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:

• The definition and symptoms of PCOS
• How it presents
• Its testing and diagnosis
• Its possible causes

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:

• Metformin (Glucophage) 
• TZDs (Avandia, Actos) 
• Inositols 
• Other medication options for those with diabetes
• Progesterone treatments for bringing on a long-overdue period

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 disturbances, insulin 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 ovulation, reducing 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

• http://verity-pcos.org.uk/guide_to_pcos/pcos_books/general_pcos - Verity's guide to books on PCOS; a more varied list than many organizations have
• American College of Obstetricians and Gynecologists (ACOG). Polycystic ovary syndrome. Washington (DC): American College of Obstetricians and Gynecologists (ACOG); 2009 Oct. 14 p. (ACOG practice bulletin; no. 108). Summary can be found here.
• http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3872139/?report=classic - 2013 review on diagnosis and treatment of PCOS

General Information about The Pill

• http://www.webmd.com/sex/birth-control/birth-control-pills - overview from webmd
• http://www.plannedparenthood.org/health-topics/birth-control/birth-control-pill-4228.htm - simple overview from Planned Parenthood
• http://en.wikipedia.org/wiki/Combined_oral_contraceptive_pill - Wikipedia entry on the combo pill
• http://women.webmd.com/features/comparing-birth-control-pill-types-combination-minipills-more - info on the various types of pills and their pros/cons
• http://www.mayoclinic.com/health/best-birth-control-pill/MY00996 - overview of different types of pills from the Mayo Clinic
• http://www.medscape.com/viewarticle/572203 - article on evaluating the cardiovascular risks of the Pill in PCOS; has info on the various types of Pills available and how they differ
• http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3469779/pdf/nihms382411.pdf - information about the main types of oral contraceptives currently in use in the United States

Information about Different Types of The Pill

• http://bedsider.org/features/89 - information about different brand names of The Pill
• http://www.medicinenet.com/oral_contraceptives_birth_control_pills/page3.htm - various versions of The Pill and the type of progestin used in each, etc.
• http://www.nlm.nih.gov/medlineplus/druginfo/meds/a601050.html - brand names of the various types of Pill and the type of estrogen and progestin in each

Information about Side Effects of The Pill

• http://www.health.com/health/condition-article/0,,20326842,00.html - various side effects of The Pill and how to deal with them

Information about PCOS and the Pill

• http://pcos.about.com/od/pcos101/a/ocp.htm - general info about the Pill and PCOS
• http://www.ovarian-cysts-pcos.com/birth-control-pills.html - general info about the Pill and PCOS
• http://www.3fatchicks.com/3-contraceptive-options-for-women-with-pcos/ - options for the Pill and PCOS in simple terms
• http://www.medscape.com/viewarticle/572203 - 2008 article on risk-benefit assessment on using the Pill for PCOS; lots of information on the various types of Pills available

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

• http://www.soulcysters.net/showthread.php?1398-MUST-READ-Do-BCP-s-*really*-help-PCOS-or-just-cover-it-up - questions whether the Pill is just a band-aid approach to symptoms and harms more than helps in the long run
• http://pcos.insulitelabs.com/blog/5/can-birth-control-pills-affect-pcos/ - questions whether the Pill harms more than helps in the long run, especially in terms of insulin resistance; note the sponsor of the site has a treatment protocol (and associated products) for alternative treatment of PCOS
• http://pcosinfo.com/birth-control-and-pcos/ - also questions the use of the Pill, although does not give study references to back up claims that BC pills worsen PCOS
• http://www.livestrong.com/article/477290-can-birth-control-pills-lower-blood-glucose/ - states that some types of the Pill can increase blood sugar/insulin resistance, although unlikely to cause diabetes on its own without other factors

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....

PCOS Treatment of Irregular Cycles: Progesterone Supplements

Poster by Amanda Kohn,www.implementingdesignism.org 

We've been talking about PCOS (Polycystic Ovarian Syndrome).

First we discussed its definition and symptoms, how it presents, its testing and diagnosis, and its possible causes.

Now we are discussing common treatment protocols for PCOS, and the pros and cons of each.

We've already discussed insulin-sensitizing medications like metformin, the TZDs, and inositol.

Then we discussed glucose-lowering medications for those who have developed overt diabetes.

