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Gynecol Endocrinol, Early Online: 1–5

! 2015 Informa UK Ltd. DOI: 10.3109/09513590.2015.1017810

REVIEW ARTICLE

Hyperprolactinemia: pathophysiology and therapeutic approach

Anna Capozzi1,2, Giovanni Scambia2, Alfredo Pontecorvi1, and Stefano Lello2
1
Department of Endocrinology and Metabolism and 2Department of Woman and Child Health, Catholic University of Rome, Rome, Italy

Abstract Keywords
Prolactin (PRL) is a hormone, mainly secreted by lactotroph cells of the anterior pituitary gland. Cabergoline, dopamine agonist,
Gynecol Endocrinol Downloaded from informahealthcare.com by University of Otago on 07/18/15

Recent studies have shown it may also be produced by many extrapituitary cells. Its well- hyperprolactinemia, oligomenorrhea
recognized PRL plays an important role in lactation during pregnancy, but it is involved in other
biological functions such as angiogenesis, immunoregulation and osmoregulation. History
Hyperprolactinemia is a typical condition producing reproductive dysfunction in both sexes,
resulting in hypogonadism, infertility and galactorrhea. It may be also asymptomatic. Received 8 January 2015
Lactotroph adenomas (prolactinoma) is one of the most common cause of PRL excess, Accepted 8 February 2015
representing approximately 40% of all pituitary tumors. Several other conditions should be Published online 6 July 2015
excluded before a clear diagnosis of hyperprolactinemia is made. Hyperprolactinemia may be
secondary to pharmacological or pathological interruption of hypothalamic–pituitary dopa-
minergic pathways or idiopathic. Stress, renal failure or hypothyroidism are other frequent
conditions to exclude in patients with hyperprolactinemia. We will review biochemical
characteristics and physiological functions of that hormone. Clinical and pharmacological
approach to hyperprolactinemia will also be discussed.
For personal use only.

Introduction In this article, molecular characteristics and biological actions

Prolactin (PRL) is a pituitary hormone firstly identified in
lactotroph cells, which mainly regulate mammalian glands
secretion during postpartum period [1]. However, PRL was
found to produce ‘‘pleiotropic’’ effects, on metabolism, osmo-
regulation and immune and the nervous systems [2]. Excess of
PRL called ‘‘hyperprolactinemia’’ is a common syndrome
affecting both sexes. It is characterized by the classical amenor-
rhea–galactorrhea and symptoms of hypogonadotrophic hypo-
gonadism [3]. There are two types of hyperprolactinemias,
according to etiopathogenesis: the organic and functional
hyperprolactinemia [4]. Organic hyperprolactinemia is mainly
due to pituitary gland tumors secreting only PRL or PRL-
associated with other pituitary tropins, such as growth hormone
(GH). Another possible cause of organic hyperprolactinemia is
the damage to the dopaminergic neurons of the hypothalamus or
non-functioning pituitary adenomas or masses compressing the
pituitary stalk [5]. Functional hyperprolactinemia occurs in such
endocrinopathies, as primary hypothyroidism and primary
adrenocortical insufficiency, or in hepatic cirrhosis and renal
failure. Hyperprolactinemia may be due to medications, for
example neuroleptics or antidepressants, or be idiopathic [1,6]. As
other biological functions of PRL have been identified in many
aspects of physiological and metabolic processes, it is not
surprising that hyperprolactinemia can also be considered a
systemic condition which may pre-dispose to numerous cardio-
vascular and immune-mediated reactions [4].
Address for correspondence: Dr Stefano Lello, Department of Woman
and Child Health, Catholic University of Rome, Largo Agostino Gemelli,
1, Rome 00168, Italy. E-mail: lello.stefano@gmail.com
of PRL are summarized. Clinical presentation, diagnosis and
treatment of hyperprolactinemia are also reviewed.
PRL: molecular characteristics
Prolactin (PRL) is a peptide hormone mainly secreted by the
lactotrophs cells of the anterior pituitary gland. It is a 23 kDa
single-chain polypeptide of 199 aminoacids [7], with three
intramolecular disulphide bonds between six cysteine residues
[7]. Human PRL gene, located on chromosome 6, is composed of
5 exons and 5 introns [4] and encodes a single PRL in humans [7].
The transcription of this gene is regulated by two independent
promoter regions. In pituitary gland, transcription starts from the
promoter of the 1b exon and PRL gene expression depends on the
pituitary-specific transcription factor Pit-1 [8]. Acting together
with Pit-1, other transcription factors such as the complex of the
estradiol-estrogen receptor or the nuclear factor-kB (NF-kB) were
found to activate PRL gene transcription in the 1b exon promoter
[8]. There are also many extrapituitary sources of PRL, including
lymphocytes, skin fibroblasts, brain, breast, decidua and prostate
and adipose tissue cells. In these sites, gene expression is driven
by an alternative upstream promoter, that of the 1a non-coding
exon (also named the ‘‘0’’ exon). While transcriptional regulation
of PRL expression is important, a large part of the differential
effects of PRL variants result also from either post-translational
modifications or from the alternative splicing of mRNA [4].
These aspects are very important to explain the pleiotropic actions
of PRL.
Prolactin receptor (PRL-R) is a transmembrane protein of the
cytokine/hematopoetin receptor superfamily, structurally related
to the GH, the granulocyte-macrophage colony stimulating factor
 2 A. Capozzi et al. Gynecol Endocrinol, Early Online: 1–5

