1.4 Premature ovarian failure

Question 1

What is the definition of premature ovarian failure?

Answer 1

Premature ovarian failure (POF) is defined as menopause occurring before the age of 40:
• Considered as a pathological state → different management approach
• Occurs in about 1% of women < 40 years of age; 0.1% in those < 30 years of age, 0.01% in those < 20 years of age

Question 2

what are the causes of POF?

Answer 2

Idiopathic (most common), chromosomal abnormalities, enzyme deficiencies,

• Autoimmune causes: hypoadrenalism, hypothyroidism, hypoparathyroidism (less common), type 1 diabetes mellitus

Genetic- Turner’s syndrome, Fragile X syndrome, autoimmune ovarian disease

Post-surgical treatment for gynaecological disorders (e.g. cystectomy, oophorectomy, hysterectomy)

Post-chemo/radiotherapy for malignancies

Question 3

What are the clinical presentations of POF?

Answer 3

POF presents with the following classic signs and cause several important long-term sequelae (essentially the same as physiological menopause → just happens too early in life):

1. Amenorrhoea (primary/secondary) → permanent loss of follicular activity (may or may not be due to follicular depletion)
2. Increased gonadotrophin levels (FSH/LH) and decreased sex steroids
3. More severe menopausal symptoms: hortflushes, urinary frequency, urgency, vaginal dryness, dyspareunia, decreased libido, low mood, memory loss, insomnia
4. Subfertility
5. May present as part of treatment planning in the work-up for a procedure likely to result in POF (e.g. chemotherapy for malignancies)

Question 4

What are the long term sequalae of POF?

Answer 4

Serious health consequences of POF refer to those with 50% higher mortality than women who experience menopause at the normal physiological age:
• Includes cardiovascular disease, osteoporosis, cognitive impairment, anxiety and depression (refer to above notes for more details)
• Typically experience more severe menopausal symptoms
• Multi-disciplinary approach is required to address physical and psychological impacts

Question 5

How is the diagnosis of POF made?

Answer 5

The diagnosis of POF is made based on the presence of the 3 following criteria:

1. Age* (< 40 years of age)
2. History of amenorrhoea (> 12 consecutive months)
3. Elevated FSH* (> 40 IU/L) in both 2 FSH tests taken 4 – 6 weeks apart
   * Pregnancy should always be excluded in any amenorrhoeic woman of reproductive age

Question 6

What are the investigations of POF?

Answer 6

1) Oestradiol levels (usually undetectable)
2) chromosomal analysis (karyotyping) for exclusion of turner
3) autoantibody screening
4) transvaginal ultrasound (Likely low antral follicle count and low ovarian volume)
5) Baseline bone density scan (Confirmed diagnosis of POF is associated with a high risk of osteoporosis → easier to recognise onset of osteoporosis in future when bone density declines past the baseline)

Question 7

life style advice for POF?

Answer 7

Patients with POF should maintain a balanced diet, adequate calcium and vitamin D intake, regular weightbearing exercise (to strengthen bones), cease smoking and excessive alcohol intake to avoid exacerbating menopausal symptoms and long-term sequelae.

Question 8

Fertily advice for POF?

Answer 8

• Women with idiopathic POF may have intermitent ovarian activity → spontaneous conception is possible (though low chance)

Assisted conception with oocyte donation; Taking an oocyte from someone else (Singapore has no oocyte bank → usually donor is found by the patient, normally a family member) then mixing it with the husband’s sperm and implanting it into the patient’s uterus → allows patient to carry pregnancy
• Most effective intervention for fertility in POF

Surrogacy: Mixing the patient’s oocyte with her husband’s sperm and implanting the zygote into another person’s (surrogate) uterus

Fertility preservation: Important to consider for women who will be receiving treatment that may cause POF (e.g. chemo/radiotherapy) from a young age:
• Includes oocyte or embryo cryopreservation

Question 9

Oestrogen replacement is recommended for all women with POF (unless there are contraindications like oestrogen-dependent cancers):
• Guideline: continue replacement until the___________________
• Aims: achieve a physiological level of oestradiol
• Preparation: oestrogen + progesterone (to protect the endometrium) → commonly using ___________ (same type of oestrogen physiologically) → better lipid profile and bone protection than the oestrogens used in most OCP preparations
o Some women may opt to take the COCP (associating HRT with old age)
• Benefits: control of menopausal symptoms, prevention of osteoporosis, lowering of long-term risk of cardiovascular disease, beneficial effect on cognitive function

Answer 9

natural age of menopause (~50 years);

17β-oestradiol