PCOS Awareness Month

Insulin Resistance in Women with PCOS: A Review of Research

By: Brea Deyette, DO

Director’s Note: Although insulin resistance is not one of the diagnostic criteria for polycystic ovary syndrome (PCOS), it affects many women with PCOS. September is PCOS Awareness Month, and the research we feature today addresses metabolic implications as well as potential subtypes of this common disorder. Dr. Brea Deyette, a former FACTS elective participant, summarized the study titled, “Evidence of Subpopulations with Different Levels of Insulin Resistance in Women with Polycystic Ovary Syndrome.” [10] It was published by Vigil et al in Human Reproduction. The lead author, Dr. Pilar Vigil, is a prominent researcher in restorative reproductive medicine and a speaker at our virtual conference in October. Learn more about her approach to diagnosis and management of irregular cycles on Saturday, October 19, 2024. Follow the link to see the full schedule and register today!

Polycystic ovary syndrome (PCOS) is an endocrine-metabolic condition associated with multiple comorbidities and commonly diagnosed using the Rotterdam criteria. The criteria require 2 of 3 conditions: hyperandrogenism (identified on physical exam or via laboratory values), menstrual irregularities, and/or polycystic ovaries on ultrasonography that meet specific size and cystic number criteria. [1] The prevalence of PCOS is about 5-10% in women of reproductive age. [2]

[3][4][5]6]Common features of PCOS include insulin resistance, increased ovarian and adrenal androgens, hyperandrogenic symptoms, and menstrual irregularity. Insulin resistance is the decreased sensitivity to insulin and the ability to use glucose for energy in the body. This can cause weight gain and affect a woman’s hormonal regulation.

“Common features of PCOS include insulin resistance, increased ovarian and adrenal androgens, hyperandrogenic symptoms, and menstrual irregularity.”

Though insulin resistance is not part of the diagnostic criteria for PCOS, previous studies have found insulin resistance in as few as 30% and as many as 76% of cases of PCOS. [3][7][8] We know insulin resistance is part of the process that may lead to diabetes; it was first linked to PCOS in the 1980s. [9]

Glucose tolerance and insulin sensitivity deteriorate with age, but this study sought to identify the magnitude and prevalence of insulin resistance in the PCOS population. [10] To that end, Vigil et al studied 69 Hispanic Chilean women who had previously been diagnosed with PCOS based on the Rotterdam criteria and had additional screening to rule out other diseases that can mimic PCOS.

Methodology

This study measured androgen hormones such as testosterone, sex hormone-binding globulin (SHBG), and dehydroepiandrosterone sulfate (DHEA-S) using immunoassays. Insulin resistance was measured via insulin sensitivity testing (IST) modified by octreotide, a synthetic form of the hormone somatostatin. Like somatostatin, octreotide suppresses endogenous insulin. With endogenous insulin suppressed using the octreotide-modified IST and a constant infusion given of glucose and exogenous insulin, they determined the insulin-mediated glucose uptake. The researchers measured the patients’ serum glucose levels every 30 minutes and then every 10 minutes for a total of 180 minutes.

Results

The average age of participants was 26 years old, ranging from age 14 to 42 years. The average body mass index (BMI) was 25 with a range from 18 to 38 (BMI < 25 in 55%, 25-30 in 25%, and > 30 in 19%).

The average total testosterone level among participants was normal at 2.76 nmol/L (range 1.35-6.69). The average fasting glucose level before insulin sensitivity testing was conducted was normal at 96 mg/dL (range 75-116). Fasting glucose levels correlated with age and had a normal distribution with no significant difference in this group compared to the normal population.

The steady state plasma glucose (SSPG) was calculated as the average of the last 4 plasma concentrations taken (at 150, 160, 170, and 180 minutes). This was used to show how the participants were utilizing the exogenous insulin and glucose being infused, and how this compared to the normal population. These values were found to be similar to non-diabetic Caucasian North American populations, though the distribution was discontinuous and multimodal. There was no significant difference between the study population and the normal population, but the study population showed three clusters of results which were significantly different. When accounting for variables such as age, BMI, and testosterone, SSPG showed a positive correlation only with BMI.

“When accounting for variables such as age, BMI, and testosterone, steady state plasma glucose showed a positive correlation only with BMI.”

Due to the three distinct clusters of SSPG found at 180 minutes, the study population was separated for analysis. Group 1 included 33 participants with an SSPG ≤ 152.5 mg/dL. This is typical within a population of non-insulin resistant individuals. Group 2 included 29 participants with an SSPG ranging from 152.5 to 300 mg/dL. Group 3 included 7 participants with an SSPG above 300 mg/dL. Among the subpopulations, BMI was the only significant variable.

