Hyperprolactinemia: Causes, Symptoms, Diagnosis, and Treatment

Hyperprolactinemia is a condition in which blood levels of prolactin, a hormone produced by the anterior pituitary gland, are elevated. This laboratory test alone does not necessarily confirm a tumor diagnosis: the increase may be physiological, drug-induced, functional, or related to diseases of the pituitary gland and other organs. In clinical practice, it is a common endocrine syndrome because it affects the menstrual cycle, ovulation, fertility, sexual function, bone health, and, if the cause is tumor-related, sometimes vision and neurological symptoms. [1]

Prolactin levels normally increase during pregnancy, breastfeeding, sleep, physical activity, and stress. Therefore, the doctor's task is not simply to see a high level, but to understand whether it is a normal response or a sign of disease. For this reason, a proper diagnosis of hyperprolactinemia is based on a step-by-step approach: first, the elevation itself is confirmed, then physiological causes, medications, and laboratory tests are ruled out, and only then do they move on to visualizing the pituitary gland and choosing a treatment. [2]

The most common pathological cause of tumor-induced hyperprolactinemia is prolactinoma —a hormonally active pituitary tumor that secretes prolactin. However, among all the causes of the syndrome, medications, primarily antipsychotics, often predominate, rather than tumors. This is crucial because the tactics in these situations differ fundamentally: with medication-induced hyperprolactinemia, a reassessment of therapy is sometimes sufficient, while with prolactinoma, long-term treatment with dopamine agonists, surgery, or, in rare resistant cases, more complex treatments may be required. [3]

Hyperprolactinemia has implications beyond the reproductive system. Long-term elevated prolactin levels can suppress the production of sex hormones, leading to decreased bone mineral density, sexual dysfunction, infertility, fatigue, and a deterioration in quality of life. In large pituitary tumors, headaches, visual field constriction, decreased visual acuity, and symptoms of deficiency of other pituitary hormones are also observed. [4]

Table 1. What is important to know about hyperprolactinemia from the very beginning. [5]

Paragraph	Brief explanation
What is this?	Increased levels of prolactin in the blood
Is it always a disease?	No, it happens during pregnancy, lactation, sleep, stress, and strain.
A common non-neoplastic cause	Medications, especially antipsychotic drugs
The main tumor cause	Pituitary prolactinoma
Main manifestations	Menstrual irregularities, breast discharge, infertility, decreased libido, erectile dysfunction
What is dangerous if it lasts for a long time?	Hypogonadism, bone loss, decreased quality of life
When it's especially important not to delay	In case of visual impairment, severe headache, signs of a large tumor

Code according to ICD-10 and ICD-11

In the International Classification of Diseases, 10th revision, hyperprolactinemia is coded as E22.1 – hyperprolactinemia. This is the code for prolactin hypersecretion syndrome. If the cause is a pituitary tumor, it is usually additionally identified with a separate tumor code, as it is clinically important to record both the endocrine disorder and the tumor itself. [6]

In the International Classification of Diseases, 11th revision, the syndrome is assigned code 5A60.1 – hyperprolactinemia. If prolactinoma is documented as a benign endocrine neoplasm of the pituitary gland, a separate tumor code from the section on benign endocrine neoplasms is used in coding practice. This distinction is important for statistics, patient routing, and accurate description of the cause of the disease. [7]

Table 2. Codes most commonly used for hyperprolactinemia. [8]

Situation	ICD-10	ICD-11	Comment
Hyperprolactinemia as a syndrome	E22.1	5A60.1	The main code of the endocrine disorder itself
Benign pituitary tumor	D35.2	2F37.Y	Used additionally if prolactinoma is confirmed
Drug-induced form	E22.1 plus external reason code	5A60.1 indicating the medicinal cause	It is important to reflect the causative drug

Epidemiology

Hyperprolactinemia is common, but its incidence varies greatly depending on the population being tested. In the general adult population, it is relatively rare, whereas among individuals with amenorrhea, oligomenorrhea, abnormal uterine bleeding, infertility, decreased libido, or erectile dysfunction, the proportion of patients with elevated prolactin is significantly higher. Among women undergoing infertility evaluation, hyperprolactinemia is detected in approximately 15-20%. [9]

