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Prolactin and hyperprolactinemia

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High prolactin, or hyperprolactinemia is one of the most common causes for the absence of menstruation (amenorrhea), accounting for 15-30% of all cases. It mostly affects young women of reproductive age and can contribute to infertility.

What does prolactin normally do, and what effects does hyperprolactinemia have?

The functions of prolactin

The main role of prolactin is to stimulate milk production for a newborn, but it also has many other physiological functions, including:

  • regulating immune functions
  • forming new blood vessels (angiogenesis)
  • growth
  • synergism with steroid hormones

During a pregnancy, the increased estrogen level causes lactotroph cells to proliferate, thereby increasing prolactin secretion starting just 8 weeks into the gestation. Prolactin levels peak at term with a ten-fold increase as compared to non-pregnancy levels. The increased prolactin together with other hormones, such as cortisol, estradiol, progesterone, and insulin cause mammary gland growth.

Since estrogen and progesterone blunt the effects of prolactin during pregnancy, lactation is inhibited until after delivery, when the two hormones fall.

One week postpartum, the serum prolactin level also declines by half. But nipple stimulation by the suckling infant will cause a short-term twofold rise in prolactin production, which is important for milk production. Generally, prolactin levels return to normal within 6 months after delivery in breastfeeding mothers and a few weeks in non-nursing mothers.

Symptoms of hyperprolactinemia

The symptoms of hyperprolactinemia can vary significantly depending on the age, gender and magnitude of the prolactin excess. Women’s symptoms are generally more obvious, including:

  • amenorrhea
  • milky nipple discharge (galactorrhea)
  • low libido
  • infertility
  • decreased bone mass.

It is worth nothing that many women with hyperprolactinemia do not have milk discharge because it also requires adequate estrogen and progesterone priming of the breast. Conversely, women with isolated galactorrhea do not typically have hyperprolactinemia, but instead likely increased sensitivity of the breast.

Low estrogen levels secondary to hyperprolactinemia may result in low bone density in the long term. This is not necessarily restored even after normalisation of prolactin levels. Therefore, it is important to seek treatment earlier rather than later.

Hyperprolactinemia in men

Hyperprolactinemia is not just a women’s dysfunction. Men can also be affected and present erectile dysfunction, decreased libido, infertility, lower bone mass, and rarely galactorrhea. Over time, patients may experience lower energy, reduced muscle mass and increased risk of fractures.

In men, prolactin can cause decreased testosterone and sperm production. The decreased testosterone may lead to low libido, impotence, infertility and oligospermia. Prostate volume is decreased also presumably due to lower testosterone levels.

What can cause hyperprolactinemia?

There are many physiological reasons that can potentially explain hyperprolactinemia, including:

  • pregnancy
  • lactation
  • intercourse
  • exercise
  • stress
  • sleep

Certain medications such as antipsychotic drugs, neuroleptic drugs, antidepressants, antiemetics, opiates, H2-receptor blockers, antihypertensives and calcium channel blockers could also increase prolactin levels.

Apart from these factors, pathological causes include:

  • renal disease and hepatic cirrhosis that decrease the clearance of prolactin
  • hypothyroidism
  • polycystic ovary syndrome (PCOS)
  • primary adrenocortical insufficiency
  • prolactinomas and other pituitary adenomas
  • hypothalamic-pituitary stalk damage
  • pituitary tumours

Pituitary tumours are common and found in 12% of pituitary glands at autopsy. They can show a diverse range of growth and hormonal activity. Prolactinomas are the most common type of hormone-secreting pituitary tumours, accounting for 40% of all pituitary tumours.

Prolactinomas are characterised by size. Those less than 10mm in diameter are called microadenomas and found in about 1% of women age 20-40. Macroadenomas are those that are larger than 10mm in diameter. They are a major cause of hyperprolactinemia in up to 46% cases of hyperprolactinemia in one study and occurs in 3.7% of the general population. Macroprolactinoma can arise from many different causes, but it is benign and usually asymptomatic.

