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Published in: Archives of Gynecology and Obstetrics 6/2016

01-12-2016 | Gynecologic Endocrinology and Reproductive Medicine

Impact of combined hormonal contraceptives on vessels functionality

Authors: Alessandro Rabiolo, Federico Corvi, Davide Monteduro, Lucia Benatti, Maria Vittoria Cicinelli, Giovanni Fogliato, Giuseppe Querques, Francesco Bandello

Published in: Archives of Gynecology and Obstetrics | Issue 6/2016

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Abstract

Purpose

To evaluate the dynamic and static retinal vascular functionality in young females using combined hormonal contraceptive (CHC).

Methods

Thirty-eight consecutive young female subjects were enrolled in this study between January 2015 and December 2015. Subjects were divided in two groups: CHC group, defined as CHC use for ≥6 months, and control group, defined as no current and prior CHC use. Participants underwent a dynamic and static retinal vessel analysis using the Dynamic Vessel Analyzer (DVA, Imedos, Jena, Germany).

Results

Seventeen subjects continuously took CHC for 54.6 ± 29.3 months, while 21 subjects belonged to control group. No difference was found between the CHC and control groups for age (p = 0.1), smoking status (p = 0.6), and systolic (p = 0.3) and diastolic (p = 0.1) blood pressure. With regard to dynamic analysis, women taking CHC exhibited a marked significant vasoconstriction following flicker stimulation in comparison with control group (−2.43 ± 2.5 vs 0.63 ± 2.1, respectively; p = 0.0002). No significant difference was observed between groups for mean arterial (p = 0.2) and venous dilatations (p = 0.3), arteriovenous ratio (p = 0.09), central retinal artery equivalent (p = 0.4), and central retinal venous equivalent (p = 0.5).

