Lactation physiology
Lactation: prolactin, oxytocin, milk ejection reflex and lactational amenorrhoea
Lactation physiology for FCPS Part 1: why milk waits for delivery of the placenta, the prolactin and milk ejection reflexes, and lactational amenorrhoea. Covers milk composition, colostrum IgA, Sheehan syndrome and drugs that raise or lower milk supply.
Stages
| Stage | Timing | Hormones |
|---|---|---|
| Mammogenesis | Pregnancy | Oestrogen: duct growth; progesterone: lobules and alveoli; prolactin, hPL, cortisol and insulin permissive |
| Secretory differentiation (lactogenesis I) | Mid-pregnancy | Alveoli can make colostrum, but high oestrogen and progesterone block copious secretion |
| Secretory activation (lactogenesis II) | 2–4 days after delivery | Triggered by the fall in progesterone once the placenta is out, with prolactin still high |
| Maintenance (galactopoiesis) | Weeks to months | Prolactin surges plus regular milk removal |
- Milk can appear a day after evacuation of a 20-week pregnancy, because the trigger is placental hormone withdrawal, not term.
- Retained placental fragments keep progesterone up and delay milk.
- Two days after delivery, the breasts change from colostrum to copious milk as progesterone falls: they become full, warm and heavy ("milk coming in").
Prolactin reflex (milk production)
- Prolactin is the only anterior pituitary hormone held mainly under inhibitory hypothalamic control, by dopamine from arcuate (tuberoinfundibular) neurones acting on D2 receptors.
- Suckling stimulates nipple afferents (4th intercostal nerve), which reach the hypothalamus and reduce dopamine release from arcuate neurones, so prolactin rises several-fold within 30 minutes of each feed.
- Surges are larger at night, so dropping night feeds reduces supply more.
- Prolactin acts through JAK2–STAT5 to switch on milk protein genes, including alpha-lactalbumin, which joins Golgi galactosyltransferase to form lactose synthase. Lactose is the main osmole that sets milk volume.
- Local control: milk left in a breast inhibits further secretion (autocrine inhibitor and alveolar stretch), so supply follows demand.
Milk ejection (let-down) reflex
- Suckling, and also conditioned cues such as the baby's cry, activate oxytocin neurones in the paraventricular and supraoptic nuclei; oxytocin from the posterior pituitary contracts the myoepithelial cells (Gq, IP3, calcium).
- Pain, anxiety and stress inhibit the reflex: full breasts but poor flow.
- Oxytocin also contracts the myometrium: afterpains during feeds, stronger in multiparous women, and faster involution. They are physiological and not by themselves a sign of retained products.
| Feature | Prolactin reflex | Milk ejection reflex |
|---|---|---|
| Hormone | Prolactin (anterior pituitary) | Oxytocin (posterior pituitary) |
| Control | Removal of dopamine inhibition | Neural release from hypothalamic axons |
| Target | Alveolar secretory cells | Myoepithelial cells |
| Speed | Over the next feed | Within a minute |
| Conditioned or inhibited by emotion | Little | Yes |
Lactational amenorrhoea
- High prolactin and frequent suckling inhibit GnRH pulses (prolactin acts on hypothalamic kisspeptin neurones), so FSH and LH stay low, follicles do not mature and ovulation is delayed. Amenorrhoea in lactation is therefore due to prolactin inhibiting GnRH, and through it LH and FSH.
- The method is about 98% effective only if the baby is under 6 months, feeding is exclusive and periods have not returned.
- Low oestrogen during lactation contributes to temporary bone loss.
Failure of lactation: Sheehan syndrome
- The pituitary enlarges in pregnancy (lactotroph hyperplasia) but its blood supply does not, so massive postpartum haemorrhage with hypotension causes ischaemic necrosis of the anterior pituitary.
- Failure to lactate is the earliest sign (no prolactin). Later: amenorrhoea, loss of pubic and axillary hair, hypothyroidism (weight gain, dry skin, lethargy) and secondary adrenal insufficiency (hypotension, hypoglycaemia). The posterior pituitary is usually spared.
Composition of milk
| Feature | Colostrum (first days) | Mature milk |
|---|---|---|
| Protein | Higher (secretory IgA, lactoferrin) | Lower |
| Fat and lactose | Lower | Higher |
| Volume | Small | About 750–800 mL/day |
- IgA is the antibody of colostrum. It is made by plasma cells in the breast and crosses the epithelium by transcytosis via the polymeric immunoglobulin receptor; the secretory component protects it from digestion. IgG reaches the fetus across the placenta instead.
