Gynura procumbens and selected metabolites: Amelioration of depressive-like behaviors in mice and risperidone-induced hyperprolactinemia in rats.

Gynura procumbens (Lour.) Merr., utilized in traditional Chinese medicine, is known for its liver-protective, liver-soothing, and depression-alleviating properties. This research examines the antidepressant and anti-hyperprolactinemia potentials of an ethanol extract from G. procumbens stems (EEGS) and specific metabolites. To model depression and hyperprolactinemia, chronic unpredictable mild stress (CUMS) was induced in mice and risperidone was administered to rats, respectively. Treatments involved administering low (5 mg/kg), medium (25 mg/kg), and high (125 mg/kg) doses of EEGS and certain metabolites to both models. Behavioral assessments were conducted in the CUMS-induced mice, while the CA3 neuronal damage in mice and histopathological alterations in rat mammary glands were evaluated using Nissl and Hematoxylin & Eosin staining techniques, respectively. EEGS decreased immobility times in the forced swimming and tail suspension tests in mice, enhancing their exploration of the central zone. It elevated the serum levels of 5-hydroxytryptamine, norepinephrine, estradiol, luteinizing hormone (LH), and testosterone in mice. Moreover, EEGS restored the neuronal cell arrangement in the CA3 area, reduced interleukin-1beta mRNA production, and increased the expression of interleukin-10 and beta-catenin mRNA. In the context of risperidone-induced hyperprolactinemia, EEGS lowered blood prolactin levels, reduced the dimensions of rat nipples, and enhanced LH, progesterone, and dopamine levels, alongside mitigating mammary hyperplasia. Among the EEGS selected metabolites, the combined effect of chlorogenic acid and trans-p-coumaric acid was found to be more effective than the action of each compound in isolation. Collectively, the findings indicate that EEGS and its selected metabolites offer promising antidepressant benefits while counteracting hyperprolactinemia.

Vitex agnus castus effects on hyperprolactinaemia.

Background: Vitex agnus castus (VAC), also known as chaste tree, is a plant from the Mediterranean area, Crimea, and central Asia. Its fruit has been used for more than 2500 years as phytotherapic agent. In the last century, VAC has been mostly used for the treatment of premenstrual syndrome (PMS), menstrual irregularities, fertility disorders, and symptoms of menopause. Since some degree of hyperprolactinaemia may be observed in patients with such disorders, VAC effects on hyperprolactinaemia have been assessed in a small number of studies and in some patient series or single case reports. It has been postulated that the diterpenes contained in VAC extract may interact with dopamine D2 receptors (D2R) and inhibit prolactin release via dopamine D2R activation in the anterior pituitary. Most of the published papers focus on the use of VAC for the management of PMS or infertility. However, due to its action on D2R, VAC could have a role in the treatment of mild hyperprolactinaemia, including patients with idiopathic hyperprolactinaemia, microprolactinoma, drug-induced hyperprolactinaemia, or polycystic ovary syndrome. Methods: We have reviewed and analysed the data from the literature concerning the use of VAC extracts in patients with hyperprolactinaemia. Results: Some evidence suggests a possible role of VAC for the management of hyperprolactinaemia in selected patients, though in an inhomogeneous way. However, there are not any large randomized controlled trials supporting the same and the precise pharmacological aspects of VAC extract in such a clinical setting still remain obscure. Conclusion: It appears that VAC may represent a potentially useful and safe phytotherapic option for the management of selected patients with mild hyperprolactinaemia who wish to be treated with phytotherapy. However, larger studies of high quality are needed to corroborate it.

Pharmacological treatment strategies for antipsychotic-induced hyperprolactinemia: a systematic review and network meta-analysis.

