Supplements for PCOS…
3 Supplements Commonly Overlooked for PCOS

Written by: Dr. Ashley Eskew MD, MSCI

Edited by: Dr. Will Haas, MD, MBA

Last updated: September 28th, 2021

Women with PCOS researching supplements on the internet

Every day it seems like there’s a new miracle supplement out there for PCOS.

Probiotic supplements…

Fish oil supplements…

Supplements for gut health…

And simply consulting Dr. Google on what to take can lead to disappointment as well as a needless drain on your bank account. 

So which supplements have evidence and which ones are actually worth your time and money?

It depends on who you ask….

And much like a diet, what works for one person, may not work for everyone. 

But knowing the evidence (even if it’s limited at times) is a good place to start. That’s why we’re dedicating this post to a few PCOS supplements we believe deserve a closer look.

Here’s a quick overview of what you’ll discover:

Nutritional Supplements vs. Prescription Medications for Polycystic Ovary Syndrome

Choosing which nutritional supplement to take for polycystic ovary syndrome (PCOS) isn’t an easy task, right? 

For starters, most physicians aren’t trained in botanical medicine or have the time to read the literature on supplements… Unfortunately, that means you likely won’t be getting the medical advice you desire at your next doctor’s appointment. 

And searching Amazon for supplement reviews seems like such a risky way to pick out your next supplement… 

Then there’s the bigger issue that supplements aren’t even regulated by the Food and Drug Administration (FDA)… meaning they might not even contain what’s on the bottle – yikes! Don’t worry, we’ll teach you how to choose quality supplements towards the end of this post. 

So why do some women choose nutritional supplements over prescription medications? 

More often than not, it comes down to the perceived lower side effect profiles of supplements compared to medications. And although this may certainly be true for some supplements, this is not always the case. (Yes, that means supplements should be treated with the same caution and respect as prescription  medication… but more on that momentarily)

On the other hand, some women reach for supplements as an economical alternative to prescription medications. When compared to the cost of infertility medications, supplements certainly are more friendly on your bank account. Of course, high-quality supplements can certainly add up in cost too. 

Finally, given the difficult-to-treat nature of some conditions such as PCOS, supplements are often seen as a more effective treatment option compared to medications such as birth control or Metformin. And yet again, sometimes this is the case and other times it’s far from the truth…

None of these considerations are mentioned to dissuade you (or any cyster) from taking supplements. We are simply here to help you make educated and empowered decisions! 

Many supplements studied for women with PCOS have actually been shown to have positive effects on insulin sensitivity, hormonal imbalance, and inflammation – all of which are important factors to control to keep your symptoms of PCOS in check.

The Role of Insulin in PCOS

And as you may recall from part 1 of our mini-series on the proper diagnosis of PCOS, elevated insulin levels and insulin resistance are thought to contribute to hyperandrogenism and PCOS symptoms in 3 interrelated ways:

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    Decreased liver production of proteins that bind up testosterone

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    Increased ovarian production of androgens (male-like sex hormones)

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    Increased adrenal production of androgens

Elevated insulin levels are also thought to contribute to inflammation in women with PCOS (1). Therefore, any supplement with anti-inflammatory properties that can also support insulin resistance and hormonal balance is potentially a good treatment option for polycystic ovarian syndrome.

Of course, as you probably know, there are SO MANY supplements to consider – things like chromium, magnesium, omega-3 fatty acids, n-acetyl cysteine (NAC), and melatonin.  And just so we don’t disappoint anyone, this is NOT going to be an all-inclusive literature review of every supplement. But fear not… we’ll cover additional PCOS supplements over subsequent posts. 

Here, we’re going to stick to the supplements that have been actually studied in women with PCOS, not animals or cells in petri dishes. More specifically, we’ll look at one that’s widely acknowledged (but somewhat misrepresented) as well as two that are lesser-known yet still important!

With that, let’s jump in!

3 PCOS Supplements That Deserve a Closer Look

If you’re jumping right into this section of the post, it’s worth reiterating that this is NOT one of those “Top 10 Supplements to Take If You Have PCOS” kind of posts… 

… you know the ones we are talking about –  the posts with lots of superficial information that references any old study on PubMed and calls it a day after 2-3 sentences. 

