Male reproductive physiology

Hypothalamic–pituitary–testicular axis

• The hypothalamus releases GnRH in pulses (about every 90 minutes); the anterior pituitary responds with LH and FSH. Pulsatile GnRH is essential; continuous GnRH agonists (leuprorelin, goserelin) first cause a flare and then down-regulate receptors, suppressing LH and FSH (used in prostate cancer).
• LH acts on Leydig cells in the interstitium to make testosterone.
• FSH, together with high local testosterone, acts on Sertoli cells to support spermatogenesis. Sertoli cells make androgen-binding protein (keeps testosterone high in the tubules), inhibin B, and in the fetus anti-Müllerian hormone.
• Feedback: testosterone (partly after conversion to oestradiol) inhibits GnRH and LH; inhibin B from Sertoli cells selectively inhibits FSH.

Testosterone

• Made from cholesterol in Leydig cells (side-chain cleavage is rate-limiting); about 98% circulates bound to SHBG and albumin.
• Its effects depend on a functional androgen receptor (a nuclear receptor). 5α-reductase converts it to the more potent dihydrotestosterone (DHT) in the prostate, skin and external genitalia; aromatase in fat converts it to oestradiol.
• In the fetus: testosterone develops the Wolffian ducts (epididymis, vas, seminal vesicles); DHT forms the penis, scrotum and prostate.
• At puberty: growth of penis and scrotum, deepening voice, muscle mass, libido, body hair, growth spurt; spermatogenesis; erythropoiesis; bone density. Androgens drive growth, but epiphyseal closure is caused by oestrogen formed by aromatisation, so growth stops even as androgen remains high.
• DHT causes prostate growth, male-pattern baldness and acne; finasteride blocks 5α-reductase.
• Testosterone replacement raises red cell mass, so haematocrit must be monitored (polycythaemia raises thrombosis risk); PSA is also checked. Exogenous testosterone suppresses LH and FSH and therefore acts as a male contraceptive.

Spermatogenesis

• Occurs in the seminiferous tubules from puberty: spermatogonia (by the basement membrane) divide by mitosis, primary spermatocytes undergo meiosis I to secondary spermatocytes, meiosis II gives spermatids, and spermiogenesis remodels spermatids into spermatozoa (acrosome, condensed nucleus, tail).
• The whole process takes about 64–74 days, so a semen analysis reflects events over two months earlier.
• Sertoli cell tight junctions form the blood–testis barrier, isolating meiotic and later cells, which carry new antigens, from the immune system.
• Spermatogenesis needs a temperature 2–3 °C below core. The scrotum, the pampiniform plexus (countercurrent cooling of arterial blood) and the cremaster maintain it. Varicocele (usually left: the left testicular vein drains at right angles into the left renal vein) pools warm venous blood around the testis, raising its temperature and impairing sperm count and motility. A new right-sided or non-emptying varicocele needs imaging for a renal or retroperitoneal mass. Cryptorchidism and fever also impair spermatogenesis.
• Sperm leave the testis immotile and gain forward motility and fertilising ability in the epididymis; capacitation occurs in the female tract. Motility depends on dynein arms in the axoneme; in Kartagener syndrome (primary ciliary dyskinesia) sperm are immotile.

Semen

• Normal ejaculate is 1.5–5 mL with at least about 15 million sperm/mL and adequate motility and morphology.
• After vasectomy, the ejaculate contains seminal vesicle and prostatic fluid only, with almost unchanged volume; azoospermia must be confirmed before relying on it.
• Azoospermia with normal external genitalia and normal hormones points to obstruction (vas deferens, epididymis, ejaculatory ducts; congenital absence of the vas in cystic fibrosis carriers); low semen volume with absent fructose suggests seminal vesicle or ejaculatory duct problems. Azoospermia with high FSH points to testicular failure.

Erection and ejaculation

• Erection is parasympathetic (pelvic splanchnic nerves, S2–S4). Nitric oxide from nerves and endothelium raises cGMP, relaxing the smooth muscle of the corpora cavernosa; arterial inflow fills the sinusoids and compresses venous outflow. PDE5 inhibitors (sildenafil) prolong the cGMP signal. Muscarinic receptors on endothelium contribute by releasing NO.
• Emission is sympathetic (T11–L2, via α1 receptors): the vas, seminal vesicles and prostate contract and the bladder neck closes.
• Ejaculation proper is somatic: the pudendal nerve drives rhythmic contraction of bulbospongiosus and ischiocavernosus.
• Failure of bladder neck closure (α1 blockers, diabetic neuropathy, prostate surgery) causes retrograde ejaculation.

Hormone patterns in male hypogonadism

• Anabolic steroids suppress LH and FSH by negative feedback, so intratesticular testosterone and FSH support fall: small, soft testes and low sperm count, plus gynaecomastia from aromatisation.
• Fertility in hypogonadotrophic hypogonadism (Kallmann): testosterone injections virilise but do not produce sperm, because intratesticular testosterone and FSH remain low. Stop testosterone and give hCG (acts like LH on Leydig cells, raising intratesticular testosterone), adding FSH if needed; pulsatile GnRH is an alternative.

Remember LH drives Leydig cells to make testosterone; FSH drives Sertoli cells; inhibin turns off FSH.

Exam trap Inhibin suppresses FSH, not LH.

Exam trap Exogenous testosterone or anabolic steroids lower LH, FSH and sperm count.

How FCPS asks about this

• Cells making testosterone: Leydig cells under LH; inhibin is made by Sertoli cells and inhibits FSH.
• Duration of spermatogenesis: about 64–74 days; sperm gain motility in the epididymis.
• Bodybuilder with small testes: suppressed LH and FSH from anabolic steroids.
• Varicocele subfertility: pooled venous blood warms the testis.
• Kallmann man wanting children: stop testosterone, give hCG then FSH.
• Ejaculate after vasectomy: seminal vesicle and prostatic fluid without sperm.
• Erection: parasympathetic S2–S4 via nitric oxide and cGMP; emission sympathetic; ejaculation via the pudendal nerve.