What Are The Most Common Causes of Hyperprolactinemia?

What Does Prolactin Normally Do?

Prolactin is made and released by a group of specialised cells present in the anterior pituitary gland. Normally, the most recognised role of prolactin is to stimulate milk production in women after childbirth. It also helps in regulating immune function, reproductive health, and the body’s response to stress. In men, the hormone regulates reproductive health, thus supporting testosterone production, sperm production, and libido.

Prolactin secretion is largely controlled by dopamine, a brain chemical that acts as a natural brake on prolactin release. When dopamine activity drops for whatever reason, prolactin levels can rise unchecked.

Generally, the normal range of prolactin in your blood should be around:

What Is Hyperprolactinemia?

Hyperprolactinemia simply means the presence of too much prolactin in your blood. When prolactin levels are too high in an individual, it can disrupt the normal balance of reproductive hormones. In women, this often leads to irregular periods or the complete absence of periods. It can also cause difficulty in getting pregnant, and sometimes even unexpected milk production from the breasts, even in those women who have never been pregnant.

While hyperprolactinemia is not life-threatening, it can cause issues with infertility. It is one of the most common hormonal disorders seen in clinical practice, and identifying the root cause of the problem is important before choosing the treatment path. Luckily, hyperprolactinemia is treatable.

Common symptoms of hyperprolactinemia include:

• Infertility
• Low libido
• Low bone mass
• Milky discharge from the nipples, even when you are not pregnant or breastfeeding.

In women, these symptoms may be seen:

• Irregular periods
• Absence of periods
• Painful intercourse

There are multiple complications related to hyperprolactinemia, including but not limited to persistent infertility, reduced bone density, impaired sexual function, cranial nerve problems, and bleeding into the tumour. Visit a doctor if you notice any of the above-mentioned symptoms to avoid the condition worsening.

How Does Hyperprolactinemia Affect Men?

When prolactin is produced in excess in males, it disrupts testosterone production. It works by inhibiting the signalling from the brain to the gonads, more precisely by suppressing a hormone known as GnRH (Gonadotropin-Releasing Hormone). The suppression of GnRH subsequently results in low levels of LH (Luteinizing Hormone) and FSH (Follicle-Stimulating Hormone), the hormones responsible for testosterone and sperm production. The problem resulting from this hormone imbalance is referred to as hypogonadism.

The effects of this hormonal imbalance can show up in several ways. Some symptoms to watch out for, especially in men, include:

• Difficulty getting or maintaining an erection
• Low levels of testosterone
• Gynecomastia: enlargement of breast tissue
• In rare cases, men may develop galactorrhea (milk discharge)

What Are The Most Common Causes Of Hyperprolactinemia?

The most common causes of hyperprolactinemia include:

Prolactinomas (Pituitary Tumours)

A pituitary tumour is the most common cause of hyperprolactinemia. It is a benign growth in the pituitary gland that causes excessive prolactin production. Pituitary tumours, or prolactinomas, can be classified into two groups based on size.

• Microprolactinomas: These non-cancerous tumours are smaller than 10 mm and are more commonly found, especially in women.
• Macroprolactinomas: They are larger than 10 mm and tend to cause more significant hormonal disruption.

With the continuous production of prolactin by the tumour cells themselves, the prolactin concentrations could be elevated above normal. For example, it may exceed 200 ng/mL in cases of macroprolactinomas. Common clinical signs include chronic galactorrhea, irregular menstrual cycles, or vision problems caused by the tumour pressing on nearby optic nerves.

Other Pituitary Tumours and Conditions

Not all pituitary tumours secrete prolactin themselves. Some non-prolactin-secreting pituitary adenomas can also raise the levels, although indirectly. These tumours compress the pituitary stalk, which is the connection between the hypothalamus and the pituitary gland.

Due to the compression, the normal flow of dopamine is affected, thus reducing the inhibitory signal. This causes the prolactin levels to rise. Other conditions, like Empty Sella Syndrome (ESS), can also mildly elevate prolactin levels.

Can Medications Cause Hyperprolactinemia?

Drug-induced hyperprolactinemia is another common occurrence when it comes to increased levels of prolactin. Any medication that disrupts dopamine receptors or reduces dopamine availability in the brain can eventually affect prolactin production.