That’s why for the purposes of this post we’ve decided to go deep and focus our attention on 1 commonly misrepresented supplement (inositol) and 2 lesser talked about supplements (cinnamon & vitamin D)

All this to say, there are certainly other dietary supplements to consider and we promise to cover them in depth elsewhere… But for now, we wanted to provide a little clarity around 3 supplements for PCOS that aren’t adequately (or accurately) being discussed. 

Bundle of cinnamon sticks for PCOS

Cinnamon:

First up is cinnamon!

Wait, what? 

Cinnamon… like the spice you occasionally put on desserts?

Yes, that one.

As you may have guessed, cinnamon is one of the lesser talked about supplements that we believe to have some good evidence supporting its use.  

Among individuals with metabolic syndrome, cinnamon supplementation has been shown to improve (2):

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    Fasting blood glucose

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    Blood pressure

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    Lean body mass

And in individuals with type 2 diabetes it’s been shown to improve (3):

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    Fasting blood sugar

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    Fasting Insulin

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    Hemoglobin A1c

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    Cholesterol levels

Given that women with polycystic ovary syndrome are at risk for these health conditions, it’s not surprising that cinnamon supplementation has been evaluated for PCOS too.

One small double-blind randomized controlled trial (RCT) of 15 women with PCOS took 333 mg of supplemental cinnamon extract for 3 weeks (4). Researchers noted a significant reduction in:

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    Fasting glucose

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    Measures of insulin sensitivity

And this was just after 8 weeks! Although this study was too small to make any sweeping recommendations, the results certainly warranted further investigation.

A more recent double-blind RCT examined the effects of cinnamon after 6 months of supplementation and noted a significant improvement in menstrual cycle regularity with 1.5 grams daily (5). Researchers didn’t find a significant difference in serum androgens, weight, or waist circumference. However, these are important findings given that regulating menstrual irregularities play an important role in optimizing PCOS. 

Another double-blind RCT noted a significant improvement in lipids and total antioxidant capacity with just 8 weeks of supplementation at 1.5g daily in women with PCOS (6).

Dosing in these clinical trials ranges anywhere from 1.0 – 1.5 grams daily for the PCOS patients who participated. If you prefer cinnamon in its natural form, you can certainly sprinkle some on your next batch of homemade granola or bake it with apples and enjoy 🙂

Although adverse effects are rare, headache, heartburn, nausea, and diarrhea have been reported. Caution should be used when also taking other antidiabetic drugs due to concerns for hypoglycemia.

Chemical structure of inositol as a supplement for PCOS

Inositol:

Next up is inositol… 

We are passionate about this supplement as it’s a tricky one that often gets misrepresented. 

Considered to be a B-vitamin-like compound, inositol is naturally occurring in our bodies. However, most of what we actually need comes from dietary intake or supplements.

The 2 forms of inositol that are most relevant when it comes to supplementation for polycystic ovary syndrome include Myo-inositol (MI) and D-chiro-inositol (DCI). 

In the body, MI and DCI typically exist in a 40:1 ratio and they carefully balance one another via different mechanisms of action. Of note, MI gets converted to DCI via an enzymatic reaction that is actually inhibited by insulin resistance.

Despite their different concentrations, MI and DCI both act as messengers inside our cells that can balance some of the metabolic disruptions that occur with insulin resistance. They also help direct the function of critical hormones, including follicle-stimulating hormone (FSH) and thyroid-stimulating hormone (TSH). And within your ovaries, DCI is involved in insulin-mediated androgen synthesis, while MI mediates glucose uptake and FSH signaling.

Now if you haven’t already, you’ll probably see inositol touted as a PCOS miracle supplement on social media…

But is inositol really that good for PCOS?

Before answering that question, data surrounding inositol for polycystic ovary syndrome must be approached with appropriate caution due to inherent limitations in the research.

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    Limitation #1: The dosage and duration of treatment vary widely among RCTs.

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    Limitation #2: Not all the studies use the same diagnostic criteria for PCOS.

