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Published in: Endocrine 1/2015

Open Access 01-05-2015 | Original Article

The effect of short-term metformin treatment on plasma prolactin levels in bromocriptine-treated patients with hyperprolactinaemia and impaired glucose tolerance: a pilot study

Authors: Robert Krysiak, Joanna Okrzesik, Boguslaw Okopien

Published in: Endocrine | Issue 1/2015

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Abstract

Metformin was found to affect plasma levels of some pituitary hormones. This study was aimed at investigating whether metformin treatment has an impact on plasma prolactin levels in bromocriptine-treated patients with hyperprolactinaemia and impaired glucose tolerance. The study included 27 patients with hyperprolactinaemia, who had been treated for at least 6 months with bromocriptine. Based on prolactin levels, bromocriptine-treated patients were divided into two groups: patients with elevated (group A, n = 12) and patients with normal (group B, n = 15) prolactin levels. The control group included 16 age-, sex- and weight-matched hyperprolactinaemia-free individuals with impaired glucose tolerance (group C).The lipid profile, fasting plasma glucose levels, the homeostatic model assessment of insulin resistance ratio (HOMA-IR), glycated haemoglobin, as well as plasma levels of prolactin, thyrotropin and insulin-like growth factor-1 (IGF-1) were assessed at baseline and after 4 months of metformin treatment (2.55–3 g daily). In all treatment groups, metformin reduced HOMA-IR, plasma triglycerides and 2-h postchallenge plasma glucose. In patients with hyperprolactinaemia, but not in the other groups of patients, metformin slightly reduced plasma levels of prolactin, and this effect correlated weakly with the metabolic effects of this drug. Our study shows that metformin decreases plasma prolactin levels only in patients with elevated levels of this hormone. The obtained results suggest that metformin treatment may bring some benefits to hyperprolactinaemic patients with coexisting glucose metabolism disturbances already receiving dopamine agonist therapy.
Literature
1.
go back to reference D. Yavuz, O. Deyneli, I. Akpinar, E. Yildiz, H. Gözü, O. Sezgin et al., Endothelial function, insulin sensitivity and inflammatory markers in hyperprolactinaemic pre-menopausal women. Eur. J. Endocrinol. 149, 187–193 (2003)CrossRefPubMed D. Yavuz, O. Deyneli, I. Akpinar, E. Yildiz, H. Gözü, O. Sezgin et al., Endothelial function, insulin sensitivity and inflammatory markers in hyperprolactinaemic pre-menopausal women. Eur. J. Endocrinol. 149, 187–193 (2003)CrossRefPubMed
2.
go back to reference C.M. dos Santos Silva, F.R. Barbosa, L. Warszawski, R. Fontes, R.C. Domingues, M.R. Gadelha, BMI and metabolic profile in patients with prolactinoma before and after treatment with dopamine agonists. Obesity (Silver Spring) 19, 800–805 (2011)CrossRef C.M. dos Santos Silva, F.R. Barbosa, L. Warszawski, R. Fontes, R.C. Domingues, M.R. Gadelha, BMI and metabolic profile in patients with prolactinoma before and after treatment with dopamine agonists. Obesity (Silver Spring) 19, 800–805 (2011)CrossRef
3.
go back to reference O. Serri, L. Li, J.C. Mamputu, M.C. Beauchamp, F. Maingrette, G. Renier, The influences of hyperprolactinaemia and obesity on cardiovascular risk markers: effects of cabergoline therapy. Clin. Endocrinol. (Oxf.) 64, 366–370 (2006) O. Serri, L. Li, J.C. Mamputu, M.C. Beauchamp, F. Maingrette, G. Renier, The influences of hyperprolactinaemia and obesity on cardiovascular risk markers: effects of cabergoline therapy. Clin. Endocrinol. (Oxf.) 64, 366–370 (2006)
4.
go back to reference K. Berinder, T. Nyström, C. Höybye, K. Hall, A.L. Hulting, Insulin sensitivity and lipid profile in prolactinoma patients before and after normalization of prolactin by dopamine agonist therapy. Pituitary 14, 199–207 (2011)CrossRefPubMed K. Berinder, T. Nyström, C. Höybye, K. Hall, A.L. Hulting, Insulin sensitivity and lipid profile in prolactinoma patients before and after normalization of prolactin by dopamine agonist therapy. Pituitary 14, 199–207 (2011)CrossRefPubMed
5.
