Hyperprolactinaemia

Hyperprolactinaemia is the presence of abnormally high levels of prolactin in the blood. Normal levels average to about 13 ng/mL in women, and 5 ng/mL in men, with an upper normal limit of serum prolactin levels being 15-25 ng/mL for both.[1] When the fasting levels of prolactin in blood exceed this upper limit, hyperprolactinemia is indicated.

Hyperprolactinaemia
Other namesHyperprolactinemia
Prolactin
SpecialtyEndocrinology

Prolactin (PRL) is a peptide hormone produced by lactotroph cells in the anterior pituitary gland.[1] PRL is involved in lactation after pregnancy and plays a vital role in breast development.[1] Hyperprolactinemia may cause galactorrhea (production and spontaneous flow of breast milk), infertility, and disruptions in the normal menstrual period in women; as well as hypogonadism, infertility and erectile dysfunction in men.

Although hyperprolactinemia can result from normal physiological changes during pregnancy and breastfeeding, it can also be caused by other etiologies. For example, high prolactin levels could result from diseases affecting the hypothalamus and pituitary gland.[2] Other organs, such as the liver and kidneys, could affect prolactin clearance and consequently, prolactin levels in the serum.[2] The disruption of prolactin regulation could also be attributed to external sources such as medications.[2]

In the general population, the prevalence of hyperprolactinemia is 0.4%.[2] The prevalence increases to as high as 17% in women with reproductive diseases, such as polycystic ovary syndrome.[2] In cases of tumor-related hyperprolactinemia, prolactinoma is the most common culprit of consistently high levels of prolactin as well as the most common type of pituitary tumor.[2] For non-tumor related hyperprolactinemia, the most common cause is medication-induced prolactin secretion.[3] Particularly, antipsychotics have been linked to a majority of non-tumor related hyperprolactinemia cases due to their prolactin-rising and prolactin-sparing mechanisms.[4] Typical antipsychotics have been shown to induce significant, dose-dependent increases in prolactin levels up to 10-fold the normal limit. Atypical antipsychotics vary in their ability to elevate prolactin levels, however, medications in this class such as risperidone and paliperidone carry the highest potential to induce hyperprolactinemia in a dose-dependent manner similar to typical antipsychotics.[5]

Signs and symptoms

In women, high blood levels of prolactin are typically associated with hypoestrogenism, anovulatory infertility, and changes in menstruation.[6][7] Menstruation disturbances experienced in women commonly manifests as amenorrhea or oligomenorrhea. In the latter case, irregular menstrual flow may result in abnormally heavy and prolonged bleeding (menorrhagia).[1] Women who are not pregnant or nursing may also unexpectedly begin producing breast milk (galactorrhea), a condition that is not always associated with high prolactin levels. For instance, many premenopausal women experiencing hyperprolactinemia do not experience galactorrhea and only some women who experience galactorrhea will be diagnosed with hyperprolactinemia. Thus, galactorrhea may be observed in individuals with normal prolactin levels and does not necessarily indicate hyperprolactinemia.[8] This phenomenon is likely due to galactorrhea requiring adequate levels of progesterone or estrogen to prepare the breast tissue. Additionally, some women may also experience loss of libido and breast pain, particularly when prolactin levels rise initially, as the hormone promotes tissue changes in the breast.[2]

In men, the most common symptoms of hyperprolactinemia are decreased libido, sexual dysfunction, erectile dysfunction/impotence, infertility, and gynecomastia.[9] Unlike women, men do not experience reliable indicators of elevated prolactin such as menstruation to prompt immediate medical consultation.[10] As a result, the early signs of hyperprolactinemia are generally more difficult to detect and may go unnoticed until more severe symptoms are present.[10] For instance, symptoms such as loss of libido and sexual dysfunction are subtle, arise gradually, and may falsely indicate a differential cause.[10] Many men with pituitary tumor-associated hyperprolactinemia may forego clinical help until they begin to experience serious endocrine and vision complications, such as major headaches or eye problems.[10]

