Friday, November 21, 2014

Increase in Cesarean Rate in Morbidly Obese Women Over Time

Here's the abstract of an interesting new study. I haven't seen the full text yet but it appears to show that while the cesarean rate has gone up over time in all sizes of women, it's gone up the most in the higher BMI categories.

In other words, a high BMI woman is far more likely to have a cesarean now than she was in 1990.

This shows that the high cesarean rate in obese women is not just about obesity itself, but also how obese women are managed in labor and the lowering of the surgical threshold for performing cesareans in high BMI women.

I've been saying this for years. Some care providers like to pretend that the high cesarean rate in obese women is only about the woman's fatness, as if this somehow prevents a fat woman from giving birth vaginally (the classic "fat vagina" theory).

But if it was really only about physical barriers, then you would see a relatively consistent cesarean rate in this group over time, and you DON'T. This study shows that there used to be much lower cesarean rates in women of size than there is today, and older studies show that the cesarean rate wasn't always higher in obese women than in average-sized women.

Critics would point out that the cesarean rate has increased in all groups over time, not just in obese women. Sad, but true.

But the cesarean rate has not increased equally in every group, as this study points out. Look at their comparison of cesarean rates between 1990 and 2012 by BMI group*:

                              1990                     2012                   Increase

Underweight         14.4%                   27.9%                  13.5%
Normal                  16.1%                   31.4%                  15.3%
Overweight           19.5%                   38.8%                  19.3%
Obese I                 22.3%                   45.1%                  22.8%
Obese II                25.0%                   50.2%                  25.2%
Obese III               26.9%                   55.2%                  28.3%

The increase in cesarean rates was not uniform across BMI categories. The increase in "normal" weight women was 15.3%, but the increase in Obese Class III women was nearly twice that at 28.3%.

In 1990, Obese class III women had a 26.9% cesarean rate in 1990....just over 1 in 4.

In 2012, Obese Class III women  had a 55.2% cesarean rate instead, or more than 1 in every 2 "morbidly obese" women.

In just 22 years, the cesarean rate in Class III Obese women went from 26.0% to 55.2%. How far will it go in the next 20 years?

Something has changed...and that something is probably how those women are managed in labor (more interventions), the exaggeration of fear around their pregnancies, and the resulting lowering of the surgical threshold for a cesarean in that group.

Similarly, research shows that cesarean rates in the same BMI group can vary dramatically between locations. For example, recent studies from Tennessee and Kentucky show an abysmal cesarean rate of nearly 60% in "morbidly obese" women. One particularly appalling study from Michigan shows a cesarean rate of over 80% in women with a BMI over 50.

Yet a large study from the U.K. shows a cesarean rate of about 30% in the same population.

This shows that practice variation is an issue not only in the overall population, but perhaps particularly in high BMI women.

It's time for care providers to examine not only how to prevent questionable cesareans in women across the board, but also to focus on how to prevent questionable cesareans in high-BMI women. Given that cesareans carry more risks in women of size, especially multiple repeat cesareans, it's inexcusable to be exposing so many of these women to these risks unnecessarily.

The cesarean rate is high is women of size, but the variation in rates over time and between locations shows it doesn't have to be, and that there are things we could be doing to bring the cesarean rate down in this group.

It's long past time to be looking into that question. Some researchers are starting to ask these questions or propose solutions, but few have actually tested these theories.

Where are the researchers and providers willing to actually study how to lower the cesarean rate in women of size?


References

J Perinat Med. 2014 Jun 10. pii: /j/jpme.ahead-of-print/jpm-2014-0126/jpm-2014-0126.xml. doi: 10.1515/jpm-2014-0126. [Epub ahead of print] Impact of maternal body mass index on the cesarean delivery rate in Germany from 1990 to 2012. Kyvernitakis I, Köhler C, Schmidt S, Misselwitz B, Großmann J, Hadji P, Kalder M. PMID: 24914711
ABSTRACT AIMS: Maternal obesity is a risk factor for cesarean delivery (CD). The aim of this analysis was to determine the association between early-pregnancy body mass index (BMI) and the rate of CD over the past two decades. METHODS: We retrospectively analyzed data from the perinatal quality registry of singleton deliveries in the state of Hesse in Germany from 1990 to 2012. We divided the patients into groups according to the WHO criteria for BMI: underweight (<18.5), normal weight (18.5-<25), overweight (25-<30), obese class I (30-<35), obese class II (35-<40), and obese class III (≥40). RESULTS: The analysis included 1,092,311 patients with available data regarding maternal BMI and mode of delivery. The CD rates for underweight (<18.5), normal weight (18.5-<25), overweight (25-<30), obese class I (30-<35), obese class II (35-<40), and obese class III (≥40) women increased from 14.4%, 16.1%, 19.5%, 22.3%, 25%, and 26.9% in the year 1990 to 27.9%, 31.4%, 38.8%, 45.1%, 50.2%, and 55.2% in the year 2012, respectively (P<0.001). CONCLUSION: Maternal BMI in early pregnancy is linearly associated with the incidence of CD. We found a disproportionate increase of CD in morbidly obese women compared with the CD incidence in the reference BMI population over the past two decades.