go back to reference X.B. Jiang, C.L. Li, D.S. He, Z.G. Mao, D.H. Liu, X. Fan et al., Increased carotid intima media thickness is associated with prolactin levels in subjects with untreated prolactinoma: a pilot study. Pituitary 17, 232–239 (2014)CrossRefPubMed X.B. Jiang, C.L. Li, D.S. He, Z.G. Mao, D.H. Liu, X. Fan et al., Increased carotid intima media thickness is associated with prolactin levels in subjects with untreated prolactinoma: a pilot study. Pituitary 17, 232–239 (2014)CrossRefPubMed
6.
go back to reference X.B. Jiang, D.S. He, Z.G. Mao, X. Fan, N. Lei, B. Hu 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. 34, 1171–1176 (2013)CrossRefPubMed X.B. Jiang, D.S. He, Z.G. Mao, X. Fan, N. Lei, B. Hu 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. 34, 1171–1176 (2013)CrossRefPubMed
8.
go back to reference H. Pijl, S. Ohashi, M. Matsuda, Y. Miyazaki, A. Mahankali, V. Kumar et al., Bromocriptine: a novel approach to the treatment of type 2 diabetes. Diabetes Care 23, 1154–1161 (2000)CrossRefPubMed H. Pijl, S. Ohashi, M. Matsuda, Y. Miyazaki, A. Mahankali, V. Kumar et al., Bromocriptine: a novel approach to the treatment of type 2 diabetes. Diabetes Care 23, 1154–1161 (2000)CrossRefPubMed
9.
go back to reference V. Kamath, C.N. Jones, J.C. Yip, B.B. Varasteh, A.H. Cincotta, G.M. Reaven et al., Effects of a quick-release form of bromocriptine (Ergoset) on fasting and postprandial plasma glucose, insulin, lipid, and lipoprotein concentrations in obese nondiabetic hyperinsulinaemic women. Diabetes Care 20, 1697–1701 (1997)CrossRefPubMed V. Kamath, C.N. Jones, J.C. Yip, B.B. Varasteh, A.H. Cincotta, G.M. Reaven et al., Effects of a quick-release form of bromocriptine (Ergoset) on fasting and postprandial plasma glucose, insulin, lipid, and lipoprotein concentrations in obese nondiabetic hyperinsulinaemic women. Diabetes Care 20, 1697–1701 (1997)CrossRefPubMed
10.
go back to reference A. Ciresi, M.C. Amato, V. Guarnotta, F. Lo Castro, C. Giordano, Higher doses of cabergoline further improve metabolic parameters in patients with prolactinoma regardless of the degree of reduction in prolactin levels. Clin. Endocrinol. (Oxf.) 79, 845–852 (2013)CrossRef A. Ciresi, M.C. Amato, V. Guarnotta, F. Lo Castro, C. Giordano, Higher doses of cabergoline further improve metabolic parameters in patients with prolactinoma regardless of the degree of reduction in prolactin levels. Clin. Endocrinol. (Oxf.) 79, 845–852 (2013)CrossRef
11.
go back to reference R.S. Auriemma, L. Granieri, M. Galdiero, C. Simeoli, Y. Perone, P. Vitale et al., Effect of cabergoline on metabolism in prolactinomas. Neuroendocrinology 98, 299–310 (2013)CrossRefPubMed R.S. Auriemma, L. Granieri, M. Galdiero, C. Simeoli, Y. Perone, P. Vitale et al., Effect of cabergoline on metabolism in prolactinomas. Neuroendocrinology 98, 299–310 (2013)CrossRefPubMed
12.
13.
go back to reference J.H. Scarpello, H.C. Howlett, Metformin therapy and clinical uses. Diab. Vasc. Dis. Res. 5, 157–167 (2008)CrossRefPubMed J.H. Scarpello, H.C. Howlett, Metformin therapy and clinical uses. Diab. Vasc. Dis. Res. 5, 157–167 (2008)CrossRefPubMed
14.
go back to reference C. Cappelli, M. Rotondi, I. Pirola, B. Agosti, E. Gandossi, U. Valentini 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 32, 1589–1590 (2009)CrossRefPubMedCentralPubMed C. Cappelli, M. Rotondi, I. Pirola, B. Agosti, E. Gandossi, U. Valentini 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 32, 1589–1590 (2009)CrossRefPubMedCentralPubMed
15.
go back to reference R.A. Vigersky, A. Filmore-Nassar, A.R. Glass, Thyrotropin suppression by metformin. J. Clin. Endocrinol. Metab. 91, 225–227 (2006)CrossRefPubMed R.A. Vigersky, A. Filmore-Nassar, A.R. Glass, Thyrotropin suppression by metformin. J. Clin. Endocrinol. Metab. 91, 225–227 (2006)CrossRefPubMed
16.
