1 Prolactin (PRL)
2 Physiology
2.1 Role of Dopamine in PRL Secretion
2.2 Role of Serotonin in PRL Secretion
2.3 Role of Other Substances in PRL Secretion
3 Diagnosis of Hyperprolactinemia (HPRL)
3.1 Normal and Elevated PRL Values
Study | Hyperprolactinemia values |
---|---|
Tsuboi et al. [69] | >18.77 ng/ml (men) >24.20 ng/ml (women) |
Geller et al. [70] | >27 ng/ml |
Citrome et al. [71] | >17.7 ng/ml (men) >29.2 ng/ml (women) |
Kikuchi et al. [72] | >20 ng/ml (men) >25 ng/ml (women) |
Nagai et al. [73] | >12.8 ng/ml (men + postmenopausal women) >30.5 ng/ml (fertile women) |
Pérez-Iglesias et al. [74] | >17.7 ng/ml (men) >29.2 ng/ml (women) |
Sugawara et al. [75] | >13.69 ng/ml (men) >29.32 ng/ml (premenopausal women) >15.39 ng/ml (postmenopausal women) |
Grootens et al. [76] | >18 ng/ml (men) >25 ng/ml (women) |
Li et al. [77] | >25 ng/ml (men) >35 ng/ml (women) |
Gopal et al. [78] | >18 ng/ml (men) >30 ng/ml (women) |
Aston et al. [79] | >15.2 ng/ml (men) >23.3 ng/ml (women) |
Arakawa et al. [80] | >12.8 ng/ml (men) |
Bushe et al. [81] | >18.77 ng/ml (men) >24.2 ng/ml (women) |
Citrome et al. [82] | >18.8 ng/ml (men) >24.2 ng/ml (women) |
Kwon et al. [83] | >23 ng/ml |
Kryzhanovskaya et al. [84] | >11 ng/ml (men) >20 ng/ml (women) |
Kim et al. [85] | >20 ng/ml |
Byerly et al. [86] | >18 ng/ml (men) >29 ng/ml (non-lactating women) |
Konarzewska et al. [87] | >17.7 ng/ml |
Liu-Seifert et al. [88] | >18.77 ng/ml (men) >24.2 ng/ml (women) |
Van Bruggen et al. [89] | ≥15 ng/ml (men) ≥22 ng/ml (women) |
Tschoner et al. [90] | >20 ng/ml (men) >25 ng/ml (women) |
Meltzer et al. [91] | >18.77 ng/ml (men) >24.20 ng/ml (women) |
Emsley et al. [92] | >18.77 ng/ml (men) >24.20 ng/ml (women) |
Kahn et al. [93] | >18 ng/ml (men) >25 ng/ml (women) |
Lu et al. [94] | >25 ng/ml (women) |
Hanssens et al. [95] | >18.8 ng/ml (men) >24.2 ng/ml (women) |
Yuan et al. [96] | >20 ng/ml (men) >25 ng/ml (women) |
Kishimoto et al. [97] | >12.78 ng/ml |
Howes et al. [98] | >14.4 ng/ml |
Kinon et al. [99] | >18.8 ng/ml (men) >24.2 ng/ml (women) |
Goffin et al. [14] | >25 ng/ml |
Kelly and Conley [100] | ≥18 ng/ml (men and women) |
Schooler et al. [101] | >18 ng/ml (men) >25 ng/ml (women) |
Volavka et al. [102] | >20 ng/ml (men) |
Addington et al. [103] | >35 ng/ml (men) >50 ng/ml (women) |
Bobes and Timdahl [104] | >20 ng/ml (men) >30 ng/ml (women) |
Montgomery et al. [105] | >18.4 ng/ml (men) >26 ng/ml (women) |
Cavallaro et al. [106] | >18 ng/ml (men) >29 ng/ml (women) |
Halbreich et al. [20] | >20 ng/ml (men) >25 ng/ml (women) |
Kinon et al. [107] | >18.77 ng/ml (men) >24,20 ng/ml (women) |
Potkin et al. [108] | >23 ng/ml |
Canuso et al. [109] | >23.2 ng/ml (premenopausal women) |
Aizenberg et al. [110] | >16 ng/ml |
Huber et al. [111] | >25 ng/ml |
David et al. [112] | >15 ng/ml (men) >20 ng/ml (women) |
Peuskens and Link [113] | ≥15 ng/ml |
Crawford et al. [114] | >13.8 ng/ml (men) >18.4 ng/ml (women) |
Prolactin plasma concentrations | |
---|---|
Normal | 20 (men) and 25 (women) ng/ml |
High | From 30–60 to 150–200 ng/ml |
Prolactinoma | |
Microprolactinomas (≤1 cm in diameter) | 50–300 ng/ml (can be as low as 30 ng/ml) |
Macroprolactinomas (≥1 cm in diameter) | 200–5,000 ng/ml (can be as high as 35,000 ng/ml) |
3.2 Measurement of PRL Levels
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All serum measurements must been done by the same laboratory.
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All bloods must have been drawn in the morning with the patient in a fasting state.
-
To confirm diagnosis, at least one repeated measurement is required after the initial elevated level.
