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Effects of different hormonal contraceptives in women's blood pressure values

Efectos de los distintos anticonceptivos hormonales en los valores de presión arterial de la mujer

ABSTRACT

Objective:

To identify evidence in the literature of the relationship between the use of different hormonal contraceptive methods and alterations in women's blood pressure values.

Method:

This is an integrative literature review, consisting of ten scientific articles published in PubMed and BVS, between 2012 and 2016, selected by keywords, available fully and free of charge, in English, Portuguese, or Spanish.

Results:

The articles showed that exogenous estrogen helps in the activation of the renin-angiotensin-aldosterone system causing hypertensive effects even in small doses; and that combined use with drospirenone reduces these effects. Routes of administration without passage through the liver and use of isolated progestin showed promising results in reducing the effects on blood pressure.

Conclusion:

There is evidence in the literature of pressure alterations associated with different hormonal contraceptives and that personal history of morbidities are to be considered in an attempt to reduce the effects on the cardiovascular system.

Descriptors:
Female Contraceptives; Oral Hormonal Contraceptives; Female Contraceptive Devices; Intrauterine Devices; Blood Pressure

RESUMEN

Objetivo:

Identificar en la literatura evidencias sobre la relación entre el uso de distintos métodos anticonceptivos hormonales y las alteraciones en los valores de presión arterial en mujeres.

Método:

Se trata de la revisión integrativa de la literatura, constituida por diez artículos científicos publicados en PubMed y BVS, entre 2012 y 2016, seleccionados por medio de palabras-clave, disponibles en su totalidad, gratuitos, en inglés, en portugués o en español.

Resultados:

Los artículos han enseñado que el estrógeno exógeno aporta en la activación del sistema renina-angiotensina-aldosterona causando efectos hipertensivos aunque en pequeñas dosificaciones; y que el uso combinado con la drospirenona reduce esos efectos. Vías de administración sin pasaje por el hígado y el uso del progestágeno aislado han enseñado resultados promisores en la reducción de los efectos sobre la presión.

Conclusión:

Hay evidencias en la literatura de alteraciones presóricas asociadas a distintos anticonceptivos hormonales y de que antecedentes personales de morbilidades deben ser considerados en el intento de reducir los efectos sobre el sistema cardiovascular.

Descriptores:
Anticonceptivos Femeninos; Anticonceptivos Orales Hormonales; Dispositivos Anticonceptivos Femeninos; Dispositivos Intrauterinos; Presión Sanguínea

RESUMO

Objetivo:

Identificar na literatura evidências sobre a relação entre o uso de diferentes métodos anticoncepcionais hormonais e as alterações nos valores de pressão arterial em mulheres.

Método:

Trata-se de revisão integrativa da literatura, constituída por dez artigos científicos publicados no PubMed e BVS, entre 2012 e 2016, selecionados por meio de palavras-chave, disponíveis na íntegra, gratuitos, em inglês, português ou espanhol.

Resultados:

Os artigos mostraram que o estrogênio exógeno contribui na ativação do sistema renina-angiotensina-aldosterona causando efeitos hipertensores mesmo em pequenas dosagens; e que o uso combinado com a drospirenona reduz esses efeitos. Vias de administração sem passagem pelo fígado e uso do progestágeno isolado mostraram resultados promissores na redução dos efeitos sobre a pressão.

Conclusão:

Há evidências na literatura de alterações pressóricas associadas a diferentes anticoncepcionais hormonais e de que antecedentes pessoais de morbidades devem ser considerados na tentativa de reduzir os efeitos sobre o sistema cardiovascular.

