Baseline Serum Prolactin Research Articles

Visual morbidity in macroprolactinoma: A retrospective cohort study.

The management of visual field damage in patients with macroprolactinomas is a major therapeutic challenge. We aimed to study the visual morbidity associated with macroprolactinoma and its outcomes following medical and surgical treatment. We aimed to identify predictors of visual recovery. We retrospectively reviewed patient's data including clinical presentation, serial pituitary magnetic resonance imaging, laboratory tests, visual symptoms and neuro-ophthalmologic examination, visual field tests and optical coherence tomography tests. The main outcome was complete visual field recovery. Descriptive analyses were conducted. Predictors of visual recovery were investigated. The study cohort included 150 patients with macroprolactinoma [median follow-up, 6.0 years (interquartile range (IQR) 2.9-10.6)]. At diagnosis, visual field defects were evident in 40 patients (26.7%). At the end of follow-up, 24 out of 39 available visual field tests (61.5%) exhibited complete recovery. Patients that achieved complete visual recovery had smaller macroadenomas at diagnosis [30.5 mm (15.0-80.0) vs. 42.0 mm (30.0-85.0), p < .01], lower baseline serum prolactin levels [1414 mcg/L (489-3586) vs. 4119 mcg/L (2715-6315), p < .01], lower rates of central hypogonadism (78.3% vs. 93.3%, p = .05) and central hypothyroidism (20.8% vs. 53.3%, p = .04), lower rates of compressive optic neuropathy (35.3% vs. 87.5%, p = .02) and a better visual acuity (better than 6/8 in both eyes, 93.7% vs. 28.6%, p < .01). In our cohort of 150 patients with macroprolactinoma, 40 patients (26.7%) presented with visual field defects, of which 61.5% achieved complete visual recovery with treatment. Patients that achieved complete visual recovery presented with smaller macroadenomas, lower serum prolactin levels, lower rates of central hypogonadism and central hypothyroidism, lower rates of compressive optic neuropathy and better visual acuity.

(303) The Predictive Role of Baseline Hormone Profile Evaluation for the Likelihood of Having a Child in Infertile Men

Abstract Introduction Sex hormone profile evaluation is commonly used in male infertility assessment to identify potential hormonal imbalances and underlying issues that can impact sperm production, sperm quality, or reproductive organ function. Objective To evaluate the likelihood of having a child in subfertile and infertile men within five years based on their serum hormone levels on their initial encounter for infertility evaluation/treatment. Methods We identified a retrospective cohort from the Subfertility, Health, and Assisted Reproduction (SHARE) study (compiled 1996-2017) linked with familial information from the Utah Population Database (UPDB) including all men with a measured value of albumin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), Free testosterone (T), total, and bioavailable T, sex hormone binding globulin (SHBG), and estradiol (E). We included men who had a semen analysis (SA) within 1 year of their hormone measurement. The primary outcome of the study was any evidence of childbirth, and the secondary outcome was the time from baseline hormone evaluation to childbirth. All men were followed for 60 months after their recorded hormone value for evidence of childbirth. Using Cox proportional hazards models, we modeled the likelihood of having a child and the time to childbirth (using linear regression) against the quintile of hormone distribution. Results A total number of 1298 men who underwent hormone profile evaluation and SA were included in this study. The mean age for the total cohort was 33 (29-37) years old. Men who had a child at the end of the study period (31 (28-36)) were significantly younger than men without a child at the end of the study with a mean age of (35.5 (32-40.25)) (p &amp;lt; 0.001). The mean sperm concentration for the total cohort was 7.6 (1-27.4) (M/ml) and the mean total progressive motile count was 9 (0.9-47) (M). Overall, semen parameters showed no significant differences between men who had a child at the end of the study follow-up versus men who did not. Our models showed that prolactin serum levels in quantile 7 have the highest ratio (2.236 (0.919-5.44) p=0.076) for the likelihood of having a child. Total testosterone in quantiles 3 and 5 showed an increased likelihood of having a child (2.119 (1.176-3.821) (p=0.012), (2.518 (1.412-4.491)) (p=0.002), respectively. Albumin in quantiles 5-9 followed a similar pattern with the highest ratio in quantile 8 (3.551 (1.486-8.487)) (p=0.004). Our results did not show meaningful patterns between semen parameters, serum hormone levels, and time to having a child. Conclusions The outcomes of this study indicate that prolactin, total testosterone, and albumin serum levels on the first visit in men with infertility concerns are associated with an increased likelihood of having a child. Abnormal semen analysis outcomes are not well associated with hypoandrogenism in infertile men. Our study shows that baseline serum prolactin, total testosterone, and albumin levels can be used to estimate the likelihood of having a child in subfertile and infertile men. These findings can provide the basis for further studies to determine an optimal screening method for male-factor infertility related to abnormal hormone levels. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Equity/salary/officer in company: Paterna bio, firmtech; Consulting: Turtle health, maximus, carrot; inherent bio.