(GM-CSF), the erythropoietin and the interleukin (IL)-2, IL-3, capacity, in contrast to the normal adaptive increases in glucose-
IL-4, IL-5, IL-6, IL-7, IL-9, IL-13 and IL-15 receptors [9]. PRL- stimulated insulin secretion and insulin sensitivity realized with
R is encoded by a single gene located on chromosome 5, close to moderately increased PRL levels. PRL enhances also androgens,
the GH receptor gene [9]. It is expressed in different tissues dihydroepiandorsterone (DHEA), together with cortisol and
including gonads, uterus, breast, liver, kidney, adrenal gland, aldosterone secretion by the adrenal cortex cells [14].
brain, heart, pituitary gland, skin and the immune system cells.
PRLR gene contains 11 exons, including the five alternative first Effects on cardiovascular system
exons E11 to E15. Each of them has its own tissue-specific
Prolactin presents vasoconstrictive actions, best established in
promoter [4]. The difference of PRL actions is made possible not
pregnancy but also demonstrated in other conditions [15,16].
only through the post-translational modification of the molecule
Many studies demonstrated high-serum PRL levels in pregnancy-
but also to the diversity of the PRL receptors.
induced hypertension and pre-eclampsia, but this association
Prolactin secretion is pulsatile and follows a circadian rhythm
remains controversal. However, Leanos-Miranda et al. [17]
with the highest plasma concentration reached during sleep, and
showed that urinary PRL excretion was markedly elevated in
the lowest observed in the morning about 2–3 h after waking up
pre-eclampsia and that this parameter can be considered a reliable
[5]. The level of that hormone increases during ovulation.
biomarker for pre-eclampsia in pregnancy. PRL blood levels were
Dopamine produced in the arcuate and paraventricular nuclei of
found higher in patients with essential hypertension [16]. PRL
the hypothalamus is the main PRL inhibitory factor by binding to
may play a role in accelerated arteriosclerosis in early menopause,
the D2 receptor of the pituitary lactotroph cells, while neuropep-
by affecting blood pressure and arterial stiffness [18]. In early
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tides such as thyrotrophin-releasing hormone (TRH), estradiol,