Descritores:
Anticoncepcionais Femininos; Anticoncepcionais Orais Hormonais; Dispositivos Anticoncepcionais Femininos; Dispositivos Intrauterinos; Pressão Sanguínea

INTRODUCTION

In Brazil, in 2015, 79% of women used some sort of contraceptive method as family planning, representing an index 28% greater than the registered in 1970. Of this group, hormonal contraception (reversible), such as contraceptive pills, was the first choice of most women, second place only for fallopian tubes ligation (irreversible)(11 Nações Unidas Brasil - ONUBR. Direitos Humanos. Cerca de 79% das brasileiras usaram métodos contraceptivos em 2015, informa ONU[Internet]. 2016 [cited 2016 Jun 22]. Available from: https://nacoesunidas.org/cerca-de-79-das-brasileiras-usaram-metodos-contraceptivos-em-2015-informa-onu/
https://nacoesunidas.org/cerca-de-79-das...
).

This type of medication is a formulation combining estrogen and progestogen or simple presentations of isolated progestogen. It can be found in several formulations (concentration of hormones) and different routes of administration (oral, intramuscular, subdermal implants, transdermal, vaginal, and associated with the intrauterine system). It acts with the purpose of blocking ovulation and changing the conditions of the uterus and the fallopian tubes, thus hindering fertilization(22 World Health Organization - WHO. Reproductive Health and Research and John Hopkins Bloomberg School of Public Health. Family planning: a global handbook for providers. Baltimore; Geneva: CCP; WHO; 2008.).

Due to the presence of estrogen and progesterone receptors in all constituent layers of the blood vessels, the effects of female sex hormones contained in contraceptives on the cardiovascular system has been subject of scientific interest(33 Brito MB, Nobre F, Vieira CS. Contracepção hormonal e sistema cardiovascular. Arq Bras Cardiol [Internet]. 2011 [cited 2016 Jun 22]; 96(4)e81-e89. Available from: http://www.scielo.br/pdf/abc/2011nahead/aop01211.pdf
http://www.scielo.br/pdf/abc/2011nahead/...
). Older studies have showed that the use of contraceptive pills potentialized the increase in systolic blood pressure (SBP) in groups of women who usually presented higher pressure levels(44 Szwarcwald C, Costa SH, Costa EA, Klein CH, Leal MC. Anticoncepcionais orais e pressão arterial: pesquisa epidemiológica de hipertensão arterial no Rio Grande do Sul. Cad Saúde Pública [Internet]. 1985 [cited 2016 Jun 22]; 1(2):177-91. Available from: http://www.scielo.br/pdf/csp/v1n2/v1n2a05.pdf
http://www.scielo.br/pdf/csp/v1n2/v1n2a0...
). Recent studies also highlight that combined hormonal contraceptives (CHC), for containing ethinylestradiol (EE), always change the blood pressure (BP), even at low doses. Despite not causing clinical repercussions in healthy women, they should be avoided by women with high blood pressure(33 Brito MB, Nobre F, Vieira CS. Contracepção hormonal e sistema cardiovascular. Arq Bras Cardiol [Internet]. 2011 [cited 2016 Jun 22]; 96(4)e81-e89. Available from: http://www.scielo.br/pdf/abc/2011nahead/aop01211.pdf
http://www.scielo.br/pdf/abc/2011nahead/...
).

The substances present in these contraceptives attempt to reproduce the properties of endogenous steroids. However, EE, due to its biological potency compared to estradiol (1,000 times more potent), intensifies the production of hepatic angiotensinogen, which, in its turn, causes elevation of blood pressure by the renin-angiotensin-aldosterone system (RAAS)(55 Oelkers WK. Effects of estrogens and progestogens on the renin aldosterone system and blood pressure. Steroids [Internet]. 1996 [cited 2016 Jun 22]; 61(4):166-71. Available from: https://doi.org/10.1016/0039-128X(96)00007-4
https://doi.org/10.1016/0039-128X(96)000...
). In addition, progestogen associated with the EE present in CHCs, although similar, does not reproduce all characteristics of natural progesterone(66 Sitruk-Ware R. New progestagens for contraceptive use. Hum Reprod Update [Internet]. 2006 [cited 2016 Jun 22]; 12(2):169-78. Available from: https://academic.oup.com/humupd/article-lookup/doi/10.1093/humupd/dmi046
https://academic.oup.com/humupd/article-...
).