Prolactinomas are the most common functioning pituitary tumors. Current reviews indicate an estimated prevalence of approximately 50 cases per 100,000 population and an incidence of approximately 3-5 new cases per 100,000 per year. These tumors are significantly more common in women aged 25-44 years, and gender differences diminish after menopause. [10]

A separate, large category is drug-induced hyperprolactinemia. Among patients with schizophrenia or other mental disorders taking certain antipsychotic medications, the prevalence of elevated prolactin levels can reach 30-75%, and in some studies, the range is even wider. This occurs especially frequently with medications that potently block dopamine receptors, including typical antipsychotics, risperidone, paliperidone, and amisulpride. [11]

Hyperprolactinemia is also common in patients with chronic kidney disease and in people undergoing dialysis. Reviews indicate that it occurs in approximately 50-70% of women undergoing chronic dialysis, and in approximately 25-50% of men. This is due not only to decreased hormone excretion but also to impaired central regulation. [12]

Table 3. Where hyperprolactinemia occurs most often. [13]

Group	Estimated frequency	Clinical significance
General adult population	Not tall	Often asymptomatic or not detected without reason
Women with infertility	About 15-20%	May be a reversible cause of anovulation
Patients on antipsychotic therapy	Often 30-75% and higher	Evaluation of symptoms and revision of therapy is important.
Patients with prolactinoma	Prevalence is about 50 per 100,000	The most common functioning pituitary tumor
Patients on chronic dialysis	Often, especially in women	Usually associated with systemic disease

Reasons

The causes of hyperprolactinemia are conveniently divided into four broad groups: physiological, medicinal, systemic, and hypothalamic-pituitary. Physiological causes include pregnancy, breastfeeding, sleep, stress, and physical activity. These causes do not require treatment as a disease, but they do require proper analysis. [14]

Drug-induced hyperprolactinemia is one of the most common forms. The most common culprits are antipsychotic drugs, but metoclopramide, domperidone, some antidepressants, verapamil, opioids, methyldopa, and a number of other drugs that affect dopamine regulation can also increase prolactin levels. The mechanism is usually associated with the blockade of dopamine receptors or the weakening of the inhibitory effect of dopamine on pituitary lactotroph cells. [15]

Systemic causes include primarily primary hypothyroidism, chronic kidney disease, liver cirrhosis, certain chest conditions, and, less commonly, seizures. Hypothyroidism increases thyrotropin-releasing hormone, which stimulates not only thyroid-stimulating cells but also lactotrophic cells. In renal failure, decreased prolactin clearance and impaired central regulation play a significant role. [16]

Hypothalamic-pituitary causes include prolactinomas, other tumors of the sella turcica and parasellar region, pituitary stalk compression, lymphocytic hypophysitis, cysts, and the consequences of surgery or trauma. It is important to distinguish between a true prolactinoma, in which the tumor itself produces prolactin, and the so-called stalk effect, in which dopamine delivery to the pituitary gland is impaired due to mechanical block. In rare cases, extra-pituitary sources of pathological prolactin secretion have been described, but this is anecdotal and not a routine clinical situation. [17]

Risk factors

Gender and age are important factors in determining the tumor type. Microprolactinomas are more often diagnosed in women of reproductive age, while in men, the tumor is often detected later, at the macroadenoma stage, when headaches, decreased vision, or severe hypogonadism develop. This does not mean that men are less likely to suffer from all forms of hyperprolactinemia, but they are more likely to be diagnosed late. [18]

Risk factors associated with the drug formulation include long-term use of drugs that block dopamine transmission. Particularly significant are first-generation antipsychotics, risperidone, paliperidone, and amisulpride, as well as long-term use of antiemetics with dopamine blocking activity. The risk is higher if the dose is increased, the drug is prescribed for a long time, and symptoms are not actively monitored. [19]

It's especially important to consider conditions that don't cause prolactinoma but increase the likelihood of the syndrome: primary hypothyroidism, chronic kidney disease, cirrhosis, polycystic ovary syndrome, chest wall lesions, and previous pituitary surgery. For the clinician, these aren't just underlying conditions, but real clues to the underlying cause. The more accurately the risk factor is identified, the fewer unnecessary tests are needed and the more appropriate the treatment. [20]

