Some scientists are of opinion that low dose COCs containing gestodene or desogestrel might have a lower risk of AMI How does oral contraceptives affect adversely the cardiovascular system (The COC and circulatory diseases)??
Q.1: Which circulatory diseases have been shown to be more common in COC users ?
1) Systemic hypertension : this is not so much a disease in its own right as it predisposes to and does its damage through the arterial circulatory diseases. However clinician should aver preset mind before such COC is prescribed for women with hypertension. Arterial diseases include Myocardial infarct, Thrombotic strokes
Haemorrhagic strokes and others arterial events such as mesenteric or retinal arteries which are very rarely seen in COC users. Synthetic oestrogens have been shown to raise arterial blood pressure both in short term challenge experiments and in longer term studies. That is why natural oestrogens containg pills have been available as COC which does not promote arterial thrombosis, venous thrombosis, not to speak arterial hypertension. In the majority of combined pill users there is a slight measurable increase in both systolic and diastolic blood pressure within the normotensive range. Early large studies showed a 1.5-3 times higher relative risk of clinical hypertension . Modern varieties with reduced biological impact of the oestrogen and progesterone have reduced such risk but not eliminated this risk. However the new progestogen drospirenone in combination with EE as Yasmin led in one premarketing study to a very small but significant fall in mean blood pressure. Whether this will translate into greater safety of that formulation for arterial disease especially when there are risk factors remains for further study and reports. Increasing the dose of progestogen leads to an increased rate of diagnosis of clinical hypertension .When oestrogen was kept constant the incidence of arterial diseases both as a group and individually was correlated with the progestogen dose . Predisposing factors include strong family history and a tendency to water retention and obesity Past pregnancy associated hypertension does not predispose to hypertension during OC use in controlled studies But the RCGP study showed that past toxemia history does predispose to myocardial infarction especially in smokers .Hypertension is an important risk factor for the arterial diseases to be considered in detail below especially heart disease and both types of stroke.
As of 2003 what do we really know about how the COC affects the various cardiovascular diseases?
CARDIOVASCULAR DISEASE AND STEROID HORMONE CONTRACEPTIVES
On 3-7 November 1997 WHO convened in Geneva a Scientific Group Meeting on Cardiovascular Disease and Steroid Hormone Contraception Acknowledging the major changes that have taken place in the hormonal content of combined oral contraceptives and prescribing patterns the Scientific Group pain particular attention to studies that included data collected after 1980 . The Scientific Group concluded that the incidence and mortality rates of all cardiovascular diseases in women of reproductive age are very low. Any additional cardiovascular disease incidence or mortality attributable to oral contraceptives is very small if the users do not smoke and do not have other cardiovascular risk factors. The background papers prepared for the meeting have been published in the journal Contraception
. Take home message :-there is increasing evidence that no formulation of COC is atherogenic unless there is first an arterial risk factor such as smoking .When such arterial risk factors are present however it remains a tenable hypothesis that these apparently lipid friendly products might reduce arterial disease risk relative to other products
2) COC induced Venous disease like, Deep venous thrombosis .Pulmonary embolism, rarely thrombosis in important single veins e. g mesenteric hepatic or retinal . Current users of COCs have a low absolute risk of VTE which is none the less 3-6 times that in non users. The risk is probably highest in the first year of use and declines thereafter but persists until discontinuation .After use of COCs is discontinued the risk of venous thrombo embolism drops rapidly to that in non users .Among users of COC preparations containing less than 50 ug of ethinylestradiol the risk of venous thrombo embolism is not related to the dose of oestrogen.
COCS containing desogestrel or gestodene probably carry a small risk of VTE beyond that attributable to COCs containing levonorgestrel …There are insufficient data to draw conclusions with regard to COCs containing Norgestimate.
The absolute risks of VTE attributable to use of oral contraceptives rise with increasing age obesity recent surgery and some forms of thrombophilia. Cigarette smoking and raised blood pressure which are important risk factors for arterial disease do not appear to elevate the risk of venous thrombo embolic disease .There are insufficient data to conclude whether there is a relation between VTE and the use of progestogen only contraceptives . The relative risks of venous thrombo embolic disease observed in users of combined oral contraceptives in developed countries appear to be applicable to developing countries
Q.3: Why and How CC cause such thrombogenic tendency?? Can any of these risks be explained by known metabolic changes induced by the artificial hormones of the COC? In particular what is the influence of the oestrogen content in the causation of arterial / venous thrombosis ?