post-menopause, PRL level correlated with the arterial blood
oxytocin, vasopressin and vasoactive intestinal polypeptide pro-
pressure, and also with the central aortic systolic and diastolic
mote PRL secretion [10].
blood pressures and the pulse wave velocity, a marker of aortic
stiffness [19]. Other studies described the influence of PRL on
PRL: Biological effects
heart rhythm and chronic heart failure [20]. These aspects are
Lactotrophic and reproductive actions probably explained by the effect of PRL in decreasing NO
bioavailability and substrate for endothelial nitric oxide synthase
The main role of PRL is promoting milk synthesis (lactogenic
(eNOS), and increasing production of oxygen-derived free
effect) and maintaining lactation (galactopoietic effect) in
radicals [20].
postpartum [11]. In the lactation period, each nipple stimulation
by the suckling infant produces a substantial, short-term increase
Effects on central nervous system
of PRL secretion which is based on a neuro-humoral axis. In
For personal use only.

pregnant women, increasing estrogen secretion stimulates prolif-
eration of the lactotrophs; as a result, PRL secretion increases.
PRL stimulates mammary gland growth together with estradiol,
progesterone, placental lactogen, insulin and cortisol [1,4],
preparing breast for postpartum lactation. At the same time, the
high estrogens concentration inhibits the lactotropic effect of PRL
in the mammary gland. This results in the initiation of lactation
after delivery when estrogens fall to non-pregnant levels.
Prolactin exerts its action by binding to membrane bound
receptor isoforms broadly classified as the long form and the short
form receptors. Both receptor isoforms are highly expressed in the
ovary as well as in the uterus. Although signaling through the long
form is believed to be more predominant, it remains unclear
whether activation of this isoform alone is sufficient to support
reproductive functions or whether both types of receptor are
required [11].
Reproductive processes represent the largest group of func-
tions attributed to PRL [12]. PRL influences the gonads either
directly or indirectly. It decreases sensitivity of the luteinizing
hormone (LH) and of the follicle-stimulating hormone (FSH)
receptors in the gonads [12]. The indirect effect is exerted by a
reduction of gonadotropin-releasing hormone (GnRH) secretion,
more specifically by its pulsatile secretion inhibition caused by
opiate system stimulation. Consequently, suppressed LH and FSH
secretion inhibits ovulation [12].
Effects on other hormones
Apart from the effects on of pituitary–gonadal axis, PRL
influences also other hormones. Direct effects of PRL on
pancreas and adrenal gland were been reported [13,14]. PRL
improves glucose homeostasis by increasing b-cell mass under
certain conditions such as pregnancy, whereas hyperprolactinemia
due to a pituitary gland adenoma tumor exacerbates insulin
resistance. In diabetic rats, it was observed high levels of PRL
exacerbate insulin resistance and impair the insulin-secretory
Prolactin contributes to neurogenesis. It can stimulate prolifer-
ation, differentiation and migration of neuronal stem cells (NSCs)
[21]. It was observed a proliferative effect of PRL on glial
progenitors and oligodendrocyte precursor cells, leading to
myelination of central nervous system (CNS) [21]. A role of
PRL in the context of possible implications in demyelinative
diseases like multiple sclerosis was discussed [21].
Effects on the immunological system
Prolactin is also produced by lymphocytes and some other
immune cells. PRL-R was found on T-lymphocytes, B-cells and
macrophages [22]. It acts as a cytokine and plays an important
role in human immune responses. PRL effects on immunological
system may depend on concentration, resulting in immunostimu-
lation at modest levels and inhibition at high levels. For example,
in many cases of autoimmune diseases, the severity of the disease
is lower or even remitted during pregnancy [23], when serum PRL
level is more elevated. On the other side, in vitro PRL was found
