Effect of ethinylestradiol dose and progestagen in combined oral contraceptives on plasma sex hormone‐binding globulin levels in premenopausal women

Stegeman, Bernardine H.; Raps, Marjolein; Helmerhorst, Frans M.; Vos, Hans L.; Vliet, Huib A.A.M. van; Rosendaal, Frits R.; Vlieg, Astrid van Hylckama

doi:10.1111/jth.12054

Cited by 15 publications

(15 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…SHBG is a marker that differentiates between combined oral contraceptives with a high and low risk of venous thrombosis [15][16][17][18][19]. In our study we did not observe a difference in APC resistance and SHBG levels between a new oral contraceptive containing DNG/E2V and a low-risk combined oral contraceptive containing LNG/EE.…”

Section: Discussioncontrasting

confidence: 43%

Section: Introductionmentioning

confidence: 99%

“…containing LNG) [3,6,[9][10][11][12][13]15]. Sex hormone binding globuline (SHBG) is another marker that differentiates between combined oral contraceptives with a high and low risk of venous thrombosis [15][16][17][18][19]. SHBG is a carrier protein, which is produced in the liver and binds estrogen and testosterone [20].…”

mentioning

confidence: 99%

“…The effect of a hormonal contraceptive on SHBG is the net result of the estrogenic effect of estradiol and the antiestrogenic effect of the progestogen, yielding the total estrogenicity of that hormonal contraceptive. This estrogenicity serves as a marker for the thrombotic risk of a hormonal contraceptive [15][16][17][18].Recently, a new, four-phasic, combined oral contraceptive containing dienogest and estradiol valerate (Qlaira â ; Bayer Schering Pharma, Berlin, Germany) was marketed. Dienogest (DNG) is a progestogen derived from the estrane structure and has antiandrogenic and no androgenic properties [23].…”

mentioning

confidence: 99%

See 3 more Smart Citations

Resistance to APC and SHBG levels during use of a four-phasic oral contraceptive containing dienogest and estradiol valerate: a randomized controlled trial

Raps

Rosendaal

Ballieux

et al. 2013

Journal of Thrombosis and Haemostasis

Self Cite

View full text Add to dashboard Cite

To cite this article: Raps M, Rosendaal F, Ballieux B, Rosing J, Thomassen S, Helmerhorst F, van Vliet H. Resistance to APC and SHBG levels during use of a four-phasic oral contraceptive containing dienogest and estradiol valerate: a randomized controlled trial. J Thromb Haemost 2013; 11: 855-61.Summary. Background: The use of combined oral contraceptives is associated with a 3-to 6-fold increased risk of venous thrombosis. This increased risk depends on the estrogen dose as well as the progestogen type of combined oral contraceptives. Thrombin generation-based activated protein C resistance (APC resistance) and sex hormone-binding globulin (SHBG) levels predict the thrombotic risk of a combined hormonal contraceptive. Recently, a four-phasic oral contraceptive containing dienogest (DNG) and estradiol valerate (E2V) has been marketed. The aim of this study was to evaluate the thrombotic risk of the DNG/E2V oral contraceptive by comparing APC resistance by measuring normalized APC sensitivity ratios (nAPCsr) and SHBG levels in users of oral contraceptives containing dienogest and estradiol valerate (DNG/E2V) and oral contraceptives containing levonorgestrel and ethinyl estradiol (LNG/EE). Methods: We conducted a single-center, randomized, open label, parallel-group study in 74 women using DNG/E2V or LNG/ EE, and measured nAPCsr and SHBG levels in every phase of the regimen of DNG/E2V. Results: During the pill cycle SHBG levels did not differ between DNG/E2V users and LNG/EE users. nAPCsr levels were overall slightly lower in DNG/E2V users than in LNG/EE users, mean difference À0.44 (95% CI, À1.04 to 0.17) for day 2, À0.20 (95% CI, À0.76 to 0.37) for day 7, À0.27 (95% CI, À0.81 to 0.28) for day 24 and À0.34 (95% CI, À0.91 to 0.24) for day 26. Conclusion: No statistical significant differences in nAPCsr and SHBG levels were found between users of the oral contraceptive containing DNG/E2V and LNG/EE, suggesting a comparable thrombotic risk Keywords: activated protein C resistance, natural estrogen, oral contraceptives, sex hormone binding globulin, thrombotic risk. IntroductionUse of combined oral contraceptives is associated with a 3-to 6-fold increased risk of venous thrombosis. This increased risk depends on the estrogen dose as well as the progestogen-type of combined oral contraceptives [1]. Socalled 'high-dose' combined oral contraceptives containing 50 lg or more ethinyl estradiol (EE) are associated with a 2-fold higher risk of thrombosis than 'low-dose' combined oral contraceptives containing 20-30 lg EE [2,3]. Furthermore, combined oral contraceptives containing the progestogens gestodene (GTD), desogestrel (DSG), cyproterone acetate (CPA) or drospirenone (DRSP) increase the risk of venous thrombosis by a factor two compared with combined oral contraceptives containing levonorgestrel (LNG) [1][2][3][4][5][6][7][8][9][10].The differences in the risk of venous thrombosis can at least partially be explained by the different effects of various combined oral contraceptives on the resistance to activated protein...

