Unique effects on hepatic function, lipid metabolism, bone and growth endocrine parameters of estetrol in combined oral contraceptives

Mawet, Marie; Maillard, C.; Klipping, C.; Zimmerman, Y.; Foidart, Jean-Michel; Bennink, H. J. T. C.

doi:10.3109/13625187.2015.1068934

Article (Scientific journals)

Unique effects on hepatic function, lipid metabolism, bone and growth endocrine parameters of estetrol in combined oral contraceptives

Mawet, Marie; Maillard, C.; Klipping, C. et al.

2015 • In European Journal of Contraception and Reproductive Health Care, 20 (6), p. 463-475

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https://hdl.handle.net/2268/193296

DOI
10.3109/13625187.2015.1068934

PubMed
26212489

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Keywords :

Bone markers; Drospirenone; Endocrinology; Estetrol; Levonorgestrel; Lipid metabolism; Liver function; Article

Abstract :

[en] Objectives Estetrol (E<inf>4</inf>) is a natural estrogen produced by the human fetal liver. In combination with drospirenone (DRSP) or levonorgestrel (LNG), E<inf>4</inf> blocks ovulation and has less effect on haemostatic biomarkers in comparison with ethinylestradiol (EE) combined with DRSP. This study evaluates the impact of several doses of E<inf>4</inf>/DRSP and E<inf>4</inf>/LNG on safety parameters such as liver function, lipid metabolism, bone markers and growth endocrine parameters.Methods This was a dose-finding, single-centre, controlled study performed in healthy women aged 18 to 35 years with a documented pretreatment ovulatory cycle. Participants received 5 mg or 10 mg E<inf>4</inf>/3 mg DRSP; 5 mg, 10 mg or 20 mg E<inf>4</inf>/150 g LNG; or 20 g EE/3 mg DRSP as a comparator for three consecutive cycles in a 24/4-day regimen. Changes from baseline to end of treatment in liver parameters, lipid metabolism, bone markers and growth endocrinology were evaluated.Results A total of 109 women were included in the study. Carrier proteins were minimally affected in the E<inf>4</inf>/DRSP and E<inf>4</inf>/LNG groups, in comparison with the EE/DRSP group, where a significant increase in sex hormone-binding globulin was observed. Similarly, minor effects on lipoproteins were observed in the E<inf>4</inf> groups, and the effects on triglycerides elicited by the E<inf>4</inf> groups were significantly lower than those in the EE/DRSP group. No imbalances in bone markers were observed in any groups. No alterations in insulin-like growth factor were observed in the E<inf>4</inf> groups.Conclusions E<inf>4</inf>-containing combinations have a limited effect on liver function, lipid metabolism, and bone and growth endocrine parameters. © 2015 The European Society of Contraception and Reproductive Health.

Disciplines :

Reproductive medicine (gynecology, andrology, obstetrics)

Author, co-author :

Mawet, Marie ; Estetra SPRL, Rue Saint Georges 5-7, Liège, Belgium

Maillard, C.; Estetra SPRL, Rue Saint Georges 5-7, Liège, Belgium

Klipping, C.; Dinox BV, Groningen, Netherlands

Zimmerman, Y.; Pantarhei Bioscience BV, Zeist, Netherlands

Foidart, Jean-Michel ; Université de Liège > Département des sciences cliniques > Département des sciences cliniques

Bennink, H. J. T. C.; Pantarhei Bioscience BV, Zeist, Netherlands

Language :

English

Title :

Unique effects on hepatic function, lipid metabolism, bone and growth endocrine parameters of estetrol in combined oral contraceptives

Publication date :

2015

Journal title :

European Journal of Contraception and Reproductive Health Care

ISSN :

1362-5187

eISSN :

1473-0782

Publisher :

Parthenon Publishing Group, Carnforth, United Kingdom

Volume :

Issue :

Pages :

