Abstract
Background:
Combined hormonal contraception (CHC) is a widely accepted contraceptive method for women of reproductive age. It is considered a safe and user-friendly option for women without risk factors for cardiovascular diseases; however, it is contraindicated in women with established cardiovascular disease or overt risk factors. CHC increases the incidence of cardiovascular events through higher risk for thromboembolic events and potential increases of blood pressure.
Objective:
The aim of this article was to explain when and how arterial hypertension should be addressed as absolute and relative contraindication for CHC use as well as a possible consequence of CHC therapy.
Methods:
This is descriptive method which should be crucial to identify women who are not suitable candidates for CHC by thoroughly assessing their medical history, including current and previous conditions, evaluating potential risk factors, calculating body mass index (BMI), and regularly monitoring blood pressure and weight.
Results and Discussion:
Several explanations have been proposed to explain blood pressure elevations. The estrogenic component in CHC stimulates renin–angiotensin–Aldosterone system (RAAS) through increased hepatic production of angiotensinogen. The regulation of anti-diuretic hormone (ADH) through osmoreceptors may also be altered. Before prescribing CHC, gynecologists should conduct a thorough cardiovascular risk assessment. This should include a targeted questionnaire addressing cardiovascular disease history and risk factors, such as smoking and elevated lipid levels. Additionally, BMI calculation and blood pressure measurement should be performed. It is advisable to assess thyroid function by measuring THS levels at the initiation of CHC and every five years thereafter, as thyroid dysfunction is associated with increased cardiovascular risk, particularly arterial hypertension Laboratory testing should include lipid profiles, glucose levels and thyroid function assessment performed prior to initiating CHC and at regular intervals during its use. This article focuses on arterial hypertension addressing its role as both an absolute and relative contraindication for CHC use as well as a possible consequence of CHC therapy.
Conclusion:
Women with well-controlled arterial hypertension may, in certain circumstances, safely use CHC. The combination of estetrol and drospirenone holds promise as an ideal choice for women with arterial hypertension seeking CHC.
Keywords: combined hormonal contraception, arterial hypertension, cardiovascular diseases, risk factors
1. CHC DOUBLES RISK FOR CARDIOVASCULAR EVENTS
Cardiovascular risks in healthy women of reproductive age are generally low, and cardiovascular end-point events very rare (1). However, receiving combined oral hormonal contraception (CHC) is associated with a twofold increase in the risk for myocardial infarction, cerebrovascular events, venous thrombosis, and peripheral obliterative artery disease (2). The presence of any of these diseases is a contraindication for CHC use.
Women of reproductive age may have risk factors for cardiovascular diseases. Classical risk factors include arterial hypertension, hyperlipidemia, obesity, smoking, physical inactivity and diabetes mellitus. The presence of any single cardiovascular risk factor increases the risk of cardiovascular events by two- to threefold, or even higher. In the case of arterial hypertension, the usual approximation is 5.4 to 9.5 times (3, 4). The combination of multiple risk factors further potentiates these effects. Moreover, emerging cardiovascular risk factors such as hypertensive disease of pregnancy (e.g. gestational hypertension, preeclampsia, hemolysis elevated liver enzymes low platelet count syndrome (HELLP)), gestational diabetes, polycystic ovary syndrome (PCOS), and migraine headaches enhance the risk for cardiovascular events in women of reproductive age (4).
2. CHC AS A PREFERRED CONTRACEPTIVE CHOICE AMONG WOMEN
The Contraceptive Choice Project conducted in the USA (5) between 2007 and 2009, followed more than 5,000 women who selected and purchased their contraceptive methods over the counter. Nearly 20% of these women opted for CHC. However, the project revealed that 24 of them (2.4%) had contraindication for CHC use: 17 had arterial hypertension, 2 had a history of venous thrombosis, 3 were smokers over the age of 35, 2 experienced migraine headaches. Contemporary data for the USA may show even worse results due to the rising obesity epidemic. Currently, one in ten women in the USA has arterial hypertension, and three-quarters of them are unaware of their condition (6).
3. PREEXISTENT ARTERIAL HYPERTENSION IN WOMEN OF REPRODUCTIVE AGE
Preexisting arterial hypertension is relatively common in women of reproductive age. While there is no study on the incidence and prevalence of arterial hypertension in this group in Europe and the USA, hypertensiologists estimate the prevalence to be as high as 10 % among women under 43 years of age (expert opinion, Slovenian Medical Society). The critical issue is whether arterial hypertension is well controlled or not. Blood pressures of 160/95 or higher are considered a contraindication for CHC. However, blood pressures in the range of 140-159/94 are regarded as a relative contraindication for CHC. In such cases, physicians can manage blood pressure effectively with appropriate medications.
