Advertisement

The effect of metformin on prolactin levels in patients with drug-induced hyperprolactinemia

Published:February 05, 2016DOI:https://doi.org/10.1016/j.ejim.2016.01.015

      Highlights

      • Metformin reduces elevated, but not normal, prolactin levels.
      • Prolactin-lowering effect of metformin is dose-dependent.
      • This effect correlates with baseline prolactin levels.
      • Metformin may bring benefits to patients with drug-induced hyperprolactinemia.

      Abstract

      Background

      In bromocriptine-treated hyperprolactinemic patients with impaired glucose tolerance, metformin was found to reduce plasma levels of prolactin. No previous study has investigated its impact on plasma prolactin in patients with drug-induced hyperprolactinemia.

      Methods

      The study included 20 women with antipsychotic-induced hyperprolactinemia and 12 normoprolactinemic women, who, because of coexisting glucose metabolism abnormalities, were treated for 6 months with metformin. Hyperprolactinemic patients with prediabetes received moderate doses of metformin (1.7 g daily), while hyperprolactinemic and normoprolactinemic patients with type 2 diabetes were treated with high-dose metformin (2.55–3 g daily). Fasting plasma glucose levels, the homeostatic model assessment 1 of insulin resistance ratio (HOMA1-IR), glycated hemoglobin, as well as plasma levels of prolactin, thyrotropin, adrenocorticotropic hormone and insulin-like growth factor-1 were assessed at baseline and after 6 months of treatment.

      Results

      Despite reducing plasma glucose, HOMA1-IR, and glycated hemoglobin in all treatment groups, metformin decreased prolactin levels only if given at high doses to patients with elevated prolactin levels. No changes in thyrotropin, adrenocorticotropic hormone, and insulin-like growth factor-1 were observed in any treatment groups.

      Conclusions

      The obtained results suggest that the effect of metformin on plasma prolactin depends on its dose and is observed only in patients with elevated levels of this hormone.

      Abbreviations:

      ACTH (Adrenocorticotropic hormone), HOMA1-IR (The homeostatic model assessment 1 of insulin resistance ratio), IGF-1 (Insulin-like growth factor-1), SD (Standard deviation)

