Polycystic Ovarian Syndrome Awareness Month
Myo-inositol for PCOS: Summary of a Systematic Review
By: Sarin Sajan Itty, DO
Director’s Note:
To mark the beginning of Polycystic Ovary Syndrome (PCOS) Awareness Month this September, we are featuring research that explores the applications of myo-inositol (MYO) for women with PCOS. Dr. Sarin Itty, a former FACTS elective participant, shares from her personal experience with a PCOS diagnosis in her summary of a review published in Gynecological Endocrinology.[1] The summary highlights the implications of MYO to improve issues ranging from insulin sensitivity to hormone optimization to oocyte quality. Beyond applications for PCOS, Itty notes the need for further research on long-term health outcomes of myo-inositol supplementation to prevent other metabolic diseases.
Introduction
According to the Centers for Disease Control and Prevention (CDC), PCOS is one of the leading causes of female infertility, affecting 6-12% of U.S. women (nearly five million women) of reproductive age.[2] While the exact cause of PCOS is unknown, women with PCOS have higher than normal androgen levels and insulin resistance. They tend to have a family history of PCOS or type 2 diabetes as well, with over half of women with PCOS developing diabetes by age 40.[2]
“Polycystic Ovary Syndrome or PCOS is one of the leading causes of female infertility, affecting 6-12% of U.S. women (nearly five million women) of reproductive age.”
Signs of PCOS include acne, hair growth, weight gain, darkening of the skin around folds/creases of the body (acanthosis nigricans) and irregular periods.[2] [3] PCOS is diagnosed with two out of three features: multiple small cysts in the ovaries, irregular or absent periods, and excess androgens, which may lead to acne, thinning of scalp hair, and excessive hair growth on the face. Although there is an association between PCOS and being overweight, PCOS can affect patients with lean bodies as well.[2]
Insulin resistance plays a key role in PCOS; losing weight and increasing physical activity can lower the risk of developing diabetes.[1][4] Metformin, a drug which increases insulin sensitivity, is useful in treating patients with hyperinsulinism in PCOS. Inositols such as myo-inositol (MYO) have been increasingly used as a safe and effective alternative in PCOS management.[1][4] Below is the summary of a 2012 article[1] published in Gynecological Endocrinology titled, “Effects of Myo-inositol in Women with PCOS: A Systematic Review of Randomized Controlled Trials.” Unfer et al provide an overview of clinical outcomes of myo-inositol to improve ovarian function as well as metabolic and hormonal markers in women with PCOS.[1]
Methodology
In 2010, Unfer et al conducted a systematic literature search of databases including Medline, Amed, and The Cochrane Library. Only randomized clinical trials (RCTs) from January 1999 to November 2010 were included, using the following search terms: “myo-inositol,” “inositol,” “polycystic ovary syndrome,” “ovarian stimulation,” “in vitro fertilization,” “ovarian function,” and “insulin resistance.”[1] There were no language restrictions. Studies investigating other drugs in combination with myo-inositol, in vitro studies, and animal studies were excluded.[1] Additional papers were identified by manually searching reference lists of recent systematic reviews.
Results
A total of 70 studies were initially identified and further narrowed to 21 trials discussing myo-inositol treatment in women with PCOS. Of these, only six studies were RCTs that met the selection criteria. Four of these studies evaluated the effect of MYO on hormonal levels while the other two studies evaluated its effect on oocyte quality and ovarian function improvement.[4] One paper was excluded from the discussion section because the patients were treated with a multivitamin complex.
The Genazzani et al study recruited 20 PCOS patients: 5 had amenorrhea and 15 were oligomenorrheic.[1][5] Ten patients were treated daily with 2g of myo-inositol plus 200µg folic acid while the control group received only folic acid. After treatment, consistent changes were seen in the treatment group in the endocrine profile, which was evaluated on day 7 of the first menstrual cycle after 10-12 weeks of treatment; plasma luteinizing hormone (LH), prolactin, LH:FSH ratio, and insulin levels were decreased significantly. The homeostatic model assessment (HOMA) score for insulin resistance was also reduced while the index of insulin sensitivity glucose/insulin ratio increased significantly.[1] [5]The patients treated with MYO had normal menstrual cycles restored while the control group remained oligomenorrheic throughout the study.
