table of contents
- Insulin, inositols, and fertility
- What do we know about myo-inositol and people who have PCOS?
- What do we know about myo-inositol and people who don’t have PCOS?
- What do we know about myo-inositol and people with sperm?
- Why are there so many different myo-inositol supplements?
- How do you know if a myo-inositol supplement could work for you?
- The bottom line on inositol supplements for people without PCOS
If you have any medical questions or concerns, please talk to your healthcare provider. The articles on Health Guide are underpinned by peer-reviewed research and information drawn from medical societies and governmental agencies. However, they are not a substitute for professional medical advice, diagnosis, or treatment.
Many non-prescription supplements claim to have magical effects on fertility and reproductive health, in part because the claims that supplement manufacturers make do not need to get vetted by the FDA. But there’s one supplement that stands out as a promising exception, with a growing body of work suggesting its effects: a group of insulin-sensitizing compounds called inositols (like myo-inositol).
Inositols have been studied in the context of insulin resistance and polycystic ovary syndrome (PCOS), and have a decent track record when it comes to regulating ovulation and altering reproductive hormone levels. Contrary to how these supplements are marketed, there’s no proof that they’re effective for everyone. What we do know so far: Inositols may help regulate ovulation and hormone levels in people with PCOS and insulin sensitivity; but even in these cases, there are more effective prescription-based medications that doctors consider as first-line treatments. If you’re someone without PCOS and without insulin resistance, there’s no evidence, so far, that inositols will boost fertility in the context of unassisted reproduction — and any evidence that they positively affect outcomes in assisted reproduction should be considered preliminary.
Want a reproductive endocrinologist’s take? Dr. Eduardo Hariton, MD, MBA, a board-certified OB-GYN and reproductive endocrinology and infertility fellow at the University of California in San Francisco, agrees that the data isn’t quite there yet to support clear benefits of myo-inositol for people without PCOS. “There is an exciting body of data growing and maybe we will find that there are benefits. But we need better and larger studies first,” he explains. “We have to be cautious to not generalize the benefits seen in PCOS patients to groups where no benefit has been proven.”
In this article, we’ll go over what the science does and doesn’t say about the use of inositols for fertility and reproductive health.
Insulin, inositols, and fertility
Hormones are able to affect a wide range of physical functions because they’re able to travel throughout the body (this is part of what makes endocrinology, the study of hormones, so complex and cool!). Insulin, a hormone made in the pancreas, is released in the bloodstream to help either turn sugar into energy that can be immediately used or store it so it can be used later. When someone is insulin-resistant, it means their cells aren’t responding in the same way to insulin in the bloodstream — and the pancreas produces more and more insulin to try and compensate and regulate glucose levels.
(Think of insulin-resistance like a gas pedal: If you push down on the pedal and the car doesn’t start moving, you’ll likely try pushing down on the pedal even harder to compensate. Your body producing more insulin is the equivalent of you increasingly pushing harder on the gas pedal.)
What does this have to do with fertility and reproductive health exactly? Insulin has an interconnected relationship with important reproductive hormones and proteins:
- Insulin receptors are found on cells in the ovary, meaning they’re capable of altering processes related to reproductive health and fertility. Specifically, insulin can result in ovaries producing higher-than-average levels of the androgen (aka “male” sex hormone) testosterone, which is a hallmark feature of polycystic ovary syndrome (PCOS).
- Insulin also plays a role in the production of sex hormone binding globulin (SHBG) — as insulin levels go up, SHBG levels go down. SHBG binds to hormones in the bloodstream, effectively making them unable to cause any physiological change. When SHBG levels are lower, which can happen due to higher insulin levels, the fraction of unbound androgens is higher so there is relatively more free hormone able to to float around and act on different parts of the body. Increased activity of androgens can exacerbate the androgen-related symptoms of PCOS.
Several prescription medications can swoop in and help reduce levels of insulin resistance:
- Insulin sensitizers: One of the most well-known and effective drugs in this class is metformin, most often prescribed for diabetes and sometimes for PCOS.
- Inositol-based supplements: Different types of inositols, like myo-inositol and d-chiro-inositol, have been proven to be effective in the context of diabetes and PCOS, and have similar physiological effects as metformin.
What do we know about myo-inositol and people who have PCOS?
