February 22, 2021
Implications of PCOS in Adolescence: A Review
By Kemi Ogunmuko
Editor’s Note: This week we share an outstanding summary of an article that addresses possible long-term consequences of polycystic ovary syndrome (PCOS) in adolescents, which makes the prompt diagnosis and treatment of PCOS a priority in this age group. Kemi Ogunmuko, a fourth-year medical student, summarized the 2020 article titled, “Polycystic ovary syndrome in adolescent girls” published in Pediatric Obesity by Ibáñez et al. She did this as part of the FACTS online fertility awareness elective and is one of 128 students to enroll in the elective since August 31, 2020. The summary concludes with an important discussion of potential benefits of charting the female cycle for all girls, and especially those at risk for PCOS.
What is PCOS?
Polycystic ovary syndrome is a multifaceted and complex endocrine disorder that affects 5-10% of childbearing women (Bremer, 2010).[i] This heterogenous syndrome can be diagnosed using the Rotterdam criteria and is characterized by features of anovulation, androgen excess (clinical findings or biochemical evidence through serology), and polycystic ovaries on imaging. Two out of these three criteria must be present to diagnose PCOS (ACOG Practice Bulletin No. 194).[ii]
Anovulation can manifest as irregular menses, oligomenorrhea or amenorrhea. Clinical findings of androgen excess include hirsutism, alopecia, and acne, among others. PCOS symptoms vary with age and frequently manifest during adolescence. Yet, the diagnosis of PCOS is different for this age group. It is defined by the dual presence of anovulation and androgen excess at least 2 years after menarche. Ovarian morphology is not included in the diagnostic criteria as it is for adult women (Ibáñez, 2020).[iii]
Why is this important?
The prevalence of PCOS is rising among adolescent populations as a result of genetics and environmental factors (Ibáñez, 2020). Some risk factors include premature pubarche before 8 years of age, family history, and obesity. With the recent rise in childhood obesity, significant metabolic consequences of PCOS can affect the quality of life a teenager may have in the future. Childhood obesity poses a major risk factor for developing metabolic syndrome, insulin resistance, type 2 diabetes, atherosclerotic disease, cardiovascular disease, and infertility (ACOG Practice Bulletin No. 194).
At the cellular level, women with PCOS have decreased insulin sensitivity by an average of 35-40% compared to the average woman (Baptiste, 2010).[iv] This is very similar to what is seen in women with type 2 diabetes. Women with PCOS are insulin resistant and have compensatory hyperinsulinemia.
The androgen excess is thought to result from an excess of central fat deposition in subcutaneous adipose tissue leading to further hyperinsulinemia and gonadotropin secretion. Evidence suggests that in women with PCOS, theca cells have increased responsiveness to insulin and luteinizing hormone (LH) stimulation compared to normal theca cells in control women. This hyperresponsiveness to insulin means women with PCOS only need the physiologic dose of insulin to activate androgen production in their theca cells, whereas the average woman needs a much higher concentration. In PCOS, the synergistic effects of hyperinsulinemia and continuous LH stimulation (due to lack of negative estrogen/progesterone feedback to the hypothalamus-pituitary) means a very high androgen production (Baptiste, 2010).
What is the treatment currently available?
There is no FDA-approved treatment for adolescent females with PCOS (Ibáñez, 2020), so the current treatment is directed at managing symptoms. Specifically, cyclic oral contraceptive pills (OCPs) are used to suppress LH production and, thus, androgen excess (ACOG Practice Bulletin No. 194). This approach purportedly helps to “regulate” menses by leading to an anovulatory pseudo-menses. The oral contraceptive pill has the benefit of preventing the unopposed estrogen action that can cause endometrial hyperplasia and endometrial cancer. Thus, this is the current recommended use even for females who are not sexually active.
Unfortunately, oral contraceptives do not solve the problem of insulin resistance. For females who have comorbidities of obesity and insulin resistance, the recommendation is weight loss and exercise along with possible metformin to improve insulin sensitivity. With the use of OCPs, young girls have the possible consequence of post-treatment rebound androgen excess and oligo-anovulatory subfertility setting the stage for adult PCOS. Obstetric complications in this patient population include a 2 to 3-fold higher risk of gestational diabetes, preeclampsia, and preterm delivery (Ibáñez, 2020).
Other recommended therapies in women with PCOS include cosmetic hair removal, eflornithine therapy for facial hirsutism combined with laser therapy, clomiphene or letrozole for ovulation induction, and other insulin sensitizing agents (ACOG Practice Bulletin No. 194).
