasma lipoproteins and coagulation factor VII. Am J Obstet Gynecol. 2002;186:44–48.
   PubMed Web of Science ®Google Scholar
• Gaspard U, Endrikat J, Desager JP, et al. A randomized study on the influence of oral contraceptives containing ethinylestradiol combined with drospirenone or desogestrel on lipid and lipoprotein metabolism over a period of 13 cycles. Contraception. 2004;69:271–278.
   PubMed Web of Science ®Google Scholar
• Taneepanichskul S, Phupong V. Influence of a new oral contraceptive with drospirenone on lipid metabolism. Gynecol Endocrinol. 2007;23:347–350.
   PubMed Web of Science ®Google Scholar
• Garn SM. The course of bone gain and the phases of bone loss. Orthop Clin North Am. 1972;3:503–520.
   PubMedGoogle Scholar
• Trémollieres F. Impact of oral contraceptive on bone metabolism. Best Pract Res Clin Endocrinol Metab. 2013;27:47–53.
   PubMed Web of Science ®Google Scholar
• Sabatier JP, Guaydier-Souquieres G, Laroche D, et al. Bone mineral acquisition during adolescence and early adulthood: a study in 574 healthy females 10-24 years of age. Osteoporos Int. 1996;6:141–148.
   PubMed Web of Science ®Google Scholar
• Vanderschueren D, Venken K, Ophoff J, et al. Sex steroids and the periosteum – reconsidering the roles of androgens and estrogens in periosteal expansion. J Clin Endocrinol Metab. 2006;91:378–382.
   PubMed Web of Science ®Google Scholar
• Polatti F, Perotti F, Gallina D, et al. Bone mass and long-term monophasic oral contraceptive treatment in young women. Contraception. 1995;51:221–224.
   PubMed Web of Science ®Google Scholar
• Lloyd T, Taylor DS, Lin HM, et al. Oral contraceptive use by teenage women does not affect peak bone mass: a longitudinal study. Fertil Steril. 2000;74:734–738.
   PubMed Web of Science ®Google Scholar
• Nappi C, Di Spiezio SA, Acunzo G, et al. Effects of a low-dose and ultra-low-dose combined contraceptive use on bone turnover and bone mineral density in young fertile women: a prospective controlled randomized study. Contraception. 2003;67:355–359.
   PubMed Web of Science ®Google Scholar
• Martins SL, Curtis KM, Glasier AF. Combined hormonal contraception and bone health: a systematic review. Contraception. 2006;73:445–469.
   PubMed Web of Science ®Google Scholar
• Hartard M, Kleinmond C, Wiseman M, et al. Detrimental effect of oral contraceptives on parameters of bone mass and geometry in a cohort of 248 young women. Bone. 2007;40:444–450.
   PubMed Web of Science ®Google Scholar
• Pikkarainen E, Lehtonen-Veromaa M, Mottonen T, et al. Estrogen-progestin contraceptiveuse during adolescence prevents bone mass acquisition: a 4-year follow-up study. Contraception. 2008;78:226–231.
   PubMed Web of Science ®Google Scholar
• Lattakova M, Borovsky M, Payer J, et al. Oral contraception usage in relation to bone mineral density and bone turnover in adolescent girls. Eur J Contracept Reprod Health Care. 2009;14:207–214.
   PubMed Web of Science ®Google Scholar
• Scholes D, Ichikawa L, LaCroix AZ, et al. Oral contraceptive use and bone density in adolescent and young adult women. Contraception. 2010;81:35–40.
   PubMed Web of Science ®Google Scholar
• Scholes D, Hubbard RA, Ichikawa LE, et al. Oral contraceptive use and bone density change in adolescent and young adult women: a prospective study of age, hormone dose, and discontinuation. J Clin Endocrinol Metab. 2011;96:1380–1387.
   PubMed Web of Science ®Google Scholar
• Cibula D, Skrenkova J, Hill M, et al. Low-dose estrogen combined oral contraceptives may negatively influence physiological bone mineral density acquisition during adolescence. Eur J Endocrinol. 2012;166:1003.
   PubMed Web of Science ®Google Scholar
• Biason TP, Goldberg TB, Kurokawa CS, et al. Low-dose combined oral contraceptive use is associated with lower bone mineral content variation in adolescents over a 1-year period. BMC Endocr Disord. 2015;15:15–22.
   PubMed Web of Science ®Google Scholar
• Liu SL, Lebrun CM. Effect of oral contraceptives and hormone replacement therapy on bone mineral density in premenopausal and perimenopausal women: a systematic review. Br J Sports Med. 2006;40:11–24.
   PubMed Web of Science ®Google Scholar
• Isley MM, Kaunitz AM. Update on hormonal contraception and bone density. Rev Endocr Metab Disord. 2011;12:93–106.
   PubMed Web of Science ®Google Scholar
• Shargil AA. Hormone replacement therapy in perimenopausal women with a triphasic contraceptive compound; a three-year prospective study. Int J Fertil. 1985;30:18–28.
   PubMedGoogle Scholar
• Volpe A, Amram A, Cagnacci A, et al. Biochemical aspects of hormonal contraception: effects on bone metabolism. Eur J Contracept Reprod Health Care. 1997;2:123–126.
   PubMedGoogle Scholar
• Gambacciani M, Spinetti A, Cappagli B, et al. Hormone replacement therapy in perimenopausal women with a low dose oral contraceptive preparation: effects on bone mineral density and metabolism. Maturitas. 1994;19:125–131.