The first formulations containing high hormone doses, used in the 1960s and 1970s, were associated with the increase not only of incidence of hypertension, but also of risk of venous thromboembolism (VTE), acute myocardial infarction (AMI), and hemorrhagic and ischemic cerebrovascular accident (CVA). Due to these events and reduction of side effects, in the early 1980s, new formulations of CHC with smaller dosages of EE and new progestogens with reduced androgenic action were introduced(77 Mishell Jr DR. Oral contraception: past, present and future perspectives. Int J Fertil [Internet]. 1992 [cited 2016 Jun 22];37(Suppl 1):7-18. Available from: https://www.ncbi.nlm.nih.gov/pubmed/1678381
https://www.ncbi.nlm.nih.gov/pubmed/1678...
-88 Kemmeren JM, Algra A, Grobbee DE. Third generation oral contraceptives and risk of venous thrombosis: meta-analysis. Br Med J [Internet]. 2001 [cited 2016 Jun 22]; 323:131-4. Available from: http://www.bmj.com/content/bmj/323/7305/131.full.pdf
http://www.bmj.com/content/bmj/323/7305/...
). First generation pills containing 150 μg of estrogen began to have concentrations smaller than 20 μg in the fourth generation. Also, progestogen more similar to endogenous ones, such as those presenting antimineralocorticoid effect were introduced to the market.

Despite the reduction in the concentration of the components and the emergence of formulations closer to the natural hormone, the widespread use of CHC still deserves attention during prescription due to the effects caused on the cardiovascular system. Therefore, there is a need to further investigate what are the effects on women's blood pressure of the different hormonal contraceptives available, with the aim of alerting which formulations or routes of administrations are safer for women with previous morbidities as well as healthy women.

OBJECTIVE

To identify evidence in the literature of the relationship between the use of different hormonal contraceptive methods and alterations in women's blood pressure values.

METHOD

This is an exploratory research of bibliographic character developed based on previously prepared material, consisting of scientific articles. The literature search was conducted using the following descriptors: Anticoncepcionais Femininos (Contraceptive Agents, Female), Anticoncepcionais Orais Hormonais (Contraceptives, Oral, Hormonal), Anticoncepcionais Hormonais Pós-Coito (Contraceptives, Postcoital, Hormonal), Dispositivos Intrauterinos (Contraceptive, Devices, Intrauterine), Pressão Sanguínea (Blood Pressure), Hipertensão (Hypertension). Those keywords were searched (in Portuguese) on the databases PubMed and Virtual Health Library (BVS), respecting the limits of publication between 2012 and 2016, in English, Portuguese, and Spanish.

The following inclusion criteria was established: articles that described the effects of hormonal contraceptives on the blood pressure values of women who used this type of medication. Exclusion criteria were: not meeting the criteria above; being published over five years; not having full text available and/or free access; and being written in a language other than English, Portuguese, and Spanish.

Figure 1
Articles selection process through the combination of descriptors and use of the filters “language”, “year of publication”, and “full text available”, Campinas, São Paulo, Brazil, 2016

Note: BVS - Biblioteca Virtual em Saúde (Virtual Health Library)


RESULTS

Of the 72 articles found, 50 were excluded for not having full text available and/or not contemplating in the abstracts the relationship between the hormonal contraceptive method and blood pressure and other 12 were excluded due to repetition in the databases. Ten articles were selected for the sample. The data are presented in Chart 1.

Chart 1
Description of the articles selected in the PubMed and Virtual Health Library databases by descriptors, Campinas, São Paulo, Brazil, 2016

DISCUSSION

Previous studies already indicated that the presence of exogenous estrogen in the body, contained in CHCs, stimulated the RAAS and caused increased systolic and diastolic pressures due to water and sodium retention, especially in hypertensive women(44 Szwarcwald C, Costa SH, Costa EA, Klein CH, Leal MC. Anticoncepcionais orais e pressão arterial: pesquisa epidemiológica de hipertensão arterial no Rio Grande do Sul. Cad Saúde Pública [Internet]. 1985 [cited 2016 Jun 22]; 1(2):177-91. Available from: http://www.scielo.br/pdf/csp/v1n2/v1n2a05.pdf
http://www.scielo.br/pdf/csp/v1n2/v1n2a0...
). Four articles included in this study(1212 Kassel LE, Odum LE. Our own worst enemy: Pharmacologic mechanisms of hypertension. Adv Chronic Kidney Dis [Internet]. 2015 [cited 2016 Jun 22]; 22(3):245-52. Available from: http://www.ackdjournal.org/article/S1548-5595(14)00166-9/pdf
http://www.ackdjournal.org/article/S1548...