An audit of high-dose and combination antipsychotic prescribing across the general adult inpatient wards in Mersey Care NHS Foundation Trust

AimsTo review the number of prescriptions of regular high-dose antipsychotics and combination antipsychotic therapy across the eight general adult inpatient wards in Mersey Care NHS Foundation Trust and examine whether these prescriptions followed Trust recommendations for high-dose antipsychotic therapy (HDAT).BackgroundThe two main rationales behind prescribing HDAT are pharmacokinetics differ in individuals and so insufficient amounts of antipsychotic may reach the effect site at maximum dose in some patients and variations in the effect site between patients may mean higher doses are required to achieve therapeutic effect.MethodThe electronic prescription records for all patients on the eight general adult inpatient wards were scrutinised. 121 patients were prescribed antipsychotic medication. Any patients on a combination of regular antipsychotic medication or on HDAT were identified. Any patient on combination therapy or HDAT was studied to determine if Clozapine had been considered. The electronic notes of HDAT patients were analysed to ascertain whether tests recommended by Trust guidelines – BMI, blood pressure (B.P), pulse rate, ECG, FBC, U and Es, LFTs, serum prolactin, serum cholesterol and HbA1c level had been performed prior to initiation and following any dose increase.Result21 of 121 patients prescribed antipsychotic medication were on combination therapy. 11 were subject to HDAT. 8 of the 11 HDAT patients were on combination therapy. Clozapine was considered before initiating HDAT in 9 of the HDAT patients. Clozapine was considered in 13 of the 21 patients on combination antipsychotic therapy, but only two were initiated on Clozapine (combined with Olanzapine or Risperidone).100% of HDAT patients had an ECG prior to initiation of HDAT; only 36% had one after dose increases above BNF maximum. 100% of HDAT patients had their BMI measured before initiation. 91% had baseline B.P and heart rate checked. Of the recommended blood tests, 100% of HDAT patients had baseline FBC, U and Es, LFTs and serum cholesterol. Fewer patients had a baseline HbA1c level (91%) or serum prolactin (46%) measured.ConclusionPrevalence of HDAT across the general adult inpatient wards in the Trust was 9%, much lower than the 28% reported in the HDAT audit completed by the Prescribing Observatory for Mental Health in 2012. Patients within Mersey Care are more likely to be prescribed combination therapy than HDAT. Not every HDAT patient has been considered for Clozapine. There is a need to ensure Trust monitoring guidelines for HDAT patients are being strictly adhered to.

Identification of an optimal prolactin threshold to determine prolactinoma size using receiver operating characteristic analysis

Prolactinomas represent the most common type of secretory pituitary neoplasms, with a therapeutic management that varies considerably based on tumour size and degree of hyperprolactinemia. The aim of the current study was to evaluate the relationship between serum prolactin (PRL) concentrations and prolactinoma size, and to determine a cut-off PRL value that could differentiate micro- from macro-prolactinomas. A retrospective cohort study of 114 patients diagnosed with prolactinomas between 2007 and 2017 was conducted. All patients underwent gadolinium enhanced pituitary MRI and receiver operating characteristic (ROC) analyses were performed. 51.8% of patients in this study were men, with a mean age at the time of diagnosis of 42.32 ± 15.04 years. 48.2% of the total cohort were found to have microadenomas. Baseline serum PRL concentrations were strongly correlated to tumour dimension (r = 0.750, p = 0.001). When performing the ROC curve analysis, the area under the curve was 0.976, indicating an excellent accuracy of the diagnostic method. For a value of 204 μg/L (4338 mU/L), sensitivity and specificity were calculated at 0.932 and 0.891, respectively. When a cut off value of 204 μg/L (4338 mU/L) was used, specificity was 93.2%, and sensitivity 89.1%, acceptable to reliably differentiate between micro- and macro- adenomas.

Recovery of Male Hypogonadism Following Successful Treatment of Prolactinoma: The Experience of an Integrated Health Network