to act as a co-stimulating factor for T lymphocytes, activated by
an unspecific mitogen or by antigen presentations [4,22]. Thus,
PRL can be secreted locally by activated and proliferating T-cells
modulating the proliferation on the basis of a positive reciprocal
circuit [22]. It may explain the association between autoimmune
diseases and moderate hyperprolactinemia, and suggests PRL is
implicated in the initiation of the autoimmune reactions, rather
than at later stages of the clinical diseases [24].
Other functions
Prolactin is involved in osmoregulation, increasing water and salt
absorption in all segments of the bowel and reducing renal Na+
and K+ excretion [25]. It was showed PRL may be associated with
increased risk of ovarian cancer, particularly in overweight and
obese women [26]. Even if in animal models raised PRL was
recognized a risk factor also for breast cancer [27], and prostate
cancer [28], such evidence need further clarification in humans.
 DOI: 10.3109/09513590.2015.1017810
PRL is proposed to be associated with the severity of psoriasis
although data reported different results [29]. In one study, in male
patients affected by psoriasis, PRL levels are higher in compari-
son with control group and returns to the same level as healthy
controls after treatment of psoriasis. However, no significant
differences were observed between PRL levels and improvement
of severity index of psoriasis (PASI score). The association of
PRL levels with the severity of psoriasis is still controversal [29].
Hyperprolactinemia
The term ‘‘hyperprolactinemia’’ refers to an increase in circulat-
ing PRL levels, usually producing reproductive problems in both
sexes particularly anovulatory infertility in women [5,6].
Causes of hyperprolactinemia
Hyperprolactinemia is classified in two types: the functional or
organic hyperprolactinemia. The most common reasons of
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functional mild to moderate hyperprolactinemia are a variety of
pharmacotherapeutic agents that reduce hypothalamic secretion of
dopamine or its action in the pituitary (Table 1) [6,30]. Functional
hyperprolactinemia is typically observed in pregnancy but it often
occurs in polycystic ovary syndrome (PCOS), renal failure,
hepatic cirrhosis and renal and lung cancers [31,32]. Pathological
functional hyperprolactinemia also recurs in endocrinopathies
such as primary hypothyroidism and primary adrenocortical
insufficiency [32]. Mild stress, including that of venipuncture, can
induce transient elevations in serum PRL [1,4].
Organic hyperprolactinemia is mainly due to sellar and
parasellar lesions, including pituitary adenomas (prolactinoma,
For personal use only.
growth hormone/PRL-secreting and adrenocorticotropic hor-
mone/PRL-secreting adenomas), non-pituitary tumors and infil-
trative conditions (such as sarcoidosis, craniopharyngioma, empty
sella syndrome, vascular malformations, pituitary metastases or
non-functioning adenomas compressing the pituitary stalk) [33].
They frequently cause raised serum PRL levels through a
disconnection that interrupts the normal dopaminergic inhibition
of lactotroph cells.
Prolactinomas are the most frequent organic cause of PRL
excess and the most common hormone-secreting pituitary tumors.
They represent approximately 40% of all pituitary tumors with an
estimated prevalence of 100 per 1 million populations [3,5].
Prolactinomas are mainly diagnosed in women aged 20–40 years.
After the fifth decade of life, frequency of prolactinomas becomes
similar in both sexes. Prolactinomas may infrequently present as a
component of multiple endocrine neoplasia type 1 (MEN1). In
that case, they seem to be more aggressive than sporadic
prolactinomas [34]. In women, microadenomas (51 cm in size)
were more common than macroadenomas (41 cm in size), while
in men the latter were more frequent [5].
In asymptomatic subjects with mild hyperprolactinemia and
negative pituitary imaging, the presence of macroprolactinemia
should be excluded [1]. Macroprolactinemia is characterized by
Table 1. Drugs causing functional hyperprolactinemia.