- Foremilk is lactose-rich; hindmilk is fat-rich.
| Human milk compared with cow's milk | Consequence |
|---|---|
| Less protein, whey-dominant | Soft curds, easy digestion |
| More lactose and oligosaccharides | Bifidobacterium-rich gut |
| Less sodium and phosphate | Cow's milk phosphate causes late neonatal hypocalcaemia |
| Low iron, but highly absorbed | Term babies keep normal iron to about 6 months |
| Low vitamin K and vitamin D | Vitamin K at birth prevents haemorrhagic disease of the newborn; vitamin D 400 units daily |
- Vitamin B12 is deficient in milk of long-term vegan mothers. Breastfeeding needs about 500 kcal/day extra.
- Breast milk jaundice is benign unconjugated jaundice in a thriving baby; a raised conjugated (direct) bilirubin is never breast milk jaundice and needs investigation for cholestasis.
Drugs and breastfeeding
- Drugs enter milk more when they are lipid-soluble, small, poorly protein-bound and weak bases (ion-trapped in slightly acidic milk).
- Oestrogen in the combined pill opposes prolactin's action on the alveolar cells and reduces established milk supply; progestogen-only methods do not.
| Effect on milk | Drugs |
|---|---|
| Lower prolactin and milk | Dopamine agonists: bromocriptine, cabergoline, levodopa; oestrogens |
| Raise prolactin (and cause galactorrhoea) | Dopamine antagonists: phenothiazines, haloperidol, risperidone, metoclopramide, domperidone |
- To suppress lactation cabergoline (one dose) is used; bromocriptine is avoided postpartum (hypertension, stroke, seizures).
- Antibiotics: for a breastfeeding mother of a jaundiced newborn with unknown G6PD status, cefalexin is the safest choice. Avoid nitrofurantoin (haemolysis in G6PD deficiency) and sulphonamides (displace bilirubin from albumin, kernicterus risk).
- Ibuprofen is the NSAID of choice in breastfeeding (short half-life, very little in milk). Sertraline is a preferred antidepressant; warfarin is compatible.
Remember Prolactin makes the milk, oxytocin moves it; suckling drives both, and emptying keeps it going.
Exam trap Milk does not flow in pregnancy despite high prolactin because placental progesterone blocks it.
Exam trap The let-down reflex, not prolactin secretion, is the part inhibited by maternal pain and anxiety.
How FCPS asks about this
- How suckling raises prolactin: reduced dopamine from arcuate neurones.
- Amenorrhoea during lactation: prolactin inhibits GnRH, so LH and FSH fall.
- Afterpains during feeds in a multipara: oxytocin contracting the myometrium.
- Milk falls after starting the combined pill: oestrogen opposing prolactin action.
- Failure to lactate after massive PPH, later lethargy: Sheehan syndrome, anterior pituitary necrosis.
- Antibody in colostrum: secretory IgA.
- Drug that decreases prolactin: bromocriptine or cabergoline (dopamine agonists).
Test yourself on this topic
5 of the 42 questions in our bank on this topic. Choose an answer to see why every option is right or wrong.
A pharmacist explains why some drugs reach higher concentrations in breast milk than in maternal plasma. Breast milk has a pH of about 7.1, slightly lower than plasma. Which drug property most favours accumulation in milk?
Answer: Lipid-soluble weak base
Unbound, lipid-soluble, unionised drug crosses the alveolar epithelium. Because milk is slightly more acidic than plasma, a weak base becomes more ionised once in milk and cannot diffuse back, so it is trapped (ion trapping). Weak acids tend to stay in plasma, and high protein binding, large molecular size and ionisation at plasma pH all limit transfer.
Drugs in breast milk
- Milk pH ~7.1 (more acidic)
- Weak bases trapped in milk
- Favoured by lipid solubility, low binding
- Large or protein-bound drugs cross poorly
Remember Acid milk traps basic drugs.
Exam trap Ion trapping applies only to the unbound, unionised fraction that can cross first.
Why the other options are wrong
- Highly protein-bound weak acid Protein binding and acidity keep it in plasma.
- Large water-soluble molecule Large polar molecules cross poorly (e.g. heparin, insulin).
- Highly ionised at plasma pH Ionised drug cannot cross membranes.
- Short half-life weak acid Weak acids are less likely to be trapped in milk.
Three weeks after delivery, a breastfeeding woman starts a combined oral contraceptive pill. Two weeks later her baby seems hungry and her milk output has clearly fallen. Which component of the pill is responsible, and how?
Answer: Oestrogen opposing prolactin action
Oestrogen inhibits milk production by blocking the action of prolactin on the alveolar epithelium, just as high oestrogen in pregnancy holds back lactation. This is why combined pills are avoided in the first 6 weeks of breastfeeding. Progestogen-only methods do not reduce milk output and are preferred.