Long-term hyperprolactinaemia can lead to detrimental changes in bone metabolism as a result of hypoestrogenism and hypoandrogenism. Studies have shown that chronically elevated prolactin levels lead to increased bone resorption and suppression of bone formation, leading to reduced bone density, increased risk of fractures, and increased risk of osteoporosis.[11] The chronic presence of hyperprolactinemia can lead to hypogonadism and osteolysis in men.[12]

Causes

Prolactin secretion is regulated by both stimulatory and inhibitory mechanisms.[3] Dopamine acts on pituitary lactotroph D2 receptors to inhibit prolactin secretion while other peptides and hormones, such as thyrotropin releasing hormone (TRH), stimulate prolactin secretion.[3] As a result, hyperprolactinemia may be caused by disinhibition (e.g., compression of the pituitary stalk or reduced dopamine levels) or excess production.[3] The most common cause of hyperprolactinemia is prolactinoma (a type of pituitary adenoma).[3] A blood serum prolactin level of 1000–5000 mIU/L (47-235 ng/mL) may arise from either mechanism, however levels >5000 mIU/L (>235 ng/mL) is likely due to the activity of an adenoma. Prolactin blood levels are typically correlated to the size the tumors. Pituitary tumors smaller than 10 mm in diameter, or microadenomas, tend to have prolactin levels <200 ng/mL. Macroadenomas larger than 10 mm in diameter possess prolactin >1000 ng/mL.[13]

Hyperprolactinemia inhibits the secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus, which in turn inhibits the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the pituitary gland and results in diminished gonadal sex hormone production (termed hypogonadism).[14] This is the cause of many of the symptoms described below.

In many people, elevated prolactin levels remain unexplained and may represent a form of hypothalamic–pituitary–adrenal axis dysregulation.[15]

Causes of hyperprolactinemia[3]
Physiologic hypersecretion
Hypothalamic-pituitary stalk damage
Pituitary hypersecretion
Systemic disorders
Drug-induced hypersecretion

Physiological causes

Physiological (i.e., non-pathological) causes include: ovulation, pregnancy, breastfeeding, chest wall injury, stress, stress-associated REM sleep, and exercise.[16][4][17] During pregnancy, prolactin levels can range up to 600 ng/mL, depending on estrogen concentration. At 6 weeks post-birth (postpartum), estradiol concentrations decrease, and prolactin concentrations return to normal even during breastfeeding. Stress-related factors include physical, exercise, hypoglycemia, myocardial infarction, and surgery. Coitus and sleep can also contribute to an increased prolactin release.[18]

Medications

Prolactin secretion in the pituitary is normally suppressed by the brain chemical dopamine, which binds to dopamine receptors. Drugs that block the effects of dopamine at the pituitary or deplete dopamine stores in the brain may cause the pituitary to secrete prolactin without an inhibitory effect. These drugs include the typical antipsychotics: phenothiazines such as chlorpromazine (Thorazine), and butyrophenones such as haloperidol (Haldol); atypical antipsychotics such as risperidone (Risperdal) and paliperidone (Invega); gastroprokinetic drugs used to treat gastro-esophageal reflux and medication-induced nausea (such as that from chemotherapy): metoclopramide (Reglan) and domperidone; less often, alpha-methyldopa and reserpine, used to control hypertension; and TRH.[19][20][21] The use of estrogen-containing oral contraceptives are also known to increase prolactin levels when taken in high doses >35 μg.[22] The sleep drug ramelteon (Rozerem) also increases the risk of hyperprolactinaemia. Particularly, the dopamine antagonists metoclopramide and domperidone are both powerful prolactin stimulators and have been used to stimulate breast milk secretion for decades. However, since prolactin is antagonized by dopamine and the body depends on the two being in balance, the risk of prolactin stimulation is generally present with all drugs that deplete dopamine, either directly or as a rebound effect.