Antipsychotic-induced hyperprolactinemia (AP-induced HPRL) occurs overall in up to 70% of patients with schizophrenia, which is associated with hypogonadism and sexual dysfunction. We summarized the latest evidence for the benefits of prolactin-lowering drugs. We performed network meta-analyses to summarize the evidence and applied Grading of Recommendations Assessment, Development, and Evaluation frameworks (GRADE) to rate the certainty of evidence, categorize interventions, and present the findings. The search identified 3,022 citations, 31 studies of which with 1999 participants were included in network meta-analysis. All options were not significantly better than placebo among patients with prolactin (PRL) less than 50 ng/ml. However, adjunctive aripiprazole (ARI) (5 mg: MD = -64.26, 95% CI = -87.00 to -41.37; 10 mg: MD = -59.81, 95% CI = -90.10 to -29.76; more than 10 mg: MD = -68.01, 95% CI = -97.12 to -39.72), switching to ARI in titration (MD = -74.80, 95% CI = -134.22 to -15.99) and adjunctive vitamin B6 (MD = -91.84, 95% CI = -165.31 to -17.74) were associated with significant decrease in AP-induced PRL among patients with PRL more than 50 ng/ml with moderated (adjunctive vitamin B6) to high (adjunctive ARI) certainty of evidence. Pharmacological treatment strategies for AP-induced HPRL depends on initial PRL level. No effective strategy was found for patients with AP-induced HPRL less than 50 ng/ml, while adjunctive ARI, switching to ARI in titration and adjunctive high-dose vitamin B6 showed better PRL decrease effect on AP-induced HPRL more than 50 ng/ml.

Guidance on the treatment of antipsychotic-induced hyperprolactinemia when switching the antipsychotic is not an option.

PURPOSE: This article aims to evaluate management options for antipsychotic-induced hyperprolactinemia and associated treatment considerations such as efficacy, tolerability, drug interactions, contraindications, and dosing regimens. SUMMARY: Hyperprolactinemia is a common adverse effect of antipsychotics. First-line management includes reducing the dose of the offending antipsychotic, discontinuing the antipsychotic, or switching to another antipsychotic associated with a lower risk of hyperprolactinemia. However, these options are not always practical and are associated with a risk of relapse of the psychiatric illness. Other management options include adjunctive aripiprazole, dopamine agonists (cabergoline and bromocriptine), metformin, and herbal supplements. A search of Embase, PubMed, and Google Scholar using key terms such as hyperprolactinemia, prolactin, antipsychotic, treatment guidelines, aripiprazole, dopamine agonist, cabergoline, bromocriptine, metformin, herbals, supplements, and medications was conducted for literature retrieval. Upon evaluation of the available literature we found the following: (1) aripiprazole is safe and effective in lowering prolactin levels within normal limits; (2) adjunctive cabergoline and bromocriptine decrease elevated prolactin levels, while cabergoline may be more effective in reducing prolactin but can also be associated with a more serious adverse effect of cardiac valvular abnormalities; (3) metformin causes a mild reduction of prolactin levels; and (4) there are limited data to support use of herbal medications (chamomile, Peony-Glycyrrhiza decoction, and shakuyaku-kanzo-to) in antipsychotic-induced hyperprolactinemia. CONCLUSION: There are treatments available for antipsychotic-induced hyperprolactinemia in patients who are unable to alter their current antipsychotic regimen. However, there remains a need for additional short- and long-term studies to determine the efficacy and safety of these treatment strategies, given that patients taking antipsychotics typically require chronic, life-long treatment for their illnesses.

Anti-hyperprolactinemic activities of aqueous extract of Uvaria chamae (P. Beauv) roots and associated biochemical changes in chlorpromazine-induced hyperprolactinemic female Wistar rats.