Contraception in lactation
- Oestrogen reduces milk volume
- Blocks prolactin action on alveoli
- Avoid combined pill < 6 weeks
- Progestogen-only does not reduce milk
Remember Oestrogen and milk do not mix.
Exam trap Progesterone delays lactogenesis before delivery, but progestogen-only pills do not reduce established milk supply.
Why the other options are wrong
- Progestogen blocking oxytocin release Progestogens do not reduce milk ejection.
- Oestrogen inhibiting oxytocin receptors Oestrogen actually increases oxytocin receptors in the uterus.
- Progestogen raising dopamine release Progestogen does not alter hypothalamic dopamine this way.
- Oestrogen destroying alveolar cells The effect is reversible; cells are not destroyed.
During pregnancy, rising placental oestrogen and progesterone prepare the breast for lactation in different ways. Which change in the breast is mainly brought about by oestrogen?
Answer: Growth of the duct system
Oestrogen mainly drives growth, elongation and branching of the ducts, along with stromal and fat growth. Progesterone, with prolactin and placental lactogen, is responsible for lobuloalveolar development. Milk protein synthesis and copious secretion need prolactin after the fall in progesterone, and myoepithelial contraction is caused by oxytocin.
Breast growth in pregnancy
- Oestrogen: ducts
- Progesterone: lobules and alveoli
- Prolactin and hPL assist
- Milk held back until placenta leaves
Remember Oestrogen builds the pipes, progesterone builds the rooms.
Exam trap Oestrogen builds the breast in pregnancy but suppresses milk secretion after delivery.
Why the other options are wrong
- Formation of secretory alveoli Mainly the work of progesterone with prolactin.
- Synthesis of milk proteins Driven by prolactin, held back by high progesterone in pregnancy.
- Contraction of myoepithelium Caused by oxytocin.
- Secretion of colostrum Needs prolactin; oestrogen actually opposes milk secretion.
A 26-year-old breastfeeding mother notices milk spurting within a minute of her baby latching on. Impulses from the nipple ascend the spinal cord to the hypothalamus. In which hypothalamic nuclei are the cell bodies of the neurons that release the hormone responsible?
Answer: Paraventricular and supraoptic
Milk ejection is caused by oxytocin. Oxytocin is made by magnocellular neurons whose cell bodies lie in the paraventricular and supraoptic nuclei; their axons run down the pituitary stalk and release the hormone from the posterior pituitary. Suckling stimulates nipple mechanoreceptors, and the afferent signal reaches these nuclei. The arcuate nucleus holds the dopamine neurons that control prolactin, not oxytocin.
Milk ejection reflex
- Suckling: nipple afferents to hypothalamus
- Oxytocin made in PVN and SON
- Released from posterior pituitary
- Contracts myoepithelial cells
Remember Oxytocin is made high and released low.
Exam trap The posterior pituitary only stores and releases oxytocin; it does not synthesise it.
Why the other options are wrong
- Arcuate and periventricular Arcuate dopamine neurons control prolactin, not milk ejection.
- Suprachiasmatic nucleus Controls circadian rhythm.
- Ventromedial and dorsomedial Concerned with satiety and feeding.
- Medial preoptic area Thermoregulation and sexual behaviour; does not make oxytocin.
Five days after a home delivery, a breastfeeding woman's milk has still not come in, although the baby sucks often. She has persistent heavy red lochia and the uterus is larger than expected. Ultrasound shows retained tissue in the uterine cavity. Why is her milk delayed?
Answer: Placental progesterone still blocking milk
Copious milk secretion (lactogenesis II) normally starts 2–4 days after birth, triggered by the abrupt fall in progesterone when the placenta is delivered. During pregnancy, high progesterone blocks the action of prolactin on the alveolar cells. Retained placental fragments keep producing progesterone, so milk production is delayed until they are removed.
Milk coming in
- Lactogenesis II at day 2–4
- Trigger: fall in progesterone
- Progesterone blocks prolactin action
- Retained placenta delays milk
Remember No placental exit, no milk surge.
Exam trap Prolactin is already high in pregnancy; it is progesterone that holds milk back.
Why the other options are wrong
- Retained tissue releasing dopamine Placental tissue does not secrete dopamine.
- Low prolactin from uterine bleeding Prolactin is high after delivery and with frequent suckling.
- Oxytocin used up by the uterus Oxytocin does not drive milk synthesis.
- Infection suppressing the hypothalamus No evidence of sepsis here; the cause is hormonal.
Where this sits in the CPSP syllabus
- Obstetrics & Gynaecology, Paper 2: Reproduction, pregnancy and labour, Lactation: prolactin and oxytocin; milk ejection reflex
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