go back to reference M.L. Isidro, M.A. Penín, R. Nemina, F. Cordido, Metformin reduces thyrotropin levels in obese, diabetic women with primary hypothyroidism on thyroxine replacement therapy. Endocrine 32, 79–82 (2007)CrossRefPubMed M.L. Isidro, M.A. Penín, R. Nemina, F. Cordido, Metformin reduces thyrotropin levels in obese, diabetic women with primary hypothyroidism on thyroxine replacement therapy. Endocrine 32, 79–82 (2007)CrossRefPubMed
17.
go back to reference A. Oride, H. Kanasaki, I.N. Purwana, K. Miyazaki, 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 13, 236–241 (2010)CrossRefPubMed A. Oride, H. Kanasaki, I.N. Purwana, K. Miyazaki, 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 13, 236–241 (2010)CrossRefPubMed
18.
go back to reference A.D. Genazzani, C. Battaglia, B. Malavasi, C. Strucchi, F. Tortolani, O. Gamba, Metformin administration modulates and restores luteinizing hormone spontaneous episodic secretion and ovarian function in nonobese patients with polycystic ovary syndrome. Fertil. Steril. 81, 114–119 (2004)CrossRefPubMed A.D. Genazzani, C. Battaglia, B. Malavasi, C. Strucchi, F. Tortolani, O. Gamba, Metformin administration modulates and restores luteinizing hormone spontaneous episodic secretion and ovarian function in nonobese patients with polycystic ovary syndrome. Fertil. Steril. 81, 114–119 (2004)CrossRefPubMed
19.
go back to reference Z. Velija-Ašimi, Evaluation of endocrine changes in women with the polycystic ovary syndrome during metformin treatment. Bosn. J. Basic Med. Sci. 13, 180–185 (2013)PubMedCentralPubMed Z. Velija-Ašimi, Evaluation of endocrine changes in women with the polycystic ovary syndrome during metformin treatment. Bosn. J. Basic Med. Sci. 13, 180–185 (2013)PubMedCentralPubMed
20.
go back to reference E. Billa, N. Kapolla, S.C. Nicopoulou, E. Koukkou, E. Venaki, S. Milingos et al., Metformin administration was associated with a modification of LH, prolactin and insulin secretion dynamics in women with polycystic ovarian syndrome. Gynecol. Endocrinol. 25, 427–434 (2009)CrossRefPubMed E. Billa, N. Kapolla, S.C. Nicopoulou, E. Koukkou, E. Venaki, S. Milingos et al., Metformin administration was associated with a modification of LH, prolactin and insulin secretion dynamics in women with polycystic ovarian syndrome. Gynecol. Endocrinol. 25, 427–434 (2009)CrossRefPubMed
21.
go back to reference B. Banaszewska, L. Pawelczyk, R.Z. Spaczynski, A.J. Duleba, Comparison of simvastatin and metformin in treatment of polycystic ovary syndrome: prospective randomized trial. J. Clin. Endocrinol. Metab. 94, 4938–4945 (2009)CrossRefPubMedCentralPubMed B. Banaszewska, L. Pawelczyk, R.Z. Spaczynski, A.J. Duleba, Comparison of simvastatin and metformin in treatment of polycystic ovary syndrome: prospective randomized trial. J. Clin. Endocrinol. Metab. 94, 4938–4945 (2009)CrossRefPubMedCentralPubMed
22.
go back to reference B. Banaszewska, L. Pawelczyk, R.Z. Spaczynski, A.J. Duleba, Effects of simvastatin and metformin on polycystic ovary syndrome after six months of treatment. J. Clin. Endocrinol. Metab. 96, 3493–3501 (2011)CrossRefPubMedCentralPubMed B. Banaszewska, L. Pawelczyk, R.Z. Spaczynski, A.J. Duleba, Effects of simvastatin and metformin on polycystic ovary syndrome after six months of treatment. J. Clin. Endocrinol. Metab. 96, 3493–3501 (2011)CrossRefPubMedCentralPubMed
23.
go back to reference R. Krysiak, B. Okopien, Thyrotropin-lowering effect of metformin in a patient with resistance to thyroid hormone. Clin. Endocrinol. 75, 404–406 (2011)CrossRef R. Krysiak, B. Okopien, Thyrotropin-lowering effect of metformin in a patient with resistance to thyroid hormone. Clin. Endocrinol. 75, 404–406 (2011)CrossRef
24.
