Prolactinoma and Pregnancy: A Study Protocol

Abstract

Introduction: Prolactinomas are the most common pituitary tumors, especially affecting women in their 3rd and 4th decades, being an important cause of irregular menses and infertility. Fertility can be restored, making pregnancy possible, in most of the cases, mainly microprolactinomas, with clinical treatment (dopamine agonist (DA)) and eventually neurosurgery. Although literature data point to safety in maternal and fetal outcomes, especially regarding symptomatic tumor growth and DA fetal exposure, there is no meta-analysis. Ideal length of DA treatment in macroprolactinomas, abortion rate and neuropsychological development are important gaps in the management of DA- induced pregnancies. Objective: This systematic review aims to evaluate the association between pregnancy and prolactinoma with respect to the control of prolactinoma and fetal/maternal outcomes. Methods: This review will be conducted according to the Joanna Briggs Institute methodology for systematic reviews of etiology and risk. We will focus on observational studies that included pregnant women with prolactinoma. The outcomes will be prolactinoma control, preterm birth, maternal adverse events related to the use of DA, worsening of preexisting diabetes or the development of gestational diabetes, spontaneous miscarriage, frequency of breastfeeding, perinatal mortality, low birth weight, small for gestational age, congenital malformations, tumor size, headache, visual impairment, apoplexy, neurosurgery, clinical/biochemical recurrence of prolactinomas/hyperprolactinemia after pregnancy. Embase, Medline, LILACS, and CENTRAL will be our source databases. Two reviewers independently will select the studies, extract data and critically appraise the eligible studies. We will use Stata Statistical Software 17 to plot similar outcomes in at least two studies in meta-analyses. For controlled studies, relative risks will be calculated with 95% confidence intervals (CIs) as an estimate of the exposure effect, and for continuous data we will calculate means and standard deviations, and the mean differences will be calculated with respective 95% CIs. For uncontrolled studies we will perform proportional meta-analyses.  The protocol of this review was registered in the PROSPERO database (registration number: CRD42021283757). Conclusions: The results of this review can help in the management of prolactinoma in women before, during and after pregnancy.