4. CHC CAN INDEPENDENTLY CONTRIBUTE TO THE DEVELOPMENT OF ARTERIAL HYPERTENSION
The issue concerning CHC and arterial hypertension can be examined from both sides. Mild elevations in blood pressure, defined as an increase in systolic blood pressure by up to 6 mm Hg and diastolic pressure by up to 1–2 mm Hg, are observed in nearly all women taking CHC (7). However, in up to 5 % of users, blood pressure elevations can be more significant, resulting in serious arterial hypertension (8).
Several explanations have been proposed to explain these blood pressure elevations. The estrogenic component in CHC stimulates renin –angiotensin –Aldosterone system (RAAS) through increased hepatic production of angiotensinogen (9). Additionally, the regulation of anti-diuretic hormone (ADH) through osmoreceptors may also be altered (10). Recent important findings suggest that certain genetic polymorphisms of estrogen receptor β may predispose some women to the development of arterial hypertension in association with CHC use (11). If CHC is discontinued early, arterial hypertension is typically reversible; however, if nephrotic damage has already occurred, the condition may be irreversible.
5. PRE-PRESCRIPTION EVALUATION BY GYNECOLOGISTS
Before prescribing CHC, gynecologists should conduct a thorough cardiovascular risk assessment. This should include a targeted questionnaire addressing cardiovascular disease history and risk factors, such as smoking and elevated lipid levels. Additionally, BMI calculation and blood pressure measurement should be performed. It is advisable to assess thyroid function by measuring THS levels at the initiation of CHC and every five years thereafter, as thyroid dysfunction is associated with increased cardiovascular risk, particularly arterial hypertension (12,13). If blood pressure and other results are within normal ranges, CHC can be safely prescribed. However, if arterial hypertension develops in subsequent months or years, CHC should be discontinued, and progestin-only pill, implants, IUD/IUS (Intrauterine device/Intrauterine Hormone Releasing System), or barrier contraception methods, should be administered (14).
To minimize the risk of deep vein thrombosis and thromboembolisms, we prescribe CHC in accordance with the recommendations of the European Medical Agency (EMA) (15). It is crucial to emphasize that CHC is not prescribed to women with a current history of a thromboembolic event (e.g. deep vein thrombosis, pulmonary embolism, heart attack, stroke, transient ischemic attack, angina pectoris), known predisposition to blood clotting disorders, a history of migraine with aura, diabetes mellitus with vascular complications, severe arterial hypertension (e.g. systolic ≥160 or diastolic ≥100mm Hg), or significantly elevated blood lipids. Other common risk factors include a BMI over 30 kg/m2, age over 35 years, and smoking. The simultaneous presence of two or more of these risk factors further constitutes a contraindication for CHC use.
6. POORLY TREATED OR UNTREATED ARTERIAL HYPERTENSION AS A CONTRAINDICATION FOR CHC
Poorly treated or untreated arterial hypertension is a contraindication for the use of CHC. On the other hand, women with treated and well-controlled arterial hypertension, maintaining optimal blood pressure levels around 115/75 mm Hg and without other cardiovascular risk factors, can receive CHC. However, women need to know that their first hormonal contraceptive choice is progestin-only oral contraception (POC) (4). In addition, they need to be informed about the associated increased cardiovascular risk, and about the importance of regularly monitoring their blood pressure as well as of taking care of their health.
7. ESTETROL AND DROSPIRENONE IN CHC: NON-HARMING/PROMISING EFFECTS ON BLOOD PRESSURE
Fortunately, newly discovered estrogen for contraception, estetrol, as well as natural estrogens, like 17-β estradiol, have less influence on RAAS compared to classical synthetic ethynyl estradiol (4, 16). Moreover, estetrol activates estrogen receptors α in vascular endothelial cells that increase the production of nitric oxide (NO) and cause vasodilatation (16). The progestogen component of CHC does not have a pro-hypertensive effect, but it is known that first- and second-generation progestins may potentiate the estrogenic influence on elevating blood pressure. (4). However, third- and fourth-generation progestins combined with estrogen no longer potentiate this influence (17). Moreover, drospirenon and dienogest have antiandrogenic and antimineralocorticoid activities. In a study involving 72 women (18), drospirenone significantly reduced blood pressure by 6 mm Hg.
8. CONCLUSION
Women with well-controlled arterial hypertension may, in certain circumstances, safely use CHC. Today, there are CHC options of estrogens with less adverse CV effects, as well as progestins that may have a protective influence on blood pressure rates. The combination of estetrol and drospirenone holds promise as an ideal choice for women with arterial hypertension seeking CHC.
Ethical Consideration:
Article represent authors opinion and ethical approval here is not indicated.
Author‘s Contributions:
All authors contributed equally in preparation this article including final proofreading..
Conflict of Interest:
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Financial support and sponsorship:
None.
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