463-475

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 15 February 2016

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Bibliography

United Nations. World contraceptive use 2011. Available from: www.unorg/esa/population/publications/.contraceptivE2011/wallchart-frontpdf
Westhoff CL, Heartwell S, Edwards S, et al. Oral contraceptive discontinuation: Do side effects matter? Am J Obstet Gynecol. 2007; 196: 412.
Bitzer J. Pharmacological profile of estrogens in oral contraception. Minerva Ginecol. 2011; 63: 299-304.
Cirillo DJ, Wallace RB, Rodabough RJ, et al. Effect of estrogen therapy on gallbladder disease. JAMA. 2005; 293: 330-9.
Kiley J, Hammond C. Combined oral contraceptives: A comprehensive review. Clin Obstet Gynecol. 2007; 50: 868-77.
Stegeman BH, de Bastos M, Rosendaal FR, et al. Different combined oral contraceptives and the risk of venous thrombosis: Systematic review and network meta-Analysis. BMJ. 2013; 347: f5298.
Rosenberg MJ, Meyers A, Roy V. Efficacy, cycle control, and side effects of low- And lower-dose oral contraceptives: A randomized trial of 20 micrograms and 35 micrograms estrogen preparations. Contraception. 1999; 60: 321-9.
Hoffmann H, Moore C, Zimmermann H, et al. Approaches to the replacement of ethinylestradiol by natural 17beta-estradiol in combined oral contraceptives. Exp Toxicol Pathol. 1998; 50: 458-64.
Holinka CF, Diczfalusy E, Coelingh Bennink HJ. Estetrol: A unique steroid in human pregnancy. J Steroid Biochem Mol Biol. 2008; 110: 138-43.
Coelingh Bennink F, Holinka CF, Visser M, et al. Maternal and fetal estetrol levels during pregnancy. Climacteric. 2008; 11(Suppl 1): 69-72.
Hammond GL, Hogeveen KN, Visser M, et al. Estetrol does not bind sex hormone binding globulin or increase its production by human HepG2 cells. Climacteric. 2008; 11(Suppl 1): 41-6.
Visser M, Coelingh Bennink HJ. Clinical applications for estetrol. J Steroid Biochem Mol Biol. 2009; 114: 85-9.
Abot A, Fontaine C, Buscato M, et al. The uterine and vascular actions of estetrol delineate a distinctive profile of estrogen receptor alpha modulation, uncoupling nuclear and membrane activation. EMBO Mol Med. 2014; 6: 1328-46.
Adlanmerini M, Solinhac R, Abot A, et al. Mutation of the palmitoylation site of estrogen receptor alpha in vivo reveals tissue-specific roles for membrane versus nuclear actions. Proc Natl Acad Sci U S A. 2014; 111: E283-90.
Coelingh Bennink HJ, Holinka CF, Diczfalusy E. Estetrol review: profile and potential clinical applications. Climacteric. 2008; 11(Suppl 1): 47-58.
Coelingh Bennink HJ, Skouby S, Bouchard P, et al. Ovulation inhibition by estetrol in an in vivo model. Contraception. 2008; 77: 186-90.
World Health Organization. Combined hormonal contraceptives (CHCs). In: Medical eligibility criteria for contraceptive use, 4th edn. Geneva: WHO 2010: 15-44.
Rikken B, van Doorn J, Ringeling A, et al. Plasma levels of insulin-like growth factor (IGF)-I, IGF-II and IGFbinding protein-3 in the evaluation of childhood growth hormone deficiency. Horm Res. 1998; 50: 166-76.
de Boer L, Hoogerbrugge CM, van Doorn J, et al. Plasma insulin-like growth factors (IGFs), IGF-binding proteins (IGFBPs), acid-labile subunit (ALS) and IGFBP-3 proteolysis in individuals with clinical characteristics of Sotos syndrome. J Pediatr Endocrinol Metab. 2004; 17: 615-27.
de Vries BB, Robinson H, Stolte-Dijkstra I, et al. General overgrowth in the fragile X syndrome: Variability in the phenotypic expression of the FMR1 gene mutation. J Med Genet. 1995; 32: 764-9.
Gyulikhandanova NE, Tsymbalenko NV, Platonova NA, et al. Regulation of ceruloplasmin gene in mammals. Bull Exp Biol Med. 2004; 137: 485-9.
De Groote D, Perrier d'Hauterive S, Pintiaux A, et al. Effects of oral contraception with ethinylestradiol and drospirenone on oxidative stress in women 18-35 years old. Contraception. 2009; 80: 187-93.
Odlind V, Milsom I, Persson I, et al. Can changes in sex hormone binding globulin predict the risk of venous thromboembolism with combined oral contraceptive pills? Acta Obstet Gynecol Scand. 2002; 81: 482-90.
Raps M, Helmerhorst F, Fleischer K, et al. Sex hormone-binding globulin as a marker for the thrombotic risk of hormonal contraceptives. J Thromb Haemost. 2012; 10: 992-7.
Stegeman BH, Helmerhorst FM, Vos HL, et al. Sex hormone-binding globulin levels are not causally related to venous thrombosis risk in women not using hormonal contraceptives. J Thromb Haemost. 2012; 10: 2061-7.
Kluft C, Skouby SO, Jespersen J, et al. Sex hormonebinding globulin as a marker for the thrombotic risk of hormonal contraceptives: A rebuttal. J Thromb Haemost. 2013; 11: 394-5.
Raps M, Helmerhorst FM, Fleischer K, et al. Sex hormone-binding globulin as a marker for the thrombotic risk of hormonal contraceptives: reply to a rebuttal. J Thromb Haemost. 2013; 11: 396-7.