ETHNOPHARAMCOLOGICAL RELEVANCE: The age-long folkloric use of Uvaria chamae roots in the management of nipple discharge that is not related to pregnancy, childbirth or nursing but as a result of excessive production of prolactin (hyperprolactinemia) is yet to be substantiated with scientific data. AIM OF THE STUDY: This study investigated the anti-hyperprolactinemic activities of aqueous extract of Uvaria chamae roots (AEUCR) and associated biochemical changes in chlorpromazine (CPZ)-induced hyperprolactinemic female Wistar rats. MATERIALS AND METHODS: A total of sixty female rats (207.40 ± 2.69 g) were assigned into 6 groups: A-F. Animals in Group A received 0.5 ml of distilled water only whilst the 7 days CPZ-treated female rats (to induce hyperprolactinemia) in groups B, C, D, E, and F also received distilled water, 2.5 mg/kg body weight of bromocriptine (reference drug), 0.71, 1.41 2.83 mg/kg body weight of AEUCR for 28 days. RESULTS: AEUCR contained a total of 15 (75%) amino acids with seven (46.67%) being essential amino acids and eight (53.33%) as non-essential amino acids. Administration of CPZ increased (p < 0.05) the levels of prolactin and testosterone, and reduced (p < 0.05) the levels of estradiol, progesterone, follicle stimulating hormone (FSH), luteinizing hormone (LH), dopamine, triiodothyronine (T3) and tetraiodothyroxine (T4). Chlorpromazine also increased the levels of serum urea, creatinine, total protein, albumin, globulin, bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) of the animals. In contrast, AEUCR significantly (p < 0.05) reduced the CPZ-induced increases in the levels of prolactin and testosterone, and increased the levels of CPZ-induced reduction in the progesterone, estradiol, FSH, LH, dopamine, T3 and T4. The AEUCR also reversed (p < 0.05) the CPZ-induced related increases in the levels of urea, creatinine, total protein, albumin, globulin, bilirubin, ALT, AST and ALP similar to the trends in the distilled water- and bromocriptine-treated controls. The CPZ-induced remarkable increase in the size of lactating alveolus and lactiferous duct distribution in the mammary gland were restored to normal tubule-alveolar female pattern mammary glands, composed of branching ducts and small alveoli budding off the ducts. CONCLUSION: The study concluded that aqueous extract of Uvaria chamae root exhibited anti-hyperprolactinemic activity by restoring prolactin and dopamine levels and tubule-alveolar female pattern in female rats. It also ameliorated CPZ-induced changes in the liver and kidney function indices. This study justifies the folkloric use of Uvaria chamae root in the management of abnormal discharge by the nipples that is unrelated to pregnancy, childbirth and nursing.

Paeoniflorin ameliorates antipsychotic-induced hyperprolactinemia in rats by attenuating impairment of the dopamine D2 receptor and TGF-ß1 signaling pathways in the hypothalamus and pituitary.

ETHNOPHARMACOLOGICAL RELEVANCE: Paeoniflorin, a prominent component in some Chinese formulas for hyperprolactinemia-associated disorders, has been found to inhibit prolactin secretion in prolactinoma cells. AIM: To examine the efficacy of paeoniflorin on hyperprolactinemia and the underlying mechanisms of action. MATERIALS AND METHODS: Hyperprolactinemia in female rats was generated by administration of olanzapine (5 mg/kg, by a gavage method, once daily, × 13 weeks). The rats were co-treated with paeoniflorin (10 and 50 mg/kg). Prolactin and TGF-ß1 concentrations were detected by ELISA. Protein expression was determined by Western blot. The effect in MMQ cells was also examined. RESULTS: Paeoniflorin inhibited olanzapine-induced increases in plasma prolactin concentration and prolactin protein overexpression in the pituitary and hypothalamus of rats. Further, paeoniflorin restored olanzapine-induced downregulation of pituitary and hypothalamic dopamine D2 receptor (D2R) protein expression. More importantly, paeoniflorin attenuated olanzapine-suppressed protein expression of transforming growth factor (TGF)-ß1 and its downstream genes, type II TGF-ß receptor, type I TGF-ß receptor and phosphorylated SMAD3 in the tissues. However, paeoniflorin did not affect plasma TGF-ß1 concentration and hepatic TGF-ß1 protein expression. In accord, olanzapine-induced increase in prolactin concentration, upregulation of prolactin protein expression, and downregulation of protein expression of the D2R and TGF-ß1 signals in MMQ cells were attenuated. CONCLUSIONS: This study demonstrates that paeoniflorin ameliorates olanzapine-induced hyperprolactinemia in rats by attenuating impairment of the D2R and TGF-ß1 signaling pathways in the hypothalamus and pituitary. Our findings may provide evidence to support the use of paeoniflorin-contained Chinese herbs and formulas for hyperprolactinemia and its associated disorders.

