Waiting for an elevated FSH--too late a marker of reduced ovarian reserve?

Aim: To assess age at which median follicle-stimulating hormone (FSH) is elevated above 10 U/L.

Background: Fertility and ovarian reserve decrease over the 4th decade with evidence that sensitive markers such as anti-Mullerian hormone fall even earlier. Despite its limitations, a basal or day 2-3 FSH is commonly used to assess ovarian reserve with levels over 10 U/L often used as a cut-point for further investigations.

Methods: Women referred to a community laboratory for 'hormone testing', including FSH and oestradiol (n = 40 254), were included in a retrospective analysis. Cases excluded were those with suppressed FSH (<1 U/L) who were likely on the oral contraceptive pill or pregnant and those with increased oestradiol (>500 pmol/L) who were likely approaching mid-cycle or pregnant. Remaining cases (n = 32 445) were analysed in five-year age bands for FSH median, mean, and 2.5 and 97.5 percentiles.

Results: Median FSH remained consistently low (≤5 U/L) in women ≤35 years of age and was 6 U/L in 35- to 40-year-olds. The mean FSH and 97.5 percentile increased steadily. The 97.5th percentile was 10 U/L or lower in women up to 30 years of age.

Conclusions: Follicle-stimulating hormone is a late indicator of known reducing ovarian reserve, and in this study, median FSH did not increase over 10 U/L until >45 years of age. FSH levels >9 U/L were above the 97.5th percentile in those <25 years of age. If fertility is a concern, FSH levels persistently above age-specific medians in women under 40 years may prompt earlier follow-up with more sensitive tests for ovarian reserve.