Conclusions

CHC may affect vessel reactivity to flicker light by increasing arteries constriction. This may reflect systemic changes in vascular functionality in subjects using CHC. Moreover, CHC should be considered as a confounding bias in studies involving DVA.
Literature
1.
go back to reference Frost JJ, Singh S, Finer LB (2007) US women’s one-year contraceptive use patterns, 2004. Perspect Sex Reprod Health 39(1):48–55CrossRefPubMed Frost JJ, Singh S, Finer LB (2007) US women’s one-year contraceptive use patterns, 2004. Perspect Sex Reprod Health 39(1):48–55CrossRefPubMed
2.
go back to reference Arowojolu AO et al (2012) Combined oral contraceptive pills for treatment of acne. Cochrane Database Syst Rev 11(7):CD004425 Arowojolu AO et al (2012) Combined oral contraceptive pills for treatment of acne. Cochrane Database Syst Rev 11(7):CD004425
3.
go back to reference Mortada R, Williams T (2015) Metabolic syndrome: polycystic ovary syndrome. FP Essent 435:30–42PubMed Mortada R, Williams T (2015) Metabolic syndrome: polycystic ovary syndrome. FP Essent 435:30–42PubMed
4.
go back to reference Larsson G et al (1992) The influence of a low-dose combined oral contraceptive on menstrual blood loss and iron status. Contraception 46(4):327–334CrossRefPubMed Larsson G et al (1992) The influence of a low-dose combined oral contraceptive on menstrual blood loss and iron status. Contraception 46(4):327–334CrossRefPubMed
5.
go back to reference Wong CL et al (2009) Oral contraceptive pill for primary dysmenorrhoea. Cochrane Database Syst Rev 7(4):CD002120 Wong CL et al (2009) Oral contraceptive pill for primary dysmenorrhoea. Cochrane Database Syst Rev 7(4):CD002120
6.
go back to reference Bozdag G, Yildiz BO (2013) Combined oral contraceptives in polycystic ovary syndrome—indications and cautions. Front Horm Res 40:115–127CrossRefPubMed Bozdag G, Yildiz BO (2013) Combined oral contraceptives in polycystic ovary syndrome—indications and cautions. Front Horm Res 40:115–127CrossRefPubMed
7.
go back to reference Yonkers KA et al (2005) Efficacy of a new low-dose oral contraceptive with drospirenone in premenstrual dysphoric disorder. Obstet Gynecol 106(3):492–501CrossRefPubMed Yonkers KA et al (2005) Efficacy of a new low-dose oral contraceptive with drospirenone in premenstrual dysphoric disorder. Obstet Gynecol 106(3):492–501CrossRefPubMed
8.
go back to reference Gierisch JM et al (2013) Oral contraceptive use and risk of breast, cervical, colorectal, and endometrial cancers: a systematic review. Cancer Epidemiol Biomarkers Prev 22(11):1931–1943CrossRefPubMed Gierisch JM et al (2013) Oral contraceptive use and risk of breast, cervical, colorectal, and endometrial cancers: a systematic review. Cancer Epidemiol Biomarkers Prev 22(11):1931–1943CrossRefPubMed
9.
go back to reference Jordan WM, Anand JK (1961) Pulmonary embolism. Lancet 278(7212):1146–1147CrossRef Jordan WM, Anand JK (1961) Pulmonary embolism. Lancet 278(7212):1146–1147CrossRef
10.
go back to reference Suzuki A et al (2010) Down-regulation of PROS1 gene expression by 17beta-estradiol via estrogen receptor alpha (ERalpha)-Sp1 interaction recruiting receptor-interacting protein 140 and the corepressor-HDAC3 complex. J Biol Chem 285(18):13444–13453CrossRefPubMedPubMedCentral Suzuki A et al (2010) Down-regulation of PROS1 gene expression by 17beta-estradiol via estrogen receptor alpha (ERalpha)-Sp1 interaction recruiting receptor-interacting protein 140 and the corepressor-HDAC3 complex. J Biol Chem 285(18):13444–13453CrossRefPubMedPubMedCentral
11.
go back to reference Bladbjerg EM et al (2002) Effects of different progestin regimens in hormone replacement therapy on blood coagulation factor VII and tissue factor pathway inhibitor. Hum Reprod 17(12):3235–3241CrossRefPubMed Bladbjerg EM et al (2002) Effects of different progestin regimens in hormone replacement therapy on blood coagulation factor VII and tissue factor pathway inhibitor. Hum Reprod 17(12):3235–3241CrossRefPubMed
12.
go back to reference Ali HO et al (2014) Oestrogen induced downregulation of TFPI expression is mediated by ERalpha. Thromb Res 134(1):138–143CrossRefPubMed Ali HO et al (2014) Oestrogen induced downregulation of TFPI expression is mediated by ERalpha. Thromb Res 134(1):138–143CrossRefPubMed