* Standard BMI classifications: 

  • "Underweight" = BMI less than 18
  • "Normal" weight = BMI 18-24.9
  • "Overweight" = BMI 25-29.9
  • Class I Obese = BMI 30-34.9
  • Class II Obese = BMI 35-39.9
  • Class III Obese = BMI of 40 plus
  • "Super Obese" = BMI of 50 plus

Thursday, November 13, 2014

See my Practice Variation Post at Science and Sensibility

My recent post on Practice Variation in Cesarean Rates went a bit viral. (Thank you to those of you who shared it on Facebook!)

The blog, Science and Sensibility (Lamaze International’s “Research Blog About Healthy Pregnancy, Birth & Beyond”), picked it up and asked to run it since it's very topical right now, what with the recent important study on Practice Variation.

I revised my very-quick original post and expanded on a few points, added some new research, reformatted it a bit, and generally prettified it up. (I spent all my time on that, so no new post here till next week.)

In the meantime, the revised post is now up on Science and Sensibility. You can go and read it here.

Sunday, November 2, 2014

Practice Variation in Cesarean Rates: Not Due to Maternal Complications

Photo courtesy "Angela"
There's a new study out that discusses the variation in cesarean rates between hospitals in the United States.

Practice variation is a serious problem in obstetrics. Women are often far more at risk for a cesarean in certain hospitals than in others, even when the hospitals serve the same geographical area and population.

Of course, care providers protest that some hospitals have higher cesarean rates because they serve higher-risk patients. This is a valid point, but it still doesn't explain the wide variation in rates between many hospitals.

For example, in the study above, the mother's risk status and diagnoses did not explain the variation in cesarean rates between hospitals:
We found that the variability in hospital cesarean rates was not driven by differences in maternal diagnoses or pregnancy complexity,” said [lead study author] Kozhimannil. “This means there was significantly higher variation in hospital rates than would be expected based on women’s health conditions. On average, the likelihood of cesarean delivery for an individual woman varied between 19 and 48 percent across hospitals.”
There were several key points highlighted in the article about the study, including:
  • Among lower risk women, likelihood of cesarean delivery varied between 8 and 32 percent across hospitals.
  • Among higher risk women, likelihood of cesarean delivery varied between 56 and 92 percent across hospitals.
  • Hospital variability did not decrease after adjusting for patient diagnoses, socio-demographics, and hospital characteristics.
This shows that practice variation in cesarean rates is real, substantive, and not just a reflection of the mother's risk level. 

Perhaps now we can stop playing the mother blame-game when we talk about cesarean rates?

This study is not the first to show that the culture of a hospital, their policies, and their routine practices all help determine how likely a woman is to "need" a cesarean in that hospital.

This is important because while cesareans can be life-saving at times, they present more risk for infection, bleeding, pain, neonatal breathing problems, and complications in future pregnancies. It matters where and with whom a woman gives birth.

But many women naively choose their care provider for pregnancy based mostly on convenience and location, not realizing that their chances of surgical birth may vary greatly depending on which hospital and caregiver they use

One leading consumer education site points out, "Research suggests that the same woman might have a c-section at one hospital but a vaginal birth if she gave birth at another, just because of the different policies and practices of those hospitals. One of the most effective ways to lower your chance of having a c-section is to have your baby in a setting with a low c-section rate."

Yet it is not always easy to find out the cesarean rates* of local hospitals in some states, and many hospitals remain largely unaccountable for sky-high cesarean rates, although we are beginning to see marginal progress in some places towards accountability. But even when a cesarean is truly necessary, there can be large discrepancies in complications afterwards between hospitals. How is a woman to know which hospital to choose?

Bottom line, more transparency and accountability are needed. As the lead author of the study states: 
Women deserve evidence-based, consistent, high-quality maternity care, regardless of the hospital where they give birth...and these results indicate that we have a long way to go toward reaching this goal in the U.S.

**An additional suggestion: Researchers should start examining cesarean practice variations in obese patients too. Research strongly suggests there are major practice variations in cesarean utilization for "obese" mothers between hospitals, yet this is a topic that is rarely broached in research. More exploration of this dichotomy might help reduce the cesarean rate in this group.

***Post received minor reference and picture edits on 11/6/14.

References

*See www.cesareanrates.com for hospital level cesarean rates in most U.S. states. Consumer Reports also has a recent article with some hospital-level c-section rates in the U.S.