13 Harvey RE, Coffman KE, Miller VM. Women-specific factors to consider in risk, diagnosis and treatment of cardiovascular disease. Womens Health [Internet]. 2015 [cited 2016 Jun 22]; 11(2):239-57. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4386625/pdf/nihms-675118.pdf
https://www.ncbi.nlm.nih.gov/pmc/article...

14 Park H, Kim K. Associations between oral contraceptive use and risks of hypertension and prehypertension in a cross-sectional study of Korean women. BMC Womens Health [Internet]. 2013 [cited 2016 Jun 22]; 13:39-45. Available from: https://bmcwomenshealth.biomedcentral.com/articles/10.1186/1472-6874-13-39
https://bmcwomenshealth.biomedcentral.co...
-1515 Steenlanda MW, Zapata LB, Brahmi D, Marchbanks PA, Curtis KM. Appropriate follow up to detect potential adverse events after initiation of select contraceptive methods: a systematic review. Contraception [Internet]. 2013 [cited 2016 Jun 22]; 87:611-24. Available from: http://www.contraceptionjournal.org/article/S0010-7824(12)00827-X/pdf
http://www.contraceptionjournal.org/arti...
), two being reviews(1212 Kassel LE, Odum LE. Our own worst enemy: Pharmacologic mechanisms of hypertension. Adv Chronic Kidney Dis [Internet]. 2015 [cited 2016 Jun 22]; 22(3):245-52. Available from: http://www.ackdjournal.org/article/S1548-5595(14)00166-9/pdf
http://www.ackdjournal.org/article/S1548...
-1313 Harvey RE, Coffman KE, Miller VM. Women-specific factors to consider in risk, diagnosis and treatment of cardiovascular disease. Womens Health [Internet]. 2015 [cited 2016 Jun 22]; 11(2):239-57. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4386625/pdf/nihms-675118.pdf
https://www.ncbi.nlm.nih.gov/pmc/article...
), indicated as result the significant increase in blood pressure by use of CHC, both in hypertensive(1313 Harvey RE, Coffman KE, Miller VM. Women-specific factors to consider in risk, diagnosis and treatment of cardiovascular disease. Womens Health [Internet]. 2015 [cited 2016 Jun 22]; 11(2):239-57. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4386625/pdf/nihms-675118.pdf
https://www.ncbi.nlm.nih.gov/pmc/article...
) and normotensive(1212 Kassel LE, Odum LE. Our own worst enemy: Pharmacologic mechanisms of hypertension. Adv Chronic Kidney Dis [Internet]. 2015 [cited 2016 Jun 22]; 22(3):245-52. Available from: http://www.ackdjournal.org/article/S1548-5595(14)00166-9/pdf
http://www.ackdjournal.org/article/S1548...
,1414 Park H, Kim K. Associations between oral contraceptive use and risks of hypertension and prehypertension in a cross-sectional study of Korean women. BMC Womens Health [Internet]. 2013 [cited 2016 Jun 22]; 13:39-45. Available from: https://bmcwomenshealth.biomedcentral.com/articles/10.1186/1472-6874-13-39
https://bmcwomenshealth.biomedcentral.co...
-1515 Steenlanda MW, Zapata LB, Brahmi D, Marchbanks PA, Curtis KM. Appropriate follow up to detect potential adverse events after initiation of select contraceptive methods: a systematic review. Contraception [Internet]. 2013 [cited 2016 Jun 22]; 87:611-24. Available from: http://www.contraceptionjournal.org/article/S0010-7824(12)00827-X/pdf
http://www.contraceptionjournal.org/arti...
) women. In addition, two articles linked the extended time of use of medication to the prevalence of hypertension(1313 Harvey RE, Coffman KE, Miller VM. Women-specific factors to consider in risk, diagnosis and treatment of cardiovascular disease. Womens Health [Internet]. 2015 [cited 2016 Jun 22]; 11(2):239-57. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4386625/pdf/nihms-675118.pdf
https://www.ncbi.nlm.nih.gov/pmc/article...
,1515 Steenlanda MW, Zapata LB, Brahmi D, Marchbanks PA, Curtis KM. Appropriate follow up to detect potential adverse events after initiation of select contraceptive methods: a systematic review. Contraception [Internet]. 2013 [cited 2016 Jun 22]; 87:611-24. Available from: http://www.contraceptionjournal.org/article/S0010-7824(12)00827-X/pdf
http://www.contraceptionjournal.org/arti...
); and one(1818 White K, Potter JE, Hopkins K, Amastae J, Grossman D. Hypertension among oral contraceptive users in El Paso, Texas. J Health Care Poor Underserved [Internet]. 2013 [cited 2016 Jun 22]; 24(4):1511-21. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4418558/pdf/nihms681627.pdf
https://www.ncbi.nlm.nih.gov/pmc/article...
) found high rates of hypertension in the user population of this type of medicine.

