National consensus on the management of patients with hyperprolactinemia (2016)


  • М. Д. Тронько V.P. Komisarenko Institute of Endocrinology and Metabolism of the NAMS of Ukraine
  • Ю. Г. Антипкін SI “Institute of Pediatrics, Obstetrics and Gynecology of the NAMS of Ukraine”
  • В. В. Камінський National Medical Academy of Postgraduate Education named after P.L. Shupyk
  • Т. Ф Татарчук SI “Institute of Pediatrics, Obstetrics and Gynecology of the NAMS of Ukraine”



national consensus, hyperprolactinemia, prolactin, pituitary tumors, dopamine agonists


Hyperprolactinemia is a steady rise prolactin in serum. Hyperprolactinemia can be physiological, pathological and pharmacological. Pathologic causes include the specific state of the anterior hypophyseal lobe, disorders of the hypothalamic-pituitary system and systemic disorders. If there is a diagnosis of hyperprolactinemia it is recommended to exclude its secondary causes: pregnancy, kidney or liver failure, hypothyroidism, parasellar tumors.

For diagnosis a single evaluation prolactin serum levels (≥ 25 ng/ml in females and ≥ 20 ng/ml in males) is enough. Laboratory tests should be evaluated in conjunction with clinical data and additional methods: evaluation of stress, breast ultrasound and/or mammography, assessment of the gonadotropins, estradiol and progesterone levels. In patients with hyperprolactinemia without clinical manifestations it should be macroprolactinemia excluded. There is pharmacological hyperprolactinemia if prolactin level ≈ 200 ng/ml, microprolactinoma if 250 ng/ml, macroprolactinoma if 500 ng/ml and above. Neuroimaging study should be performed in patients with any degree of hyperprolactinemia to exclude hypothalamic-pituitary area pathology.

Treatment goal is normalize the prolactin level, to restore gonadal function and galactorrhea termination and, in the case of prolactinoma to reduce the tumor mass and local compression effects. Treatment often includes administration of dopamine agonists such as bromocriptine or cabergoline, or the use of herbal medicines with dopaminergic action, containing standardized extracts of Vitex agnus castus. Cabergoline is the drug of first line as the most effective against the normalization of prolactin levels and reduce the size of the pituitary tumor.

Surgical treatment (transsphenoidal surgery) is recommended for patients with intolerance to high doses of cabergoline and resistance to other drugs in this group. Radiation therapy

should be used when radical surgery is impossible, in cases of intolerance or resistance to dopamine agonists, while aggressive prolactinoma or carcinomas.

Author Biographies

М. Д. Тронько, V.P. Komisarenko Institute of Endocrinology and Metabolism of the NAMS of Ukraine

MD, professor, academician of the NAMS of Ukraine, corresponding member of the NAMS of Ukraine, director 

Ю. Г. Антипкін, SI “Institute of Pediatrics, Obstetrics and Gynecology of the NAMS of Ukraine”

MD, academician of the NAMS of Ukraine, Director, president of the Association of Pediatricians of Ukraine

В. В. Камінський, National Medical Academy of Postgraduate Education named after P.L. Shupyk

MD, professor, corresponding member of the NAMS of Ukraine, head of the Obstetrics, Gynecology and Reproductology Department, chief specialist in Obstetrics and Gynecology at the Ministry of Health of Ukraine, executive director of the Association of Obstetricians and Gynecologists of Ukraine

Т. Ф Татарчук, SI “Institute of Pediatrics, Obstetrics and Gynecology of the NAMS of Ukraine”

MD, professor, corresponding member of the NAMS of Ukraine, deputy director for research work, сhief of the Endocrine Gynecology Department, chief specialist in Pediatric Gynecology at the Ministry of Health of Ukraine


Ben-Jonathan, N., LaPensee, C.R., LaPensee, E.W. ”What can we learn from rodents about prolactin in humans?” Endocr Rev 29 (2008): 1–41.