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    Limitation #3: Studies have been done in different populations of women with PCOS. (Infertile women with PCOS undergoing IVF vs. overweight women with PCOS not trying to conceive vs. normal-weight women with PCOS without proven fertility but not trying to conceive)

Obviously, it’s challenging to compare the results from different studies when women, who may or may not meet the diagnosis for PCOS, are given a supplement at differing doses for different periods of time. 

It’s also important to mention that many of the studies involving specific formulations of MI:DCI have been industry-sponsored (meaning that the manufacturer is likely invested in a positive outcome).

Okay, okay, limitations notwithstanding, there is definitely some compelling data for inositol and PCOS… Let’s review some of the higher-quality studies and see what you think for yourself.

An early double-blind randomized controlled trial (n=44) assessing DCI supplementation in women with PCOS showed (7):

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    No significant difference in insulin sensitivity, HDL, or LDL

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    Significant decrease in plasma TG

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    Improved ovulation

Since then, a few other studies have looked at DCI supplementation alone, however, evidence has suggested that MI is superior when compared directly with DCI (8). As we mentioned previously, MI occurs in a naturally higher ratio in the body, so most studies have focused on either MI alone or MI + DCI which is the more common supplemental pattern.

So what about MI supplementation then?

Another double-blind, placebo-controlled trial (n=50) of overweight women with PCOS undergoing IVF were treated with 2 grams of MI plus 200 mcg of folic acid vs. 400 mcg of folic acid alone for 12 weeks and showed (9):

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    Improved insulin sensitivity

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    A higher number of oocytes retrieved

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    Higher clinical pregnancy rates & live birth rates

Interestingly, when compared to metformin, 12 weeks of MI supplementation resulted in significantly decreased androgen levels, improved hirsutism (unwanted hair growth), and decreased markers of inflammation (10). And another study even found improved mental health with MI compared to metformin (11).

Now if you recall, we mentioned that MI and DCI exist in a 40:1 ratio within the body. So what has evidence shown in terms of relative amounts of combined MI & DCI supplementation?

Well, an RCT of 46 women with obesity and PCOS looked at 550 mg MI + 13.8 mg DCI + 200 mcg folic acid versus folic acid alone for 6 months (12). Researchers found that the MI + DCI group had significantly improved:

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    Insulin sensitivity

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    Androgen levels

These findings have been potentiated by findings from two separate meta-analyses evaluating inositol supplementation. One showed improvement in insulin sensitivity and SHBG, but no significant difference in testosterone levels (13).  While the other noted significantly higher ovulation rates, menstrual cyclicity, and improved androgen levels.

Remember, these studies must be interpreted with some caution for the reasons we mentioned earlier including differing interventions (either DCI, MI, or a combination), treatment duration, medication dose, and population being studied.

One final point… 

It’s important to note that NONE of the studies above mentioned significant differences in weight loss and there’s a reason for that…

… data has NOT consistently shown weight loss as an added benefit with any formulation or duration of treatment when taking inositol. We highlight this point not to be discouraging, but because we see social media commonly touting this as one of the benefits of taking inositol and the date simply does not support the claim. 

Inositol is generally well tolerated with minimal side effects (it’s occasionally been noted to cause dizziness, fatigue, headache, and nausea). 

Bottom line…  Most data support supplementation of MI alone, whereas a combination of MI:DCI is okay too (the latter is just typically much more costly). DCI alone is generally not recommended.

Ray of sunshine and vitamin D as a supplement for PCOS

Vitamin D:

One of our favorite vitamins… Not only because it’s best obtained from the sun, but because of all the various health and wellness benefits it has been shown to have.

This is the other supplement that we think doesn’t get enough attention for women with PCOS. 

There are 2 forms of vitamin D that are physiologically important, ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3 – the one you see in supplemental form). 

Vitamin D2 actually comes from ergosterol (a plant sterol), whereas vitamin D3  is synthesized in the body. Both vitamin D2 and vitamin D3 are biologically inactive and require hydroxylation to form the active metabolite, calcitriol.