Specific diseases

Prolactinoma or other tumors arising in or near the pituitary — such as those that cause acromegaly may block the flow of dopamine from the brain to the prolactin-secreting cells, likewise, division of the pituitary stalk or hypothalamic disease. Other causes include chronic kidney failure, hypothyroidism, bronchogenic carcinoma and sarcoidosis. Some women with polycystic ovary syndrome may have mildly-elevated prolactin levels.

Nonpuerperal mastitis may induce transient hyperprolactinemia (neurogenic hyperprolactinemia) of about three weeks' duration; conversely, hyperprolactinemia may contribute to nonpuerperal mastitis.[23]

Apart from diagnosing hyperprolactinemia and hypopituitarism, prolactin levels are often checked by physicians in those who have had a seizure, when there is need to differentiate between epileptic seizure or a non-epileptic seizure. Shortly after epileptic seizures, prolactin levels often rise, whereas they are normal in non-epileptic seizures.[24]

Diagnosis

An appropriate diagnosis of hyperprolactinemia starts with conducting a complete clinical history before performing any treatment. Physiological causes, systemic disorders, and the use of certain drugs must be ruled out before the condition is diagnosed. Screening is indicated for those who are asymptomatic and those with elevated prolactin without an associated cause.

The most common causes of hyperprolactinemia are prolactinomas, drug-induced hyperprolactinemia, and macroprolactinemia. Individuals with hyperprolactinemia may present with symptoms including galactorrhea, hypogonadism effects, and/or infertility. The magnitude that prolactin is elevated can be used as an indicator of the etiology of the hyperprolactinemia diagnosis. Prolactin levels over 250 ng/mL may suggest prolactinoma. Prolactin levels less than 100 ng/mL may suggest drug-induced hyperprolactinemia, macroprolactinemia, nonfunctioning pituitary adenomas, or systemic disorders.[25][14]

Elevated prolactin blood levels are typically assessed in women with unexplained breast milk secretion (galactorrhea) or irregular menses or infertility, and in men with impaired sexual function and milk secretion. If high prolactin levels are present, all known conditions and medications which raises prolactin secretion must be assessed and excluded for diagnosis.[2][26] After ruling out other causes and prolactin levels remain high, TSH levels are assessed.[2] If TSH levels are elevated, hyperprolactinemia is secondary to hypothyroidism and treated accordingly.[2] If TSH levels are normal, an MRI or CT scan is conducted to assess for any pituitary adenomas.[2] Although hyperprolactinemia is often uncommon in postmenopausal women, prolactinomas detected after menopause are typically macroadenomas.[27] While a plain X-ray of the bones surrounding the pituitary may reveal the presence of a large macroadenoma, small microadenomas will not be apparent. Magnetic resonance imaging (MRI) is the most sensitive test for detecting pituitary tumors and determining their size.[2] MRI scans may be repeated periodically to assess tumor progression and the effects of therapy.[2] Computed Tomography (CT scan) is another indicator of abnormalities in pituitary gland size; it also gives an image of the pituitary, but is less sensitive than the MRI.[28] In addition to assessing the size of the pituitary tumor, physicians also look for damage to surrounding tissues, and perform tests to assess whether production of other pituitary hormones are normal. Depending on the size of the tumor, physicians may request an eye exam that includes the measurement of visual fields.[1]

However, a high measurement of prolactin may also result from the presence of macroprolactin, otherwise known as 'big prolactin' or 'big-big prolactin', in the serum.[2] Macroprolactin occurs when prolactin polymerizes together and can bind with IgG to form complexes.[2] Although this can result in high prolactin levels in some assay tests, macroprolactin is biologically inactive and will not cause symptoms typical of hyperprolactinemia.[2] In those who are asymptomatic or without obvious causes of hyperprolactinemia, macroprolactin should be assessed and ruled out.[3][26][14]

