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Healthcare (Basel, Switzerland) May 2023So far, neuroendocrine studies conducted in schizophrenic patients have yielded conflicting results. Many of these discrepancies may be explained by the diversity of... (Review)
Review
So far, neuroendocrine studies conducted in schizophrenic patients have yielded conflicting results. Many of these discrepancies may be explained by the diversity of factors that influence the hormonal levels (at baseline and in response to pharmacological stimuli), the heterogeneity of the populations studied, the absence of standardization of test challenges and the confounding and long-lasting effects of previous treatments. Numerous studies have used apomorphine (APO) in the evaluation of dopaminergic (DA) function in schizophrenic patients. APO, a direct acting DA receptor agonist, decreases prolactin (PRL) and stimulates growth hormone (GH), adrenocorticotropic hormone (ACTH) and cortisol secretion. Therefore, the magnitude of hormonal responses to APO is an indirect assessment of the functionality of DA receptors at the hypothalamic-pituitary level. This review provides an update on the applications of the APO test in schizophrenia in clinical, pathophysiological and therapeutic fields.
PubMed: 37239772
DOI: 10.3390/healthcare11101487 -
Pharmacology & Therapeutics Jul 2023Women experience chronic pain more often than men with some pain conditions being specific to women while others are more prevalent in women. Prolactin, a neuropeptide... (Review)
Review
Women experience chronic pain more often than men with some pain conditions being specific to women while others are more prevalent in women. Prolactin, a neuropeptide hormone with higher serum levels in women, has recently been demonstrated in preclinical studies to sensitize nociceptive sensory neurons in a sexually dimorphic manner. Dysregulation of prolactin and prolactin receptors may be responsible for increased pain especially in female predominant conditions such as migraine, fibromyalgia, and pelvic pain. In this review, we focus on the role of prolactin in endometriosis, a condition characterized by pelvic pain and infertility that affects a large proportion of women during their reproductive age. We discuss the symptoms and pathology of endometriosis and discuss how different sources of prolactin secretion may contribute to this disease. We highlight our current understanding of prolactin-mediated mechanisms of nociceptor sensitization in females and how this mechanism may apply to endometriosis. Lastly, we report the results of a systematic review of clinical studies conducted by searching the PubMed and EMBASE databases to identify association between endometriosis and blood levels of prolactin. The results of this search strongly indicate that serum prolactin levels are increased in patients with endometriosis and support the possibility that high levels of prolactin may promote pelvic pain in these patients and increase vulnerability to other comorbid pain conditions likely by dysregulating prolactin receptor expression. Targeting of prolactin and prolactin receptors may improve management of pain associated with endometriosis.
Topics: Female; Humans; Endometriosis; Prolactin; Receptors, Prolactin; Pelvic Pain; Chronic Pain
PubMed: 37169264
DOI: 10.1016/j.pharmthera.2023.108435 -
Cureus Feb 2023The management of dopamine agonist (DA)-resistant prolactinomas unresponsive to second and third-line treatment is challenging and requires alternative medical therapy.... (Review)
Review
The management of dopamine agonist (DA)-resistant prolactinomas unresponsive to second and third-line treatment is challenging and requires alternative medical therapy. The presence of estrogen receptors on pituitary tumors, and the variable behavior of pituitary tumors in the presence of estrogen, prompted investigation of the role of anti-estrogen in the treatment of DA-resistant prolactinomas. The goal of this paper is to perform a systematic review of the role of tamoxifen in the treatment of DA-resistant prolactinomas. A systematic review was conducted. Inclusion criteria were case reports, case series, and experimental studies using tamoxifen in DA-resistant prolactinomas. Exclusion criteria included review articles, DA-sensitive prolactinomas, and those that were not previously treated with DA. Data were analyzed using descriptive statistics. For continuous data, the mean was used. For dichotomous data, frequencies and percentages were used. Data on 22 patients were extracted from the seven included studies. Twenty patients (90.9%) responded positively to the use of tamoxifen with a mean reduction in prolactin levels of 57.4%. Ten patients (45.5%) showed normalization of prolactin post-tamoxifen administration. Regression of tumor size and stability of tumor growth were reported in four out of 22 cases (18.2%). Combination therapy with DA and tamoxifen increased DA sensitivity and had a clinically significant inhibitory effect on prolactin secretion. Furthermore, tamoxifen may be considered an effective adjuvant for tumor size control. Therefore, further studies are needed to draw more clinically and statistically robust conclusions.
