Thursday, October 2, 2014

PCOS and Birth Control Pills, part 2: Obesity



As a follow-up to PCOS Awareness Month, we are continuing our periodic series on PCOS, Polycystic Ovarian Syndrome.

Here are some of the previous entries so far in the series:
Now we are discussing common treatment protocols for PCOS (and the pros and cons of each) ─ from a Health At Every Size®, size-friendly point of view (meaning improving health without making the scale the focus; no diet/weight loss talk).

We've already discussed:
Now we are talking about using birth control pills to regulate the menstrual cycle, reduce androgen levels, and control unpleasant PCOS symptoms like hirsutism, acne, and alopecia.

Part One was background about how oral contraceptives work, the different types available, and side effects to be aware of.

Today, in Part Two, we discuss whether there are special considerations for oral contraceptive use in women of size.

The next entry will discuss the use of oral contraceptives to treat PCOS symptoms.

Oral Contraceptives and Obesity

One important controversy is whether the Pill is a good choice for "obese" women.

This is an important issue for women of size in general, regardless of whether or not they have PCOS.

We deserve to have accurate information about efficacy and risks of any medication prescribed to us, with data specific to our size. We cannot truly give informed consent to medication use if we do not have data specific to our population.

Since most women with PCOS have increased bodyweight and may be taking medications that are contraindicated during pregnancy, this is a particularly vital issue for those with PCOS as well.

The important questions are:
  • Whether oral contraceptives are as effective in preventing pregnancy in women of size
  • Whether oral contraceptives increase complications such as blood clotting, glucose intolerance, and cardiovascular risks in women of size
Of course, the question of contraceptive effectiveness is a bitterly ironic one for those with PCOS, since fertility is often already compromised with PCOS.

However, fertility can spontaneously come and go with PCOS, and therefore those who don't want children, are delaying a family, or are done with childbearing still need contraception. Still others need to have absolutely fool-proof contraception while on anti-androgenic medications that increase the risk for birth defects. So the question of efficacy is still a valid one, even in PCOS women with fertility issues.

And of course, since PCOS itself increases the risks for glucose intolerance, insulin resistance, blood clotting issues, and possibly cardiovascular risks, it's important to know whether taking oral contraceptives would further increase that risk.

Remember, as discussed in Part One, there are two main types of oral contraceptives ─ combination pills (which contain both estrogen and a progestin) and mini-pills (which contain only progestin). Estrogens are usually the same in every pill but doses differ; progestins differ greatly between pills, and different "generations" of drugs tend to have different risk profiles. So when discussing risks, a great deal depends which oral contraceptive you are referring to and the specifics of its formulation.

Oral Contraceptive Efficacy in Obese Women

The first key question is whether oral contraceptives are as effective in preventing pregnancy in obese women as they are for average-sized women.

Unfortunately, there is conflicting evidence on this question.

Initially, early research did not find that the combination Pill was less effective in women of size. However, this research was done with high-dose pills. More recent versions of the Pill have lower doses of estrogen to lower the risk for blood clots, and these lower-dose pills may not be as effective at preventing pregnancy in obese women.

For example, one study found that the risk of unintended pregnancy was 70% higher in women with a BMI over 32. The actual numerical risk was still very small, mind, but was increased for women of size. A number of resources list the actual numerical risk as an additional 2-4 pregnancies per 100 woman-years.

But why would weight interfere with efficacy in the Pill? Researchers speculate there may be several reasons. First, greater stores of body fat are thought to sequester the estrogen, keeping it from being used fully or taking it longer to reach and maintain effective levels. Second, up-regulated liver enzymes in some may break down the hormones faster. Third, women of size have a larger body mass and blood circulation volume. The combination of having more body tissue to circulate through, more sequestering of hormones in body fat, and less time in which the hormones are active may result in lower circulating levels of hormones.

There may be other factors as well. As one review put it:
High BMI affects absorption, metabolism, distribution, protein binding, and clearance of various drugs. It is important to study the contraceptive efficacy of available hormonal methods in women at the extremes of body weight.
However, although it is biologically plausible that a higher body weight could lessen the effectiveness of oral contraceptives, follow-up research has not really confirmed whether the Pill is less effective in obese women. 