   PubMed Web of Science ®Google Scholar
• Gambacciani M, Spinetti A, Taponeco F, et al. Longitudinal evaluation of perimenopausal vertebral bone loss: effects of a low-dose oral contraceptive preparation on bone mineral density and metabolism. Obstet Gynecol. 1994;83:392–396.
   PubMed Web of Science ®Google Scholar
• Gambacciani M, Cappagli B, Ciaponi M, et al. Hormone replacement therapy in perimenopause: effect of a low dose oral contraceptive preparation on bone quantitative ultrasound characteristics. Menopause. 1999;6:43–48.
   PubMed Web of Science ®Google Scholar
• Gambacciani M, Ciaponi M, Cappagli B, et al. Longitudinal evaluation of perimenopausal femoral bone loss: effects of a low-dose oral contraceptive preparation on bone mineral density and metabolism. Osteoporos Int. 2000;11:544–548.
   PubMed Web of Science ®Google Scholar
• Gambacciani M, Cappagli B, Lazzarini V, et al. Longitudinal evaluation of perimenopausal bone loss: effects of different low dose oral contraceptive preparations on bone mineral density. Maturitas. 2006;54:176–180.
   PubMed Web of Science ®Google Scholar
• Elkazaz AY, Salama K. The effect of oral contraceptive different patterns of use on circulating IGF-1 and bone mineral density in healthy premenopausal women. Endocrine. 2015;48:272–278.
   PubMed Web of Science ®Google Scholar
• Cartwright B, Robinson J, Seed PT, et al. Hormone replacement therapy versus the combined oral contraceptive pill in premature ovarian failure: a randomized controlled trial of the effects on bone mineral density. J Clin Endocrinol Metab. 2016;101:3497–3505.
   PubMed Web of Science ®Google Scholar
• Gersten J, Hsieh J, Weiss H, et al. Effect of extended 30 μg ethinyl estradiol with continuous low-dose ethinyl estradiol and cyclic 20 μg ethinyl estradiol oral contraception on adolescent bone density: a randomized trial. J Pediatr Adolesc Gynecol. 2016;29:635–642.
   PubMedGoogle Scholar
• Sørdal T, Grob P, Verhoeven C. Effects on bone mineral density of a monophasic combined oral contraceptive containing nomegestrol acetate/17β-estradiol in comparison to levonorgestrel/ethinylestradiol. Acta Obstet Gynecol Scand. 2012;91:1279–1285.
   PubMed Web of Science ®Google Scholar
• Lopez LM, Grimes DA, Schulz KF, et al. Steroidal contraceptives: effect on bone fractures in women. Cochrane Database System Rev. 2014;6:CD006033.
   PubMed Web of Science ®Google Scholar
• Scholes D, LaCroix AZ, Hubbard RA, et al. Oral contraceptive use and fracture risk around the menopausal transition. Menopause. 2016;23:166–174.
   PubMed Web of Science ®Google Scholar
• Seeman E, Szmukler GI, Formica C, et al. Osteoporosis in anorexia nervosa: the influence of peak bone density, bone loss, oral contraceptive use, and exercise. J Bone Miner Res. 1992;7:1467–1474.
   PubMed Web of Science ®Google Scholar
• Mehler PS. Osteoporosis in anorexia nervosa: prevention and treatment. Int J Eat Disord. 2003;33:113–126.
   PubMed Web of Science ®Google Scholar
• Klibanski A, Biller BM, Schoenfeld DA, et al. The effects of estrogen administration on trabecular bone loss in young women with anorexia nervosa. J Clin Endocrinol Metab. 1995;80:898–904.
   PubMed Web of Science ®Google Scholar
• Golden NH, Lanzkowsky E, Schebendach J, et al. The effect of estrogen-progestin treatment on bone mineral density in anorexia nervosa. J Pediatr Adolesc Gynecol. 2002;15:135–143.
   PubMedGoogle Scholar
• Warren MP, Millerb KK, Olsonc WH, et al. Effects of an oral contraceptive (norgestimate/ethinyl estradiol) on bone mineral density in women with hypothalamic amenorrhea and osteopenia: an open-label extension of a double-blind, placebo-controlled study. Contraception. 2005;72:206–211.
   PubMed Web of Science ®Google Scholar
• Strokosch GR, Friedman AI, Wu S-CH, et al. Effects of an Oral Contraceptive (Norgestimate/Ethinyl Estradiol) on bone mineral density in adolescent females with anorexia nervosa: a double-blind, placebo-controlled study. J Adolesc Health. 2006;39:819–827.
   PubMed Web of Science ®Google Scholar
• Legroux-Gerot I, Vignau J, Collier F, et al. Factors influencing changes in bone mineral density in patients with anorexia nervosa-related osteoporosis: the effect of hormone replacement therapy. Calcif Tissue Int. 2008;83:315–323.
   PubMed Web of Science ®Google Scholar
• DiVasta AD, Feldman HA, Beck TJ, et al. Does hormone replacement normalize bone geometry in adolescents with anorexia nervosa? J Bone Miner Res. 2014;29:151–157.
   PubMed Web of Science ®Google Scholar
• Robinson E, Bachrach LK, Katzman DK. Use of hormone replacement therapy to reduce the risk of osteopenia in adolescent girls with anorexia nervosa. J Adolesc Health. 2000;26:343–348.
   PubMed Web of Science ®Google Scholar