It is not known so far whether CHCs cause hypertension or simply bring out the high blood pressure that already exists and that would eventually appear spontaneously. In the article by White et al.(1818 White K, Potter JE, Hopkins K, Amastae J, Grossman D. Hypertension among oral contraceptive users in El Paso, Texas. J Health Care Poor Underserved [Internet]. 2013 [cited 2016 Jun 22]; 24(4):1511-21. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4418558/pdf/nihms681627.pdf
https://www.ncbi.nlm.nih.gov/pmc/article...
), the hypothesis for a high number of hypertensive women was developed due to the older age of the participants and not exclusively due to the use of the medication. On the other hand, the study by Kharbanda et al.(1717 Kharbanda EO, Parker ED, Sinaiko AR, Daley MF, Margolis KL, Becker M, et al. Initiation of oral contraceptives and changes in blood pressure and body mass index in healthy adolescents. J Pediatr [Internet]. 2014 [cited 2016 Jun 22]; 165(5):1029-33. Available from: http://www.jpeds.com/article/S0022-3476(14)00696-9/pdf
http://www.jpeds.com/article/S0022-3476(...
), observing the cardiovascular effects of CHCs in adolescents, found no changes in blood pressure.

The evaluation of the previous history of hormonal contraceptive use in postmenopausal women and its relationship with the development of hypertension, of an Australian study, did not find an association between the events in different age groups above 45 years old. This finding was common for both use and time of use, the latter divided into 0 to 5 years; 5 to 10 years; and more than 10 years(1919 Chiu LC, Lind JM. Past oral contraceptive use and self-reported high blood pressure in postmenopausal women. BMC Public Health [Internet]. 2015 [cited 2016 Jun 22]; 15:54-60. Available from: https://bmcpublichealth.biomedcentral.com/articles/10.1186/s12889-015-1392-3
https://bmcpublichealth.biomedcentral.co...
).

The fact is that the mechanism of development of hypertension induced by the medication is still unknown, although hemodynamic changes in the RAAS, on insulin sensitivity, and erythrocyte-cation transport have already been identified(2020 Abrahão SB, Mion Jr D. Hipertensão arterial e contraceptivos orais. Rev Bras Hipertens [Internet]. 2000 [cited 2016 Jun 22]; 7(4):392-95. Available from: http://departamentos.cardiol.br/dha/revista/7-4/015.pdf
http://departamentos.cardiol.br/dha/revi...
). The correlation between exogenous hormones and regulation of blood pressure by the sympathetic nervous system, was also studied by Harvey et al.(2121 Harvey RE, Hart EC, Charkoudian N, Curry TB, Carter JR, Fu Q, et al. Oral contraceptive use, muscle sympathetic nerve activity, and systemic hemodynamics in young women. Hypertension [Internet]. 2015 [cited 2016 Jun 22]; 66(3):590-7. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4537364/pdf/nihms696119.pdf
https://www.ncbi.nlm.nih.gov/pmc/article...
) and, although the results did not show changes in muscle sympathetic activity between users of CHC and non-users, in low-dose hormonal phases, placebo and follicular phase of the menstrual cycle, respectively, the average blood pressure was higher in the first group (89±1 mmHg) comparing to the second (85±1 mmHg), reinforcing the hypertensive effects of the medication for other causes.