Freeman, M.E., Kanyicska, B., Lerant, A., Nagy, G. “Prolactin: structure, function, and regulation of secretion.” Physiol Rev 80 (2000): 1523–1631.

Grattan, D.R. “Behavioural significance of prolactin signalling in the central nervous system during pregnancy and lactation.” Reproduction 123 (2002): 497–506.

Grattan, D.R., Kokay, I.C. “Prolactin: a pleiotropic neuroendocrine hormone.” J Neuroendocrinol 20 (2008): 752–63.

Guyatt, G.H., Oxman, A.D., Vist, G.E., et al. “GRADE: an emerging consensus on rating quality of evidence and strength of recommendations.” BMJ 336 (2008): 924–26.

Prabhakar, V.K.B., Davis, J.R.E. “Hyperprolactinaemia.” Best Pract Res Clin Obstet Gynecol 22 (2008): 341–53.

Kars, M., Souverein, P.C., Herings, R.M.C., et al. “Estimated age- and sex-specific incidence and prevalence of dopamine agonist-treated hyperprolactinemia.” J Clin Endocrinol Metab 94.8 (2009): 2729–34.

Brue, T., Delemer, B. “Diagnosis and management of hyperprolactinemia: expert consensus – French Society of Endocrinology.” Ann Endocrinol (Paris) 68 (2007): 58–64.

Melmed, S., Kleinberg, D. “Anterior pituitary.” In: Williams textbook of endocrinology. 11th ed. Ed. by H.M. Kronenberg, S. Melmed, K.S. Polonsky, P.R. Larsen. Philadelphia. Saunders Elsevier (2008): 185–261.

Klibanski, A. “Clinical practice. Prolactinomas.” N Engl J Med 362 (2010): 1219–26.

Saeger, W., Lüdecke, D.K., Buchfelder, M., et al. “Pathohistological classification of pituitary tumors: 10 years of experience with the German Pituitary Tumor Registry.” Eur J Endocrinol 156 (2007): 203–16.

Buurman, H., Saeger, W. “Subclinical adenomas in postmortem pituitaries: classification and correlations to clinical data.” Eur J Endocrinol 154 (2006): 753–58.

Melmed, S., Casanueva, F.F., Hoffman, A.R., et al.; Endocrine Society. “Diagnosis and treatment of hyperprolactinemia: an Endocrine Society clinical practice guideline.” J Clin Endocrinol Metab 96.2 (2011): 273–88.

Fernandez, A., Karavitaki, N., Wass, J.A.H. “Prevalence of pituitary adenomas: a community-based, cross-sectional study in Banbury (Oxfordshire, UK).” Clin Endocrinol (Oxf) 72 (2010): 377–82.

Daly, A.F., Rixhon, M., Adam, C., et al. “High prevalence of pituitary adenomas: a cross-sectional study in the province of Liege, Belgium.” J Clin Endocrinol Metab 91 (2006): 4769–75.

Vilar, L., Czepielewsk, M.A., Naves, L.A., et al. “Substantial shrinkage of adenomas cosecreting growth hormone and prolactin with use of cabergoline therapy.” Endocr Pract 13 (2007): 396–402.

Bonert, V.S., Melmed, S. “Acromegaly with moderate hyperprolactinemia caused by an intrasellar macroadenoma.” Nat Clin Pract Endocrinol Metab 2 (2006): 408–12.

Mancini, T., Casanueva, F.F., Giustina, A. “Hyperprolactinemia and prolactinomas.” Endocrinol Metab Clin North Am 37 (2008): 67–99.

Holley, J.L. “The hypothalamic-pituitary axis in men and women with chronic kidney disease.” Adv Chronic Kidney Dis 11 (2004): 337–41.

Hou, S.H., Grossman, S., Molitch, M.E. “Hyperprolactinemia in patients with renal insufficiency and chronic renal failure requiring hemodialysis or chronic ambulatory peritoneal dialysis.” Am J Kidney Dis 6 (1985): 245–49.

