Krysiak Robert, Kowalcze Karolina, Cucinella Gaspare, Gullo Giuseppe, Zaami Simona, Ott Johannes, Okopień Bogusław
Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia, Medyków 18, Katowice, 40-752, Poland.
Department of Pediatrics in Bytom, School of Health Sciences in Katowice, Medical University of Silesia, Bytom, 41-902, Poland.
J Endocrinol Invest. 2025 Jul 25. doi: 10.1007/s40618-025-02645-x.
Subnormal prolactin concentrations were found to be associated with increased risk of metabolic complications. Thus, many patients with prolactin deficiency may be candidates for treatment with insulin-sensitizing drugs. The aim of this pilot prospective cohort study was to investigate metformin action on cardiometabolic risk factors in women with iatrogenic hypoprolactinemia.
The study included three groups of reproductive-age women (18-50 years old) with recently diagnosed prediabetes or type 2 diabetes: 18 women with cabergoline-induced hypoprolactinemia (prolactin below 5 ng/mL) [group A], 19 normoprolactinemic women receiving cabergoline treatment because of previous prolactin excess [group B] and 25 cabergoline-naïve women with prolactin levels within the reference range [group C]. The groups were matched for age, fasting glucose and insulin sensitivity. All participants were treated with metformin for the following six months. The outcomes of interest included: glucose homeostasis markers, prolactin, testosterone, plasma lipids, concentrations of uric acid, high-sensitivity C-reactive protein [hsCRP], homocysteine and fibrinogen, and the urinary albumin-to-creatinine ratio [UACR].
Fifty-eight patients (17 in group A, 18 in group B and 23 in group C) completed the study. There were no statistical differences between groups A and B in cabergoline dose (1.19 ± 0.52 mg vs. 1.05 ± 0.46 mg weekly), cabergoline treatment duration (43 ± 12 vs. 47 ± 14 weeks), and long-term glycemic control (HbA in the range between 6.4 ± 0.5% and 6.6 ± 0.5%). At baseline, uric acid, hsCRP, fibrinogen and UACR were higher in group A than in the remaining two groups, while the opposite relationships were found for prolactin and testosterone. Metformin decreased glycated hemoglobin, fasting glucose, HOMA1-IR and hsCRP in all study groups, but this effect was less pronounced in group A than in groups B and C -6 ± 8% vs. -12 ± 8% and - 11 ± 7% [HbA], -13 ± 10% vs. -25 ± 14% and - 23 ± 15% [glucose], -26 ± 20% vs. -52 ± 25% and - 53 ± 30% [HOMA1-IR], -45 ± 30% vs. -47 ± 35% and - 53 ± 30% [HOMA1-IR]). The decrease in triglycerides, uric acid, homocysteine and UACR was observed only in normoprolactinemic women, not differing between groups B (-13 ± 19% -49 ± 31%), and C (-16 ± 23% -58 ± 26%). In neither group did the drug affect levels of prolactin and total testosterone.
Coexisting hypoprolactinemia may attenuate cardiometabolic effects of metformin in women.
发现催乳素水平低于正常与代谢并发症风险增加有关。因此，许多催乳素缺乏的患者可能是胰岛素增敏药物治疗的候选者。这项前瞻性队列研究的目的是调查二甲双胍对医源性低催乳素血症女性心脏代谢危险因素的作用。
该研究纳入了三组近期诊断为糖尿病前期或2型糖尿病的育龄女性（18 - 50岁）：18名因卡麦角林导致低催乳素血症（催乳素低于5 ng/mL）的女性[甲组]，19名因既往催乳素过高而接受卡麦角林治疗的正常催乳素水平女性[乙组]，以及25名催乳素水平在参考范围内且未使用过卡麦角林的女性[丙组]。三组在年龄、空腹血糖和胰岛素敏感性方面相匹配。所有参与者接受二甲双胍治疗六个月。感兴趣的结局指标包括：血糖稳态指标、催乳素、睾酮、血脂、尿酸浓度、高敏C反应蛋白[hsCRP]、同型半胱氨酸和纤维蛋白原，以及尿白蛋白与肌酐比值[UACR]。
58名患者（甲组17名，乙组18名，丙组23名）完成了研究。甲组和乙组在卡麦角林剂量（每周1.19±0.52 mg对1.05±0.46 mg）、卡麦角林治疗持续时间（43±12周对47±14周）以及长期血糖控制（糖化血红蛋白在6.4±0.5%至6.6±0.5%之间）方面无统计学差异。基线时，甲组的尿酸、hsCRP、纤维蛋白原和UACR高于其余两组，而催乳素和睾酮则相反。二甲双胍降低了所有研究组的糖化血红蛋白、空腹血糖、HOMA-IR和hsCRP，但甲组的这种作用不如乙组和丙组明显——[糖化血红蛋白]分别为-6±8%对-12±8%和-11±7%，[血糖]分别为-13±10%对-25±14%和-23±15%，[HOMA-IR]分别为-26±20%对-52±25%和-53±30%，[HOMA-IR]分别为-45±30%对-47±35%和-53±30%）。仅在正常催乳素水平的女性中观察到甘油三酯、尿酸、同型半胱氨酸和UACR降低，乙组（-13±19% -49±31%）和丙组（-16±23% -58±26%）之间无差异。两组中该药物均未影响催乳素和总睾酮水平。
并存的低催乳素血症可能减弱二甲双胍对女性心脏代谢的作用。
