National Adolescent Health Month
Implications of Teenage Menstrual, Hormonal, and Metabolic Dysfunction
By: Alyssa Heric
Director’s Note: May marks National Adolescent Health Month, and today we feature research summarized by Alyssa Heric, a medical student and former participant in the FACTS elective. The study authors identified a link between untreated oligomenorrhea and the onset of metabolic dysfunction.[1] Their research adds to the existing data that presents a strong case to educate young women about fertility awareness-based methods (FABMs) to identify menstrual abnormalities and prevent later diseases. This aligns with the ACOG recommendation that adolescent girls should learn to track their menstrual cycle as a vital sign of health.
Introduction
When oligomenorrhea persists for more than two years after the onset of menses, it often indicates dysfunction, such as androgen and estrogen imbalance or the presence of polycystic ovary syndrome (PCOS). Left untreated, the metabolic and hormonal disturbances associated with oligomenorrhea can be significant risk factors for the development of metabolic disease and obesity later in life. In this study, researchers assessed the relationship between childhood menstrual, hormonal, and metabolic irregularities and the development of metabolic syndrome and obesity in young adulthood.[1]
“Left untreated, the metabolic and hormonal disturbances associated with oligomenorrhea can be significant risk factors for the development of metabolic disease and obesity later in life.”
Methodology
In this study, researchers followed 865 patients of Black and Caucasian descent through annual visits at the Cincinnati Clinic of National Growth and Health Study from age 9-10 through age 24-25. The primary goal was to identify risk factors for developing Class III obesity or metabolic syndrome during young adulthood. Eighty-nine percent of participants completed ten annual visits from ages 9-10 to 18-19, and further investigator-initiated studies were completed through age 24-25. Several data points were followed, including fasting insulin, estradiol, dehydroepiandrosterone sulfate (DHEA-S), free testosterone, sex hormone-binding globulin (SHBG), lipid profiles, apolipoprotein A-1 (apoA-1), and blood pressure as well as body mass index (BMI), waist circumference, and menstrual cycle length.
As a marker of insulin resistance, fasting insulin was measured at entry into the study and at 10 and 16 years of age. Sex steroid hormones, SHBG, lipid profiles, apoA-1, and blood pressure were measured at ages 10, 12, and 14. Hyperandrogenism was defined as DHEAS > 280 mcg/dl, SHBG ≤ 6 nmol/l for black patients and ≤ 7 nmol/l for white patients, or free testosterone ≥ 2.13 pg/ml.
Menstrual cycle patterns were assessed at each annual visit from ages 10 to 19 by asking patients how many days it had been since the first day of their last menstrual cycle. Oligomenorrhea was defined as ≥ 42 days since the last menses. At age 14, patients were categorized as cycling regularly, oligomenorrheic, or PCOS, and were assessed for metabolic syndrome. Patients were reassessed for metabolic syndrome and obesity at age 24.
Statistical analysis was performed using Fisher’s p to evaluate associations between age-24 metabolic syndrome and the data points detailed above. Age-24 obesity was similarly evaluated. Additionally, Wilcoxon non-parametric tests of difference and stepwise logistic regression models were used to assess associations between age-14 oligomenorrhea and explanatory factors, as well as age-14 correlates for age-24 metabolic syndrome and Class III obesity.
Results
In 14-year-old girls, a significant difference in free testosterone (1.41 [0.93-2.12] vs. 1.07 [0.70-1.51], p=.0059) as well as waist circumference (72.9 [64.3-87.2] vs. 68.0 [64.4-73.8], p=.026) was demonstrated between those with and without oligomenorrhea. Only high free testosterone was found to be a significant explanatory variable for age-14 oligomenorrhea. No significant differences were found between any of the other measured data points in this group.
Full regression models were obtained for 324 patients to assess for variables associated with metabolic syndrome and for 333 patients to assess for variables associated with Class III obesity. Both the development of age-24 metabolic syndrome and Class III obesity were found to have independent, positive associations with high age-14 free testosterone, low age-14 SHBG, high childhood insulin, age-14 metabolic syndrome, and PCOS. Additionally, age-24 class III obesity was also associated with age-14 oligomenorrhea and black race. Of note, when age-14 oligomenorrhea was replaced with the number of reports of oligomenorrhea from ages 14 to 19, the statistical models remained essentially unchanged.