Today, we start discussing treatments for regulating the menstrual cycle.

This mainly includes progesterone treatments and oral contraceptives for bringing on a period.

Today, we discuss progesterone treatments.

Disclaimer: I am not a medical health-care professional. While the following information is based on my best understanding of the research, 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 plan.

Trigger Warning: Passing mention of the possible weight effects of several medications, and passing mention of weight loss as the usual recommended treatment for menstrual irregularity.

Why It's Important to Treat for Menstrual Irregularity

Many women with PCOS experience irregular periods. It is probably the most common symptom of PCOS, and the one that brings the most attention to the syndrome in medical journals (along with infertility).

In a normal menstrual cycle, the lining of the uterus (endometrium) is exposed to various hormones produced by the body, especially estrogen. These hormones cause the lining to thicken and proliferate in anticipation of a possible pregnancy.

Once ovulation occurs, progesterone levels increase strongly in order to help sustain any pregnancy until the developing placenta can take over progesterone production. If pregnancy does not occur, a precipitous drop in progesterone levels will bring on the woman's period to flush out the unneeded extra lining.

Many women with PCOS have abnormally low levels of progesterone. They don't produce enough progesterone to bring on a period and flush out the uterine lining. This, plus egg follicles that don't develop properly, is why many women with PCOS have irregular periods. Some only skip a month now and again, while others may have only a few periods in a year. Still others may go years without a period.

Women with PCOS also tend to be estrogen-dominant, and as a result, the un-flushed uterine lining can be exposed to excessive levels of estrogen for prolonged periods. This can lead to abnormal overgrowth of the uterine lining (endometrial hyperplasia) and eventually, endometrial cancer.

Therefore, one of the most important treatment goals in PCOS is to regulate the menstrual cycle. There are two reasons that this is important:

• to improve ovulation for the purposes of fertility if children are desired
• to reduce the overgrowth of the endometrium and thereby reduce the chance for endometrial cancer later in life

The most common medication for regulating the menstrual cycle is the birth control pill, or The Pill. This ensures your body has a period every month. Most doctors see this as the treatment of choice for cycle regulation in PCOS.

However, if you've gone a long time without a period, many doctors will choose to use a progesterone medication first to "flush out" the uterine lining before trying other medications to regulate the cycle.

Although the focus of this series of posts is progesterone treatments and oral contraceptives, there are alternative treatments out there for regulating menstrual cycles. 

These will be covered in more detail in other posts, but can include lifestyle approaches (moderating carb intake, enhancing nutrition, and increasing exercise), acupuncture, herbs like vitex/chasteberry, the previously-discussed insulin-sensitizing medications like metformin or inositol, and perhaps vitamin D supplementation.

Care providers often also strongly promote weight loss for regulating menstrual cycles. This can be effective for some women but studies are often short-term and do not show what happens if weight loss is regained with time (as so often happens), nor do they acknowledge that weight loss can have risks as well as benefits (see the Weight References section of the blog). And while care providers make it sound like a sure thing, weight loss is not effective for regulating the periods in everyone; a number of women with PCOS still experience missed periods even after considerable weight loss. It is another tool that can be considered if you wish, but it's far from the magic bullet that doctors like to pretend it is.

Remember, there is no one "right" treatment protocol. Each woman must find the right combination of treatments that work best for her circumstances.

For some, this may include progesterone treatment to bring on a long-overdue period.

Progesterone Treatment for Menstrual Regularity 

Prometrium, image from Wikimedia

Progesterone supplements are usually used with a woman who hasn't had a menstrual cycle for quite a while. 

How long is too long? Some sources say at least 6 weeks between periods; others say at least six months between periods. The threshold at which progesterone supplements are prescribed will vary from provider to provider, but women should definitely not be going many months or even years between periods.

There are two main types of progesterone treatments for bringing on a period (withdrawal bleeding):

• Provera is the name of a synthetic type of progesterone (progestin) treatment; the generic name is medroxyprogesterone. This is the progesterone medication most often prescribed by care providers in the past. It is close to but not exactly like the progesterone produced in your own body
• Prometrium is the name of another progesterone supplement. It is synthesized from plants but is chemically identical to the progesterone made in your body. Some providers are moving to Prometrium more often these days, especially if pregnancy is desired, since Prometrium is safer to use in pregnancy than Provera

These medications have two main purposes for PCOS. They can be used for inducing a period in women who have not cycled on their own for a while and for managing ongoing abnormal uterine bleeding. In addition, they can be used to manage severe menopausal symptoms in older women.

