Macroprolactin vs. Prolactin

What's the Difference?

Macroprolactin and prolactin are both hormones produced by the pituitary gland that play a crucial role in lactation and reproductive functions. However, they differ in their molecular structure and biological activity. Prolactin is the biologically active form of the hormone, responsible for stimulating milk production and regulating the menstrual cycle. On the other hand, macroprolactin is an inactive form of prolactin, where the hormone is bound to immunoglobulins. This binding reduces its biological activity, resulting in a longer half-life and decreased ability to stimulate lactation. While prolactin levels are commonly measured to diagnose conditions like hyperprolactinemia, it is important to differentiate between macroprolactin and prolactin to accurately assess the hormonal status and determine the appropriate treatment.


DefinitionHigh molecular weight form of prolactinPolypeptide hormone produced by the pituitary gland
StructureConsists of prolactin bound to immunoglobulin G (IgG)Single-chain polypeptide
FunctionMay have reduced biological activity compared to prolactinStimulates milk production, regulates reproductive function
MeasurementDetected through polyethylene glycol (PEG) precipitationMeasured using immunoassays
PrevalenceRelatively common, can be found in some individualsNormal form of prolactin in most individuals
Clinical SignificanceMacroprolactinemia may lead to misdiagnosis of hyperprolactinemiaElevated levels may indicate pituitary disorders or other conditions

Further Detail


Prolactin is a hormone produced by the pituitary gland in the brain. It plays a crucial role in various physiological processes, particularly in the female reproductive system. However, sometimes a variant of prolactin called macroprolactin can be present in the blood. Macroprolactin is a larger form of prolactin that is bound to immunoglobulins, which can affect its biological activity. In this article, we will explore the attributes of macroprolactin and compare them to those of prolactin.


Prolactin and macroprolactin share a similar structure, both being polypeptide hormones composed of a single chain of amino acids. However, macroprolactin is characterized by its larger size due to the presence of immunoglobulins. This difference in size can affect the clearance and biological activity of macroprolactin in the body.

Biological Activity

Prolactin is primarily responsible for stimulating milk production in the mammary glands after childbirth. It also plays a role in regulating the menstrual cycle, promoting breast development, and influencing maternal behavior. On the other hand, macroprolactin has reduced biological activity compared to prolactin. This is due to the binding of immunoglobulins, which prevents macroprolactin from interacting with its receptors effectively. As a result, macroprolactin is less efficient in stimulating milk production and other prolactin-mediated functions.

Diagnostic Implications

The presence of macroprolactin in the blood can lead to diagnostic challenges. When measuring total prolactin levels, immunoassays may not differentiate between prolactin and macroprolactin, leading to an overestimation of prolactin levels. This can potentially lead to misdiagnosis and unnecessary treatment. To accurately assess prolactin levels, it is important to perform a macroprolactin screening test, such as polyethylene glycol (PEG) precipitation. This test selectively removes macroprolactin from the sample, allowing for the measurement of prolactin levels without interference.

Clinical Significance

Macroprolactinemia, the presence of elevated levels of macroprolactin in the blood, is generally considered a benign condition. Unlike hyperprolactinemia, which is associated with various clinical manifestations, macroprolactinemia is often asymptomatic and does not require treatment. However, in some cases, macroprolactinemia can lead to misdiagnosis and unnecessary investigations or interventions. Therefore, it is crucial to differentiate between macroprolactin and prolactin to avoid unnecessary medical interventions.


The prevalence of macroprolactinemia varies among different populations. Studies have reported varying rates, ranging from 5% to 40% of patients with hyperprolactinemia. The wide range of prevalence can be attributed to differences in laboratory techniques, patient populations, and the criteria used to define macroprolactinemia. It is important for laboratories to establish appropriate cutoff values and screening methods to accurately identify macroprolactinemia.

Clinical Evaluation

When macroprolactinemia is suspected, further clinical evaluation is necessary to determine the cause of hyperprolactinemia symptoms. This may involve assessing the patient's medical history, conducting a physical examination, and performing additional laboratory tests. Magnetic resonance imaging (MRI) of the pituitary gland is often recommended to rule out the presence of pituitary tumors or other structural abnormalities that could cause hyperprolactinemia. Differentiating between macroprolactin and prolactin is crucial in guiding appropriate clinical management.

Treatment Considerations

As mentioned earlier, macroprolactinemia is generally considered a benign condition and does not require specific treatment. However, in cases where hyperprolactinemia symptoms are present, it is important to confirm the absence of pituitary tumors or other underlying causes. If symptoms persist and are attributed to prolactin excess, treatment options such as dopamine agonists may be considered. These medications work by reducing prolactin secretion and can effectively alleviate symptoms associated with hyperprolactinemia.


In summary, macroprolactin and prolactin are two forms of the same hormone that differ in their structure and biological activity. Macroprolactin is a larger form of prolactin bound to immunoglobulins, which reduces its biological activity. The presence of macroprolactin can lead to diagnostic challenges, requiring specific screening tests to accurately measure prolactin levels. While macroprolactinemia is generally considered benign, it is important to differentiate between macroprolactin and prolactin to avoid unnecessary medical interventions. Further research is needed to better understand the prevalence, clinical implications, and long-term effects of macroprolactinemia.

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