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Prolactin is a lactogenic hormone derived from pituitary and play a significant role in a variety of reproductive functions. The hormone is synthesized and released by lactotroph cells of anterior pituitary.
Prolactin is a lactogenic hormone derived from pituitary and play a significant role in a variety of reproductive functions. The hormone is synthesized and released by lactotroph cells of anterior pituitary. It is structurally like human growth hormone (HGH) and human placental lactogen (HPL)1.
Prolactin is a 23 kDa polypeptide hormone (198 amino acid) synthesized in the lactotroph cells of the anterior pituitary gland. Its secretion is pulsatile and increases with sleep, stress, food ingestion, pregnancy, chest wall stimulation, and trauma.
Synthesis and Release
Hormone is synthesized and released by lactotroph cells of anterior pituitary. Unlike other tropic hormones, release of prolactin (PRL) is controlled primarily by negative inhibitory mechanism of dopamine. It negatively controls the secretion of other pituitary hormones responsible for gonadal function like LH, FSH.
Several factors exert a stimulatory effect on prolactin secretion especially
Important clinical manifestations are associated with hyperprolactinemia with elevation of TRH secretion that occurs primarily in hypothyroidism 2.
Prolactin homeostasis is reflected by prolactin itself feeding back on the dopamine releasing neurons.
Extra pituitary sources of PRL
These are PRL secreted by breast, endometrium, and decidua
It’s persistent suckling PRL levels remain elevated. Lactational amenorrhoea continues, and this works as a natural contraceptive method3
Endometrium and Decidual PRL
Specialized endometrium of the luteal phase of menstrual cycle.
Human decidual tissue of placental source synthesized and release PRL
Causes of hyperprolactinemia4,5
A) Impaired dopamine delivery
Neuroleptics: Haloperidol, Phenothiazine
Antihypertensive: Calcium-channel blockers and methyldopa
Psychotropic drugs: Tricyclic antidepressant and SSRI
Antiulcer agent: H2 antagonist
2) Neurogenic: Chest wall injury, breast stimulation, breast feeding
3) Pituitary stock compression: Pituitary tumours like adenoma, acromegaly etc
B) Enhanced lactotrophic cell stimulation
Hypothyroidism (increased TRH)
Pituitary adenoma (Prolactinoma)
C) Impaired hepatic and renal clearance
Prolactin cleared less rapidly from systemic circulation thus increasing the blood level.
D) Sometimes there may be abnormal molecules of PRL (big big prolactin). They are not significant in clinical diagnosis.
Hyperprolactinemia in infertility
Hyperprolactinemia is amongst the most common causes of secondary amenorrhoea. If present in pre menarche years may present as delayed puberty primary amenorrhoea. They are the candidates who might present as primary infertility. So, serum PRL should be checked with amenorrhoea (<15-20ng/mL). Circulating PRL can increase transiently during C exercise, breast stimulation and means. Mildly elevated PRL levels should be repeated before the diagnosis of hyperprolactinemia.
Hyperprolactinemia results in anovulation and amenorrhoea: – Stimulates a generalized increase in hypothalamic dopaminergic neuronal activity to suppress PRL secretion but also inhibiting GnRH neurons leading to disruption of GnRH pulse rhythm→ Low GnRH
Consequences of GnRH pulsatility owing to excess PRL may leads to subtle ovulatory disfunction to anovulation or hypogonadotropic hypogonadism.
Mild hyperprolactinemia (20-50ng/mL)
Moderate Hyperprolactinemia (50-100ng/mL)
Higher level (>100ng/mL)
Action on adrenal gland
Prolactin receptors having identified in human adrenal gland and PRL can increase adrenal DHEA production invitro. Prolactin stimulates the adrenal gland which leads to increase in androgen production results in chronic anovulation.
Action on ovaries
Elevated PRL levels result in a spectrum of ovulatory dysfunction ranging from short luteal phase to anovulatory cycles.
Hyperprolactinemia leads to abnormal gonadotropin secretion
Abnormality in GnRH pulsatility is the principal drivers of abnormal gonadotropin secretion pattern that commonly encounter in PCOS as well as obesity related ovulatory dysfunction.
Hyperprolactinemia from any cause and treatment with GnRH analogues (Prostatic cancer) GnRH analogues, androgen (anabolic steroids), glucocorticoids or opiates can suppress gonadotropin secretion. Critical illness or injury (head injury, chronic systemic illness (type II DM) or malnutrition also have been associated with hypogonadotropic hypogonadism.
Fig 1: Overview of diagnosis and management of hyperprolactinemia
A blood test is used to detect excess prolactin levels. If prolactin levels are high, more tests are usually done to check thyroid hormone. Normal thyroid hormone levels rule out hypothyroidism as a cause of hyperprolactinemia.
If a prolactinoma is suspected, an MRI (magnetic resonance imaging) of the brain and pituitary is often the next step.
Treatment for hyperprolactinemia
Treatment is based on the cause. Some people with high prolactin levels, but few have no signs and symptoms, do not need any treatment.
Options for treating tumours include
Prescription medicines: Dopamine Agonists like bromocriptine and cabergoline decrease prolactin production. Bromocriptine is taken 2-3 times a day and Cabergoline is long acting and used twice weekly.
Surgery to remove a tumour: Surgery may be used if medicines have not been effective. Surgery is sometimes needed if the tumour is affecting vision.
Radiation: Rarely, if medicines and surgery have not been effective, radiation is used to shrink the tumour.
Hypothyroidism is treated with synthetic thyroid hormone, which should bring prolactin levels back to normal. If high prolactin levels are caused by prescription medications, other types of medications can be explored.
Picture Credit: Hyperprolactinemia – MSR Blog
|Dr. Saktirupa Chakraborty DGO., MD., FICOG Consultant Visiting Gynaecologist/Obstetrician, Attached to IRM, AMRIHospital, AMWI, Kolkata.|