PLoS Med. 2014 Oct 21;11(10):e1001745. doi: 10.1371/journal.pmed.1001745. eCollection 2014. Maternal Clinical Diagnoses and Hospital Variation in the Risk of Cesarean Delivery: Analyses of a National US Hospital Discharge Database. Kozhimannil KB1, Arcaya MC2, Subramanian SV2. PMID: 25333943
BACKGROUND: Cesarean delivery is the most common inpatient surgery in the United States, where 1.3 million cesarean sections occur annually, and rates vary widely by hospital. Identifying sources of variation in cesarean use is crucial to improving the consistency and quality of obstetric care. We used hospital discharge records to examine the extent to which variability in the likelihood of cesarean section across US hospitals was attributable to individual women's clinical diagnoses. METHODS AND FINDINGS: Using data from the 2009 and 2010 Nationwide Inpatient Sample from the Healthcare Cost and Utilization Project-a 20% sample of US hospitals-we analyzed data for 1,475,457 births in 1,373 hospitals. We fitted multilevel logistic regression models (patients nested in hospitals). The outcome was cesarean (versus vaginal) delivery. Covariates included diagnosis of diabetes in pregnancy, hypertension in pregnancy, hemorrhage during pregnancy or placental complications, fetal distress, and fetal disproportion or obstructed labor; maternal age, race/ethnicity, and insurance status; and hospital size and location/teaching status. The cesarean section prevalence was 22.0% (95% confidence interval 22.0% to 22.1%) among women with no prior cesareans. In unadjusted models, the between-hospital variation in the individual risk of primary cesarean section was 0.14 (95% credible interval 0.12 to 0.15). The difference in the probability of having a cesarean delivery between hospitals was 25 percentage points. Hospital variability did not decrease after adjusting for patient diagnoses, socio-demographics, and hospital characteristics (0.16 [95% credible interval 0.14 to 0.18]). A limitation is that these data, while nationally representative, did not contain information on parity or gestational age. CONCLUSIONS: Variability across hospitals in the individual risk of cesarean section is not decreased by accounting for differences in maternal diagnoses. These findings highlight the need for more comprehensive or linked data including parity and gestational age as well as examination of other factors-such as hospital policies, practices, and culture-in determining cesarean section use.
Am J Obstet Gynecol. 2007 Jun;196(6):526.e1-5. Variation in the rates of operative delivery in the United States. Clark SL1, Belfort MA, Hankins GD, Meyers JA, Houser FM. PMID: 17547880
OBJECTIVES: This study was undertaken to examine the national and regional rates of operative delivery among almost one quarter million births in a single year in the nation's largest healthcare delivery system, using variation as an arbiter of the quality of decision making. STUDY DESIGN: We compared the variation in rates of primary cesarean and operative vaginal delivery in facilities of the Hospital Corporation of America during the year 2004. RESULTS: In 124 facilities representing almost 220,000 births during a 1-year period, the primary cesarean and operative vaginal delivery rates were 19% +/- 5% (range 9-37) and 7% +/- 4% (range 1-23). Within individual geographic regions, we consistently found variations of 200-300% in rates of primary cesarean delivery and variations approximating an order of magnitude for operative vaginal delivery. CONCLUSION: Within broad upper and lower limits, rates of operative delivery in the United States are highly variable and suggest a pattern of almost random decision making. This reflects a lack of sufficient reliable, outcomes-based data to guide clinical decision making.
Neonatology. 2014 Oct 4;107(1):8-13. [Epub ahead of print] Women Are Designed to Deliver Vaginally and Not by Cesarean Section: An Obstetrician's View. Visser GH. PMID: 25301178
Worldwide, there is a rapid increase in deliveries by cesarean section. The large differences among countries, from about 16% to more than 60%, suggest that the cesarean delivery (CD) rate has little to do with evidence-based medicine. In this review, the background for the increasing CD rate is discussed as well as the limited positive effects on neonatal outcome in both term and preterm neonates. Negative effects of CD, including direct maternal morbidity, complications of subsequent pregnancies and iatrogenic early delivery resulting in increased neonatal morbidity, are discussed in addition to long-term implications for the offspring involving altered development of the immune system. The 'battle' to lower the CD rate will be difficult, but we should not forget that women are designed to deliver vaginally and not by cesarean section. 

Tuesday, October 21, 2014

A Weight-Inclusive Approach to Health


J Obes. 2014;2014:983495. doi: 10.1155/2014/983495. Epub 2014 Jul 23. The weight-inclusive versus weight-normative approach to health: evaluating the evidence for prioritizing well-being over weight loss. Tylka TL1, Annunziato RA2, Burgard D3, Daníelsdóttir S4, Shuman E5, Davis C2, Calogero RM6. PMID: 25147734 Free full text available here.
Using an ethical lens, this review evaluates two methods of working within patient care and public health: the weight-normative approach (emphasis on weight and weight loss when defining health and well-being) and the weight-inclusive approach (emphasis on viewing health and well-being as multifaceted while directing efforts toward improving health access and reducing weight stigma). 
Data reveal that the weight-normative approach is not effective for most people because of high rates of weight regain and cycling from weight loss interventions, which are linked to adverse health and well-being. Its predominant focus on weight may also foster stigma in health care and society, and data show that weight stigma is also linked to adverse health and well-being. 
In contrast, data support a weight-inclusive approach, which is included in models such as Health at Every Size for improving physical (e.g., blood pressure), behavioral (e.g., binge eating), and psychological (e.g., depression) indices, as well as acceptability of public health messages. 
Therefore, the weight-inclusive approach upholds nonmaleficience and beneficience, whereas the weight-normative approach does not. We offer a theoretical framework that organizes the research included in this review and discuss how it can guide research efforts and help health professionals intervene with their patients and community.

Wednesday, October 15, 2014

PCOS and Birth Control Pills, Part 3: Use for PCOS


In honor of the recent 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 and acne.

Part One was background about how oral contraceptives work, the different types available, and side effects to be aware of. Part Two looked at whether there were special considerations for oral contraceptive use in women of size.

Today, we discuss more about the use of oral contraceptives for treating symptoms of PCOS.
Disclaimer: I am not a medical health-care professional. Always do your own research. This information is not a complete explanation of all the risks and benefits of a particular medication, nor is it medical advice about a health condition or treatment. Consult your healthcare provider before making any decisions about your care.
Advantages of The Pill for PCOS

Among care providers trained in the traditional medical model, the use of oral contraceptives is considered standard of care for women with PCOS who are not actively trying to conceive.

