Vitamin D status determines the impact of metformin on circulating prolactin levels in premenopausal women

Krysiak, Robert; Kowalcze, Karolina

doi:10.1111/jcpt.13447

Cited by 4 publications

(7 citation statements)

References 41 publications

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“…To reduce gonadotropin levels, patients have to receive high doses of metformin, commonly used in type 2 diabetes but higher than recommended to prediabetic women [40]. However, chronic treatment with 2.55-3 g metformin daily was well tolerated by the participants of the current study, and there were no cases of serious adverse effects associated with high-dose metformin treatment in our previous studies [26,27]. Moreover, a network meta-analysis showed that 6-month treatment of overweight and obese subjects without diabetes with 3 g metformin daily was well tolerated and superior to treatment with lower doses in reducing body weight and improving glucose homeostasis [28].…”

Section: Discussionmentioning

confidence: 65%

“…This finding suggests that even mild disturbances in vitamin D homeostasis may impair the impact of metformin on overactive gonadotropes. Considering the correlations between 25-hydroxyvitamin D levels and treatment-induced changes in gonadotropins and prolactin [26], it may be assumed that a deteriorating effect of hypovitaminosis D on the pituitary effects of metformin increases with its severity, which may be of importance in cases of patients with extremely high gonadotropin levels. Importantly, the impact of metformin on FSH and LH levels seems to be determined by actual vitamin D status.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, we have reported that metformin and vitamin D may interact at the level of pituitary cells. Metformin reduced circulating prolactin concentration only in subjects with 25-hydroxyvitamin D levels within the reference range [26]. Moreover, in women with vitamin D insufficiency, the TSH-lowering effect of metformin was observed only if this drug was administered together with exogenous calciferol but not if it was administered alone [27].…”

Section: Introductionmentioning

confidence: 96%

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Vitamin D Status Determines the Impact of Metformin on Gonadotropin Levels in Postmenopausal Women

Krysiak

Kowalcze

Szkróbka

2023

JCM

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Metformin was found to decrease elevated levels of anterior pituitary hormones. Its impact on lactotrope secretory function was absent in women with vitamin D insufficiency. This study investigated whether vitamin D status determines metformin action on overactive gonadotropes. We compared the effect of six-month metformin treatment on the plasma levels of gonadotropins, TSH, prolactin, ACTH, estradiol, free thyroid hormones, IGF-1, and 25-hydroxyvitamin D, as well as on glucose homeostasis markers between three matched groups of postmenopausal women at high risk for diabetes: untreated subjects with vitamin D insufficiency (group A), untreated women with normal vitamin D status (group B), and individuals receiving vitamin D supplementation with normal 25-hydroxyvitamin D levels (group C). Only in groups B and C did metformin reduce FSH levels and tend to decrease LH levels, and these effects correlated with baseline gonadotropin levels, baseline 25-hydroxyvitamin D levels, and the improvement in insulin sensitivity. Follow-up gonadotropin levels were higher in group A than in the other two groups. The drug did not affect circulating levels of TSH, prolactin, ACTH, estradiol, free thyroid hormones, IGF-1, or 25-hydroxyvitamin D. The obtained results suggest that the impact of metformin on gonadotropin secretion in women after menopause is determined by vitamin D status.

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Section: Discussionmentioning

confidence: 65%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

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Vitamin D Status Determines the Impact of Metformin on Gonadotropin Levels in Postmenopausal Women

Krysiak

Kowalcze

Szkróbka

2023

JCM

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“…Actually, it also correlated with the improvement in insulin sensitivity. Since the vitamin D status was not neutral to the glucose and insulin response to metformin [ 233 ], it is not possible to say whether the vitamin D-dependent action of metformin on the lactotroph function was direct or indirect, mediated by the improvement in insulin sensitivity.…”

Section: Metformin Actions On Pituitary Tumor Cells and Gastroenteropancreatic Neuroendocrine Tumor Cellsmentioning

confidence: 99%

Integrated or Independent Actions of Metformin in Target Tissues Underlying Its Current Use and New Possible Applications in the Endocrine and Metabolic Disorder Area