Pratap, B., Sundaram, V., Abraham, G., et al. “Cessation of galactorrhea in a chronic kidney disease patient with non-tumoral hyperprolactinemia after renal transplantation.” J Assoc Physicians India 56 (2008): 54–55.

Ahmed, M., Banna, M., Sakati, N., Woodhouse, N. “Pituitary gland enlargement in primary hypothyroidism: a report of 5 cases with follow-up data.” Horm Res 32 (1989): 188–92.

Raber, W., Gessl, A., Nowotny, P., Vierhapper, H. “Hyperprolactinaemia in hypothyroidism: clinical significance and impact of TSH normalization.” Clin Endocrinol (Oxf) 58 (2003): 185–91.

Keye, W.R., Yuen, B.H., Knopf, R.F., Jaffe, R.B. “Amenorrhea, hyperprolactinemia and pituitary enlargement secondary to primary hypothyroidism. Successful treatment with thyroid replacement.” Obstet Gynecol 48 (1976): 697–702.

Bracero, N., Zacur, H.A. “Polycystic ovary syndrome and hyperprolactinemia.” Obstet Gynecol Clin North Am 28 (2001): 77–84.

Molitch, M.E. “Medication-induced hyperprolactinemia.” Mayo Clin Proc 80 (2005): 1050–7.

Romeo, J.H., Dombrowski, R., Kwak, Y.S., et al. “Hyperprolactinaemia and verapamil: prevalence and potential association with hypogonadism in men.” Clin Endocrinol (Oxf) 45 (1996): 571–5.

Luciano, A.A., Sherman, B.M., Chapler, F.K., et al. “Hyperprolactinemia and contraception: a prospective study.” Obstet Gynecol 65 (1985): 506–10.

Sluijmer, A.V., Lappöhn, R.E. “Clinical history and outcome of 59 patients with idiopathic hyperprolactinemia.” Fertil Steril 58 (1992): 72–7.

Casanueva, F.F., Molitch, M.E., Schlechte, J.A., et al. “Guidelines of the Pituitary Society for the diagnosis and management of prolactinomas.” Clin Endocrinol (Oxf) 65 (2006): 265–73.

Bolyakov, A., Paduch, D.A. “Prolactin in men’s health and disease.” Curr Opin Urol 21 (2011): 527–34.

Vestergaard, P., Jorgensen, J.O.L., Hagen, C., et al. “Fracture risk is increased in patients with GH deficiency or untreated prolactinomas – a casecontrol study.” Clin Endocrinol (Oxf) 56 (2002): 159–67.

Fideleff, H.L., Boquete, H.R., Sequera, A., et al. “Peripubertal prolactinomas: clinical presentation and long-term outcome with different therapeutic approaches.” J Pediatr Endocrinol Metab 13 (2000): 261–7.

Eren, E., Yapici, S., Cakir, E.D.P., et al. “Clinical course of hyperprolactinemia in children and adolescents: a review of 21 cases.” J Clin Res Pediatr Endocrinol 3 (2011): 65–9.

Karavitaki, N., Thanabalasingham, G., Shore, H.C.A., et al. “Do the limits of serum prolactin in disconnection hyperprolactinaemia need re-definition? A study of 226 patients with histologically verified non-functioning pituitary macroadenoma.” Clin Endocrinol (Oxf) 65 (2006): 524–9.

Moreno, B., Obiols, G., Paramo, C., Zugasti, A. “Guia clinica del manejo del prolactinoma y otros estados de hiperprolactinemia.” Endocrinol Nutr 52 (2005): 9–17.

Chahal, J., Schlechte, J. “Hyperprolactinemia.” Pituitary 11 (2008): 141–6.

Petakov, M.S., Damjanović, S.S., Nikolić-Durović, M.M., et al. “Pituitary adenomas secreting large amounts of prolactin may give false low values in immunoradiometric assays. The hook effect.” J Endocrinol Invest 21 (1998): 184–8.

