concentration of prolactin can be given in mass concentration (µg/l or ng/ml), molar concentration (nmol/l or pmol/l), or international units (typically miu/l). the current iu is calibrated against the third international standard for prolactin, is 84/500. reference ampoules of is 84/500 contain 2.5 µg of lyophilized human prolactin and have been assigned an activity of .053 international units. measurements that are calibrated against the current international standard can be converted into mass units using this ratio of grams to ius; prolactin concentrations expressed in miu/l can be converted to µg/l by dividing by 21.2. previous standards use other ratios. the first international reference preparation (or irp) of human prolactin for immunoassay was established in 1978 (75/504 1st irp for human prolactin) at a time when purified human prolactin was in short supply. previous standards relied on prolactin from animal sources. purified human prolactin was scarce, heterogeneous, unstable, and difficult to characterize. a preparation labeled 81/541 was distributed by the who expert committee on biological standardization without official status and given the assigned value of 50 miu/ampoule based on an earlier collaborative study. it was determined that this preparation behaved anomalously in certain immunoassays and was not suitable as an is. three different human pituitary extracts containing prolactin were subsequently obtained as candidates for an is. these were distributed into ampoules coded 83/562, 83/573, and 84/500. collaborative studies involving 20 different laboratories found little difference between these three preparations. 83/562 appeared to be the most stable. this preparation was largely free of dimers and polymers of prolactin. on the basis of these investigations, 83/562 was established as the second is for human prolactin. once stocks of these ampoules were depleted, 84/500 was established as the third is for human prolactin. reference ranges general guidelines for diagnosing prolactin excess (hyperprolactinemia) define the upper threshold of normal prolactin at 25 µg/l for women and 20 µg/l for men. similarly, guidelines for diagnosing prolactin deficiency (hypoprolactinemia) are defined as prolactin levels below 3 µg/l in women and 5 µg/l in men. however, different assays and methods for measuring prolactin are employed by different laboratories and as such the serum reference range for prolactin is often determined by the laboratory performing the measurement. furthermore, prolactin levels vary according to factors as age, sex, menstrual cycle stage and pregnancy. the circumstances surrounding a given prolactin measurement (assay, patient condition, etc.) must therefore be considered before the measurement can be accurately interpreted. the following chart illustrates the variations seen in normal prolactin measurements across different populations. prolactin values were obtained from specific control groups of varying sizes using the immulite assay. typical prolactin values proband prolactin, µg/l women, follicular phase (n = 803) 12.1 women, luteal phase (n = 699) 13.9 women, mid-cycle (n = 53) 17 women, whole cycle (n = 1555) 13.0 women, pregnant, 1st trimester (n = 39) 16 women, pregnant, 2nd trimester (n = 52) 49 women, pregnant, 3rd trimester (n = 54) 113 men, 21–30 (n = 50) 9.2 men, 31–40 (n = 50) 7.1 men, 41–50 (n = 50) 7.0 men, 51–60 (n = 50) 6.2 men, 61–70 (n = 50) 6.9 inter-method variability the following table illustrates variability in reference ranges of serum prolactin between some commonly used assay methods (as of 2008), using a control group of healthy health care professionals (53 males, age 20–64 years, median 28 years; 97 females, age 19–59 years, median 29 years) in essex, england: assay methodmeanprolactinlower limit 2.5th percentileupper limit 97.5th percentile µg/lmiu/lµg/lmiu/lµg/lmiu/l females centaur7.921683.357116.4348 immulite9.251963.547518.7396 access9.061923.637719.3408 aia9.522573.8910520.3548 elecsys10.52224.158823.2492 architect10.62254.629821.1447 males access6.891462.745813.1277 centaur7.881672.976312.4262 immulite7.451583.307013.3281 aia7.812113.308913.5365 elecsys8.491803.407215.6331 architect8.871884.018514.6310 an example of the use of the above table is, if using the centaur assay to estimate prolactin values in µg/l for females, the mean is 7.92 µg/l and the reference range is 3.35–16.4 µg/l. conditions elevated levels hyperprolactinaemia, or excess serum prolactin, is associated with hypoestrogenism, anovulatory infertility, oligomenorrhoea, amenorrhoea, unexpected lactation and loss of libido in women and erectile dysfunction and loss of libido in men. physiological coitus exercise lactation pregnancy sleep stress depression pharmacological anesthetics anticonvulsant antihistamines (h2) antihypertensives cholinergic agonist drug-induced hypersecretion catecholamine depletor dopamine receptor blockers dopamine synthesis inhibitor estrogens oral contraceptives oral contraceptive withdrawal antipsychotics neuropeptides opioids and opioid receptor antagonists pathological hypothalamic-pituitary stalk damage granulomas infiltrations radiation rathke's cyst trauma pituitary stalk resection suprasellar surgery tumors craniopharyngioma germinoma hypothalamic metastases meningioma suprasellar pituitary mass extension surgery pituitary acromegaly idiopathic lymphocytic hypophysitis or parasellar mass macroadenoma (compressive) macroprolactinemia plurihumoral adenoma prolactinoma systemic disorders chest-neurologic chest wall trauma herpes zoster chronic renal failure cirrhosis cranial radiation epileptic seizures polycystic ovarian disease pseudocyesis chronic low levels of thyroid hormone decreased levels main article: hypoprolactinemia hypoprolactinemia, or serum prolactin deficiency, is associated with ovarian dysfunction in women, and arteriogenic erectile dysfunction, premature ejaculation, oligozoospermia, asthenospermia, hypofunction of seminal vesicles and hypoandrogenism in men. in one study, normal sperm characteristics were restored when prolactin levels were raised to normal values in hypoprolactinemic men. hypoprolactinemia can result from hypopituitarism, excessive dopaminergic action in the tuberoinfundibular pathway and ingestion of d2 receptor agonists such as bromocriptine. in medicine prolactin is available commercially for use in other animals, but not in humans. it is used to stimulate lactation in animals. the biological half-life of prolactin in humans is around 15–20 minutes. the d2 receptor is involved in the regulation of prolactin secretion, and agonists of the receptor such as bromocriptine and cabergoline decrease prolactin levels while antagonists of the receptor such as domperidone, metoclopramide, haloperidol, risperidone, and sulpiride increase prolactin levels. d2 receptor antagonists like domperidone, metoclopramide, and sulpiride are used as galactogogues to increase prolactin secretion in the pituitary gland and induce lactation in humans.