Ans:. Alternations in clotting factor levels induced by oestrogen might be thrombogenic. More important changes include reduced levels of anti thrombin III and protein S but there are also increased levels of fibrinogen and several of the vitamin K dependent coagulation factors . These changes help to explain the increased risk of venous thrombosis particularly if the woman already has congenital or acquired predisposition such as factor V Leiden and antiphospholipid antibodies .However it is likely that if there is already significant arterial wall disease oestrogen might also promote superimposed arterial thrombosis . COCs alter the plasma concentrations of many components of both the coagulation and fibrinolytic systems . These changes are les marked with COCs containing low doses of ethinylestradiol and even less so with progestogen only contraceptives Hereditary conditions such as anti thrombin III defect and factor V Leiden mutation predispose women to venous thrombo embolism . These disorders might underlie a large proportion of idiopathic venous thromboembolic events perhaps one third of those seen in Caucasian women . this effect is increased in women using COCs,
The prevalence of hereditary conditions such as anti thrombin defect and factor V Leiden mutation is about 5% in Caucasian women but is lower in other populations. The positive predictive value of screening for these disorders is very low.
Q.4: But in clinical practice we don’t see quite often the arterial or venous thrombosis. What is your explanation in this regard?? Ans: Surprisingly, there is evidence of a compensatory increased fibrinolytic activity which is also an oestogen effect. This might in part explain the rarity of overt disease especially arterial disease in non smoking pill users.
Q. 5: What may be the altered metabolic profile after administration of oestrogens?? Ans: A series of biochemical changes are possible after administration of oestrogens. Fortunately some are counteracted by Progesterone administration simultaneously. For instance, hepatic secretion of many different proteins is stimulated by oestrogens . Such proteins are involved in the transport of hormones, vitamins and minerals and thereby indirectly control blood pressure and immunological processes . As mentioned earlier, when oestrogen is given the stimulatory effect can sometimes be suppressed by concomitant administration of a progestogen. But the interactions are complex there might also be synergism or independence of the effects and differences between progestagens.
Q.6: What may be advantage of progesterone?? Ans: The risk of venous thrombo embolism which still seems to be primarily caused by oestrogen might be modified by progestogens in some way as yet to be fully explained
Q7: What about HDL?? Many studies have shown that if a constant dose of oestrogen is given then the oestrogen induced high density lipoprotein cholesterol increase is reversed by LNG . .
Q. 8: Does COC promote Acute myocardial infarction??
Data are available which show that increasing age, cigarette smoking, diabetes, hypertension and raised total bold cholesterol are important risk factors for AMI in young women. The scientific Group concluded that the incidence of fatal ad non fatal AMI is very low in women of reproductive age . As such women who do not smoke , who have their blood pressure checked and who do not have hypertension or diabetes are at no increased risk of AMI if they use COCs when compared with never users of the same age. There is no increase in the risk of AMI with increasing duration of use of COCs Thee is no increase in the relative risk of AMI in past users of COCs too. But women with hypertension have an increased absolute risk of AMI . The relative risk of AMI in current users in of COCs with hypertension is at least three times that in current users without hypertension.
What about smokers?? The increased absolute risk of AMI in women who smoke is greatly elevated by use of COCs especially in heavy smokers . The relative risk of AMI in heavy smokers who use COCs might be as high as 10 times than in non smokers who use COCs .Given the relevance of smoking as a serious risk people take for granted it is salutary to not that the 1985 report of the RCGP showed that the pill user who also smoked was not only more likely consequence - a higher case fatality rate was noted in smokers.
What about aged women and use of COC?? Although the incidence of AMI increases exponentially with age the relative risk of AMI in current users of COCs does not change with increasing age. The available data do not allow the effect of the dose of oestogen on the relative risk of AMI to be evaluated independently of the type and dose of progestogen. The incidence of fatal and non fatal ischaemic stroke is very low in women of reproductive age but increases with increasing age
Q.10 What about dose of oestrogens and CVS risks?? Some scientists are of opinion that low dose COCs containing gestodene or desogestrel might have a lower risk of AMI. There are insufficient data to assess whether the risk of AMI in users of low dose COCs is modified by the type of progestogen. The suggestion that users of low dose COCs containing gestodene or desogestrel might have a lower risk of AMI than users of low dose formulations containing levonorgestrel remains to be substantiated
The above conclusions appear to apply equally to women in developed and developing countries.
Ischaemic stroke
The scientific Group concluded that
The reported estimates of relatives risk of ischaemic stroke associated with use of combined oral contraceptives have decreased since the earliest epidemiological studies linking use of oral contraceptives with stroke.
