Pearls in My Ovaries: The PCOS Guide

Imagine a situation where the body feels trapped in unrelenting chaos -regular periods seem like a distant reality, the face is filled with stubborn acne and unwanted hair, weight gain strikes without any warning, and mood swings have no rhyme or reason. For 8-13% of women of reproductive age, this isn’t a dream but the daily struggle of living with Polycystic Ovarian Syndrome (PCOS). What is more surprising is that 70% of these women remain undiagnosed, enduring the disease silently, unsure of where to seek help.

PCOS was first described by Stein and Levinthal in 1935. However, even after nine decades, it remains a puzzle for the scientists. Its rising incidence leaves researchers debating whether to classify it as an ancient condition ( whose prevalence is attributed to improved diagnostics) or a modern 20th-century phenomenon.

What is PCOS?

Since its discovery, PCOS has worn many labels. The different names reflect the evolving understanding of its complexities. PCOS was earlier named Stein Levinthal syndrome, after its discoverers. Currently, it is known by names like Polycystic Ovarian Disease, Functional Ovarian Hyperandrogenism, Ovarian Hyperthecosis, and Sclerocystic Ovary Syndrome.

PCOS is a complex condition with a chronic course. A heterogenic endocrine disorder, PCOS typically begins during adolescence and is characterised by an imbalance in the hormones, increased androgens and lack of ovulation. Although its name mainly focuses on multiple ovarian cysts (metaphorically referred as pearls), PCOS impacts several systems in the body. Long-term disease predisposes the individual to obesity, metabolic syndrome, heart diseases, diabetes, infertility and psychosocial struggles.

Risk Factors

Studies have shown that PCOS is caused by the intricate interaction of three major risk factors. They include genetics, lifestyle and exposure to environmental agents.

Genetic studies revealed that PCOS is not just multifactorial, but also polygenic. The role of many genes has been implicated – particularly those involved in the formation of ovarian and adrenal steroids, signalling of steroids, regulation of gonadotropins, secretion of insulin etc. Nevertheless, the precise understanding of the underlying molecular mechanisms is still obscure.

Physical inactivity and improper diet are crucial lifestyle causes of the disease. Inadequate sleep and stress are known to alter hormones. Moreover, processed food increases inflammation, worsening the associated metabolic features of the disease.

Exposure to endocrine-disrupting chemicals or EDCs interferes with the endocrine system by imitating the hormones. Despite their names, these are common chemicals, often encountered in daily life. They include compounds like BPA (in plastics, and food containers), dioxins (a by-product of industrial processes and waste incineration), DDT (pesticides), parabens (cosmetics and personal care products) and triclosan (antibacterial soap and cleaning products).

Pathophysiology

The disruption in the normal function of the ovaries outlines the underlying pathophysiology of PCOS. The ovaries are made up of many follicles which can be considered tiny sacs. One of the follicles mature each month. A surge in the hormone LH breaks this follicle and releases the egg(oocyte). The ruptured follicle turns into the corpus luteum, which secretes progesterone to prepare the uterus for pregnancy. If pregnancy does not occur, the progesterone support disappears, and the lining of the uterus is shed as blood.

In PCOS, the pulse frequency of gonadotropins is prolonged. This results in increased levels of LH which causes the ovaries to produce more androgens (male hormone).8 This is the inciting event of the catastrophic disorder. These androgens are folliculotoxic. They arrest follicular maturation and create multiple cysts in the ovaries. These cysts are just unruptured follicles. Increased LH throughout the cycle along with folliculotoxicity contributes to anovulation leading to infertility. Without ovulation, there is little to no progesterone, resulting in irregular periods.

Insulin resistance also contributes to increased androgens. It decreases the protein that binds with androgen (SHBG: Sex Hormone Binding Globulin). The absence of SHBG increases free androgen and causes hirsutism, acne, and alopecia9. Insulin resistance also increases bad cholesterol, predisposing the individual to diabetes and heart disease.

40-80% of females with PCOS are obese. Obesity further aggravates insulin resistance. The excess androgens get converted into estrogen in the fat tissue, increasing the risk of endometrial cancer, ovarian cancer and also liver disease (NASH: Non-alcoholic steatohepatitis).

When to suspect PCOS?

PCOS presents in many ways. While obesity is a key symptom, even females with normal or low body weight can get this condition. Despite the name, even the presence of multiple ovarian cysts is not sine non qua of the syndrome. Certain symptoms which occur in most females are:

• Irregular menstrual cycles

• Growth of thick, coarse hair on the face/body (hirsutism)

• Acne

• Hair thinning (Alopecia)

• Unexplained weight gain, especially around the abdomen (Central obesity)

• Infertility

• Dark patches of skin in the nape of the neck, underarms, under the breast or groin region (Acanthosis nigricans).

  
  

PCOS: Diagnosis.

The guidelines for diagnosing PCOS have evolved over the years. In addition to the usual lab investigations to assess the hormone levels, certain criteria must be met for a diagnosis.

The earliest guidelines, given by the National Institute of Health in 1990, had only two aspects: Ovulatory dysfunction and Hyperandrogenism. In 2003, Rotterdam’s criteria expanded by including Polycystic Ovarian Morphology (≥ 12 follicles, 2-9 mm size). Diagnosis could be made if any of the two criteria were met. The American Society of Reproductive Medicine or the NIH 2012 extension of ESHRE stated two of the three criteria with phenotype identification are required for diagnosis. The criteria were:

1. Ovulatory dysfunction (OD)

2. Hyperandrogenism (HA)

3. Polycystic ovarian morphology. (PCOM)

4. Phenotype :

   1. HA+OD+PCOM

   2. HA + OD

   3. HA + PCOM

   4. OD + PCOM

   
   

Management

There is currently no pharmacological cure for the syndrome. Due to its varied presentation, treatment modalities must be tailored to each individual's clinical presentation.

Given its chronic nature and the increased risk of diabetes and heart disease, the incorporation of lifestyle changes is a simple approach to managing the condition. Implementation of physical activity, dietary modification, and positive changes in attitude can regularize menstruation in a few cases.

Oral contraceptive pills are commonly prescribed to regulate periods and manage hirsutism. Ovulation-inducing drugs like Clomiphene or Letrozole are used to treat infertility. Insulin sensitizers like Metformin and Thiazolidinediones can combat insulin resistance. Laparoscopic ovarian drilling that destroys the theca cells is considered a second-line treatment for infertility. In vitro fertilization is recommended for females more than 35 years and is considered a third-line choice of therapy.

Conclusion

PCOS is not a mere reproductive health issue. Often undiagnosed, Danielle R. Stratton correctly describes, “the journey a person takes from prior to and after diagnosis (of PCOS) is like Dorothy’s journey along the Yellow Brick Road,” - a journey full of discovery, challenges and growth.

PCOS is a syndrome that has much to teach us all. For researchers, it provides an opportunity to delve deeper and investigate the underlying mysteries of the disease. For doctors, it emphasizes the need to address the societal stigma and the mental stress that accompanies the diagnosis. It teaches patients the importance of adopting a healthier lifestyle and seeking earlier consultation. When researchers, physicians and patients collaborate, significant strides can be made in improving the quality of life for those affected by PCOS, reducing long-term complications, and fostering hope for a brighter future.

References:

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