Drugs
Antipsychotics Phenothiazines, haloperidol,
Risperidone, reserpine
Antidepressants Tricyclic and tetracyclic agents,
MAO inhibitors, SSRI
Antihypertensives a-Methyldopa, verapamil, reserpine
Anti-emetics Metoclopramide, domperidone
Opiates Morphine, methadone
Others Estrogens, Cocaine, Cimetidine
Hyperprolactinemia 3
the presence of a molecular mass of PRL greater than 150 kDa as
the predominant molecular form of circulating PRL [35].
Macroprolactin is mostly a complex of PRL with IgG, especially
anti-PRL autoantibodies. Anti-PRL autoantibodies bind to PRL
(molecular mass of 23 kDa), forming a large immune complex of
PRL with IgG (macroprolactin) which tends to increase serum
PRL concentrations [35]. Macroprolactinemia is present in 3.68%
in general population and in 10–25% in patients with hyperpro-
lactinemia [35]. Hyperprolactinemia tends to develop in patients
with macroprolactinemia due to the delayed clearance of
macroprolactin [35]. Patients presenting macroprolactinemia
often lack typical clinical symptoms of hyperprolactinemia [1].
Neither medications nor further examinations are recommended if
free PRL concentrations are normal because the biological
activity of macroprolactin is low and in women pregnancy is
possible without any treatment [35]. Although macroprolactine-
mia is considered a benign condition, pituitary imaging, dopamine
agonists (DA) treatment and prolonged follow-up were suggested
in certain cases, like in patients affected by prolactinomas [35].
If hyperprolactinemia does not present discernible reason is
considered an idiopathic functional hyperprolactinemia [4].
Clinical presentation
Clinical manifestations of hyperprolactinemia are gender-specific
[4]. Hyperprolactinemia is associated to hypogonadotrophic
hypogonadism in both sexes [36].
Women generally present oligo- and amenorrhea and anovula-
tory cycles (due to inhibition of LH and FSH pulsatile secretion),
galactorrhea (due to lactotropic effect of PRL) and infertility
(caused by hypogonadotrophic hypogonadism). They are often
affected by premenstrual syndrome, dyspareunia, hirsutism and
tendency to anxiety and depression [4,32,33].
Male hyperprolactinemia is usually characterized by impo-
tence and loss of libido, gynecomastia and galactorrhea (due to
mammotropic action of PRL) and infertility [4]. However, in men,
symptoms can be subtle and often only diagnosed at advanced
stage [36]. Bone loss and progressive atherosclerosis due to an
indirect decrease in estrogens secretion can also occur as a
consequence of hypogonadism in both sexes [37]. Besides,
patients with hyperprolactinemia have an altered body compos-
ition with increased fat mass and reduced lean mass [3]. This
latter finding is also in line with the well-known incidence
of osteoporosis and osteopenia mainly due to secondary hypo-
gonadism [37].
When hyperprolactinemia is caused by a pituitary macro-
adenoma additional condition should be considered in differential
diagnosis: the presence of signs and symptoms of hypopituitar-
ism, headaches induced by elevated intracranial pressure, optic
chiasm compression accompanied by visual field defects and
compression of intracavernous segments of the cranial nerves (III,
IV, ophthalmic V1, maxillary V2, VI) with consequent diplopia
and sella enlargement [4]. Colao et al. found in 219 patients with
prolactinoma at diagnosis, a difference in clinical presentation
between men and women as men generally were admitted due to
symptoms of tumor compression, while women for gonadal
dysfunction and galactorrhea. Infertility and weight gain were
complained by women more than by men [5].
Diagnosis
A careful anamnesis is the first step to study hyperprolactinemia:
by a detailed history, it is possible to include or exclude
physiological, pharmacological and pathological causes of
hyperprolactinemia. If the patient’s medical history includes
drug use, an unhealthy lifestyle and the occurrence of kidney
and liver diseases, these should be taken into consideration.
 4 A. Capozzi et al. Gynecol Endocrinol, Early Online: 1–5