The ancient Chinese formula Longdan Xiegan Tang improves antipsychotic-induced hyperprolactinemia by repairing the hypothalamic and pituitary TGF-ß1 signaling in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Antipsychotics often induce hyperprolactinemia. The transforming growth factor (TGF)-beta1 signaling in the pituitary and hypothalamus inhibits prolactin synthesis and secretion, and its impairment is implicated in neuropsychiatric disorders. Longdan Xiegan Tang (LXT) alone or together with antipsychotics have been used to treat various neuropsychiatric diseases and hyperprolactinemia-associated disorders. AIM OF THE STUDY: To investigate the effect of LXT on hyperprolactinemia and involvement of the TGF-beta1 signaling. MATERIALS AND METHODS: Male rats were co-administered with olanzapine (5 mg/kg) and LXT extract (50 and 500 mg/kg) (p.o., × 8 weeks). Plasma concentrations of prolactin and TGF-beta1 were determined by ELISA. Protein expression was analyzed by Western blot. RESULTS: Treatment of rats with LXT extract suppressed olanzapine-induced increase in plasma prolactin concentration and overexpression of pituitary and hypothalamic prolactin protein. Importantly, LXT restored olanzapine-induced decrease in protein expression of the key components of the TGF-beta1 signaling, TGF-beta1, type II TGF-beta receptor, type I TGF-beta receptor and phosphorylated SMAD3 in the pituitary and hypothalamus. Further, it antagonized downregulation of pituitary and hypothalamic dopamine D2 receptor (D2R) protein level, and inhibited pituitary estrogen receptor (ER) alpha and ERbeta protein expression. CONCLUSIONS: The present results suggest that LXT ameliorates antipsychotic-induced hyperprolactinemia in rats by repairing the pituitary and hypothalamic TGF-beta1 signaling possibly via D2R, ERs or/and other pathways. Our findings may also provide scientific elucidation for use of the ancient Chinese formula to treat the impaired TGF-beta1 signaling-associated neuropsychiatric disorders.

Using domperidone to induce and sustain hyperprolactinemia in late-pregnant gilts.

Prolactin controls mammary development as well as the lactogenic and galactopoietic processes in sows and increasing prolactin during gestation can augment milk yield. The dopamine receptor antagonist domperidone can increase circulating prolactin concentrations in pigs, but the ideal dose to achieve sustained hyperprolactinemia remains unknown. An experiment was performed to develop a protocol for using domperidone in studies of rapid and sustained hyperprolactinemia in late-pregnant gilts. On day 90 of gestation, gilts were divided into 4 groups: (1) intramuscular (IM) injections of canola oil (3 mL, controls [CTL], n = 9), (2) IM injections with 0.1 mg/kg BW of domperidone (low [LO], n = 8), (3) IM injections with 0.5 mg/kg BW of domperidone (medium [ME], n = 11), and (4) IM injections with 1.0 mg/kg BW of domperidone (high [HI], n = 11). Injections were given daily at 8:05 from days 90 to 109 of gestation. Treated gilts also received domperidone per os (0.5 mg/kg BW) at 8:00 and 20:00 on days 89, 90, and 91 of gestation. Three jugular blood samples were collected from all gilts at 6-h intervals on days 89, 90, and 91 of gestation, then twice daily on days 92, 93, and 94. Thereafter, samples were obtained at 8:00 every other day until day 114 of gestation. Blood was sampled serially from 9 CTL and 11 HI gilts on days 89 and 94 of gestation. On day 89 of gestation, prolactin concentrations for LO, ME, and HI gilts increased within 6 h of domperidone per os (P < 0.001). From days 89 until 93 of gestation, the area under the curve (AUC) for LO, ME, and HI gilts was greater than that for CTL gilts (P < 0.001), whereas from days 89 until 114, ME and HI gilts had greater AUC than CTL and LO gilts (P < 0.05). Results demonstrate that the combination of per os treatment with IM injections of 0.5 mg/kg of domperidone in an oil emulsion leads to the rapid and sustained release of prolactin over 24 d in late-pregnant gilts. Higher doses of domperidone failed to further increase circulating prolactin levels. These findings provide a useful strategy to induce sustained hyperprolactinemia in late-pregnant gilts.

Hormonal Risk Factors for Osteoporosis: Different Profile Among Antipsychotics.