In the interests of space, here we will only discuss their use for bringing on a period in women who have not cycled in a while.

Provera

Provera is a synthetic progestin which is similar but not quite identical to your body's own progesterone. Typically, Provera for inducing a period is prescribed as follows:

For the treatment of stopped menstrual periods (amenorrhea) and abnormal bleeding from the uterus, take this drug usually once daily for 5-10 days during the second half of the planned menstrual cycle or as directed by your doctor. Withdrawal bleeding usually occurs within 3-7 days after you stop taking the medication.

Provera comes in 2.5, 5.0, and 10 mg capsules. It's common to take a 5 mg or 10 mg capsule once a day for 5, 7, or 10 days (depending on your doctor's orders) in order to bring on the period. Other sources say to take Provera for 10 to 14 days every one to three months.

Provera works by simulating the high progesterone levels that occur near the end of your menstrual cycle, just before your period begins. It tricks your body into thinking that ovulation has occurred. Stopping the progesterone supplement simulates the drop in progesterone that occurs in a normal cycle when fertilization has not occurred, and should bring on your period within 2 weeks of stopping the medication. However, sometimes women do start their periods while still taking the Provera.

Some care providers only prescribe progesterone supplements periodically in women with PCOS. Others prefer to prescribe it regularly, about every few months, in order to promote a regular period and reduce the risk of endometrial hyperplasia. Discuss your situation with your care provider and decide what the best treatment routine is for you. 

If you are planning to try to become pregnant soon, you might want to reconsider whether or not to take Provera to bring on a period shortly before fertility treatment. Two recent studies found that taking Provera shortly before trying to conceive made the uterine lining more thin and women less likely to conceive. However, more research is needed to confirm this finding.

Side Effects and Risks of Provera

Side effects of Provera can be considerable, although short-term use for inducing a period is less risky than long-term use for menopause symptoms. The most common short-term symptoms include:

• dizziness
• headache 
• abdominal pain and cramping
• breast tenderness

Longer-term symptoms can include:

• breasts that are tender or produce a liquid
• changes in menstrual flow
• irregular vaginal bleeding or spotting
• acne
• growth of hair on face
• loss of hair on scalp
• difficulty falling asleep or staying asleep
• drowsiness
• upset stomach
• weight gain or loss

More uncommon (but serious) symptoms include:

• pain, swelling, warmth, redness, or tenderness in one leg only
• slow or difficult speech
• dizziness or faintness
• weakness or numbness of an arm or leg
• shortness of breath
• coughing up blood
• sudden sharp or crushing chest pain
• fast or pounding heartbeat
• sudden vision changes or loss of vision
• double vision
• blurred vision
• bulging eyes
• missed periods
• depression
• yellowing of the skin or eyes
• fever
• hives
• skin rash
• itching
• difficulty breathing or swallowing
• swelling of the hands, feet, ankles, or lower legs
• increased blood pressure

Although not always listed as a possible side effect, many women report that they have experienced extreme irritability and mood swings while on progestin medications. This is one of the most distressing side effects for many women.

Some lab animals which were given medroxyprogesterone developed breast tumors, but it is not clear whether this translates to development of breast cancer in humans. Medroxyprogesterone may also increase the chance of blood clots that move to the lungs (pulmonary embolism) or brain (stroke). Again, these risks are more related to long-term use than short-term use, but it's still important to be aware of the possibility.

Contraindications to Provera include prior history of breast, ovarian, or uterine cancer; blood clots; stroke; seizures; migraines; depression; unexplained vaginal bleeding; incomplete miscarriage; asthma; high blood pressure; diabetes; or heart, kidney, or liver disease.

Provera may create negative drug interactions with St. John's Wort, Rifampin, 

aminoglutethimide (Cytadren), certain anti-seizure medications, and other meds. If you are on any drugs (or any herbs), be sure to discuss that with your care provider before taking Provera.