Table 4. Main causes and risk factors. [21]

Category	Examples	How does prolactin increase?
Physiological	Pregnancy, lactation, sleep, stress, workload	Normal adaptive secretion
Medicinal	Antipsychotics, metoclopramide, domperidone, antidepressants, opioids, verapamil	Weakening of dopamine inhibition
Systemic	Primary hypothyroidism, chronic kidney disease, cirrhosis	Increased stimulation or decreased clearance
Pituitary	Prolactinoma	Autonomous secretion by a tumor
Parasellar	Inactive macroadenomas, craniopharyngioma, other space-occupying lesions	Stem effect
Rare	Extra-pituitary secretion, infiltrative diseases	Unusual mechanisms require in-depth diagnostics

Pathogenesis

Normally, prolactin secretion is under constant inhibitory influence from dopamine, which flows from the hypothalamus to the pituitary gland via the portal system. This distinguishes prolactin from many other pituitary hormones, which are primarily stimulated rather than inhibited. Therefore, any condition that reduces dopamine control can lead to an increase in prolactin. [22]

If the cause is a prolactinoma, lactotroph cells begin to secrete the hormone autonomously, and prolactin levels typically increase with tumor size. If the cause is not a tumor, but compression of the pituitary stalk, hypothalamic dopamine is less able to reach the lactotrophs, resulting in a so-called stalk effect. This is why elevated prolactin levels also occur in non-functioning pituitary tumors, which do not produce this hormone themselves. [23]

Excess prolactin suppresses the hypothalamic-pituitary-gonadal axis. Simply put, it reduces the normal pulsation of hormones that trigger estrogen and testosterone production. This leads to anovulation, amenorrhea, infertility, decreased libido, erectile dysfunction, and, if prolonged, bone loss and an increased risk of osteopenia and osteoporosis. [24]

The pathogenesis of complications depends not only on the prolactin level itself, but also on the duration of the disease, the degree of hypogonadism, and the tumor size. With large adenomas, endocrine disturbances are accompanied by mass effect: compression of the optic chiasm, headache, and deficiency of other pituitary hormones. This is why two patients with the same "high prolactin" levels can have completely different clinical presentations. [25]

Table 5. How hyperprolactinemia develops. [26]

Mechanism	What's happening	Clinical outcome
Decreased dopamine inhibition	The pituitary gland receives less inhibitory signal	Increased prolactin
Autonomous secretion by a tumor	Prolactinoma produces hormones itself	Severe and persistent hyperprolactinemia
Amplification of stimulating signals	For example, with hypothyroidism	Moderate or marked increase
Lowering the ground clearance	For chronic kidney disease and some systemic conditions	Accumulation of hormone in the blood
Suppression of the sex axis	Decreased estrogen and testosterone	Infertility, sexual dysfunction, bone loss
Tumor mass effect	Compression of the chiasm and pituitary tissue	Visual and neurological symptoms

Symptoms

In women of reproductive age, hyperprolactinemia most often manifests as menstrual irregularities, lack of ovulation, infertility, breast discharge outside of pregnancy and breastfeeding, decreased libido, and vaginal dryness. Sometimes the first symptom is not the menstrual cycle itself, but the inability to conceive. Some patients also experience dyspareunia, low mood, and fatigue. [27]

In men, the clinical picture is often less pronounced at the outset, leading to a delay in diagnosis. Decreased libido, erectile dysfunction, decreased sperm count, infertility, gynecomastia, and sometimes galactorrhea are typical. With prolonged progression, muscle weakness, hair loss, anemia, and bone loss may develop, accompanied by decreased testosterone. [28]

If the cause is a large pituitary tumor, headache, visual field loss, decreased visual acuity, double vision, and signs of other pituitary hormone deficiency may become prominent. This can occur in both sexes, but in men, macrotumors are diagnosed more often and later, so mass effect is particularly common in them. The larger the tumor, the less the symptoms resemble a "pure" reproductive problem and the more they resemble a neuroendocrine disorder. [29]

