By Elaine Pope
Editor’s Note: Although the last few decades of research have clarified some of the pathophysiology of polycystic ovary syndrome (PCOS), this common condition remains a challenge in clinical practice. While on the FACTS elective, Elaine Pope summarized a 2014 review article by Rojas et al [1] that explored the knowledge to date about PCOS and its relationship to insulin resistance and obesity. By learning to track her cycles with fertility awareness-based methods (FABMs), a woman can learn to notice hormonal effects and clinical signs of PCOS and other conditions. Through a restorative approach, a physician trained in FABMs can interpret a woman’s chart to diagnose and treat many of these conditions, including PCOS. Learn more about this comprehensive approach in Part D of the FACTS CME course.
Introduction
Polycystic ovary syndrome (PCOS) is a highly prevalent yet poorly understood endocrine-metabolic disorder that results in hyperandrogenemia, insulin resistance, and hyperinsulinemia. The diagnosis of PCOS is often associated with obesity, and several studies identify insulin resistance as the fundamental link between these two conditions. However, insulin resistance associated with PCOS may also be present in women who are not obese.
All women diagnosed with PCOS are at risk for chronic inflammation and its consequences on reproductive health, including high rates of infertility. It is imperative to understand the pathophysiology of PCOS to prevent and treat these outcomes. Fertility awareness-based methods (FABMs) can play a significant role in the diagnosis and treatment of PCOS.
Role of the Ovaries in PCOS
The primary cause of PCOS has not been determined, but it appears to be multifactorial. PCOS is understood as a complex interplay between genetic factors and aberrant hormone levels that disrupt physiologic events in the ovarian cycle. The genetic predisposition to PCOS may be attributed to mutations in genes of the androgen receptor, sex hormone binding globulin (SHBG), and enzymes that lead to hyperandrogenemia. Patients with PCOS have increased levels of gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH), which induce androgen synthesis in ovarian theca cells. Additionally, elevated levels of anti-Müllerian hormone (AMH) inhibit follicles from maturing properly and also disrupt dominant follicle selection. This constant cycle of follicle initiation without selection of a dominant follicle results in the classic “polycystic” or “poly-follicular” manifestation of PCOS.
“Patients with PCOS have increased levels of gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH), which induce androgen synthesis in ovarian theca cells.”
Clinical Signs & Symptoms
The diagnosis of PCOS is based on its physical manifestations. Although the National Institute of Health, the European Society of Human Reproduction and Embryology, and the American Society of Reproductive Medicine listed different criteria for PCOS at the time of Rojas et al’s review, all recognized oligo/anovulation and clinical or biochemical hyperandrogenism as common symptoms. Some of the clinical or biochemical manifestations of elevated androgens include hirsutism, acne, alopecia, seborrhea, and brittle nails.
It is important to recognize that oligo/anovulation cannot be identified by the presence or absence of eumenorrhea. A cycle can be accurately identified as oligo/anovulatory by measuring progesterone levels <3-4 ng/mL in the post-peak phase of the menstrual cycle. The post-peak phase can be identified accurately by analyzing the chart of a woman who uses an FABM.
Hormonal and Metabolic Changes
In PCOS, the impact of insulin resistance and elevated insulin levels on the development of hyperandrogenemia is best understood as a cycle; they likely stimulate each other in a reciprocal way. The cycle of hyperinsulinemia and hyperandrogenemia is complex and involves various hormones acting on different organs. Insulin impacts key hormones in the ovarian cycle; it may potentiate GnRH gene transcription, causing increased GnRH synthesis and secretion. A rise in GnRH and LH contributes to androgen synthesis in ovarian theca cells. Insulin itself appears to augment adrenal cortex sensitivity to ACTH stimulation, causing increased androgen secretion. Hyperinsulinemia is also associated with decreased levels of SHBG and increased bioavailability of androgens.
The evidence suggests increased androgens in PCOS may affect insulin sensitivity. Androgens appear to upregulate adrenergic receptors in adipose tissue. They also decrease insulin-sensitive fibers in skeletal muscle. The impact of insulin resistance, hyperinsulinemia, and hyperandrogenemia on infertility should not be underestimated.