Prometrium

Some care providers promote the use of bio-identical progesterones like Prometrium instead of synthetic progestins. They believe it will more closely mimic the body's natural process and result in better outcomes.

In some research, about 80% of women who took Prometrium (oral micronized progesterone) were able to re-start their periods.

Anecdotally, some women with PCOS report that they have had better results with Prometrium. Many report less moodiness, less dizziness, and fewer PMS-like symptoms. However, while many people have fewer side effects with Prometrium, others have had more. You have to test out which version is better for your body.

Prometrium is taken for the same reasons as Provera. It tricks the body into thinking it has ovulated; withdrawing the Prometrium will cause a drop in progesterone, hopefully triggering the woman's period within about 2 weeks. However, Prometrium is not as potent as Provera, so it needs a much higher dosage.

For bringing on a period, some sources recommend 100-300 mg of Prometrium for the last 10-12 days of what should be a 28-day cycle. Other sources suggest 400-600 mg per day.

For women who experience very strong estrogen dominance and wild fluctuations of symptoms when going on and off progesterone, some care providers recommend a low continuous dose of Prometrium, rather than constantly going on and off the progesterone.

Prometrium is available as an oral capsule, and can also be used as a vaginal suppository. There is a similar form available as an injectable intramuscular progesterone, or as a vaginal gel (Crinone). There may be fewer side effects with the vaginal versions but it can be a bit messy. The oral form might be best taken at bedtime because it can cause significant drowsiness in many women.

One major disadvantage of Prometrium is that it is much more expensive. Provera is available in a generic form so it can be much more affordable.

Provera should not be used if a woman might conceive a pregnancy. It has mild androgenic effects and can negatively affect a developing male fetus. In contrast, Prometrium is often prescribed by care providers to help lessen the risk for miscarriage in early pregnancy (more on that below).

Side Effects and Risks of Prometrium

Prometrium has many of the same side effects as Provera; re-read the above list to review these side effects. It is especially important to watch for possible signs of blood clots or allergic reaction.

The progesterone in Prometrium is micronized and suspended in a peanut oil solution to make it more bioavailable; the injectable form of intramuscular progesterone is suspended in sesame oil. People with peanut allergies need to avoid Prometrium and people with sesame allergies need to avoid intramuscular progesterone.

Although most women have fewer side effects with Prometrium, some women report more, especially dizziness, drowsiness, headache, acne or bloating/fluid retention. Weight gain is not uncommon with prolonged use of any progesterone supplement, but most non-menopausal women with PCOS will not take it long enough to experience this.

Some sources report that ketoconazole, an anti-fungal medication sometimes used for hair loss with PCOS, inhibits the absorption of Prometrium in the liver and therefore may potentiate its effects. However, oral ketoconazole is rarely prescribed these days as the FDA has recently warned of its potential for liver toxicity and adrenal damage. Furthermore, this warning does not extend to ketoconazole shampoo, which is the form used most often with hair loss concerns. It is unclear at this time whether the mere use of the shampoo would potentiate the effects of Prometrium. Discuss this possibility with your provider.

Controversy Over Use in Pregnancy

One big controversy these days is whether or not Prometrium should be given to women in early pregnancy to try and prevent miscarriage. Many providers are quite comfortable with doing this, while others contend it is not beneficial and may carry risks.

Why would Prometrium be given in pregnancy? Progesterone is important is sustaining a pregnancy, and women with PCOS tend to have low progesterone levels and higher miscarriage rates. The hope is that by supplementing progesterone, the risk for miscarriage will be lessened in this group.

In a woman without PCOS, the corpus luteum (the remains of the egg follicle on the ovary) produces progesterone for the pregnancy until the placenta is developed enough to take over progesterone production. Because follicular development tends to be weaker in women with PCOS, they may not produce enough progesterone to sustain a pregnancy. Supplementing progesterone is thought to help lessen the chance for miscarriage. Prometrium is the only viable choice for this because Provera is contraindicated in pregnancy.

However, using progesterone supplements in pregnancy is somewhat controversial. Many care providers do not believe that progesterone supplements are necessary or helpful for preventing miscarriage and will not prescribe them at all. Others regularly prescribe Prometrium for women with PCOS, especially if there is a history of miscarriage. Many providers also prescribe it for women who have gone through In Vitro Fertilization treatments, or for those experiencing threatened miscarriage.

