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

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

Title	Year/ Language	Design	Methodology	Outcome
Transdermal contraception and the renin-angiotensin-aldosterone system in premenopausal women⁽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... ⁾	2015 English	Prospective, non-randomized Premenopausal women (N = 30).	Application of negative pressure chamber into three groups: control (10), using contraceptive pill (10), and using contraceptive patch (10), for activation of RAAS and observation of systemic changes.	The results suggest that the use of contraceptives in the form of patches is associated with a low RAAS activation and low response by this system to caused orthostatic stress. The hypothesis is: the absence of estrogen (contained in the patch) passing through the liver reduces the production of angiotensinogen.
Modification of 24-h ambulatory blood pressure and heart rate during contraception with the vaginal ring: a prospective study⁽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... ⁾	2013 English	Cross-sectional Healthy women (N = 18).	Blood pressure was monitored every 30 minutes for 41 hours, with an oscillometric device. Each participant used vaginal rings for six cycles, and pressure measurements were taken in the last days of the sixth cycle.	The results showed increased values in the 24h monitoring for diastolic pressure and average pressure. Even the smaller dose of estrogen, as contained in the vaginal ring, can stimulate the synthesis of angiotensinogen.
Effects of progestin-only long-acting contraception on metabolic markers in obese women⁽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... ⁾	2013 English	Prospective, non-randomized Obese women, with no previous use of contraceptive pills (N = 25).	The participants were divided into three groups: non-hormonal contraceptive (8), subdermal implant (8), and Mirena IUD (9). Three visits (0, 3, and 6 months) were carried out to collect laboratory tests and perform clinical evaluations. Non-change of life habits (diet and physical activity) was guaranteed during the research.	No statistically significant differences were observed in the pressure values of the groups and in the periods of data collection.
Our Own Worst Enemy: Pharmacologic Mechanisms of Hypertension⁽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... ⁾	2015 English	Literature review	Broad categorization of different drugs and topical discussion of the effects of each one on blood pressure and emergence of hypertension.	The articles show that the endogenous estrogen of hormonal contraceptives activates the RAAS, producing angiotensinogen by the liver and contributing to the retention of sodium and water. New generation medications, with smaller amounts of hormones, increase in 8 and 6 mmHg the systolic and diastolic pressures, respectively, when compared to non-users of hormonal contraceptives. Another conclusion taken from other articles is that hypertension is found in up to 2.8% of users.
Women-specific factors to consider in risk, diagnosis and treatment of cardiovascular disease⁽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... ⁾	2015 English	Literature review	Discussion in topics of the biological mechanisms of the different sexes, followed by the specifically female conditions, such as the use of hormonal contraceptives.	The chronic use of combined oral contraceptives (COCs), regardless of the concentration of estrogen, can increase blood pressure values both in normotensive and hypertensive women (8 mmHg). In addition, some articles have shown that the use of COCs may increase the risk of venous thrombosis, heart attack, and CVA.
Associations between oral contraceptive use and risks of hypertension and prehypertension in a cross-sectional study of Korean women⁽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... ⁾	2013 English	Retrospective and observational Women, selected from a database (N = 3,356).	Information on sociodemographic characteristics and use of oral contraceptive were collected, including time of use. Blood pressure was measured while the women were in a sitting position with their back supported, after 5 minutes of rest. A mercury gauge was used in the right arm, and three measurements were carried out. The final value was the average of the last two measurements.	The average of systolic and diastolic pressures was higher in participants who have been using oral contraceptive for longer periods. In addition, there was a significant relationship between time of use of contraceptives and prevalence of hypertension: 34.8% in the group of users for more than 24 months, against 18.1% in the group of non-users. The same relationship was observed for the prevalence of prehypertension.
Appropriate follow up to detect potential adverse events after initiation of select contraceptive methods: a systematic review⁽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... ⁾	2013 English	Systematic review Articles (N = 15)	From the selected articles via PubMed, five approached incidence of SAH and use of CHC, seven of pelvic inflammatory disease and IUD, and three on weight gain and use of medroxyprogesterone. We did not find any studies on migraine and CHC.	Regarding the use of CHC and SAH: the articles, in general, showed a small percentage of women who developed high blood pressure after use for 24 months of combined contraceptives. The evidence from the study were limited, as some of the studied articles did not use the recommended methodology for pressure measurement, and one of them had a small sample size.
Effects of a contraceptive containing drospirenone and ethinylestradiol on blood pressure, metabolic profile and neurohumoral axis in hypertensive women at reproductive age⁽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... ⁾	2014 English	Prospective and controlled Controlled hypertensive women (N = 56).	The participants were divided into two groups: volunteers (30) to use combined hormonal contraceptives (20mcg ethinylestradiol and 3 mg drospirenone) and volunteers (26) to use non-hormonal contraceptives. All evaluations were made in the same menstrual period. Blood pressure was measured by the auscultation method following the current recommendations, with a calibrated mercury sphygmomanometer.	Regarding blood pressure: there were no significant changes in systolic and diastolic blood pressure after 6 months in any of the groups.
Initiation of Oral Contraceptives and Changes in Blood Pressure and Body Mass Index in Healthy Adolescents⁽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(... ⁾	2014 English	Observational. Adolescents (N = 1,422).	The participants, selected through a medication dispensing system, were divided into two groups: using COC (510) and not using hormonal methods (912). Considering the baseline, the measures of weight, height, and blood pressure were taken in the first month of medication dispensing, and other measurements were taken during the medical visits performed after starting the medication (every 3 months). Blood pressure measures were taken in accordance with the recommendations, by trained professionals and properly calibrated instruments.	There was no statistically significant difference in systolic and diastolic blood pressure among adolescents using COC and the control group in the 3^rd, 6^th, and 12^th month of follow-up.
Hypertension among Oral Contraceptive Users in El Paso, Texas⁽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... ⁾	2013 English	Prospective cohort. Women (N = 941).	The participants were divided into two groups: those who received the pills from USA clinics and those who received them from Mexican pharmacies. Four interviews were conducted, with three-month intervals between them, two (first and fourth) in person and two (second and third) by phone. Information on demographic data, history of use of contraceptive pills, presence of hypertension, and blood pressure measurement values were collected. In the last interview, blood pressure was measured.	Seven per cent of the women who took pills from the USA clinics had hypertension, against 10.5% of those who got their medication from Mexican pharmacies. The conclusion of the study was that there was a high prevalence of hypertension in women who used oral contraceptives compared to other studies, regardless of where they got their medication. In addition, the authors associated this result to the older age of the women who participated in the study.

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[1] CORRESPONDING AUTHOR: Cristiane Crisp Martins Ribeiro. E-mail: criscrisp@gmail.com