Klinik Araştırma
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Impact of Hyperprolactinemia on Hemoglobin and Neutrophil-to-Lymphocyte Ratio: A Cross-Sectional Study in Patients with Prolactinoma

Yıl 2025, Cilt: 5 Sayı: 2, 68 - 75, 29.08.2025

Öz

Introduction: Hyperprolactinemia is implicated in anemia of chronic disease and low-grade systemic inflammation, yet robust clinical data controlling for confounding factors remain limited. This study examined hematologic parameters in patients with newly-diagnosed prolactinoma after carefully excluding nutritional, hormonal, and organ-related confounders.
Materials and Methods: Fifty-eight treatment-naïve patients (13 men, 45 women) with MRI-confirmed prolactinoma and 65 age- and sex-matched healthy controls were enrolled between January 2022 and March 2023. All participants had normal iron studies (ferritin, TSAT), vitamin B12, folate, renal, and hepatic profiles. Testosterone levels were measured in all male participants. Primary outcomes were hemoglobin (Hb) concentration and neutrophil-to-lymphocyte ratio (NLR). Anemia was defined using WHO criteria (Hb <13.0 g/dL in men, <12.0 g/dL in women).
Results: Prolactin levels were significantly elevated in patients versus controls (median 87.5 ng/mL [IQR 54.3–156.9] vs 9.8 [7.2–13.5], p < 0.001). Men with prolactinoma demonstrated lower Hb levels compared to male controls (13.9 ± 1.2 g/dL vs 15.2 ± 0.8 g/dL, Cohen's d = 1.29, p < 0.001) and anemia prevalence of 23.1% versus 0%. Women showed no significant difference in Hb levels (12.8 ± 1.1 vs 12.9 ± 0.9 g/dL, p = 0.63). NLR was significantly elevated in both sexes (2.3 ± 0.9 vs 1.7 ± 0.5, p < 0.001). After multivariable adjustment, prolactin levels correlated negatively with Hb in men (β = -0.51, p = 0.003) and positively with NLR in the overall cohort (β = 0.34, p = 0.002).
Conclusion: In the absence of nutritional or organ-related confounders, hyperprolactinemia demonstrates significant associations with reduced hemoglobin levels and increased anemia prevalence in men, while correlating with elevated inflammatory markers (NLR) in both sexes. The sex-specific hemoglobin pattern suggests complex hormonal interactions requiring further longitudinal investigation.

Kaynakça

  • Ben-Jonathan N, LaPensee CR, LaPensee EW. What can we learn from rodents about prolactin in humans? Endocr Rev. 2008;29(1):1-41.
  • Melmed S. Pituitary-tumor endocrinopathies. N Engl J Med. 2020;382(10):937-950.
  • Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism:an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715-1744.
  • Rudman Y, Mishani D, Koren R, et al. Hemoglobin decline as a signal for hyperprolactinemia onset prior to prolactinoma diagnosis in hypogonadal men. Andrology. 2023;11(7):1398-1407.
  • Corona G, Giagulli VA, Maseroli E, et al. Therapy of endocrine disease:testosterone supplementation and body composition:results from a meta-analysis of observational studies. Eur J Endocrinol. 2016;174(3):R99-116.
  • Fernández-Balsells MM, Murad MH, Lane M, et al. Clinical review 1:Adverse effects of testosterone therapy in adult men:a systematic review and meta-analysis. J Clin Endocrinol Metab. 2010;95(6):2560-2575.
  • Cappellini MD, Musallam KM, Taher AT. Iron deficiency anaemia revisited. J Intern Med. 2020;287(2):153-170.
  • Borba VV, Zandman-Goddard G, Shoenfeld Y. Prolactin and autoimmunity. Front Immunol. 2018;9:73.
  • Legorreta-Haquet MV, Santana-Sánchez P, Chávez-Sánchez L, Chávez-Rueda AK. The effect of prolactin on immune cell subsets involved in SLE pathogenesis. Front Immunol. 2022;13:1016427.
  • Dogusan Z, Hooghe R, Verdood P, Hooghe-Peters EL. Cytokine-like effects of prolactin in human mononuclear and polymorphonuclear leukocytes. J Neuroimmunol. 2001;120(1-2):58-66.
  • Zahorec R. Neutrophil-to-lymphocyte ratio---past, present and future perspectives. Bratisl Lek Listy. 2021;122(7):474-488.
  • Templeton AJ, McNamara MG, Šeruga B, et al. Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors:a systematic review and meta-analysis. J Natl Cancer Inst. 2014;106(6):dju124.
  • Infante M, Pieri M, Lupisella S, et al. Low testosterone levels and high estradiol to testosterone ratio are associated with hyperinflammatory state and mortality in hospitalized men with COVID-19. Eur Rev Med Pharmacol Sci. 2021;25(19):5889-5903.
  • Casanueva FF, Molitch ME, Schlechte JA, et al. Guidelines of the Pituitary Society for the diagnosis and management of prolactinomas. Clin Endocrinol (Oxf). 2006;65(2):265-273.
  • Coviello AD, Kaplan B, Lakshman KM, et al. Effects of graded doses of testosterone on erythropoiesis in healthy young and older men. J Clin Endocrinol Metab. 2008;93(3):914-919.
  • Bachman E, Travison TG, Basaria S, et al. Testosterone induces erythrocytosis via increased erythropoietin and suppressed hepcidin:evidence for a new erythropoietin/hemoglobin set point. J Gerontol A Biol Sci Med Sci. 2014;69(6):725-735.
  • Huang W, Molitch ME. Evaluation and management of galactorrhea. Am Fam Physician. 2012;85(11):1073-1080.
  • Jelkmann W, Wolff M. Estradiol stimulates erythropoiesis via estrogen receptor-mediated transcriptional up-regulation of GATA-1. Haematologica. 2020;105(4):1026-1034.
  • Olavarría VH, Figueroa JE, Mulero V. Prolactin-induced activation of phagocyte NADPH oxidase in the teleost fish gilthead seabream involves the phosphorylation of p47phox by protein kinase C. Dev Comp Immunol. 2012;36(1):216-221.
  • Shah N, Parikh V, Patel N, et al. Neutrophil lymphocyte ratio significantly improves the Framingham risk score in prediction of coronary heart disease mortality:insights from the National Health and Nutrition Examination Survey-III. Int J Cardiol. 2014;171(3):390-397.