What about ischaemic stroke with pills ?? Are nonsmokers are absolutely safe?? Ans:-In women who do not smoke who have their blood pressure checked and who do not have hypertension the risk of ischaemic stroke is increased about 1.5 fold in current users of low dose combined oral contraceptives compared with non users. There is no further increase in the risk of ischaemic stroke with increasing duration of use of COCs. Women who have stopped taking COC are at no greater risk of ischaemic stroke than women who have never used oral contraceptives. About women with hypertension have an increased absolute risk of ischaemic stroke . The relative risk of ischaemic stroke in current users of COCs with hypertension appears to be at least three times that in current users without hypertension.
The absolute risk of ischaemic stroke in women who smoke is about 1.5-2 times that in non smokers this risk is multiplied by a factor of 2-3 if such women are current users of COCs .The risk of ischaemic stroke in users of COCs containing high doses if oestrogen is higher than that in users of COCs containing low doses of oestrogen. There are insufficient data to allow any conduction to be drawn about whether the risk of ischaemic stroke is related to the type or dose of progestogen contained in low dose COCs .These conclusions appear to apply equally in developed and developing countries. The incidence of fatal and non fatal haemorrhagic stroke is very low in women of reproductive age in both developed and developing countries .
What is the take home message on ischaemic stroke? In women aged less than 35 years who do not smoke and who do not have hypertension the relative risk of haemorrhagic stroke associated with use of COCs is not increased. There is no increase in the risk of haemorrhagic stroke with increasing duration of use of oral contraceptives. Women who have previously used oral contraceptives are at no greater risk of haemorrhagic stroke than women who have never used them.
What about haemorrhagic stroke?? Ans: Women with hypertension have an increased absolute risk of haemorrhagic stroke. The relative risk of hemorrhagic stroke in current users of COCs with hypertension might be 10 times that in current users of COCs with hypertension might be to times that in current users without hypertension. The risk of haemorrhagic stroke in women who smoke is up to twice that in non smokers in women who are current users of COCs and who smoke the relative risk is about 3 times than age matched. The incidence of hemorrhagic stroke increases with age and current use of COCs appears to magnify this effect of ageing .There is no evidence that either the oestrogen or the progestogen constituent of COCs is related to the risk of haemorrhagic stroke.
Possible biological mechanisms for cardiovascular effects
. COCs affect lipoprotein and carbohydrate metabolism haemostasis and mechanisms regulating blood pressure. An influences on the functioning of the endothelium of blood vessels and arterial tone also seems likely The Scientific Group suggested that the potential significance of these changes should be investigated and interpreted using new models of vascular pathophysiology the scientific Group concluded that .The biological mechanisms underlying cardiovascular disease involve a complex interplay between lipoprotein metabolism humoral regulators such as insulin coagulation and fibrinolysis the rennin angiotensin aldosterone system and the functioning of the endothelium of blood vessels.
Does COC cause Diabetes?? Ans: COCs do not increase the risk of developing diabetes mellitus . They have little effect on fasting plasma concentrations of glucose and insulin but cause modest elevations in the plasma levels of glucose and insulin after an oral glucose challenge and might increase insulin resistance. The clinical significance of such changes in otherwise healthy young women is unknown especially in relation to arterial disease.
What about COC & the changes in metabolism of lipoproteins in plasma ?? Ans: changes in metabolism of lipoproteins in plasma induced by uses of COCs have been extensively studied low dose COCs increase fasting plasma levels of triglycerides but have only minor effects on low density lipoproteins lipoprotein or total cholesterol. The effect on HDL depends on the balance of oestrogen and progestogen the clinical significance of such changes is uncertain in the content of current low dose formulations .
Even low dose COCs cause modest elevations in blood pressure that might increase the risk of arterial disease . In healthy young women with a low background risk of arterial disease small increases in blood pressure attributable to use of COC are likely to have minimal effects on the absolute risk of arterial disease.
Comparative studies of users of low dose COCs suggest that the done and type of the progestogen component influence the effect of these preparations on lipid and lipoprotein metabolism and haemostasis . The clinical significance of these differences is uncertain.
Recommendations for further research
The scientific Group made a number of recommendations regarding areas of future research related to the risk of cardiovascular disease and the use of steroid contraception – interested readers are referred to the last edition of this book or to WHO Technical Report 857 .
Making informed choices about COCs
Any assessment of the risk of cardiovascular disuse associated with COCs is complex,. Nevertheless it is clear that mortality rates from cardiovascular disease are extremely low among women of reproductive age and that the added risk of using steroid contraceptives is also very low Within the context of the everyday risks of modern life steroid contraceptives are safe. Factors that need to be taken into account when determining a woman ‘s risk of cardiovascular disuse while using COCs include.