Hattori, N. “Macroprolactinemia: a new cause of hyperprolactinemia.” J Pharmacol Sci 92 (2003): 171–7.

Donadio, F., Barbieri, A., Angioni, R., et al. “Patients with macroprolactinaemia: clinical and radiological features.” Eur J Clin Invest 37 (2007): 552–7.

Amadori, P., Dilberis, C., Marcolla, A., et al. “Macroprolactinemia: predictability on clinical basis and detection by PEG precipitation with two different immunometric methods.” J Endocrinol Invest 26 (2003): 148–56.

Smith, T.P., Suliman, A.M., Fahie-Wilson, M.N., McKenna, T.J. “Gross variability in the detection of prolactin in sera containing big prolactin (macroprolactin) by commercial immunoassays.” J Clin Endocrinol Metab 87 (2002): 5410–5.

Colao, A., Savastano, S. “Medical treatment of prolactinomas.” Nat Rev Endocrinol 7 (2011): 267–78.

Volavka, J., Czobor, P., Cooper, T.B., et al. “Prolactin levels in schizophrenia and schizoaffective disorder patients treated with clozapine, olanzapine, risperidone, or haloperidol.” J Clin Psychiatry 65 (2004): 57–61.

Misra, M., Papakostas, G.I., Klibanski, A. “Effects of psychiatric disorders and psychotropic medications on prolactin and bone metabolism.” J Clin Psychiatry 65 (2004): 1607–18.

Spitzer, M., Sajjad, R., Benjamin, F. “Pattern of development of hyperprolactinemia after initiation of haloperidol therapy.” Obstet Gynecol 91 (1998): 693–5.

Cavallaro, R., Cocchi, F., Angelone, S.M., et al. “Cabergoline treatment of risperidone-induced hyperprolactinemia: a pilot study.” J Clin Psychiatry 65 (2004): 187–90.

Smith, S. “Neuroleptic-associated hyperprolactinemia. Can it be treated with bromocriptine?” J Reprod Med 37 (1992): 737–40.

Verhelst, J., Abs, R., Maiter, D., et al. “Cabergoline in the treatment of hyperprolactinemia: a study in 455 patients.” J Clin Endocrinol Metab 84 (1999): 2518–22.

Webster, J., Piscitelli, G., Polli, A., et al. “A comparison of cabergoline and bromocriptine in the treatment of hyperprolactinemic amenorrhea. Cabergoline Comparative Study Group.” N Engl J Med 331 (1994): 904–9.

Colao, A., Di Sarno, A., Sarnacchiaro, F., et al. “Prolactinomas resistant to standard dopamine agonists respond to chronic cabergoline treatment.” J Clin Endocrinol Metab 82 (1997): 876–83.

Colao, A., Di Sarno, A., Cappabianca, P., et al. “Withdrawal of long-term cabergoline therapy for tumoral and nontumoral hyperprolactinemia.” N Engl J Med 349 (2003): 2023–33.

Gillam, M.P., Molitch, M.E., Lombardi, G., Colao, A. “Advances in the treatment of prolactinomas.” Endocr Rev 27 (2006): 485–534.

Zada, G., Woodmansee, W.W., Ramkissoon, S., et al. “Atypical pituitary adenomas: incidence, clinical characteristics, and implications.” Neurosurg 114 (2011): 336–44.

Kars, M., Dekkers, O.M., Pereira, A.M., Romijn, J.A. “Update in prolactinomas.” Netherl J Med 68 (2010): 104–12.

Yefymenko, O.A. “Current view on the hyperprolactinemia problem.” Health Protection of Ukraine. Gynecology. Obstetrics. Reproduction 1.5 (2012): 50–2.

Wuttke, W., Seidlova-Wuttke, D., Jarry, H., Artymuk, N. “Der Stellenwert des Mönchspfeffers (Vitex agnus-castus) in der gynäkologischen Endokrinologie.“ Zeitschrift Phytotherapie 31 (2010): 294–8.