Hiperprolaktineminin Hemoglobin ve Nötrofil-Lenfosit Oranı Üzerindeki Etkisi: Prolaktinoma Hastalarında Kesitsel Çalışma

Yıl 2025, Cilt: 5 Sayı: 2, 68 - 75, 29.08.2025

Öz

Amaç: Hiperprolaktinemi kronik hastalık anemisi ve düşük dereceli sistemik enflamasyonla ilişkilendirilmekle birlikte, confounding faktörleri kontrol eden güçlü klinik veriler sınırlıdır. Bu çalışma, demir eksikliği, vitamin B12/folat eksikliği, kronik böbrek hastalığı veya karaciğer hastalığı gibi confounding faktörleri dikkatli bir şekilde dışladıktan sonra yeni tanı prolaktinoma hastalarında hematolojik parametreleri incelemiştir.
Gereç ve Yöntemler: Ocak 2022-Mart 2023 tarihleri arasında MRI ile doğrulanmış prolaktinomlu 58 tedavi naif hasta (13 erkek, 45 kadın) ve 65 yaş ve cinsiyet eşleştirmeli sağlıklı kontrol alındı. Tüm katılımcılarda normal demir çalışmaları (ferritin, TSAT), vitamin B12, folat, böbrek ve karaciğer profilleri mevcuttu. Erkek katılımcılarda testosteron seviyeleri ölçüldü. Primer sonlanım noktaları hemoglobin (Hb) konsantrasyonu ve nötrofil-lenfosit oranı (NLR) idi. Anemi WHO kriterlerine göre tanımlandı (erkeklerde Hb <13.0 g/dL, kadınlarda <12.0 g/dL).
Bulgular: Prolaktin seviyeleri hastalarda kontrollere göre anlamlı olarak yüksekti (medyan 87.5 ng/mL [IQR 54.3–156.9] vs 9.8 [7.2–13.5], p < 0.001). Prolaktinomalı erkekler kontrol erkeklere göre düşük Hb seviyelerine sahipti (13.9 ± 1.2 g/dL vs 15.2 ± 0.8 g/dL, Cohen's d = 1.29, p < 0.001) ve anemi prevalansı %23.1 vs %0 idi. Kadınlarda Hb seviyeleri açısından anlamlı fark yoktu (12.8 ± 1.1 vs 12.9 ± 0.9 g/dL, p = 0.63). NLR her iki cinste de anlamlı olarak yüksekti (2.3 ± 0.9 vs 1.7 ± 0.5, p < 0.001). Çok değişkenli analizde prolaktin seviyeleri erkeklerde Hb ile negatif korelasyonlu (β = -0.51, p = 0.003), genel kohorda NLR ile pozitif korelasyonluydu (β = 0.34, p = 0.002).
Sonuç: Nutrisyonel veya organ ilişkili confounding faktörlerin yokluğunda, hiperprolaktinemi erkeklerde düşük hemoglobin seviyeleri ve artmış anemi prevalansı ile, her iki cinste ise yüksek enflamatuar belirteçler (NLR) ile anlamlı ilişki göstermektedir. Cinsiyete özgü hemoglobin paterni, daha ileri boylamsal araştırma gerektiren karmaşık hormonal etkileşimleri düşündürmektedir.