show abstract

Section: Discussioncontrasting

confidence: 43%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Resistance to APC and SHBG levels during use of a four-phasic oral contraceptive containing dienogest and estradiol valerate: a randomized controlled trial

Raps

Rosendaal

Ballieux

et al. 2013

Journal of Thrombosis and Haemostasis

Self Cite

View full text Add to dashboard Cite

show abstract

“…26 Certain combined oral contraceptive agents associated with increased venous thrombosis have also been found to lead to elevated SHBG and activated protein C resistance. 27,28 In the Women's Health Initiative trials of postmenopausal hormone therapy, although TFPI was reduced by HT, this reduction was not associated with an increased risk of ischemic stroke. 29 Our further analysis within the HT users alone revealed that estrogen-only users who had elevated levels of SHBG had elevated CRP levels, but among estrogen and progesterone users, those with higher levels of SHBG had lower CRP levels.…”

Section: Figmentioning

confidence: 99%

Association of Serum Sex Hormones with Hemostatic Factors in Women On and Off Hormone Therapy: The Multiethnic Study of Atherosclerosis

Williams

Cushman

Ouyang

et al. 2016

Journal of Women's Health

View full text Add to dashboard Cite

Background: Hormone therapy (HT) is associated with increased risk of both venous and arterial thrombosis, which are multifactorial in origin. Objectives: Our objectives were twofold: first, we sought to examine associations between endogenous serum sex hormone levels and biomarkers of thrombosis and/or coagulation in postmenopausal hormone nonusers. Second, we separately studied the associations between serum sex hormone levels and biomarkers of thrombosis and/or coagulation in postmenopausal hormone users considering the fact that pattern of circulating hormones is different in women taking exogenous hormones. Patients/Methods: We performed a cross-sectional analysis of postmenopausal women enrolled in a large multiethnic community-based cohort study, The Multiethnic Study of Atherosclerosis. We hypothesized that higher levels of estrogen-related sex hormones would be associated with biomarkers of thrombosis, suggesting mechanisms for differences in thrombotic risk from HT. Women (n = 2878) were included if they were postmenopausal and had thrombotic biomarkers (homocysteine, fibrinogen, C-reactive protein [CRP], factor VIII, and d-dimer) and sex hormone levels (total testosterone [T], bioavailable testosterone, sex hormone binding globulin [SHBG], estradiol [E2], and dehydroepiandrosterone [DHEA]) measured. A smaller random sample of 491 women also had von Willebrand factor (vWF), plasminogen activator inhibitor (PAI-1), and tissue factor pathway inhibitor (TFPI) levels measured. Results and Conclusions: We found that elevated levels of estradiol and SHBG in HT users were associated with elevated levels of CRP and lower levels of TFPI, both of which may be related to a prothrombotic milieu in HT users. HT nonusers had far more prothrombotic associations between elevated serum sex hormone levels and thrombotic biomarkers when compared with HT users.

show abstract

Hormonal Factors in Women's Sexual Pain Disorders

Goldstein¹

2020

Female Sexual Pain Disorders

View full text Add to dashboard Cite

Effect of ethinylestradiol dose and progestagen in combined oral contraceptives on plasma sex hormone‐binding globulin levels in premenopausal women

Cited by 15 publications

References 7 publications

Resistance to APC and SHBG levels during use of a four-phasic oral contraceptive containing dienogest and estradiol valerate: a randomized controlled trial

Resistance to APC and SHBG levels during use of a four-phasic oral contraceptive containing dienogest and estradiol valerate: a randomized controlled trial

Association of Serum Sex Hormones with Hemostatic Factors in Women On and Off Hormone Therapy: The Multiethnic Study of Atherosclerosis

Hormonal Factors in Women's Sexual Pain Disorders

Contact Info

Product

Resources

About