The age specific incidence of each cardiovascular condition
The strength of the association between use of COCs and each cardiovascular outcome the woman’s age and presence of other risk factors for cardiovascular disuse such as smoking and a history of hypertension . Whether there are important differences in risk between particular formulations of COC and if so the choice of formulation.The number of cardiovascular events attributable to the use of COCs is very small especially among users of all ages who do not smoke and among younger users who smoke. The number of associated deaths is even smaller and again is highly dependent on whether the user is a considered against the very high contraceptive efficacy of COCs and the rapid reversibility of this effect after they are stopped. The use of less reliable alternative methods of contraception exposes women to an increased risk of pregnancy a condition that is associated with a higher incidence of venous thromboembolic disuse than that associated with the use of any of the currently available low dose COCs In addition COCs are associated with many non contraceptive benefits including a reduced risk of endometrial and ovarian cancer. By any standard all of the currently available low dose COCs can be regarded as safe
The study Group concluded that
Any increase in incidence of or mortality from cardiovascular disease attributable to use of COC is very small if users do not smoke and do not have other risk factors for cardiovascular disease . for example among users of COCs who do not have risk factors for cardiovascular disease the annual risk of death attributable to use of oral contraceptives is approximately 2 deaths per million users at 20-24 years of age , 2-5 per million users at 30-34 years of age and
The risk of mortality from cardiovascular disease attributable to use of oral contraception is much greater among women aged 40-44 than among women aged 20-24 years
At any given age a woman who smokes but who does not use oral contraceptives is at greater risk of death from arterial disease than a user of oral contraceptives who does not smoke.
The benefits of blood pressure measurement in reducing the risk of cardiovascular disease attributable to use of oral contraception increase with the age of the user.
Venous thrombo embolic disease is the most common cardiovascular event among users of oral contraceptives However it contributes very little to any increase in the number of deaths since the associated mortality is relatively low compared with that associated with arterial diseases. Long term disability from non fatal venous thrombo embolic disease is also low.
What is the difference between relative risk and absolute or attributable risk?
This is most important distinction which is not often understood by either patients or journalists notably in relation to venous thrombo embolism Twice almost nothing out of a million is still almost nothing Pill takers can relate to the analogy that being given a second lottery ticket does not make you hugely more likely to win even though doubling your chances.
A small relative risk might easily cause more attributable cases than a large one if the background prevalence is high and vice versa
The frequency of hepatic cellular adenoma in controls as compared with COC users using older 50 ug plus pills. The second set come from Table 5.8 which itself is from the 1998 report of the WHO’s special Scientific Group They apply to smokers aged 40-44 who would have an increase in relative risk of acute myocardial infarction of only 1.5 if they additionally took the modern low dose pills at that age but the attributable number of extra cases is 85 per million Contrast only 19 extra cases of hematoma in the first set of figures despite a 20 fold greater relative risk.
Neither statistics is good news . but the difference in the excess number of cases caused explains why it was reasonable to accept for 50 ug plus pills a 20 fold increase in the risk of benign liver tumours . however a mere 50 % increase in AMI through more modern pills is widely considered unacceptable for smokers above age 40
Dr Pal , shall we refund the COC which we have purchased after promulgation of Lock Down and purchase condom in lieu of that ? What is your honest unbiased advice?? Adv: Life is pretty risky believe it or not each year one has a 1:1000 chance of having to visit a Casualty Department through a home injury from a bottle or a can . The risk of dying through pill taking is less than one hundredth of the risk of death through smoking 20 cigarettes a day for example.. Potential users can be reminded that there are many other risks in life excluding COVID-19. And Pill induced VTE, Myocardial. However intelligent and educated couple (most of our patients / relatives who seek advice over phone ) are amazingly risk illiterate on medical aspect . Contraceptive seekers (they are not Patients ) are naturally anxious about the known adverse effects of the combined pill on cancer and circulatory disease . Assuming they otherwise wish to use the method how can this anxiety be reduced?
The media / regional magazines do the general public a disservice by tending to exaggerate the bad systemic effects and by not pointing out the counterbalancing non contraceptive benefits aside from the advantages of efficacy reversibility and convenience .Many risks are far greater than pill taking yet cause minimal concern for example having babies or travelling by car – let alone smoking .For those who are not very numerate risks are best expressed in relative terms . At least three deaths have been reported at the Brampton hospital through allergy to hamsters. Finally prospective pill takers can be reminded that the tiny risks of the COC can be further reduced by careful prescribing of lower dose preparations with good subsequent monitoring
Q.1: Which circulatory diseases have been shown to be more common in COC users ?