With drug-induced hyperprolactinemia, symptoms may be less specific. In a review of drug-induced hyperprolactinemia, the most frequently reported symptoms were menstrual irregularities, milk and lactation complaints, and sexual dysfunction; among studies that analyzed symptoms in detail, infertility occurred in 15-31% of patients. This is a good example of how even a "drug side effect" can have serious consequences for quality of life and reproductive health. [30]

Classification, forms and stages

There is no single, universal staging system for hyperprolactinemia as a syndrome. In practice, doctors classify it by the cause, the degree of prolactin elevation, the presence or absence of a tumor, and, if a tumor is present, its size and invasiveness. This approach is more useful for choosing treatment than attempting to divide the condition into formal "stages." [31]

Based on its origin, hyperprolactinemia is classified as physiological, drug-induced, idiopathic, systemic, and tumor-induced. It is considered idiopathic when prolactin levels are consistently elevated, but no clear cause or tumor can be identified based on imaging data. Some such patients typically have a benign course, while in others, prolactin levels spontaneously normalize over time. [32]

When discussing tumor types, it is common to speak of microprolactinoma, macroprolactinoma, and giant prolactinoma. Microprolactinomas are less than 10 millimeters in size, macroprolactinomas are 10 millimeters or more, and giant variants are very large and typically have a pronounced mass effect. For prognosis, not only the number of millimeters is important, but also whether the tumor extends into the cavernous sinus and how well it responds to dopamine agonist therapy. [33]

Based on clinical severity, the tumor can be divided into asymptomatic, reproductive-symptomatic, and compressive forms. In the first form, a person may have no complaints at all; in the second, menstrual, fertility, and sexual dysfunction are predominant; and in the third, neurological and ophthalmological signs arise due to the tumor's size. This working classification is particularly useful for explaining the disease to patients in simple terms. [34]

Table 6. Practical classification of hyperprolactinemia. [35]

Classification principle	Options	What does this change?
Because of	Physiological, medicinal, systemic, idiopathic, tumor	Defines the main approach to treatment
By symptoms	Asymptomatic, reproductive, compression	Helps to assess urgency
By tumor substrate	No tumor, microprolactinoma, macroprolactinoma, giant form	Affects the choice between medication and surgery
By response to treatment	Sensitive, incomplete, resistant	Needed for planning long-term tactics

Complications and consequences

The main chronic consequence of hyperprolactinemia is hypogonadism. In women, it manifests as anovulation, infertility, and estrogen deficiency; in men, it manifests as decreased testosterone, impaired spermatogenesis, and sexual dysfunction. If the condition persists, it affects not only reproductive function but also overall well-being, sleep, mood, and performance. [36]

A very important complication is decreased bone mineral density. Excess prolactin and sex hormone deficiency together shift the balance of bone remodeling toward resorption. Modern reviews emphasize that bone structure impairment can persist even after biochemical control of the disease, with men being particularly at risk for long-term bone loss. [37]

With large tumors, complications are associated not only with the hormone but also with the tumor's mass. Progressive narrowing of the visual fields, decreased visual acuity, ophthalmoplegia, deficiency of other pituitary hormones, and, in rare cases, an aggressive course requiring combined treatment are possible. This is why macroprolactinoma is not simply a "higher test," but a potentially serious neuroendocrine disorder. [38]

In patients with drug-induced complications, complications also cannot be underestimated. Even if the underlying cause is the drug, prolonged hypogonadism in this setting can lead to decreased bone mass, sexual dysfunction, and decreased adherence to psychiatric treatment. This is one of the reasons why the modern approach calls for not ignoring symptoms, but rather actively discussing them with relevant specialists. [39]

When to see a doctor

You should consult an endocrinologist, gynecologist, andrologist, or general practitioner if you experience amenorrhea, significant prolongation of your cycle, breast discharge outside of pregnancy and breastfeeding, decreased libido, infertility, or erectile dysfunction. Even if the symptoms seem "minor," they may be the first sign of a persistent hormonal imbalance. It is especially important not to delay a visit if symptoms persist beyond several cycles or worsen. [40]

Urgent examination is necessary for headaches, decreased vision, visual field loss, double vision, sudden deterioration of health associated with a known pituitary tumor, or a marked increase in prolactin levels. Current guidelines emphasize that the combination of hyperprolactinemia and visual disturbances requires prompt neuroimaging and an ophthalmological examination rather than prolonged observation. In this situation, speed is essential, as a macroadenoma with optic chiasm compression may be present. [41]

