PCOS and hirsutism

Question 1

Match the following;
A. oligomenorrhoea
B. amenhorrhoea
C. Virilisation
D. Hirsutism

1. extreme manifistaitons of androgen exposure
2. complete absence of menstruation or cycle length >6months
3. hair growth in areas usually associated with male sexual maturity
4. menstrual cycle length >6 weeks but <6months

Answer 1

A4
B2
C1
D3

Virilisation – extreme manifistaitons of androgen exposure, e.g. temporal hair recession, clitoromegaly, increased muscle mass, breast atrophy, deepening of voice
Hirutism – hair growth in areas usually associated with male sexual maturity, e.g. face, lower abdomen, anterior thigh, periareolar region.

Question 2

What is the most common endocrine disorder in reproductive women?

Answer 2

• Present with hyperandrogenism, anovulation, and polycystic ovaries on ultrasound
• The clinical features of PCOS are oligo/amenorrhoea, ovarian morphology, androgenisation, metabolic.

Question 3

Clinical features of PCOS.

Answer 3

Oligo/amenorrohoea
- anovulatory cycles, infertility 
Ovarian morphology 
- Ring of pearls on ovarian ultrasound, pelvic pain
Androgenisation
- hirsutism, acne, male patten hair loss
Metabolic 
- acanthosis nigricans, obesity, IGT, T2DM, hypertension, obstructive sleep apnoea

Question 4

How is PCOS diagnosed?

Answer 4

• Firstly requires the presence of irregular menstrual cycles to be present to consider diagnosis PCOS
• Follow up includes calculated free testosterone, FAI, or bioavailable testosterone to assess biochemical hyperandrogenism
• If testosterone is normal then check androstenedione and DHEAS (high=adrenal dysfynction)
• If androgens are high then consider other causes of biochemical hyperadnrogenism

Question 5

What assay is required for testosterone measure in women?

Answer 5

The assessment of testosterone requires the use of LCMS or extraction/chromatography immunoassays, because normal immunoassays have poor specificity in women

Question 6

What is the pathogenesis of PCOS?

Answer 6

Range of aetiological factors that contribute to the progression of the disorder, such as hypothalamic, pituitary, ovarian, metabolic, sympathetic nervous system, and genetic.

Question 7

Hypothalamic cause of PCOS

Answer 7

The pulse generator becomes faulty adn resists negative feedback of progesterone - mediated by androgen excess.
- Results in high GnRH pulse frequencies favouring LH production rather than FSH

Question 8

Ovarian cause of PCOS

Answer 8

The faulty pulse generator drives steroidogensis in ovarian theca cells.

• The conversion of androgen to oestrogen is limited by aromatase, which causes excess androgen interfering with normal follicular development
• The annovulation leads to low progesterone levels, limiting the negative feedback on GnRH pulse generator
• So now there is no negative feedback to the pulse generator

Question 9

Adrenal cause of PCOS

Answer 9

The hyperandrogenaemai will result in hyperinsulinaemia.

• Insulin potentiates ovarian and corticotropin mediated adrenal androgen production
• Insulin increases free testosterone by inhibiting synthesis of SHBG

Question 10

AMH function in folliculogenesis

Answer 10

AMH regulate follicular growth initation and development.

• AMH inhibts early follicular recruitment preventing premature exhaustion of oocytes
• AMH inhibits cyclic follicular recruitmetn by reducing FSH sensitivity
• AMH inhibits FSH- induced pre antral follicle growth
• Development switches to FSH dependent after selection of dominant follicle
• AMH reduces the number of LH receptors in granulosa cells, induced by FSH
• inhibits FSH induced aromatas expression, reducing E2 levels

Question 11

Describe the follicular arrest in PCOS causing cysts

Answer 11

In normal development when E2 reach threshold in large antral follicles, AMH is inhibted by ERbetaR, overcoming FSH and switching from AMH to E2 tone. Increases production of E2 inhibits AMH directly

In PCOS, large follicles lack FSH induced E2 production and high levels of AMH impair the shift from AMH to E2 tone. This causes the arrest. Small antral cant progress to large antral

Question 12

Clinical evaluation of PCOS

Answer 12

History and physical examination

• History: onset, menstrual pattern
• physical: ferryman-Gallwey scoring system

Question 13

Radiological investigation of PCOS

Answer 13

main form of imaging used is ultrasound looking for thickened capsule, multiple 3-5mm cysts, hyperechogenic stroma, may also reveal virilising ovarian tumours.

Question 14

Biochemical investigation to PCOS

Answer 14

• Gonadotrophins + E2 (increased LH:FSH with low E2 is classical)
• Prolactin (mild hyperprolactinaemia)
• Testosterone (MS assay) + SHBG - free androgen index <4.5%
• Androstenedione + DHEAS slightly elevated
• 17OHP- elevated in late onset CAH
• AMH

Question 15

Describe the utility of androstenedione in PCOS

Answer 15

Androstenedione predicts the metabolic risk. It had a strong negative association with insulin sensitivity and a positive correlation with dysglycaemia incidence
- It is a sensitive indicator of androgen excess- more effective than testosterone

Question 16

What is the treatment of PCOS?

Answer 16

Weight loss, mechanical hair removal (hirsutism), combined OCP, cyproterone acetate spironolactone, metformin, clomiphene citrate, ovarian drilling