1) Systemic hypertension : this is not so much a disease in its own right as it predisposes to and does its damage through the arterial circulatory diseases. However clinician should aver preset mind before such COC is prescribed for women with hypertension. Arterial diseases include Myocardial infarct, Thrombotic strokes
Haemorrhagic strokes and others arterial events such as mesenteric or retinal arteries which are very rarely seen in COC users. Synthetic oestrogens have been shown to raise arterial blood pressure both in short term challenge experiments and in longer term studies. That is why natural oestrogens containg pills have been available as COC which does not promote arterial thrombosis, venous thrombosis, not to speak arterial hypertension. In the majority of combined pill users there is a slight measurable increase in both systolic and diastolic blood pressure within the normotensive range. Early large studies showed a 1.5-3 times higher relative risk of clinical hypertension . Modern varieties with reduced biological impact of the oestrogen and progesterone have reduced such risk but not eliminated this risk. However the new progestogen drospirenone in combination with EE as Yasmin led in one premarketing study to a very small but significant fall in mean blood pressure. Whether this will translate into greater safety of that formulation for arterial disease especially when there are risk factors remains for further study and reports. Increasing the dose of progestogen leads to an increased rate of diagnosis of clinical hypertension .When oestrogen was kept constant the incidence of arterial diseases both as a group and individually was correlated with the progestogen dose . Predisposing factors include strong family history and a tendency to water retention and obesity Past pregnancy associated hypertension does not predispose to hypertension during OC use in controlled studies But the RCGP study showed that past toxemia history does predispose to myocardial infarction especially in smokers .Hypertension is an important risk factor for the arterial diseases to be considered in detail below especially heart disease and both types of stroke.
As of 2003 what do we really know about how the COC affects the various cardiovascular diseases?
CARDIOVASCULAR DISEASE AND STEROID HORMONE CONTRACEPTIVES
On 3-7 November 1997 WHO convened in Geneva a Scientific Group Meeting on Cardiovascular Disease and Steroid Hormone Contraception Acknowledging the major changes that have taken place in the hormonal content of combined oral contraceptives and prescribing patterns the Scientific Group pain particular attention to studies that included data collected after 1980 . The Scientific Group concluded that the incidence and mortality rates of all cardiovascular diseases in women of reproductive age are very low. Any additional cardiovascular disease incidence or mortality attributable to oral contraceptives is very small if the users do not smoke and do not have other cardiovascular risk factors. The background papers prepared for the meeting have been published in the journal Contraception
. Take home message :-there is increasing evidence that no formulation of COC is atherogenic unless there is first an arterial risk factor such as smoking .When such arterial risk factors are present however it remains a tenable hypothesis that these apparently lipid friendly products might reduce arterial disease risk relative to other products
2) COC induced Venous disease like, Deep venous thrombosis .Pulmonary embolism, rarely thrombosis in important single veins e. g mesenteric hepatic or retinal . Current users of COCs have a low absolute risk of VTE which is none the less 3-6 times that in non users. The risk is probably highest in the first year of use and declines thereafter but persists until discontinuation .After use of COCs is discontinued the risk of venous thrombo embolism drops rapidly to that in non users .Among users of COC preparations containing less than 50 ug of ethinylestradiol the risk of venous thrombo embolism is not related to the dose of oestrogen.
COCS containing desogestrel or gestodene probably carry a small risk of VTE beyond that attributable to COCs containing levonorgestrel …There are insufficient data to draw conclusions with regard to COCs containing Norgestimate.
The absolute risks of VTE attributable to use of oral contraceptives rise with increasing age obesity recent surgery and some forms of thrombophilia. Cigarette smoking and raised blood pressure which are important risk factors for arterial disease do not appear to elevate the risk of venous thrombo embolic disease .There are insufficient data to conclude whether there is a relation between VTE and the use of progestogen only contraceptives . The relative risks of venous thrombo embolic disease observed in users of combined oral contraceptives in developed countries appear to be applicable to developing countries
Q.3: Why and How CC cause such thrombogenic tendency?? Can any of these risks be explained by known metabolic changes induced by the artificial hormones of the COC? In particular what is the influence of the oestrogen content in the causation of arterial / venous thrombosis ?
