Hyperprolactinemia mostly affects women. Ladies can have menstrual disorders, problems with getting pregnant, depressive states or even seemingly trivial but nagging headaches. Too high levels of prolactin can also be a problem for men, and it manifests itself in, for example, impotence. When is it worth seeing a doctor? What causes hyperprolactinemia?
Prolactin is an important hormone secreted by the pituitary gland. Excess prolactin is calledhyperprolactinemiaand can be caused by a variety of physiological and pathological factors. How is hyperprolactinemia diagnosed? What are the consequences of hyperprolactinemia?
What is prolactin?
Prolactin is a hormone produced, stored and secreted by the lactotropic cells of the anterior pituitary gland. In addition, prolactin can be secreted by the endometrium, placenta, cells of the immune system, the mammary glands and even some types of cancer.
The secretion of prolactin is inhibited by dopamine and gamma-aminobutyric acid (GABA). On the other hand, the secretion of prolactin is stimulated by:
- Gonadoliberin (GnRH),
- estrogens,
- thyreoliberin (TRH),
- serotonin,
- substance P,
- vasoactive intestinal peptide (VIP).
Prolactin is secreted in pulses in the form of peaks and the highest concentration is reached at night, lower in the morning and lowest in the afternoon.
Prolaktyna, among others :
- stimulates the development of the breast gland,
- initiates and maintains lactation,
- stimulates the production of progesterone by the corpus luteum.
It is also worth knowing that prolactin in the body occurs in various forms:
- monomeric form with a mass of 22-23 kDa, which is about 80-95% of circulating prolactin; is the most biologically active,
- large prolactin, which is a combination of two monomeric forms of prolactin, which accounts for 10-20% of circulating prolactin; its mass is 45-60 kDa,
- big-big prolactin (macroprolactin) with a mass greater than 150 kDa, which is a complex of many prolactin molecules or a complex of prolactin molecules with IgG4 antibodies; makes up about 2% of circulating prolactin and has poor biological activity.
When the concentration of prolactin in the blood is excessivelyincreases, we are talking about the phenomenon of hyperprolactinemia.
Hyperprolactinemia mainly affects women aged 25-34 . It also occurs in men, but much less frequently.
Causes of hyperprolactinemia
Hyperprolactinemia is usually not a disease in itself, but a symptom that may indicate dysfunction of other organs. Hyperprolactinemia can be caused by both physiological and pathological factors.
The pathological factors causing hyperprolactinaemia include:
- pituitary adenomas e.g. prolactin tumor
- changes in the central nervous system, e.g. gliomas, meningiomas, Rathke's pocket tumors, sarcoidosis, tuberculosis
- damage to the pituitary stalk in the course of surgery or trauma
- drugs:
- antidepressants e.g. tricyclic and serotonin reuptake inhibitors
- neuroleptics, e.g. phenothiazine, butyrophenone, thioxanthin derivatives
- hormonal containing estrogens, androgens, progestogens
- used in peptic ulcer disease, e.g. cimetidine, meclosine
- used in arterial hypertension, e.g. reserpine, verapamil, labetalol
- opiates e.g. morphine
- drugs that improve intestinal peristalsis, e.g. metoclopramide, domperidone, cisapride
- endocrine diseases:
- hypothyroidism
- acromegaly
- Nelson's team
- diabetes
- Addison's disease
- adrenal cortex cancer
- Sheehan's band
- polycystic ovary syndrome
- chronic renal failure
- liver failure
- changes in the thoracic area, e.g. thoracotomy
- alleged pregnancy
The physiological factors causing hyperprolactinaemia include:
- eating a large meal, especially one high in protein or high in fat
- sexual intercourse
- nipple irritation
- lactation
- doing physical exercise
- stress
- sleep (highest prolactin secretion is between 3 and 5 a.m.)
- pregnancy
Hyperprolactinemia and pregnancy
Hyperprolactinaemia is normal during pregnancy. In the eighth week of pregnancy, there is a constant increase in blood prolactin, which reaches its maximum in the perinatal period (up to 400 ng / ml).
After giving birth in women who are not breastfeeding, hyperprolactinemia resolves after about 3 to 6 weeks.
Symptoms of hyperprolactinemia
Hyperprolactinemia is more common in women and can manifest itself in:
- missed or irregular periods
- with anovulatory cycles causing infertility
- corpuscular insufficiency
- milk flow
- menstrual tension syndrome
- moderate hirsutism
- weight gain
- prone to swelling
- osteopenia
- decreased libido
- orgasm disorder
- hyperactivity and anxiety reactions
It is worth noting that in women the presence of symptoms such as amenorrhea, galactorrhoea and fertility disorders should be the first step in the diagnosis of hyperprolactinemia.
In men, the symptoms of hyperprolactinemia are:
- decreased libido
- erectile dysfunction
- decrease in sperm motility
- testicular hypotrophy
- reduction of muscle mass and body hair
- increase in body weight and tendency to accumulate fat in the abdominal area
- depressive and anxiety disorders
- osteopenia
- gynecomastia and galactorrhoea (rare)
Hyperprolactinemia - stimulation test with metoclopramide
When the prolactin level is 25-150 µg / L perform a stimulation test with metoclopramide. The metoclopramide stimulation test is performed to diagnose the causes of hyperprolactinaemia - organic (e.g., a tumor) or functional.
The test consists in administering metoclopramide to the patient, which stimulates the secretion of prolactin. The normal level of prolactin after administration of metoclopramide should be 2-6 times the baseline level. A result greater than a 6-fold increase from baseline indicates functional hyperprolactinemia.
On the other hand, an increase of less than 2 times the baseline value may indicate pseudoprolactinoma, i.e. changes damaging the hypothalamus or causing pressure on the pituitary gland. No increase in prolactin levels at high baseline levels after administration of metoclopramide indicates a prolactin tumor.
Hyperprolactinaemia - macroprolactin
Hyperprolactinemia may be caused by a complex of prolactin and IgG4 antibodies (called macroprolactin) and not by the monomeric form of prolactin itself. Macroprolactin is less biologically active than its monomeric form.
It is estimated that 10-15% of hyperprolactinaemia cases are caused by macroprolactinemiaand cannot be distinguished from clinical symptoms alone from "common" hyperprolactinemia. Macroprolactinemia can only be indicated by a very high level of prolactin in the blood with at the same time poorly expressed clinical symptoms.
Therefore, when macroprolactinemia is suspected in the laboratory, macroprolactin precipitation is used. For this purpose, 12.5% polyethylene glycol (PEG) solution is added to the patient's serum.
Treatment of hyperprolactinaemia
The goal of stabilizing prolactin levels is always to find the cause of hyperprolactinemia. Treatment of hyperprolactinaemia can be divided into pharmacological and operative treatments. Drug treatment involves the use of dopamine agonists:
- Bromocriptine(Parlodel) - the cheapest of this group of drugs, but with a lot of side effects
- Cabergoline(Dostinex) - the most expensive of this group of drugs, but with no side effects
The use of drugs is mainly aimed at restoring the proper functioning of the gonads, restoring fertility and preventing other symptoms of hypogonadism, e.g. osteoporosis.
Hyperprolactinaemia in the course of hypothyroidism, renal or hepatic failure requires first treatment of disorders of these organs. In cases of drug induced hyperprolactinemia, drug discontinuation and replacement with drugs with similar effects, but not prolactin-elevating, should be considered.
Surgical treatment is used for pituitary tumors.
- Female hormones: estrogens, progesterone, androgens, prolactin, thyroid hormones
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