Background Information
Definition
PCOS is a heterogeneous endocrine disorder that appears to emerge at puberty, characterised by 1) hyperandrogenism, 2) ovulation disorder, and 3) polycystic ovarian morphology.
Cause and Pathophysiology
The exact cause is unknown, likely to be multifactorial (both genetic and environmental factors)
The primary driving event is peripheral insulin resistance and subsequent hyperinsulinaemia, which results in:
- Hyperandrogenism
- ↑ LH secretion and disrupted LH/FSH balance
Complications
Main complications:
- Pregnancy-related problems
- Infertility – PCOS is the single most common cause of infertility in young women
- Pregnancy complications (miscarriage, gestational diabetes, pregnancy-induced hypertension)
- Endometrial cancer (chronic anovulation → absence of progesterone production → unopposed oestrogen effect)
- CVDCardiovascular disease, metabolic syndrome, NAFLDNon-alcoholic fatty liver disease
- Obstructive sleep apnoea
- Psychological disorders (mainly mood and anxiety disorders)
Diagnosis
Clinical Features
Key clinical features can be grouped as follows:
| Category | Features |
|---|---|
| Disrupted LF/FSH balance |
|
| Hyperandrogenism features |
NB that PCOS does NOT cause features of virilisation (e.g. deep voice, reduced breast size, increased muscle bulk, and clitoral hypertrophy) |
| Hyperinsulinaemia features |
|
Diagnostic Criteria
PCOS can be diagnosed if at least 2 out of 3 of the following are present (Rotterdam criteria):
| Category | Description |
|---|---|
| Ovulatory dysfunction | Manifested as oligomenorrhoea / amenorrhoea |
| Hyperandrogenism (clinical OR biochemical evidence is sufficient) | Clinical evidence:
|
Biochemical evidence:
Androstenedione and DHEASDehydroepiandrosterone sulfate should only be measured if total testosterone is NOT elevated (both would be ↑ in PCOS) Note that ↑ LH:FSH ratio is supportive of PCOS, but no longer recommended to guide diagnosis |
|
| Supportive ultrasound findings | ≥20 follicles in at least 1 ovary |
NICE CKS notes that in adolescent girls, BOTH irregular menstrual cycles and hyperandrogenism are required to diagnose PCOS.
PCOS is diagnosed using the Rotterdam criteria (2 out of 3).
If both ovulatory dysfunction and hyperandrogenism are present, the diagnosis can be made without pelvic ultrasound.
Excluding Differential Diagnoses
Perform ALL the following tests to exclude other causes of oligomenorrhoea and amenorrhoea in patients with suspected PCOS:
| Test | Purpose |
|---|---|
| LH and FSH | Exclude premature ovarian failure
↑ LH:FSH ratio is supportive of PCOS (but no longer recommended to guide diagnosis, but common in exams). However, note that isolated ↑ FSH suggests ovarian insufficiency |
| Prolactin | Hyperprolactinaemia can cause subfertility and menstrual disturbances |
| TSH | Hyperthyroidism and hypothyroidism can cause menstrual disturbances |
Non-PCOS causes of hyperandrogenism (such as late-onset congenital adrenal hyperplasia, Cushing’s syndrome, or androgen-secreting tumours) are more likely if any of the following features are present:
- Signs of virilisation (e.g. deep voice, reduced breast size, increased muscle bulk, and clitoral hypertrophy)
- Rapidly progressing hirsutism (<1 year between hirsutism being noticed and seeking medical advice)
- Significantly elevated total testosterone level (>5 nmol/L or >2x the upper limit of normal)
Management
Approach:
- All patients → cardiovascular and metabolic risk management
- If patient is NOT trying to conceive → focus on symptom management
- If patient IS trying to conceive → focus on infertility management (as most symptom management options are not appropriate in pregnancy)
Cardiovascular and Metabolic Risk Management
| Aspect | Tests / management |
|---|---|
| Encourage a healthy lifestyle |
|
| Optimise weight management |
|
| Smoking cessation |
|
| Blood pressure |
|
| Glycaemic status |
|
| Lipid status |
|
PCOS Symptom Management
Treatment is generally tailored to the patient’s most prominent symptoms:
| PCOS symptom | Management |
|---|---|
| Menstrual disturbances (oligomenorrhoea and amenorrhoea) |
|
| Hyperandrogenism (hirsutism / acne / female pattern hair loss) |
|
| BMI ≥25 kg/m² (metabolic / hyperinsulinaemia feature) |
|
COCP is generally considered the 1st line pharmacological treatment for PCOS patients who are NOT trying to conceive. It uniquely provides all the following benefits:
- Treats hyperandrogenism (↓ ovarian androgen production, ↑ SHBG)
- Regulates menstrual cycles
- Provides endometrial protection
- Provides effective contraception
If the patient is trying to conceive → most treatment options outlined here are inappropriate:
- COCP → contraindicated
- Anti-androgens → contraindicated
- Acne medications → retinoids are contraindicated (both topical and oral), antibiotics apart from erythromycin are contraindicated (see the Acne Vulgaris article for more information)
The only safe medication for patients who are trying to conceive is metformin.
Infertility Management
Symptom Management
As mentioned above, most standard treatment options to manage PCOS symptoms are NOT appropriate if the patient is trying to conceive:
- COCP → contraindicated
- Anti-androgens → contraindicated
- Acne medications → retinoids are contraindicated (both topical and oral), antibiotics apart from erythromycin are contraindicated (see the Acne Vulgaris article for more information)
The only safe medication for patients who are trying to conceive is metformin.
Interventions to Improve Fertility
Optimise preconception health and lifestyle (to be implemented prior to and alongside medical treatments):
- Healthy lifestyle (healthy eating and regular physical activity)
- Weight management (aim to maintain 18.5-24.9 kg/m2)
- Optimise blood pressure, smoking cessation, alcohol intake, sleep, and mental / emotional health
Interventions:
- 1st line: ovulation induction with letrozole (aromatase inhibitor)
- Alternative: clomiphene citrate and/or metformin
- 2nd line: gonadotrophins OR laparoscopic ovarian surgery (ovarian drilling)
- 3rd line: assisted reproductive technology (IVF +/- ICSIIn vitro fertilisation +/- intracytoplasmic sperm injection)
For those who take clomiphene citrate:
- Offer ultrasound monitoring during at least 1st cycle of treatment to ensure the lowest effective dose (due to risk of multiple pregnancy and ovarian hyperstimulation syndrome)
- Do not continue treatment for >6 months
Endometrial Protection
If there is prolonged amenorrhoea (<1 period every 3 months) or abnormal vaginal bleeding → give cyclical progesterone to induce a withdrawal bleed, then refer for TVUSTrans-vaginal ultrasound to assess endometrial thickness
- If endometrial thickness >10mm / unusual appearance → endometrial sampling
- If normal endometrium → offer treatment to prevent endometrial hyperplasia
- Cyclical progestogen (e.g. medroxyprogesterone)
- Low-dose COCPCombined oral contraceptive pill
- LNG-IUDLevonorgestrel-releasing intrauterine device
References
NICE CKS Polycystic ovary syndrome
NICE guideline Fertility problems: assessment and treatment