Premature ovarian insufficiency — structured SAQ (15 marks)

(a) Definition and confirmation (3 marks)

One mark per point. [1][2]

• Definition (ESHRE 2024): premature ovarian insufficiency is loss of ovarian activity before age 40, characterised by menstrual disturbance (amenorrhoea or oligomenorrhoea) plus two serum FSH levels over 25 IU/L taken at least 4 weeks apart.
• Confirmation: exclude pregnancy first (done — negative), then repeat the FSH at least 4 weeks later — never diagnose on a single test, because POI fluctuates.
• Do NOT use anti-Mullerian hormone to diagnose POI.

(b) Cause-finding workup (4 marks)

One mark per point. [1][4]

• Karyotype — to identify 45,X mosaicism (Turner) and other X-chromosome abnormalities; the most common chromosomal cause.
• FMR1 premutation screen (CGG repeat, 55 to 200) — fragile X-associated POI (FXPOI).
• 21-hydroxylase antibodies (plus TSH and anti-thyroid antibodies) — to screen for coexisting Addison disease; an undiagnosed adrenal insufficiency can cause a fatal adrenal crisis. This is the must-not-miss.
• DEXA for bone density at diagnosis (low BMD is common — about 58% in the Bachelot cohort) and a cardiovascular risk assessment.

(c) Hormone therapy (5 marks)

One mark per point. [1][3]

• Offer HRT or a combined hormonal contraceptive (NICE NG23 1.7.6), unless contraindicated. HRT is generally preferred for long-term use (better blood-pressure profile, bone-protective); the COC is acceptable and contraceptive.
• Regimen: oestrogen plus a progestogen (she has a uterus); micronised progesterone is the modern progestogen of choice. Tibolone is an alternative.
• Duration: continue until at least the average age of natural menopause (around 51), unless contraindicated. Premature stopping is the common error.
• Rationale: this is physiologic replacement of hormones her ovaries are not making — NOT menopausal HRT. The baseline risk of breast cancer and cardiovascular disease is very low in women under 40, so the benefits outweigh the risks.
• The WHI risk numbers do NOT apply to her — they were for women with a mean age of 63 started years past menopause. Withholding HRT in POI is the error.

(d) Fertility counselling (3 marks)

One mark per point. [1][3]

• Spontaneous pregnancy is possible but uncommon (around 5 to 10% in some series) — POI fluctuates. Do not over-promise.
• Donor-oocyte IVF is the most realistic fertility option, with good success rates per cycle.
• Do not offer post-diagnosis oocyte freezing — the diagnosis means the reserve is already depleted. Fertility preservation (oocyte or embryo cryopreservation) must happen BEFORE gonadotoxic therapy, not after.