13.
go back to reference Van Den Bosch MA et al (2003) The RATIO study: oral contraceptives and the risk of peripheral arterial disease in young women. J Thromb Haemost 1(3):439–444CrossRef Van Den Bosch MA et al (2003) The RATIO study: oral contraceptives and the risk of peripheral arterial disease in young women. J Thromb Haemost 1(3):439–444CrossRef
14.
go back to reference Harvey RE, Coffman KE, Miller VM (2015) Women-specific factors to consider in risk, diagnosis and treatment of cardiovascular disease. Womens Health (Lond Engl) 11(2):239–257CrossRef Harvey RE, Coffman KE, Miller VM (2015) Women-specific factors to consider in risk, diagnosis and treatment of cardiovascular disease. Womens Health (Lond Engl) 11(2):239–257CrossRef
15.
go back to reference Kang AK, Miller JA (2002) Effects of gender on the renin-angiotensin system, blood pressure, and renal function. Curr Hypertens Rep 4(2):143–151CrossRefPubMed Kang AK, Miller JA (2002) Effects of gender on the renin-angiotensin system, blood pressure, and renal function. Curr Hypertens Rep 4(2):143–151CrossRefPubMed
16.
go back to reference John S et al (2000) Effects of oral contraceptives on vascular endothelium in premenopausal women. Am J Obstet Gynecol 183(1):28–33CrossRefPubMed John S et al (2000) Effects of oral contraceptives on vascular endothelium in premenopausal women. Am J Obstet Gynecol 183(1):28–33CrossRefPubMed
17.
go back to reference Fallah S et al (2012) Influence of oral contraceptive pills on homocysteine and nitric oxide levels: as risk factors for cardiovascular disease. J Clin Lab Anal 26(2):120–123CrossRefPubMed Fallah S et al (2012) Influence of oral contraceptive pills on homocysteine and nitric oxide levels: as risk factors for cardiovascular disease. J Clin Lab Anal 26(2):120–123CrossRefPubMed
18.
19.
go back to reference Garhofer G et al (2010) Use of the retinal vessel analyzer in ocular blood flow research. Acta Ophthalmol 88(7):717–722CrossRefPubMed Garhofer G et al (2010) Use of the retinal vessel analyzer in ocular blood flow research. Acta Ophthalmol 88(7):717–722CrossRefPubMed
20.
go back to reference Polak K, Schmetterer L, Riva CE (2002) Influence of flicker frequency on flicker-induced changes of retinal vessel diameter. Invest Ophthalmol Vis Sci 43(8):2721–2726PubMed Polak K, Schmetterer L, Riva CE (2002) Influence of flicker frequency on flicker-induced changes of retinal vessel diameter. Invest Ophthalmol Vis Sci 43(8):2721–2726PubMed
21.
go back to reference Luksch A et al (2006) ETa-receptor blockade, but not ACE inhibition, blunts retinal vessel response during isometric exercise. Am J Physiol Heart Circ Physiol 290(4):H1693–H1698CrossRefPubMed Luksch A et al (2006) ETa-receptor blockade, but not ACE inhibition, blunts retinal vessel response during isometric exercise. Am J Physiol Heart Circ Physiol 290(4):H1693–H1698CrossRefPubMed
22.
go back to reference Riva CE, Logean E, Falsini B (2005) Visually evoked hemodynamical response and assessment of neurovascular coupling in the optic nerve and retina. Prog Retin Eye Res 24(2):183–215CrossRefPubMed Riva CE, Logean E, Falsini B (2005) Visually evoked hemodynamical response and assessment of neurovascular coupling in the optic nerve and retina. Prog Retin Eye Res 24(2):183–215CrossRefPubMed
23.
go back to reference Patel SR et al (2012) Abnormal retinal vascular reactivity in individuals with impaired glucose tolerance: a preliminary study. Invest Ophthalmol Vis Sci 53(9):5102–5108CrossRefPubMed Patel SR et al (2012) Abnormal retinal vascular reactivity in individuals with impaired glucose tolerance: a preliminary study. Invest Ophthalmol Vis Sci 53(9):5102–5108CrossRefPubMed
24.
go back to reference Lim M et al (2013) Systemic associations of dynamic retinal vessel analysis: a review of current literature. Microcirculation 20(3):257–268CrossRefPubMed Lim M et al (2013) Systemic associations of dynamic retinal vessel analysis: a review of current literature. Microcirculation 20(3):257–268CrossRefPubMed