Ans:. Alternations in clotting factor levels induced by oestrogen might be thrombogenic. More important changes include reduced levels of anti thrombin III and protein S but there are also increased levels of fibrinogen and several of the vitamin K dependent coagulation factors . These changes help to explain the increased risk of venous thrombosis particularly if the woman already has congenital or acquired predisposition such as factor V Leiden and antiphospholipid antibodies .However it is likely that if there is already significant arterial wall disease oestrogen might also promote superimposed arterial thrombosis . COCs alter the plasma concentrations of many components of both the coagulation and fibrinolytic systems . These changes are les marked with COCs containing low doses of ethinylestradiol and even less so with progestogen only contraceptives Hereditary conditions such as anti thrombin III defect and factor V Leiden mutation predispose women to venous thrombo embolism . These disorders might underlie a large proportion of idiopathic venous thromboembolic events perhaps one third of those seen in Caucasian women . this effect is increased in women using COCs,
The prevalence of hereditary conditions such as anti thrombin defect and factor V Leiden mutation is about 5% in Caucasian women but is lower in other populations. The positive predictive value of screening for these disorders is very low.
Q.4: But in clinical practice we don’t see quite often the arterial or venous thrombosis. What is your explanation in this regard?? Ans: Surprisingly, there is evidence of a compensatory increased fibrinolytic activity which is also an oestogen effect. This might in part explain the rarity of overt disease especially arterial disease in non smoking pill users.
Q. 5: What may be the altered metabolic profile after administration of oestrogens?? Ans: A series of biochemical changes are possible after administration of oestrogens. Fortunately some are counteracted by Progesterone administration simultaneously. For instance, hepatic secretion of many different proteins is stimulated by oestrogens . Such proteins are involved in the transport of hormones, vitamins and minerals and thereby indirectly control blood pressure and immunological processes . As mentioned earlier, when oestrogen is given the stimulatory effect can sometimes be suppressed by concomitant administration of a progestogen. But the interactions are complex there might also be synergism or independence of the effects and differences between progestagens.
Q.6: What may be advantage of progesterone?? Ans: The risk of venous thrombo embolism which still seems to be primarily caused by oestrogen might be modified by progestogens in some way as yet to be fully explained
Q7: What about HDL?? Many studies have shown that if a constant dose of oestrogen is given then the oestrogen induced high density lipoprotein cholesterol increase is reversed by LNG . .
Q. 8: Does COC promote Acute myocardial infarction??
Data are available which show that increasing age, cigarette smoking, diabetes, hypertension and raised total bold cholesterol are important risk factors for AMI in young women. The scientific Group concluded that the incidence of fatal ad non fatal AMI is very low in women of reproductive age . As such women who do not smoke , who have their blood pressure checked and who do not have hypertension or diabetes are at no increased risk of AMI if they use COCs when compared with never users of the same age. There is no increase in the risk of AMI with increasing duration of use of COCs Thee is no increase in the relative risk of AMI in past users of COCs too. But women with hypertension have an increased absolute risk of AMI . The relative risk of AMI in current users in of COCs with hypertension is at least three times that in current users without hypertension.
What about smokers?? The increased absolute risk of AMI in women who smoke is greatly elevated by use of COCs especially in heavy smokers . The relative risk of AMI in heavy smokers who use COCs might be as high as 10 times than in non smokers who use COCs .Given the relevance of smoking as a serious risk people take for granted it is salutary to not that the 1985 report of the RCGP showed that the pill user who also smoked was not only more likely consequence - a higher case fatality rate was noted in smokers.
What about aged women and use of COC?? Although the incidence of AMI increases exponentially with age the relative risk of AMI in current users of COCs does not change with increasing age. The available data do not allow the effect of the dose of oestogen on the relative risk of AMI to be evaluated independently of the type and dose of progestogen. The incidence of fatal and non fatal ischaemic stroke is very low in women of reproductive age but increases with increasing age
Q.10 What about dose of oestrogens and CVS risks?? Some scientists are of opinion that low dose COCs containing gestodene or desogestrel might have a lower risk of AMI. There are insufficient data to assess whether the risk of AMI in users of low dose COCs is modified by the type of progestogen. The suggestion that users of low dose COCs containing gestodene or desogestrel might have a lower risk of AMI than users of low dose formulations containing levonorgestrel remains to be substantiated
The above conclusions appear to apply equally to women in developed and developing countries.
Ischaemic stroke
The scientific Group concluded that
The reported estimates of relatives risk of ischaemic stroke associated with use of combined oral contraceptives have decreased since the earliest epidemiological studies linking use of oral contraceptives with stroke.
