American Diabetes Awareness Month
Insulin Resistance in Adolescents with Menstrual Irregularities
By: Janice Prescod, DO
Editor’s Note: As we conclude American Diabetes Awareness Month, we are featuring a 2005 research study published in the Journal of Pediatric and Adolescent Gynecology. Janice Prescod, a former FACTS elective participant, summarized the research that established a link between insulin resistance and irregular menstrual irregularities. Since 2018, more than 700 students have completed our FACTS elective, expanding their knowledge of fertility awareness-based methods, but we cannot do this work without you. With your support this Giving Tuesday, we can impact even more lives, so please make a contribution today, so we can give the gift of knowledge. Thank you!
Introduction
For female adolescents, going through puberty can be a challenging experience. Menarche, or the start of menstruation, is marked by physical changes in appearance and may indicate the start of fertility. Following the onset of menarche, many adolescents present with anovulatory and irregular menstruation because of the immature hypothalamus-pituitary-ovarian (HPO) axis. [1] This process usually normalizes after the first two years.
“Following the onset of menarche, many adolescents present with anovulatory and irregular menstruation because of the immature hypothalamus-pituitary-ovarian (HPO) axis.”
In some adolescents, irregular menstrual cycles persist beyond the first two years of menarche, usually associated with pathological issues causing ovarian dysfunction.[2] A study by Fernandes et al. examined the incidence of polycystic ovarian syndrome (PCOS) and insulin resistance in adolescents with persistent menstrual disorders. [2] Using a case-control study, they determined that 95% of the adolescents with menstrual irregularities have PCOS and have quantifiably higher levels of insulin compared to adolescents with regular menstrual cycles.
Methodology
Thirty-four adolescents aged 12 to 18 participated in this case-control study. All participants were 2 to 4 years post-menarche and presented to the clinic for routine examinations. The researchers classified participants into two groups: 22 adolescents with a history of either oligomenorrhea, amenorrhea or polymenorrhea and 12 control participants with regular menstrual cycles. Clinical hyperandrogenism was assessed using a Ferriman-Gallway index — a score of eight or more was consistent with hyperandrogenism. A diagnosis of PCOS was given when a patient had oligomenorrhea (less than six menstrual cycles a year) or amenorrhea and signs of clinical and/or laboratory hyperandrogenism.
Testosterone, dehydroepiandrostenedione sulfate (DHEA-S), and 17-hydroxyprogesterone levels were tested to assess hyperandrogenism. Researchers also obtained fasting blood glucose, insulin levels, and post-oral glucose tolerance tests with 75g of dextrose at 30-minute intervals for 120 minutes. Prolactin, thyroid-stimulating hormone (TSH), and thyroid levels were also obtained to exclude any other potential causes of anovulation. Additionally, luteinizing hormone (LH) and follicular stimulating hormone (FSH) were collected, as the LH/FSH ratio can be elevated in patients with PCOS. Finally, transabdominal pelvic ultrasounds or transvaginal ultrasounds during the follicular phase were performed to determine the physical morphology of the ovaries.
All the collected data were analyzed using the Mann-Whitney test for control and case groups. Researchers set the statistical significance at p <0.05.
Results
Researchers observed no statistically significant differences in 17-hydroxyprogesterone, prolactin, TSH, LH and FSH hormone levels between the two groups of participants. Interestingly, they did observe some differences in androgen levels between groups. Both groups fell within normal levels of DHEA-S and testosterone, but in the first group — the patients with menstrual irregularities — showed a higher mean value than the control group. These adolescents also had greater ovarian volume in both ovaries compared to the control patients with regular menstrual cycles. Using measured insulin and glucose levels, the area below the curve was calculated to determine overall glucose intolerance. No statistically significant changes in glucose levels were observed between groups. However, the insulin levels under the curve were higher in the first group, indicating higher insulin resistance among adolescents with menstrual irregularities.