25.
go back to reference Nagel E, Vilser W, Lanzl I (2004) Age, blood pressure, and vessel diameter as factors influencing the arterial retinal flicker response. Invest Ophthalmol Vis Sci 45(5):1486–1492CrossRefPubMed Nagel E, Vilser W, Lanzl I (2004) Age, blood pressure, and vessel diameter as factors influencing the arterial retinal flicker response. Invest Ophthalmol Vis Sci 45(5):1486–1492CrossRefPubMed
26.
go back to reference Reimann M et al (2009) Retinal vessel analysis in hypercholesterolemic patients before and after LDL apheresis. Atheroscler Suppl 10(5):39–43CrossRefPubMed Reimann M et al (2009) Retinal vessel analysis in hypercholesterolemic patients before and after LDL apheresis. Atheroscler Suppl 10(5):39–43CrossRefPubMed
27.
go back to reference Kotliar KE et al (2011) Dynamic retinal vessel response to flicker in obesity: a methodological approach. Microvasc Res 81(1):123–128CrossRefPubMed Kotliar KE et al (2011) Dynamic retinal vessel response to flicker in obesity: a methodological approach. Microvasc Res 81(1):123–128CrossRefPubMed
28.
go back to reference Garhofer G et al (2011) Effect of regular smoking on flicker induced retinal vasodilatation in healthy subjects. Microvasc Res 82(3):351–355CrossRefPubMed Garhofer G et al (2011) Effect of regular smoking on flicker induced retinal vasodilatation in healthy subjects. Microvasc Res 82(3):351–355CrossRefPubMed
29.
go back to reference Kneser M et al (2009) Age related decline of microvascular regulation measured in healthy individuals by retinal dynamic vessel analysis. Med Sci Monit 15(8):CR436–CR441PubMed Kneser M et al (2009) Age related decline of microvascular regulation measured in healthy individuals by retinal dynamic vessel analysis. Med Sci Monit 15(8):CR436–CR441PubMed
30.
go back to reference Yatsuya H et al (2010) Retinal microvascular abnormalities and risk of lacunar stroke: atherosclerosis risk in communities study. Stroke 41(7):1349–1355CrossRefPubMedPubMedCentral Yatsuya H et al (2010) Retinal microvascular abnormalities and risk of lacunar stroke: atherosclerosis risk in communities study. Stroke 41(7):1349–1355CrossRefPubMedPubMedCentral
31.
go back to reference Witt N et al (2006) Abnormalities of retinal microvascular structure and risk of mortality from ischemic heart disease and stroke. Hypertension 47(5):975–981CrossRefPubMed Witt N et al (2006) Abnormalities of retinal microvascular structure and risk of mortality from ischemic heart disease and stroke. Hypertension 47(5):975–981CrossRefPubMed
32.
go back to reference Mitchell P et al (2005) Retinal microvascular signs and risk of stroke and stroke mortality. Neurology 65(7):1005–1009CrossRefPubMed Mitchell P et al (2005) Retinal microvascular signs and risk of stroke and stroke mortality. Neurology 65(7):1005–1009CrossRefPubMed
33.
go back to reference Wong TY et al (2001) Retinal microvascular abnormalities and incident stroke: the atherosclerosis risk in communities study. Lancet 358(9288):1134–1140CrossRefPubMed Wong TY et al (2001) Retinal microvascular abnormalities and incident stroke: the atherosclerosis risk in communities study. Lancet 358(9288):1134–1140CrossRefPubMed
34.
go back to reference La Spina C et al (2016) Static characteristics and dynamic functionality of retinal vessels in longer eyes with or without pathologic myopia. Graefes Arch Clin Exp Ophthalmol 254:827–834CrossRefPubMed La Spina C et al (2016) Static characteristics and dynamic functionality of retinal vessels in longer eyes with or without pathologic myopia. Graefes Arch Clin Exp Ophthalmol 254:827–834CrossRefPubMed
35.
go back to reference Corvi F et al (2015) Dynamic and static retinal vessel analyses in patients with macular edema secondary to retinal vein occlusion. Retina 35(10):2052–2059CrossRefPubMed Corvi F et al (2015) Dynamic and static retinal vessel analyses in patients with macular edema secondary to retinal vein occlusion. Retina 35(10):2052–2059CrossRefPubMed
36.
