Polycystic Ovary Syndrome (PCOS) is a common endocrine disorder characterized by excess of male hormones and abnormal development of female reproductive organs. PCOS affects approximately 1% of women and is associated with obesity, insulin resistance, hypertension, hyperandrogenism and infertility.1,2 Although it is known that PCOS may have genetic components,3–6 its etiology remains unknown.1 The effects of PCOS on quality of life and long-term health are serious. For example, women with PCOS have a higher incidence of type 2 diabetes, hypertension, cardiovascular disease and endometrial cancer than the general population.7,8
The pathogenesis of PCOS is multifactorial and, despite many studies, there are no definitive diagnostic tests. Metabolic factors, including insulin resistance and a predisposition to central obesity, are involved in the pathogenesis of PCOS.9PCOS is also associated with increased production of androgens (e.g.
testosterone and DHEA).1,10
The main and most studied feature of PCOS is the presence of small cysts (hence the name) in the ovaries. The significance of these cysts is still enigmatic.
It is thought that these cysts are remnants of follicles that did not reach the surface of the ovary and degenerated. However, recent studies have found a positive relation between the size of the cyst and the production of male hormones such as androgens.1
Insulin resistance has been suggested to be key factor in the pathogenesis of PCOS. It is believed that the elevated levels of androgens (e.g.
testosterone) lead to increased stimulation of the insulin receptors in the hypothalamus and in the ovary. The elevated levels of androgens in the blood also increase the amount of insulin-like growth factor (IGF-1). IGF-1 is a hormone that helps regulate cell growth. IGF-1 also has the ability to increase the amount of androgens in the body. The increased levels of IGF-1 and androgens can eventually cause the ovary to produce more male hormones. This causes an increase in ovarian androgen production. The rise in male hormones can lead to the signs and symptoms of PCOS.1
Insulin resistance in women with PCOS occurs before end organ damage (e.g.
heart disease). This suggests that hormonal factors, such as hyperandrogenism and increased levels of IGF-l, are involved in the pathogenesis of PCOS.1
Androgens: Androgens are male hormones that are involved in the development and maintenance of male sexual characteristics.1 The main androgen found in women with PCOS is testosterone.
High levels of testosterone are thought to contribute to the hepatic formation of excess amounts of androgens.
Insulin-Like Growth Factor-1 (IGF-1): IGF-1 is a hormone that falls into the same family as insulin. It can be found in most body tissues and is able to have anabolic effects (i.e.
it increases growth). It is also involved in the metabolism of carbohydrates, proteins and lipids.1 The levels of IGF-1 are correlated with those of insulin. In fact, IGF-1 levels can be used as a marker of insulin resistance. It is also thought that IGF-1 may play a role in the ovaries’ stimulation of androgen production. It has been shown that IGF-1 can increase the rate of androgen production in ovarian theca cells.
Insulin: Elevated levels of circulating insulin have been found in most women with PCOS. This elevation in insulin is thought to be a contributing factor in the subsequent development of insulin resistance.
Insulin resistance: Changes in the tissue response to insulin. In PCOS, this is mainly in target tissues (e.g.
liver, muscle and adipose tissue). These changes result in elevated levels of both free (unbound) and total insulin in the blood.
Androgen Excess: Androgen excess is the term used to describe the elevated levels of testosterone and other androgens in women with PCOS. These elevated androgen levels are thought to contribute to the development of hirsutism, acne, and other signs of PCOS.
Other Factors: There are two other possible factors that may play a role in the pathogenesis of PCOS; these include genetic factors and environmental factors.
Genetic factors: It has been suggested that there is a genetic predisposition to the development of PCOS. This may explain why the incidence of PCOS among first-degree relatives (i.e.
mother, sister) of women with PCOS is significantly higher than the rest of the population.
Environmental factors may also play a role in the pathogenesis of PCOS. These include increased exposure to pollutants (e.g.
dioxin) and other endocrine disruptors (e.g. organochlorines). These may contribute to the development of insulin resistance and androgen excess in women with PCOS.
A thorough past medical history should be taken, paying particular attention to:
Current and past gastrointestinal problems (e.g.
Crohn’s disease, irritable bowel syndrome)
Eating habits (e.g.
vegetarian, binge eater)
Current stress levels
History of smoking and alcohol intake
A family history of menstrual disorders, diabetes and cardiovascular disease should be assessed. A menstrual history should be taken, including the length of each menstrual cycle, date of the last menstrual period, and whether or not the patient has been menstruating every month.
A pregnancy history should be assessed as well.
A physical examination should take place to assess the patient’s height and weight. It is important to measure body mass index (BMI), which is calculated by dividing weight in kilograms by height in square metres.
A BMI of greater than 30 is considered obese.2
A pelvic examination should be carried out to assess the size of the uterus and ovaries. In PCOS, the ovaries are often enlarged.