Some research found a small effect, but once the data was adjusted for other variables, this effect was not significant. Other recent research did not find any increased contraceptive failure in high BMI women, including those with a BMI over 40.

Some researchers question whether the effect might be stronger in very high BMI women versus those with borderline BMIs, something most data has not looked at with sufficient sample sizes for strong conclusions. It may be that because most data involved women with moderate obesity (where a mild correlation disappeared after adjusting for confounding factors), a statistically significant correlation in higher BMIs may have been missed.

The latest Cochrane review concluded:
The evidence did not generally show an association of BMI with effectiveness of hormonal contraceptives. However, the evidence was limited for any individual contraceptive method.
They also noted that the quality of evidence was poor and that more data is needed that stratifies results by BMI levels instead of weight.

Even if efficacy were to be slightly decreased in heavy women, experts point out that the success rate is still quite good, and that most women of size will not become pregnant on the Pill. However, data is extremely limited for those with very high BMIs. 

For those who absolutely don't want to (or absolutely should not) conceive while on the Pill, a back-up method is probably a good idea, especially for women with the highest BMIs, since we have little data about efficacy in this group.

Increased Risks in Obese Women?

Another vital question is whether the risk of complications associated with the Pill is greater in women of size. Some resources state outright that the risk of complications is greater in obese women. Others state that "severe obesity" is a contraindication to prescribing the combination Pill at all, and some recommend considering only the mini-pill in obese women.

Since women of size with PCOS already tend to have an increased risk for cardiovascular issues, insulin resistance, diabetes, and blood clots, it is only logical to ask whether oral contraceptives will further increase these risks.

At this point, there is limited data on this question, but what data we have does suggest an additional risk for some complications.

Glucose Intolerance

As noted in Part One of this series, the question of whether the Pill increases a woman's risk for developing diabetes is difficult to answer.

Some studies have found an increase in insulin resistance/decrease in insulin sensitivity in women on oral contraceptives, while other studies have not. Some have found an increased rate of pre-diabetes or a marginal increase in glucose levels, while others have found lower blood glucose levels or no increase in diabetes cases.

A recent Cochrane review found "no major differences in carbohydrate metabolism between different hormonal contraceptives in women without diabetes." However, the authors noted, "We still know very little about [oral contraceptive use in] women at risk for metabolic problems due to being overweight. More than half of the trials had weight restrictions as inclusion criteria."

So while oral contraceptives do not seem to worsen carbohydrate metabolism in average-sized women without diabetes, we are still not clear on their effect in obese women, let alone obese women with PCOS.

A great deal probably depends on which oral contraceptive is being used; high-dose combination pills (30 mcg+ of ethinyl estradiol) seem to have a more negative effect on insulin sensitivity. Low-dose pills seem to have less effect. Mini-pills (progestin only) seem to have a modest effect.

If there is a metabolic effect in most women, it probably is a very mild one, especially with low-dose combination pills. However, if you are borderline already, some types of oral contraceptives may increase your susceptibility to diabetes or glucose intolerance.

As a result, some women who feel particularly at risk for diabetes or insulin resistance due to family history or other considerations choose to avoid oral contraceptives completely.

For others, care providers prescribe a combination of low-dose combination oral contraceptives and metformin (to help counteract any increase in insulin resistance from the oral contraceptives) for women who they feel are particularly at risk for diabetes and metabolic syndrome.

Blood Clots

Obese people are already at increased risk for blood clots, even before adding oral contraceptives or PCOS into the mix. A higher waist circumference seems to be particularly related to the risk for blood clots.

A Cochrane review found that oral contraceptives are clearly associated with an increased risk for blood clots. Low-dose combination pills and type of progestins used may mitigate this risk somewhat, but even with low-dose combination pills and lower-risk progestins, oral contraceptives are still clearly a risk factor for blood clots.

So an important question is whether obesity plus oral contraceptives increases the risk for blood clots even more, and if so, whether that increased risk is outweighed by the potential benefits.

Unfortunately, there does seem to be an increased risk for blood clots in obese women who are on birth control pills. 

One study found ten times the risk for blood clots in overweight/obese women who were on oral contraceptives. Another study found twenty-four times the risk for blood clots in obese women on oral contraceptives (compared to average-sized women not on oral contraceptives).

Again, remember that the absolute numerical risk is not large, but it is increased.