Though there usually isn’t a ton of evidence about the effectiveness of non-FDA regulated compounds and supplements, myo-inositol stands out as an exception: There’s a growing body of peer-reviewed data (from individual studies, reviews, and meta-analyses) suggesting it can improve cycle regularity, ovulation, and hormone levels in the subset of people with PCOS who have high androgen levels and insulin resistance.
Here are a couple of spotlights from the existing data:
- A study of over 130 people with PCOS and insulin resistance found that people who were treated with myo-inositol were six times as likely to report regular menstrual cycles as compared to people who got the placebo. They also treated a third group with d-chiro-inositol, and found no differences between the myo-inositol and d-chiro-inositol groups.
- One study comparing ovulation frequency in people with PCOS who got treated with myo-inositol or placebo found that while 70% of people who got myo-inositol ovulated, only 21% of people in the placebo group did. People treated with myo-inositol also saw significant decreases in their testosterone levels. (An older study with a similar design found similar results when treating people with d-chiro-inositol.)
- A 2016 study put myo-inositol and metformin head-to-head, and found that the effects on menstrual cycle regularity were the same for these two treatments.
In short, the science behind myo-inositol, ovulation, and people with PCOS and insulin resistance is promising: Myo-inositol may help regulate ovulation and reproductive hormone levels. While the studies that have been published do suggest that myo-inositol may have positive effects, sample sizes here are still small — one of the most recent meta-analyses on the topic aggregated data from less than 400 people — meaning we need more data before being able to say anything with confidence.
Based on what’s been published so far, do inositols seem like a good option for people with PCOS and insulin resistance who are looking to regulate their cycles? According to Dr. Hariton, there’s no harm in trying it out for a few months and keeping close track of what happens to your cycles. If things don’t seem to be changing, though, it’s best to try out something like combined oral contraceptives, a hormonal IUD, or an implant. This is because there are health risks (like increased risk of endometrial cancer) to having anovulatory cycles and the unopposed estrogen levels that accompany them. Medications that contain progestins or affect the endometrium can be *key* in helping mitigate these risks. Talking to your doctor about your reproductive goals and symptoms is important to figure out which treatment options may be best for you.
While signs seem to be pointing to myo-inositol affecting ovulation and hormones in specific groups, there’s less evidence that taking myo-inositol could influence other aspects of fertility: Myo-inositol doesn’t seem to increase clinical pregnancy rates or live birth rates for people with PCOS in the context of unassisted conception, or in cases where assisted reproductive technology (ART) like in vitro fertilization (IVF) is used.
All of this said, the American Society of Reproductive Medicine (ASRM) still recommends more traditional fertility treatments like clomiphene citrate (Clomid) and letrozole (Femara) over metformin and inositol as first-line drug candidates for anovulation in people with PCOS.
What do we know about myo-inositol and people who don’t have PCOS?
Here’s where the science gets a little more sparse. While there’s data showing that myo-inositol can be helpful in regulating ovulation and hormone levels for a subset of people with PCOS, it isn’t as clear whether it can do the same for people who don’t have PCOS: There are no placebo-controlled studies we could find looking at whether myo-inositol increases ovulation regularity or changes hormone levels in people who don’t have PCOS. Similarly, there aren’t studies assessing whether time to pregnancy or pregnancy rates are influenced by myo-inositol supplementation among people who don’t have PCOS.
There are some *super preliminary* and limited-quality studies on the effects of myo-inositol in people who don’t have PCOS and are using ART:
- One study compared ART outcomes in people undergoing ovarian hyperstimulation procedures, and one group of participants got the usual hyperstimulation meds + folic acid + myo-inositol. Clinical pregnancy and implantation rates were comparable in both groups, but in the group that also got inositol, lower doses of the hyperstimulation meds were needed. The same outcomes with less hyperstimulation meds could suggest that myo-inositol had some positive effect on egg development, but the authors emphasized that follow-up studies are needed.
- A 2021 randomized controlled trial of 60 people classified as “poor ovarian responders” found that people who got myo-inositol along with their other hyperstimulation meds (like meds with hormones that signal the release of hormones from the ovaries or testes) had the same number of of eggs retrieved, number of embryos, and pregnancy rates. Only fertilization rates were higher in the myo-inositol group. We need a larger study to know if a difference exists but wasn’t detected because not enough people were included.
- A teeny-tiny study of people with infertility found some hints that myo-inositol supplementation could have antioxidant and anti-inflammatory effects, which some suggest may boost fertility. Though these initial findings are encouraging and merit further study, follow-up studies with more robust methods and larger sample sizes are required before really getting excited.