Table 2. Comparison between Bromocriptine and Carbergoline in the treatment of hyperprolactinemia (modified from Ref. [39]).

Bromocriptine Cabergoline
Dopamine receptor target sites D1 and D2 D1 (low affinity) and D2 (high affinity)
Duration of action 8–12 h 7–14 days
Half-life (h) 3.3 65
Available doses 1.0 and 2.5 mg scored tablets; 5 and 10 mg capsules 0.5 mg scored tablets
Typical dose 2.5 mg/day in divided doses 0.5 mg/week or twice-weekly
Dosing regimens, starter Start on 1.25–2.5 mg/day at bedtime. Gradually increase Start at 0.25–0.5 mg twice-weekly. Adjust by
packs, dosage to a median of 5.0–7.5 mg/day and a maximum of 0.25 mg twice-weekly up to 1 mg twice-weekly
15–20 mg/day every 2–4 months according to serum prolactin
levels
Advantages Long history of use; does not appear to be teratogenic; Good efficacy; low frequency of adverse events;
inexpensive may be useful in bromocriptine-resistant patients;
weekly or twice-weekly dose
Disadvantages Tolerance; recurrence; resistance; multiple daily dosing Not yet indicated for use during pregnancy
Common side effects Nausea, headache, dizziness, abdominal pain, syncope, Milder and less frequent compared with
orthostatic hypotension, fatigue bromocriptine
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The physical examination should be directed towards evaluation
of signs of hypothyroidism, hypogonadism, renal failure and
visual field defects.
The main investigations in the diagnosis of a hyperprolacti-
nemia are hormonal and radiological. As PRL is a pulsatile
hormone, a single measurement of serum level resulting above the
upper limit of normal obtained without excessive venipuncture
stress is sufficient for the diagnosis of hyperprolactinemia [1].
Blood samples should be collected in the morning from the
patient in a fasting state, who should be in a comfortable setting
For personal use only.
relevant cause. For example, it may involve suspension of a
particular medication for 3 days or substitution of an alternative
drug, followed by reassessment of PRL or measures to reduce
stress levels [1,39].
Medical therapy is of first choice in patients with prolactino-
mas and consists of use of DAs as first-line treatment to reduce
tumor size and PRL levels [1,3]. In patients with asymptomatic
microprolactinoma, no treatment needs to be given and a regular
follow-up with serial PRL measurements and pituitary imaging
should be organized [1]. The majority of patients with

