How to prepare for the ‘Prolactin’ test: rules for taking it

Prolactin is a pituitary hormone that most often ‘lets patients down’ with falsely high results. Its level is affected by the stress of the blood draw itself, sleep, physical exertion, breast stimulation and dozens of drugs. The editorial team explains how to prepare for the test and how to distinguish genuine hyperprolactinemia from a laboratory artefact.

What prolactin is and why it is measured

Prolactin is synthesised by the lactotroph cells of the anterior pituitary. Its main known function is to stimulate lactation, but the hormone also affects the reproductive system of both sexes. Its secretion is inhibited by dopamine coming from the hypothalamus; that is precisely why drugs that block dopamine receptors raise prolactin.

An excess of prolactin suppresses the release of gonadotropin-releasing hormone, and therefore LH and FSH. In women this manifests as cycle disorders, infertility, galactorrhea. In men — as reduced libido, erectile dysfunction, secondary reduction of testosterone, sometimes gynecomastia.

The test is ordered for the indicated symptoms, in infertility, in low testosterone with low or normal LH, as well as when a pituitary tumour is suspected. The Endocrine Society clinical guideline on hyperprolactinemia (Melmed et al., 2011) describes how to diagnose this condition correctly.

A mistake at the blood-draw stage is especially costly here: a falsely high prolactin may become a reason for pituitary MRI, additional consultations and even unnecessary treatment. That is why proper preparation is the first and cheapest step.

Rules for preparing for the test

Prolactin is a ‘stress hormone’ in the broad sense: its release rises in response to physical and psychological stress, pain, hypoglycemia. Even the vein puncture itself in an anxious person can cause a moderate rise.

Prolactin secretion is also linked to sleep: during sleep the hormone level rises, and after waking it gradually decreases. That is why blood is usually recommended to be taken not immediately after waking, but after some time — in the first half of the day.

• do not take it immediately after waking: a draw 2–3 hours after getting up, in the first half of the day, is usually advised;
• fasting or after a light breakfast without a large amount of protein — check the laboratory's requirements;
• for 24 hours avoid sexual contact, breast stimulation, sauna and intense training;
• do not smoke or consume alcohol the day before and on the day of the test;
• sit calmly for 15–20 minutes before the draw;
• inform the doctor about all medications and supplements, in particular biotin in high doses, which the FDA names as a possible cause of false immunoassay results.

The Endocrine Society guideline notes that a single measurement of prolactin is sufficient for diagnosis if the blood was taken without excessive stress during venipuncture. If the result is only slightly elevated, it is logical to repeat the draw — sometimes after rest with a venous catheter placed in advance, in order to rule out a reaction to the needle.

Drugs and conditions that raise prolactin

Drug-induced hyperprolactinemia is one of the most common causes of an elevated result. The guideline by Melmed and colleagues (2011) recommends ruling out the intake of such drugs before searching for a pituitary tumour.

Do not discontinue prescribed drugs on your own — especially antipsychotics or antidepressants. If the doctor considers it necessary, they may temporarily change the therapy and repeat the test or order an MRI.

Among physiological and pathological conditions, prolactin is raised by pregnancy and breastfeeding, primary hypothyroidism, chronic kidney disease, liver cirrhosis, chest injuries, as well as tumours and other lesions of the hypothalamic-pituitary region. That is why TSH, creatinine and a pregnancy test are often ordered together with prolactin.

In the sports community there is much talk about the ‘prolactin’ side effects of certain anabolic steroids. The evidence base on this is limited, but the very fact of taking any hormonal agents must be reported to the doctor — it directly affects the search for the cause.

Macroprolactin and the ‘hook effect’

Prolactin circulates in the blood in several forms. The main one is monomeric prolactin, which is biologically active. But in some people macroprolactin predominates — a complex of the hormone with IgG-class antibodies. It has low biological activity, yet reacts in immunoassays and gives an ‘elevated’ result without clinical manifestations.

The review by Fahie-Wilson and Smith (2013) describes this problem in detail: macroprolactinemia occurs quite often among people with elevated prolactin and is a cause of unnecessary examinations. To detect it, laboratories use polyethylene glycol (PEG) precipitation, after which the residual monomeric prolactin is measured.

If prolactin is elevated but there are no symptoms, the doctor usually asks the laboratory to perform a macroprolactin test. The Endocrine Society guideline recommends this test precisely in asymptomatic patients with hyperprolactinemia.

The opposite situation is the ‘hook effect’. With very large tumours the prolactin concentration may be so high that it saturates the reagents, and the analyser shows a moderate or even normal value. If a person has a large pituitary lesion but prolactin is ‘only slightly elevated’, the laboratory repeats the measurement with a diluted sample.

When and how to repeat the test

A repeat test is appropriate if the first result slightly exceeds the norm, if the draw took place under stressful conditions or if preparation was violated. It is worth repeating it in the same laboratory so that the results are comparable.

The Pituitary Society guidance (Casanueva et al., 2006) emphasises that the prolactin level generally correlates with the size of a prolactinoma, but a moderate rise has many non-tumour causes. Therefore the assessment always combines the figure with the clinical picture, the list of drugs and, if necessary, imaging.

The units of measurement differ: ng/mL, µg/L or mIU/L. The conversion factor between mass and international units depends on the standard to which the test is calibrated, so comparing results from different laboratories without taking this into account is incorrect.

If you are monitoring prolactin over time, for example during treatment, create identical conditions: the same time of day, the same interval after waking, the same preparation.

Editorial conclusions

Prolactin is extremely sensitive to draw conditions. Stress, recent waking, training, sexual contact and breast stimulation can raise the result without any disease at all.

Proper preparation, accounting for drugs and, if necessary, a macroprolactin test help avoid misdiagnosis. A slight rise requires a repeat test rather than immediate treatment.

The final interpretation, choice of additional examinations and treatment are determined by an endocrinologist.

The editorial team recommends also reading our materials on preparing for the LH, total testosterone and estradiol tests.

References

1. Melmed S, Casanueva FF, Hoffman AR, et al. Diagnosis and treatment of hyperprolactinemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(2):273–288.
2. Casanueva FF, Molitch ME, Schlechte JA, et al. Guidelines of the Pituitary Society for the diagnosis and management of prolactinomas. Clin Endocrinol (Oxf). 2006;65(2):265–273.
3. Fahie-Wilson M, Smith TP. Determination of prolactin: the macroprolactin problem. Best Pract Res Clin Endocrinol Metab. 2013;27(5):725–742.
4. Strauss JF, Barbieri RL (eds). Yen & Jaffe's Reproductive Endocrinology. 8th ed. Elsevier; 2019.
5. U.S. Food and Drug Administration. The FDA warns that biotin may interfere with lab tests: FDA safety communication. 2017.