Dr.Álvaro Monterrosa Castro, MD
The effect of oral contraceptives on the cardiovascular system of women has been the subject of great controversy, speculation, and epidemiological and physiological research for nearly 30 years. years(33).
Likewise, it has been asserted that the greatest health risks posed by contraceptive pills have to do with pathologies of the circulatory system (1,167).Thromboembolism, arterial hypertension, cerebrovascular accident, both thrombotic and hemorrhagic, and acute myocardial infarction, have been stated (49).
Therefore, the mechanisms by which which the pill can cause cardiovascular disease are:
- Action of estrogens on the coagulation system.
- Action of progestins on lipid metabolism.
- Effects of the estrogen-gestagen combination on blood pressure and carbohydrate metabolism (6,18,73).
In the 1960s, it was first suspected that oral contraceptives increased the relative risk of venous and arterial vascular diseases (4.18).Furthermore, the investigations carried out in the following years showed a direct relationship between these accidents and the high doses of estrogens and gestagens present up to that date in contraceptive pills (6,49).
Subsequently, it was noted that cardiovascular risk is not related to the duration of use of the oral contraceptive and that this risk persists a few weeks after stopping use (168).
At the same time, it became evident that those users who were also smokers.They had an even higher risk of having a traffic accident.As well as those that presented some characteristics that exposed them to contracting these diseases (167,169).
Likewise, there is now evidence that shows that microdoses have a lower risk of cardiovascular disorders (18)if the woman is healthy and non-smoker (49,167,140).And this is demonstrated in the study recently carried out and published by Gerstman et al in 1991 (170).
More recently Lobo and Col(120)in 1996, based on epidemiological studies.They suggest that oral contraceptives are very likely not associated with an increased risk of atherosclerosis or myocardial infarction.
Based on the positive impact on HDL-C and LDL-C.They suggest that a possible beneficial, cardioprotective effect may occur with prolonged use of the pill.They comment that since young women, non-smokers.They have a low incidence of cardiovascular disease, their hypothesis may be difficult to test.
Consequently, there appears to be no evidence that microdose pill users.That they are over 35 years old, that they do not smoke, nor are they at risk of contracting diseases of the circulatory system.face a higher chance of having a stroke or heart attack than younger users (40).
In addition, the Royal Collage of General Practitioners between 1977 and 1981 determined that Ethinyl-estradiol is responsible for complications in the venous system such as thrombosis and embolisms.While the progestogen component is responsible for arterial complications and especially the development of arterial hypertension (25).
1.Thromboembolism and Oral Contraceptives
Thromboembolic disease is a difficult entity to diagnose and with variable clinical expression (73).Thromboembolism is the obstruction of a blood vessel by a clot (49).
Likewise, it was considered that the most frequent thromboembolism among users of oral contraceptives is that caused by in the veins of the lower limbs.The clots reach the lungs, becoming potentially fatal pulmonary embolisms (49).
In addition, in 1996 Darney (33)asserts that embolism It is a rare consequence induced by oral contraceptives.The risk of developing thromboembolism was found to be 4.4 to 9 times higher than non-users (49).
Also, studies from the University of Oxford- Family Planning Association (oxford/FPA), the Royal College of General Practitioners (RCGP) and the Walnut Creeek cohort studies, among others (5).They showed that with a lower dose of estrogen there was a lower risk of developing thromboembolism.
Consequently, the relative risk among users of the new contraceptives compared to non-users was lower than 8.3 to 2.8.(49).Pills with low estrogen content have less effects on blood clotting and anticoagulant factors than pills with more than 50 ug of estrogen(5, 33).
On the other hand, at least 11 case-control studies indicate that the use of oral contraceptives increases the opportunity for venous thromboembolism.The risk being much higher in users who smoke (76).These studies suggest that the risk remains constant even if the time of use is prolonged and does not persist when the method is suspended (76).
In addition, various publications in which evaluate the association of low doses of estrogens with a third generation progestin.They consider greater progress to be made in reducing the risk of thromboembolism and its complications (5,6,73).
However, in October 1995 the Committee on Safety of Medicines (CSM) of the United Kingdom (171).Based on three epidemiological studies (129,130,172)not yet published on that date.It alerted and informed the Doctors and Pharmacists of Great Britain that the risk of thromboembolic disease was four times higher in women who used oral contraceptives than in non-users.
It also communicated that a possible increase in the risk of thromboembolism had been observed, up to three times greater in users who used pills containing Gestodene or Desogestrel.When compared with users of pills containing Levonorgestrel (120,130).
Therefore, similar communications were distributed in Germany and Norway by Health authorities (12 ).The World Health Organization, author of two of the studies (129,130).In its “News Release” No. 2/95 of October 23, 1995. It advises that until more extensive information is available, microdose oral contraceptives other than those containing Desogestrel and Gestodene should be preferred.