Background: Hypogonadism is the most prevalent deficiency in male patients with prolactinomas (PrL). The recovery rates of hypogonadism (HGo) following treatment of PrL is variable and can be as high as 62%. In this study we aimed to identify predictors of HGo recovery in mean with PrL. We hypothesized that younger and leaner men and smaller tumor size predict HGo recovery after successful PrL treatment. We also hypothesized that higher baseline serum T predicts HGo recovery. Methods: We conducted a retrospective review of the electronic medical records of adult males with a diagnosis of hyperprolactinemia or PrL who were treated at Allegheny Health Network (Pittsburgh, PA) between January 1, 2016 and December 31, 2019. Serum prolactin and testosterone (T) levels, and pituitary tumor size (microadenoma <10mm, macroadenoma 10-39mm, or giant adenoma ≥ 40 mm) on MRI scan at diagnosis and up to 2 years follow up were analyzed. HGo was defined as serum T below reference range at diagnosis. HGo recovery was defined as total T in the reference range within 2 years from PrL treatment onset in the absence of T replacement. Results: We screened 215 male patients who met initial search criteria. Of the 37 subjects who met eligibility criteria, 26 had HGo while 11 had normal serum T (Fig 1). Mean age of men with HGo was 44.6 ± 13.7 years (range 21 – 64). Median serum prolactin at diagnosis was 283.5 ng/mL (range 31-14,830), and mean serum T was 167.07 ± 61.12 ng/dL. Median tumor (max) diameter was 17.5 mm (range 4-81mm). Of the included 26 patients 20 (77%) achieved normal prolactin with therapy after a median of 5 months. Only 10 of the 26 men with HGo (38.5%) attained recovery of HGo following treatment of PrL, and the mean time to recovery was 8.8 ± 6.9 months. HGo recovery was predictably more common in persons with microadenoma (n=6) while none of patients with giant Prl achieved HGo recovery. Baseline serum prolactin and T levels and baseline tumor size predicted subsequent HGo recovery, while age did not. Baseline serum prolactin was lower in men whose HGo recovered (median = 105 ng/mL, IQR = 202) than in men who did not (median = 931 ng/mL, IQR = 3714); p = 0.014. Baseline serum T was higher in men who attained HGo recovery (173.2 ± 59.6) than in men who failed to do so (103.1 ± 85.9); p = 0.03. Mean tumor size was significantly smaller in men who attained HGo recovery (max diam: 9.8 ± 5.5 mm) than in men who did not (31.8 ± 20.3 mm); p = .003. There were no statistically significant differences between men categorized by remission status with respect to age (p = .367) nor weight at the time of diagnosis (p = .591). Conclusion: In this retrospective study of 26 males with PrL and low T at presentation, 38.5% achieved HGo recovery. Lower baseline serum prolactin, smaller tumor size and higher baseline T predicted recovery of HGo, while presenting age and weight did not. This study was limited by its retrospective nature and small sample size.

The effect of berberine adjunctive treatment on glycolipid metabolism in patients with schizophrenia: A randomized, double-blind, placebo-controlled clinical trial

Previous studies have shown that berberine can improve metabolic disturbances in non-psychiatric patients, but no clinical research has been conducted in schizophrenia. This study was a randomized, double-blind, placebo-controlled clinical trial. Eligible patients diagnosed with schizophrenia were randomized to receive placebo or berberine (900mg/day) as an adjunctive treatment for eight weeks. Peripheral glycolipid metabolism parameters were measured at baseline, week 4, and week 8. Sixty-five patients were included, and forty-nine patients completed the 8-week trial. Berberine led to significant declines in total cholesterol, low-density lipoprotein cholesterol, fasting serum insulin, and insulin resistance(all p<0.05) compared with placebo. Baseline body mass index and serum prolactin concentration could predict the effect of berberine on insulin resistance. Berberine adjunctive treatment may reduce the risk of glycolipid metabolic disturbances in patients with schizophrenia.

Serum anti-Mullerian hormone, prolactin and estradiol concentrations in infertile women with endometriosis

Objective Endometriosis is a benign gynecological disease, which significantly impairs fertility. However, the contribution of specific hormonal parameters to the proper diagnosis of endometriosis in infertility states has not been adequately determined. The aim of this study was to compare ant-Mullerian hormone (AMH), prolactin and estradiol concentrations between infertile women with and without endometriosis, as well as to estimate the effect of endometrioid heterotopia on ovarian reserve. Methods In this cross-sectional study, mean baseline serum AMH, prolactin and estradiol levels were assessed in infertile women with and without endometriosis. Descriptive statistics are presented in the form of arithmetic mean ± standard deviation (SD). The comparison of indicators was performed by using parametric (t-test) and non-parametric criteria (Mann–Whitney). Results Seventy-two infertile women with endometriosis (group A; mean age: 32 ± 4.3 years) and 77 infertile women without endometriosis (group B; mean age: 32.4 ± 3.7 years) were studied. Mean baseline prolactin concentrations were higher in group A (16.9 ± 5.7 ng/mL) compared with group B (15 ± 4.3 ng/mL; p = .023), whereas mean AMH concentrations were lower (2.8 ± 1.9 ng/mL and 3.5 ± 1.8 ng/mL, respectively; p = .018). The highest prolactin and the lowest AMH concentrations were found in women with ovarian endometriomas than in those with deep infiltrative endometriosis and adenomyosis. There was no difference in estradiol levels between groups. Conclusions Infertile women with endometriosis demonstrated higher prolactin and lower AMH concentrations, compared with infertile women without endometriosis. The highest prolactin and the lowest AMH concentrations were observed in patients with ovarian endometriomas.