Table 7. Symptoms that require a visit to the doctor and signs that require urgent attention. [42]

Situation	How urgent is it?
Menstrual irregularities, infertility, galactorrhea	Scheduled visit coming soon
Decreased libido, erectile dysfunction, gynecomastia	Scheduled visit
Persistently elevated prolactin in the analysis	Scheduled visit to confirm the cause
Headache due to high prolactin levels	Accelerated examination
Visual field loss, decreased visual acuity, double vision	Urgently
Known pituitary tumor and worsening symptoms	Urgently

Diagnostics

Diagnosis begins not with an MRI, but with a proper blood test. Current guidelines recommend taking blood in the morning, usually 2-3 hours after waking, preferably on an empty stomach or under conditions close to standard, especially if the elevation is mild. If the blood draw went smoothly, one high-quality test is usually sufficient, but if the elevation is borderline, it's wise to double-check the results. [43]

The next step is to rule out the most common causes. The doctor will check for pregnancy, lactation, and the use of antipsychotics, metoclopramide, domperidone, and other medications. They will also check thyroid function and evaluate for chronic kidney and liver disease. It is at this stage that unnecessary CT scanning can often be avoided, as the cause turns out to be drug-related or systemic. [44]

Laboratory tests are very important. If the patient has no typical symptoms and prolactin is moderately elevated, it's worth checking macroprolactin—a large molecular form of the hormone with low biological activity, which can create the impression of "disease" with minimal clinical symptoms. If a very large pituitary tumor is detected and prolactin is only moderately elevated, be aware of the high-dose hook effect and ask the lab to repeat the test with a serum dilution. [45]

Once true hyperprolactinemia is confirmed, the physician considers imaging the pituitary gland. If elevated prolactin levels are confirmed and there is no obvious non-neoplastic cause, contrast-enhanced magnetic resonance imaging of the pituitary gland is performed. If visual disturbances are present, an ophthalmological examination and neuroimaging are urgently needed. [46]

Further diagnosis is refined based on the situation. If hypogonadism is suspected, sex hormones are assessed; in the case of large tumors, other pituitary functions are assessed; and in cases of long-term progression and the risk of bone complications, bone mineral density is measured using dual-energy X-ray absorptiometry. This step-by-step approach is important because it does not overlook dangerous causes, but it also does not make every patient with a single elevated prolactin level a candidate for excessive testing. [47]

Table 8. Step-by-step diagnosis of hyperprolactinemia. [48]

Step	What is being done?	For what
1	Morning blood test for prolactin	Confirm the fact of increase
2	Repeat analysis if the result is borderline	Eliminate transient rise
3	Assessment of pregnancy, lactation, stress, medications	Exclude common non-neoplastic causes
4	Thyroid function tests, kidney and liver assessment	Find the systemic cause
5	Testing for macroprolactin	Do not confuse the biologically inactive form with the true disease
6	Serum dilution in case of large tumor and "unexpectedly low" prolactin	Eliminate the hook effect
7	Magnetic resonance imaging of the pituitary gland	Confirm or exclude a tumor
8	Visual fields, pituitary hormones, bone tissue assessment as indicated	Determine the severity and complications

Differential diagnosis

The main goal of differential diagnosis is to determine whether elevated prolactin levels are actually caused by a prolactinoma. To do this, the doctor compares the clinical presentation, hormone levels, medication history, and imaging data. With a prolactinoma, prolactin levels usually correspond to the tumor size, while with an inactive stalked macroadenoma, the increase is often more moderate. [49]

In the early stages, it's especially important not to confuse true hyperprolactinemia with macroprolactinemia, and the tumor-induced form with drug-induced hyperprolactinemia. If the patient is receiving an antipsychotic and the complaints appear after its prescription, the drug-induced hypothesis becomes very likely. However, if the timing is inconsistent, the hormone level is very high, or there are visual symptoms, a tumor-induced cause should be actively sought, rather than blaming the medication. [50]