“The impact of insulin resistance, hyperinsulinemia, and hyperandrogenemia on infertility should not be underestimated.”
Women with PCOS are often prescribed insulin-sensitizing medications to improve hyperandrogenemia and ovarian function. Medical consultants trained in FABMs endorse these interventions and often prescribe myo-inositol and metformin to support ovulation and fertility in women with PCOS.
Obesity is Not Universal in PCOS
Obesity is commonly associated with PCOS, but it is not essential to the diagnosis. Obesity magnifies the manifestations of PCOS by causing elevated estrogen levels from increased subcutaneous adipose tissue. Estrogen stimulates LH and inhibits FSH, contributing to ovarian hyperplasia and androgen synthesis. Subcutaneous adipose tissue also secretes leptin, causing leptin overactivity and resistance. This results in insufficient LH signaling to stimulate optimal LH pulse secretion for ovulation.
Women who are not obese but have manifestations of PCOS often have hyperinsulinemia, although it is likely due to beta-cell hypersecretion rather than insulin resistance. Rojas et al listed various theories that could account for PCOS in women who are not obese, such as altered opioid signaling, adrenal androgen excess, or impaired lipolysis; yet, the leading theory points to genetic mutations in proinflammatory genes. Regardless of a woman’s body habitus, PCOS is a chronic, low-grade inflammatory disorder that warrants accurate diagnosis and treatment.
“Women who are not obese but have manifestations of PCOS often have hyperinsulinemia, although it is likely due to beta-cell hypersecretion rather than insulin resistance.”
Discussion
The review by Rojas et al is highly relevant to women’s health and family planning. PCOS is a common cause of infertility, and its pathophysiology can be intimidating. This article [1] contributes to the understanding of this complex disease process as of the time of publication, describing PCOS as a cycle of hyperinsulinemia and hyperandrogenism. This fails to pinpoint the root cause of PCOS, and more research is still needed on the defining aspect of these hormonal disturbances, if one exists.
Fertility awareness-based methods enable women diagnosed with PCOS to understand and manage this condition. By accurately charting her cycles with an FABM, a woman can identify patterns, such as irregular or long cycles and anovulation, that may aid her clinician in diagnosing PCOS. Hormone monitoring done in conjunction with FABMs can help diagnose hormonal abnormalities during a woman’s cycle. Management of PCOS may include hormone supplementation as well as lifestyle interventions, such as physical activity and dietary changes.
Many FABM medical consultants learn to treat PCOS without hormonal contraceptives; instead, they prescribe medications such as metformin and myo-inositol and, at times, refer patients for ovarian wedge resection and ovarian drilling. Women with PCOS who hope to achieve pregnancy can accurately target days of fertility when charting their cycles. FABMs support a woman’s health by helping to diagnose and treat common conditions such as PCOS and restoring the natural function of a woman’s cycle so she may pursue and achieve her family planning goals.
References
[1] Rojas J, Chávez M, Olivar L, Rojas M, Morillo J, Mejías J, Calvo M, Bermúdez V. Polycystic Ovary Syndrome, Insulin Resistance, and Obesity: Navigating the Pathophysiologic Labyrinth. International Journal of Reproductive Medicine. 2014;2014:719050. doi:10.1155/2014/719050
ABOUT THE AUTHOR
Elaine Pope is a fourth-year medical student at the University of Kansas School of Medicine in Kansas City, Kansas. She completed an undergraduate degree in English at the University of Kansas in Lawrence, Kansas. She plans to pursue residency in family medicine and is interested in women’s health and international mission work. She enrolled in the FACTS elective to gain a well-rounded understanding of the female cycle and to provide her patients with options for natural family planning. She is excited to empower women of all ages to understand their cycles and work with the natural function of their bodies.
Inspired by what you read?
You can support the ongoing work of FACTS here. To connect with a member of our team, please email development@FACTSaboutFertility.org. Interested in becoming an individual or organizational member? You can learn more and register here. To discuss with a member of our team, please email membership@FACTSaboutFertility.org.