Predictors of Chronic LH-Testosterone Axis Suppression in Male Macroprolactinomas With Normoprolactinemia on Cabergoline.

Data are limited regarding prevalence, predictors, and mechanisms of persistent hypogonadotropic hypogonadism (HH) in males with a macroprolactinoma who achieve normoprolactinemia on dopamine-agonist therapy. None of the previous studies provide cutoffs to predict the achievement of eugonadism. The objective of this work is to evaluate the prevalence of persistent HH and its determinants in men with a macroprolactinoma who achieve normoprolactinemia on cabergoline monotherapy. This retrospective study with prospective cross-sectional evaluation took place at a tertiary health care center. Study participants included men with a macroprolactinoma and baseline HH who achieved normoprolactinemia on cabergoline monotherapy. Outcome measures of this study included the prevalence of persistent HH and its predictors. Thirty participants (age, 38.3 ± 10.1 years) with baseline tumor size of 4.08 ± 1.48 cm and median (interquartile range) prolactin of 2871 ng/mL (range, 1665-8425 ng/mL) were included. Eight of 30 participants achieved eugonadism after a median follow-up of 3 years. Patients with persistent HH had suppression of the luteinizing hormone (LH)-testosterone axis with sparing of other anterior pituitary hormonal axes, including follicle-stimulating hormone-inhibin B. Baseline prolactin (1674 vs 4120 ng/mL; P = .008) and maximal tumor diameter (2.55 ± 0.36 vs 4.64 ± 1.32 cm; P = .003) were lower in patients who achieved eugonadism. Baseline maximal tumor diameter less than or equal to 3.2 cm (sensitivity: 75%, specificity: 63.6%) and serum prolactin less than or equal to 2098 ng/mL (sensitivity: 87.5%, specificity: 77.3%) best predicted reversal of HH. Recovery of the LH-testosterone axis occurred in 26.7% of men with a macroprolactinoma who achieved normoprolactinemia on cabergoline monotherapy. Higher baseline tumor size and serum prolactin predict persistent HH. Our data favor chronic functional modification of the hypothalamic-pituitary-gonadal axis over gonadotroph damage as the cause of persistent HH.

Prolactin concentration in various stages of endometriosis in infertile women.

Objective:The relation between excessive prolactin and endometriosis-related infertility is debatable. Anovulation or defective luteal phase occurs frequently due to hyperprolactinemia in subfertile women. In this investigation, we evaluated the association between serum prolactin levels and the severity of endometriosis.Methods:This retrospective cohort study carried out at the Babol Infertility Research Center looked into the baseline serum prolactin levels of 114 infertile women with endometriosis and compared them to the levels seen in 101 infertile women without endometriosis (controls). Statistical analysis included independent t-test, chi-square, Welch test and ROC curve analysis. Results:Infertile women with endometriosis had significantly higher serum prolactin levels than infertile women without endometriosis (p=0.003). A significant difference was detected between controls and individuals with endometriosis stages III/IV (p-value=0.009). Prolactin was found to have diagnostic value to detect endometriosis stages III/IV vs. stages I/II in AUC=0.65, 95% CI (0.55, 0.76). Prolactin values with a cut off set at 20.08 ng/mL had a sensitivity of 0.74 and specificity of 0.54 in detecting disease stages III/IV vs. I/II. The prognostic capability of prolactin in detecting endometriosis in cases vs. controls by ROC curve analysis had an AUC=+0.67, 95% CI (0.60, 0.74). Prolactin values with a cut off set at 17.5 ng/mL had a sensitivity of 0.64 and specificity of 0.63 in segregating subjects with and without endometriosis.Conclusion:Higher prolactin levels were observed in infertile women with more severe endometriosis when compared to infertile women without endometriosis. Prolactin levels act as a probable prognostic biomarker to detect endometriosis stages III/IV vs. I/II and segregate infertile women with endometriosis from subjects without endometriosis.

Hyperprolactinemia in end-stage renal disease and effects of frequent hemodialysis.

