Dorte Glintborg1, Magda Altinok2, Hanne Mumm2, Kristian Buch2, Pernille Ravn3, Marianne Andersen2. 1. Department of Endocrinology and Metabolism, Odense University Hospital, 5000 Odense C, Denmark dorte.glintborg@rsyd.dk. 2. Department of Endocrinology and Metabolism, Odense University Hospital, 5000 Odense C, Denmark. 3. Department of Gynecology and Obstetrics, Odense University Hospital, 5000 Odense C, Denmark.
Abstract
STUDY QUESTION: Is there an association between prolactin and markers of metabolic risk in polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: Low serum prolactin was a metabolic risk marker in PCOS. WHAT IS KNOWN ALREADY: Prolactin is routinely measured to exclude endocrine diseases in PCOS. Recent studies have suggested that prolactin can be used as a marker for metabolic and cardiovascular risk. STUDY DESIGN, SIZE, DURATION: Retrospective cross-sectional study in an academic tertiary-care medical center. Data were collected during 1997-2012. Premenopausal women (n = 1007) with hirsutism and/or PCOS and 116 healthy, age-matched controls were included. Prolactin levels were measured in blood samples taken in the morning after a minimum of 2 h awakening time. Macroprolactinemia was excluded by the precipitation of serum with polyethylene glycol in patients with increased prolactin levels. PARTICIPANTS/MATERIALS, SETTING, METHODS: Serum prolactin levels were measured along with a clinical evaluation (Ferriman-Gallwey score, BMI, waist circumference, blood pressure) plus hormone analyses (sex hormones, fasting lipids, insulin, glucose), transvaginal ultrasound, and oral glucose tolerance (n = 234) and adrenocorticotrophic hormone tests (n = 201). All patients had prolactin levels below the upper reference limit (23 µg/l). MAIN RESULTS AND THE ROLE OF CHANCE: Prolactin levels were significantly lower in patients versus controls; median (quartiles) prolactin levels 7 (5-10) versus 9 (7-13) µg/l (P < 0.001). In the patient population prolactin levels were inversely associated with age, smoking status, waist circumference, total cholesterol, triglyceride and low-density lipoprotein (LDL) and positively associated with high-density lipoprotein, estradiol, total testosterone, dehydroepiandrosterone sulfate, 17-hydroxyprogesterone and cortisol levels. In multiple regression analyses, prolactin was inversely associated with LDL and positively associated with estradiol, 17-hydroxyprogesterone and cortisol after correcting for age, BMI and smoking status in patients with PCOS. LIMITATIONS, REASONS FOR CAUTION: The study design was cross-sectional and prospective studies are needed to further determine the impact of prolactin levels on cardiovascular outcomes. Patients included in the study were relatively lean and only 20 had diabetes, which could have affected our findings. In addition, the collection of blood samples when estrogen levels were low (follicular phase) could be related to the lower levels of prolactin. Furthermore, as prolactin is secreted in a pulsatile manner, several measures of prolactin may be needed to further investigate associations between prolactin and metabolic risk. WIDER IMPLICATIONS OF THE FINDINGS: Our findings of inverse associations between prolactin levels and metabolic risk markers are supported by studies in populations of women without PCOS. The association between prolactin and adrenal activity should be evaluated in future studies. STUDY FUNDING/COMPETING INTERESTS: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector. There are no conflicts of interest to declare.
STUDY QUESTION: Is there an association between prolactin and markers of metabolic risk in polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: Low serum prolactin was a metabolic risk marker in PCOS. WHAT IS KNOWN ALREADY: Prolactin is routinely measured to exclude endocrine diseases in PCOS. Recent studies have suggested that prolactin can be used as a marker for metabolic and cardiovascular risk. STUDY DESIGN, SIZE, DURATION: Retrospective cross-sectional study in an academic tertiary-care medical center. Data were collected during 1997-2012. Premenopausal women (n = 1007) with hirsutism and/or PCOS and 116 healthy, age-matched controls were included. Prolactin levels were measured in blood samples taken in the morning after a minimum of 2 h awakening time. Macroprolactinemia was excluded by the precipitation of serum with polyethylene glycol in patients with increased prolactin levels. PARTICIPANTS/MATERIALS, SETTING, METHODS: Serum prolactin levels were measured along with a clinical evaluation (Ferriman-Gallwey score, BMI, waist circumference, blood pressure) plus hormone analyses (sex hormones, fasting lipids, insulin, glucose), transvaginal ultrasound, and oral glucose tolerance (n = 234) and adrenocorticotrophic hormone tests (n = 201). All patients had prolactin levels below the upper reference limit (23 µg/l). MAIN RESULTS AND THE ROLE OF CHANCE: Prolactin levels were significantly lower in patients versus controls; median (quartiles) prolactin levels 7 (5-10) versus 9 (7-13) µg/l (P < 0.001). In the patient population prolactin levels were inversely associated with age, smoking status, waist circumference, total cholesterol, triglyceride and low-density lipoprotein (LDL) and positively associated with high-density lipoprotein, estradiol, total testosterone, dehydroepiandrosterone sulfate, 17-hydroxyprogesterone and cortisol levels. In multiple regression analyses, prolactin was inversely associated with LDL and positively associated with estradiol, 17-hydroxyprogesterone and cortisol after correcting for age, BMI and smoking status in patients with PCOS. LIMITATIONS, REASONS FOR CAUTION: The study design was cross-sectional and prospective studies are needed to further determine the impact of prolactin levels on cardiovascular outcomes. Patients included in the study were relatively lean and only 20 had diabetes, which could have affected our findings. In addition, the collection of blood samples when estrogen levels were low (follicular phase) could be related to the lower levels of prolactin. Furthermore, as prolactin is secreted in a pulsatile manner, several measures of prolactin may be needed to further investigate associations between prolactin and metabolic risk. WIDER IMPLICATIONS OF THE FINDINGS: Our findings of inverse associations between prolactin levels and metabolic risk markers are supported by studies in populations of women without PCOS. The association between prolactin and adrenal activity should be evaluated in future studies. STUDY FUNDING/COMPETING INTERESTS: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector. There are no conflicts of interest to declare.
Authors: Teodor T Postolache; Laura Del Bosque-Plata; Serge Jabbour; Michael Vergare; Rongling Wu; Claudia Gragnoli Journal: Am J Med Genet B Neuropsychiatr Genet Date: 2019-02-06 Impact factor: 3.568
Authors: Antonio J Ponce; Tomás Galván-Salas; Ricardo M Lerma-Alvarado; Xarubet Ruiz-Herrera; Tomás Hernández-Cortés; Rodrigo Valencia-Jiménez; Laura E Cárdenas-Rodríguez; Gonzalo Martínez de la Escalera; Carmen Clapp; Yazmín Macotela Journal: Endocrine Date: 2020-01-09 Impact factor: 3.633
Authors: A A Veloso; K B Gomes; I S Silva; C N Ferreira; L B X Costa; M O Sóter; L M L Carvalho; J de C Albuquerque; M F Sales; A L Candido; F M Reis Journal: J Endocrinol Invest Date: 2021-09-15 Impact factor: 4.256