As a result, some medical organizations discourage providers from recommending combined oral contraceptives to women with a BMI over 35. Some recommend the mini-pill (progestin-only pill) instead because it does not increase the risk for blood clots.

On the other hand, some reviews suggest that oral contraceptives are reasonably safe in "carefully screened obese women without known risk factors for cardiovascular disease" and say they can be used as long as a few restrictions are observed. These restrictions usually include smoking, personal or family history of blood clotting disorders, uncontrolled hypertension, and sometimes age over 35.

So bottom line, oral contraceptives do increase the risk for blood clots in obese women, but many providers feel the risk is still within reasonable levels in obese women who do not have additional risk factors and who are prescribed low-dose combination pills. 

Whether PCOS should be considered an additional high-risk contraindication is not clear. Some providers feel it is and recommend against use of combined oral contraceptives in women with PCOS, yet combined pills are prescribed all the time for this group for their anti-androgenic effects.

Cardiovascular Disease, Stroke, and Mortality

Because oral contraceptives increase the risk for blood clots fairly consistently, many researchers have speculated that there would therefore be an increase in risk for heart attacks, strokes, and deaths in users.

However, data on this is inconsistent due to differences in pill formulations (how much estrogen and what type of progestin is used), the general low-risk health status of most pill users studied (young women), and differences in risk factors in populations studied.

The risk for arterial clots (heart attacks or strokes) probably is somewhat increased in oral contraceptive users, but the risk may differ between groups. For example, one review noted a small increase in the risk of stroke, but this risk lay particularly in smokers, women with high blood pressure, those with a history of migraines, and possibly in women over 35.

Although cardiovascular risks may be increased, the absolute numerical risk is low and not all research has found an increase in risk. The risk seems to be lower in those taking low-dose combination pills than higher-dose pills and the type of progestin may affect risk also. For example, those using oral contraceptives using desogestrel, gestodene and especially cyproterone acetate and drospirenone seem to be at higher risk for blood clots.

But that's not the end of the story; risks also have to be balanced with benefits. 

Some data shows that while the risk for blood clot-related disease is increased among oral contraceptive users, the risk for ovarian and endometrial cancers is simultaneously decreased. Therefore, when risks for blood clots and cancers are considered together, some researchers have concluded that the risk for death from oral contraceptive use is probably not increased and may even be slightly decreased.

How this cardiovascular and mortality data from the general population translates into risk for obese women is unclear. One study found that in obese women, the risk for mortality in oral contraceptive ever-users was slightly increased but the effect was quite modest.

Obviously, we need more data with cardiovascular risks and cancer risks delineated by body mass index and type of oral contraceptive. 

Little Data on the Highest BMIs

Sadly, the vast majority of the research on the long-term safety of oral contraceptive use has been done on women of average size or those with only moderately higher weights. How do we know how this translates into safety for women with higher BMIs? Care providers mostly just extrapolate the data and assume it is also relatively safe for very high BMI women.

One review of the oral contraceptives and obesity confirmed that there is little data available on oral contraceptive safety in "morbidly obese" women; what little data we have usually covers women of only moderate obesity, about 130% of "ideal weight" or below. In fact, in many studies of oral contraceptives, very obese women were deliberately excluded from study populations.

Yet "morbidly obese" and "super obese" women are put on oral contraceptives all the time. This is a tremendous concern.

It is absolutely appalling that substantial research into the efficacy and risks of oral contraceptives in women with very high BMIs has not been done before now.

It is long past time for deeper research into this topic. Women of size cannot adequately consider the pros and cons of oral contraceptives for themselves until more complete information on efficacy and risks is available.

Care providers are playing Russian Roulette with our health when they prescribe these contraceptives for high BMI women without having adequate safety data.

What Care Providers Do

Despite the lack of good research, most care providers do prescribe oral contraceptives for their obese patients, even their super obese patients (BMI over 50). They reason that the risks associated with unplanned pregnancy are far greater than the possible risks that might be associated with birth control pills, which is a valid point.

However, this only compares oral contraceptives with NO contraceptive use. Other contraceptive options exist that present far less risk than oral contraceptives, including barrier methods, fertility awareness, and intrauterine contraception. If an oral contraceptive is desired, the progestin-only mini-pill also provides good protection against pregnancy while also providing no increased blood clot risks than combined pills. But while these other contraception options may present less clotting risk, they come with the possible trade-off of a slightly lower success rate.