The differential diagnosis also includes pregnancy, primary hypothyroidism, chronic kidney disease, cirrhosis, polycystic ovary syndrome, chest wall lesions, hypophysitis, and other tumors of the chiasmatic-sellar region. Sometimes the clinical manifestations are similar, but the mechanisms are different, and therefore the treatments are different. Therefore, a competent differential diagnosis of hyperprolactinemia is not a formality, but the key to avoiding treating the wrong disease. [51]

Table 9. What is most often used to differentiate hyperprolactinemia? [52]

State	What speaks in his favor
Pregnancy	Physiological increase, characteristic anamnesis
Lactation	Normal postpartum increase
Dosage form	Association with initiation or intensification of therapy
Macroprolactinemia	High laboratory values with weak clinical signs
Primary hypothyroidism	Elevated thyroid stimulating hormone, symptoms of hypothyroidism
Chronic kidney disease	Renal failure, uremic background
Inactive macroadenoma	Large tumor and relatively moderate prolactin
Prolactinoma	Marked and persistent increase, consistent with tumor size
Hypophysitis and other sellar diseases	Mass effect, inflammatory or infiltrative context

Treatment

Treatment for hyperprolactinemia always begins not with a one-size-fits-all pill, but with determining why prolactin is elevated in this particular patient. If the increase is physiological, no treatment is necessary. If the cause is medication-related, the primary goal is to discuss with a specialist the possibility of discontinuing, replacing, or reducing the dosage of the medication, rather than automatically prescribing a dopamine agonist. This approach reduces the risk of unnecessary therapy and better aligns with modern personalized management. [53]

In drug-induced hyperprolactinemia, the first step is to discontinue the drug for several days or replace it with an alternative, if clinically feasible and safe. This should be done with particular caution in patients taking antipsychotics: unintentional discontinuation is unacceptable, as mental health is more important than a "pretty test result." If discontinuation or replacement is impossible and the patient remains asymptomatic, international guidelines generally do not recommend active treatment of prolactin itself. If severe hypogonadism or low bone mass is present, sex hormone replacement therapy and multidisciplinary management may be considered. [54]

If hyperprolactinemia is caused by primary hypothyroidism, the underlying condition is treated first. With adequate thyroid hormone replacement therapy, prolactin levels often decrease on their own, as the stimulating effect of thyrotropin-releasing hormone is eliminated. Similarly, with systemic causes, such as chronic kidney disease or cirrhosis, the emphasis is on correcting the underlying condition and assessing the extent to which it explains the elevated hormone levels. This is an important principle: don't treat the number separately from the cause. [55]

For prolactinomas, dopamine agonists remain the first-line treatment, and cabergoline remains the most popular. It is more effective and generally better tolerated than bromocriptine, helping to normalize prolactin levels, reduce tumor size, and restore gonad function. Current reviews and guidelines emphasize that cabergoline is the initial therapy for most patients, especially those with symptoms, infertility, or tumor substrate. [56]

With cabergoline treatment, many patients achieve not only biochemical control but also tumor shrinkage. A 2025 review indicated that therapy with doses of up to 2 milligrams per week for at least 6 months leads to prolactin normalization in most patients, tumor reduction by at least 30%, and restoration of gonadal function. The dose is selected individually: it is usually started cautiously and then adjusted based on test results, tolerability, and tumor dynamics. [57]

Bromocriptine has not disappeared from clinical practice, but its role today is more often a backup. It can be used in cases of cabergoline intolerance, in certain reproductive scenarios, and in situations where a large body of historical safety data is needed. However, overall, the current paradigm has shifted in favor of cabergoline due to its superior efficacy and better tolerability. [58]

Surgical treatment is no longer considered only as a "last resort after failure of oral medications." International consensus and current reviews emphasize that transsphenoidal surgery may be a reasonable first choice in some patients with microprolactinomas and well-demarcated macroprolactinomas, particularly in young women planning pregnancy, in cases of intolerance to long-term drug therapy, or by informed patient choice. However, such a strategy is primarily justified in settings where an experienced, high-volume neurosurgical center is available. [59]