Objectives: Osteoporosis is a major risk factor for fracture and treatment is mainly preventive. Patients with severe psychiatric condition and treated with antipsychotics are at risk for vitamin D deficiency and iatrogenic hyperprolactinemia, two serious risk factors of osteoporosis. We aim to determine whether all antipsychotics are similar regarding the risk of osteoporosis in young patients. Methods: From January 2009 to March 2015, we determined the vitamin D blood level (VDBL) among 484 inpatients and from January 2012 to March 2015, we determined the prolactin blood level (PBL) among 205 inpatients. We systematically recorded well-documented risk factors (e.g., age, gender, ethnic origin, body mass index, or season) and suspected risk factors (e.g., disease type or antipsychotic treatment). Results: Up to 89% of the inpatients had a VDBL under the recommended threshold. Up to 60% of the inpatients had hyperprolactinemia. The multivariate model found a significant effect on VDBL for seasonality (higher VDBL in summer), ethnicity (lower VDBL in Black individuals), and treatment exposure. The multivariate model found a significant effect on PBL for gender and treatment exposure. In both models, aripiprazole had a safer profile compared with other antipsychotics. Conclusion: Because adolescence is a period of bone construction and a critical window of opportunity for maximizing bone mass, we recommend vitamin D supplementation in young patients with severe mental condition. It could be interesting to reconsider to regularly monitor PBL among youth patients treated with antipsychotic, with the exception of aripiprazole.

Expression of prolactin receptors in the duodenum, kidneys and skeletal system during physiological and sulpiride-induced hyperprolactinaemia.

INTRODUCTION AND AIM: Hyperprolactinaemia in pregnancy leads to mild and reversible changes in the maternal skeletal system, and medicamentous hyperprolactinemia causes more detrimental effects. We conducted an experimental study to evaluate differences between Prlr gene expression in the duodenum, vertebrae and kidneys during physiological and medicamentous hyperprolactinaemia, which could influence calcium homeostasis. METHODS: Experimental animals (18 weeks old, Wistar female rats) were divided as follows: group P (nine rats that were 3 weeks pregnant), group M (ten rats that were intramuscularly administrated sulpiride (10 mg/kg) twice daily for 3 weeks), and the control group (C, ten age-matched nulliparous rats, 18-week-old). Laboratory investigations included measurements of serum ionized calcium, phosphorus, urinary calcium and phosphorus excretion, osteocalcin (OC), serum procollagen type 1 N-terminal propeptide (P1NP), vitamin D, parathyroid hormone (PTH) and prolactin (PRL). Relative quantification of gene expression for prolactin receptors in the duodenum, vertebrae and kidneys was determined using real-time PCR. RESULTS: Expression of the Prlr gene was significantly higher in the duodenum (p < 0.001) and lower in vertebrae (p < 0.001) and kidneys (p < 0.01) in rats with physiological hyperprolactinaemia (PHP) than in the control group. Significantly lower Prlr expression in the duodenum was verified (p < 0.001), along with increased Prlr gene expression in vertebrae (p < 0.001) and kidneys (p < 0.01), in rats with medicamentous hyperprolactinaemia (MHP) than in the C group. CONCLUSIONS: Downregulation of Prlr gene expression in the duodenum may explain the diminished intestinal calcium absorption in medicamentous hyperprolactinaemia. Prolactin takes calcium from the skeletal system following increased Prlr gene expression in the vertebrae to maintain calcium homeostasis, which increases the harmful effect on bone metabolism compared to that of physiological hyperprolactinaemia.

Calcium and Vitamin D Supplementation in Boys with Risperidone-Induced Hyperprolactinemia: A Randomized, Placebo-Controlled Pilot Study.