“The insulin levels … were higher in the first group, indicating higher insulin resistance among adolescents with menstrual irregularities.”
Discussion
This research is highly relevant to women’s health, especially for young females, as PCOS is one of the leading causes of menstrual irregularities and fertility issues. [3] Patients with PCOS are also at risk for additional health concerns, including insulin resistance and type II diabetes. [3] Prompt identification of these patients, especially in adolescence, has the potential to improve future health outcomes. Awareness of cycle irregularities can be further facilitated by introducing girls to fertility awareness-based methods (FABMs). Teaching adolescents to chart their cycles and grow familiar with the normal patterns of their bodies’ natural biomarkers enables trained educators and medical professionals to help identify abnormalities and pursue early treatment.
Previous studies investigating menstrual irregularities have demonstrated that adolescent girls with PCOS may experience profound metabolic derangements. [4] This study by Fernandes et al. confirmed these prior observations, evidenced by insulin resistance in adolescents with PCOS, and confirmed the diagnosis in those with documented prolonged menstrual irregularities.
The study also provides guidelines for medical professionals, suggesting that an adolescent patient two years post-menarche with persistent irregular menstrual cycles warrants further workup. These patients will likely have a higher incidence of PCOS and insulin resistance and it is important not to immediately attribute these irregularities to the immaturity of the HPO axis, but to thoroughly investigate potential underlying pathologies.
“The study also provides guidelines for medical professionals, suggesting that an adolescent patient two years post-menarche with persistent irregular menstrual cycles warrants further workup.”
The present study is an excellent preliminary investigation demonstrating a correlation between menstrual irregularities and insulin resistance in adolescents. However, it has several limitations hampering the generalizability of the findings, including a small sample size. Additionally, study participants were recruited from patients of two clinics in Brazil, which may impact the ability to extrapolate findings to a broader population. Finally, the researchers mention that several confounding factors were not controlled for, including family history of PCOS and early pubarche in ethnic groups of Hispanic or African descent. Genetic predisposition and environmental factors may increase the incidence of polycystic ovaries without increasing androgen levels, warranting the need for future studies among more diverse populations that also control for other variables Additional research within this population will facilitate better understanding of the early incidence of PCOS and underlying causes of menstrual irregularities.
Sources
[1] van Hooff, M., Voorhorst, F., Kaptein, M., Hirasing, R., Koppenaal, C. and Schoemaker, J., 1998. Relationship of the menstrual cycle pattern in 14-17 year old old adolescents with gynaecological age, body mass index and historical parameters. Human Reproduction, 13(8), pp.2252-2260.
[2] Fernandes, A., de Sá Rosa e Silva, A., Romão, G., Pata, M. and dos Reis, R., 2005. Insulin Resistance in Adolescents with Menstrual Irregularities. Journal of Pediatric and Adolescent Gynecology, 18(4), pp.269-274.
[3] Bellver, J., Rodríguez-Tabernero, L., Robles, A., Muñoz, E., Martínez, F., Landeras, J., García-Velasco, J., Fontes, J., Álvarez, M., Álvarez, C. and Acevedo, B., 2017. Polycystic ovary syndrome throughout a woman’s life. Journal of Assisted Reproduction and Genetics, 35(1), pp.25-39.
[4] Lewy, V., Danadian, K., Witchel, S. and Arslanian, S., 2001. Early metabolic abnormalities in adolescent girls with polycystic ovarian syndrome. The Journal of Pediatrics, 138(1), pp.38-44.
ABOUT THE AUTHOR
Janice Prescod, DO
Janice Prescod, DO is a pediatric resident at Children’s Hospital of Michigan in Detroit, Michigan. She graduated from Michigan State University College of Osteopathic medicine where she participated in the online FACTS course as a medical student. Janice is interested in social determinants of health and advocacy. She completed the FACTS elective to learn more about FABMs and ways to support adolescent patients and their families.