Therefore, obese women who want or need the best possible success rate or who want to decrease PCOS symptoms like irregular periods and hirsutism may feel that combined oral contraceptives are worth the risk.
But finding the right combined pill for women of size often involves a trade-off of risks. Low-dose pills may have an increased chance of unintended pregnancy but a lower chance of blood clots. High-dose pills are more effective against pregnancy but have a higher risk for clots.

In addition, certain types of progestins (levonorgestrel, for example) tend to increase androgenic side effects, something a woman with PCOS wants to avoid. The combined pills with the most effective anti-androgenic progestins (drospirenone and cyproterone acetate, for example) tend to have much higher risks for blood clots.

This means that it is difficult to know the best combined oral contraceptive for women of size, especially those with the highest BMIs and those who have PCOS. A lot will depend on the priority of the provider and the patient.

Here is a summary of common practices, depending on the top priority for the prescription. Obviously, choices will vary from provider to provider.

Preventing Pregnancy

If the top priority is preventing pregnancy, some providers prescribe a pill with a higher estrogen content for their high-BMI patients because these have better efficacy.

A few providers promote continuous low-dose oral contraceptives instead (with no break to allow for a period) in order to maintain hormone levels high enough and sustained enough for best efficacy.

Many providers (especially in Europe) prefer not to prescribe high-dose combination pills at all because of the risk for blood clots and potential impact on carbohydrate metabolism. Instead, they may choose a progestin-only Mini-Pill for obese patients, especially those with a history of blood clot disease, high blood pressure, or high triglycerides. However, the trade-off is that the Mini-Pill has decreased efficacy compared to combination pills and does not lessen PCOS symptoms like hirsutism or acne.

Another option is to prescribe low-dose combination pills or Mini-Pills but ask the woman to use a back-up birth control method (barriers) to lessen the risk for pregnancy. Back-up contraception might be a particularly important suggestion for those PCOS women on anti-androgenic medications that strongly increase the risk for birth defects, or for those who absolutely do not want to get pregnant.

Alternatively, some providers strongly promote the use of hormonal intrauterine contraception as a highly-effective alternative to oral contraceptives. These are very effective at preventing pregnancy, help relieve endometrial overgrowth, and do not increase the risk for blood clots.

Preventing Clots

If the main priority is to use oral contraceptives for birth control or PCOS symptoms but minimize the risk for clots, then low-dose combination pills are the usual choice. Although the risk for blood clots is still raised with low-dose pills, they are far safer than high-dose pills.

The type of progestin used in the pill is also important; later progestins (like drospirenone and also cyproterone acetate) tend to strongly increase the risk for blood clots compared to second-generation progestins like levonorgestrel.

To counteract possible clotting risks of third- and fourth-generation combination pills, some women may be advised to take a low-dose aspirin. This is not routine advice, however, since taking low-dose aspirin can increase the risk for internal bleeding.

For obese women with a personal or family history of blood clots, uncontrolled hypertension, or other strong risk factors for clots, the mini-pill is usually chosen because it does not increase the risk for clots. The trade-off is slightly lower efficacy, so a back-up birth control may be suggested for some. Another option is a hormone-releasing intrauterine device, which provides very effective birth control without an increase in blood clots.

Preventing Glucose Intolerance

For obese women at extra strong risk for developing diabetes, care providers will often prescribe a low-dose combination pill with the addition of metformin in order to counteract any possible decrease in insulin sensitivity or glucose tolerance. In addition, some are beginning to prescribe low-dose combination pills with inositols.

PCOS Symptoms

A more detailed discussion on the typical use of oral contraceptives for treatment of menstrual regularity and androgenic PCOS symptoms will occur in the next post in this series.

In summary, many care providers prescribe low-dose combination oral contraceptives for women with PCOS, but which pill is a matter of significant controversy (and even whether any oral contraceptive should be used at all).

Some prescribe combo pills with third- and fourth-generation progestins (which tend to be the most anti-androgenic), but this does increase the risk for blood clots considerably. As a result, many care providers prescribe these pills in conjunction with low-dose aspirin. Others prescribe them in conjunction with metformin or inositols to lower insulin resistance and the risk for glucose intolerance.