BACKGROUND: The chronic use of antipsychotics has been associated with impaired bone mineralization, partially mediated by hyperprolactinemia. We examined if calcium and vitamin D supplementation promote bone mineral accrual in boys with risperidone-induced hyperprolactinemia. METHODS: Between February 2009 and November 2013, medically healthy, 5- to 17-year-old boys were enrolled in a 36-week double-blind, placebo-controlled study, examining the skeletal effects of supplementation with 1250 mg calcium carbonate and 400 IU of vitamin D3 in risperidone-induced hyperprolactinemia. Anthropometric, dietary, physical activity, and psychiatric assessments were conducted at baseline and week 18 and 36. Plasma prolactin and vitamin D concentrations were measured at baseline and week 36. Total body less head bone mineral content (BMC) and radius trabecular bone mineral density (BMD) were measured at baseline, week 18, and week 36, using dual-energy X-ray absorptiometry and peripheral quantitative computed tomography, respectively. Linear mixed-effects regression analysis examined the longitudinal effect of treatment on skeletal outcomes. RESULTS: Forty-seven boys (mean age: 11.0 ± 2.6 years) were randomized and 38 completed the study. At study entry, the average dietary calcium intake was below the recommended limit, but the average vitamin D concentration was normal. Calcium and vitamin D supplementation failed to significantly increase BMC or trabecular BMD. It also failed to affect several other skeletal and anthropometric outcomes, including plasma vitamin D concentration. CONCLUSIONS: In this 9-month long pilot study, supplementation with a modest dose of calcium and vitamin D did not increase bone mass accrual in risperidone-treated boys with hyperprolactinemia. Alternative approaches should be investigated to optimize bone health in this population to prevent future morbidity and premature mortality. ClinicalTrials.gov Identifier: NCT00799383.

Paeoniflorin and liquiritin, two major constituents in Chinese herbal formulas used to treat hyperprolactinemia-associated disorders, inhibits prolactin secretion in prolactinoma cells by different mechanisms.

ETHNOPHARMACOLOGICAL RELEVANCE: Paeoniflorin and liquiritin are major constituents in some Chinese herbal formulas, such as Yiru Tiaojing (YRTJ) Granule (a hospitalized preparation) and Peony-Glycyrrhiza Decoction, used for hyperprolactinemia-associated disorders. AIM OF THE STUDY: To investigate the effect of paeoniflorin and liquiritin on prolactin secretion. MATERIALS AND METHODS: The effect of YRTJ Granule on metoclopramide-induced hyperprolactinemia was tested in rats. Paeoniflorin and liquiritin in the YRTJ Granule extract were identified and quantified by HPLC. The effects of paeoniflorin and liquiritin on prolactin secretion were examined in prolactinoma cells that were identified morphologically and by Western blot. The concentration of prolactin was determined by ELISA. The gene expression was analyzed by Western blot. RESULTS: YRTJ Granule ameliorated metoclopramide-induced hyperprolactinemia in rats. The contents of paeoniflorin and liquiritin in YRTJ Granule were 7.43 and 2.05mg/g extract, respectively. Paeoniflorin, liquiritin and bromocriptine (a dopamine D2 receptor (D2R) agonist) decreased prolactin concentration in MMQ cells expressing D2R. However, the effect of liquiritin and bromocriptine was abolished in GH3 cells lacking D2R expression. Interestingly, paeoniflorin still decreased prolactin concentration in GH3 cells in the same manner. Furthermore, paeoniflorin suppressed prolactin protein expression, and was without effect on D2R protein expression in both MMQ and GH3 cells. CONCLUSIONS: The present results suggest that paeoniflorin and liquiritin play a role in YRTJ Granule-elicited improvement of hyperprolactinemia. While the effect of liquiritin is D2R-dependent, paeoniflorin D2R-independently inhibits prolactin secretion in prolactinoma cells that may especially benefit the hyperprolactinemic patients who are refractory to dopaminergic therapies.

Peony-Glycyrrhiza Decoction for Antipsychotic-Related Hyperprolactinemia in Women With Schizophrenia: A Randomized Controlled Trial.

OBJECTIVES: An herbal preparation called peony-glycyrrhiza decoction (PGD) may have the potential in reducing antipsychotic-related hyperprolactinemia (hyperPRL). This double-blind, randomized placebo-controlled study aimed to reevaluate the efficacy of PGD against antipsychotic-related hyperPRL. METHODS: Ninety-nine schizophrenic women who were under antipsychotic therapy and had symptomatic hyperPRL were randomly assigned to additional treatment with placebo (n = 50) or PGD (n = 49, 45 g/d) for 16 weeks. The severity of hyperPRL, psychosis, and abnormal involuntary movements was assessed at baseline and weeks 8 and 16 using standard instruments including the Prolactin Related Adverse Event Questionnaire. Blood levels of prolactin (PRL) and related pituitary and sex hormones were measured at the same time points. RESULTS: Peony-glycyrrhiza decoction treatment produced a significantly greater reduction of the Prolactin Related Adverse Event Questionnaire score at weeks 8 and 16 and a greater improvement on abnormal involuntary movements at end point compared with placebo, without altering the severity of psychosis. The group treated with PGD showed significantly higher proportion of having overall improvement on hyperPRL symptoms (χ = 4.010, P = 0.045) and menstrual resumption (χ = 4.549, P = 0.033) at week 8 than placebo. Serum PRL levels were similar in the 2 groups. CONCLUSIONS: Peony-glycyrrhiza decoction is effective in reducing antipsychotic-related hyperPRL and abnormal involuntary movement symptoms, but no reduction in blood PRL concentrations was observed. The underlying mechanisms of PGD's effects need further investigation (trial registration of NCT01852331 at www.clinicaltrials.gov).