What about ischaemic stroke with pills ?? Are nonsmokers are absolutely safe?? Ans:-In women who do not smoke who have their blood pressure checked and who do not have hypertension the risk of ischaemic stroke is increased about 1.5 fold in current users of low dose combined oral contraceptives compared with non users. There is no further increase in the risk of ischaemic stroke with increasing duration of use of COCs. Women who have stopped taking COC are at no greater risk of ischaemic stroke than women who have never used oral contraceptives. About women with hypertension have an increased absolute risk of ischaemic stroke . The relative risk of ischaemic stroke in current users of COCs with hypertension appears to be at least three times that in current users without hypertension.
The absolute risk of ischaemic stroke in women who smoke is about 1.5-2 times that in non smokers this risk is multiplied by a factor of 2-3 if such women are current users of COCs .The risk of ischaemic stroke in users of COCs containing high doses if oestrogen is higher than that in users of COCs containing low doses of oestrogen. There are insufficient data to allow any conduction to be drawn about whether the risk of ischaemic stroke is related to the type or dose of progestogen contained in low dose COCs .These conclusions appear to apply equally in developed and developing countries. The incidence of fatal and non fatal haemorrhagic stroke is very low in women of reproductive age in both developed and developing countries .
What is the take home message on ischaemic stroke? In women aged less than 35 years who do not smoke and who do not have hypertension the relative risk of haemorrhagic stroke associated with use of COCs is not increased. There is no increase in the risk of haemorrhagic stroke with increasing duration of use of oral contraceptives. Women who have previously used oral contraceptives are at no greater risk of haemorrhagic stroke than women who have never used them.
What about haemorrhagic stroke?? Ans: Women with hypertension have an increased absolute risk of haemorrhagic stroke. The relative risk of hemorrhagic stroke in current users of COCs with hypertension might be 10 times that in current users of COCs with hypertension might be to times that in current users without hypertension. The risk of haemorrhagic stroke in women who smoke is up to twice that in non smokers in women who are current users of COCs and who smoke the relative risk is about 3 times than age matched. The incidence of hemorrhagic stroke increases with age and current use of COCs appears to magnify this effect of ageing .There is no evidence that either the oestrogen or the progestogen constituent of COCs is related to the risk of haemorrhagic stroke.
Possible biological mechanisms for cardiovascular effects
. COCs affect lipoprotein and carbohydrate metabolism haemostasis and mechanisms regulating blood pressure. An influences on the functioning of the endothelium of blood vessels and arterial tone also seems likely The Scientific Group suggested that the potential significance of these changes should be investigated and interpreted using new models of vascular pathophysiology the scientific Group concluded that .The biological mechanisms underlying cardiovascular disease involve a complex interplay between lipoprotein metabolism humoral regulators such as insulin coagulation and fibrinolysis the rennin angiotensin aldosterone system and the functioning of the endothelium of blood vessels.
Does COC cause Diabetes?? Ans: COCs do not increase the risk of developing diabetes mellitus . They have little effect on fasting plasma concentrations of glucose and insulin but cause modest elevations in the plasma levels of glucose and insulin after an oral glucose challenge and might increase insulin resistance. The clinical significance of such changes in otherwise healthy young women is unknown especially in relation to arterial disease.
What about COC & the changes in metabolism of lipoproteins in plasma ?? Ans: changes in metabolism of lipoproteins in plasma induced by uses of COCs have been extensively studied low dose COCs increase fasting plasma levels of triglycerides but have only minor effects on low density lipoproteins lipoprotein or total cholesterol. The effect on HDL depends on the balance of oestrogen and progestogen the clinical significance of such changes is uncertain in the content of current low dose formulations .
Even low dose COCs cause modest elevations in blood pressure that might increase the risk of arterial disease . In healthy young women with a low background risk of arterial disease small increases in blood pressure attributable to use of COC are likely to have minimal effects on the absolute risk of arterial disease.
Comparative studies of users of low dose COCs suggest that the done and type of the progestogen component influence the effect of these preparations on lipid and lipoprotein metabolism and haemostasis . The clinical significance of these differences is uncertain.
Recommendations for further research
The scientific Group made a number of recommendations regarding areas of future research related to the risk of cardiovascular disease and the use of steroid contraception – interested readers are referred to the last edition of this book or to WHO Technical Report 857 .
Making informed choices about COCs
Any assessment of the risk of cardiovascular disuse associated with COCs is complex,. Nevertheless it is clear that mortality rates from cardiovascular disease are extremely low among women of reproductive age and that the added risk of using steroid contraceptives is also very low Within the context of the everyday risks of modern life steroid contraceptives are safe. Factors that need to be taken into account when determining a woman ‘s risk of cardiovascular disuse while using COCs include.