“Both the development of age-24 metabolic syndrome and Class III obesity were found to have independent, positive associations with high age-14 free testosterone, low age-14 SHBG, high childhood insulin, age-14 metabolic syndrome, and PCOS.”
In a sub-group analysis, 12 of the 30 girls with oligomenorrhea met the Rotterdam criteria for PCOS. At age 24, 33% of girls with PCOS presented with metabolic syndrome, while 33% had developed Class III obesity. In comparison, rates of age-24 metabolic syndrome and obesity in girls without oligomenorrhea were significantly lower: 7.8% and 8.4%, respectively.
Discussion
The results of this study make a strong case for additional medical workup and treatment for young teen girls who report oligomenorrhea. Assessment of fasting insulin and sex steroid hormones is valuable in this adolescent patient population, as treatment and reversal of any abnormalities could play a significant role in preventing further morbidity in young adulthood. The study findings also suggest it is appropriate to initiate a hormonal and metabolic workup during the early teenage years, as age-14 oligomenorrhea was found to be just as strong of a predictor of future obesity and metabolic disease as oligomenorrhea reported from ages 14 to 19.
“Assessment of fasting insulin and sex steroid hormones is valuable in this adolescent patient population, as treatment and reversal of any abnormalities could play a significant role in preventing further morbidity in young adulthood.”
Limitations of this study include a significant difference in dropout rate in white (43%) compared to black (26%) participants, which may affect generalizability for the white population. Oligomenorrhea was defined based only on the number of days since the onset of the most recent menses prior to annual appointments. This method of data collection may have resulted in an underestimation of oligomenorrhea depending on the timing of the annual visit in relation to the last menses. Efforts were made to minimize this possible effect by collecting menstrual length data from ages 14 to 19. Additionally, some menstrual data may be inaccurate as participants were not required to chart their cycles.
In light of the study findings, early identification and treatment of hormonal dysfunction and PCOS is imperative to improve long-term health outcomes. The authors of this research paper suggest the implementation of diet and lifestyle changes as well as consideration of oral contraceptives and metformin once oligomenorrhea is identified. The addition of fertility awareness-based methods to these recommendations as a powerful diagnostic and therapeutic tool could improve outcomes.
“Early identification and treatment of hormonal dysfunction and PCOS is imperative to improve long-term health outcomes.”
FABMs enable clinicians to identify specific menstrual cycle dysfunction earlier and provide the opportunity for root-cause-oriented treatment that would truly support teens’ gynecologic health while preserving future fertility. The potential, lifelong impact of such an approach cannot be overstated. Addressing the risk factors discussed in this paper is imperative to decrease the likelihood of severe obesity and metabolic syndrome in oligomenorrheic girls. Identifying and addressing these risk factors through FABMs could be an effective way to directly address the causes of menstrual, hormonal, and metabolic irregularities while preventing future morbidity.
Sources
[1] Glueck CJ, Morrison JA, Daniels S, Wang P, Stroop D. Sex hormone-binding globulin, oligomenorrhea, polycystic ovary syndrome, and childhood insulin at age 14 years predict metabolic syndrome and class III obesity at age 24 years. J Pediatr. 2011;159(2):308-13.e2. doi:10.1016/j.jpeds.2011.01.018.
ABOUT THE AUTHOR
Alyssa Heric
Alyssa Heric is a fourth-year medical student at Rowan University School of Osteopathic Medicine in Stratford, NJ. She earned her undergraduate degree in music at Eastern University in St. Davids, PA. She plans to complete residency in internal medicine at Lankenau Medical Center in Wynnewood, PA and pursue a career in cardiology with a functional medicine approach. She enrolled in the FACTS elective to gain a better understanding of natural family planning methods and the applications of FABMs to address the root cause of gynecologic disorders.
