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Current Psychiatry Reports Nov 2023Despite clear evidence that sex differences largely impact the efficacy and tolerability of antipsychotic medication, current treatment guidelines for schizophrenia... (Review)
Review
PURPOSE OF REVIEW
Despite clear evidence that sex differences largely impact the efficacy and tolerability of antipsychotic medication, current treatment guidelines for schizophrenia spectrum disorders (SSD) do not differentiate between men and women. This review summarizes the available evidence on strategies that may improve pharmacotherapy for women and provides evidence-based recommendations to optimize treatment for women with schizophrenia.
RECENT FINDINGS
We systematically searched PubMed and Embase for peer-reviewed studies on three topics: (1) sex differences in dose-adjusted antipsychotic serum concentrations, (2) hormonal augmentation therapy with estrogen and estrogen-like compounds to improve symptom severity, and (3) strategies to reduce antipsychotic-induced hyperprolactinemia. Based on three database studies and one RCT, we found higher dose-adjusted concentrations in women compared to men for most antipsychotics. For quetiapine, higher concentrations were specifically found in older women. Based on two recent meta-analyses, both estrogen and raloxifene improved overall symptomatology. Most consistent findings were found for raloxifene augmentation in postmenopausal women. No studies evaluated the effects of estrogenic contraceptives on symptoms. Based on two meta-analyses and one RCT, adjunctive aripiprazole was the best-studied and safest strategy for lowering antipsychotic-induced hyperprolactinemia. Evidence-based recommendations for female-specific pharmacotherapy for SSD consist of (1) female-specific dosing for antipsychotics (guided by therapeutic drug monitoring), (2) hormonal replacement with raloxifene in postmenopausal women, and (3) aripiprazole addition as best evidenced option in case of antipsychotic-induced hyperprolactinemia. Combining these strategies could reduce side effects and improve outcome of women with SSD, which should be confirmed in future longitudinal RCTs.
Topics: Female; Humans; Male; Aged; Antipsychotic Agents; Schizophrenia; Aripiprazole; Hyperprolactinemia; Raloxifene Hydrochloride; Estrogens
PubMed: 37864676
DOI: 10.1007/s11920-023-01460-6 -
Journal of Medicine and Life Nov 2023Polycystic ovary syndrome (PCOS) is one of the most prevalent metabolic diseases during female reproductive life, often associated with insulin resistance and... (Randomized Controlled Trial)
Randomized Controlled Trial
Effects of combined metformin and cabergoline versus metformin alone on ovarian and hormonal activities in Iraqi patients with PCOS and hyperprolactinemia: a randomized clinical trial.
Polycystic ovary syndrome (PCOS) is one of the most prevalent metabolic diseases during female reproductive life, often associated with insulin resistance and hyperprolactinemia. The efficacy of metformin and cabergoline for managing PCOS remains debated in the literature. This three-arm interventional study in Iraq assessed the effects of these drugs on body mass index (BMI), hormonal balance, and uterine artery blood flow in 75 women with PCOS and hyperprolactinemia. Participants were randomized into three groups: metformin (500 mg twice daily), cabergoline (0.5 mg weekly), and a combination of both, with 25 patients in each group. Baseline and 90-day follow-up characteristics included BMI, serum hormonal levels, and ultrasound features. Metformin resulted in significant weight reduction (p=0.038); however, the addition of cabergoline caused a more significant reduction in body mass index (p=0.001). The combined treatment significantly lowered testosterone levels (p=0.008). In addition, this combination significantly reduced the level of LH (p=0.043) and increased the level of FSH (p=0.047). The results suggest that metformin and cabergoline when used together, act synergistically and safely to reduce BMI, testosterone, and LH levels while increasing FSH levels. Furthermore, this combination improved endometrial blood flow and ovulation in women with PCOS.