Radiation therapy is not a routine first-line treatment. It is reserved for rare, resistant, invasive, or aggressive tumors when drugs and surgery fail to provide control. It has a slower response and carries a risk of late complications, including hypopituitarism, so it is reserved for carefully selected cases, usually after discussion at a multidisciplinary team. [60]

New and truly important modern approaches concern resistant and aggressive prolactinomas. In such situations, temozolomide is being discussed, and in isolated complex cases, radionuclide therapy, intracellular signaling pathway inhibitors, tyrosine kinase inhibitors, and even immunotherapy are being considered. However, it's important not to create false expectations: these approaches remain niche, the evidence base is limited, and their use is only possible in specialized centers. [61]

Pregnancy is a special scenario. Current data and reviews support a strategy in which, after pregnancy is confirmed, dopamine agonists are typically discontinued in women with microprolactinoma or non-compressing macrotumors and followed by clinical observation. Exceptions include large invasive tumors or existing compressive symptoms, in which case continuation or re-initiation of therapy may be necessary. After delivery, the condition is reevaluated, as remission or decreased disease activity may occur in some women. [62]

Treatment does not end with medication or surgery. The patient requires prolactin monitoring, repeat magnetic resonance imaging (MRI) as indicated, visual field assessment for large tumors, dopamine agonist tolerance monitoring, and bone tissue monitoring. For macroprolactinomas, MRI is often repeated 3-6 months after the start of therapy, and if cabergoline is successfully discontinued, long-term, virtually lifelong laboratory monitoring is necessary due to the risk of relapse. [63]

Table 10. Main methods of treatment of hyperprolactinemia. [64]

Situation	The basic approach	Comment
Physiological increase	Observation	Does not require treatment
Asymptomatic dosage form	Frequently observed	Priority - assessment of the need for a causative drug
Dosage form with symptoms	Drug substitution, interdisciplinary tactics	Unauthorized discontinuation of antipsychotics is unacceptable.
Primary hypothyroidism	Treatment of hypothyroidism	Prolactin often decreases secondarily
Microprolactinoma	Cabergoline or, in some patients, surgery	The choice depends on symptoms and preferences.
Macroprolactinoma	Cabergoline is usually the first line	It is important to monitor the vision and size of the tumor.
Intolerance or resistance	Surgery, less commonly radiation therapy, specialized methods	An expert center is needed
Pregnancy	Individual tactics	Dopamine agonists are often discontinued after pregnancy is confirmed.

Prevention

There is no specific prevention for all forms of hyperprolactinemia, as it is a syndrome with various causes. However, the risk of late diagnosis and complications can be reduced by addressing menstrual irregularities, galactorrhea, erectile dysfunction, and infertility. The earlier the cause is identified, the less likely it is to develop long-term hypogonadism and bone loss. [65]

An important part of prevention is the rational use of medications that increase prolactin. If a patient requires an antipsychotic or antiemetic drug, the physician should be aware of the possible endocrine consequences, and the patient should report sexual dysfunction, menstrual irregularities, and breast discharge. These are not "embarrassing complaints," but clinically significant information that can alter therapy. [66]

Prevention of complications includes bone protection and long-term monitoring. In cases of persistent hypogonadism, it is necessary to promptly address the issue of restoring hormonal status, and in cases of long-term tumor progression, assess bone mineral density. Even after prolactin normalization, monitoring may be necessary for a long time, because metabolic and skeletal consequences do not always resolve immediately. [67]

Forecast

The prognosis is generally favorable if the underlying cause is identified and treated specifically. In drug-induced and systemic forms, prolactin levels often normalize after correction of the underlying factor. In microprolactinomas, the response to cabergoline is usually good, and in some patients, after prolonged prolactin normalization, cautious discontinuation of therapy can be discussed. [68]

Macroprolactinomas also often have a good prognosis, but the road to control is usually longer. Here, not only normalizing hormone levels is important, but also shrinking the tumor, restoring vision, preserving pituitary function, and preventing recurrence. Invasive, resistant, or aggressive tumors have a more serious prognosis and require monitoring in a specialized center. [69]

In some patients, particularly those with idiopathic hyperprolactinemia, spontaneous normalization of prolactin levels is possible. Old, but still clinically relevant, data indicate that spontaneous normalization occurs in approximately 30% of such patients, and that the transition from microprolactinoma to macroprolactinoma is rare. However, even with good biochemical control, bone sequelae, especially in men, may persist longer than expected, so a good test does not always mean complete recovery from the disease. [70]