Okay, enough basic science talk… 

Similar to the other dietary supplements we’ve discussed, vitamin D3 is thought to modulate insulin activity. Interestingly enough, population-based research has shown that people with lower vitamin D levels have a higher risk of developing type 2 diabetes (14).

When we look at vitamin D levels among women with PCOS, we discover some pretty striking results… Based upon a secondary analysis from one of the largest clinical trials of women with PCOS (PPCOS II), those who were vitamin D deficient had an 18% lower likelihood of ovulation and a 37% lower likelihood of live birth compared to those with normal levels (15). 

Vitamin D deficient women with polycystic ovary syndrome have also been shown to have a higher likelihood of moderate and severe insulin resistance as well as elevated androgen levels. 

Now let’s turn our attention to vitamin D supplementation in women with PCOS…

Most research regarding supplementation has only shown benefits when used among women with vitamin D deficiency. On the other hand, routine supplementation in the absence of deficiency hasn’t been shown to be as beneficial. With that said, vitamin D deficiency is fairly common. 

Risk factors for vitamin D deficiency include:

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    Higher BMI

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    Darker skin tones

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    Living far from the equator

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    Staying indoors during the daytime (nightshift, anyone?)

After 12 weeks of daily supplementation with 12,000 IUs of vitamin D3, women with polycystic ovary syndrome were noted to have improved markers of insulin sensitivity and blood pressure. And despite these positive findings, we should point out that this RCT was fairly small (only 22 women finished the study) (16).

Another RCT of 70 women with PCOS noted that those who received 50,000 IU of vitamin D3 every 2 weeks vs placebo had significantly lower fasting glucose and insulin levels (17).

Studies assessing the seasonal effects on vitamin D status have been shown to influence outcomes in women with PCOS who struggle with excess body weight or obesity (18). According to a study in Fertility & Sterility, an inverse correlation was noted with vitamin D3 levels and changes in waist circumference and cholesterol. Ultimately this study concluded that obesity and cardiovascular risk factors improved in vitamin D deficient women with PCOS over a 20-week lifestyle intervention during which vitamin D status improved with seasonal change. 

Vitamin D3 is generally well tolerated when taken in the appropriate doses (2000 IU/day or 50,000IU weekly), but as with all supplements extremely high doses aren’t harmless (side effects include: elevated calcium levels, azotemia, and anemia). 

Bottom line… Based on the above findings, data would certainly support D3 supplementation when you’re deficient, so make sure to get your levels checked!

Infographic of 3 PCOS Supplements That Deserve a Closer Look

How to Choose Quality Supplements for PCOS, and Why the Source Matters

Now that you have a better understanding of 3 key supplements for PCOS! But…

How do you choose a quality product among the sea of supplements online? 

From misleading claims… to unnecessary additives… to fancy packaging… 

There’s a lot to consider. 

At a high level, here are a few considerations when you shop for your next supplement: 

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    No bold claims…

    Technically, the FDA does not allow supplement manufacturers to make specific health claims about supplements or vitamins. So if you see a bold claim on the bottle, then beware of the product.

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    High-quality ingredients… 

    Micronutrients and botanicals come in many different forms, and some are much easier to absorb and more active than others. It’s important to do your homework about the active ingredient before making a purchase.

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    Minimal additives…

    Manufacturers should test for contaminants such as mold and heavy metals. However, that doesn’t stop them from including unneeded fillers such as gluten, artificial flavoring, or preservatives. Good products will use hypoallergenic fillers if absolutely necessary.

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    Appropriate dosage…

    We’ve said it before, but more is not always better when it comes to supplements or vitamins. Make sure you know the appropriate dose for the condition or symptom you are trying to manage.

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    3rd party testing…

    A quality supplement manufacturer will typically have their products verified by 3rd party testing groups. Look for stamps on the bottle from ConsumerLab, NSF International, or US Pharmacopeia. 

Of course, there are certainly other considerations when it comes to choosing the best supplement for managing your PCOS symptoms… But these pointers, along with personalized recommendations from your physician will help you avoid a poor quality supplement.

When to Consider Metformin for PCOS

We know what you might be thinking… 

I thought we were talking about supplements, not prescription medications?