Kaynakça

  • Ben-Jonathan N, LaPensee CR, LaPensee EW. What can we learn from rodents about prolactin in humans? Endocr Rev. 2008;29(1):1-41.
  • Melmed S. Pituitary-tumor endocrinopathies. N Engl J Med. 2020;382(10):937-950.
  • Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism:an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715-1744.
  • Rudman Y, Mishani D, Koren R, et al. Hemoglobin decline as a signal for hyperprolactinemia onset prior to prolactinoma diagnosis in hypogonadal men. Andrology. 2023;11(7):1398-1407.
  • Corona G, Giagulli VA, Maseroli E, et al. Therapy of endocrine disease:testosterone supplementation and body composition:results from a meta-analysis of observational studies. Eur J Endocrinol. 2016;174(3):R99-116.
  • Fernández-Balsells MM, Murad MH, Lane M, et al. Clinical review 1:Adverse effects of testosterone therapy in adult men:a systematic review and meta-analysis. J Clin Endocrinol Metab. 2010;95(6):2560-2575.
  • Cappellini MD, Musallam KM, Taher AT. Iron deficiency anaemia revisited. J Intern Med. 2020;287(2):153-170.
  • Borba VV, Zandman-Goddard G, Shoenfeld Y. Prolactin and autoimmunity. Front Immunol. 2018;9:73.
  • Legorreta-Haquet MV, Santana-Sánchez P, Chávez-Sánchez L, Chávez-Rueda AK. The effect of prolactin on immune cell subsets involved in SLE pathogenesis. Front Immunol. 2022;13:1016427.
  • Dogusan Z, Hooghe R, Verdood P, Hooghe-Peters EL. Cytokine-like effects of prolactin in human mononuclear and polymorphonuclear leukocytes. J Neuroimmunol. 2001;120(1-2):58-66.
  • Zahorec R. Neutrophil-to-lymphocyte ratio---past, present and future perspectives. Bratisl Lek Listy. 2021;122(7):474-488.
  • Templeton AJ, McNamara MG, Šeruga B, et al. Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors:a systematic review and meta-analysis. J Natl Cancer Inst. 2014;106(6):dju124.
  • Infante M, Pieri M, Lupisella S, et al. Low testosterone levels and high estradiol to testosterone ratio are associated with hyperinflammatory state and mortality in hospitalized men with COVID-19. Eur Rev Med Pharmacol Sci. 2021;25(19):5889-5903.
  • Casanueva FF, Molitch ME, Schlechte JA, et al. Guidelines of the Pituitary Society for the diagnosis and management of prolactinomas. Clin Endocrinol (Oxf). 2006;65(2):265-273.
  • Coviello AD, Kaplan B, Lakshman KM, et al. Effects of graded doses of testosterone on erythropoiesis in healthy young and older men. J Clin Endocrinol Metab. 2008;93(3):914-919.
  • Bachman E, Travison TG, Basaria S, et al. Testosterone induces erythrocytosis via increased erythropoietin and suppressed hepcidin:evidence for a new erythropoietin/hemoglobin set point. J Gerontol A Biol Sci Med Sci. 2014;69(6):725-735.
  • Huang W, Molitch ME. Evaluation and management of galactorrhea. Am Fam Physician. 2012;85(11):1073-1080.
  • Jelkmann W, Wolff M. Estradiol stimulates erythropoiesis via estrogen receptor-mediated transcriptional up-regulation of GATA-1. Haematologica. 2020;105(4):1026-1034.
  • Olavarría VH, Figueroa JE, Mulero V. Prolactin-induced activation of phagocyte NADPH oxidase in the teleost fish gilthead seabream involves the phosphorylation of p47phox by protein kinase C. Dev Comp Immunol. 2012;36(1):216-221.
  • Shah N, Parikh V, Patel N, et al. Neutrophil lymphocyte ratio significantly improves the Framingham risk score in prediction of coronary heart disease mortality:insights from the National Health and Nutrition Examination Survey-III. Int J Cardiol. 2014;171(3):390-397.
Toplam 20 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Endokrinoloji
Bölüm Araştırma Makaleleri
Yazarlar

İsmail Engin 0000-0002-6493-9194

Yayımlanma Tarihi 29 Ağustos 2025
Gönderilme Tarihi 23 Temmuz 2025
Kabul Tarihi 4 Ağustos 2025
Yayımlandığı Sayı Yıl 2025 Cilt: 5 Sayı: 2

Kaynak Göster

Vancouver Engin İ. Impact of Hyperprolactinemia on Hemoglobin and Neutrophil-to-Lymphocyte Ratio: A Cross-Sectional Study in Patients with Prolactinoma. HTD / HMJ. 2025;5(2):68-75.

e-ISSN: 2791-9935