Even with the reduction in the concentration of ethinylestradiol in new-generation contraceptives and in the creation of different routes of administration for the medication, the effects on blood pressure are still being observed. The article by Cagnacci et al.(1010 Cagnacci A, Zanin R, Napolitano A, Arangino S, Volpe A. Modification of 24-h ambulatory blood pressure and heart rate during contraception with the vaginal ring: a prospective study. Contraception [Internet]. 2013 [cited 2016 Jun 22]; 88:539-43. Available from: http://www.contraceptionjournal.org/article/S0010-7824(13)00127-3/pdf
http://www.contraceptionjournal.org/arti...
) showed that administration in low concentration (15 mcg/day) and via vaginal ring, whose pharmacokinetics is completely different, was able to stimulate the synthesis of angiotensinogen and increase SBP and diastolic blood pressure (DBP), with this result being observed in 24-hour monitoring of blood pressure.

The article by Odutayo et al.(99 Odutayo A, Cherney D, Miller J, Ahmed SB, Lai V, Dunn S, et al. Transdermal contraception and the renin-angiotensin-aldosterone system in premenopausal women. Am J Physiol Ren Physiol [Internet]. 2015 [cited 2016 Jun 22]; 308(6):535-40. Available from: http://ajprenal.physiology.org/content/ajprenal/308/6/F535.full.pdf
http://ajprenal.physiology.org/content/a...
), comparing the response of the cardiovascular system to the use of oral and patch contraceptives, found a low, but present, activation of RAAS by the dermal route when stimulating orthostatic stress. The hypothesis raised by the authors was based on the absence of passage of the medication through the liver, due to its presentation, reducing the production of angiotensinogen.

In addition to the change of the route of administration, the isolated presence of progestogen, as happens in the Mirena IUD (levonorgestrel) and subcutaneous implant (etonogestrel), has also been studied as minimizer of cardiovascular effects in women. Bender et al.(1111 Bender NM, Segall-Gutierreza P, Najera SOL, Stanczyka FZ, Montoroa M, Mishell Jr DR. Effects of progestin-only long-acting contraception on metabolic markers in obese women. Contraception [Internet]. 2013 [cited 2016 Jun 22]; 88:418-25. Available from: http://www.contraceptionjournal.org/article/S0010-7824(12)01048-7/pdf
http://www.contraceptionjournal.org/arti...
), studying the use of simple progestin contraceptives in healthy and obese women, found no statistically significant increase of pressure values.

The results of these three studies can be based on the theory that the progestogens of second and third generations, as cited above, probably do not present a significant sodium retainer effect, however are devoid of antimineralocorticoid action. Therefore, they are able to, in isolation, maintain the pressure values; but, in combination, are unable to control the sodium retention caused by EE, even if in small doses(55 Oelkers WK. Effects of estrogens and progestogens on the renin aldosterone system and blood pressure. Steroids [Internet]. 1996 [cited 2016 Jun 22]; 61(4):166-71. Available from: https://doi.org/10.1016/0039-128X(96)00007-4
https://doi.org/10.1016/0039-128X(96)000...
,2222 Narkiewicz K, Graniero GR, Mattarei M, Zonzin P, Palatini P. Ambulatory blood pressure in mild hypertensive women taking oral contraceptives: a case-control study. Am J Hypertens [Internet]. 1995 [cited 2016 Jun 22]; 8:249-53. Available from: https://www.ncbi.nlm.nih.gov/pubmed/7794573
https://www.ncbi.nlm.nih.gov/pubmed/7794...
).