In their view, the many potential benefits outweigh any potential risks. It is considered a standard-of-care first-line therapy for PCOS women who are not trying to conceive.

From this point of view its biggest benefit is that it regulates the cycle, preventing the missed periods so common to many women with PCOS. In this way, it is thought to strongly reduce the risk for the endometrial cancer, which is increased in women with PCOS. But while some short-term and long-term evidence is promising on its effectiveness against endometrial cancer, high-quality long-term evidence is still somewhat lacking. We need more long-term studies to be sure it truly lowers the risk for endometrial cancer.

The risk for ovarian cancer may also be increased in women with PCOS, and oral contraceptives clearly lower the risk for ovarian cancer, so that is a solid advantage to using oral contraceptives.

In addition, oral contraceptives tend to decrease Luteinizing Hormone (LH) levels and this leads to a subsequent decrease in androgen production. Oral contraceptives also increase Sex Hormone Binding Globulin (SHBG) production, decreasing free testosterone levels.

Because the Pill tends to lower androgen levels, it often lessens acne, hirsutism, and other skin-related symptoms common to PCOS. To many women with PCOS, this is a very important benefit.

Oral contraceptives also inhibit development of egg follicles. Fewer follicles may lessen the severity of polycystic ovaries, and therefore lower additional production of androgens.

Research shows that oral contraceptives can greatly improve menstrual regularity in women with PCOS, and that certain types can also lessen androgens and distressing symptoms of PCOS like hirsutism and acne.

In this way, the use of oral contraceptives in PCOS has significant benefits.

Risks of the Pill for PCOS

As we have discussed more extensively in Part One and Part Two of this series, oral contraceptives are associated with several risks that are particularly pertinent for women with PCOS. These include:
  • a possibly increased risk for insulin resistance/glucose intolerance
  • a definitely increased risk for blood clots
  • an unknown risk for cardiovascular disease and mortality
Therefore, the choice about using oral contraceptives has to consider the balance of benefits vs. risks, which may be unique to each woman.

Glucose Tolerance

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 fasting glucose, while others have found lower blood glucose levels or no increase in diabetes cases.

Since there are so many formulations, a lot depends on the type of oral contraceptive 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 or even possibly beneficial effects.

Most studies focus on non-diabetic women of average BMI in the general population; less is known about its effect in obese women, let alone obese women with PCOS. But one recent review concluded that while there were mild fluctuations in glucose and insulin levels in a few studies, overall there was "no significant effect" of oral contraceptives on carbohydrate metabolism in women with PCOS.

If there is an effect in women with PCOS, it probably is a very modest one, especially with low-dose combination pills. However, for very high-BMI women, those with severe insulin resistance, or those who are borderline diabetic already, it's possible that some types of oral contraceptives may somewhat increase the susceptibility to diabetes or glucose intolerance.

As a result, some care providers prescribe a combination of certain oral contraceptives (for their anti-androgenic effects) plus metformin or inositol (to help counteract any increase in insulin resistance from the oral contraceptives) for women with PCOS who are particularly at risk for diabetes and metabolic syndrome. This combination of oral contraceptives and an insulin sensitizing medication seems particularly effective for some women with PCOS.

Blood clots

Oral contraceptives of any dose clearly increase the risk for blood clots in the general population, particularly in the first year of use. The risk is strongest with high-dose pills (50 mcg ethinyl estradiol) and mildest with low-dose pills (20 mcg ethinyl estradiol). Risk also depends on the type of progestin used.

However, what the clot risk is in women with PCOS is less clear. Research shows that women with PCOS tend to have a higher risk for blood clots than the rest of the population; the concern is that use of the Pill in women with PCOS might elevate that risk even further.

And in fact, one study showed that women with PCOS on the Pill had about twice the risk for blood clots as other women on the Pill, and women with PCOS not taking the Pill had about 1.5x the risk for clots.

However, not all studies agree; one large study found oral contraceptives to be mildly protective against blood clots in women with PCOS.

Further muddying the waters is the fact that the progestins with the most potent anti-androgenic properties tend to be the ones associated with the greatest risk for blood clots. The progestins associated with the least risk of clots tend to have strong androgenic side effects.

Therein lies the dilemma for women with PCOS; if you use the oral contraceptive with the most potent anti-androgen effects, there is a considerably higher risk for blood clots. If you opt for the safer oral contraceptives in order to at least regulate your cycles, you will not help and may even worsen any hirsutism and acne.

All women with PCOS who are considering the Pill should discuss the risk for blood clots with their care providers. If you have further risk for clots, such as a first-degree relative who has experienced blood clots or poorly-controlled hypertension, you will need to consider the use of the Pill especially carefully with a care provider. They might suggest you consider other alternatives instead.

Cardiovascular Disease

Most PCOS research does not follow its subjects long-term, so there is a dearth of research on the long-term risks for cardiovascular disease and mortality in women with PCOS.

Because of an increase in blood clots plus risk factors like hypertension, diabetes, and abnormal lipids, most researchers have assumed for years that women with PCOS are at extremely high risk for cardiovascular disease and early death. Women with the hyperandrogenic "classic" PCOS phenotype have been thought to be particularly at risk.

Interestingly, what research we have so far does NOT suggest an increase in cardiovascular and mortality risk for women with PCOS, and only a small increase for non-fatal cerebrovascular disease. One very small study that followed women for 21 years found more hypertension and lipid abnormalities in women with PCOS, but no more heart attacks, strokes, or mortality than the controls from the general population.