PubMed: 36950000
DOI: 10.7759/cureus.35171 -
Headache May 2023To systemically review preclinical studies investigating the implication of prolactin signaling in headache and migraine pathophysiology. (Review)
Review
OBJECTIVE
To systemically review preclinical studies investigating the implication of prolactin signaling in headache and migraine pathophysiology.
BACKGROUND
The features of migraine attacks, including characteristics, duration, frequency, and prevalence, are sex-dependent with variability across a lifetime, indicating the involvement of the hypothalamus-pituitary-gonadal axis. Prolactin is a key regulator of this axis, and a new line of evidence implicates prolactin signaling in sex-related differences in pain perception.
METHODS
In this systematic review, we searched PubMed and EMBASE for the terms prolactin, hyperprolactinemia, macroprolactinemia, hypoprolactinemia, migraine, headache, head pain, and trigeminal pain pathway to find preclinical studies investigating prolactin signaling in headache and migraine. Two reviewers independently screened 841 articles for population, intervention, comparison, outcome, and study design. Studies were restricted to the English language and were excluded if they had a nonexperimental methodology.
RESULTS
Of a total of 15 preclinical articles selected, 11 were both ex vivo and in vivo, 3 were ex vivo, and 1 was an in vivo study. The main findings were that prolactin receptors are distributed in the trigeminal pain pathway, and prolactin induced migraine-like behavior in rodents. Moreover, prolactin signaling has a crucial role in calcitonin gene-related peptide (CGRP) release, a key molecule in migraine pathogenesis, and prolactin gene deletion attenuated CGRP-induced migraine-like behavior.
CONCLUSION
Preclinical data indicate a key role of prolactin and its receptors in mechanisms causing migraine. Further randomized and placebo-controlled clinical studies targeting prolactin signaling are needed to further clarify the influences of prolactin in migraine-attack initiation.
Topics: Humans; Calcitonin Gene-Related Peptide; Headache; Migraine Disorders; Pain; Prolactin; Animals; Mice; Rats
PubMed: 36752584
DOI: 10.1111/head.14412 -
Cephalalgia : An International Journal... Feb 2023To systemically review clinical studies investigating the role of prolactin and its receptors in headache and migraine. (Review)
Review
OBJECTIVE
To systemically review clinical studies investigating the role of prolactin and its receptors in headache and migraine.
BACKGROUND
Migraine prevalence is more common in women compared to men. As prolactin is a crucial regulator of the hypothalamus-pituitary-gonadal axis, prolactin and its receptors might contribute to signaling mechanisms underlying migraine.
METHODS
In this systematic review, we searched PubMed and EMBASE with the terms: prolactin, hyperprolactinemia, macroprolactinemia, hypoprolactinemia, migraine, headache, head pain and trigeminal pain pathway for clinical studies investigating prolactin signaling in headache and migraine. Two reviewers independently screened 841 articles for population, intervention, comparison, outcome, and study design. Studies were restricted to the English language and were excluded if they had a nonexperimental methodology.
RESULTS
Nineteen clinical studies met the inclusion criteria and were included in the qualitative and quantitative analysis. The main findings were that serum prolactin levels were found to be higher in individuals with migraine compared to healthy controls, and prolactinomas (prolactin-secreting pituitary adenomas) were correlated with higher incidence of headache in otherwise healthy individuals and migraine attacks in individuals with migraine.
