What are the recommended further investigations and management for a 37-year-old patient with elevated Follicle-Stimulating Hormone (FSH) levels greater than 60 on two occasions?

Management of Elevated FSH >60 in a 37-Year-Old Woman

A 37-year-old woman with FSH >60 on two occasions has premature ovarian insufficiency (POI), and NICE guidelines recommend confirming the diagnosis with repeat FSH measurement, checking estradiol levels, performing thyroid function tests, screening for autoimmune conditions, and considering karyotype analysis if under 40 years of age. 1

Diagnostic Confirmation

The diagnosis of premature ovarian insufficiency requires:

• Elevated FSH >40 IU/L on two separate occasions (your patient already meets this criterion with FSH >60) 1
• Estradiol level <50 pmol/L to confirm hypoestrogenism 1
• Measurements should be taken at least 4-6 weeks apart to account for potential fluctuation in ovarian function 1

Essential Further Investigations

Mandatory Testing

• Thyroid function tests (TSH, free T4) - thyroid dysfunction commonly coexists with POI and affects the hypothalamic-pituitary-gonadal axis 2, 1
• Autoimmune screen including:
  • Anti-thyroid peroxidase antibodies
  • Anti-adrenal antibodies (21-hydroxylase antibodies)
  • Consider screening for polyendocrinopathy 1
• Karyotype analysis - essential in women under 40 years of age to identify chromosomal abnormalities, particularly X chromosome abnormalities like Turner syndrome mosaicism 1
• Bone mineral density (DEXA scan) - untreated POI significantly increases osteoporosis risk due to prolonged hypoestrogenism 1

Additional Considerations

• Prolactin level - to exclude hyperprolactinemia as a contributing factor 2
• FSH receptor gene polymorphisms and inhibin B mutations may be considered in specialized centers, though not routinely required 1

Management Recommendations

Hormone Replacement Therapy

Hormone therapy is the mainstay of treatment and must be continued until at least age 51 (the average age of natural menopause). 1 This is critical because:

• Untreated POI increases risk of osteoporosis, cardiovascular disease, dementia, cognitive decline, and Parkinsonism 1
• The goal is physiological hormone replacement, not contraception-level dosing 1

Fertility Counseling

• Spontaneous ovulation may still occur intermittently despite elevated FSH, though pregnancy rates are very low 1
• Donor oocyte IVF offers the best chance of achieving pregnancy in women with confirmed POI 1
• Referral to reproductive endocrinology should be offered if fertility is desired 1

Specialist Referral

Women with POI should be seen in a specialist unit capable of addressing their multiple needs including: 1

• Endocrine management
• Bone health monitoring
• Cardiovascular risk assessment
• Psychological support (as this diagnosis can be difficult to accept, particularly at age 37) 1
• Fertility counseling 1

Important Caveats

• Do not prescribe exogenous testosterone or other androgens - these can further suppress the hypothalamic-pituitary axis 3
• FSH levels >60 IU/L indicate severe ovarian dysfunction, but occasional spontaneous ovulation can still occur, so contraception should be discussed if pregnancy is not desired 1
• Karyotype is particularly important at age 37 as chromosomal abnormalities may have implications for family planning and genetic counseling 1
• Ensure adequate calcium and vitamin D supplementation alongside hormone therapy for bone protection 1