Tulipano

2021

IJMS

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Metformin is considered the first-choice drug for type 2 diabetes treatment. Actually, pleiotropic effects of metformin have been recognized, and there is evidence that this drug may have a favorable impact on health beyond its glucose-lowering activity. In summary, despite its long history, metformin is still an attractive research opportunity in the field of endocrine and metabolic diseases, age-related diseases, and cancer. To this end, its mode of action in distinct cell types is still in dispute. The aim of this work was to review the current knowledge and recent findings on the molecular mechanisms underlying the pharmacological effects of metformin in the field of metabolic and endocrine pathologies, including some endocrine tumors. Metformin is believed to act through multiple pathways that can be interconnected or work independently. Moreover, metformin effects on target tissues may be either direct or indirect, which means secondary to the actions on other tissues and consequent alterations at systemic level. Finally, as to the direct actions of metformin at cellular level, the intracellular milieu cooperates to cause differential responses to the drug between distinct cell types, despite the primary molecular targets may be the same within cells. Cellular bioenergetics can be regarded as the primary target of metformin action. Metformin can perturb the cytosolic and mitochondrial NAD/NADH ratio and the ATP/AMP ratio within cells, thus affecting enzymatic activities and metabolic and signaling pathways which depend on redox- and energy balance. In this context, the possible link between pyruvate metabolism and metformin actions is extensively discussed.

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“…However, prolactin and vitamin D interactions are poorly understood. Metformin has been found to reduce prolactin levels only if 25-hydroxyvitamin D levels were within the reference range, and this effect correlated with 25-hydroxyvitamin D levels [ 30 ]. However, metformin’s inhibitory effect on lactotrope secretory function was clearly inferior to that of dopaminergic agents, and the study focused on metformin’s prolactin-lowering properties [ 31 ].…”

Section: Introductionmentioning

confidence: 99%

Vitamin D Status Determines Cardiometabolic Effects of Cabergoline in Women with Elevated Prolactin Levels: A Pilot Study

et al. 2023

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Both hyperprolactinemia and vitamin D deficiency appear to be associated with increased cardiometabolic risk. This study aimed to determine whether vitamin D status influences the cardiometabolic effects of cabergoline. The study included three matched groups of women with mild to moderate hyperprolactinemia: vitamin D-naive subjects with vitamin D insufficiency (group A), women with vitamin D deficiency/insufficiency successfully treated with vitamin D (group B), and vitamin D-naive individuals with normal vitamin D status (group C). Plasma prolactin, 25-hydroxyvitamin D, estradiol, glucose homeostasis markers, lipids, high-sensitivity C-reactive protein (hsCRP), fibrinogen, homocysteine, and uric acid, as well as the urinary albumin-to-creatinine ratio (UACR), were measured at study entry and after four months of cabergoline treatment. Although cabergoline reduced prolactin levels and increased estradiol levels in all study groups, the effect on prolactin was more pronounced in groups B and C compared to group A. In groups B and C, the drug enhanced glucose homeostasis, increased HDL-cholesterol, and decreased triglycerides, hsCRP, fibrinogen, homocysteine, uric acid, and UACR. In group A, only insulin resistance, hsCRP, and homocysteine were reduced by cabergoline. The effects on insulin sensitivity, HDL-cholesterol, triglycerides, hsCRP, fibrinogen, homocysteine, uric acid, and UACR were proportional to the decrease in prolactin and baseline levels of 25-hydroxyvitamin D. The obtained results suggest that vitamin D status determines cabergoline’s cardiometabolic effects.

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Vitamin D status determines the impact of metformin on circulating prolactin levels in premenopausal women

Cited by 4 publications

References 41 publications

Vitamin D Status Determines the Impact of Metformin on Gonadotropin Levels in Postmenopausal Women

Vitamin D Status Determines the Impact of Metformin on Gonadotropin Levels in Postmenopausal Women

Integrated or Independent Actions of Metformin in Target Tissues Underlying Its Current Use and New Possible Applications in the Endocrine and Metabolic Disorder Area

Vitamin D Status Determines Cardiometabolic Effects of Cabergoline in Women with Elevated Prolactin Levels: A Pilot Study

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