• Antipsychotic medications: First-generation antipsychotic medications are particularly likely to raise prolactin significantly. On the other hand, second-generation antipsychotic medications can differ from medicine to medicine. While some may cause elevation, others pose a lower risk.
• Antidepressants: Certain antidepressants, like SSRIs and tricyclics, can induce a slight to moderate increase in prolactin levels.
• Antiemetics: These are dopamine receptor blockers, commonly prescribed for nausea and gastroparesis. The patients taking these medicines for prolonged periods are especially vulnerable.
• Opioids: Prolonged exposure to opioids causes a decrease in dopamine secretion, allowing prolactin secretion to increase. This is why people dependent on opioids suffer from various hormonal imbalances, including lower testosterone in men and menstrual problems in women.
• Others: Other medications like birth control pills and high blood pressure medications can also result in hyperprolactinemia.

Other Causes Of Hyperprolactinemia

Another cause of hyperprolactinemia is primary hypothyroidism, where the thyroid gland is underactive. When thyroid hormone levels decrease, the brain responds by increasing thyrotropin-releasing hormone (TRH) production, attempting to stimulate the thyroid. While TRH does stimulate the thyroid, it also stimulates the pituitary gland to release more prolactin.

• Chronic Kidney Disease (CKD) is also a cause of hyperprolactinemia. In healthy individuals, the kidneys help by clearing prolactin from the bloodstream. When kidney function deteriorates, as in various forms of CKD, prolactin clearance is significantly reduced, leading to its accumulation in the body.
• Liver diseases like liver cirrhosis can also cause hyperprolactinemia in people. Since the liver is involved in the metabolism and degradation of various hormones, severe liver diseases such as cirrhosis can impair these processes.
• Other issues, like physiological stress and excessive exercise, can lead to hyperprolactinemia in some. However, these causes are usually transient and do not lead to chronically elevated prolactin. In the case of stress, be it physical (trauma, surgery, etc) or physiological (acute anxiety), prolactin acts as a stress-responsive hormone, leading to its rise. As for vigorous exercise, prolonged aerobic activity can cause a short-term spike in the prolactin levels.

What Is Idiopathic Hyperprolactinemia?

Some individuals may have elevated prolactin levels without any plausible cause. This phenomenon is known as idiopathic hyperprolactinemia. In such cases, no real cause is identified despite the person having undergone exhaustive testing, including MRI of the pituitary gland, thyroid function tests, kidney and liver function tests, and an assessment of any medications they may be on.

A possible cause of some of these cases can be macroprolactinemia. In this condition, the prolactin hormone binds itself with immunoglobulin antibodies, forming macroprolactin. Although these large molecules are biologically inactive, their presence in the bloodstream is still recognised by standard prolactin assays. This results in falsified readings. People with this condition are generally asymptomatic or mildly symptomatic.

Treatment Methods For High Prolactin Levels

Before treatment comes the diagnosis. A prolactin test measures the hormone's levels in a blood sample. There is little to no risk associated with a blood test, and the entire procedure may take only about five minutes. You might have to wait for a couple of days for the results. Diagnosis also includes ruling out other causes, like pregnancy. An MRI scan may also be required to look for pituitary tumours, if any.

Once test results confirm that your prolactin levels are higher than usual, your healthcare provider may suggest one of the following treatments or management options, depending on the underlying cause.

• Medication: Dopamine agonists may be prescribed to regulate the prolactin levels. These work by shrinking the prolactinoma tumours.
• Surgery: In case medication does not work for you, you may need to undergo surgery to remove the prolactinoma.
• Radiation Therapy: In extremely rare cases, pituitary tumours may have to be treated by radiation therapy if all else fails.

Keep in mind that you may not have to get any treatment at all if prolactin levels are high with no or few symptoms.

Conclusion

Hyperprolactinemia is a hormonal signal that suggests something is affecting the body's normal production of prolactin. The causes of hyperprolactinemia can range from pituitary tumours or prolactinomas to dopamine-blocking medications. Some less obvious triggers can include hypothyroidism, chronic kidney disease, liver disease, stress, and even excessive exercise.

Getting an accurate diagnosis through proper blood tests is extremely important for effective treatment. If you are experiencing symptoms like a low sex drive, irregular or absent periods, unexpected breast milk production in both men and women, or unexplained fertility issues, these could all be signs of elevated prolactin. Make sure to discuss the issue at hand with a healthcare professional, as early detection can lead to better outcomes.