Topics: Female; Humans; Polycystic Ovary Syndrome; Metformin; Cabergoline; Luteinizing Hormone; Iraq; Hyperprolactinemia; Follicle Stimulating Hormone; Testosterone
PubMed: 38406771
DOI: 10.25122/jml-2023-0317 -
Revista Brasileira de Ginecologia E... 2024
Topics: Humans; Hyperprolactinemia; Female
PubMed: 38765533
DOI: 10.61622/rbgo/2024FPS04 -
Endocrine Regulations Apr 2022Proton pump inhibitors (PPIs) are the most widely prescribed medications in the world. According to numerous studies, PPIs have been linked to hyperprolactinemia, which... (Review)
Review
Proton pump inhibitors (PPIs) are the most widely prescribed medications in the world. According to numerous studies, PPIs have been linked to hyperprolactinemia, which can lead to a variety of sexual and reproductive issues. This review summarizes the effects of numerous PPIs on the blood prolactin levels and associated sexual dysfunctions, which have an effect on the patient's life quality and fertility. The study is taken into account all the available resources till January 31, 2021. Out of total 364, only 27 relevant resources were involved in this review. In certain studies, short-term PPIs use has been shown to have little or no effect on the blood prolactin and other reproductive hormones levels. PPIs have been linked to the development of hyperprolactinemia in several case studies with varying degrees of the blood prolactin levels increase seen in individuals taking PPI alone or in combination with medications, like prokinetics. The relative risk of the sexual consequences development, such as gynecomastia, has been documented using lansoprazole and omeprazole in various cohort studies. On the other hand, other bits of data are insufficient to establish a definite relationship that can turn a possibility into certainty. The majority of the literature data is comprising of double-blind, randomized, crossover studies, case reports, and adverse drug reaction incidents reported to various pharmacovigilance centers. To investigate this link, high-quality studies in patients taking PPIs for a longer time period are needed. We conclude this article with a comprehensive discussion of the hyperprolactinemia clinical implications and the PPIs' function.
Topics: Humans; Hyperprolactinemia; Male; Prolactin; Proton Pump Inhibitors; Randomized Controlled Trials as Topic
PubMed: 35489049
DOI: 10.2478/enr-2022-0015 -
BMJ (Clinical Research Ed.) Sep 2003
Review
Topics: Anovulation; Body Weight; Electrocoagulation; Female; Hormones; Humans; Hyperprolactinemia; Hypogonadism; Hypothyroidism; Infertility, Female; Menopause, Premature; Ovulation Induction; Polycystic Ovary Syndrome
PubMed: 12958117
DOI: 10.1136/bmj.327.7414.546 -
Frontiers in Endocrinology 2021The second generation antipsychotic drug clozapine represents the most effective pharmacotherapy for treatment-resistant psychosis. It is also associated with low rates... (Review)
Review
The second generation antipsychotic drug clozapine represents the most effective pharmacotherapy for treatment-resistant psychosis. It is also associated with low rates of extrapyramidal symptoms and hyperprolactinemia compared to other antipsychotic drugs. However, clozapine tends to be underutilized in clinical practice due to a number of disabling and serious side-effects. These are characterized by a constellation of metabolic side-effects which include dysregulation of glucose, insulin, plasma lipids and body fat. Many patients treated with clozapine go on to develop metabolic syndrome at a higher rate than the general population, which predisposes them for Type 2 diabetes mellitus and cardiovascular disease. Treatments for the metabolic side-effects of clozapine vary in their efficacy. There is also a lack of knowledge about the underlying physiology of how clozapine exerts its metabolic effects in humans. In the current review, we focus on key studies which describe how clozapine affects each of the main symptoms of the metabolic syndrome, and cover some of the treatment options. The clinical data are then discussed in the context of preclinical studies that have been conducted to identify the key biological substrates involved, in order to provide a better integrated overview. Suggestions are provided about key areas for future research to better understand how clozapine causes metabolic dysregulation.