Then, other researchers (172)analyzing medical data in the United Kingdom.They observed that users of Gestodene and Desogestrel were almost twice as likely to suffer fatal thromboembolism than users of Levonorgestrel.
The results of these three studies were contrary to what was expected, based on the known effects on maternal metabolism(73).This information created a new stir in oral contraceptive research.Event that has been called Pill Scare II (second pill scare) (173).
Finally, the conclusions of the three studies (129,130,172)to date are strongly debated (12,63,173,174)and are analyzed by Balash and Calaf (73).To date the positions are very mixed.The Human Reproduction Magazine in its Volume 11 No. 4 of 1996. It presents us in the debates section, the opinion of 6 authors on the association of oral contraceptives and thromboembolic disease (174).
Finally, further research should be done on the effects of oral contraceptives on the coagulation system (12,63).One must be very rigorous in the evaluation of the patient’s possible risk factors for thromboembolic disease before prescribing an oral contraceptive, whatever it may be (12,73).
In-vitro determination of Leydin factor 5.It is being used to try to identify those patients genetically predisposed to thrombo-embolic phenomena.
(Read Also: Oral Contraceptives Contraindications)
2.Event modified by age and predisposing risk factors, especially cigarette consumption (13,167,175).The pathogenesis may be related to the coagulation system, metabolic changes, and increased blood pressure.
In addition, some evidence suggests that thrombosis and not atherosclerosis is the cause of many or almost all of the cardiovascular risks inherent to the use of oral contraceptives.Since these thrombotic events are related to the amount of estrogen received.
Consequently, with preparations with low estrogen content the risk of stroke can be greatly reduced(176,177, 178 ).If the above is true, microdose users would have a lower risk of stroke than reports suggest (76).
Therefore, the World Health Organization Health in a multicenter, international case-control study.It established that the incidence of ischemic stroke is low in women of reproductive age.And that the risk attributable to the use of oral contraceptives is low.This risk can be further reduced if the woman is not a smoker and has no history of high blood pressure (13).
Finally, the same group established that the risk of stroke Vascular hemorrhagic disease attributable to pill use is not found in young women and only slightly in older women (175).The estimated excess risk for both types of stroke, associated with microdose and macrodose oral contraceptives, is 2 and 8 respectively per 100,000 woman-years (175).
3.Acute Myocardial Infarction and Oral Contraceptives
Acute myocardial infarction is an extremely rare event in women users of oral contraceptives.Additionally, it is usually limited to women over 35 who smoke.Concept widely known since 1981, thanks to the prospective analysis of the Royal College of General Practitioners of the United Kingdom (179).
First, in 1987 the Oxford study of Family Planning did not found a direct association between oral contraceptives and myocardial infarction (180).Croff and Hannaford (181)identified several factors that increase the risk of myocardial infarction in young women, and smoking has a significant risk.
Consequently, the Consuming less than 15 cigarettes/day carries a 1.7-fold increased risk.More than 15 cigarettes/day increases it to 4.3 times.A history of pregnancy-induced hypertension has a relative risk of 2.8.The presence of high blood pressure has a relative risk of 2.4.And diabetes has a relative risk of 6.9.
These data and others (182)amply confirm that the real risk of myocardial infarction in users of oral contraceptives is cigarette consumption (180,183).The possible mechanisms are: increased atherogenesis, increased coronary thrombosis and coronary artery spasm.
Old contraceptives with high doses of progestogens were associated with an adverse change in the lipid profile (184).Decrease in HDL-C and elevation in LDL-C, creating an atherogenic condition (183).Estrogens in themselves raise HDL-C and decrease LDL-C.Therefore, the lipid profile depends on the balance between the estrogenic and progestogenic effect.
Most likely, Ethinyl-estradiol in oral contraceptives can directly protect the coronary arteries from atherogenesis.By inhibiting LDL-C from the walls of blood vessels (183).
Third-generation progestogens are considered to have neutral lipid action, therefore oral contraceptives combinations that contain them, would cause favorable lipid changes (183).Which leads one to think that they are not atherogenic nor do they increase the risk of myocardial infarction in non-smoking patients (1, 167).
A recent publication ( 120)cites a study that states that the RR of myocardial infarction among young users of microdose combined oral contraceptives is 0.2.Therefore, the use of these new formulas by non-smoking women could be associated with a cardioprotective effect.There is no conclusive evidence in this regard(18).
Norgestimate, Desogestrel and Gestodene cause an increase in HDL-C, protective lipoproteins.But it is not known whether these biochemical changes are important from a clinical point of view (121,122,123).
Engel et al (185)performing coronary angiogram In women who had suffered a myocardial infarction, he found that 36% of those who used oral contraceptives had diffuse atherosclerosis.This point of view supports the cardioprevention hypothesis of microdose oral contraceptives that include latest generation progestogens.Stated by Lobo and Col (120).
.