It is important to do a bimanual examination in order to assess for the presence of any polycystic appearing ovaries. Palpation may also be painful due to the development of cysts on the ovaries. An assessment of pubic hair should also be carried out. There is an association between hirsutism and PCOS, therefore a full assessment of the presence or absence of any pubic hair is needed.3
There are no specific screening tests available for PCOS. Rather, a combination of clinical manifestations and laboratory findings are used to confirm the diagnosis.
In addition to a medical history and physical assessment, the following tests are usually ordered:
Ovarian Ultrasound: An ultrasound of the ovaries can be used to detect the presence of multiple ovarian cysts.
A transvaginal ultrasound is more sensitive in the diagnosis of polycystic appearing ovaries, however this procedure is not without complications. It has been shown to increase the risk of vaginal bleeding post-procedure, and consequently pelvic inflammatory disease.4
Determining the precise number of cysts present on the ovaries is difficult. A rough estimate may be made based on the number of cysts observed.
A minimum of two or three cysts is required to make a diagnosis of PCOS.
Liver Function Tests: Elevations in liver enzymes have been noted in women with PCOS. This may be due to the development of fatty liver, or it may be a result of insulin resistance.
A1C: A1C, also known as hemoglobin A1C, indicates the average blood glucose level over the past 2 to 3 months. Elevated A1C levels are consistent with diabetes.
Thyroid Function Tests: Women with PCOS have an increased risk of developing thyroid disease. As such, it is important to assess thyroid function.
Prolactin: Elevated prolactin levels are commonly seen in women with PCOS. This is most likely due to the presence of insulin resistance.
Determining the Cause of PCOS
The cause of PCOS is still unknown. It is likely a combination of genetic and environmental factors that lead to the development of the condition.
Genetic Factors: There appears to be a strong genetic link with the development of PCOS. First-degree female relatives of those with PCOS are at a higher risk of developing the condition themselves.5
The ovaries are responsible for the production of several reproductive hormones, including estrogen, progesterone, and testosterone. These hormones are responsible for the normal development and cyclical function of the female reproductive system.
In women with PCOS, the ovaries produce increased amounts of androgens. The ovaries are also unable to produce adequate amounts of other hormones.
This disruption in hormone production is believed to be responsible for the wide range of symptoms present in PCOS.
Insulin Resistance: The exact cause of insulin resistance in PCOS is unknown. Insulin resistance has been linked to other conditions such as metabolic syndrome, obesity, and type 2 diabetes.
The pancreas releases insulin in response to rising blood glucose levels. Insulin promotes the absorption of glucose into cells.
In PCOS, the cells are insulin resistant. This means more insulin is needed to allow glucose to enter the cells. The pancreas can’t increase insulin production fast enough, leading to elevated blood glucose levels.
Elevated androgen levels have also been shown to contribute to insulin resistance. This is evident in women with PCOS who become insulin resistant following ovary removal.
Stress: Psychological stress has been shown to worsen various symptoms of PCOS, such as infertility and hirsutism (excessive hair growth). This is especially true if stress leads to worsening of insulin resistance and other metabolic factors.
Smoking: More than half of women with PCOS smoke, more than the general population. Women with PCOS are also more likely to develop nicotine dependence than other women.
This could be due to increased stress, or it could be that smoking has some direct effects on androgen levels.
Obesity: Obesity is one of the major risk factors for developing PCOS. As previously mentioned, obesity leads to an increase in androgen levels due to hormonal changes associated with being overweight.
There is evidence that PCOS also leads to an increased likelihood of obesity, due to the hormonal disturbances it causes.
Sources & references used in this article:
- Endometrial adenocarcinoma and polycystic ovary syndrome: risk factors, management, and prognosis. (JL Elliott, SL Hosford, RI Demopoulos… – Southern medical …, 2001 – europepmc.org)
- Anti-Műllerian hormone–a prognostic marker for metformin therapy efficiency in the treatment of women with infertility and polycystic ovary syndrome (M Neagu, C Cristescu – Journal of medicine and life, 2012 – ncbi.nlm.nih.gov)
- Polycystic ovary syndrome and endometrial carcinoma (P Hardiman, OS Pillay, W Atiomo – The lancet, 2003 – Elsevier)
- The Rotterdam criteria for polycystic ovary syndrome: evidence-based criteria? (R Wang, BWJ Mol – Human Reproduction, 2017 – academic.oup.com)
- Prognostic factors for ovulatory response with clomiphene citrate in polycystic ovary syndrome (T Kurabayashi, M Suzuki, K Fujita, H Murakawa… – European Journal of …, 2006 – Elsevier)
- High singleton live birth rate confirmed after ovulation induction in women with anovulatory polycystic ovary syndrome: validation of a prediction model for clinical … (SM Veltman-Verhulst, BCJM Fauser, MJ Eijkemans – Fertility and sterility, 2012 – Elsevier)
- Body composition and polycystic ovary syndrome (L Zabuliene, J Tutkuviene – Medicina (Kaunas, Lithuania), 2010 – ncbi.nlm.nih.gov)