Treatment

Treatment for hyperprolactinemia is usually dependent upon its cause, ranging from hypothyroidism, drug-induced hyperprolactinemia, hypothalamic disease, idiopathic hyperprolactinemia, macroprolactin, or prolactinoma. Therefore, in order to provide the proper management of hyperprolactinemia, the pathological form and physiological increase in prolactin levels are differentiated, and the correct cause of hyperprolactinemia must be identified before treatment. For functional asymptomatic hyperprolactinemia, the treatment of choice is removing the associated cause, including antipsychotic therapy. However, prolactin levels should be drawn and monitored both prior to any discontinuation or changes to therapy, and afterwards. With symptomatic hyperprolactinemia, stopping antipsychotic drugs for a short trial period are not recommended due to the risk of exacerbation or relapse of symptoms. Options for treatment include decreasing the dose of antipsychotics, adding aripiprazole as an adjunctive therapy, and switching antipsychotics as a last resort.[4] In pharmacologic hyperprolactinemia, the concerning drug can be switched to another treatment or discontinued entirely.[29] Vitex agnus-castus extract may be tried in cases of mild hyperprolactinemia.[30] No treatment is required in asymptomatic macroprolactin and instead, serial prolactin measurements and pituitary imaging is monitored in a regular follow-up appointments.[16]

Medical therapy is the preferred treatment in prolactinomas.[3] In most cases, medications that are dopamine agonists, such as cabergoline[31] and bromocriptine (often preferred when pregnancy is possible), are the treatment of choice used to decrease prolactin levels and tumor size upon the presence of microadenomas or macroadenomas.[1][32][33] A systematic review and meta-analyses has shown that cabergoline is more effective in treatment of hyperprolactinemia than bromocriptine.[34] Other dopamine agonists that have been used less commonly to suppress prolactin include dihydroergocryptine, ergoloid, lisuride, metergoline, pergolide, quinagolide, and terguride.[35][36] If the prolactinoma does not initially respond to dopamine agonist therapy, such that prolactin levels are still high or the tumor is not shrinking as expected, the dose of the dopamine agonist can be increased in a stepwise fashion to the maximum tolerated dose.[3] Another option is to consider switching between dopamine agonists. It is possible for the prolactinoma to be resistant to bromocriptine but respond well to cabergoline and vice versa.[3] Surgical therapy can be considered if pharmacologic options have been exhausted.[3]

There is evidence to support improvement in outcomes of hyperprolactinemic individuals who have shown to be resistant to or intolerant of the treatment of choice, dopamine agonists, through radiotherapy and surgery.[34]