Though there’s no convincing data that myo-inositol can actually boost fertility in people without PCOS, some have tried it during pregnancy to improve insulin sensitivity. Data aggregated from 502 pregnant people across four trials suggests that myo-inositol supplementation is associated with a lower incidence of gestational diabetes, but the quality of the aggregated data is very low — better studies are needed before we can weigh in with confidence on this subject.
What do we know about myo-inositol and people with sperm?
Though most of the research on myo-inositol as a fertility supplement focuses on people with ovaries, there’s a growing body of work looking at the supplement as a way to boost fertility in people with sperm.
Several studies have noted improvements in metrics of sperm quantity and quality after people start taking myo-inositol, but any of these studies didn’t include a control group — which makes the results a bit harder to interpret. The exact mechanism by which myo-inositol would affect semen parameters isn’t crystal clear, but it’s possible that myo-inositol makes cells in the testes more sensitive to hormones like FSH, which also play a role in testicular sperm production.
Why are there so many different myo-inositol supplements?
Given the relatively small number of people who could benefit from myo-inositol supplementation (at least based on the data we currently have), there’s a surprisingly large number of myo-inositol supplements out there with general fertility claims. Because these are supplements, companies don’t have to provide the FDA with their own data that they can back up any of their claims — and when they do reference studies, they’re often ones conducted with people who have PCOS. What we’ve seen is that myo-inositol works for a subset of people with PCOS, but this doesn’t mean it’ll work for all people with PCOS, or for people who don’t have PCOS.
All of that said, there aren’t clear harms to taking myo-inositol — and its side effects are pretty mild (think things like fatigue and headaches at high doses). This means that even if myo-inositol supplementation won’t help everyone, it likely won’t hurt them either. But spending time and money on myo-inositol supplements may mean less time and money spent on other, more science-backed ways to boost ovulation regularity like clomiphene citrate and letrozole, which are the medications that ASRM recommends for everyone as first-line treatments over things like inositol and metformin. (Though you can take myo-inositol and clomiphene citrate or letrozole together.)
How do you know if a myo-inositol supplement could work for you?
Based on what we currently know about myo-inositol and fertility, there’s one group of people it could have significant benefit for: people with PCOS, insulin resistance, and high testosterone levels who aren’t ovulating regularly. To know whether you fall in this category, here are some proactive steps you can take:
- Check in on your reproductive hormone levels. PCOS is associated with differences in anti-Mullerian hormone (AMH), testosterone, and the ratio of follicle-stimulating hormone (FSH) to luteinizing hormone (LH). Getting a picture of your hormonal baseline is a good first step in understanding ovarian function.
- Track your LH to better understand ovulation. LH tests are the best at-home ways to determine whether you’re ovulating regularly. People with PCOS may see that they’re ovulating infrequently or not at all.
- Talk to a doctor about your hormone levels, menstrual and ovulatory patterns, and any other relevant data points or symptoms that may be related to reproductive health.
Again, it’s important to keep in mind that reproductive endocrinologists may not recommend a form of inositol as a first-line treatment to someone who’s hoping to ovulate more regularly. Though insulin-sensitizing agents may help regulate ovarian function in some people, when compared head-to-head with medications like clomiphene citrate, they aren’t as effective in promoting ovulation or pregnancy.
The bottom line on inositol supplements for people without PCOS
Inositol-based supplements are often marketed as being the key to “balancing” hormones, regulating ovulation, and promoting reproductive health. While it’s true that these supplements may impact hormone levels and regulate ovulation for a specific subset of people, they aren’t proven to work in all people, and in no subset of people are they more effective than prescription ovulation induction medications. There are no known harms of taking myo-inositol or other inositol-based supplements; that being said, if you’re experiencing any symptoms that lead you to thinking myo-inositol may be for you, it’s best to talk to a doctor first.
“I love when my patients read up and educate themselves so we can partner and find the best treatment for them. You can seek trusted sources like board-certified physicians, peer-reviewed studies (especially randomized controlled trials), or articles like this one from which have been reviewed by experts and cite their sources,” says Dr. Hariton. “That said, it is always wise to consult with your physician prior to starting any new treatment to make sure it’s the best option for you.”
For a deeper dive into the fertility medications that have *tons* of science backing them up, read up on the research here.
This article was reviewed by Dr. Eduardo Hariton, an OB-GYN and reproductive endocrinology and infertility fellow at the University of California in San Francisco.