go back to reference A. Borai, C. Livingstone, G.A. Ferns, The biochemical assessment of insulin resistance. Ann. Clin. Biochem. 44(Pt 4), 324–342 (2007)CrossRefPubMed A. Borai, C. Livingstone, G.A. Ferns, The biochemical assessment of insulin resistance. Ann. Clin. Biochem. 44(Pt 4), 324–342 (2007)CrossRefPubMed
25.
go back to reference World Health Organization, Waist circumference and waist–hip ratio: report of a WHO Expert Consultation Geneva, 8–11 December 2008 World Health Organization, Waist circumference and waist–hip ratio: report of a WHO Expert Consultation Geneva, 8–11 December 2008
26.
go back to reference G. Mancia, R. Fagard, K. Narkiewicz, J. Redón, A. Zanchetti, M. Böhm et al., 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J. Hypertens. 31, 1281–1357 (2013)CrossRefPubMed G. Mancia, R. Fagard, K. Narkiewicz, J. Redón, A. Zanchetti, M. Böhm et al., 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J. Hypertens. 31, 1281–1357 (2013)CrossRefPubMed
27.
go back to reference Diabetes Prevention Program Research Group, Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N. Engl. J. Med. 346, 393–403 (2002)CrossRefPubMedCentral Diabetes Prevention Program Research Group, Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N. Engl. J. Med. 346, 393–403 (2002)CrossRefPubMedCentral
28.
go back to reference R.C. Turner, R.R. Holman, I.M. Stratton, UK Prospective Diabetes Study: Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 352, 854–865 (1998)CrossRef R.C. Turner, R.R. Holman, I.M. Stratton, UK Prospective Diabetes Study: Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 352, 854–865 (1998)CrossRef
29.
go back to reference R. Krysiak, B. Okopien, The effect of metformin on androgen production in diabetic women with non-classic congenital adrenal hyperplasia. Exp. Clin. Endocrinol. Diabetes (2014). doi:10.1055/s-0034-1382048 R. Krysiak, B. Okopien, The effect of metformin on androgen production in diabetic women with non-classic congenital adrenal hyperplasia. Exp. Clin. Endocrinol. Diabetes (2014). doi:10.​1055/​s-0034-1382048
30.
go back to reference R. Krysiak, B. Okopien, Thyrotropin-lowering effect of metformin in a patient with resistance to thyroid hormone. Clin. Endocrinol. (Oxf.) 75, 404–406 (2011)CrossRef R. Krysiak, B. Okopien, Thyrotropin-lowering effect of metformin in a patient with resistance to thyroid hormone. Clin. Endocrinol. (Oxf.) 75, 404–406 (2011)CrossRef
31.
go back to reference R. Krysiak, A. Gdula-Dymek, B. Okopien, Lymphocyte-suppressing, endothelial-protective and systemic anti-inflammatory effects of metformin in fenofibrate-treated patients with impaired glucose tolerance. Pharmacol. Rep. 65, 429–434 (2013)CrossRefPubMed R. Krysiak, A. Gdula-Dymek, B. Okopien, Lymphocyte-suppressing, endothelial-protective and systemic anti-inflammatory effects of metformin in fenofibrate-treated patients with impaired glucose tolerance. Pharmacol. Rep. 65, 429–434 (2013)CrossRefPubMed
32.
go back to reference R. Krysiak, A. Gdula-Dymek, B. Okopien, Monocyte-suppressing effect of high-dose metformin in fenofibrate-treated patients with impaired glucose tolerance. Pharmacol. Rep. 65, 1311–1316 (2013)CrossRefPubMed R. Krysiak, A. Gdula-Dymek, B. Okopien, Monocyte-suppressing effect of high-dose metformin in fenofibrate-treated patients with impaired glucose tolerance. Pharmacol. Rep. 65, 1311–1316 (2013)CrossRefPubMed
33.
go back to reference C.J. Glueck, N. Goldenberg, P. Wang, Metformin-diet ameliorates coronary heart disease risk factors and facilitates resumption of regular menses in adolescents with polycystic ovary syndrome. J. Pediatr. Endocrinol. Metab. 22, 815–826 (2009)CrossRefPubMed C.J. Glueck, N. Goldenberg, P. Wang, Metformin-diet ameliorates coronary heart disease risk factors and facilitates resumption of regular menses in adolescents with polycystic ovary syndrome. J. Pediatr. Endocrinol. Metab. 22, 815–826 (2009)CrossRefPubMed
34.
go back to reference G. Iván, N. Szigeti-Csúcs, M. Oláh, G.M. Nagy, M.I. Góth, Treatment of pituitary tumors: dopamine agonists. Endocrine 28, 101–110 (2005)CrossRefPubMed G. Iván, N. Szigeti-Csúcs, M. Oláh, G.M. Nagy, M.I. Góth, Treatment of pituitary tumors: dopamine agonists. Endocrine 28, 101–110 (2005)CrossRefPubMed
35.