End-stage renal disease is associated with elevations in circulating prolactin concentrations, but the association of prolactin concentrations with intermediate health outcomes and the effects of hemodialysis frequency on changes in serum prolactin have not been examined. The FHN Daily and Nocturnal Dialysis Trials compared the effects of conventional thrice weekly hemodialysis with in-center daily hemodialysis (6 days/week) and nocturnal home hemodialysis (6 nights/week) over 12 months and obtained measures of health-related quality of life, self-reported physical function, mental health and cognition. Serum prolactin concentrations were measured at baseline and 12-month follow-up in 70% of the FHN Trial cohort to examine the associations among serum prolactin concentrations and physical, mental and cognitive function and the effects of hemodialysis frequency on serum prolactin. Among 177 Daily Trial and 60 Nocturnal Trial participants with baseline serum prolactin measurements, the median serum prolactin concentration was 65 ng/mL (25th-75th percentile 48-195 ng/mL) and 81% had serum prolactin concentrations >30 ng/mL. While serum prolactin was associated with sex (higher in women), we observed no association between baseline serum prolactin and age, dialysis vintage, and baseline measures of physical, mental and cognitive function. Furthermore, there was no significant effect of hemodialysis frequency on serum prolactin in either of the two trials. Serum prolactin concentrations were elevated in the large majority of patients with ESRD, but were not associated with several measures of health status. Circulating prolactin levels also do not appear to decrease in response to more frequent hemodialysis over a one-year period.

Effect of Aripiprazole on Cognitive Function and Hyperprolactinemia in Patients with Schizophrenia Treated with Risperidone

ObjectiveThis study aimed to assess the efficacy of aripiprazole for the management of cognitive impairments and hyperprolactinemia in patients with schizophrenia on a stable dose of risperidone.MethodsThirty-five subjects stabilized on risperidone (3-6 mg/day) for a minimum of 3 months were enrolled in a double-blind, placebo-controlled phase for 12 weeks and an open-label phase for another 12 weeks. Subjects were randomly assigned to receive 10 mg/day aripiprazole (n=17) or placebo (n=18). Over the following 12 weeks, the the aripiprazole group received a flexible dose of aripiprazole while tapering risperidone. At baseline, week 12, and week 24, subjects were evaluated using the Positive and Negative Syndrome Scale (PANSS), Extrapyramidal Syndrome Rating Scale (ESRS), and standardized neuropsychological assessments. Serum prolactin levels were checked at baseline, week 1, week 2, and week 24.ResultsThe mean change in total PANSS and cognitive function test scores between baseline and endpoint were similar in the aripiprazole and placebo groups. Scores on the ESRS and negative subscale of PANSS differed significantly between groups in both phases of the study (p<0.05), indicating a positive effect of aripiprazole. Compared with placebo, aripiprazole significantly reduced mean baseline serum prolactin levels within 1 week (p=0.015).ConclusionAdjunctive treatment with and switching to aripiprazole were not associated with improved cognitive function in patients with schizophrenia receiving risperidone; however, aripiprazole treatment decreased negative symptoms and risperidone-induced motor side effects and lowered serum prolactin levels.

Sex-specific associations of serum prolactin concentrations with cardiac remodeling: Longitudinal results from the Study of Health Pomerania (SHIP)

BackgroundPrevious experimental and patient-based studies suggest that prolactin (PRL) and its 16kDa fragment influence cardiovascular phenotypes by modulating angiogenesis. The association between serum PRL and cardiac remodeling in the general population is unknown. MethodsWe evaluated 804 individuals (441 women) from the population-based Study of Health in Pomerania, aged ≥45 years, with available baseline serum PRL who underwent serial echocardiography at baseline and five-year follow-up. Left ventricular mass (LVM) was calculated and left ventricular hypertrophy (LVH) defined by sex-specific distributions of LVM. LV geometry was defined on the basis of relative wall thickness (RWT) and LVH. Sex-specific multivariable regression analyses were performed relating PRL (independent variable modelled as a continuous variable and as sex-specific quartiles) to change in LVM, RWT, and to incident LVH and abnormal geometry. ResultsBaseline PRL concentrations were inversely associated with LVM change in men, but not in women (β per 10% decrease in PRL: 0.37; 95% CI, 0.13–0.60 in men and −0.02; 95% CI, −0.21 to 0.17 in women, respectively). In men, baseline PRL concentrations were also inversely associated with incident LVH [first vs. fourth PRL quartile: relative risk (RR) 2.26 (95% CI, 1.20–4.24)] and altered LV geometry on follow-up [RR for incident concentric hypertrophy per 10% decrease in PRL: 1.20 (95% CI, 1.06–1.37)]. None of the longitudinal associations were observed in women. ConclusionWe observed inverse associations of PRL with LVM change, incident LVH, and altered LV geometry in men, but not in women. Additional studies are warranted to confirm our findings and to elucidate the mechanisms underlying these sex-specific associations.

Prolactin—A Biomarker for Antipsychotic Treatment Response?