Since oral contraceptives tend to worsen lipid profiles, increase the risk for blood clots, and perhaps worsen cardiovascular risks in the short-term, the question is whether oral contraceptive use would worsen cardiovascular risks in women with PCOS. Bottom line, we just don't have much data on this:
Only a few studies assessing the metabolic effects of OCPs in PCOS are available in the literature. The randomized controlled trials are even fewer. Most of the studies had a small number of participants with a limited follow-up period, and several confounding factors that might have influenced the results were not taken into account in these studies...the use of OCPs combined with other treatment modalities such as antiandrogens or insulin sensitizers remain largely unknown. Larger randomized controlled studies are undoubtedly needed to resolve controversies about OCPs....
Several sources have speculated that oral contraceptives may actually be protective against cardiovascular issues in women with PCOS in the long run. One review suggested that the lack of increased cardiovascular disease and mortality seen thus far in PCOS women may actually suggest "unproven preventive alterations" of oral contraceptives because the Pill is such a common treatment in PCOS. However, without specific data on outcomes in PCOS women who are on oral contraceptives vs. those who are not, this is completely speculative at this point.

Of course, even if oral contraceptives did increase the risk for cardiovascular disease, you also have to remember that oral contraceptives probably lower the risk for ovarian cancer and possibly endometrial cancer. So there is a trade-off of risk to consider.

At this point, it is anyone's guess how much risk vs. benefit oral contraceptives have in the long run for women with PCOS.

More long-term data is urgently needed.

Which Pill should be prescribed for PCOS?

There are SO many oral contraceptives to choose from that it is difficult to know which is the best version for women with PCOS.

Oral contraceptives differ by estrogen dose (20 mcg, 25 mcg, 30 mcg, 35 mcg, 50 mcg), by whether medications change throughout the cycle (monophasic, biphasic, triphasic, etc.), and by cycle length (traditional cycle length vs. extended or continuous cycle formulations).

In addition, they differ by type and generation of progestins used (1st generation = norethindrone and ethynodiol acetate pills; 2nd generation = levonorgestrel and norgestrel; 3rd generation = desogestrel, gestodene and norgestimate; 4th generation = drospirenone and dienogest).

In addition, oral contraceptive availability and formulation can differ significantly by country. In the United States alone, one survey found 88 different formulations of oral contraceptives ─ and that doesn't include oral contraceptives using gestodyne and dienogest, which are not currently available in the U.S. Outside the U.S., some countries also have combined oral contraceptives using cyproterone acetate for treating severe acne and hirsutism but not as an oral contraceptive alone.

As noted, some oral contraceptives with the best anti-androgen activity have even greater risks for blood clots, so a delicate balance between anti-androgen benefits and clotting risks must be walked. The interaction between different PCOS phenotypes and a person's personal medical history and risk factors may also influence which oral contraceptive is most appropriate, making the discussion even more complicated.

Therefore, a specific discussion of which oral contraceptive is best for PCOS is far beyond the scope of this blog. No medical advice should be inferred.

Only general considerations will be presented below. Discuss your medical history and treatment goals with your provider to determine the best choice for your situation.

Oral Contraceptives to Treat PCOS Symptoms

As we have seen, oral contraceptives can help lessen some of the most distressing PCOS symptoms, such as acne or excess body and facial hair. They also help regulate the menstrual period, hopefully lowering the risk for endometrial overgrowth and cancer.

However, all oral contraceptives are not alike. Some work better for PCOS than others.

For example, combination oral contraceptives that use progestins like levonorgestrel tend to worsen androgenic symptoms in women with PCOS, so they are often avoided. However, because these pills tend to have the best safety profile, some providers prescribe them anyway to women with PCOS in order to achieve menstrual regulation while incurring the least risk for blood clots. Some care providers feel they are fine for PCOS women with mild androgenic symptoms, but avoid them for women with strong androgenic symptoms.

Some resources report that pills using progestins desogestrel, norgestimate, and gestodene are less androgenic compared with those using levonorgestrel, norethindrone, or norgestrel. At least one source considers oral contraceptives using norgestrel to be "unsuitable" for women with PCOS.

Oral contraceptives with later generations of progestins are often prescribed for women with PCOS, as these tend to be more anti-androgenic. These include dienogest and drospirenone, as well as cyproterone acetate:
Cyproterone acetate is derived from 17-hydroxyprogesterone, whereas dienogest and drospirenone are derivatives of 19-nortestosterone and 17-α-spirolactone, respectively. Cyproterone acetate is the most potent antiandrogenic progestin...Drospirenone was approved by the U.S. Food and Drug Administration (FDA); in 2000, whereas cyproterone acetate and dienogest containing OCPs are not marketed in the United States.
In areas outside the U.S., low-dose combination pills with anti-androgenic progestins like drospirenone and cyproterone acetate are usually favored. Research shows that these pills have greatly helped many women with significant facial hair and acne. One study showed that cyproterone acetate was more effective over the longer-term than drospirenone or desogestrel.

Again, low-dose combination pills with these anti-androgenic progestins also present more risk for blood clots. Therefore, some providers avoid these progestins, preferring other combination pills with more neutral androgen profiles. Others prescribe combined pills with drospirenone or cyproterone acetate but advise taking a low-dose aspirin with them to help counteract the clotting risk.