CONCLUSION
Considerable evidence suggests a key role of prolactin and its receptors in migraine pathophysiology. Further randomized and placebo-controlled clinical studies targeting prolactin signaling are needed to further clarify influences of prolactin in migraine attack initiation.
Topics: Male; Humans; Female; Prolactin; Headache; Prolactinoma; Migraine Disorders; Hyperprolactinemia; Pituitary Neoplasms
PubMed: 36718026
DOI: 10.1177/03331024221136286 -
NPJ Schizophrenia May 2021Early intervention is essential for favorable long-term outcomes in schizophrenia. However, there is limited guidance in the scientific literature on how best to choose... (Review)
Review
Early intervention is essential for favorable long-term outcomes in schizophrenia. However, there is limited guidance in the scientific literature on how best to choose between dopamine D receptor (DR) partial agonists and DR antagonists in early stages of schizophrenia. The aim of this meta-analysis was to directly compare DR partial agonists with DR antagonists for efficacy and tolerability, using randomized controlled trials (RCTs) that involved participants diagnosed with first-episode psychosis, schizophrenia, or related psychotic disorders with a duration of illness ≤5 years. Fourteen RCTs, involving 2494 patients, were included in the meta-analysis. Aripiprazole was the only identified DR partial agonist, and was not significantly different from pooled DR antagonists for overall symptom reduction or all-cause discontinuation. However, aripiprazole was more favorable than pooled DR antagonists for depressive symptoms, prolactin levels, and triglyceride levels. Specifically, aripiprazole was more favorable than paliperidone for triglyceride levels and more favorable than risperidone and olanzapine, but less favorable than ziprasidone, for weight gain. In addition, aripiprazole was less favorable for akathisia compared with second-generation DR antagonists, in particular olanzapine and quetiapine, and less favorable for discontinuation due to inefficacy than risperidone. Lastly, aripiprazole was more favorable than haloperidol for various efficacy and tolerability outcomes. In conclusion, aripiprazole's efficacy did not differ substantially from DR antagonists in the early course of schizophrenia, whereas differential tolerability profiles were noted. More double-blind RCTs are required comparing the efficacy and tolerability of aripiprazole as well as other DR partial agonists with DR antagonists in early stages of schizophrenia.
PubMed: 34035313
DOI: 10.1038/s41537-021-00158-z -
Journal of Clinical Pharmacy and... Aug 2019Dopamine D receptor (DRD2) polymorphisms are inconsistently associated with elevated prolactin levels related to risperidone treatment. The aim of this systematic review... (Meta-Analysis)
Meta-Analysis
WHAT IS KNOWN AND OBJECTIVE
Dopamine D receptor (DRD2) polymorphisms are inconsistently associated with elevated prolactin levels related to risperidone treatment. The aim of this systematic review and meta-analysis was to investigate whether DRD2 polymorphisms could modulate prolactin levels in patients treated with risperidone.
METHODS
Three electronic databases (PubMed, EMBASE and the Cochrane Library) were searched for studies investigating the effect of DRD2 polymorphisms on prolactin levels in patients treated with risperidone until May 2018. Summary standard mean differences (SMDs) and 95% confidence intervals (CIs) were calculated with Hedges' g tests for effect estimates using random effects models. The heterogeneity, sensitivity, univariable meta-regression, subgroup analyses and publication biases were calculated.
