2 Neuroscience2.8 Modulators, hormones and inflammatory responses

2.8.7 HPG axis and mental health

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Written by Resident Doctor Committee · Published

New in the 2027 syllabus

The College added this topic for exams from January 2027.

How the axis works

The hypothalamic-pituitary-gonadal (HPG) axis links brain signals to reproductive function.

  • Gonadotrophin-releasing hormone (GnRH) comes from the hypothalamus. Released in pulses, it stimulates the anterior pituitary to release luteinising hormone (LH) and follicle-stimulating hormone (FSH).

  • Sustained GnRH stimulation can suppress release instead, because the receptors become desensitised.

  • LH and FSH act on the gonads. They link hypothalamic timing to steroid production, gamete development and reproductive function.

Site

LH action

FSH action

Ovary

Stimulates theca cell androgen production, ovulation and luteal function

Supports follicle development and granulosa cell aromatisation to oestradiol

Testis

Stimulates Leydig cell testosterone production

Acts on Sertoli cells to support sperm production (spermatogenesis)

Feedback

  • Sex steroids usually inhibit the hypothalamus and pituitary by negative feedback. Inhibin preferentially suppresses FSH.

  • Just before ovulation, sustained high oestradiol switches feedback to positive. This produces the LH surge needed for ovulation.

  • After ovulation, the corpus luteum makes progesterone, so levels rise. If pregnancy does not occur, ovarian steroids fall and menstruation follows.

The main loop shows usual negative feedback. Sustained high preovulatory oestradiol can instead produce positive feedback and an LH surge; inhibin preferentially suppresses FSH. Pulsatile GnRH and continuous stimulation have different effects. Original illustration drawn in Python for MRCPsychiatrist; see images/ATTRIBUTION.md

Psychiatric connections

  • Low energy availability and stress can suppress GnRH pulses. Gonadotrophins are then low or inappropriately normal, and the gonads make less steroid.

  • Prolactin. Dopamine normally holds prolactin in check. Blocking D2 receptors in the pituitary raises prolactin. This suppresses GnRH and can contribute to menstrual disturbance, sexual dysfunction or hypogonadism.

  • Effects on the brain. Gonadal steroids influence neural signalling through nuclear and membrane-associated mechanisms. Progesterone metabolites also modulate gamma-aminobutyric acid type A (GABA-A) receptors.

  • Reproductive transitions. Symptoms around these times may reflect sensitivity to changing hormone signals rather than consistently abnormal hormone concentrations.

Reading gonadotrophin levels

  • Primary gonadal failure: negative feedback is lost, so LH and FSH tend to rise.

  • Hypothalamic or pituitary dysfunction: LH and FSH are low or inappropriately normal.

Revision material for the MRCPsych examinations. Not clinical guidance, and not for use in patient care.