Wuttke, W., et al. “Behandlung zyklusabhängiger Brustschmerzen mit einem Agnus castus haltigen Arzneimittel.“ Geburtshilfe und Frauenheilkunde 57 (1997): 569–74.

Halaska, M., Beles, P., Gorkow, C., et al. “Treatment of cyclical mastalgia with a solution containing a vitex Agnus castus extract: results of a placebo controlled double blind study.” The Breast 8 (1999): 175–81.

Prilepskaya, V.N., et al. “Vitex agnus castus: Successful treatment of moderate to severe premenstrual syndrome.” Maturitas 1.55 (2006): 64–74.

Smetnik, V.P., Butareva L.B. “Experience of phytodrug «Cyclodynon» use in patients with failure of the corpus luteum function and hyperprolactinemia.” Reproductive Problems 5 (2005): 1–4.

Gerhard, I., Patek, A., et al. “Mastodynon® bei weiblicher Sterilität (Mastodynon for female infertility). Randomisierte, plazebokontrollierte klinische Doppelblindstudie.” Forsch Komplementärmed 20 (1998): 272–8.

Tatarchuk, T.F., Tutchenko, T.N. “Correction of hyperprolactinemia in treatment of endometrial hyperplasia.” Reproductive Endocrinology 2 (2013).

Atmaca, M., et al. “Fluoxetine versus Vitex Agnus castus extract in the treatment of premenstrual dysphoric disorder.” Human Psychopharmacology Clin Exp 18 (2003): 191–5.

Jarry, H., et al. “Agnus castus als dopaminerges Wirkprinzip in Mastodynon®.” N Zschr Phytotherapie 12 (1991): 77–82.

Kubista, E., Müller, G., et al. “Behandlung der Mastopathie mit zyklischer Mastodynie: Klinische Ergebnisse und Hormonprofile (Treatment of mastopathy with cyclic mastodynia: clinical results and hormone profiles).” Gynäk Rdsch 26 (1986): 65–79.

Liebl A. “Behandlung des prämenstruellen Syndroms – Agnus-castus-haltiges Kombinationsarzneimittel im Test.“ TW Gynäkologie 5 (1992): 147–54.

Burdina, L.M. “Therapeutic possibilities of Chaste Tree extracts (Vitex agnus castus) in gynecological practice.” Reproduction Problems 4 (2009).

Breast cancer and gynecological diseases. Ed. by V.E. Radzinsky. Moscow. StatusPraesens (2012).

Kilicdag, E.B., Tarim, E., Bagis, T., et al. “Fructus agni and bromcriptine for treatment of hyperprolactinemia and mastalgia.” International Journal of Gynecology and Obstetrics 85 (2004): 292–3.

Carmichael, R. “Can Vitex agnus castus be used for the treatment of mastalgia? What is the current evidence?” Evid Based Complement Alternat Med 5.3 (2008): 247–50. DOI: 10.1093/ecam/nem074

Dubossarskaya, Z.M., Dubossarskaya, Y.A. Reproductive endocrinology (prenatal, obstetrical and gynecological aspects): manual. Dnipropetrovsk. Lira LTD (2008): 200–209.

Melnichenko, G.A., Dzeranova, L.K., Pigarova, E.A., et al. “Federal guidelines for the clinic, diagnosis, differential diagnosis and treatment methods of hyperprolactinemia.” Endocrinology Problems 59.6 (2013): 19–26.

Tatarchuk, T.F., Yefymenko, O.A. “Hyperprolactinemia as a symptom, syndrome, diagnosis.” Health of Ukraine 1 (2013): 47–9.

Lennartsson, A.-K., et al. “Prolactin in response to acute psychosocial stress in healthy men and women.” Psychoneuroendocrinology 36.10 (2011): 1530–9.





National consensus