With that in mind, drospirenone, a synthetic progestogen similar to endogenous progesterone, began to be prescribed, first as hormone replacement therapy and subsequently as birth control, due to its antimineralocorticoid properties and anti-adrenergic activities(2323 White WB, Pitt B, Preston RA, Hanes V. Antihypertensive effects of drospirenone with 17 beta-estradiol, a novel hormone treatment in postmenopausal woman with stage 1 hypertension. Circulation [Internet]. 2005 [cited 2016 Jun 22]; 1121979-80. Available from: http://circ.ahajournals.org/content/112/13/1979.long
http://circ.ahajournals.org/content/112/...
). This drug has the effect not only of neutralizing the RAAS induction caused by estrogen, but also of blocking receptors for testosterone, reducing the androgenic effects in women(2424 Rübig A. Drospirenone: a new cardiovascular-active progestin with antialdosterone and antiandrogenic properties. Climateric [Internet]. 2003 [cited 2016 Jun 22];6(Suppl-3):49-54. Available from: https://www.ncbi.nlm.nih.gov/pubmed/15018248
https://www.ncbi.nlm.nih.gov/pubmed/1501...
-2525 Krattenmaccher R. Drospirenone: pharmacology and pharmacokinetics of a unique progestogen. Contraception [Internet]. 2000 [cited 2016 Jun 22]; 6229-38. Available from: http://www.contraceptionjournal.org/article/S0010-7824(00)00133-5/pdf
http://www.contraceptionjournal.org/arti...
). De Moraes et al.(1616 Morais TL, Giribela C, Nisenbaum MG, Guerra G, Mello N, Baracat E, et al. Effects of a contraceptive containing drospirenone and ethinylestradiol on blood pressure, metabolic profile and neurohumoral axis in hypertensive women at reproductive age. Eur J Obstet Gynecol Reprod Biol [Internet]. 2014 [cited 2016 Jun 22]; 182113-7. Available from: http://www.ejog.org/article/S0301-2115(14)00474-6/pdf
http://www.ejog.org/article/S0301-2115(1...
), in their study with hypertensive women undergoing regular treatment with antihypertensive drugs and combined EE contraceptives and drospirenone, observed this neutralizer effect when they were unable to find any significant changes in the blood pressure values of the participants.

Despite this and the use for decades of this combination of hormones, drospirenone, as well as other progestins, maintains an increased risk of thrombolytic effects in the body. Data from the Dutch study MEGA (Multiple environmental and genetic assessment of risk factors for venous thrombosis-study), published in 2009, revealed risk for VTE of approximately four times for combinations containing levonorgestrel regarding risk for non-users. The risks increased about six to seven times for other progestin: gestodene, desogestrel, cyproterone acetate, and drospirenone(2626 Van Hylckama Vlieg A, Helmerhorst FM, Vandenbroucke JP, Doggen CJ, Rosendaal FR. The venous thrombotic risk of oral contraceptives, effects of oestrogen dose and progestogen type: results of the MEGA case-control study. BMJ [Internet]. 2009 [cited 2016 Jun 22];339:b2921. Available from: http://www.bmj.com/content/bmj/339/bmj.b2921.full.pdf
http://www.bmj.com/content/bmj/339/bmj.b...
).

A Danish cohort study published in the same year presented similar numbers, i.e., the relative risk of VTE in users of pills of 30 mg of ethinylestradiol and levonorgestrel was 2.9, about two times lower than the observed for desogestrel (6.6), gestodene (6.2), and drospirenone (6.4)(2727 Lidegaard Ø, Nielsen LH, Skovlund CW, Skjeldestad FE, Løkkegaard E. Risk of venous thromboembolism from use of oral contraceptives containing different progestogens and oestrogen doses: Danish cohort study, 2001-9. BMJ [Internet]. 2011 [cited 2016 Jun 22];343:d6423. Available from: http://www.bmj.com/content/bmj/343/bmj.d6423.full.pdf
http://www.bmj.com/content/bmj/343/bmj.d...
).

