A 25-year-old woman presents with prolonged amenorrhoea, having had only three periods in the last year, with the most recent two months ago. She has a history of irregular periods since menarche and was diagnosed with polycystic ovary syndrome (PCOS) as a teenager. She has a family history of endometrial cancer in her mother and maternal aunt.


She denies abdominal pain, bloating, fatigue, early satiety, or intermenstrual bleeding. Her medical history is unremarkable, and her BMI is 21.




Urine dip is clear with negative beta-hCG.

||||
|---------------------------|:-------:|------------------------------|
|Thyroid Stimulating Hormone|2.1 mU/L|0.3 - 4.2|
|Luteinising Hormone|10.85 IU/L|1 - 11 (Luteal)|
|Follicle Stimulating Hormone|3.1 IU/L|2 - 8 (Luteal)|
|Testosterone|2.6 nmol/L|(M) 9.9 - 27.8, (F) 0.2 - 2.9|
|Prolactin|450 IU/L|(M) 90 - 320, (F) 100 - 500||



What is the best next management step for this patient?

Options:
explanation: This would be a reasonable option to help regulate this patient's menstrual cycle and additionally provide hormonal contraception (although this patient did not state contraception was her main priority). It would be useful for this patient to have an ultrasound scan after a withdrawal bleed to assess the endometrium and so a short daily course of oral medroxyprogesterone would be used to achieve this. The three-monthly depo injection is less likely to induce a withdrawal bleed as quickly as a two week course of oral medroxyprogesterone because the progestogen dose is spread over a longer period of time. If the patient's ultrasound scan showed an endometrium of normal thickness and morphology, then a three-monthly progesterone injection would be an option - although the patient would not benefit from the anti-androgen effects of oestrogen within the COCP
name: Intramuscular injection of medroxyprogesterone (Depo Provera) every three months
label: b
answer: no
explanation: This patient does require a TVUS to assess endometrial thickness and morphology, although a withdrawal bleed would need to be induced prior to scanning to accurately measure the endometrial thickness. For this the patient should be provided with oral medroxyprogesterone (Provera) for 14 days to induce a withdrawal bleed
name: Transvaginal ultrasound scan (TVUS)
label: c
answer: no
explanation: This patient is rightly concerned about her risk of endometrial cancer - having PCOS and having two family members who developed endometrial cancer places her at high risk. It would be reasonable to refer to genetic screening to determine if she, or her family, was genetically predisposed to endometrial cancer e.g. Lynch syndrome (mutation in MLH1 mismatch repair gene) or Cowden Syndrome (Mutations in PTEN tumour suppressor gene). The priority at this stage, however, is to investigate and manage her secondary amenorrhoea, and to reassure her there are no signs of malignancy
name: Refer for genetic screening
label: e
answer: no
explanation: The most likely cause for this patient's secondary amenorrhoea (less that one period every three months) is her PCOS. Her LH:FSH Ratio is 3.5 and so makes PCOS more likely than premature ovarian failure (elevated FSH and LH), hypothalamic/hypopituitary amenorrhoea (low FSH, LH, testosterone, and prolactin), Hypothyroidism (low or high TSH), or androgen-secreting tumour/late onset congenital adrenal hyperplasia (raised testosterone). There is nothing in the question pointing to her amenorrhoea being weight, exercise, or stress-related.
 

 She is rightly concerned about her increased risk of endometrial cancer with PCOS and amenorrhoea. This is due to prolonged exposure of the endometrium to unopposed oestrogen. She will need referral for a transvaginal ultrasound (TVUS) to assess for endometrial thickness, although prior to this she will need to induce a withdrawal bleed to correctly interpret the ultrasound findings as her endometrium will be thickened given she has not menstruated for two months. To induce a withdrawal bleed in this patient, an oral cyclical progestogen such as medroxyprogesterone is given for 14 consecutive days. Following this, a TVUS should be conducted.
 

 If endometrial thickening is present (greater than 10mm) or the endometrium has an abnormal appearance, then she will need referral for endometrial sampling to exclude endometrial hyperplasia or cancer (unlikely in this patient's case). If the endometrium is of normal thickness and appearance, then the options to reduce risk of endometrial cancer are either:
 

 - An oral cyclical progestogen e.g. medroxyprogesterone for 14 days every 1-3 months
 - Low-dose combined oral contraceptive pill (COCP)
 - Levonorgestrel-releasing intrauterine system (e.g. Mirena®)
 

 If the patient is unwilling to take these, then they would likely need regular ultrasound scans every 6-12 months to assess the endometrium
name: Oral medroxyprogesterone (Provera) for 14 days
label: a
answer: yes
explanation: This would be a reasonable option to help regulate this patient's menstrual cycle and additionally provide hormonal contraception (although this patient did not state contraception was her main priority). It would be useful for this patient to have an ultrasound scan after a withdrawal bleed to assess the endometrium and so a short daily course of oral medroxyprogesterone would be used to achieve this. The three-monthly depo injection is less likely to induce a withdrawal bleed as quickly as a two week course of oral medroxyprogesterone because the progestogen dose is spread over a longer period of time. If the patient's ultrasound scan showed an endometrium of normal thickness and morphology, then a three-monthly progesterone injection would be an option - although the patient would not benefit from the anti-androgen effects of oestrogen within the COCP
name: Insertion of levonorgestrel-releasing intrauterine system (e.g. Mirena®)
label: d
answer: no

Correct answer: a

Oral medroxyprogesterone (Provera) for 14 days

Learning point: Prolonged anovulation in PCOS increases endometrial cancer risk due to unopposed oestrogen