Well sometimes, supplements aren’t enough to manage your PCOS symptoms 🙁

And because we see Metformin get such a bad wrap on social media, we thought it best to let you know that this medication does have its place when used appropriately…

Metformin pill bottle as a treatment for PCOS

… oh, and here’s a fact that most experts on social media also forget to mention…

 Metformin was originally developed from natural compounds found in the plant Galega officinalis, also known as French lilac (19). 

Similar to many of the supplements recommended for PCOS, one of Metformin’s primary mechanisms of action is to improve insulin and glucose regulation as we briefly discussed in our post on diet and PCOS. And not only does Metformin make your body more sensitive to insulin, but it also acts to decrease the liver’s production of glucose.

Due to the central role of insulin resistance in the pathophysiology of PCOS researchers initially tried to use metformin to boost ovulation which ultimately did not pan out when compared to other ovulation induction medications like clomiphene citrate and letrozole (20). 

Ultimately, letrozole alone has demonstrated higher live birth rates compared to metformin, or metformin + clomiphene citrate (21). Moral of the study… Metformin alone likely won’t boost your chances of getting pregnant. 

Based on expert recommendations, lifestyle modifications in addition to metformin may be considered for the treatment of the weight gain as well as the metabolic outcomes related to PCOS (22). However, empiric treatment of PCOS with Metformin alone is NO longer broadly recommended. 

The most common side effects of metformin include things like gastrointestinal (GI) upset (nausea, vomiting, and diarrhea) and abdominal discomfort. More often than not, these symptoms can be avoided by starting at a low dose in the evening and gradually working up from there. 

Unfortunately, we often see women without impaired glucose tolerance or insulin resistance being given this drug, only to experience miserable nausea and diarrhea, which often suppresses their appetite further. Although not everyone will experience those side effects, it certainly would seem more pleasant to make some simple dietary swaps and add in a supplement or two to reduce the risk of insulin resistance and elevated glucose levels. 

It’s important to note that long-term use of metformin has also been associated with vitamin B12 deficiency. So, it’s important to keep that in mind, especially if your goal is to get pregnant. 

Final Thoughts

There you have it! Our thoughts on 1 commonly misrepresented supplement (inositol) and 2 lesser talked about supplements (cinnamon & vitamin D). 

For those of you already taking inositol, we certainly aren’t suggesting that you stop using it. We simply want you to be informed about the current evidence. Please don’t get fooled into thinking it has magical powers that will counteract a half-gallon of ice cream (it’s sad, but we’ve seen this supplement represented that way). 

As for cinnamon and vitamin D, these can be great additions to your PCOS treatment plan, especially if you struggle with insulin resistance. Cinnamon is great to use in its whole food form so you can avoid another pill, and vitamin D should definitely be repleted if you’re deficient.  

No matter what you choose, always make sure to select quality supplements when you shop and speak with your healthcare provider or fertility specialist about YOUR unique circumstances to see what’s right for you!

With Love & Empowerment,
Dr. Ashley Eskew and Dr. Will Haas

References:

  1. Riley JK, Jungheim ES. Is there a role for diet in ameliorating the reproductive sequelae associated with chronic low-grade inflammation in polycystic ovary syndrome and obesity? Fertil Steril. 2016;106(3):520-7.

  2. Qin B PK, Anderson RA. Cinnamon: Potential Role in the Prevention of Insulin Resistance, Metabolic Syndrome and Type 2 Diabetes. Journal of Diabetes Science and Technology. 2010;4(3):685-93.

  3. Khan A SM, Ali Khan MM, Khattak KN, Anderson RA. Cinnamon improves glucose and lipids of people with type 2 diabetes. Diabetes Care. 2003;26:3215-8.

  4. Wang JG, Anderson RA, Graham GM, 3rd, Chu MC, Sauer MV, Guarnaccia MM, et al. The effect of cinnamon extract on insulin resistance parameters in polycystic ovary syndrome: a pilot study. Fertil Steril. 2007;88(1):240-3.