The Costantino et al study recruited 42 patients; 23 received 2g MYO and 200 µg folic acid twice a day while 19 received 400 µg of folic acid.[1][6] Four patients in the MYO group and three in the control group had impaired glucose tolerance. Patients treated with MYO had a reduction in systolic and diastolic blood pressure values and lower plasma triglycerides and total cholesterol.[1][6]Insulin sensitivity significantly increased for the treatment group.[1][6]Ovulation was restored in 70% (n=16) of the women in the MYO group and 21% (n=4) of the control group; after treatment, progesterone peak was higher in the MYO group, with a significant reduction in total serum and free testosterone and an increase in sex hormone binding globulin.[6]
The Papaleo et al study enrolled sixty women to evaluate the effect of MYO on oocyte quality and the ovarian stimulation protocol. Half of them received MYO 2g plus 200µg folic acid twice a day while the other half (the control group) only received folic acid.[1][7] In the treatment group, the total recombinant FSH and number of stimulation days were significantly reduced, and estradiol (E2) levels after HCG administration were significantly lower, resulting in a significantly lower number of canceled cycles.[1][7]In the MYO group, the number of immature oocytes and degenerated oocytes was also significantly reduced.[1][7]
The Gerli et al study recruited 92 patients to assess MYO’s impact on ovarian/metabolic factors; 42 patients were interested in conceiving. Forty-five women received 2g MYO with 200µg folic acid twice daily, while 47 patients received 400µg folic acid as placebo.[1][8] In the placebo group, 1 out of 19 conceived while in the MYO group, 4 out of 23 conceived. Eight of the 45 women in the treatment group failed to ovulate compared to 17 of 47 patients in the placebo group.[1][8] The MYO group had a significant increase in E2 levels (p = 0.03) and a significant decrease in BMI (p = 0.04); furthermore, LDL trended towards reduction while HDL levels were significantly increased in the MYO group.[1][8]
The Rafone et al study enrolled 120 women to compare the effects of metformin vs. MYO on patients with PCOS. Sixty patients were treated with metformin 1500mg/day while 60 patients received MYO 4g plus 400µg folic acid.[1][9] In the metformin group, spontaneous ovulation was restored in 50%, with ovulation occurring at a mean of 16.7 days into the menstrual cycle; however, 7 patients dropped out due to side effects.[1][9] In the MYO group, 65% of the patients restored spontaneous ovulation activity with ovulation occurring at a mean of 14.8 days into the cycle. There was a significant difference in time for ovulation between metformin and MYO groups (p< 0.003).[1][9]
Discussion
Myo-inositol plays an important role in follicular oocyte development by mediating calcium release and supporting quality oocytes.[1][4] It also influences glucose metabolism as well as FSH and insulin signaling.[4][10]Myo-inositol can be used to treat insulin resistance, metabolic syndrome, PCOS, and gestational diabetes; it inhibits duodenal glucose absorption and reduces blood glucose elevations while also increasing muscle glucose uptake.[10][11]
From the Unfer et al systematic review, it is evident myo-inositol improves oocyte maturation, pregnancy rates, and hormonal parameters; improvements in total cholesterol, HDL, BMI, and the glucose:insulin ratio were also reported.[1] This is relevant because myo-inositol can lead to marked improvement in the health and symptoms of patients with PCOS. Interestingly, no side effects of myoinositol at 2g and 4g were reported in any of the studies in the systematic review, which also demonstrated high patient compliance in the MYO group, whereas the metformin group lost patients due to side effects.[1][9]
“Myo-inositol improves oocyte maturation, pregnancy rates, and hormonal parameters (as well as) total cholesterol, HDL, BMI, and the glucose:insulin ratio.”
Strengths of this systematic review include similar outcomes for the multiple studies, which further consolidates the beneficial role of myo-inositol in patients with PCOS. Limiting factors include the relatively small sample sizes for the RCTs and the reduced number of databases included within the literature search. The RCT exclusion criteria may decrease the internal validity of the research.
For patients with PCOS, there are multiple advantages to using MYO, including hormonal, metabolic, and reproductive health benefits. Myo-inositol even improved the pregnancy rate slightly more than metformin and, on average, induced ovulation earlier in the cycle.[1] As a woman diagnosed with PCOS, I had never heard of myo-inositol for PCOS treatment until taking the FACTS elective course. Based upon the research I have completed, I am considering myo-inositol to improve my PCOS symptoms. Still, these research studies should be repeated on a much larger scale to solidify the outcomes. Additionally, it would be interesting to explore the longer-term health outcomes of myo-inositol supplementation and its potential use to prevent diabetes, metabolic syndrome, and similar conditions.