These findings reinforce the health field concern with the increased risk of cardiovascular diseases, not just the VTE, but also CVA and AMI in women users of combined oral contraceptives(2828 Borges, TFC, Tamazato APS, Ferreira MSC. Terapia com hormônios sexuais femininos e fenômenos tromboembólicos: uma revisão de literatura. Rev Ciênc Saúde [Internet]. 2015 [cited 2016 Jun 22]; 5(2):158-68. Available from: http://200.216.240.50:8484/rcsfmit/ojs-2.3.3-3/index.php/rcsfmit_zero/article/view/334/256
http://200.216.240.50:8484/rcsfmit/ojs-2...
). Thus, various aspects have been discussed as risk factors in studies, including the high doses of ethinylestradiol contained in various formulations, the androgenic properties of different types of progesterone of the various generations developed over the years, hypertension, smoking, hypercholesterolemia, diabetes mellitus, migraines, diseases background, and age (especially after 35 years old), among others(2020 Abrahão SB, Mion Jr D. Hipertensão arterial e contraceptivos orais. Rev Bras Hipertens [Internet]. 2000 [cited 2016 Jun 22]; 7(4):392-95. Available from: http://departamentos.cardiol.br/dha/revista/7-4/015.pdf
http://departamentos.cardiol.br/dha/revi...
).

It is important to emphasize that, despite the new generations of medication with reduced concentrations of hormones and the creation of new routes of administration, choosing the best medication to be prescribed must be associated with complete anamnesis and clinical evaluation, taking into consideration the personal history of morbidities and the risk-benefit of the treatment(2828 Borges, TFC, Tamazato APS, Ferreira MSC. Terapia com hormônios sexuais femininos e fenômenos tromboembólicos: uma revisão de literatura. Rev Ciênc Saúde [Internet]. 2015 [cited 2016 Jun 22]; 5(2):158-68. Available from: http://200.216.240.50:8484/rcsfmit/ojs-2.3.3-3/index.php/rcsfmit_zero/article/view/334/256
http://200.216.240.50:8484/rcsfmit/ojs-2...
-2929 Pallavee P, Samal S, Samal R. Peripheral arterial disease in a female using high-dose combined oral contraceptive pills. Indian J Pharmacol [Internet]. 2013 [cited 2016 Jun 22]; 45(3):303-4. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3696309/
https://www.ncbi.nlm.nih.gov/pmc/article...
). Hypertension is the first risk factor for cardiovascular diseases, and its prevention and control are priority issues for public health.

Study limitations

The limitations of the study are related to the exclusion of incomplete articles, abstracts, and those in languages other than English, Portuguese, and Spanish.

Contributions to the field of nursing, health, or public policies

Studies like this contribute to the understanding of the effects of synthetic hormones in women's blood pressure values, aiding health workers in the search for better practices and correct therapies.

CONCLUSION

We conclude that there is evidence in the literature of pressure changes associated with different combined hormonal contraceptives. The presence of exogenous estrogen in the bloodstream, regardless of concentration, activates the RAAS and causes water and sodium retention. Progestogen, in its turn, is not capable of, in isolation, causing the same effects on blood pressure and, when its formulation has antimineralocorticoid properties, it is able to neutralize the effect of the estrogen administered in combination.

Despite the evolution in the formulation of the medication, they still must be prescribed in accordance with the personal history and presence of morbidities, in an attempt to reduce the effects on the cardiovascular system concerning the incidence of diseases such as hypertension.

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Publication Dates

  • Publication in this collection
    2018

History

  • Received
    14 June 2017
  • Accepted
    01 Sept 2017
Associação Brasileira de Enfermagem SGA Norte Quadra 603 Conj. "B" - Av. L2 Norte 70830-102 Brasília, DF, Brasil, Tel.: (55 61) 3226-0653, Fax: (55 61) 3225-4473 - Brasília - DF - Brazil
E-mail: reben@abennacional.org.br