Discussion

Based on the SSPG, which was being used to monitor glucose utilization and insulin sensitivity, a large portion of the studied population did not have insulin resistance. More than 47% of participants, which made up group 1, did not show insulin resistance. Another important finding was the discovery of at least three subpopulations within this PCOS population showing different patterns of insulin resistance. Yet, BMI was the only variable showing a significant difference between the subgroups and the SSPG, which would be the case in a normal population as well.

This study only observed 69 women, all of whom were located in Chile, which is a limitation when trying to generalize to women all over the world. The age range was wide, which serves as a strength in evaluating women aged 14 to 42. This study also referenced a 2001 research paper, citing obesity within PCOS populations is geographically distributed; this may change the distribution of BMI in a replicated study in a different region. [11]

Based on the study findings, approximately 53% of participants had insulin resistance, which is known to cause weight gain and difficulty losing weight. However, only 44% of the study population was considered overweight based on BMI, and only 13.2% of participants had a BMI considered medically obese (BMI ≥ 30). It is likely many of these women did not know they had insulin resistance or had overt symptoms of it. They would all benefit from knowing they have insulin resistance and learning about lifestyle and medical interventions to regulate their hormones and prevent complications that could impact their fertility, family planning, and overall health.

“Approximately 53% of participants had insulin resistance… However, only 44% of the study population was considered overweight based on BMI.”

A susceptibility gene region for PCOS that regulates adrenal and androgen biosynthesis has been identified on chromosome 19p13.2. [12]Insulin resistance in the general population is understood to be consistent with a genetic defect within the insulin signal transduction pathway. This research may reveal a need for genetic testing in relation to insulin resistance within PCOS, as it may also have a genetic predisposition unique to patients with PCOS.

The study designers believe the subpopulations discovered in this paper may suggest a genetic subpopulation or subphenotype within the PCOS population. For women with PCOS, genetic identification may help identify proper treatment and other possible comorbidities linked to this chromosome. This may offer solutions for women with infertility due to PCOS beyond improving their overall health.

References

[1] Rotterdam ESHRE/ASRM-Sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 2004a;19: 41–47. doi:10.1016/s0010-7824(97)00040-1.
[2] Franks S. Polycystic ovary syndrome. N Engl J Med 1995;333:853–861.
[3] Dunaif A. Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr Rev 1997;18:774–800.
[4] Morin-Papunen L. Insulin resistance in polycystic ovary syndrome. Acta Univ Oul 2000;D605:1–89.
[5] Benítez R, Sir-Petermann T, Palomino A, Ángel B, Maliqueo M, Pérez F, Calvillán M. Prevalencia familiar de patologías metabólicas en pacientes con síndrome de ovario poliquístico. Rev Méd Chile 2001;129:707–712.
[6] Biro FM. Body morphology and its impacts on adolescent and pediatric gynecology, with a special emphasis on polycystic ovary syndrome. Curr Opin Obstet Gynecol 2003;15:347–351.
[7] Carmina E, Koyama T, Chang L, Stanczyk FZ, Lobo RA. Does ethnicity influence the prevalence of adrenal hyperandrogenism and insulin resistance in polycystic ovary syndrome? Am J Obstet Gynecol 1992;167:1807–1812.
[8] del Río MJ, Ramírez JP, Cortés ME, Martí G, Godoy A, Vigil P. Análisis de resistencia insulínica, tolerancia a la glucosa y testosterona en mujeres jóvenes con síndrome de ovario poliquístico agrupadas por índice de masa corporal. Rev Chil Obstet Ginecol 2006;71:299–306.
[9] Burghen GA, Givens JR, Kitabchi AE. Correlation of hyperandrogenism with hyperinsulinism in polycystic ovarian disease. J Clin Endocrinol Metab 1980;50:113–116.
[10] Vigil P, Contreras P, Alvarado JL, Godoy A, Salgado AM, Cortés ME. Evidence of subpopulations with different levels of insulin resistance in women with polycystic ovary syndrome. Hum Reprod. 2007;22(11):2974-2980. doi:10.1093/humrep/dem302
[11] Hoeger K. Obesity and weight loss in polycystic ovary syndrome. Obstet Gynecol Clin North Am 2001;28:85–97.
[12] Urbanek M, Woodroffe A, Ewens KG, Diamanti-Kandarakis E, Legro RS, Strauss JF, Dunaif A, Spielman RS. Candidate gene region for polycystic ovary syndrome on chromosome 19p13.2. J Clin Endocrinol Metab 2005;90:6623–6629.

ABOUT THE AUTHOR

Brea Deyette, DO

Brea Deyette, DO is a pathology resident at Emory University in Atlanta, GA. She earned her medical degree from Philadelphia College of Osteopathic Medicine Georgia, and completed her undergraduate and Master of Public Health degrees at Georgia State University. She is passionate about women’s health, patient advocacy, and education. As a medical student, she enrolled in the FACTS elective to gain a better understanding of natural family planning methods and ways to share them to educate and empower others and help further medical research in women’s health.

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