Anecdotally, many women with PCOS who experienced repeated miscarriages report that progesterone supplements helped them to finally carry a pregnancy to term. Therefore there is fierce support for this practice on some PCOS boards.

However, progesterone supplements during pregnancy have occasionally been associated with hypospadias, an abnormal placement of the hole at the end of the penis in male babies. Rare complications have included cases of cleft lip, cleft palate, and cardiac issues. Whether this is true for all progesterone supplements, however, is not clear. Although some Prometrium-related websites caution against its use in pregnancy, it may actually only be the synthetic progesterones like Provera that carry this added risk. Some doctors' websites state outright that natural progesterone does not carry any additional risk, while others state that there may be a small increased risk. If in doubt, discuss this with your provider.

Prometrium is considered a Category B medication in pregnancy. The safest rating is a Category A. Category B means that animal studies have shown no increased risks to the fetus, but that there haven't been enough tests in humans to confirm this lack of harm. Given the natural reluctance of researchers to experiment on pregnant women, this rating is unlikely to change soon, but most providers seem to consider Prometrium a relatively safe drug for early pregnancy.

A 2013 Cochrane Collaboration review of the use of progesterones for preventing miscarriage found no evidence for its routine use in preventing miscarriages. However, in the subgroup of women with a history of repeated miscarriage, progesterones strongly lowered the risk for miscarriage and did not increase the risk for adverse outcomes like birth defects.

Another Cochrane review noted that progesterone supplements strongly lowered the rate of miscarriage in women experiencing threatened miscarriages. Both reviews noted that the research trials were of relatively poor quality and that more research is needed to guide clinicians on this topic.

So the bottom line so far appears to be that progesterone supplements should not be used routinely in all women in order to prevent miscarriage, but that there is probably a role for it under certain conditions, such as a threatened miscarriage or in women with a strong history of recurrent miscarriages.

Whether or not it should be used routinely in women with PCOS and no other risk factors has not been studied adequately. It may behoove women with PCOS to ask their providers to track their progesterone levels early in pregnancy and consider prescribing a natural progesterone if their levels appear low.

One other potential benefit of vaginal progesterone in pregnancy is that some research suggests that it may lower the rate of spontaneous pre-term birth in women with a shortened cervix in the second trimester.

Since the pregnancies of women with PCOS tend to be at increased risk for cervical insufficiency and pre-term birth, it is interesting to speculate whether low progesterone levels may be part of this risk, and whether or not early supplementation with Prometrium or vaginal progesterone may help prevent some cases of preterm birth in this group. However, at this time, this possibility remains speculative.

Summary

It is very important that women have regular periods so that the uterine lining does not build up and become cancerous over time.

There are many approaches that can help regulate the menstrual cycle in women with PCOS. For many, just taking metformin is enough to make periods more regular. For some, a lifestyle approach can make periods more regular. Alternative approaches that some find helpful include acupuncture or herbs like vitex (vitex often helps bring the body's hormones into balance and improves progesterone levels). There are also natural progesterone creams that contain much lower levels of progesterone than the medications discussed here and which may be useful for women with only mild progesterone deficiencies.

But some women with PCOS do not cycle even with these approaches. For these women, an oral contraceptive may be needed to have regular periods and prevent endometrial overgrowth. More on that in our next post.

However, if it has been more than a few months since you've had a period, care providers usually want to flush out the endometrium before beginning other treatments. The most common way to do this is to prescribe progesterone to bring on a period. Provera (a synthetic progestin) is the most commonly prescribed form, but Prometrium (a bio-identical progesterone) is gaining favor among many providers because side effects are often less severe.

Bringing on a long-overdue period with progesterone is not an easy process, and many women report significant bloating, cramps, and mood swings, as well as an extremely heavy period afterwards. This can be truly miserable for some women.

Because it can be such a difficult process, some women with PCOS avoid treatment with progesterones, preferring simply to avoid the bother of a period altogether. However, this will increase their long-term risk for endometrial cancer. As tough as it is to endure a long-overdue period, it is important to do so for your long-term health.