Some providers favor continuous combined pills in women with severe androgen excess. In this approach, low-dose combined pills are given for 3-6 months, with no placebo pills for withdrawal bleeding. Some research has shown this approach to be quite effective for those with severe hirsutism, and of course has significant benefits to those with endometriosis, iron-deficiency anemia, or debilitating periods. Another advantage is that continuous oral contraceptives tend to have less breakthrough bleeding, which can be an issue with some oral contraceptives. However, some critics question how an unrelenting dose of hormones might affect a woman's long-term health. Short-term safety data seems acceptable, but longer-term studies and research that looks at multiple endpoints (including cardiovascular, breast cancer, and bone health) are urgently needed.

A low-dose combination pill with the addition of metformin or inositol is another option favored by many providers for some in order to counteract the significant insulin resistance common to many with PCOS, while also countering any possible decrease in insulin sensitivity or glucose tolerance due to the Pill. A low-dose aspirin may also be suggested by some providers for anti-clotting purposes, although this must be carefully monitored due to the risk of internal bleeding.

Some providers prefer progestin-only Mini-Pills for very obese women with PCOS, seeing these women as at extremely high risk for blood clots. They reason that Mini-Pills provide contraception, do not increase risk for blood clots, only minimally increase risks for insulin resistance, and regulate the menstrual cycle (thus lessening the risk for endometrial cancer). Since some countries strongly counsel against the prescription of any combined oral contraceptives to women with a BMI over 40, Mini-Pills can be one alternative for these women.

Some researchers have suggested that ALL oral contraceptives be avoided for women with PCOS with significant risk factors like strong insulin resistance, clotting disorders, hypertension, metabolic syndrome, or other cardiovascular risk factors. They have suggested that vaginal contraceptive rings or hormonal intrauterine devices be used instead. These will not help androgen-related symptoms like hirsutism or acne, but will help menstrual regularity and may lessen endometrial cancer risk.

Summary

Obviously, there is not a general consensus on the "best" oral contraceptive (if any) for women with PCOS. Complicating the decision is the huge variety of oral contraceptive formulations available and the variation of risk profiles among women with PCOS.

It is vitally important to consult your health care provider to determine what the best oral contraceptive (if any) is best for your circumstances.

Don't restrict yourself to only the information above to make your choice; discuss the pros and cons in great detail with your care provider. You may also want to consider getting a second opinion since different providers often provide different perspective and advice.

Specific topics to discuss with your provider include:
  • Low-dose vs. high-dose pills
  • Type of progestin used, how anti-androgenic it is, and the benefit/risk of each type of progestin
  • Your family's medical history of diabetes and blood clots (including heart attacks and strokes)
  • Other significant risk factors like smoking, age, hypertension, or other co-morbid conditions 
  • Your PCOS symptoms 
  • Your PCOS treatment goals (menstrual regularity, androgenic issues, insulin resistance, etc.)
  • Your tolerance of risk vs. benefit trade-offs
Only when all of these factors are weighed can an individualized decision be made about which type of oral contraceptive (if any) is best for you.

Concerns with the Use of The Pill for PCOS

Of course, not everyone thinks that The Pill is a great idea for women with PCOS.

The main objection seems to be that The Pill simulates normalcy through added hormones, instead of promoting normal functioning of your own systems.  In the words of one site:
Taking the pill will provide your body with artificial hormones to simulate what a normal cycle is supposed to be...[but] the pill is not really regulating your cycle because it is not allowing your body to do the work, it is doing the work for your body.  
In other words, the Pill is a band-aid approach to treating a symptom. It simulates a period but does not help your body create a true regular menstrual cycle. It does not adequately address the underlying cause of problems or help the body to normalize its own insulin signaling and hormone levels.

People who feel this way believe that the best treatment for PCOS is to help a woman's body correct her own hormone levels and insulin signaling, instead of superimposing artificial hormones on it to create a fake semblance of normalcy.

Furthermore, the use of the Pill to regulate irregular cycles in young women may delay diagnosis and effective treatment of other PCOS symptoms. Many teens with irregular cycles are placed on the Pill to regulate their cycles without being told they may have PCOS and without receiving counseling about treatments to improve other PCOS symptoms.

As noted above, another significant concern is whether the Pill worsens insulin resistance, already a concern for PCOS women. Critics argue that at the very least, being put on the Pill alone does not lessen the underlying insulin resistance common to PCOS, and at worst, may actually make it worse. It certainly doesn't fix any defects in insulin signaling that may be happening.

For some women with PCOS, treating the underlying insulin resistance may regulate the cycle without needing birth control pills, while for others, a combination of insulin-sensitizing medications and oral contraceptives may be needed.

Long-term study of the relative benefits and risks of various protocols ─ with a focus on clinical endpoints of diabetes, heart disease, hypertension, and mortality specific to women with PCOS and not just extrapolated from other populations ─ is urgently needed.

Anecdotally, some women with PCOS find that when they come off of oral contraceptives in preparation for trying to conceive, their cycles are so messed up that it's very difficult to regulate them again or to re-establish ovulation. It's like their body has "forgotten" how to do it on its own and they often feel that they would have been better off not being on oral contraceptives at all. This is difficult to prove, but is plausible.

Some limited research supports this idea that regulating cycles with oral contraceptives before trying to conceive does not improve or may even harm the odds of success during fertility treatment. However, some research is contradictory and more data is needed.