RESULTS AND DISCUSSION
After initially identifying 886 studies, 772 patients from eight studies were included. Summary SMDs indicated that compared with A1 non-carriers, Taq1A A1 carriers did not have different risperidone-related prolactin levels (SMD: 0.13; 95% CI: -0.18 to 0.43; P = 0.423) among patients with schizophrenia (SCZ; SMD: 0.07; 95% CI: -0.14 to 0.29; P = 0.505) or among those without SCZ (SMD: 0.16; 95% CI: -0.39 to 0.71; P = 0.562). There was no significant difference between Del carriers and Del non-carriers with regard to risperidone-related prolactin levels (SMD: -0.00; 95% CI: -0.59 to 0.58; P = 0.996). In an Asian subgroup analysis, we also noted that compared with Taq1A A1A2 carriers, Taq1A A1A1 carriers had lower prolactin levels (SMD: -0.34; 95% CI: -0.66 to -0.02; P = 0.040). However, there was no significant difference in prolactin levels between A1A1 carriers and A2A2 carriers (SMD: -0.27; 95% CI: -0.60 to 0.05; P = 0.098), or between A2 carriers and A2 non-carriers (SMD: 0.29; 95% CI: -0.01 to 0.59; P = 0.059). Based on univariable meta-regression analyses, the effects of publication year, study design, ethnicity, comparison groups and study quality could bias the identified association of DRD2 Taq1A with risperidone-related prolactin levels.
WHAT IS NEW AND CONCLUSION
The findings of this study suggest that there is no significant difference between Taq1A A1 carriers and non-A1 carriers with regard to risperidone-related prolactin levels. As there were few A1 homozygotes, large prospective studies with robust designs are still needed to investigate whether A1A1 could affect risperidone-related prolactin levels in the Asian population.
Topics: Asian People; Humans; Polymorphism, Genetic; Prolactin; Receptors, Dopamine D2; Risperidone
PubMed: 31056781
DOI: 10.1111/jcpt.12843 -
Journal of Minimally Invasive Gynecology 2019To compare the diagnostic accuracy of different hormonal biomarkers and to find the most effective hormonal biomarker for the diagnosis of endometriosis. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To compare the diagnostic accuracy of different hormonal biomarkers and to find the most effective hormonal biomarker for the diagnosis of endometriosis.
DATA SOURCES
We conducted a systematic search using PubMed, EMBASE, Cochrane Library, and China Biomedical Literature to identify relevant studies from the first day of databases to August 2018.
METHODS OF STUDY SELECTION
Two independent reviewers screened for study eligibility and extracted data. Random controlled trials, cross-sectional studies, case-control studies, and cohort studies evaluating the diagnostic accuracy of hormonal markers for endometriosis were included.
TABULATION, INTEGRATION, AND RESULTS
We included 17 studies that involved 1279 participants and evaluated 7 hormonal biomarkers. The pooled sensitivity and specificity in endometriosis were .79 (.71, .86) and .89 (.82, .94) for aromatase, .30 (.18, .46) and .80 (.65, .90) for human chorionic gonadotropin/luteinizing hormone receptor, .75 (.66, .83) and .47 (.34, .60) for estrogen receptor (ER)-α, .65 (.56, .74) and .68 (.55, .80) for ER-β, .45 (.38-.52) and .92 (.85-.97) for serum prolactin, .69 (.51, .83) and .30 (.16, .49) for estrogen sulfotransferase, and .73 (.60-.84) and .48 (.33-.63) for 17β-hydroxysteroid dehydrogenase type 2 (17βHSD2). Compared with human chorionic gonadotropin/luteinizing hormone receptor, ER-α, ER-β, estrogen sulfotransferase, and 17βHSD2, aromatase had a higher sensitivity, specificity, positive likelihood ratio, and diagnostic odds ratio. The specificities of aromatase and serum prolactin were comparable, but the sensitivity, positive likelihood ratio, and positive likelihood ratio of serum prolactin were much lower than that of aromatase.
CONCLUSION
Aromatase may be an excellent diagnostic test for endometriosis. However, because of the moderate quality of the included studies and the limited sample size, this result requires more research to validate. (PROSPERO registration number: PROSPERO 2018 CRD42018105126.).