To the Editor: Antipsychotic-induced hyperprolactinemia, due to blockade of D2 receptors in the tubulo-infundibular dopaminergic pathway,1 has been examined predominantly from the perspectives of adverse effects.2 Interestingly, the “neuroleptic threshold” construct conceptualizes the D2/3 occupancy to underlie the clinical efficacy of antipsychotics.3 Antipsychotic-induced hyperprolactinemia, being a proxy indicator of D2 receptor occupancy of antipsychotics, is reported to be associated with clinical improvement in a short-term study.4 Intriguingly, prolactin has even been hypothesized to mediate the adaptive effects of antipsychotics.5 In this report, we describe association between hyperprolactinemia and clinical improvement during a 5-month treatment period. Method. Clinical records of 10 patients with DSM-IV schizophrenia (mean ± SD age = 29.3 ± 6.5 years; 9 women) attending the Metabolic Clinic in Psychiatry at the National Insitute of Mental Health & Neurosciences (Bangalore, India) from 2008 to 2010 were examined in this study. Four of the patients were on monotherapy with risperidone, 3 were on combination treatment with risperidone and another antipsychotic (1 each with amisulpride, quetiapine, and chlorpromazine), 2 were on treatment with olanzapine alone, and 1 was on combination treatment with olanzapine and amisulpride. Baseline data were taken from the time of registration, and follow-up data were from their most recent visit. Pearson correlation test was applied between baseline serum prolactin level and follow-up Clinical Global Impressions–Improvement scale (CGI-I)6 score and between baseline prolactin level and antipsychotic dose (chlorpromazine equivalent).7,8 Results. There was a significant negative correlation between baseline serum prolactin level (mean ± SD = 102.0 ± 51.6 ng/mL) and CGI-I score (mean ± SD = 1.5 ± 0.5) at follow-up (P = .016; r = −0.731), ie, the higher the prolactin level, the lower the CGI-I score, indicating those who had a higher prolactin level at baseline had better improvement at follow-up. Serum prolactin level did not correlate significantly with the baseline antipsychotic dose (mean ± SD = 302.7 ± 78.5 mg/d) (P = .609; r = −0.185). There was no significant difference between the antipsychotic dose at baseline (302.7 ± 78.5 mg/d) and that at follow-up (267.8 ± 127.3 mg/d) (P = .468). Our findings lend further support to the possible association between serum prolactin level and clinical improvement with antipsychotics. Our findings are in accord with an earlier short-term study reporting association between hyperprolactinemia and clinical improvement.4 Findings of our study can have potential clinical implication as prolactin elevation could serve as a proxy indicator of D2 receptor occupancy—the mechanism of action of antipsychotics.3 Prolactin elevation is seen to occur rapidly after just a single parenteral or oral dose of antipsychotic.9 Hence, it can be used to predict treatment response even before clinical improvement with an antipsychotic happens and may, thus, help in formulation of individualized therapy. Though our sample size is modest, this observation is valuable, especially in the context of the paucity of similar studies. Retrospective design might also be considered a limitation; however, this method avoided the rater bias on CGI assessment. In summary, this report suggests a potential role for prolactin to be used as a biomarker for treatment response in schizophrenia, warranting further systematic evaluation.

Prevalence of Hypothyroidism in Benign Breast Disorders and Effect of Thyroxine Replacement on the Clinical Outcome

The aim of this study was to determine the prevalence of hypothyroidism in patients with benign breast disorders (BBD). We then asked if thyroxine replacement in hypothyroid patients has any impact on the clinical outcome of the BBD. This prospective study included 201 women with BBD. None of the included patients had previously suspected hypothyroidism. Clinical, laboratory, and follow-up details of the patients were noted. Baseline serum thyroxine, thyroid-stimulating hormone (TSH), and prolactin estimation was done in all cases. Thyroid peroxidase antibody (TPOAb) estimation was done in hypothyroid patients and/or patients with a goiter. In addition to the standard conservative management protocol, hypothyroid patients were given thyroxine replacement therapy. Their response to treatment was assessed at 3-month intervals. The clinical outcomes of euthyroid and hypothyroid groups were compared. The mean age of the patients was 34 +/- 8 years, and the mean length of follow-up was 13.0 +/- 4.2 months. The overall prevalence of hypothyroidism was 23.2% (nipple discharge 37%, mastalgia 23%, lump/lumpiness 17.4%). The rate of hypothyroidism and the mean serum TSH concentration were significantly higher among patients with nipple discharge than among those with mastalgia (P = 0.001) or a lump (P = 0.01). In all, 39% of hypothyroid women had TSH concentrations >10 mIU/l, and 53% had an elevated TPOAb titer. BBD symptoms were alleviated in 83% of the hypothyroid patients with only thyroxine replacement. The final clinical outcomes of hypothyroid patients with nipple discharge and mastalgia were significantly better than that of their euthyroid counterparts (P = 0.028 and 0.001, respectively); no significant difference was noted in patients with lumpiness (P = 0.144). All women with BBD should be screened for hypothyroidism because the prevalence of hypothyroidism is high among this group and correction of hypothyroidism results in significant clinical improvement of BBD in most of these patients.