Up to 30% of hyperprolactinemia are classified as “idiopathic”, meaning no cause has been determined. In many cases, small prolactinomas may be present but evade the detection of radiological examinations. Long-term follow-ups in these patients found that many have normal prolactin levels (30%), whereas others experience a further increase in prolactin (10-15%).

Diagnosis of hyperprolactinemia

Normal prolactin levels are usually:

  • Women: <440mIU/L (<25ng/mL)
  • Men: <350mIU/L (<20ng/mL)

The level of prolactin can vary during the day and is highest during sleep. Slight elevations of less than twofold could be due to stress and the test should be repeated.

If a non-prolactin-secreting tumour is present, the prolactin level is rarely above 250ng/mL. Higher levels may suggest a macroadenoma. However, some drugs such as risperidone can also drive prolactin levels to higher than 200ng/mL.

Treatment

Once the causes of hyperprolactinemia have been identified, treatment options are decided on the symptoms and treatment goals. First line treatment usually involves restoring ovarian function, normalising estrogen production and ovulation, suppressing lactation, preventing reductions in bone density, and controlling tumour growth in patients with prolactinomas. Dopamine agonists are usually used to reduce prolactin levels and tumour size.

Asymptomatic patients or those with microadenomas do not necessarily require treatment as 93% of microadenomas do not enlarge over a 4-6 year period.

If you have any questions regarding hyperprolactinemia, get in touch with Dr Alex Polyakov’s team and see how we can help!

References

Textbook of Assisted Reproduction, 2020

Newborn’s temperature: a slight difference matters

While a small rise in temperature is not critical in older children or adults, it can be a vital indicator of a fever in newborns that needs urgent medical attention. Digital thermometers are considered the quickest and most accurate, but will they ever go wrong too?

In a recent episode of the podcast Babytalk, Catherine’s newborn felt hot to this second-time new mum. But the digital thermometer indicated a normal temperature. Luckily, she trusted her instinct and sought confirmation with a mercury thermometer, which showed 38°C, a clear sign of fever.

After she rushed to the hospital, her baby was diagnosed with meningitis, which could lead to death and severe brain injuries if untreated. Thanks to her quick action, Catherine’s boy was given antibiotics promptly and went home with no brain damage.

From this real story, we can learn the importance of correctly reading a newborn’s temperature. Although a fever itself is not a bad thing as it’s just a sign of the body trying to fight an infection, it could be an alarm for something more serious.

What’s a normal temperature for babies and children?

There is not a normal temperature but a range. For babies and children, it is about 36.5°C to 37.5°C. When the temperature rises above 38°C, it is considered significantly high for a baby under three months of age. For older babies, 38.5°C is a high fever.

The normal temperature range also varies depending on how you are taking the temperature. Internal temperatures (oral, rectal) should be slightly higher than an external temperature (armpit).

Are there other signs to look out for?

Just like Catherine, you or your partner as the parents are in the best position to notice anything unusual with the baby. For example, if your baby:

  • feel hotter than usual to touch
  • feel sweaty or clammy
  • have flushed checks
  • are more or less sleepy than usual
  • are more sluggish and tired
  • have wheezing or the chest movement is different

How should you take your child’s temperature safely and accurately?

There are several methods of taking a baby’s temperature such under the tongue, under the arm, in the ear or forehead. The method you choose may be dependent on what thermometer you are using. A digital thermometer should give you a fast and accurate reading, assuming that it is a high-quality thermometer used correctly. Generally, digital thermometer is used for taking under the arm temperature.

The ear thermometer is another option for babies as it can give a reading in just one second. However, it is more expensive, and you must follow the instructions carefully for an accurate reading. If you don’t put the thermometer in the ear correctly, the reading may be misleading.

Strip type thermometers are very basic thermometers that you simply hold against your baby’s forehead. These show the temperature of the skin rather than the body and are not very accurate.

Mercury thermometers were the standard way of temperature testing but have been phasing out in recent years. It can be dangerous if the thermometers break into small pieces and release poisonous mercury. As such, the use of mercury thermometers in infants is generally avoided.

If you are still unsure how to take a baby’s temperature, get in touch with Dr Alex Polyakov’s team and see how we can help!