Reproductive Endocrinology and Neuroendocrinology
Core physiology
The hypothalamic–pituitary–ovarian axis is a pulsatile system. GnRH pulses drive gonadotrophin release; fast pulses favor LH, slow pulses favor FSH. Estradiol feedback is biphasic: negative at low/moderate levels, positive at sustained high levels for ~50 hours (the basis of the midcycle LH surge). Progesterone slows the pulse generator, which is why luteal-phase LH pulses are slow.
Know the two-cell two-gonadotrophin model: LH acts on theca cells to make androgens; FSH drives granulosa aromatase to convert them to estradiol. Inhibin B (granulosa) and inhibin A (corpus luteum) selectively suppress FSH.
Traps in questions
- Confusing Kallmann syndrome (anosmia + hypogonadotrophic hypogonadism, failed GnRH neuron migration) with constitutional delay.
- Missing that hyperprolactinaemia suppresses GnRH via dopamine, producing hypogonadotrophic hypogonadism-not a primary ovarian problem.
- Forgetting that thyroid disease and obesity both perturb SHBG and ovulation.
- Assuming an elevated FSH alone diagnoses menopause in a woman on combined hormonal contraception.
Worked rule of thumb
A 24-year-old with amenorrhoea, low FSH/LH, low estradiol, and anosmia: the lesion is hypothalamic (Kallmann). Pulsatile GnRH or gonadotrophins will induce ovulation; clomiphene will not, because it requires an intact hypothalamic–pituitary feedback axis.
Thyroid and adrenal context
Screen TSH and prolactin in anovulation. Untreated hypothyroidism raises TRH, which raises prolactin. Congenital adrenal hyperplasia and Cushing disease are rarer causes of anovulation but appear as distractors.