3.3 Incidence of HPRL
4 Causes of Elevated PRL Values and HPRL
Physiological |
Pregnancy |
Breast-feeding |
Stress (causes temporary increase in prolactin secretion) |
Physical activity: intensive effort (causes temporary increase in prolactin secretion) |
Sexual activity |
Sleep (causes temporary increase in prolactin secretion) |
Neonatal age |
Pathological |
Pituitary disorders |
Prolactinomas |
Mixed pituitary adenomas |
Cushing’s disease |
Acromegaly |
Not secreting adenomas |
Empty sella syndrome |
Pituitary stalk section or tumors |
Lymphoid hypophysitis |
CNS disorders |
Tumors |
Craniopharygioma |
Sarcoidosis |
Spinal cord lesions |
Granulomatous diseases |
Vascular disorders |
Autoimmune disorders |
Hypothalamic tumors or metastasis |
Cranial irradiation |
Seizures |
Systemic diseases |
Severe hypothyroidism |
Empathic cirrhosis |
Chronic renal insufficiency |
Polycystic ovary syndrome |
Estrogen-secreting tumors |
Pseudocyesis |
Stage immediately following an epileptic fit |
Pharmacological |
D2 receptor antagonists |
First-generation antipsychotics |
Phenothiazines |
Thioxanthenes |
Butyrophenones |
Second-generation antipsychotics |
Paliperidone |
Risperidone |
Quetiapine |
Olanzapine |
Benzamides (amisulpride) |
Other dopamine (D2) antagonists |
Amoxapine |
Metoclopramide |
Antidepressants |
Tricyclic |
Amitriptyline |
Desipramine |
Clomipramine |
Amoxapine |
Tetracyclic |
MAO-inhibitors (mono-amine oxidase inhibitors) |
Pargyline |
Clorgyline |
SSRIs (selective serotonin reuptake inhibitors) |
Paroxetine, citalopram and fluvoxamine (all bring about a minimal increase, although not above normal values) |
Other |
Prolactin increases were not observed with the long-term use of nefazodone, bupropion, venlafaxine or trazodone |
Opiates and cocaine |
Antihypertensives |
Methyldopa |
Verapamil |
Reserpine |
Labetalol |
Gastrointestinal medication |
Metoclopramide |
Domperidone (metoclopramide and domperidone are both dopamine receptor blockers) |
H2 receptor antagonists (?) |
Ranitidine |
Cimetidine |
Hormone preparations |
Estrogens |
Oral contraceptive pills |
Antiandrogens |
Protease inhibitors (?) |
Benzodiazepines (occasionally) |
Alprazolam |
Other |
Fenfluramine |
Alcohol |
5 Methods
6 PRL and Antipsychotics
6.1 General Remarks
6.2 PRL and First-Generation Antipsychotics (FGAs)
6.3 PRL and Second-Generation Antipsychotics (SGAs)
6.3.1 PRL and SGAs in Adults
6.3.1.1 Amisulpride
6.3.1.2 Aripiprazole
6.3.1.3 Clozapine
6.3.1.4 Olanzapine
6.3.1.5 Paliperidone
6.3.1.6 Quetiapine
6.3.1.7 Risperidone
6.3.1.8 Sertindole
6.3.1.9 Ziprasidone
6.3.2 PRL and SGAs in Children and Adolescents
6.3.2.1 Aripiprazole
6.3.2.2 Olanzapine
6.3.2.3 Quetiapine
6.3.2.4 Risperidone
6.3.2.5 Ziprasidone
6.3.3 PRL and SGAs in First-Episode Patients
6.3.3.1 Amisulpride
6.3.3.2 Aripiprazole
6.3.3.3 Olanzapine
6.3.3.4 Quetiapine
6.3.3.5 Risperidone
6.3.3.6 Ziprasidone
6.4 PRL and Newly Approved Antipsychotics
6.4.1 Asenapine
6.4.2 Iloperidone
6.4.3 Lurasidone
Prolactin elevation | |
---|---|
Amisulpride | +++ |
Aripiprazole | 0 |
Asenapine | + |
Clozapine | + |
Iloperidone | + |
Lurasidone | ++ |
Olanzapine | ++ |
Paliperidone | +++ |
Quetiapine | +/− |
Risperidone | +++ |
Sertindole | + |
Ziprasidone | ++ |
6.5 Possible Explanations of the PRL-Elevating Tendency of Antipsychotics
7 Consequences of HPRL
Irregular menstrual cycle |
Amenorrhea: complete absence of menstruation |
Menorrhagia: excessive menstrual bleeding |
Oligomenorrhea: long and irregular intervals between two successive menstrual periods |
Anovulation (absence of ovulation) |
Polymenorrhea: short and irregular intervals between two menstrual periods |
Abnormal semen production |
Hypospermia (low sperm count) |
Azoospermia (complete absence of sperm cells in the semen) |
Fertility disorders/infertility |
Galactorrhea (secretion of milk from the nipples in men and the same phenomenon in non-lactating women) and gynecomastia (excessive development of the male mammary glands) |
Sexual dysfunction |
Decreased libido, impaired arousal, impaired orgasm |
Erectile dysfunction and ejaculation dysfunction |
Impotence |
Hypogonadism |
Inadequate functioning of the sex glands (gonads), as a result of which the levels of testosterone in the blood in men and of estrogen in women are abnormally low |
Hirsutism (male hair growth) and acne in women, due to relative androgen excess compared with low estrogen levels |
Obesity |
Decreased bone mineral density, which may lead to increased risk of osteoporosis |
Breast cancer (?) |