The age specific incidence of each cardiovascular condition
The strength of the association between use of COCs and each cardiovascular outcome the woman’s age and presence of other risk factors for cardiovascular disuse such as smoking and a history of hypertension . Whether there are important differences in risk between particular formulations of COC and if so the choice of formulation.The number of cardiovascular events attributable to the use of COCs is very small especially among users of all ages who do not smoke and among younger users who smoke. The number of associated deaths is even smaller and again is highly dependent on whether the user is a considered against the very high contraceptive efficacy of COCs and the rapid reversibility of this effect after they are stopped. The use of less reliable alternative methods of contraception exposes women to an increased risk of pregnancy a condition that is associated with a higher incidence of venous thromboembolic disuse than that associated with the use of any of the currently available low dose COCs In addition COCs are associated with many non contraceptive benefits including a reduced risk of endometrial and ovarian cancer. By any standard all of the currently available low dose COCs can be regarded as safe
The study Group concluded that
Any increase in incidence of or mortality from cardiovascular disease attributable to use of COC is very small if users do not smoke and do not have other risk factors for cardiovascular disease . for example among users of COCs who do not have risk factors for cardiovascular disease the annual risk of death attributable to use of oral contraceptives is approximately 2 deaths per million users at 20-24 years of age , 2-5 per million users at 30-34 years of age and
The risk of mortality from cardiovascular disease attributable to use of oral contraception is much greater among women aged 40-44 than among women aged 20-24 years
At any given age a woman who smokes but who does not use oral contraceptives is at greater risk of death from arterial disease than a user of oral contraceptives who does not smoke.
The benefits of blood pressure measurement in reducing the risk of cardiovascular disease attributable to use of oral contraception increase with the age of the user.
Venous thrombo embolic disease is the most common cardiovascular event among users of oral contraceptives However it contributes very little to any increase in the number of deaths since the associated mortality is relatively low compared with that associated with arterial diseases. Long term disability from non fatal venous thrombo embolic disease is also low.
What is the difference between relative risk and absolute or attributable risk?
This is most important distinction which is not often understood by either patients or journalists notably in relation to venous thrombo embolism Twice almost nothing out of a million is still almost nothing Pill takers can relate to the analogy that being given a second lottery ticket does not make you hugely more likely to win even though doubling your chances.
A small relative risk might easily cause more attributable cases than a large one if the background prevalence is high and vice versa
The frequency of hepatic cellular adenoma in controls as compared with COC users using older 50 ug plus pills. The second set come from Table 5.8 which itself is from the 1998 report of the WHO’s special Scientific Group They apply to smokers aged 40-44 who would have an increase in relative risk of acute myocardial infarction of only 1.5 if they additionally took the modern low dose pills at that age but the attributable number of extra cases is 85 per million Contrast only 19 extra cases of hematoma in the first set of figures despite a 20 fold greater relative risk.
Neither statistics is good news . but the difference in the excess number of cases caused explains why it was reasonable to accept for 50 ug plus pills a 20 fold increase in the risk of benign liver tumours . however a mere 50 % increase in AMI through more modern pills is widely considered unacceptable for smokers above age 40
Dr Pal , shall we refund the COC which we have purchased after promulgation of Lock Down and purchase condom in lieu of that ? What is your honest unbiased advice?? Adv: Life is pretty risky believe it or not each year one has a 1:1000 chance of having to visit a Casualty Department through a home injury from a bottle or a can . The risk of dying through pill taking is less than one hundredth of the risk of death through smoking 20 cigarettes a day for example.. Potential users can be reminded that there are many other risks in life excluding COVID-19. And Pill induced VTE, Myocardial. However intelligent and educated couple (most of our patients / relatives who seek advice over phone ) are amazingly risk illiterate on medical aspect . Contraceptive seekers (they are not Patients ) are naturally anxious about the known adverse effects of the combined pill on cancer and circulatory disease . Assuming they otherwise wish to use the method how can this anxiety be reduced?
The media / regional magazines do the general public a disservice by tending to exaggerate the bad systemic effects and by not pointing out the counterbalancing non contraceptive benefits aside from the advantages of efficacy reversibility and convenience .Many risks are far greater than pill taking yet cause minimal concern for example having babies or travelling by car – let alone smoking .For those who are not very numerate risks are best expressed in relative terms . At least three deaths have been reported at the Brampton hospital through allergy to hamsters. Finally prospective pill takers can be reminded that the tiny risks of the COC can be further reduced by careful prescribing of lower dose preparations with good subsequent monitoring
No comments:
Post a Comment