go back to reference C.L. Li, C.Y. Pan, J.M. Lu, Y. Zhu, J.H. Wang, X.X. Deng et al., Effect of metformin on patients with impaired glucose tolerance. Diabet. Med. 16, 477–481 (1999)CrossRefPubMed C.L. Li, C.Y. Pan, J.M. Lu, Y. Zhu, J.H. Wang, X.X. Deng et al., Effect of metformin on patients with impaired glucose tolerance. Diabet. Med. 16, 477–481 (1999)CrossRefPubMed
36.
go back to reference M.S. Arslan, O. Topaloglu, M. Sahin, E. Tutal, A. Gungunes, E. Cakir et al., Preclinical atherosclerosis in patients with prolactinoma. Edocr. Pract. 20, 447–451 (2014)CrossRef M.S. Arslan, O. Topaloglu, M. Sahin, E. Tutal, A. Gungunes, E. Cakir et al., Preclinical atherosclerosis in patients with prolactinoma. Edocr. Pract. 20, 447–451 (2014)CrossRef
37.
go back to reference S.M. Twigg, M.C. Kamp, T.M. Davis, E.K. Neylon, J.R. Flack, Australian Diabetes Society; Australian Diabetes Educators Association: Prediabetes: a position statement from the Australian Diabetes Society and Australian Diabetes Educators Association. Med. J. Aust. 186, 461–465 (2007)PubMed S.M. Twigg, M.C. Kamp, T.M. Davis, E.K. Neylon, J.R. Flack, Australian Diabetes Society; Australian Diabetes Educators Association: Prediabetes: a position statement from the Australian Diabetes Society and Australian Diabetes Educators Association. Med. J. Aust. 186, 461–465 (2007)PubMed
38.
39.
go back to reference L. Vilar, M. Fleseriu, M.D. Bronstein, Challenges and pitfalls in the diagnosis of hyperprolactinaemia. Arq. Bras. Endocrinol. Metabol. 58, 9–22 (2014)CrossRefPubMed L. Vilar, M. Fleseriu, M.D. Bronstein, Challenges and pitfalls in the diagnosis of hyperprolactinaemia. Arq. Bras. Endocrinol. Metabol. 58, 9–22 (2014)CrossRefPubMed
40.
go back to reference P. Iglesias, J.J. Díez, Macroprolactinoma: a diagnostic and therapeutic update. QJM 106, 495–504 (2013)CrossRefPubMed P. Iglesias, J.J. Díez, Macroprolactinoma: a diagnostic and therapeutic update. QJM 106, 495–504 (2013)CrossRefPubMed
41.
go back to reference K. Labuzek, D. Suchy, B. Gabryel, A. Bielecka, S. Liber, B. Okopien, Quantification of metformin by the HPLC method in brain regions, cerebrospinal fluid and plasma of rats treated with lipopolysaccharide. Pharmacol. Rep. 62, 956–965 (2010)CrossRefPubMed K. Labuzek, D. Suchy, B. Gabryel, A. Bielecka, S. Liber, B. Okopien, Quantification of metformin by the HPLC method in brain regions, cerebrospinal fluid and plasma of rats treated with lipopolysaccharide. Pharmacol. Rep. 62, 956–965 (2010)CrossRefPubMed
42.
43.
go back to reference J.A. Clemens, C.J. Shaar, Control of prolactin secretion in mammals. Fed. Proc. 39, 2588–2592 (1980)PubMed J.A. Clemens, C.J. Shaar, Control of prolactin secretion in mammals. Fed. Proc. 39, 2588–2592 (1980)PubMed
44.
go back to reference M.E. Freeman, B. Kanyicska, A. Lerant, G. Nagy, Prolactin: structure, function, and regulation of secretion. Physiol. Rev. 80, 1523–1631 (2000)PubMed M.E. Freeman, B. Kanyicska, A. Lerant, G. Nagy, Prolactin: structure, function, and regulation of secretion. Physiol. Rev. 80, 1523–1631 (2000)PubMed
Metadata
Title
The effect of short-term metformin treatment on plasma prolactin levels in bromocriptine-treated patients with hyperprolactinaemia and impaired glucose tolerance: a pilot study
Authors
Robert Krysiak
Joanna Okrzesik
Boguslaw Okopien
Publication date
01-05-2015
Publisher
Springer US
Published in
Endocrine / Issue 1/2015
Print ISSN: 1355-008X
Electronic ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-014-0428-2

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