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to European Journal of Internal Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • dos Santos Silva C.M.
        • Barbosa F.R.
        • Lima G.A.
        • Warszawski L.
        • Fontes R.
        • Domingues R.C.
        • et al.
        BMI and metabolic profile in patients with prolactinoma before and after treatment with dopamine agonists.
        Obesity (Silver Spring). 2011; 19: 800-805
        • Berinder K.
        • Nyström T.
        • Höybye C.
        • Hall K.
        • Hulting A.L.
        Insulin sensitivity and lipid profile in prolactinoma patients before and after normalization of prolactin by dopamine agonist therapy.
        Pituitary. 2011; 14: 199-207
        • Jiang X.B.
        • He D.S.
        • Mao Z.G.
        • Fan X.
        • Lei N.
        • Hu B.
        • et al.
        BMI, apolipoprotein B/apolipoprotein A-I ratio, and insulin resistance in patients with prolactinomas: a pilot study in a Chinese cohort.
        Tumour Biol. 2013; 34: 1171-1176
        • Jiang X.B.
        • Li C.L.
        • He D.S.
        • Liu D.H.
        • Fan X.
        • Hu B.
        • et al.
        Increased carotid intima media thickness is associated with prolactin levels in subjects with untreated prolactinoma: a pilot study.
        Pituitary. 2014; 17: 232-239
        • Serri O.
        • Li L.
        • Mamputu J.C.
        • Beauchamp M.C.
        • Maingrette F.
        • Renier G.
        The influences of hyperprolactinemia and obesity on cardiovascular risk markers: effects of cabergoline therapy.
        Clin Endocrinol (Oxf). 2006; 64: 366-370
        • Yavuz D.
        • Deyneli O.
        • Akpinar I.
        • Yildiz E.
        • Gözü H.
        • Sezgin O.
        • et al.
        Endothelial function, insulin sensitivity and inflammatory markers in hyperprolactinemic pre-menopausal women.
        Eur J Endocrinol. 2003; 149: 187-193
        • Greenman Y.
        • Tordjman K.
        • Stern N.
        Increased body weight associated with prolactin secreting pituitary adenomas: weight loss with normalization of prolactin levels.
        Clin Endocrinol (Oxf). 1998; 48: 547-553
        • Schmid C.
        • Goede D.L.
        • Hauser R.S.
        • Brandle M.
        Increased prevalence of high body mass index in patients presenting with pituitary tumours: severe obesity in patients with macroprolactinoma.
        Swiss Med Wkly. 2006; 136: 254-258
        • Doknic M.
        • Pekic S.
        • Zarkovic M.
        • Medic-Stojanoska M.
        • Dieguez C.
        • Casanueva F.
        • et al.
        Dopaminergic tone and obesity: an insight from prolactinomas treated with bromocriptine.
        Eur J Endocrinol. 2002; 147: 77-84
        • Kumar V.
        • Aithal S.
        • Baleed S.R.
        • Patil U.N.
        Bromocriptine, a dopamine (D2) receptor agonist, used alone and in combination with glipizide in sub-therapeutic doses to ameliorate hyperglycaemia.
        J Clin Diagn Res. 2013; 7: 1904-1907
        • Grunberger G.
        Novel therapies for the management of type 2 diabetes mellitus: part 1. pramlintide and bromocriptine-QR.
        J Diabetes. 2013; 5: 110-117
        • Voicu V.
        • Medvedovici A.
        • Ranetti A.E.
        • Rădulescu F.Ş.
        Drug-induced hypo- and hyperprolactinemia: mechanisms, clinical and therapeutic consequences.
        Expert Opin Drug Metab Toxicol. 2013; 9: 955-968
        • Molitch M.E.
        Medication-induced hyperprolactinemia.
        Mayo Clin Proc. 2005; 80: 1050-1057
        • Kelly D.L.
        • Wehring H.J.
        • Earl A.K.
        • Sullivan K.M.
        • Dickerson F.B.
        • Feldman S.
        • et al.
        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. 2013; 13: 214
        • Ajmal A.
        • Joffe H.
        • Nachtigall L.B.
        Psychotropic-induced hyperprolactinemia: a clinical review.
        Psychosomatics. 2014; 55: 29-36
        • Tran L.
        • Zielinski A.
        • Roach A.H.
        • Jende J.A.
        • Householder A.M.
        • Cole E.E.
        • et al.
        The pharmacologic treatment of type 2 diabetes: oral medications.
        Ann Pharmacother. 2015; 49: 540-556
        • Scarpello J.H.
        • Howlett H.C.
        Metformin therapy and clinical uses.
        Diab Vasc Dis Res. 2008; 5: 157-167
        • Genuth S.
        The UKPDS and its global impact.
        Diabet Med. 2008; 25: 57-62
        • Diabetes Prevention Program Research Group
        Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin.
        N Engl J Med. 2002; 346: 393-403
        • Labuzek K.
        • Suchy D.
        • Gabryel B.
        • Bielecka A.
        • Liber S.
        • Okopien B.
        Quantification of metformin by the HPLC method in brain regions, cerebrospinal fluid and plasma of rats treated with lipopolysaccharide.
        Pharmacol Rep. 2010; 62: 956-965
