PCOS/PCOD

PCOS: An Insight Into the Parasol of Hormonal Imbalance

Affecting over 6 to 15% of women of reproductive age group, Polycystic ovarian syndrome (PCOS) is the most common endocrinopathy in females.

PCOS is an oligogenic disorder where the combination of several genetic and environmental factors determine the heterogeneous, clinical, and biochemical phenotype of the disease. The diagnosis and treatment of PCOS are not complicated, and requires only the judicious application of a few well-standardized diagnostic methods and appropriate therapeutic approaches. These approaches should address hyperandrogenism, the consequences of ovarian dysfunction and the associated metabolic disorders.

Fundamentals of PCOS

The etiology of PCOS has both genetic and environmental roots, although it is also believed to even occur due to elevated levels of androgens.

The pathophysiology of PCOS involves primary defects in the hypothalamic-pituitary axis, insulin secretion and action, and ovarian function.

Clinical signs of PCOS include elevated luteinizing hormone (LH) and gonadotropin-releasing hormone (GnRH) levels, whereas follicular-stimulating hormone (FSH) levels are muted or unchanged. The increased GnRH, stimulates the ovarian thecal cells to produces excess LH. This LH in turn stimulates ovarian androgen production, whereas a relative deficit in FSH impairs follicular development.

PCOS and Hormone Dysfunction

  • Testosterone ↑↑ – is a hormone often thought of as a male hormone, although all women usually produce small amounts of it.
  • Luteinizing Hormone (LH)↑↑ – this stimulates ovulation but may conversely affect the ovaries if levels are too high.
  • Sex hormone-binding globulin (SHBG)↓↓ – is a protein in the blood that binds to testosterone and reduces its effect.
  • Prolactin (PRL)↑↑ *only in some women with PCOS* – Prolactin is synthesized by lactotrophs in the anterior pituitary gland. The number of lactotrophs will increase during pregnancy in response to the physiological need to develop breast tissues and to prepare for milk production.

The exact reason why these hormonal changes occur is not known.

Physiological Outcomes:

Hyperandrogenism

The most significant clinical manifestation of PCOS is hyperandrogenism. Excessive androgen production by ovaries and adrenals contributes to hyperandrogenism. Being the hallmark feature, it manifests as hirsutism, acne, and alopecia. Hair is commonly seen on the upper lip, on the chin, around the nipples, and along the linea alba of the lower abdomen. Some patients have acne and/or male-pattern hair loss (androgenic alopecia).

Insulin resistance

It is a fundamental pathogenic component of PCOS, both in lean and overweight–obese patients. Insulin resistance is present in at least 50% of PCOS women and it appears to be due to excessive serine phosphorylation of the insulin receptor. A factor extrinsic to the insulin receptor, presumably a serine/threonine kinase, causes this abnormality. Serine phosphorylation modulates the activity of the key regulatory enzyme of androgen biosynthesis, P450c17.

It is thus possible that a single defect produces both insulin resistance and hyperandrogenism in some PCOS women. The sluggish response can cause glucose to accumulate in the blood and eventually change how the body deals with sugar. Worsening insulin resistance eventually leads to diabetes.

Following are a few signs seen in an insulin resistant PCOS patient:

  • Cravings for sweets and salty foods
  • Darkening of skin in the groin, armpits, or behind the neck, also known as Acanthosis nigricans
  • Fatigue, malaise
  • Frequent or increased urination (Polyuria)
  • Increased hunger or thirst (Polydipsia)
  • Tingling sensation in the hands or feet (Diabetic neuropathy, in cases of uncontrolled blood sugar

Infertility

PCOS is the most common cause of menstrual irregularities such as amenorrhea, oligomenorrhea, and is the primary cause of anovulatory infertility. Ovulation may not occur due to an increase in testosterone production or because follicles on the ovaries do not mature.

Even if ovulation occurs, an imbalance in hormones may prevent the lining of the uterus from developing properly to allow for the implantation of the mature egg. Due to hormonal imbalance, ovulation and menstruation can be irregular. Unpredictable menstrual cycles can also make it difficult to get pregnant.

Women seeking help from health care professionals to resolve issues of obesity, acne, amenorrhea, excessive hair growth, and infertility often receive a diagnosis of PCOS.

Treatment

Treatment should target specific manifestations and individualized patient goals. When choosing a treatment regimen, physicians must take into account comorbidities and the patient’s desire for pregnancy.

  • Non Pharmacological management: Lifestyle change is the first-line treatment for infertility in obese women with PCOS. The composition of the optimal diet for women with polycystic ovary syndrome (PCOS) is not yet known. However, such a diet must not only assist short term with weight management, symptoms and fertility but also specifically target the long-term risks of type 2 diabetes, CVD and certain cancers. On the balance of evidence to date, a diet low in saturated fat and high in fiber from predominantly low-glycemic-index-carbohydrate foods is recommended.
  • Pharmacological management: Metabolic concerns of PCOS include excess body weight and insulin resistance. Insulin lowering therapies also improve menstrual regularity. When excess androgen is the main target for therapy, antiandrogen and/or oral contraceptives are typically chosen. Metformin and thiazolidinediones both improve hyperinsulinemia but their differential effects on body weight must be considered. The combination of metformin and clomiphene citrate (CC) in CC-resistant patients provides additional benefit to a subset of patients, not responsive to metformin alone. In the absence of ovulation for three cycles of CC at the highest dose (150 mg/day), the woman can be considered non-responsive and another drug should be introduced as an adjuvant or substitute for CC. Another approach to combat androgenic symptoms of PCOS is Spironolactone. It is the most common adjuvant anti-androgen medication prescribed after Oral Contraceptive Pills; it is a nonselective mineralocorticoid receptor antagonist and suppresses testosterone levels. Spironolactone also has additional benefits regarding the risk of CVD compared to OCP.
  • Supplementation: Various supplements have been tried and tested to work on PCOS :
  1. Magnesium: Helps increase insulin sensitivity hence, lowers blood sugar levels. Hypomagnesemia may worsen insulin resistance (IR) due to the role magnesium (Mg) plays in glucose metabolism.
  2. Inositol: Myoinositol (MI) and D-chiro-inositol (DCI) are involved in a number of biochemical pathways within oocytes having a role in oocyte maturation, fertilization, implantation, and post-implantation development. Both Inositols have a role in insulin signaling and hormonal synthesis in the ovaries.
  3. Vitamin D: Increases insulin sensitivity as well as lowers androgen-induced male pattern baldness in women with PCOS.

Symptoms vary between individuals, and so treatment is not always the same. However, treatment can increase the chances of conceiving in those who wish to become pregnant. It can also help people to manage their symptoms. Maintaining a healthy weight can help improve this metabolic cum lifestyle disorder.

Author:

img 20200807 201350 209 1 (1) Dr. Prachi Sinha is an MBBS graduate from Smt. N.H.L Municipal Medical College, Ahmedabad. She makes her home currently in Ahmedabad with her family, a tiny undisciplined garden, and a growing number of incomplete baking projects. She has garnered much acclaim for her animal activism and adoption drives across Ahmedabad. When she is not working in the hospital, Prachi spends most of her time conducting online webinars for unprivileged women and catching her treasured Bollywood movies. An admitted food fanatic, she feeds her addiction to sushi by taking on her favorite sushi joints on Sunday afternoons

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