Because of the substantial risk for blood clots, however, some care providers skip the third- and fourth-generation pills and stick with second-generation combined pills with levonorgestrel. This still offers the benefits of menstrual regularity and prevention of endometrial overgrowth, but it may increase androgenic side effects.

Others choose progestin-only Mini-Pills to regulate menstrual cycles without increasing blood clot risk, especially in PCOS women at highest risk for cardiovascular issues. Hormone-releasing intrauterine contraception may also help treat endometrial overgrowth without increasing clot risk.

The bottom line in PCOS is that there is no one "ideal" oral contraceptive. Every option is a trade-off of benefits and risks. Choice for any one woman must be made on the basis of individual history, risk factors, and treatment goals.

Summary

Obviously, consensus is limited on the best use of oral contraceptives in women of size, especially women of size who also have other considerations like PCOS, a very high BMI, a family history of blood clots, or other co-morbidities.

It is important to be as educated as possible about the pros and cons of various types of oral contraceptives, and to be as up-front as possible with your provider about your co-morbidities and your treatment priorities.

You may get completely different advice from different providers. That's why it's important to get second opinions and also to do your own research on the pros and cons of each choice.

Conclusion

The use of oral contraceptives in obese women has some special concerns.

One of the most thorough reviews of obesity and oral contraceptives made several key points (my emphasis):
  • Effectiveness of oral contraception (combined and/or progestin only) may be impaired in overweight and obese women
  • Healthy obese women using combined hormonal contraception...moderately increase their risk of VTE [venous thromboembolism, or blood clot] as compared to nonobese combined hormonal contraceptive users, but this is not a contraindication to use as it is still less than the risk of VTE associated with pregnancy
  • [Little] safety information exists regarding the use of any type of contraceptive method in women with a BMI ≥40 mg/kg2, but this is not an absolute contraindication to use
In addition, the review concluded with this point:
Previous contraceptive studies have deliberately excluded obese women. This practice is no longer conscionable, as obese individuals make up a significant portion of our population. Future contraceptive studies, in particular efficacy studies, must be a better reflection of our current population
The efficacy and safety of oral contraceptives for women of size ─ especially very high BMI women ─ remains an CRITICAL topic for future research.

However, most providers will still prescribe oral contraceptives to obese women, even those with very high BMIs, because:
  • the risks of blood clots in pregnancy far outweigh the risks of blood clots due to oral contraceptive use
  • the combined oral contraceptive pill provides one of the highest success rates for pregnancy prevention 
  • oral contraceptives can help regulate cycles and minimize PCOS symptoms for those with this condition
For obese women simply looking for birth control, barrier methods and fertility awareness (in those with regular cycles) are much less risky than combined oral contraceptives. For those who want the very highest success rates but without the blood clot risks, a hormonal intra-uterine contraceptive can be considered.

Some major medical organizations recommend that obese women consider a progestin-only oral contraceptive instead of a combination pill in order to minimize blood clot risk. Mini-Pills have good success rates but are not quite as successful as combined pills.

For those women of size who want combination oral contraceptives, low-dose formulations probably present the lowest risk for blood clots, but perhaps at the expense of a minor degree of efficacy.

Those with PCOS will want to consider brand formulations very carefully as some combination pills are very androgenic and others have a potent anti-androgenic effect. Typically, women with PCOS tend to be prescribed an anti-androgenic low-dose combination pill concurrently with metformin in order to minimize the risk for glucose intolerance and lessen insulin resistance. Other options include oral contraceptives with inositol, or oral contraceptives with low-dose aspirin.

Whatever your choice, consult your care provider carefully about the best contraception and PCOS treatment options for your personal situation and needs. Be sure to provide as complete a medical history as you can and educate yourself beforehand about your choices.