Once the endometrial lining has been flushed out, then other approaches to regulating the menstrual cycle can be tried. Lifestyle approaches, herbs, acupuncture and insulin-sensitizing medications can all help address the underlying hormonal imbalances that cause periods to be irregular. If all else fails, an oral contraceptive (The Pill) can be used, although many women with PCOS prefer to avoid this if possible.

Bottom line, women with PCOS need to prevent endometrial hyperplasia by some means or other. What method is best will depend on your individual circumstances and responsiveness, but progesterone can sometimes be part of that treatment strategy.

In addition, bio-identical progesterone may also hold promise for preventing some cases of miscarriage, and perhaps also for preventing some cases of preterm birth, although more study is needed.

Although they certainly carry risks and should not be over-utilized, progesterone supplements definitely have a role to play in treating some aspects of PCOS. 

References

Books About PCOS

• http://verity-pcos.org.uk/guide_to_pcos/pcos_books/general_pcos - Verity's guide to books on PCOS; a more varied list than many organizations have

PCOS Information 

• http://www.uptodate.com/contents/polycystic-ovary-syndrome-pcos-beyond-the-basics
• http://www.hormonehelpny.com/column/pcos.htm

General Information about Progesterone for Regulating Cycles

• http://www.nlm.nih.gov/medlineplus/druginfo/meds/a682470.html - information about medroxyprogesterone (Provera) for regulating menstrual cycles
• - information about Prometrium for regulating menstrual cycles
• http://www.womenlivingnaturally.com/articlepage.php?id=106 - information about bioidentical progesterone for regulating cycles (instead of synthetic progestins)
• http://www.soulcysters.net/showthread.php/9789-Provera-vs-Prometrium - anecdotal experiences of Provera vs. Prometrium in women with PCOS
• http://www.project-aware.org/Resource/articlearchives/differences.shtml - information about the differences between natural and synthetic progesterones, written by a pharmacist

Studies on Provera and PCOS

Obstet Gynecol. 2012 May;119(5):902-8. doi: 10.1097/AOG.0b013e31824da35c. Endometrial shedding effect on conception and live birth in women with polycystic ovary syndrome. Diamond MP, Kruger M, Santoro N, Zhang H, Casson P, Schlaff W, Coutifaris C, Brzyski R, Christman G, Carr BR, McGovern PG, Cataldo NA, Steinkampf MP,Gosman GG, Nestler JE, Carson S, Myers EE, Eisenberg E, Legro RS; Eunice Kennedy Shriver National Institute of Child Health and Human Development Cooperative Reproductive Medicine Network. PMID: 22525900

OBJECTIVE: To estimate whether progestin-induced endometrial shedding, before ovulation induction with clomiphene citrate, metformin, or a combination of both, affects ovulation, conception, and live birth rates in women with polycystic ovary syndrome (PCOS). METHODS: A secondary analysis of the data from 626 women with PCOS from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Cooperative Reproductive Medicine Network trial was performed. Women had been randomized to up to six cycles of clomiphene citrate alone, metformin alone, or clomiphene citrate plus metformin. Women were assessed for occurrence of ovulation, conception, and live birth in relation to prior bleeding episodes (after either ovulation or exogenous progestin-induced withdrawal bleed). RESULTS: Although ovulation rates were higher in cycles preceded by spontaneous endometrial shedding than after anovulatory cycles (with or without prior progestin withdrawal), both conception and live birth rates were significantly higher after anovulatory cycles without progestin-induced withdrawal bleeding (live births per cycle: spontaneous menses 2.2%; anovulatory with progestin withdrawal 1.6%; anovulatory without progestin withdrawal 5.3%; P<.001). The difference was more marked when rate was calculated per ovulation (live births per ovulation: spontaneous menses 3.0%; anovulatory withprogestin withdrawal 5.4%; anovulatory without progestin withdrawal 19.7%; P<.001). CONCLUSION: Conception and live birth rates are lower in women with PCOS after a spontaneous menses or progestin-induced withdrawal bleeding as compared with anovulatory cycles without progestin withdrawal. The common clinical practice of inducing endometrial shedding with progestin before ovarian stimulation may have an adverse effect on rates of conception and live birth in anovulatory women with PCOS.