Topics: Biomarkers; Case-Control Studies; Cross-Sectional Studies; Diagnostic Techniques, Endocrine; Diagnostic Techniques, Obstetrical and Gynecological; Diagnostic Tests, Routine; Endometriosis; Female; Hormones; Humans; Predictive Value of Tests; Reproducibility of Results; Sensitivity and Specificity
PubMed: 30965114
DOI: 10.1016/j.jmig.2019.04.004 -
The Journal of Clinical Endocrinology... Jul 2019To determine the current state of knowledge and provide evidence-based recommendations that could be valid for all specialists taking care of female pattern hair loss... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To determine the current state of knowledge and provide evidence-based recommendations that could be valid for all specialists taking care of female pattern hair loss (FPHL), a common form of hair loss in women that is characterized by the reduction of hair density in the central area of the scalp, whereas the frontal hairline is generally well conserved.
PARTICIPANTS
An expert task force appointed by the Androgen Excess and PCOS Society, which included specialists from dermatology, endocrinology, and reproductive endocrinology.
DESIGN
Levels of evidence were assessed and graded from A to D. Peer-reviewed studies evaluating FPHL published through December 2017 were reviewed. Criteria for inclusion/exclusion of the published papers were agreed on by at least two reviewers in each area and arbitrated by a third when necessary.
CONCLUSIONS
(i) The term "female pattern hair loss" should be used, avoiding the previous terms of alopecia or androgenetic alopecia. (ii) The two typical patterns of hair loss in FPHL are centrifugal expansion in the mid scalp, and a frontal accentuation or Christmas tree pattern. (iii) Isolated FPHL should not be considered a sign of hyperandrogenism when androgen levels are normal. (iv) The assessment of patients with FPHL is primarily clinical. (v) In all patients with FPHL, assessment of a possible androgen excess is mandatory. Measurement of vitamin D, iron, zinc, thyroid hormones, and prolactin are optional but recommended. (vi) Treatment of FPHL should start with minoxidil (5%), adding 5α-reductase inhibitors or antiandrogens when there is severe hair loss or hyperandrogenism.
Topics: 5-alpha Reductase Inhibitors; Alopecia; Androgen Antagonists; Female; Humans; Hyperandrogenism; Low-Level Light Therapy; Mineralocorticoid Receptor Antagonists; Minoxidil; Platelet-Rich Plasma; Polycystic Ovary Syndrome; Scalp; Spironolactone; Vasodilator Agents
PubMed: 30785992
DOI: 10.1210/jc.2018-02548 -
World Neurosurgery Apr 2019It is rare for breast carcinoma to metastasize to the pituitary gland; this finding indicates extensive metastasis of the primary tumor.
BACKGROUND
It is rare for breast carcinoma to metastasize to the pituitary gland; this finding indicates extensive metastasis of the primary tumor.
CASE DESCRIPTION
Herein, we present a 57-year-old patient with pituitary gland metastasis from breast cancer that was treated with extensive radical mastectomy 16 years prior. The pituitary was the sole site of metastasis. The patient was admitted with the chief complaint of blurred vision for 1 year and episodic headaches for 1 month. Magnetic resonance imaging revealed a solid mass in the sellar region with heterogenous contrast enhancement. The preoperative diagnosis was a pituitary adenoma. Neuroendoscopy-assisted tumor resection was conducted through a single-nostril sphenoid sinus approach. A pinkish-white, firm neoplasm was found, with an abundant blood supply and an indistinct boundary between the neoplasm and normal pituitary tissue; complete resection was achieved. The results of immunohistochemical analysis were positive for cytokeratin, Ki-67antigen, estrogen receptors, progesterone receptors, and prolactin-induced protein. The neoplasm was negative for spalt-like transcription factor 4, mammaglobin, and the alpha subunit of the glycoprotein hormones. These results were used to reach a final diagnosis of pituitary gland metastasis from a primary breast carcinoma. The patient's vision improved significantly after surgery, and no recurrence was detected during 1 year of follow-up.
CONCLUSIONS
Pituitary gland metastasis is rare and difficult to differentiate from a pituitary adenoma without a pathologic diagnosis. Surgery is the first choice for treatment. Surgery, radiotherapy, and chemotherapy are combined with endocrine therapy to tailor treatment to the results of immunohistochemistry.
PubMed: 30630045
DOI: 10.1016/j.wneu.2018.12.126