Topics: Animals; Antipsychotic Agents; Clozapine; Diabetes Mellitus, Type 2; Drug-Related Side Effects and Adverse Reactions; Humans; Hyperprolactinemia; Metabolic Syndrome; Psychotic Disorders; Risk Factors
PubMed: 33716966
DOI: 10.3389/fendo.2021.609240 -
Neuroendocrinology 2019Hyperprolactinemia is not a common finding in postmenopausal women. Prolactinomas detected after menopause are usually macroadenomas. Due to atypical clinical features... (Review)
Review
Hyperprolactinemia is not a common finding in postmenopausal women. Prolactinomas detected after menopause are usually macroadenomas. Due to atypical clinical features they may remain unrecognized for a long period of time. Interestingly the growth potential of prolactinomas remains after menopause. Most tumors are invasive and present with high prolactin levels. They respond to medical treatment with dopamine agonists in terms of prolactin normalization, tumor shrinkage, and improvement in pituitary function. Treatment with dopamine agonists is usually long term. Reducing doses of cabergoline to the lowest that keeps prolactin levels normal prior to withdrawal is proposed to patients with macroprolactinomas who normalize prolactin after > 5 years of treatment and who do not have cavernous sinus invasion. Cabergoline can achieve a high percentage of remission maintenance in the first years after withdrawal. However, the percentage of relapse-free patients 5 years after withdrawal is significantly lower. Besides recurrent hyper-prolactinemia in a subgroup of macroprolactinomas after a long-interval tumor regrowth may be detected. Menopause cannot ensure remission of the tumor so long-term surveillance is suggested. In patients with microadenomas data on long-term remission rates (normalization of prolactin and disappearance of the tumor) after suspension of treatment with dopamine agonists are highly variable. The current strategy for microprolactinomas is not to treat hyperprolactinemia in menopause if it recurrs after discontinuation of dopamine agonists. This is based on: (1) reports that elevated prolactin levels may normalize in some women after menopause, (2) the fact that the association between prolactin levels and breast cancer is inconsistent in postmenopausal women, (3) the lack of clinical evidence that normalization of prolactin levels in postmenopausal women improves bone mineral density or reduces the risk of fracture, and (4) the fact that, concerning the metabolic syndrome, no data are available on metabolic parameters after suspension of treatment with dopamine agonists. For a change in strategy, i.e., for the potential benefits from treatment of hyperprolactinemia in the postmenopausal period with dopamine agonists concerning weight loss, improved insulin sensitivity, decreased fracture risk, and improved sexuality, more evidence is needed.
Topics: Aged; Female; Humans; Hyperprolactinemia; Middle Aged; Pituitary Neoplasms; Postmenopause; Prolactinoma
PubMed: 30347396
DOI: 10.1159/000494725 -
Clinical & Developmental Immunology 2012Macroprolactinemia is characterized by a large molecular mass of PRL (macroprolactin) as the main molecular form of PRL in sera, the frequent elevation of serum PRL... (Review)
Review
Macroprolactinemia is characterized by a large molecular mass of PRL (macroprolactin) as the main molecular form of PRL in sera, the frequent elevation of serum PRL (hyperprolactinemia), and the lack of symptoms. Macroprolactin is largely a complex of PRL with immunoglobulin G (IgG), especially anti-PRL autoantibodies. The prevalence of macroprolactinemia is 10-25% in patients with hyperprolactinemia and 3.7% in general population. There is no gender difference and a long-term followup demonstrates that macroprolactinemia develops before middle age and is likely a chronic condition. Polyethylene-glycol- (PEG-) precipitation method is widely used for screening macroprolactinemia, and gel filtration chromatography, protein A/G column, and I125-PRL binding studies are performed to confirm and clarify its nature. The cross-reactivity of macroprolactin varies widely according to the immunoassay systems. The epitope on PRL molecule recognized by the autoantibodies is located close to the binding site for PRL receptors, which may explain that macroprolactin has a lower biological activity. Hyperprolactinemia frequently seen in macroprolactinemic patients is due to the delayed clearance of autoantibody-bound PRL. When rats are immunized with rat pituitary PRL, anti-PRL autoantibodies are produced and hyperprolactinemia develops, mimicking macroprolactinemia in humans. Screening of macroprolactinemia is important for the differential diagnosis of hyperprolactinemia to avoid unnecessary examinations and treatments.
