Polycystic ovarian syndrome

Polycystic ovarian syndrome (PCOS), also known as hyperandrogenic anovulation, is a chronic anovulation syndrome associated with androgen excess. 

The Rotterdam criteria is used to make the diagnosis of PCOS and require any two of the following three criteria for the diagnosis, as well as the exclusion of other etiologies (e.g. congenital adrenal hyperplasia, Cushing syndrome, and/or an androgen-secreting tumor) ^4,18:

1. ovulatory dysfunction (oligo- and/or anovulation)

2. clinical and/or biochemical signs of hyperandrogenism

3. polycystic ovarian morphology on ultrasound or elevated serum AMH ²³

Hence, ultrasound is not necessary for the diagnosis if features of both ovulatory dysfunction and hyperandrogenism are present, or if one of these features is found in conjunction with an elevated serum AMH. The latter diagnostic criterion was added in the 2023 edition of the International Evidence-based Guideline for the assessment and management of polycystic ovary syndrome ²³.

Terminology

"Hyperandrogenic anovulation" has been proposed as a more accurate and potentially less confusing term, as the ovarian feature is of multiple follicles and not cysts ¹³. At this stage, however, "polycystic ovarian syndrome" remains the term that is widely known and used.

Epidemiology

The estimated prevalence is 8-13% of women of reproductive age but this varies (up to 20%) depending on the diagnostic criteria used ¹¹. 

Associations

• subfertility and recurrent pregnancy loss

• long-term increased risk of

  • type 2 diabetes mellitus

  • hyperlipidemia 

  • cardiovascular disease

  • endometrial cancer (two to six-fold increased risk) ^6,18

• high prevalence of anxiety and depression

• women with polycystic ovarian morphology are at increased risk of OHSS when undergoing IVF, regardless of whether they have PCOS ¹⁵

Clinical presentation

The classic triad of PCOS is:

1. oligomenorrhea and/or anovulation

2. hirsutism

3. obesity

In addition to this, patients may have infertility, acne, alopecia or biochemically show increased androgen levels.

Pathology

Markers 

Biochemical hyperandrogenism is based on the measurement of free testosterone, free androgen index, or calculated bioavailable testosterone, androstenedione and dehydroepiandrosterone sulphate ²⁰.

Anti-Müllerian hormone (AMH) levels are generally increased, and there is emerging evidence for the utility of AMH in the diagnosis of PCOS. The most recent (2023) diagnostic criteria had added AMH as an alternative to ultrasound appearance of polycystic ovarian morphology ²³. 

Radiographic features

Ultrasound

Ovaries may be normal in PCOS, and conversely, polycystic ovarian morphology (PCOM) may be seen in women without the syndrome. However, it is well accepted that women with PCOS tend to have larger ovaries with an increased number of follicles.

The specific diagnostic cut-offs, however, have been the subject of debate and revision. The updated diagnostic criteria at the time of review (c. 2024) are based on the 2023 international consensus guideline ²³. 

In patients >8 years post menarche, criteria for PCOM are:

• follicle number per ovary (FNPO) ≥20 in at least one ovary, and/or

• follicle number per section (FNPS) ≥10 in at least one ovary, and/or

• ovarian volume ≥10 mL, ensuring no corpora lutea, cysts or dominant follicles are present

FNPO is considered the most accurate marker for PCOM. The latter two criteria should only be considered if using older technology or image quality is insufficient to allow for an accurate assessment of follicle counts throughout the entire ovary ²³.

FNPO should include any follicles measuring 2-9 mm. Other ovarian features and/or pathology including ovarian cysts, corpus lutea and dominant follicles ≥10 mm should not be included in ovarian follicle counts or volume calculations.

The diagnostic criteria are adjusted in adolescent females (defined as within 8 years of menarche, or age <20 years) ^18,23, in whom ultrasound should not be used for the diagnosis of PCOS due to the high incidence of multi-follicular ovaries in this life stage ²².

This supersedes the initial Rotterdam criteria of ≥12 follicles and interim recommendations of 24 or 25 follicles per ovary. The presence of a single multifollicular ovary is sufficient to provide the sonographic criterion for PCOS ².

Other morphological features have been described, but do not contribute to formal diagnostic criteria:

• hyperechoic central stroma

• peripheral location of follicles (string of pearls sign)

• follicles of similar size measuring 2-9 mm

MRI

MRI is not warranted routinely in the investigation of PCOS, nonetheless, pelvic MRI may show most or all of the above sonographic features. Signal characteristics include:

• T1: small uniform follicles are low in signal while the central stroma is of intermediate signal (vs normal myometrium)

• T2: follicles have high T2 signal while the central stroma is of comparatively low T2 signal ⁸

History and etymology

The syndrome was first described by I F Stein and M L Leventhal in 1935 ⁷.

Practical points

• with a lack of consensus sometimes it is easier to report the number of follicles in each ovary rather than attempt to label the ovaries as "polycystic" or "multifollicular"

• ultrasound should not be used for the diagnosis of PCOS in patients <8 years after menarche due to the high incidence of multi-follicular ovaries in this life stage

• as the individual age of menarche may not be known, an age cut-off of 20 years is suggested for the utility of ultrasound in this diagnosis (based on the median age at menarche being approximately 12 years)

• post menopause, a new or continuing diagnosis of PCOS could be considered based on past history and clinical evidence of persistent hyperandrogenism

• postmenopausal women presenting with new-onset, severe or worsening hyperandrogenism including hirsutism, require further investigation to rule out androgen-secreting tumors and ovarian hyperthecosis