[Treatment of Olanzapine-induced Hyperprolactinemia by Shaoyao Gancao Decoction].

Objective To observe the efficacy and safety of Shaoyao Gancao Decoction (SGD) in treating olanzapine induced hyperprolactinemia. Methods Totally 120 schizophrenia patients who took Olanzapine Tablet (OT) were assigned to the treatment group and the control group by random number table, 60 in each group. All patients took OT. Those in the treatment group additionally took SGD. The ther- apeutic course for all was 8 weeks. Serum levels of prolactin were measured before treatment and at the end of week 2, 4, and 8 after treatment. The spiritual symptoms of patients were assessed by Positive and Negative Syndrome Scale (PANSS) before treatment and at the end of week 8 after treatment. Adverse reactions were assessed using Treatment Emergent Symptom Scale (TESS) before treatment and at the end of week 8 after treatment. Results Compared with before treatment in the same group, ser- um levels of prolactin were significantly reduced in the treatment group at the end of week 4 and 8 after treatment (P <0. 05). There was no statistical difference in serum levels of prolactin in the control group among each time points (P > 0. 05). Compared with the control group, serum levels of prolactin de- creased significantly in the treatment group at the end of week 4 and 8 after treatment (P <0. 01). There was no statistical difference in PANSS between the two groups at the end of week 8 after treatment (P> 0. 05). Adverse reactions occurred in 5 cases (943%) of the treatment group and 4 cases (7. 14%) in the control group. They were manifested as insomnia, headache, constipation, and incapability of sitting quietly. There was no statistical difference in adverse reaction between the two groups (P'>0. 05). Con- clusions SGD could effectively improve olanzapine-induced hyperprolactinemia, and had no obvious effect on psychotic symptoms. It showed no obvious adverse reactions.

Clinical Management of Antipsychotic-Induced Hyperprolactinemia.

PURPOSE: This article describes the physiology and mechanisms of prolactin and the assessment and clinical management strategies of antipsychotic-induced hyperprolactinemia. CONCLUSIONS: Hyperprolactinemia is a disorder of the hypothalamic-pituitary axis which can be caused by several mechanisms. Typical antipsychotic agents are more likely to cause hyperprolactinemia than atypical antipsychotic agents, with the exception of amisulpride, paliperidone, and risperidone. PRACTICE IMPLICATIONS: Switching from prolactin-elevating to prolactin-sparing agents is recommended. Providing adjunctive treatment and prescribing substitutive hormones are alternatives. Education and lifestyle modification should be a major health promotion strategy. Taking patients' history and conducting physical examinations should be done during follow-up.

Studies on the regulatory effect of Peony-Glycyrrhiza Decoction on prolactin hyperactivity and underlying mechanism in hyperprolactinemia rat model.

Clinical trials have demonstrated the beneficial effects of Peony-Glycyrrhiza Decoction (PGD) in alleviating antipsychotic-induced hyperprolactinemia (hyperPRL) in schizophrenic patients. In previous experiment, PGD suppressed prolactin (PRL) level in MMQ cells, involving modulating the expression of D2 receptor (DRD2) and dopamine transporter (DAT). In the present study, hyperPRL female rat model induced by dopamine blocker metoclopramide (MCP) was applied to further confirm the anti-hyperpPRL activity of PGD and underlying mechanism. In MCP-induced hyperPRL rats, the elevated serum PRL level was significantly suppressed by either PGD (2.5-10 g/kg) or bromocriptine (BMT) (0.6 mg/kg) administration for 14 days. However, in MCP-induced rats, only PGD restored the under-expressed serum progesterone (P) to control level. Both PGD and BMT administration restore the under-expression of DRD2, DAT and TH resulted from MCP in pituitary gland and hypothalamus. Compared to untreated group, hyperPRL animals had a marked reduction on DRD2 and DAT expression in the arcuate nucleus. PGD (10 g/kg) and BMT (0.6 mg/kg) treatment significant reversed the expression of DRD2 and DAT. Collectively, the anti-hyperPRL activity of PGD associates with the modulation of dopaminergic neuronal system and the restoration of serum progesterone level. Our finding supports PGD as an effective agent against hyperPRL.