“For patients with PCOS, there are multiple advantages to using myo-inositol, including hormonal, metabolic, and reproductive health benefits. Myo-inositol even improved the pregnancy rate … and induced ovulation earlier in the cycle.”
References
[1] Unfer, V., Carlomagno, G., Dante, G., & Facchinetti, F. (2012). Effects of myo-inositol in women with PCOS: A systematic review of randomized controlled trials. Gynecological Endocrinology, 28(7), 509–515. https://doi.org/10.3109/09513590.2011.650660.
[2] Centers for Disease Control and Prevention. (2020, March 24). PCOS (polycystic ovary syndrome) and diabetes. Centers for Disease Control and Prevention. Retrieved September 8, 2022, from https://www.cdc.gov/diabetes/basics/pcos.html.
[3] Barbieri, R., & Ehrmann, MD (2022). Diagnosis of polycystic ovary syndrome. In J. UpToDate. Retrieved September 7, 2022, from https://www-uptodate.com/contents/diagnosis-of-polycystic-ovary-syndrome-in-adults.
[4] Monastra, G., Unfer, V., Harrath, A. H., & Bizzarri, M. (2017). Combining treatment with myo-inositol and D -chiro-inositol (40:1) is effective in restoring ovary function and metabolic balance in PCOS patients. Gynecological Endocrinology, 33(1), 1–9. https://doiorg.ezproxylocal.library.nova.edu/10.1080/09513590.2016.1247797
[5] Genazzani AD, Lanzoni C, Ricchieri F, Jasonni VM. (2008). Myo-inositol administration positively afects hyperinsulinemia and hormonal parameters in overweight patients with polycystic ovary syndrome. Gynecol Endocrinol 2008;24:139–14.
[6] Costantino D, Minozzi G, Minozzi E, Guaraldi C. (2009) Metabolic and hormonal effects of myo-inositol in women with polycystic ovary syndrome: a double-blind trial. Eur Rev Med Pharmacol Sci 2009;13:105–110.
[7] Papaleo E, Unfer V, Baillargeon JP, Fusi F, Occhi F, De Santis L. (2009). Myo-inositol may improve oocyte quality in intracytoplasmic sperm injection cycles. A prospective, controlled, randomized trial. Fertil Steril 2009;91:1750–1754.
[8] Gerli S, Mignosa M, Di Renzo GC. (2003). Effects of inositol on ovarian function and metabolic factors in women with PCOS: a randomized double blind placebo-controlled trial. Eur Rev Med Pharmacol Sci 2003;7:151–159.
[9] Rafone E, Rizzo P, Benedetto V. (2010). Insulin sensitiser agents alone and in co-treatment with r-FSH for ovulation induction in PCOS women. Gynecol Endocrinol 2010;26:275–2.
[10] DiNicolantonio JJ, H O’Keefe J. (2022). Myo-inositol for insulin resistance, metabolic syndrome, polycystic ovary syndrome and gestational diabetes Open Heart 2022;9:e001989. doi: 10.1136/openhrt-2022-001989.
[11] Chukwuma CI, Ibrahim MA, Islam MS. (2016). Myo-inositol inhibits intestinal glucose absorption and promotes muscle glucose uptake: a dual approach study. J Physiol Biochem 2016;72:791–801.doi:10.1007/s13105-016-0517-1.
[12] Merviel, P., James, P., Bouée, S. et al. (2021). Impact of myo-inositol treatment in women with polycystic ovary syndrome in assisted reproductive technologies. Reprod Health 18, 13 https://doi.org/10.1186/s12978-021-01073-3.
[13] Kamenov Z, Gateva A. Inositols in PCOS. Molecules. (2020). Nov 27;25(23):5566. doi: 10.3390/molecules25235566. PMID: 33260918; PMCID: PMC7729761.
ABOUT THE AUTHOR
Sarin Sajan Itty, DO
Sarin Sajan Itty, DO is a family medicine resident at the Institute for Family Health. She graduated from Nova Southeastern University Kiran Patel College of Osteopathic Medicine in Fort Lauderdale, Florida. Dr. Itty chose this topic due to her interest in women’s health. She enrolled in the FACTS elective to understand various natural family planning methods better to benefit her future patients.