go back to reference Corvi F et al (2015) Impact of intravitreal ranibizumab on vessel functionality in patients with retinal vein occlusion. Am J Ophthalmol 160(1):45–52 (e1) CrossRefPubMed Corvi F et al (2015) Impact of intravitreal ranibizumab on vessel functionality in patients with retinal vein occlusion. Am J Ophthalmol 160(1):45–52 (e1) CrossRefPubMed
37.
go back to reference Noonan JE et al (2014) Flicker-induced retinal arteriole dilation is reduced by ambient lighting. Invest Ophthalmol Vis Sci 55(9):5476–5481CrossRefPubMed Noonan JE et al (2014) Flicker-induced retinal arteriole dilation is reduced by ambient lighting. Invest Ophthalmol Vis Sci 55(9):5476–5481CrossRefPubMed
38.
go back to reference Hubbard LD et al (1999) Methods for evaluation of retinal microvascular abnormalities associated with hypertension/sclerosis in the atherosclerosis risk in communities study. Ophthalmology 106(12):2269–2280CrossRefPubMed Hubbard LD et al (1999) Methods for evaluation of retinal microvascular abnormalities associated with hypertension/sclerosis in the atherosclerosis risk in communities study. Ophthalmology 106(12):2269–2280CrossRefPubMed
39.
go back to reference Ross R (1993) The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 362(6423):801–809CrossRefPubMed Ross R (1993) The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 362(6423):801–809CrossRefPubMed
40.
go back to reference Buerk DG, Riva CE (2002) Adenosine enhances functional activation of blood flow in cat optic nerve head during photic stimulation independently from nitric oxide. Microvasc Res 64(2):254–264CrossRefPubMed Buerk DG, Riva CE (2002) Adenosine enhances functional activation of blood flow in cat optic nerve head during photic stimulation independently from nitric oxide. Microvasc Res 64(2):254–264CrossRefPubMed
41.
go back to reference Donati G et al (1995) Nitric oxide controls arteriolar tone in the retina of the miniature pig. Invest Ophthalmol Vis Sci 36(11):2228–2237PubMed Donati G et al (1995) Nitric oxide controls arteriolar tone in the retina of the miniature pig. Invest Ophthalmol Vis Sci 36(11):2228–2237PubMed
42.
go back to reference Dorner GT et al (2003) Nitric oxide regulates retinal vascular tone in humans. Am J Physiol Heart Circ Physiol 285(2):H631–H636CrossRefPubMed Dorner GT et al (2003) Nitric oxide regulates retinal vascular tone in humans. Am J Physiol Heart Circ Physiol 285(2):H631–H636CrossRefPubMed
43.
44.
go back to reference Boger RH et al (2000) Plasma concentration of asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase, is elevated in monkeys with hyperhomocyst(e)inemia or hypercholesterolemia. Arterioscler Thromb Vasc Biol 20(6):1557–1564CrossRefPubMed Boger RH et al (2000) Plasma concentration of asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase, is elevated in monkeys with hyperhomocyst(e)inemia or hypercholesterolemia. Arterioscler Thromb Vasc Biol 20(6):1557–1564CrossRefPubMed
45.
go back to reference Zeiher AM et al (1993) Endothelium-mediated coronary blood flow modulation in humans. Effects of age, atherosclerosis, hypercholesterolemia, and hypertension. J Clin Invest 92(2):652–662CrossRefPubMedPubMedCentral Zeiher AM et al (1993) Endothelium-mediated coronary blood flow modulation in humans. Effects of age, atherosclerosis, hypercholesterolemia, and hypertension. J Clin Invest 92(2):652–662CrossRefPubMedPubMedCentral
46.
go back to reference Merki-Feld GS, Imthurn B, Keller PJ (2002) Effects of two oral contraceptives on plasma levels of nitric oxide, homocysteine, and lipid metabolism. Metabolism 51(9):1216–1221CrossRefPubMed Merki-Feld GS, Imthurn B, Keller PJ (2002) Effects of two oral contraceptives on plasma levels of nitric oxide, homocysteine, and lipid metabolism. Metabolism 51(9):1216–1221CrossRefPubMed
Metadata
Title
Impact of combined hormonal contraceptives on vessels functionality
Authors
Alessandro Rabiolo
Federico Corvi
Davide Monteduro
Lucia Benatti
Maria Vittoria Cicinelli
Giovanni Fogliato
Giuseppe Querques
Francesco Bandello
Publication date
01-12-2016
Publisher
Springer Berlin Heidelberg
Published in
Archives of Gynecology and Obstetrics / Issue 6/2016
Print ISSN: 0932-0067
Electronic ISSN: 1432-0711
DOI
https://doi.org/10.1007/s00404-016-4170-2

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