What does the present article suggest?
This article suggests enhancing the effects of lifestyle measures by increasing energy expenditure and reducing total abdominal visceral fat by switching fat deposition from ectopic to eutopic depots. Another recommendation is to consider low dose SPIOMET therapy (Ibáñez, 2020). SPIOMET is a combination of three medications: spironolactone, pioglitazone, and metformin. The hope is that this alternative recommendation can restore ovulation rates, prevent later subfertility, and prevent clinical manifestations of cardiovascular disease related to PCOS. As a potent anti-androgen, spironolactone can help improve the cutaneous manifestations of hyperandrogenism. Compared to oral contraceptives, SPIOMET therapy has shown a 2.5-fold increased ovulation rate and a 6-fold higher prevalence of normal ovulation (Ibáñez, 2017).[v]
PCOS is associated with significant morbidity, including metabolic, cardiovascular, reproductive, and psychosocial dysfunction. Its psychological impact is significant, with an increased prevalence of depression, anxiety, and eating disorders in adolescent girls with PCOS. There is also an increased risk of endometrial cancer, as unopposed estrogen leads to proliferation of the endometrium.
Given that current evidence is of low quality with limited treatment options, the goal of care should focus on improving quality of life early on and preventing long term health complications. Adolescent females would benefit from learning about fertility awareness and how to chart their biological signs by tracking their menstrual cycles at the onset of menarche to establish a baseline early in their pubertal growth. Such charting serves as a “5th vital sign” that helps a young woman recognize healthy cycle parameters and identify unhealthy cycles. This is, in fact, recommended by the American College of Obstetricians and Gynecologists (ACOG) and the American Academy of Pediatrics (AAP).
Fertility awareness-based methods (FABMs) can expedite the diagnosis of PCOS in young women. FABMs also empower young women and improve adolescents’ body literacy. Charting cycles along with targeted medical therapy (SPIOMET) and lifestyle modifications may help prevent future complications of PCOS.
[i] Bremer A. A. (2010). Polycystic ovary syndrome in the pediatric population. Metabolic syndrome and related disorders, 8(5), 375–394. https://doi.org/10.1089/met.2010.0039.
[ii] American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins—Gynecology. ACOG Practice Bulletin No. 194: Polycystic Ovary Syndrome. Obstet Gynecol. 2018 Jun;131(6):e157-e171. doi: 10.1097/AOG.0000000000002656. PMID: 29794677.
[iii] Ibáñez L., Zehger, F. (2020). Polycystic ovary syndrome in adolescent girls. Pediatric Obesity, 15(2). https://onlinelibrary.wiley.com/doi/abs/10.1111/ijpo.12586.
[iv] Baptiste, C. G., Battista, M. C., Trottier, A., & Baillargeon, J. P. (2010). Insulin and hyperandrogenism in women with polycystic ovary syndrome. The Journal of steroid biochemistry and molecular biology, 122(1-3), 42–52. https://doi.org/10.1016/j.jsbmb.2009.12.010.
[v] Ibáñez, L., del Río, L., Díaz, M., Sebastiani, G., Pozo, Ó. J., López-Bermejo, A., & de Zegher, F. (2017). Normalizing ovulation rate by preferential reduction of hepato-visceral fat in adolescent girls with polycystic ovary syndrome. Journal of Adolescent Health, 61(4), 446–453. https://pubmed.ncbi.nlm.nih.gov/28712591/.
About the Author
Kemi Ogunmuko is a fourth-year medical student at Lincoln Memorial University – DeBusk College of Osteopathic Medicine. She is pursuing a career as an obstetrics and gynecology physician. Kemi recently completed the FACTS medical student elective at Georgetown University School of Medicine where she learned about fertility awareness-based methods for family planning and restorative reproductive women’s healthcare.
Bonus Live Webinar | March 1st
Expand your knowledge and TUNE IN next Monday, March 1st at 5:00 pm EST, to hear Dr. Joseph Stanford present on the topic of Miscarriage, or Early Pregnancy Loss, Early pregnancy loss occurs in 10–20% of clinically recognized pregnancies. In this presentation, Dr. Stanford will describe how early pregnancy loss is classified, review the known causes and risk factors associated with miscarriage, and discuss how a restorative reproductive approach including lifestyle modification, charting the female cycle, and medical interventions can be used to evaluate and treat women at risk for early pregnancy loss. The presentation will last approximately 1 hour.
Can’t attend on Monday? Dr. Stanford will also be presenting on this topic at our 2021 Virtual Conference on May 14-15. Click here to learn more.