Prolactin levels and examination with breast ultrasound or mammography

Stresses including surgery, exercise, nipple stimulation, and chest wall injury such as mechanical trauma, burns, surgery, herpes zoster of thoracic dermatomes, hypoglycaemia and acute myocardial infarction cause significant elevation of prolactin levels. The aim of the present study was to evaluate the changes in prolactin level during mammography and ultrasonographic examination. Seventy-four premenopausal (mean age, 32.1+/-7.3 y) and 81 post-menopausal women (mean age, 48.3+/-8.9 y) were enrolled into the study. Premenopausal women were evaluated with ultrasound (Senographe 600 T [General Electric]) and post-menopausal women were examined with mammography (Mammomat 3000 [Siemens]). Blood samples for prolactin were taken prior to ultrasound or mammography and 15, 30 and 45 min after ultrasound or mammography. Mean baseline serum prolactin level was 7.2+/-0.9 ng/ml in premenopausal women before ultrasound. Mean baseline serum prolactin level was 5.4+/-0.4 ng/ml in post-menopausal women before mammography. It was found that there were no significant changes in prolactin levels after ultrasound or mammography (P > 0.05). Mean levels of baseline prolactin were statistically significant higher in premenopausal than in post-menopausal women (P = 0.03). Mammography and ultrasonographic examination have no acute effect on serum prolactin levels in either group. There is no need to wait before measuring the prolactin level after mammographic or ultrasonographic breast examination.

Cabergoline in the Treatment of Hyperprolactinemia: A Study in 455 Patients

Many hyperprolactinemic patients do not tolerate bromocriptine or other dopamine agonists and, even if they do, often must take them two or three times each day. Cabergoline is a long-lasting dopamine agonist whose action lasts up to 2 weeks after a single dose so that it may be taken once or twice a week. This study evaluated cabergoline in 353 women and 102 men with pathologic hyperprolactinemia. Roughly 40 percent of the group had a microadenoma, and the same proportion had a macroadenoma. No cause was evident in 16 percent of cases. Of 292 patients who previously had received bromocriptine, 140 were intolerant and 58 were resistant to the drug. The median baseline serum prolactin was 124 μg/liter. Cabergoline therapy usually began at a dose of 0.25 or 0.5 mg twice weekly, and the dose was adjusted at 2- to 3-month intervals as needed to consistently reduce the prolactin level. Patients then were followed up every 4 to 6 months. Menstrual function became normal during cabergoline therapy in 89 percent of the women evaluated, several of whom became pregnant and delivered healthy children. The visual fields became normal in 70 percent of 47 patients. Migraine symptoms lessened significantly in 72 percent of 71 patients. Prolactin levels became normal in 86 percent of all patients and decreased by 75 percent or more in more than half of the others. The median lowest serum prolactin level, achieved in 8 months on average, was 5.6 μg/liter. The tumor shrank to some degree in two thirds of patients. At the end of follow-up, the median dose of cabergoline was 0.5 mg/week. Minor side effects were reported by 8.5 percent of patients, and major or persistent symptoms were reported by 4 percent. Headache and postural hypotension were the most common adverse effects. Of the 14 patients who withdrew because of intolerance, 12 had also failed to tolerate bromocriptine. Only 9 percent of bromocriptine-intolerant patients were also intolerant of cabergoline. Patients harboring a microprolactinoma required lower doses and were more likely than those with macroadenomas to achieve a normal serum prolactin level. The baseline and lowest serum prolactin levels correlated weakly but significantly. In more than two thirds of patients who had been resistant to bromocriptine, control was achieved with cabergoline. This large-scale study affirms the effectiveness and tolerance of cabergoline when used to treat pathologic hyperprolactinemia. J Clin Endocrinol Metab 1999;84:2518–2522

Risperidone is associated with blunting of D-fenfluramine evoked serotonergic responses in schizophrenia

The high 5-HT affinity of some atypical antipsychotic agents is thought to contribute to their clinical efficacy. We examined central 5-HT responses in two groups of ten schizophrenic patients by measuring serum prolactin and cortisol responses to the neuroendocrine challenge D-fenfluramine. One group of patients with schizophrenia was tested after a 2-week neuroleptic free period. A similar group were tested after a mean of 12 weeks treatment with the atypical antipsychotic risperidone. A significant elevation of baseline serum prolactin levels, consistent with dopaminergic antagonism was seen after risperidone treatment. Significantly reduced 5-HT mediated serum prolactin responses were seen in risperidone treated patients. D-fenfluramine evoked serum prolactin responses were positively correlated with positive but not negative schizophrenic symptoms for all 20 patients. Risperidone treatment was associated with a significant functional in-vivo 5-HT antagonism similar to clozapine. 5-HT antagonism may contribute to the efficacy of risperidone against positive schizophrenic symptoms.