References

References About PCOS
General Information about The Pill
Information about Different Types of The Pill
    Information about The Pill and Obesity
    Efficacy of The Pill in Obese Women

    J Am Assoc Nurse Pract. 2013 May;25(5):223-33. doi: 10.1111/1745-7599.12011. Epub 2013 Feb 27. Contraception and the obese woman. Reifsnider E1, Mendias N, Davila Y, Bever Babendure J. PMID: 24170564
    ...CONCLUSIONS: The evidence is largely supportive of combined oral contraceptive (COC) use in carefully screened obese women without known risk factors for cardiovascular disease. The efficacy of COCs may be slightly reduced in obese women because of increased body mass. Other types of hormonal contraceptives have varying safety and efficacy reports when used by obese women. Intrauterine devices do not have reduced efficacy nor increased risks for obese women but insertion may be more difficult. Obesity has no effect on efficacy of barrier methods of contraception.
    Obstetrics and Gynecology. January 2005, Vol. 105, No. 1, pp. 46–52.  Body Mass Index, Weight, and Oral Contraceptive Failure Risk. Holt, V. L., Scholes, D., Wicklund, K. G., Cushing-Haugen, K. L., and Daling, J. R. PMID: 15625141
    ...Our results suggest that being overweight may increase the risk of becoming pregnant while using OCs. If causal, this association translates to an additional 2-4 pregnancies per 100 woman-years of use among overweight women, for whom consideration of additional or effective alternative contraceptive methods may be warranted.
    Ann Epidemiol. 2006 Aug;16(8):637-43. Epub 2006 Mar 3. Body mass index and risk for oral contraceptive failure: a case-cohort study in South Carolina. Brunner Huber LR, et al. PMID: 16516489
    ...In this heterogeneous population, we found a suggestion that overweight and obese women may be at increased risk for OC failure. However, long-term prospective studies are needed to study this association in diverse populations.
    Contraception. 2009 Jun;79(6):424-7. Epub 2009 Mar 4. Association between efficacy and body weight or body mass index for two low-dose oral contraceptives. Burkman RT, et al.  PMID: 19442776
    ...This analysis investigated the association of oral contraceptive efficacy with body weight and body mass index (BMI) for hypothesis-generating purposes... CONCLUSION:Women in the higher body weight or BMI category showed a small increase in the risk of pregnancy with these oral contraceptives, but this increase was not statistically significant overall or for either formulation studied.
    Obstet Gynecol. 2013 Mar;121(3):585-92. doi: 10.1097/AOG.0b013e31828317cc. Contraceptive failures in overweight and obese combined hormonal contraceptive users. McNicholas C, Zhao Q, Secura G, Allsworth JE, Madden T, Peipert JF. PMID: 23635622
    METHODS: Females enrolled in a large contraceptive study offering the reversible method of their choice at no cost were followed-up for 2-3 years. We compared the failure rates (pregnancy) among users of the OCP, transdermal patch, and contraceptive vaginal ring stratified by BMI. RESULTS: Among the 7,486 participants available for this analysis, 1,523 chose OCPs, patch, or ring at enrollment. Of the 334 unintended pregnancies, 128 were found to be a result of OCP, patch, or ring failure. Three-year failure rates were not different across BMI categories (BMI less than 25 8.44%, 95% confidence interval [CI] 6.1-11.5; BMI 25-30 11.03%, 95% CI 7.5-16.0; BMI more than 30 8.92%, 95% confidence interval 7.6-11.5). Increasing parity (hazard ratio [HR] 3.06, CI 1.31-7.18) and history of a previous unintended pregnancy (HR 2.82, CI 1.63-4.87), but not BMI, were significant risk factors for unintended pregnancy. CONCLUSION: Overweight and obese females do not appear to be at increased risk for contraceptive failure when using the OCP, patch, or vaginal ring.
    Cochrane Database Syst Rev. 2013 Apr 30;4:CD008452. doi: 10.1002/14651858.CD008452.pub3. Hormonal contraceptives for contraception in overweight or obese women. Lopez LM, Grimes DA, Chen M, Otterness C, Westhoff C, Edelman A, Helmerhorst FM. PMID: 23633356
    MAIN RESULTS: We found nine reports with data from 13 trials that included a total of 49,712 women. Five reports from 2002 to 2012 compared BMI groups; of those, one reported a higher pregnancy risk for overweight or obese women. In that trial, women assigned to an oral contraceptive containing norethindrone acetate 1.0 mg plus EE 20 µg and having a BMI at least 25 had greater pregnancy risk compared to those with BMI less than 25 (reported RR 2.49; 95% CI 1.01 to 6.13). The comparisons reported in the other four studies were not significantly different for pregnancy. These included studies of a combined oral contraceptive (COC), a transdermal patch, an implant, and an injectable. The COC study showed no trend by BMI or weight... AUTHORS' CONCLUSIONS: The evidence did not generally show an association of BMI with effectiveness of hormonal contraceptives. However, the evidence was limited for any individual contraceptive method. Studies using BMI (rather than weight alone) can provide more information about whether body composition is related to contraceptive effectiveness. The efficacy of subdermal implants and injectable contraceptives may be unaffected by body mass. The contraceptive methods examined here are among the most effective when the recommended regimen is followed.The overall quality of evidence was low for this review. More recent reports provided moderate quality evidence, while the older studies provided evidence of low or very low quality for our purposes. Investigators should consider adjusting for potential confounding related to BMI. Trials should be designed to include sufficient numbers of overweight or obese women to adequately examine effectiveness and side effects of hormonal contraceptives within those groups.
    Risk for Blood Clots in Obese Women Using The Pill