Some women with PCOS believe that their hair loss issues (alopecia) were worsened by use of oral contraceptives, even as it helped with issues like acne and menstrual regularity. This is hard to prove and little research exists on it, but should be mentioned as a possible consideration for those already struggling with hair loss.

Bottom line, while birth control pills can be very effective for regulating menstrual cycles, decreasing androgenic side effects, and for decreasing the risk for ovarian and possibly endometrial cancer, it may neglect addressing the underlying cause of PCOS and may worsen metabolic profiles and certain symptoms in some.

Alternatives to Oral Contraceptives 

As we've discussed before, there are alternative treatments out there. It's important to keep reminding women with PCOS that the usual prescriptions of oral contraceptives, weight loss, and anti-androgen drugs are not the only way to treat PCOS.

Alternatives can include acupuncture, herbs like vitex/chasteberry, insulin-sensitizing medications like metformin and inositol, and perhaps vitamin D supplementation. It can also include lifestyle approaches that are compatible with Health At Every Size® and do not fixate on weight loss; these might include moderating carb intake, enhancing nutrition, increasing exercise, avoiding hormone-laden foods, and avoiding gluten. Although good long-term research is needed, many PCOS women find results just as good with these approaches as they do with traditional medical treatments.

Women with PCOS should also be checked for hypothyroidism. A number of studies have found that women with PCOS have a higher rate of abnormal thyroid function. Some studies suggest that hypothyroidism is associated with menstrual disturbancesinsulin resistance, and infertility. A number of women with PCOS have found that treating even marginal cases of hypothyroidism helped improve menstrual regularity.

Of course, weight loss is often considered the top therapy for PCOS, even over oral contraceptives, since some research shows it can be effective for resuming ovulationreducing androgens, and lowering insulin resistance in some women. However, studies on this have many weaknesses; they are often very small, extremely short-term, and do not show what happens if weight loss rebounds (which happens to most). Nor do they acknowledge that weight loss/weight cycling has risks as well as benefits, and that the oft-quoted "just a 5% weight loss" can trigger a rebound to a higher weight than before the diet.

Furthermore, not everyone responds to weight loss; quite a number of women with PCOS still experience missed periods and significant symptoms even after considerable weight loss. It is another tool that can be considered if you wish, but it is far from the magic bullet that doctors pretend it is and may actually be counter-productive for many due to regain and yo-yoing. For some, it even leads to eating disorders and unhealthy behaviors.

Because of these issues, hypocaloric diets for PCOS should not be mandatory for all PCOS women. Those who want to partake in them should be supported, but those who decline them should have their right to patient autonomy respected. Nor should weight loss be a requirement for accessing fertility services or other treatment, a restriction fraught with ethical issues and more than a whiff of the repulsive stench of eugenics.

Remember, there is no one "right" treatment protocol for PCOS. Each woman must find the right combination of treatments that work best for her circumstances and needs. For some, this may include oral contraceptives/birth control pills or even weight loss. For others, it may involve alternative therapies. For many, it involves a combination of a number of different approaches, but no one approach should be mandated across the board.

Summary

For some women with PCOS, oral contraceptives are extremely helpful in regulating menstrual cycles, preventing endometrial hyperplasia, reducing the risk for ovarian cancer, and probably also in decreasing the risk for endometrial cancer.

In addition, some combined oral contraceptives have an anti-androgen effect, so problems such as hirsutism and acne may be lessened while on The Pill.

However, not all women with PCOS feel that oral contraceptives are beneficial in the long run. PCOS communities online tend to be very divided in their views of oral contraceptives for PCOS. Many believe that greater improvement will result from addressing underlying hormonal issues and insulin resistance, seeing oral contraceptives as a "band-aid" that treats the symptoms instead of the cause.

Some women with PCOS find oral contraceptives to be a lifeline in their treatment of the condition, while others report that using them was not helpful or even harmful. Some find insulin-sensitizing medications (metformin, TZDs, the inositols) more useful. Still others benefit most from a combination approach (oral contraceptives plus insulin-sensitizing medications or anti-androgens) or from alternative protocols (herbs, lifestyle modifications, or alternative medicine).

Each woman with PCOS has to make up her own mind on the value of these approaches for treating her PCOS.

As always, you have to determine the right treatment protocol for your needs.


References

*These are just a few sample references. Many more can be found in the links inside the post.

References About PCOS
General Information about The Pill
Information about Different Types of The Pill
Information about Side Effects of The Pill
Information about PCOS and the Pill
Research Studies on PCOS and the Pill