See also

References
  1. Thapa, Sudan; Bhusal, Kamal (2021), "Hyperprolactinemia", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID 30726016, retrieved 2021-07-27
  2. Majumdar, Abha; Mangal, Nisha Sharma (2013). "Hyperprolactinemia". Journal of Human Reproductive Sciences. 6 (3): 168–175. doi:10.4103/0974-1208.121400. ISSN 0974-1208. PMC 3853872. PMID 24347930.
  3. Melmed, Shlomo; Casanueva, Felipe F.; Hoffman, Andrew R.; Kleinberg, David L.; Montori, Victor M.; Schlechte, Janet A.; Wass, John A. H. (2011). "Diagnosis and Treatment of Hyperprolactinemia: An Endocrine Society Clinical Practice Guideline". The Journal of Clinical Endocrinology & Metabolism. 96 (2): 273–288. doi:10.1210/jc.2010-1692. ISSN 0021-972X. PMID 21296991.
  4. Samperi, Irene; Lithgow, Kirstie; Karavitaki, Niki (2019). "Hyperprolactinaemia". Journal of Clinical Medicine. 8 (12): 2203. doi:10.3390/jcm8122203. ISSN 2077-0383. PMC 6947286. PMID 31847209.
  5. Kelly, Deanna L.; Wehring, Heidi J.; Earl, Amber K.; Sullivan, Kelli M.; Dickerson, Faith B.; Feldman, Stephanie; McMahon, Robert P.; Buchanan, Robert W.; Warfel, Dale; Keller, William R.; Fischer, Bernard A. (2013). "Treating symptomatic hyperprolactinemia in women with schizophrenia: presentation of the ongoing DAAMSEL clinical trial (Dopamine partial Agonist, Aripiprazole, for the Management of Symptomatic Elevated prolactin)". BMC Psychiatry. 13 (1): 214. doi:10.1186/1471-244X-13-214. ISSN 1471-244X. PMC 3766216. PMID 23968123.
  6. Critchley, Hilary O. D.; Maybin, Jacqueline A.; Armstrong, Gregory M.; Williams, Alistair R. W. (2020). "Physiology of the Endometrium and Regulation of Menstruation". Physiological Reviews. 100 (3): 1149–1179. doi:10.1152/physrev.00031.2019. hdl:20.500.11820/36236a4e-a35e-4818-abe3-5d8b278c66f8. ISSN 1522-1210. PMID 32031903. S2CID 211063583.
  7. Mann, W. Alexander (2011). "Treatment for prolactinomas and hyperprolactinaemia: a lifetime approach". European Journal of Clinical Investigation. 41 (3): 334–342. doi:10.1111/j.1365-2362.2010.02399.x. ISSN 1365-2362. PMID 20955213.
  8. Sakiyama, R.; Quan, M. (1983). "Galactorrhea and hyperprolactinemia". Obstetrical & Gynecological Survey. 38 (12): 689–700. doi:10.1097/00006254-198312000-00001. ISSN 0029-7828. PMID 6361641. S2CID 2846310.
  9. De Rosa, Michele; Zarrilli, Stefano; Di Sarno, Antonella; Milano, Nicola; Gaccione, Maria; Boggia, Bartolomeo; Lombardi, Gaetano; Colao, Annamaria (2003). "Hyperprolactinemia in men". Endocrine. 20 (1): 75–82. doi:10.1385/ENDO:20:1-2:75. ISSN 1559-0100. PMID 12668871. S2CID 24140780.
  10. Buvat, J. (2003). "Hyperprolactinemia and sexual function in men: a short review". International Journal of Impotence Research. 15 (5): 373–377. doi:10.1038/sj.ijir.3901043. ISSN 1476-5489. PMID 14562140. S2CID 34712756.
  11. di Filippo, Luigi; Doga, Mauro; Resmini, Eugenia; Giustina, Andrea (2020). "Hyperprolactinemia and bone". Pituitary. 23 (3): 314–321. doi:10.1007/s11102-020-01041-3. ISSN 1573-7403. PMID 32219718. S2CID 214647438.
  12. Naidoo, U.; Goff, D. C.; Klibanski, A. (2003). "Hyperprolactinemia and bone mineral density: the potential impact of antipsychotic agents". Psychoneuroendocrinology. 28 Suppl 2: 97–108. doi:10.1016/s0306-4530(02)00129-4. PMID 12650684. S2CID 22543496.{{cite journal}}: CS1 maint: url-status (link)