Jasmine flower extract lowers prolactin.

BACKGROUND: Antipsychotic drugs frequently cause amenorrhoea and galactorrhoea. Jasmine flowers used topically were as effective as oral Bromocriptine in suppressing puerperal lactation. This study aims to evaluate the efficacy and safety of intranasal jasmine flower extract (JFE) to reduce prolactin levels of patients on stable doses of antipsychotic drugs. METHOD: This is a randomized, double blind, crossover clinical trial. An aqueous-ethanol extract of jasmine flowers was prepared and used as nasal drops. A decrease in serum prolactin of ≥25 ng/mL was considered a significant response. RESULTS: Ten out of 35 women had a significant drop in the serum prolactin while on the JFE. The non-responders to JFE were on higher doses of antipsychotic drugs. The main side effect was a transient and mild burning sensation in the nose. A cost analysis favoured JFE over dopamine agonists. CONCLUSION: JFE contains a prolactin-lowering substance which needs further characterisation.

Effect of Chinese medical herbs-Huiru Yizeng Yihao on hyperprolactinemia and hyperplasia of mammary gland in mice.

The study investigated the pharmacodynamism and mechanism of Chinese medicinal formula-Huiru Yizeng Yihao (NO.1 HRYZ) on the model rats of hyperpro-lactinemia and the model rats of hyperplasia of mammary gland (HMG), and studied the internal connection between hyperprolactinemia and HMG.. The hyperprolactinemia rat models were established by injecting metoclopramide dihydrochloride in the back of rats. The model rat of HMG was prepared by injecting estradiol in the thigh muscle of the rats and progesterone consecutively, while the tails of rats were clipped with tongs. Rats were treated with either NO.1 HRYZ or positive control drugs for four weeks. The concentrations of sex hormone in rat serum were examined using ELISA kits, and the morphology of mammary gland tissue in all group rats was observed with microscope. NO.1 HRYZ significantly decreased prolactin (PRL) and increased estradiol (E2), progesterone (P), follicle stimulating hormone (FSH), luteinizing hormone (LH) concentrations of hyperprolactinemia rats. It decreased E2, PRL, FSH, gonadotropin-releasing hormone (GnRH), 5-hydroxytryptamine (5-HT) and increased P concentrations of HMG rat. It also eliminated hyperplasia of lobules and gland alveolus compared with the model group. Treatment with NO.1 HRYZ could significantly regulate the sex hormone disorder of hyperprolactinemia and HMG rat models, and could eliminate the formation of HMG. Hyperprolactinemia was closely correlated with HMG, and hyperprolactinemia promoted the formation of HMG.

Hyperprolactinemia-induced ovarian acyclicity is reversed by kisspeptin administration.

Hyperprolactinemia is the most common cause of hypogonadotropic anovulation and is one of the leading causes of infertility in women aged 25-34. Hyperprolactinemia has been proposed to block ovulation through inhibition of GnRH release. Kisspeptin neurons, which express prolactin receptors, were recently identified as major regulators of GnRH neurons. To mimic the human pathology of anovulation, we continuously infused female mice with prolactin. Our studies demonstrated that hyperprolactinemia in mice induced anovulation, reduced GnRH and gonadotropin secretion, and diminished kisspeptin expression. Kisspeptin administration restored gonadotropin secretion and ovarian cyclicity, suggesting that kisspeptin neurons play a major role in hyperprolactinemic anovulation. Our studies indicate that administration of kisspeptin may serve as an alternative therapeutic approach to restore the fertility of hyperprolactinemic women who are resistant or intolerant to dopamine agonists.