Committee for Medical Products for Human Use (CPMP). Guideline on clinical investigation of steroid contraceptives in women. London: European Medicines Agency. 2005.
Akhter S, Shamsuzzaman AK, Banarjee M, et al. Serum copper in rural women taking combined oral contraceptive. Mymensingh Med J. 2006; 15: 25-9.
Berg G, Kohlmeier L, Brenner H. Effect of oral contraceptive progestins on serum copper concentration. Eur J Clin Nutr. 1998; 52: 711-5.
Benes B, Spevackova V, Smid J, et al. Effects of age, BMI, smoking and contraception on levels of Cu, Se and Zn in the blood of the population in the Czech Republic. Cent Eur J Public Health. 2005; 13: 202-7.
Agren UM, Anttila M, Maenpaa-Liukko K, et al. Effects of a monophasic combined oral contraceptive containing nomegestrol acetate and 17beta-oestradiol compared with one containing levonorgestrel and ethinylestradiol on haemostasis, lipids and carbohydrate metabolism. Eur J Contracept Reprod Health Care. 2011; 16: 444-57.
Sitruk-Ware R. Pharmacology of different progestogens: The special case of drospirenone. Climacteric. 2005; 8(Suppl. 3): 4-12.
Endrikat J, Klipping C, Cronin M, et al. An open label, comparative study of the effects of a dose-reduced oral contraceptive containing 20 microg ethinyl estradiol and 100 microg levonorgestrel on hemostatic, lipids, and carbohydrate metabolism variables. Contraception. 2002; 65: 215-21.
Scharnagl H, Petersen G, Nauck M, et al. Double-blind, randomized study comparing the effects of two monophasic oral contraceptives containing ethinylestradiol (20 microg or 30 microg) and levonorgestrel (100 microg or 150 microg) on lipoprotein metabolism. Contraception. 2004; 69: 105-13.
Skouby SO, Endrikat J, Dusterberg B, et al A 1-year randomized study to evaluate the effects of a dose reduction in oral contraceptives on lipids and carbohydrate metabolism: 20 microg ethinyl estradiol combined with 100 microg levonorgestrel. Contraception. 2005; 71: 111-7.
Tuppurainen M, Klimscheffskij R, Venhola M, et al. The combined contraceptive vaginal ring (NuvaRing) and lipid metabolism: A comparative study. Contraception. 2004; 69: 389-94.
Josse AR, Garcia-Bailo B, Fischer K, et al. Novel effects of hormonal contraceptive use on the plasma proteome. PLoS One. 2012; 7: e45162.
Hurwitz BE, Henry N, Goldberg RB. Long-Term oral contraceptive treatment, metabolic syndrome and measures of cardiovascular risk in pre-menopausal women: National Health and Nutrition Examination Survey. 1999-2004. Gynecol Endocrinol. 2009; 25: 441-9.
Coelingh Bennink HJ, Heegaard AM, Visser M, et al. Oral bioavailability and bone-sparing effects of estetrol in an osteoporosis model. Climacteric. 2008; 11(Suppl. 1): 2-14.
Delmas PD. Biochemical markers of bone turnover for the clinical assessment of metabolic bone disease. Endocrinol Metab Clin North Am. 1990; 19: 1-18.
Robins SP. Biochemical markers of bone metabolism. CPD Bull Clin Biochem. 1999; 1: 116-21.
Rosen HN, Moses AC, Garber J, et al. Serum CTX: A new marker of bone resorption that shows treatment effect more often than other markers because of low coefficient of variability and large changes with bisphosphonate therapy. Calcif Tissue Int. 2000; 66: 100-3.
Di Carlo C, Gargano V, Sparice S, et al. Short-Term effects of an oral contraceptive containing oestradiol valerate and dienogest on bone metabolism and bone mineral density: An observational, preliminary study. Eur J Contracept Reprod Health Care. 2013; 18: 388-93.
Massaro M, Di Carlo C, Gargano V, et al. Effects of the contraceptive patch and the vaginal ring on bone metabolism and bone mineral density: A prospective, controlled, randomized study. Contraception. 2010; 81: 209-14.
Balogh A, Kauf E, Vollanth R, et al. Effects of two oral contraceptives on plasma levels of insulin-like growth factor I (IGF-I) and growth hormone (hGH). Contraception. 2000; 62: 259-69.
Weissberger AJ, Ho KK, Lazarus L. Contrasting effects of oral and transdermal routes of estrogen replacement therapy on 24 h growth hormone (GH) secretion, insulin-like growth factor I, and GH-binding protein in postmenopausal women. J Clin Endocrinol Metab. 1991; 72: 374-81.
Thijs C, Knipschild P. Oral contraceptives and the risk of gallbladder disease: A meta-Analysis. Am J Public Health. 1993; 83: 1113-20.
Gargano V, Massaro M, Morra I, et al. Effects of two low-dose combined oral contraceptives containing drospirenone on bone turnover and bone mineral density in young fertile women: A prospective controlled randomized study. Contraception. 2008; 78: 10-5.
Paoletti AM, Orru M, Lello S, et al. Short-Term variations in bone remodeling markers of an oral contraception formulation containing 3 mg of drospirenone plus 30 microg of ethinyl estradiol: Observational study in young postadolescent women. Contraception. 2004; 70: 293-8.