    Thromb Haemost. 2003 Mar;89(3):493-8. Obesity: risk of venous thrombosis and the interaction with coagulation factor levels and oral contraceptive use. Abdollahi M, Cushman M, Rosendaal FR.  PMID: 12624633
    We evaluated the risk of thrombosis due to overweight and obesity using data from a large population based case-control study. Four hundred and fifty-four consecutive patients with a first episode of objectively diagnosed thrombosis from three Anticoagulation Clinics in the Netherlands were enrolled in a case-control study...Obesity (BMI >/=30 kg/m(2)) increased the risk of thrombosis twofold (CI 95: 1.5 to 3.4), adjusted for age and sex...Evaluation of the combined effect of obesity and oral contraceptive pills among women aged 15-45 revealed that oral contraceptives further increased the effect of obesity on the risk of thrombosis, leading to 10-fold increased risk amongst women with a BMI greater than 25 kg/m(2) who used oral contraceptives. Obesity is a risk factor for deep vein thrombosis. Among women with a BMI greater than 25 kg/m(2) the synergistic effect with oral contraceptives should be considered when prescribing these.
    Br J Haematol. 2007 Oct;139(2):289-96. Risk of venous thrombosis: obesity and its joint effect with oral contraceptive use and prothrombotic mutations. Pomp ER, et al.  PMID: 17897305
    In the Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis (MEGA study), body weight, height and body mass index (BMI) were evaluated as risk factors. Additionally, the joint effect of obesity together with oral contraceptive use and prothrombotic mutations on the risk of venous thrombosis were analysed...Obese women who used oral contraceptives had a 24-fold higher thrombotic risk (OR(adj) 23.78, 95% CI 13.35-42.34) than women with a normal BMI who did not use oral contraceptives...Body height, weight and obesity increase the risk of venous thrombosis, especially obesity in women using oral contraceptives.
    Clin Chest Med. 2009 Sep;30(3):489-93, viii. Obesity and thromboembolic disease. Stein PD, Goldman J.  PMID: 19700047
    Various abnormalities of hemostasis have been described in obesity, mainly concerning increased levels of plasminogen activator inhibitor-1, but other abnormalities of coagulation and platelet activation have been reported as well. Circulating microparticles have also been observed in obese patients. These suggest that obesity would be a risk factor for venous thromboembolism (VTE). Analysis of the database of the National Hospital Discharge Survey showed compelling evidence that obesity is, in fact, a risk factor for VTE. Obesity is also a risk factor for recurrent VTE. A synergistic effect of oral contraceptives with obesity has been shown.
    Eur J Contracept Reprod Health Care. 2000 Dec;5(4):265-74. The effects of age, body mass index, smoking and general health on the risk of venous thromboembolism in users of combined oral contraceptives. Nightingale AL, et al.  PMID: 11245554
    The UK MediPlus Database and the General Practice Research Database were searched to identify women with evidence of venous thromboembolism while exposed to combined oral contraceptives...The incidence rate of idiopathic venous thromboembolism among oral contraceptive users was 39.4 per 100,000 exposed woman-years. The age-specific incidence rates were found to rise sharply after the age of 39 years. Factors identified as being significantly associated with idiopathic venous thromboembolism in women using combined oral contraceptives were: body mass index of 25 kg/m2 and over, the association rising dramatically in women with a body mass index of 35 kg/m2 or more; smoking; general ill health; and asthma.

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