Secretory patterns of serum prolactin in Asian (Elephas maximus) and African (Loxodonta africana) elephants during different reproductive states: Comparison with concentrations in a noncycling African elephant

Serum prolactin was quantified in adult female Asian (Elephas maximus) and African (Loxodonta africana) elephants during various reproductive states and the profiles compared to that in a noncycling African elephant. In reproductively normal elephants, there was no effect of season, estrous cycle stage, or lactational status on quantitative or qualitative prolactin secretion (P > 0.05), nor where there any differences (P > 0.05) in overall prolactin concentrations between species. In pregnant elephants, prolactin concentrations remained at baseline for the first 4–6 months of gestation. Thereafter, concentrations during early pregnancy averaged ∼four-fold higher than those during the estrous cycle, increasing to ∼100-fold over baseline during mid- to late gestation in both species. In contrast to cycling elephants, prolactin concentrations in an African elephant exhibiting chronic anovulation (on the basis of an acyclic serum progesterone profile) and mild galactorrhea were consistently about five-fold higher (P < 0.05), suggesting she is hyperprolactinemic. Other endocrinological assesments confirmed the hypogonadal state of this female. Serum estradiol concentrations were consistently at or below detectable levels. Additionally, no preovulatory luteinizing hormone (LH) surges occurred in daily serum samples analyzed over a 12-month period. The pituitary was not totally refractory, however, and responded with a several-fold increase in serum LH concentration (peak, 3.07 ng/ml) over baseline (0.75 ng/ml) after i.v. injection of gonadotropin-releasing hormone. This study describes normal baseline serum prolactin values for Asian and African elephants and is the first to identify hyperprolactinemia as a possible cause of reproductive acyclicity and galactorrhea in an African elephant. Zoo Biol 16:149–159, 1997. © 1997 Wiley-Liss, Inc.

Relationship between serum prolactin, lactation and changes in maternal blood B-cell (CD19+) percents during the first 8 months post-partum

Lactation is an immunologically unique state when immune factors are produced by the mother for the protection of the infant rather than the mother. While several studies have focused on the immunological composition of human milk, much less information is available on maternal immune status during lactation. Sixty-four lactating and 43 bottlefeeding women at 1–2 weeks, 1, 2, 4 or 8 months post-partum were studied in a cross-sectional design, with 14 nulliparous women as controls. Flow cytometry analysis of peripheral blood lymphocytes showed dynamic, post-partum changes in the B-cell subpopulation. Among lactating women, the relative percents of CD19+ B-cells were significantly lower ( P < 0.05) than control levels at 1–2 weeks and 1 month post-partum, but showed a significant, polynomial-linear rise ( P < 0.05) over time, reaching control values by 2–4 months post-partum. Bottle-feeding women had an earlier rise in the percentage of CD 19 + cells, with relative percents always significantly higher than their lactating counterparts. The differing patterns may be due to changes in serum prolactin concentrations because, among the post-partum women, relative percents of CD19+ cells were negatively correlated with baseline serum prolactin concentrations. These results have implications for maternal immunization programs designed to enhance maternal and/or infant well-being as well as other maternal health effects related to breastfeeding.

Stress and stress-related hormones during in-vitro fertilization treatment.

Whether stress and infertility are linked as cause or consequence is unclear, and there is no consensus on the most appropriate methods for measuring stress in infertile women. To address this question, we measured changes in biochemical and questionnaire-based assessments of stress in infertile women. Median baseline, follicular phase and pre-operative serum prolactin (229, 311 and 457 mIU/l) cortisol (278, 369 and 496 nmol/l) and state anxiety score (38, 40 and 49) respectively all increased during stimulated in-vitro fertilization (IVF) treatment. There was no such increase in a control group having similar laparoscopic surgery unrelated to infertility, or in women having unstimulated IVF without laparoscopy, suggesting that anxiety levels are greatest in stimulated IVF, increase as a result of the treatment, and are adequately reflected by state anxiety scores. Baseline serum prolactin in unstimulated IVF (384 mIU/l) was significantly higher than control (177 mIU/l), although this was not reflected in serum cortisol or state anxiety score. Trait anxiety was constant within and between groups, suggesting that stress is not contributing greatly to the infertility. Women who achieved a pregnancy had similar state anxiety scores to those who failed, suggesting that the degree of anxiety observed during IVF treatment is unlikely to influence the chance of pregnancy. There was a trend towards lower trait anxiety in women who became pregnant, but the numbers were small.