  5. Kort DH, Lobo RA. Preliminary evidence that cinnamon improves menstrual cyclicity in women with polycystic ovary syndrome: a randomized controlled trial. Am J Obstet Gynecol. 2014;211(5):487 e1-6.

  6. Borzoei A, Rafraf M, Niromanesh S, Farzadi L, Narimani F, Doostan F. Effects of cinnamon supplementation on antioxidant status and serum lipids in women with polycystic ovary syndrome. J Tradit Complement Med. 2018;8(1):128-33.

  7. Nestler JE JD, Reamer P, Gunn,  Allan G. Ovulatory and Metabolic Effects of d-Chiro-Inositol in the Polycystic Ovary Syndrome. NEJM. 1999;340:1314-20.

  8. Unfer V. Myo-inositol rather than D-chiro-inositol is able to improve oocyte quality in intracytoplasmic sperm injection cycles. A prospective, controlled, randomized trial. Eur Rev Med Pharmacol Sci. 2011;15(4):452-7.

  9. Artini PG, Di Berardino OM, Papini F, Genazzani AD, Simi G, Ruggiero M, et al. Endocrine and clinical effects of myo-inositol administration in polycystic ovary syndrome. A randomized study. Gynecol Endocrinol. 2013;29(4):375-9.

  10. Jamilian M. et al. Comparison of myo-inositol and metformin on clinical, metabolic and genetic parameters in polycystic ovary syndrome: A randomized controlled clinical trial. Clin Endocrinol (Oxf). 2017;87:194-200.

  11. Jamilian M. et al. Comparison of myo-inositol and metformin on mental health parameters and biomarkers of oxidative stress in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial. J Psychosom Obstet Gynaecol. 2018;39:307-314.

  12. Benelli E, Del Ghianda S, Di Cosmo C, Tonacchera M. A Combined Therapy with Myo-Inositol and D-Chiro-Inositol Improves Endocrine Parameters and Insulin Resistance in PCOS Young Overweight Women. Int J Endocrinol. 2016;2016:3204083.

  13. Unfer V, Facchinetti F, Orru B, Giordani B, Nestler J. Myo-inositol effects in women with PCOS: a meta-analysis of randomized controlled trials. Endocr Connect. 2017;6(8):647-58.

  14. Park SK, et al. Plasa 25-hydroxyvitamin D concentration and risk of type 2 diabetes and pre-diabetes: 12 year cohort study. PLOS One. https://doi.org/10.1371/journal.pone.0193070

  15. Butts SF SD, Koelper N, Senapati S, Sammel MD, Hoofnagle AN, Kelly A, Krawetz SA, Santoro N, Zhang H, Diamond MP, Legro Rs. Vitamin D Deficiency is Associated with Poor Ovarian Stimulation Outcome in PCOS but not Unexplained Infertility. J Clin Endocrinol Metab. 2018.

  16. Raja-Khan N, Shah J, Stetter CM, Lott ME, Kunselman AR, Dodson WC, et al. High-dose vitamin D supplementation and measures of insulin sensitivity in polycystic ovary syndrome: a randomized, controlled pilot trial. Fertil Steril. 2014;101(6):1740-6.

  17. Maktabi M, Chamani M, Asemi Z. The Effects of Vitamin D Supplementation on Metabolic Status of Patients with Polycystic Ovary Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial. Horm Metab Res. 2017;49(7):493-8.

  18. Thomson RL, Spedding S, Brinkworth GD, Noakes M, Buckley JD. Seasonal effects on vitamin D status influence outcomes of lifestyle intervention in overweight and obese women with polycystic ovary syndrome. Fertil Steril. 2013;99(6):1779-85.

  19. Shen M. A second look at the ancient drug: new insights into metformin. Ann Transl Med. 2014;2(6):51.

  20. Legro RS. et al. Clomiphene, metformin or both for infertility in the polycystic ovary syndrome. N Engl J Med 2007;356:551-566.

  21. Legro RS. et al. Letrozole versus clomiphene for infertility in the polycystic ovary syndrome. N Engl J Med 2014;371:119-29.

  22. Teede et al. Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Fertil Steril. 2018;110:364-379.

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