A present study of nondiabetic women and men with prolactinomas showed that even short-term treatment with cabergoline can significantly improve anthropometric and metabolic profile (including BMI, WC, lipid profile, and FPG) and hypogonadism. Moreover, the TyG index as a surrogate marker of insulin resistance decreased significantly after the reduction of PRL by dopamine agonist treatment. Furthermore, despite the older age and higher values for BMI, WC, SBP, and MetS prevalence among men at baseline examination compared to women, the effect of treatment was generally similar among both genders except that the improvement of MetS prevalence and the uric acid level was seen only among men and women, respectively.
Some studies revealed that reducing PRL level using dopamine agonists significantly improve metabolic impairments(3, 4, 10–15); however, no study has examined the effect of this treatment on the TyG index. The findings of previous studies regarding the effect of normalization of PRL on anthropometric measures were inconsistent. BMI did not change (3, 4, 15) or significantly decreased after treatment among different patients (11, 14, 16). Moreover, in the study by Berinder et.al, improvement in anthropometric measures was only seen among men(12). Our results showed that treatment with cabergoline was related to a decreasing trend in BMI that was statistically significant after 6 months. Similarly, WC significantly decreased in both the short term (3-month) and long term (6 months) follow-ups; the pattern was similar among both genders. Some possible physiopathological mechanisms involved in weight gain among these patients are reduction in dopaminergic tone, leptin resistance, decreased adiponectin levels, increased hypothalamic pressure, and hypogonadism (4). We found no study regarding the effect of dopamine agonists therapy on BP among patients with prolactinoma and our study showed no change in BP except for a decrease in DBP after 6- month follow-up only among women.
With regard to metabolic parameters, treatment with dopamine agonists was associated with a decrease in cholesterol, LDL-C, in most (4, 12–16), but not all studies(3) in this field. Besides, data on the effect of hyperprolactinemia treatment on TG and HDL is more controversial. Similarly, most but not all studies have documented a reduction in FPG after treatment. Enhanced suppression of endogenous glucose products, increased splanchnic glucose uptake after glucose ingestion, and/or a central action in the hypothalamus are potential mechanisms by which dopamine agonists could improve glucose metabolism. In our patients, among both genders, treatment with cabergoline improved lipid profile and FPG levels. Furthermore, prolactinoma seems to be associated with metabolic syndrome(10). Few studies (11, 13, 16) revealed a significant decline in metabolic syndrome prevalence in patients with hyperprolactinemia receiving treatment with dopamine-agonists that might be a consequence of the significant improvement in body weight, glucose, and lipid profile. Findings of the current study showed no significant change in MetS syndrome prevalence among women whereas the declining trend from baseline to 3-month evaluation was significant among men.
To our knowledge, discordant results have been reported about the effects of dopamine agonists on insulin sensitivity. Using HOMA-IR, some studies (3, 13, 14) revealed a significant improvement in IR while others (4, 16) found no effects. Moreover, using euglycemic hyperinsulinemic clamps, Berinder et al,(12) found a trend to improve that was not statistically significant (P = 0.08). Triglyceride-glucose (TyG) index calculated using fasting triglyceride (TG) and fasting glucose measurements as a surrogate marker of insulin resistance is strongly associated with diabetes, nonalcoholic fatty liver disease, obesity, and metabolic syndrome(17–20) and has been used to predict cardiovascular events (21). Moreover, it is demonstrated that the TyG index is more accurate than FPG, TG, HDL, small dense LDL, and even HOMA-IR in diagnosing metabolic syndrome (22, 23). To the best of our knowledge, this is the first study that showed the TyG index significantly diminished after treatment with dopamine agonists.
As for the strengths of our study, it is the first to be conducted among an Iranian population with a high CVD burden (24). Other strengths are the relatively large sample size, using the TyG index for the first time, and reporting results in both genders. Nevertheless, there are some important limitations. First, it’s an observational study so we couldn’t conclude the relationship between parameters. The short duration of the study is other limitation.
In conclusion, short-term treatment with cabergoline can significantly improve cardiovascular risk factors including the TyG index; results that were generally similar among both genders. Hence, it might be important to consider the metabolic profile, when approaching patients with hyperprolactinemia.