Int J Clin Exp Pathol. 2013 May 15;6(6):1157-63. Print 2013. Does progesterone-induced endometrial withdrawal bleed before ovulation induction have negative effects on IUI outcomes in patients with polycystic ovary syndrome? Dong X, Zheng Y, Liao X, Xiong T, Zhang H. PMID: 23696936

...The present study was performed to investigate whether progesterone-induced endometrial bleed before ovulation induction affects pregnancy in patients with PCOS who underwent intrauterine insemination (IUI) treatment. A total of 241 IUI cycles were retrospectively analyzed. Patients enrolled in this study underwent ovulation induction with IUI treatment from Jan. 2011 to Dec. 2012. The study group consisted of 184 cycles with progesterone-withdrawal bleed before ovulation induction. The control group included 57 cycles with spontaneous menses. The clinical characteristics, ovulation induction parameters and IUI outcomes, such as pregnancy rate and live birth/ongoing pregnancy rate, were compared between the two groups...In conclusion, our study showed that progesterone exerted a negative effect on endometrial development, which seemed to be associated with reduced pregnancy results in ovulation induction with IUI cycles.

 Prometrium Studies

Fertil Steril. 1991 Dec;56(6):1040-7. Factors associated with withdrawal bleeding after administration of oral micronized progesterone in women with secondary amenorrhea. Shangold MM, Tomai TP, Cook JD, Jacobs SL, Zinaman MJ, Chin SY, Simon JA. PMID: 1743319

OBJECTIVE: To compare two dosages of oral micronized progesterone (P) and placebo for withdrawal bleeding and side effects. DESIGN: Prospective, randomized, double-blind... INTERVENTIONS: A 10-day course of (1) oral micronized P 300 mg, (2) oral micronized P 200 mg, or (3) placebo...RESULTS: Withdrawal bleeding occurred in 90% of women taking 300 mg, 58% of women taking 200 mg, and 29% of women taking placebo (P less than 0.0002 for 300 mg versus placebo). Side effects occurred similarly among the groups (P = not significant). Lipid concentrations were unchanged. Endogenous E2 and treatment P concentrations were of limited predictive value for withdrawal bleeding. CONCLUSIONS: Progesterone 300 mg induced significantly more withdrawal bleeding than placebo, with similar side effects...

Love Your Cervix, Learn Your Body

Do you know what a cervix looks like? Do you know how it changes during a woman's monthly menstrual cycle? Have you ever seen a cervix in real-life pictures, up close? If you are a woman, have you ever seen your own cervix?

Do you know the subtle fertility signs a woman's body puts out that can help you determine when you are most likely to get pregnant and when you are not? Do you know about the Fertility Awareness Method of birth control? (No, it's not the rhythm method.)

Do you know why the fluids your body gives off "down there" (yes, from your vagina) change from day to day? Why sometimes they are copious and slippery, why sometimes they are tacky and kind of dry, why sometimes they are in-between----and what these changes indicate?

There is a new and very cool website out there that records--in pictures--the changes in one woman's cervix over one menstrual cycle. If you answered "no" to any of the above questions, you should definitely check out this woman's site. Even if you answered yes to all of the above questions, you'd probably find the site fascinating, as it documents everything you've already learned but in more detail than you've probably seen.

The site is called "My Beautiful Cervix" and an explanation about it can be found at http://beautifulcervix.com/about/.The actual daily pictures of her cervix can be found at http://beautifulcervix.com/photos-of-cervix/.

Be aware that these pictures are very detailed, and that the first pictures start during her menstrual flow, so proceed at your own "squick" factor. But unless you are extremely upset by these sorts of things, I highly recommend this site to you, male or female. It's important to expand our knowledge about the human body, and in this case, it's so helpful in learning about fertility, menstruation, and how best to achieve....or avoid....pregnancy.

Some Basic Information About Fertility

Unfortunately, very few women in our patriarchal society really understand how their body changes over their menstrual cycle, know their own fertility signs, have really seen their own genitals, or know how to control their own fertility without having to rely on artificial drugs, barriers, or chemicals.

If you have never read the book, Taking Charge of Your Fertility, by Toni Weschler, you really should check it out. It is an amazing book, and so educational. It is particularly helpful for women with PCOS and for women whose cycles last longer or shorter than the usual 28-day cycle doctors consider "typical." It's also very helpful if you want to find a less chemical form of birth control, or conversely, if you plan to try and conceive soon.