Table 11. What the forecast depends on. [71]

Factor	Impact on prognosis
Reason for the increase	Physiological and medicinal forms are usually more favorable
Tumor size	The larger the tumor, the higher the risk of mass effect and prolonged treatment
Response to cabergoline	A good early response improves the prognosis
Tumor invasiveness	Increases the risk of incomplete remission
Duration of hypogonadism	Affects bones and quality of life
Patient's gender	Men often have a later diagnosis and a higher risk of bone complications.

FAQ

Can any elevated prolactin level be considered a sign of a prolactinoma?
No. The most common causes of elevated levels are physiological conditions, medications, hypothyroidism, chronic kidney disease, and only then some pituitary causes. This is why a prolactinoma diagnosis is not based on a single number, but on a combination of tests, clinical findings, and magnetic resonance imaging. [72]

Does hyperprolactinemia always need to be treated?
No. Physiological elevations don't require treatment, and in asymptomatic cases, active prolactin therapy itself is often unnecessary. Treatment isn't focused on the laboratory values themselves, but on the underlying cause, symptoms, and consequences for fertility, bone tissue, vision, and quality of life. [73]

What drug is usually the first choice for prolactinoma?
Cabergoline is most often used. It is more effective and better tolerated than bromocriptine, and in many patients, it leads to normalization of prolactin levels, tumor shrinkage, and restoration of reproductive function. [74]

Is hyperprolactinemia dangerous for bones?
Yes, especially if it is long-term and accompanied by estrogen or testosterone deficiency. Recent reviews show that hyperprolactinemia increases the risk of decreased bone mineral density, and in men, bone disorders may persist even after the disease is controlled. [75]

Is it possible to become pregnant with hyperprolactinemia?
Yes, in many cases, especially after prolactin levels are normalized and ovulation is restored with therapy. Furthermore, treatment of prolactinoma with dopamine agonists often restores fertility, so pregnancy planning should be discussed in advance. [76]

What should you do if your prolactin levels are elevated but there are few symptoms?
In this situation, it's especially important to rule out macroprolactinemia, medications, and laboratory errors. If the elevation is moderate and the clinical signs are poor, hasty treatment without clarifying the cause may be a mistake. [77]

When is surgery necessary?
Surgery is considered in cases of intolerance or resistance to dopamine agonists, in some cases of microprolactinomas and well-circumscribed macroprolactinomas, and in patient selection, especially if an experienced neurosurgical center is available. The role of surgery has become significantly broader in recent years than previously. [78]

Can cabergoline be discontinued after improvement?
Sometimes yes, but only after a long period of prolactin normalization and favorable magnetic resonance imaging results. Even after successful discontinuation, long-term monitoring is necessary, as relapse is possible. [79]

Key points from experts

Maria Flecheriu, MD, professor of medicine and neurosurgery and director of the Pituitary Center at Oregon Health & Science University, emphasizes in recent reviews and consensus documents that the management of prolactinomas should be individualized and multidisciplinary. The key message in her work and collaborative publications is that success is not only about normal prolactin levels but also about restoration of gonadal function, tumor shrinkage, preservation of vision, and an acceptable quality of life. [80]

Shlomo Melmed, MD, Professor Emeritus of Medicine and one of the world's leading experts on pituitary tumors, consistently advocates a causal approach to hyperprolactinemia. His work and clinical guidelines emphasize that medications remain the most common non-neoplastic cause, with cabergoline being the preferred treatment option for prolactinoma. Furthermore, this school of thought has particularly clearly articulated the idea that elevated prolactin levels cannot be interpreted outside of a clinical context. [81]

Mark Molitch, MD, professor of endocrinology, has been shaping the clinical approach to hyperprolactinemia and pregnancy for many years. His thesis remains virtually unchanged today: treatment should restore fertility and control the tumor, but not create excessive risks, especially in pregnant women. Modern practice largely continues this line: in most women with microprolactinoma, dopamine agonists are discontinued after pregnancy, with continued close clinical monitoring. [82]