Gynecol Endocrinol. 2008 Oct;24(10):590-600. The effects of Diane-35 and metformin in treatment of polycystic ovary syndrome: an updated systematic review. Jing Z, et al. PMID: 19012104
...A systematic review and meta-analysis were conducted. Randomized controlled studies applying Diane-35 and metformin for treating PCOS were included. The primary outcome was hirsutism...Twelve studies were included. The effect on improving hirsutism was not different between Diane-35 and metformin. Compared with Diane-35, metformin appeared to protect patients against glucose metabolic abnormality with treatment of at least 6 months. Except for triglycerides, no difference in lipid profile existed between Diane-35 and metformin. The evidence that Diane-35 deteriorates lipid and glucose metabolism was insufficient. Diane-35 could result in hypertension and headache. Methodological quality was still the key problem for studies. CONCLUSIONS: Diane-35 is superior to metformin in reducing androgens, but inferior to metformin in reducing insulin. Whether Diane-35 deteriorates lipid metabolism and insulin resistance is still unclear. [Diane-35 is not available in the U.S. or France because of the risk for clots with cyproterone acetate. The 35 stands for 35 mcg ethinyl estradiol dose. It is available as an acne medication in Canada and many other countries.]
Cochrane Database Syst Rev. 2007 Jan 24;(1):CD005552. Insulin-sensitising drugs versus the combined oral contraceptive pill for hirsutism, acne and risk of diabetes, cardiovascular disease, and endometrial cancer in polycystic ovary syndrome. Costello M, Shrestha B, Eden J, Sjoblom P, Johnson N.  PMID: 17253562
...Insulin-sensitizing drugs (ISDs) have recently been advocated as possibly a safer and more effective long-term treatment than the oral contraceptive pill (OCP) in women with polycystic ovary syndrome (PCOS). It is important to directly compare the efficacy and safety of ISDs versus OCPs in the long-term treatment of women with PCOS...Six trials were included for analysis, four of which compared metformin versus OCP (104 participants) and two of which compared OCP combined with metformin versus OCP alone (70 participants)...AUTHORS' CONCLUSIONS: Up to 12-months treatment with the OCP is associated with an improvement in menstrual pattern and serum androgen levels compared with metformin; but metformin treatment results in a reduction in fasting insulin and lower triglyceride levels than with the OCP. Side-effect profiles differ between the two drugs. There is either extremely limited or no data on important clinical outcomes such as the development of diabetes, cardiovascular disease, or endometrial cancer. There are no data comparing ISDs other than metformin (that is rosiglitazone, pioglitazone, and D-chiro-inositol) versus OCPs (alone or in combination).
CMAJ. 2012 Dec 3. [Epub ahead of print] Risk of venous thromboembolism in women with polycystic ovary syndrome: a population-based matched cohort analysis. Bird ST, Hartzema AG, Brophy JM, Etminan M, Delaney JA. PMID: 23209115
...RESULTS:The incidence of venous thromboembolism among women with PCOS was 23.7/10 000 person-years, while that for matched controls was 10.9/10 000 person-years. Women with PCOS taking combined oral contraceptives had an RR for venous thromboembolism of 2.14 (95% confidence interval [CI] 1.41-3.24) compared with other contraceptive users. The incidence of venous thromboembolism was 6.3/10 000 person-years among women with PCOS not taking oral contraceptives; the incidence was 4.1/10 000 personyears among matched controls. The RR of venous thromboembolism among women with PCOS not taking oral contraceptives was 1.55 (95% CI 1.10-2.19). INTERPRETATION: We found a 2-fold increased risk of venous thromboembolism among women with PCOS who were taking combined oral contraceptives and a 1.5-fold increased risk among women with PCOS not taking oral contraceptives. Physicians should consider the increased risk of venous thromboembolism when prescribing contraceptive therapy to women with PCOS.
Possible Disadvantages of The Pill for PCOS
Contraception. 2009 Feb;79(2):111-6. Epub 2008 Oct 16.  Insulin sensitivity and lipid metabolism with oral contraceptives containing chlormadinone acetate or desogestrel: a randomized trial. Cagnacci A, et al. PMID: 19135567
...Second-generation and third-generation oral contraceptives containing 30 mcg or more of ethinylestradiol (EE) decrease insulin sensitivity (SI). In this study, we investigated whether SI is decreased by contraceptives containing lower doses EE or by progestins with antiandrogenic properties...Twenty-eight young healthy women were randomly allocated to receive 20 mcg of EE and 150 mcg of desogestrel (DSG) (n=14) or 30 mcg of EE and 2 mg of chlormadinone acetate (CMA) (n=14) for 6 months. SI and glucose utilization independent of insulin (Sg) were investigated by the minimal model method. Lipid modifications were also analyzed...The present study confirms that DSG, even when associated with low EE dose, decreases SI. By contrast, EE/CMA does not deteriorate SI and induces a favorable lipid profile.
Int J Clin Pract. 2009 Jan;63(1):160-9. Epub 2008 Sep 13. Metabolic and cardiovascular impact of oral contraceptives in polycystic ovary syndrome. Soares GM, et al. PMID: 18795969
...This paper presents a critical evaluation of combined oral contraceptives (COCs) metabolic effect - carbohydrate metabolism and insulin sensitivity, lipid metabolism, haemostasis, body weight, arterial pressure and cardiovascular impact - on PCOS women. Because of the paucity of data on the impact of COCs on cardiovascular and metabolic parameters in PCOS patients, most of there commendations are based on studies involving ovulatory women. The use of low-dose COCs is preferable in PCOS, especially among patients with glucose intolerance, insulin resistance and uncomplicated diabetes mellitus. Although reported as a side effect of COCs, marked weight gain has not been confirmed among users. However, when arterial hypertension or elevated risk for thromboembolism is present, progestogen-only hormonal contraceptives should be used instead of COCs. Regarding dyslipidaemia, COCs reduce low-density lipoprotein and total cholesterol and elevate high-density lipoprotein and triglycerides, and therefore are not recommended for women with high triglycerides levels. The choice of a COC, which alleviates the PCOS-induced hyperandrogenism without significant negative impact on cardiovascular risk, is one of the greatest challenges faced by gynaecologists nowadays....

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.