after a good night’s sleep at least 2–3 h after waking up [4].
Assay-specific normal values are higher in women than in men
and generally lower than 25 mg/l. Many dynamic functional tests
have been proposed to differentiate idiopathic from tumoral
hyperprolactinemia but actually none is recommended for the
diagnosis [1,38]. Macroprolactinemia should be considered in all
serum samples of patients with asymptomatic hyperprolactinemia
for the differential diagnosis as it is one of the major causes of
hyperprolactinemia. The screening of macroprolactinemia is
performed by polyethyleneglycol- (PEG-) precipitation method,
and the confirmative and qualitative examinations include gel
chromatography, protein A/G column and 125I-PRL binding
studies [35]. In patients with clinical symptoms of hyperprolacti-
nemia but PRL in the normal range, the high-dose ‘‘hook effect’’
needs to be excluded. It may occur if large quantities of antigen
(PRL) in the immunoassay system impair antigen–antibody
binding, resulting in a low antigen (PRL) determination. In that
case, the correct measurement of PRL is obtained after a dilution
of the serum sample [1]. PRL levels greater than 500 mg/l are
commonly considered diagnostic for a macroprolactinoma. PRL
levels 250 mg/l usually indicate the presence of a prolactinoma;
however, prolactinoma cannot be excluded in the presence of
lower levels, and PRL levels 4100 mg/l are present in some
patients with idiopathic hyperprolactinemia. Several drugs may
cause PRL elevations above 200 mg/l [1,30]. After hyperprolacti-
nemia is confirmed, imaging with magnetic resonance imaging
(MRI) or computerized tomography (CT) are necessary to define
the presence of a lesion compatible with a pituitary tumor [3].
Treatment of hyperprolactinemia
For the right management of hyperprolactinemia, it is firstly
suggested to differentiate pathological form from physiological
increase in PRL levels, excluding pregnancy or assumption of
anti-dopaminergic drugs. The preferred treatment for patients
with functional asymptomatic hyperprolactinemia is removing the
prolactinomas, both micro- and macroprolactinomas, can be
successfully treated with DAs, with normalization of PRL
secretion and gonadal function, and significant tumor shrinkage
in a high percentage of cases [3]. Currently, the most commonly
used DAs are cabergoline (CAB), bromocriptine (BRC), pergolide
(PER) and quinagolide (QG). CAB seems to have the most
favorable profile according to plasma half-life, efficacy and
tolerability among all Das (Table 2). CAB normalizes PRL levels
and decreases tumor size, restoring gonadal function in 95% of
microprolactinomas and 80% of macroprolactinomas, generally at
the median dose of 0.5 mg per week and 1 mg per week,
respectively [3]. BRC has the longest history of use and is a safe,
inexpensive and effective therapy option, with the therapeutic
doses in the range of 2.5–15 mg per day (median: 7.5 mg). Doses
as high as 20–30 mg per day may be necessary in approximately
30% of patients. However, BRC requires multiple daily dosing
and some patients are resistant or intolerant to this therapy [39]. If
PRL levels are well controlled with DAs, gradual tapering of the
dose to the lowest effective amount is recommended, and
sometimes medication can be stopped after several years [1].
Patients resistant to DAs should benefit of a trial of an alternative
DA, an increase of the DA beyond conventional doses [1] or
experimental treatments [3]. A number of experimental therapies
(somatostatin analogues, nerve growth factor, interferon-a and
dopastatins) in various phases of development are available, but
none of these approaches has received approval or a clear
demonstration to be beneficial [40].
Trans-sphenoidal surgical resection of the prolactinoma
remains the main option for patients who may refuse or do not
respond to long-term pharmacological therapy [1]. Radiotherapy
and/or estrogens are also reasonable choices if surgery fails.
Chemotherapy with temozolamide is limited to resistant and
malignant prolactinomas [1].
In pregnant patients with prolactinomas, DA therapy should be
immediately stopped, unless growth of a macroprolactinoma or
pressure symptoms occur. Current data suggest CAB and QG have
 DOI: 10.3109/09513590.2015.1017810
a good safety profile for women who wish to conceive, but hard
evidence demonstrating DAs do not provoke congenital malfor-
mations when taken during early pregnancy is currently only
available for BRC [1,3].
Conclusions
Hyperprolactinemia is a pituitary hormone disorder usually found
in both sexes with abnormal sexual and/or reproductive function or
with galactorrhea. Physiological causes of hyperprolactinemia are
pregnancy, lactation and mild stress. Medications including anti-
dopaminergic drugs can also induce functional hyperprolactine-
mia, while idiopathic hyperprolactinemia accounts for 30–40% of
cases. The most frequent cause of persistent pathological
hyperprolactinemia is the presence of a micro- (510 mm diameter)
or macroprolactinoma (10 mm). Prolactinomas account for
approximately 40% of all pituitary adenomas and are an important
cause of hypogonadism and infertility. Pharmacological therapy
with DAs, usually CAB, represents the mainstay of treatment of
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hyperprolactinemia and is highly effective in the majority of cases.
Surgery may also be an appropriate alternative in certain circum-
stances. The main goal of therapy for prolactinomas is restoration
or achievement of eugonadism through the normalization of
hyperprolactinemia and the control of tumoral growth.
Monotherapy with DAs is often sufficient for management of
prolactinomas, but resistance to DAs, pregnancy and giant or
aggressive prolactinomas may require multiple approach involving
surgery, radiotherapy or both. Studies about the mechanisms
underlying the pathogenesis of prolactinomas may enable future
development of novel molecular therapies for treatment-resistant
For personal use only.
cases. Pleiotropic effects of PRL may be also used in future for the
treatment of many cardiovascular or autoimmunological diseases.
Declaration of interest
The authors declared no conflict of interest.
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