  13. Yatavelli, Rajini Kanth R.; Bhusal, Kamal (2021), "Prolactinoma", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID 29083585, retrieved 2021-07-30
  14. Vilar, Lucio; Vilar, Clarice Freitas; Lyra, Ruy; Freitas, Maria da Conceição (2019). "Pitfalls in the Diagnostic Evaluation of Hyperprolactinemia". Neuroendocrinology. 109 (1): 7–19. doi:10.1159/000499694. ISSN 1423-0194. PMID 30889571.
  15. Jackson, Jo; Safranek, Sarah; Daugird, Allen (2005). "Clinical inquiries. What is the recommended evaluation and treatment for elevated serum prolactin?". The Journal of Family Practice. 54 (10): 897–898, 901. ISSN 0094-3509. PMID 16202380.
  16. Capozzi, A.; Scambia, G.; Pontecorvi, A.; Lello, S. (2015). "Hyperprolactinemia: Pathophysiology and therapeutic approach". Gynecological Endocrinology. 31 (7): 506–510. doi:10.3109/09513590.2015.1017810. PMID 26291795. S2CID 28930221. Retrieved 2021-07-26.{{cite journal}}: CS1 maint: url-status (link)
  17. Levine, Samara; Muneyyirci-Delale, Ozgul (2018). "Stress-Induced Hyperprolactinemia: Pathophysiology and Clinical Approach". Obstetrics and Gynecology International. 2018: 9253083. doi:10.1155/2018/9253083. ISSN 1687-9589. PMC 6304861. PMID 30627169.
  18. Alex, Ashley; Bhandary, Eva; McGuire, Kandace P. (2020). "Anatomy and Physiology of the Breast during Pregnancy and Lactation". Advances in Experimental Medicine and Biology. 1252: 3–7. doi:10.1007/978-3-030-41596-9_1. ISBN 978-3-030-41595-2. ISSN 0065-2598. PMID 32816256. S2CID 221202364.
  19. Kantrowitz, Joshua; Citrome, Leslie (2007). "Paliperidone: the evidence of its therapeutic value in schizophrenia". Core Evidence. 2 (4): 261–271. ISSN 1555-1741. PMC 3012441. PMID 21221191.
  20. Torre DL, Falorni A (2007). "Pharmacological causes of hyperprolactinemia". Therapeutics and Clinical Risk Management. 3 (5): 929–51. PMC 2376090. PMID 18473017.
  21. Baumgartner A, Gräf KJ, Kürten I (1988). "Prolactin in patients with major depressive disorder and in healthy subjects. II. Longitudinal study of basal prolactin and post-TRH-stimulated prolactin levels". Biological Psychiatry. 24 (3): 268–85. doi:10.1016/0006-3223(88)90196-5. PMID 3135848. S2CID 40784598.
  22. Alvarez-Tutor, E.; Forga-LLenas, L.; Rodriguez-Erdozain, Rosa; Goñi-Iriarte, Maria Jose; Menendez-Torre, Edelmiro; Alvarez-Tutor, Jorge (1999). "Persistent increase of PRL after oral contraceptive treatment". Archives of Gynecology and Obstetrics. 263 (1–2): 45–50. doi:10.1007/s004040050261. ISSN 0932-0067. PMID 10728629. S2CID 22718652.
  23. Peters F, Schuth W (1989). "Hyperprolactinemia and nonpuerperal mastitis (duct ectasia)". JAMA. 261 (11): 1618–20. doi:10.1001/jama.1989.03420110094030. PMID 2918655.
  24. Wang, Yan-Qiu; Wen, Yi; Wang, Ming-Min; Zhang, Yi-Wei; Fang, Zhi-Xu (2021). "Prolactin levels as a criterion to differentiate between psychogenic non-epileptic seizures and epileptic seizures: A systematic review". Epilepsy Research. 169: 106508. doi:10.1016/j.eplepsyres.2020.106508. ISSN 0920-1211. PMID 33307405. S2CID 227156239.
  25. Melgar, Virgilio; Espinosa, Etual; Sosa, Ernesto; Rangel, María José; Cuenca, Dalia; Ramírez, Claudia; Mercado, Moisés (2016). "[Current diagnosis and treatment of hyperprolactinemia]". Revista Medica del Instituto Mexicano del Seguro Social. 54 (1): 111–121. ISSN 2448-5667. PMID 26820213.