        • Vigersky R.A.
        • Filmore-Nassar A.
        • Glass A.R.
        Thyrotropin suppression by metformin.
        J Clin Endocrinol Metab. 2006; 91: 225-227
        • Cappelli C.
        • Rotondi M.
        • Pirola I.
        • Agosti B.
        • Gandossi E.
        • Valentini U.
        • et al.
        TSH-lowering effect of metformin in type 2 diabetic patients: differences between euthyroid, untreated hypothyroid, and euthyroid on L-T4 therapy patients.
        Diabetes Care. 2009; 32: 1589-1590
        • Isidro M.L.
        • Penín M.A.
        • Nemiña R.
        • Cordido F.
        Metformin reduces thyrotropin levels in obese, diabetic women with primary hypothyroidism on thyroxine replacement therapy.
        Endocrine. 2007; 32: 79-82
        • Morteza Taghavi S.
        • Rokni H.
        • Fatemi S.
        Metformin decreases thyrotropin in overweight women with polycystic ovarian syndrome and hypothyroidism.
        Diab Vasc Dis Res. 2011; 8: 47-48
        • Krysiak R.
        • Okopien B.
        The effect of metformin on the hypothalamic–pituitary–thyroid axis in women with polycystic ovary syndrome and subclinical hypothyroidism.
        J Clin Pharmacol. 2015; 55: 45-49
        • Oride A.
        • Kanasaki H.
        • Purwana I.N.
        • Miyazaki K.
        Effects of metformin administration on plasma gonadotropin levels in women with infertility, with an in vitro study of the direct effects on the pituitary gonadotrophs.
        Pituitary. 2010; 13: 236-241
        • Genazzani A.D.
        • Battaglia C.
        • Malavasi B.
        • Strucchi C.
        • Tortolani F.
        • Gamba O.
        Metformin administration modulates and restores luteinizing hormone spontaneous episodic secretion and ovarian function in nonobese patients with polycystic ovary syndrome.
        Fertil Steril. 2004; 81: 1114-1119
        • Billa E.
        • Kapolla N.
        • Nicopoulou S.C.
        • Koukkou E.
        • Venaki E.
        • Milingos S.
        • et al.
        Metformin administration was associated with a modification of LH, prolactin and insulin secretion dynamics in women with polycystic ovarian syndrome.
        Gynecol Endocrinol. 2009; 25: 427-434
        • Banaszewska B.
        • Pawelczyk L.
        • Spaczynski R.Z.
        • Duleba A.J.
        Comparison of simvastatin and metformin in treatment of polycystic ovary syndrome: prospective randomized trial.
        J Clin Endocrinol Metab. 2009; 94: 4938-4945
        • Banaszewska B.
        • Pawelczyk L.
        • Spaczynski R.Z.
        • Duleba A.J.
        Effects of simvastatin and metformin on polycystic ovary syndrome after six months of treatment.
        J Clin Endocrinol Metab. 2011; 96: 3493-3501
        • Krysiak R.
        • Okrzesik J.
        • Okopien B.
        The effect of short-term metformin treatment on plasma prolactin levels in bromocriptine-treated patients with hyperprolactinaemia and impaired glucose tolerance: a pilot study.
        Endocrine. 2014; 49: 242-249
        • Hekimsoy Z.
        • Kafesçiler S.
        • Güçlü F.
        • Ozmen B.
        The prevalence of hyperprolactinaemia in overt and subclinical hypothyroidism.
        Endocr J. 2010; 57: 1011-1015
        • Cortet-Rudelli C.
        • Sapin R.
        • Bonneville J.F.
        • Brue T.
        Etiological diagnosis of hyperprolactinemia.
        Ann Endocrinol (Paris). 2007; 68: 98-105
        • Oh M.C.
        • Kunwar S.
        • Blevins L.
        • Aghi M.K.
        Medical versus surgical management of prolactinomas.
        Neurosurg Clin N Am. 2012; 23: 669-678
        • Mann W.A.
        Treatment for prolactinomas and hyperprolactinaemia: a lifetime approach.
        Eur J Clin Invest. 2011; 41: 334-342
        • Vottero A.
        • Guzzetti C.
        • Loche S.
        New aspects of the physiology of the GH-IGF-1 axis.
        Endocr Dev. 2013; 24: 96-105
        • Oleandri S.E.
        • Maccario M.
        • Rossetto R.
        • Procopio M.
        • Grottoli S.
        • Avogadri E.
        • et al.
        Three-month treatment with metformin or dexfenfluramine does not modify the effects of diet on anthropometric and endocrine-metabolic parameters in abdominal obesity.
        J Endocrinol Invest. 1999; 22: 134-140
        • Krysiak R.
        • Szkrobka W.
        • Okopien B.
        The effect of metformin on the hypothalamic–pituitary–thyroid axis in patients with type 2 diabetes and subclinical hyperthyroidism.
        Exp Clin Endocrinol Diabetes. 2015; 123: 205-208
        • Krysiak R.
        • Okopien B.
        Thyrotropin-lowering effect of metformin in a patient with resistance to thyroid hormone.
        Clin Endocrinol (Oxf). 2011; 75: 404-406
        • Beaulieu J.M.
        • Gainetdinov R.R.
        The physiology, signaling, and pharmacology of dopamine receptors.
        Pharmacol Rev. 2011; 63: 182-217