Topics: Animals; Autoantibodies; Humans; Hyperprolactinemia; Immunoglobulin G; Prolactin; Receptors, Prolactin
PubMed: 23304187
DOI: 10.1155/2012/167132 -
International Journal of Medical... 2023Hyperprolactinemia (HPRL) and polycystic ovary syndrome (PCOS) are common causes of infertility in women of reproductive age. A pituitary adenoma (PA) is the most... (Review)
Review
Hyperprolactinemia (HPRL) and polycystic ovary syndrome (PCOS) are common causes of infertility in women of reproductive age. A pituitary adenoma (PA) is the most common type of brain tumor that causes HPRL. In the neurosurgical field, the co-existence of PA and PCOS is not common. However, neurosurgeons often treat patients who are referred from gynecology. Because most of these patients are young and reproductive-aged, it is difficult for a neurosurgeon to come up with a treatment plan alone. In this study, we investigated the prevalence of PAs in PCOS patients, the cutoff prolactin (PRL) level to detect PAs, and the treatment strategy, then assessed the relationship between these diseases via a literature review. Medical records from November 2009 to March 2020 were reviewed at our institute. A total of 657 PCOS patients were enrolled. Initial prolactin levels were investigated and hyperprolactinemic patients were selected. As a result of sella magnetic resonance imaging (MRI), patients were divided into 2 groups of those with hyperprolactinemia but without PAs (group A) and those with both hyperprolactinemia and PAs (group B), respectively. We then compared and analyzed each group to find the characteristics and statistical differences. Receiver operating characteristic (ROC) curve analysis was performed to determine a cutoff value of the serum PRL level that could detect PAs in hyperprolactinemic PCOS patients. Of 657 patients diagnosed with PCOS, 76 patients had hyperprolactinemia (76/657, 11.6%). Sella MRI was performed in 56 patients, excluding 20 patients for various reasons. Patients in groups A and B numbered 43 and 13, respectively, and the mean serum prolactin level significantly differed between the groups (39.89 ± 41.64 vs. 108.59 ± 60.70 ng/mL, < 0.001). Based on the ROC curve analysis of the prolactin threshold level for predicting PAs in PCOS patients, the area under the ROC curve was 0.853 (95% confidence interval, 0.733-0.934; < 0.001), and the sensitivity and specificity were 76.9% and 86.1%, respectively. Ultimately, the cutoff value for prolactin level was 52.9 ng/mL. PCOS and hyperprolactinemia are common causes of infertility in reproductive-age women. PCOS patients with a PRL level of ≥ 52.9 ng/mL may need to undergo sella MRI for detecting PAs. To help ensure a favorable clinical course for these patients, systematic diagnosis, treatment, and follow-up plan should be established. Therefore, a multidisciplinary approach involving both neurosurgery and gynecology is essential.
Topics: Humans; Female; Adult; Prolactin; Hyperprolactinemia; Pituitary Neoplasms; Polycystic Ovary Syndrome; Adenoma; Infertility
PubMed: 37057215
DOI: 10.7150/ijms.80891 -
Acta Bio-medica : Atenei Parmensis Jan 2019Hyperprolactinemia (HPrl) is considered as a rare endocrinopathy in childhood. In children and adolescent girls, there are three major categories of HPrl causes;... (Review)
Review
Hyperprolactinemia (HPrl) is considered as a rare endocrinopathy in childhood. In children and adolescent girls, there are three major categories of HPrl causes; physiological, pathological and iatrogenic. Through hypogonadotropic hypogonadism, prolactin hypersecretion and production leads to the typical functional syndrome which is observed in female children and adolescents; delayed puberty, primary or secondary amenorrhea and/or galactorrhea. Regarding prolactinomas, clinical signs manifest with mass compression of the optic chiasm and anterior pituitary gland or prolactin hypersecretion. Targeted identification of HPrl is of significant importance for proper management and follow-up. The aim of this review is to focus on the evaluation of HPrl in adolescent and young girls. In addition, we aimed to summarize the current knowledge regarding the proper management of such cases.
Topics: Adolescent; Child; Female; Humans; Hyperprolactinemia
PubMed: 30889169
DOI: 10.23750/abm.v90i1.8142