  26. Delcour, Clémence; Robin, Geoffroy; Young, Jacques; Dewailly, Didier (2019). "PCOS and Hyperprolactinemia: what do we know in 2019?". Clinical Medicine Insights. Reproductive Health. 13. doi:10.1177/1179558119871921. ISSN 1179-5581. PMC 6734626. PMID 31523136.
  27. Pekić, Sandra; Medic Stojanoska, Milica; Popovic, Vera (2019). "Hyperprolactinemia/Prolactinomas in the Postmenopausal Period: Challenges in Diagnosis and Management". Neuroendocrinology. 109 (1): 28–33. doi:10.1159/000494725. ISSN 1423-0194. PMID 30347396. S2CID 53039562.
  28. Chaudhary, V.; Bano, S. (2011). "Imaging of the pituitary: Recent advances". Indian Journal of Endocrinology and Metabolism. 15 (Suppl3): S216–S223. doi:10.4103/2230-8210.84871. PMC 3183511. PMID 22029027.
  29. Glezer, Andrea; Bronstein, Marcello D. (2015). "Prolactinomas". Endocrinology and Metabolism Clinics of North America. 44 (1): 71–78. doi:10.1016/j.ecl.2014.11.003. ISSN 0889-8529. PMID 25732643.
  30. Kilicdag EB, Tarim E, Bagis T, Erkanli S, Aslan E, Ozsahin K, Kuscu E (2004). "Fructus agni casti and bromocriptine for treatment of hyperprolactinemia and mastalgia". International Journal of Gynaecology and Obstetrics. 85 (3): 292–3. doi:10.1016/j.ijgo.2004.01.001. PMID 15145274. S2CID 38664195.
  31. Verhelst J, Abs R, Maiter D, van den Bruel A, Vandeweghe M, Velkeniers B, Mockel J, Lamberigts G, Petrossians P, Coremans P, Mahler C, Stevenaert A, Verlooy J, Raftopoulos C, Beckers A (1999). "Cabergoline in the treatment of hyperprolactinemia: a study in 455 patients". The Journal of Clinical Endocrinology and Metabolism. 84 (7): 2518–22. doi:10.1210/jcem.84.7.5810. PMID 10404830.
  32. dos Santos Nunes, Vania; El Dib, Regina; Boguszewski, César Luiz; Nogueira, Célia Regina (2011). "Cabergoline versus bromocriptine in the treatment of hyperprolactinemia: a systematic review of randomized controlled trials and meta-analysis". Pituitary. 14 (3): 259–265. doi:10.1007/s11102-010-0290-z. ISSN 1573-7403. PMID 21221817. S2CID 41767167.
  33. Colao A, Di Sarno A, Guerra E, De Leo M, Mentone A, Lombardi G (2006). "Drug insight: Cabergoline and bromocriptine in the treatment of hyperprolactinemia in men and women". Nature Clinical Practice Endocrinology & Metabolism. 2 (4): 200–10. doi:10.1038/ncpendmet0160. PMID 16932285. S2CID 21104519.
  34. Wang, A. T.; Mullan, R. J.; Lane, M. A.; Hazem, A.; Prasad, C.; Gathaiya, N. W.; Fernandez-Balsells, M. M.; Bagatto, A.; Coto-Yglesias, F. (2012). "Treatment of hyperprolactinemia: a systematic review and meta-analysis". Systematic Reviews. Centre for Reviews and Dissemination (UK). 1: 33. doi:10.1186/2046-4053-1-33. PMC 3483691. PMID 22828169.
  35. Di Sarno A, Landi ML, Marzullo P, Di Somma C, Pivonello R, Cerbone G, Lombardi G, Colao A (2000). "The effect of quinagolide and cabergoline, two selective dopamine receptor type 2 agonists, in the treatment of prolactinomas". Clinical Endocrinology. 53 (1): 53–60. doi:10.1046/j.1365-2265.2000.01016.x. PMID 10931080. S2CID 31677949.
  36. Bankowski BJ, Zacur HA (2003). "Dopamine agonist therapy for hyperprolactinemia". Clin Obstet Gynecol. 46 (2): 349–62. doi:10.1097/00003081-200306000-00013. PMID 12808385. S2CID 29368668.
This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.