In Fertility Awareness, you track your body's fertility by keeping track of 2 or 3 primary fertility signs, usually Basal Body Temperature (BBT, a temp taken first thing in the morning on a special thermometer), cervical mucus, and cervical position.

You are not equally fertile on all days of your cycle. Your cervical mucus gets more slippery and copious as you get more fertile, and on your days of highest fertility it has more of an "egg-white" quality, looking like you have egg whites stretched between your fingers when you check it. (The picture above shows one example of fertile mucus.)

Similarly, your cervix will change position too, getting higher or lower, softer or harder, less or more open, depending on where you are in your cycle.

Your BBT will spike once ovulation has taken place, because the body has upped its production of progesterone in order to support a pregnancy if fertilization were to occur. This jump in temperature will stay elevated until just before your period starts; once your menses begins, your temperature will decrease significantly as progesterone production drops off.

However, if you are pregnant, your temperature will remain elevated. This is often the first sign of pregnancy and can tell you that you are pregnant well before any pregnancy test will.

Utility of Fertility Awareness

I can't tell you how useful this information is, in so many ways, even if you don't use it as a form of birth control (or to help you conceive).

So many women see the increased/changing fluids during their cycles and wonder if they have some sort yeast infection. You have to wonder how much unnecessary over-the-counter yeast medicine is being bought each year, simply because women have not been taught about their natural variations in cervical mucus!

Also, if you have unusual-length or highly variable cycles, knowing the signs of fertility and ovulation can help you know when to expect your period. If your cycles vary a lot, this can be a god-send!

The time from ovulation to the start of your period is pretty uniform in most women. It varies from woman to woman, averaging anywhere from 12-16 days or so, but within the same woman, this "luteal phase" length stays pretty consistent. So if you recognize the signs of ovulation, you can predict with pretty good accuracy about when your period will arrive afterwards.

It can also keep you from panicking too much about whether or not you are pregnant! When I was first married, I had many scares wondering whether I could be pregnant because my period simply didn't show up when the doctors said it should. Even once I knew my cycles were longer than "typical," I was never sure when I should start worrying, always wondering if our birth control method had failed somehow. Fertility Awareness would have saved a lot of money on unnecessary pregnancy tests!

Fertility Awareness can also help prevent unwanted pregnancies. Many women have a mistaken idea of when they are fertile and when they are not. I know I had a lot of incorrect ideas about this, and it helped to lead to my first child! It was a welcome surprise, mind, at a time in life when we were ready for it, but not everyone is ready to be so welcoming. Looking back with FA knowledge, I could understand exactly why we goofed, and I was able to prevent any repeat of this surprise until I was ready for more kids.

Once you decide you are ready for children, Fertility Awareness is great at helping you achieve that. Once my first pregnancy was done, a friend of mine taught me about Fertility Awareness. When my husband and I were ready to try for #2, we used Fertility Awareness and were able to achieve pregnancy the first month we tried. Same for my later children, despite being an old geezer by obstetric standards.

Turns out I ovulate much later than most women (thus the longer cycles). Trying to conceive during the usual times recommended would not have worked for us....too far away from my normal ovulation times. Learning my cycles made the process so much easier and less stressful.

It was also fantastic to know really early on from my temperature charts that I was pregnant. Helped remind me to take my prenatals plus extra folic acid religiously, and to be extra careful of my nutrition and exercise.

Despite having PCOS, I was able to get pregnant without any problems. I am fortunate in that my case is fairly mild on the PCOS spectrum. But in many women, PCOS prevents them from ovulating, or they ovulate only irregularly. Fertility Awareness is helpful in establishing whether or not they are really ovulating, and at what point in their cycle this is taking place. If they ovulate irregularly, Fertility Awareness can help them clue in on the signs that ovulation may be about to occur so they can take advantage of it.

Like any birth control method, Fertility Awareness has its pros and cons. It's not for everyone, at least as a birth control method. And using it as a conception aid won't guarantee you'll get pregnant. But even so, it's a great idea to learn about your body and its natural cycles, to learn what your cervix really looks like up close, and to understand exactly how your body works.

I highly recommend visiting the Beautiful Cervix website, and reading up more about Fertility Awareness.

*Image from Wikimedia Commons.